A Multi-center, Open-label Study of the Human Anti-TNF Monoclonal Antibody Adalimumab to Evaluate the Efficacy and the Long-term Safety and Tolerability of Repeated Administration of Adalimumab in Pediatric Subjects With Crohn's Disease Who Have Demonstrated a Clinical Response in the M06-806 Study
Phase: PHASE3
Conditions: Crohn's Disease
Sponsor: AbbVie (prior sponsor, Abbott)

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1.0
Title Page
CLINICAL TRIAL PROTOCOL M06-807
A Multi-center, Open-label Study of the Human 
Anti-TNF Monoclonal Antibody Adalimumab to 
Evaluate the Efficacy and the Long-term Safety and 
Tolerability of Repeated Administration of 
Adalimumab in Pediatric Subjects with 
Crohn's Disease Who Have Demonstrated a Clinical 
Response in the M06-806 Study
Incorporating Administrative Changes 1 and 2, 
Amendment 1, Administrative Changes 3, 4, 5, 6, 7, 8 
and 9 and Amendments 2, 3, 4, 5 and 6 and 
Amendment 7 for Poland
AbbVie Number/ 
Investigational Product:
Adalimumab
Date: 
26 May 2015
Development Phase:
3
Study Design: 
A multi-center, open-label safety and tolerability pediatric study in the 
United States, Canada and Europe.
EudraCT Number: 
2007-006494-90
Investigator:
Multicenter (Investigator information on file at AbbVie).
Sponsor:
European Union Countries:
AbbVie Deutschland GmbH & Co. KG 
Knollstrasse
67061 Ludwigshafen
Germany
Non European Union Countries:
AbbVie
1 North Waukegan Road
North Chicago, IL  60064
Emergency Contact:
This study will be conducted in compliance with the protocol, Good Clinical Practice and all other applicable regulatory 
requirements, including the archiving of essential documents.
Confidential Information
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
/$5

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1.1
Protocol Amendment:  Summary of Changes
The purpose of this amendment is the following:
●
Administrative Changes 8 and 9 were incorporated.
●
Add subject visits through Week 408 throughout the protocol.
Rationale of Change:  Extension of this open-label study is necessary to allow 
for continued collection of long-term safety and efficacy information and 
provision for study to continue until local regulatory approval and 
reimbursement.
●
Add the Complaint and Product Complaint definition to Section 6.0, 
Section 6.2.1 and Section 6.2.2 as well as the reporting requirements for 
Product Complaints.
●
Section 8.1.5, Interim Analysis, has been updated.
An itemized list of all changes made to the protocol under this amendment can be found 
in Appendix U.

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2.0
Table of Contents
1.0
Title Page..................................................................................1
1.1
Protocol Amendment:  Summary of Changes ...........................................2
2.0
Table of Contents.....................................................................3
3.0
Introduction .............................................................................7
4.0
Study Objective......................................................................14
5.0
Investigational Plan...............................................................14
5.1
Overall Study Design and Plan:  Description ..........................................14
5.2
Selection of Study Population..................................................................19
5.2.1
Inclusion Criteria .....................................................................................19
5.2.2
Exclusion Criteria ....................................................................................20
5.2.3
Prior and Concomitant Therapy...............................................................22
5.2.3.1
Prior Therapy ...........................................................................................22
5.2.3.2
Concomitant Therapy...............................................................................23
5.2.3.3
Rescue Therapy........................................................................................24
5.2.3.4
Prohibited Therapy...................................................................................24
5.3
Efficacy, and Safety Assessments/Variables ...........................................24
5.3.1
Efficacy and Safety Measurements Assessed and Flow Chart ................24
5.3.1.1
Study Procedures .....................................................................................34
5.3.2
Drug Concentration Measurements .........................................................43
5.3.2.1
Collection of Samples for Analysis .........................................................44
5.3.2.2
Handling/Processing of Samples .............................................................45
5.3.2.3
Disposition of Samples ............................................................................45
5.3.2.4
Measurement Methods.............................................................................45
5.3.3
Efficacy Variables....................................................................................46
5.3.4
Safety Variables.......................................................................................46
5.3.5
Pharmacokinetic Variables ......................................................................46
5.4
Removal of Subjects from Therapy or Assessment.................................46
5.4.1
Discontinuation of Individual Subjects....................................................46
5.4.2
Discontinuation of Entire Study...............................................................47
5.4.3
Stopping Rules.........................................................................................48
5.5
Treatments................................................................................................48

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5.5.1
Treatments Administered.........................................................................48
5.5.2
Identity of Investigational Product...........................................................50
5.5.2.1
Packaging and Labeling...........................................................................50
5.5.2.2
Storage and Disposition of Study Drug ...................................................51
5.5.3
Method of Assigning Subjects to Treatment Groups...............................51
5.5.4
Selection and Timing of Dose for Each Subject......................................51
5.5.5
Blinding....................................................................................................53
5.5.6
Treatment Compliance.............................................................................53
5.5.7
Drug Accountability.................................................................................53
5.6
Discussion and Justification of Study Design..........................................54
5.6.1
Discussion of Study Design and Choice of Control Groups....................54
5.6.2
Appropriateness of Measurements...........................................................54
5.6.3
Suitability of Subject Population .............................................................55
5.6.4
Selection of Doses in the Study ...............................................................55
6.0
Complaints .............................................................................56
6.1
Medical Complaints.................................................................................56
6.1.1
Definitions................................................................................................56
6.1.1.1
Adverse Event..........................................................................................56
6.1.1.2
Serious Adverse Events ...........................................................................57
6.1.2
Adverse Event Severity............................................................................58
6.1.3
Relationship to Study Drug......................................................................59
6.1.4
Adverse Event Collection Period.............................................................59
6.1.5
Adverse Event Reporting.........................................................................60
6.1.5.1
Collection of Data Regarding Known Manifestations of the 
Disease Under Study................................................................................61
6.1.6
Pregnancy.................................................................................................61
6.2
Product Complaint ...................................................................................62
6.2.1
Definition .................................................................................................62
6.2.2
Reporting..................................................................................................62
7.0
Protocol Deviations................................................................63
8.0
Statistical Methods and Determination of Sample 
Size ..........................................................................................64
8.1
Statistical and Analytical Plans................................................................64

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8.1.1
Analyzable Population.............................................................................64
8.1.2
Planned Methods of Statistical Analysis..................................................64
8.1.2.1
Demographics and Baseline Characteristics............................................64
8.1.2.2
Efficacy Analysis.....................................................................................65
8.1.3
Other Analyses.........................................................................................65
8.1.4
Safety Analyses........................................................................................65
8.1.4.1
Pharmacokinetic Analyses.......................................................................66
8.1.5
Interim Analysis.......................................................................................66
8.2
Determination of Sample Size .................................................................67
8.3
Randomization Methods ..........................................................................67
9.0
Ethics.......................................................................................67
9.1
Independent Ethics Committee (IEC) or Institutional Review 
Board (IRB) .............................................................................................67
9.2
Ethical Conduct of the Study...................................................................68
9.3
Subject Information and Consent.............................................................68
10.0
Source Documents and Case Report Form 
Completion .............................................................................69
10.1
Source Documents ...................................................................................69
10.2
Case Report Forms...................................................................................69
11.0
Data Quality Assurance ........................................................70
12.0
Use of Information and Publication.....................................71
12.1
Use of Information...................................................................................71
12.2
Internet Sites ............................................................................................72
13.0
Completion of the Study .......................................................72
14.0
Investigators Agreement.......................................................74
15.0
Reference List ........................................................................75
List of Tables
Table 1.
Study Activities........................................................................................25
Table 2.
Clinical Laboratory Tests.........................................................................39
Table 3.
Identity of Investigational Products.........................................................50
Table 4.
Study Drug Packaging and Administration .............................................50

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List of Figures
Figure 1.
Study Schematic.......................................................................................17
Figure 2.
Dosing Schematic After Amendment 4 ...................................................19
Figure 3.
Adverse Event Collection ........................................................................60
List of Appendices
Appendix A.
List of Abbreviations and Definition of Terms........................................78
Appendix B.
List of Protocol Signatories......................................................................80
Appendix C.
Documents Required Prior to Initiation of the Study ..............................81
Appendix D.
Responsibilities of the Clinical Investigator............................................83
Appendix E.
CDC Treatment of Tuberculosis Infection (Preventive Therapy) ...........85
Appendix F.
Non-Drug Materials Provided to the Study Site(s)..................................87
Appendix G.
Pediatric Crohns Disease Activity Index (PCDAI)..................................88
Appendix H.
PCDAI Users Guide and Guideline for Reference Weight and 
Reference Height......................................................................................90
Appendix I.
Crohns Disease Activity Index (CDAI)...................................................96
Appendix J.
Subject CDAI Diary.................................................................................97
Appendix K.
IMPACT III Questionnaire......................................................................98
Appendix L.
Excluded Medications............................................................................106
Appendix M.
Day 70 Phone Call .................................................................................107
Appendix N.
Unscheduled Outpatient Visits, Emergency Room Visits and 
Hospitalizations......................................................................................108
Appendix O.
Subject Medication Log.........................................................................109
Appendix P.
Subject Dosing Diary.............................................................................110
Appendix Q.
Self Injection Instructions......................................................................134
Appendix R.
Standard Weights...................................................................................149
Appendix S.
Subject AbbVie Site Drug Accountability Form...................................151
Appendix T.
Work Productivity and Activity Impairment Questionnaire: 
Crohns Disease (WPAI-CD) – Caregiver..............................................152
Appendix U.
Protocol Amendment:  List of Changes.................................................154

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3.0
Introduction
Crohns Disease (CD) is a chronic, debilitating, and currently incurable inflammatory 
disease that can affect the entire digestive system as well as extraintestinal organs.  CD is 
primarily manifested by focal asymmetric, transmural, and occasionally, granulomatous 
inflammation affecting any segment of the gastrointestinal tract1 which can consist of 
mucosal edema, aphthous and linear ulcerations, asymmetrical narrowing and strictures.  
Noncaseating granulomas are virtually diagnostic in the correct clinical setting.  The most 
commonly involved area of the bowel is the small bowel, particularly the distal ileum, 
which is involved in 70% of cases often in combination with colitis, occurring in 50% of 
cases.  Extraintestinal manifestations can also occur, and include symptoms of joint, 
ocular and hepatic inflammation.  Genetic, geographic, ethnic, and environmental risk 
factors have all been described, but the basic etiology of the disease remains unknown.
The incidence in North America is similar to that in other western nations and is estimated 
from 3.1 to 14.6 cases per 100,000 person years and prevalence ranges from 26 to 
199 cases per 100,000 persons.2  The disease can affect persons of any age but the most 
common age of onset is in the second and third decades with a female preponderance.  
While predominantly a disease of adults, approximately 10% to 15% of CD cases are 
diagnosed before adulthood.3
In addition, the incidence of CD in patients less than 18 years of age appears to be 
increasing in both North America and Europe.4,5  Reported incidence rates range from 
1.2 to 4.9 per 100,000 persons in the UK, Europe, and North America6-12 with one study 
reporting an incidence of 4.6 per 100,000 persons in the United States.5  CD has been 
reported at all ages but is rare in early childhood.  In one study of patients with CD, 
17 years of age and younger, 9.1% of the patients were diagnosed before the age of 6.13  
In a second study of patients diagnosed with CD before the age of 15, 7.5% of the patients 
were under the age of 5.14
Despite obvious physiologic and development differences, the presentation of CD in the 
pediatric population is generally similar to that seen in older patients and is heterogeneous 

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with regard to anatomic localization and clinical severity.5,15,16  The unique aspect of this 
disease in children is its impact on nutrition and growth, with marked growth retardation 
being a prominent component of the disease in this age group.17-19  The use of accepted 
methodologies for assessing nutritional status, including the anthropometric measures of 
height, weight, triceps skin fold thickness and mid arm circumference as well as linear 
growth (height velocity and assessment of height velocity for chronological age "z-score") 
have documented the growth impairment that can occur in this age group, and also have 
been used to assess the efficacy of interventions.20  Profound impairment of bone 
formation and increased bone resorption are associated complications and are related to 
the effect of glucocorticoids,21,22 delayed puberty,22,23 decreased mobility,24 as well as to 
the effects of cytokines on bone formation.25
Initial symptoms are often subtle, and there is an average delay of almost six months 
between onset of symptoms and diagnosis.  The most common presentation is with 
abdominal pain, diarrhea, loss of appetite and weight loss.  However, isolated weight loss, 
anorexia, perianal disease and extraintestinal manifestations can occur in the absence of 
GI symptoms in a substantial number of patients.
The general approach to the treatment of CD in children is similar to adults with the goals 
being induction and maintenance of remission, prevention of relapse and hospitalizations, 
improved quality of life, and avoidance of disease and drug related complications.  
Restoration and/or preservation of normal growth and pubertal development are additional 
therapeutic goals.  The medical armamentarium is likewise similar to adults and includes 
induction of remission with corticosteroids, and ongoing maintenance therapy of 
immunomodulators, aminosalicylates and nutritional therapy.  Anti-tumor necrosis factor 
(TNF) therapy with infliximab has been evaluated for the therapy of CD in this age group 
as it has in adults.  The FDA and EMEA have recently approved Infliximab for use in 
children with CD.
Adalimumab is a recombinant human immunoglobulin (IgG1) monoclonal antibody 
exclusively containing human peptide sequences.  It is produced by recombinant 
deoxyribonucleic acid (DNA) technology in a mammalian cell expression system.  

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Adalimumab consists of 1330 amino acids and has a molecular weight of approximately 
148 kilodaltons.  It binds specifically with high affinity to the soluble and transmembrane 
forms of TNFα and inhibits the binding of TNFα with its receptors.
TNF is a naturally occurring cytokine that is involved in normal inflammatory and 
immune responses.  Elevated levels of TNF play an important role in pathologic 
inflammation.  Adalimumab binds specifically to TNF and neutralizes the biological 
function of TNF by blocking its interaction with the p55 and p75 cell surface TNF 
receptors.
Adalimumab was first approved for treatment of rheumatoid arthritis (RA) on 
31 Dec 2002 in the United States (US), on 08 Sep 2003 in the European Union (EU) and 
through August 2008 in a total of 76 countries.  Indication extensions to include treatment 
of psoriatic arthritis and early RA were granted in the EU on 01 Aug 2005 and in the US 
on 03 Oct 2005.  A further indication extension to include treatment of ankylosing 
spondylitis was approved in the EU on 01 Jun 2006 and was approved in the US on 
28 Jul 2006.  Adalimumab was approved for the treatment of Crohns disease in the United 
States on 27 Feb 2007, in the European Union on 04 Jun 2007 and in Canada on 
05 July 2007 for the adult population.  In December 2007 and January 2008, respectively, 
adalimumab was approved for the treatment of psoriasis in adult patients in the EU, 
Canada and USA.  Additionally, adalimumab was approved for the treatment of juvenile 
idiopathic arthritis in the USA in February 2008.
Adalimumab has been shown to be a safe and effective treatment of moderately to 
severely active Crohns disease.  In the CD development program, adalimumab was 
studied in over 1400 adult subjects in three pivotal studies (two induction studies and a 
maintenance study).
Study M02-403 was a multicenter, randomized, double-blind, placebo-controlled 
Phase 2/3 study to evaluate the efficacy and safety of adalimumab for the induction of 
remission in subjects with moderate to severe CD.26  A total of 299 subjects were 
randomized to receive one of four proposed induction treatment regimens (three active 

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treatment groups or placebo):  adalimumab 160 mg at Baseline (Week 0) followed by 
80 mg at Week 2, adalimumab 80 mg at Baseline followed by 40 mg at Week 2, 
adalimumab 40 mg at Baseline followed by 20 mg at Week 2 or placebo at Baseline and 
Week 2.  Eligible subjects could not have been previously treated with any anti TNF 
agent.  Only the group of subjects treated with adalimumab 160/80 mg had a statistically 
significantly greater remission rate at Week 4 (primary endpoint) compared to placebo 
(35.5% vs. 12.2%; p = 0.001).  In addition, statistically significantly greater proportions of 
subjects in the adalimumab 160/80 mg group than in the placebo group experienced
clinical response CR-100 (48.7% and 24.3%, respectively) and clinical response CR-70 
(57.9% and 36.8%, respectively) at Week 4.
Study M04-691, a second induction study, was a multicenter, randomized, double-blind, 
placebo-controlled, Phase 3 study to evaluate the efficacy and safety of adalimumab as 
induction treatment for subjects with moderate to severe CD who either initially 
responded to administration of infliximab but stopped responding or were intolerant.27  
A total of 325 subjects were randomized to receive adalimumab 160/80 mg or placebo.  
Eligible subjects must have previously been treated with infliximab and discontinued use 
due to loss of response to or intolerance to infliximab therapy.  The proportion of subjects 
who achieved clinical remission at Week 4 (primary endpoint) was statistically 
significantly greater in the adalimumab 160/80 mg group compared to the placebo group 
(21.4% vs. 7.2%).  The proportion of subjects achieving clinical response CR-100 and 
CR-70 at Week 4 was statistically significantly greater in the adalimumab 160/80 mg 
group (38.4% and 51.6%, respectively) compared to the placebo group (24.7% and 
33.7%, respectively).
Study M02-404 was a multicenter, randomized, double-blind, placebo-controlled Phase 3 
study to assess the efficacy and safety of adalimumab for the maintenance of clinical 
remission in subjects with moderate to severe CD.27  A total of 854 subjects (both naïve to 
or previously treated with TNF antagonists [primarily infliximab]) were enrolled and 
received open-label adalimumab 80 mg at Baseline (Week 0) and adalimumab 40 mg at 
Week 2.  At Week 4, subjects were stratified by responder status (subjects who achieved 

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clinical response CR-70) and previous anti-TNF use and were randomized in a 1:1:1 ratio 
to one of three blinded treatment groups:  adalimumab 40 mg every week (ew), 
adalimumab 40 mg every other week (eow), or placebo.  Subjects who met clinical 
response CR-70 after Week 8 could be tapered from corticosteroids.
The proportion of Week 4 responders (N = 499) who achieved clinical remission at 
Weeks 26 and 56 (co-primary endpoint) were statistically significantly greater in the 
adalimumab 40 mg eow (39.5% and 36.0%, respectively) and 40 mg ew (46.5% and 
41.4%, respectively) groups compared to the placebo group (17.1% and 11.8%, 
respectively).  The differences between the adalimumab 40 mg eow and 
adalimumab 40 mg ew groups at both of these time points were not statistically 
significant.  The median time in first clinical remission was greater in the adalimumab 
40 mg eow group (378 days) compared to the placebo group (127 days).  The median time 
in remission could not be estimated in the adalimumab 40 mg ew group because more 
than 50% remained in clinical remission at the end of the study.  Approximately six times 
as many subjects treated with adalimumab maintenance therapy compared to placebo 
were able to discontinue corticosteroids for at least 90 days and achieve remission at 
Week 26 and Week 56.  Efficacy was independent of Baseline C-reactive protein (CRP), 
concomitant therapies, such as corticosteroids or immunosuppressants, or prior anti-TNF 
experience.  The adalimumab safety profile in CD was similar to that seen in the other 
rheumatologic populations previously studied, except for expected manifestations of CD.
Currently, there are two ongoing extension studies of adalimumab therapy in adult 
subjects with CD.  M04-690 trial is a long-term safety and tolerability study of repeated 
administration of adalimumab in adult subjects with CD who had previously participated 
in M02-404 or M04-691.  The other trial is a long-term open-label extension study 
following the initial first-year study period of the M02-433 study.
The efficacy and safety of adalimumab in children has recently been demonstrated in 
juvenile rheumatoid arthritis (JRA).28  One hundred and seventy-one pediatric patients 
(4 to 17 years of age) were initially enrolled into a 16-week open label segment and 
133 subjects continued in a 32-week double blind segment.  Clinically significant 

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improvements were noted in ACR30, ACR50 and ACR70 as well as other indices of 
arthritis activity.  Adverse events (AEs) were similar as those noted in adult RA patients.  
There were no deaths, malignancies, or opportunistic infections, including tuberculosis 
(TB).  Thirteen serious adverse events (SAEs) in 8 subjects were observed in the 16-week 
open label portion of the study.  These included 4 subjects with JRA, one patient with 
two episodes of leukopenia/neutropenia, and one case each of femur fracture, herpes 
simplex, and pneumonia.  Six SAEs were observed in 6 subjects (2 placebo, 
4 adalimumab) during the 32-week double blind portion (closed head injury, 
gastroduodenitis, retinal detachment, appendicitis, abdominal pain and urinary tract 
infection).  Infections, AEs at least possibly related to study drug, and injection site 
reactions were reported by similar proportions of patients in all treatment groups during 
the double-blind therapy (32 weeks).
Fatalities, serious infections, and sepsis have been reported with the use of TNF 
antagonists. Many of the serious infections have occurred in subjects on concomitant 
immunosuppressive therapy that, in addition to their underlying immune disorder, could 
predispose them to infections.  TB has also been observed in subjects treated with TNF 
antagonists, including adalimumab.  The event rate for TB in the CD development 
program is consistent with the global adalimumab rate.29
TNF antagonists, including adalimumab, have been associated with cases of malignancy 
and demyelinating disease.  Serious allergic adverse reactions have been reported in RA 
subjects following subcutaneous (SC) administration of adalimumab; none were reported 
in the CD program.
A detailed discussion of the pre-clinical toxicology, metabolism, pharmacology, and 
safety experience can be found in the current Investigators Brochure.
The goal of this study is to demonstrate the efficacy of adalimumab in the maintenance of 
clinical response and to demonstrate the long-term safety and tolerability of repeated 
administration of adalimumab in pediatric subjects with Crohns disease.  The subject 
population will consist of subjects who participated in and successfully completed the 

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M06-806 study and who meet all the inclusion and none of the exclusion criteria of 
Protocol M06-807.  Qualifying subjects will administer open-label adalimumab by SC 
injection.  Subjects receiving every other weekly therapy who continue to have a disease 
flare or develop another flare may be switched to every week therapy at the investigators 
discretion.  Subjects receiving weekly therapy who continue to have a disease flare or 
develop another flare may be withdrawn from the study at the Investigators discretion.  
For a detailed description of the study please see Section 5.0.
Safety Information
In 2008 FDA issued an early communication about an ongoing safety review of TNF 
blockers and the development of lymphoma and other cancers in children and adolescents.
As of the December 2009 FDA Pediatric advisory committee, it was noted that in general, 
adverse events seen in studies submitted for the JIA indication were similar to those in the 
adult population, both in type and frequency.
Due to the relatively rare occurrence of these cancers, the limited number of pediatric 
patients treated with TNF blockers, and the possible role of other immunosuppressive 
therapies used concomitantly with TNF blockers, the FDA was unable at that time to fully 
characterize the strength of the association between using TNF blockers and developing a 
malignancy.  Product labeling for all anti-TNF agents now includes language regarding
the risk of pediatric malignancies as requested by the FDA.
Furthermore, in November 2011 the FDA requested that all manufacturers of TNF 
inhibitors undertake a coordinated effort to better understand the risks for malignancies 
that develop in patients who are 30 years of age and younger at the time of diagnosis.  
Reporting requirements for these events can be found in Section 6.1.5 Adverse Event 
Reporting.  A detailed discussion of the pre-clinical toxicology, metabolism, 
pharmacology, and safety experience with adalimumab can be found in the current 
Investigator's Brochure.

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4.0
Study Objective
The objective of the study is to evaluate the long-term maintenance of clinical response, 
safety and tolerability of repeated administration of adalimumab in pediatric subjects with 
Crohns disease who participated in, and successfully completed, Protocol M06-806 
through Week 52 and who meet all the inclusion and none of the exclusion criteria of 
Protocol M06-807.
5.0
Investigational Plan
5.1
Overall Study Design and Plan:  Description
This study is a multi-center, open-label study of the human anti-TNF monoclonal 
antibody adalimumab.  Approximately 31 sites that have enrolled subjects in the M06-806 
clinical trial will participate in the M06-807 clinical trial.  Approximately 130 pediatric 
subjects were expected to enroll in this study; final enrollment was 100 subjects.  
The Week 52 visit from the M06-806 study will be the Baseline Visit for those subjects 
entering study M06-807.  The visit window for M06-806 Week 52 visit is 364 ± 7 days 
from the Baseline Visit date of M06-806.
Subjects may be allowed to enroll in the M06-807 study if they have participated in, and 
successfully completed Protocol M06-806 through Week 52.  A subject must be a 
responder at any time point during the M06-806 study.  A responder is defined as a 
subject who had a PCDAI score that was at least 15 points lower than the M06-806 
baseline score.
All subjects will be on open-label maintenance therapy.  Subjects who enroll into the 
study from blinded therapy in Study M06-806 will receive open-label therapy at a dose 
dependent on their body weight.  Subjects who weigh ≥ 40 kg at Baseline will receive 
40 mg eow of adalimumab, while subjects who weigh < 40 kg at Baseline will receive 
20 mg eow of adalimumab.  Beginning at Week 8, subjects who have a disease flare may 
be switched to ew treatment at the same dose of adalimumab received while on eow 

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treatment.  A disease flare is defined as an increase in the Pediatric Crohns Disease 
Activity Index (PCDAI) of ≥ 15 points when compared to the PCDAI score obtained at 
the subjects previous visit.
Subjects who enroll into the study from open-label therapy in Study M06-806 will 
continue to receive the same dose they were receiving (i.e., 40 mg ew or 20 mg ew) at the 
Week 52 visit of the M06-806 study. 
Subjects who develop a flare while receiving ew open-label therapy or have a PCDAI 
score ≥ 15 points when compared to their Baseline (the Week 52 visit of the M06-806 
study) PCDAI score (regardless of study visit), may be discontinued from the study at the 
discretion of the Investigator. 
Beginning from Week 8, the dose of adalimumab may be increased to 40 mg, at the 
discretion of the Investigator, for subjects whose body weight has increased from < 40 kg 
to ≥ 40 kg from the Baseline (Week 52 of the M06-806 Study) visit.  The site will enter 
the subjects body weight into the Interactive Voice Response System (IVRS) and the dose 
will be adjusted, if applicable. 
Reductions in concomitant therapy will be allowed for Crohns treatment related toxicities 
(e.g., leukopenia, anemia, neuropathy) of Grade 3 or higher.
Subjects may be allowed to decrease prednisone (or equivalent) and budesonide if 
qualifications are met (please see Section 5.2.3.2 for required timing and rate of taper).
Subjects may be allowed to adjust their Crohns specific concomitant medications as 
specified in Section 5.2.3.2.
The duration of the study could last up to 408 weeks (approximately 8 years).  Subjects 
who complete, or who early terminate from the study will be contacted 70 days after their 
last dose of study drug to obtain information on any ongoing and new AEs.  

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This study will conclude approximately 12 weeks after the following criteria have been 
satisfied:
●
Study drug receives country and local (if applicable) regulatory approval for 
pediatric Crohns Disease.
●
All applicable local reimbursement procedures are completed.
Sites will be notified once these criteria are met.
Following country and local (if applicable) regulatory approval and applicable local 
reimbursement approval of the study drug in a country, subjects should return to their next 
scheduled study visit as specified in the protocol.  The termination visit should be 
conducted in place of their regular scheduled study visit.  These subjects should be 
considered as having completed the study.
A schematic of the study design is shown in Figure 1 (prior to Amendment 4) and in 
Figure 2 (after Amendment 4).

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M06-807 Protocol Amendment 7 for Poland
EudraCT 2007-006494-90
17
Figure 1.
Study Schematic

Adalimumab
M06-807 Protocol Amendment 7 for Poland
EudraCT 2007-006494-90
18

Adalimumab
M06-807 Protocol Amendment 7 for Poland
EudraCT 2007-006494-90
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Figure 2.
Dosing Schematic After Amendment 4
F: 
Subjects who have a disease flare may be switched to the next higher treatment level.
R: 
Subjects who responded to their current treatment may be switched to the next lower treatment level at the 
discretion of the investigator after discussion with the medical monitor.  Response is defined as a) a ≥ 15 points 
decrease in PCDAI compared to the last observation prior to dose escalation in patients who dose-escalated or 
b) a ≥ 15 points decrease in PCDAI compared to Baseline of Study M06-806 in patients who did not 
dose-escalate.
BW: Subjects with an increase in body weight to ≥ 40 kg may increase their dose to the next higher level at the 
discretion of the investigator after discussion with the medical monitor.  Subjects with a decrease in body weight 
to < 40 kg may decrease their dose to the next lower level at the discretion of the investigator after discussion 
with the medical monitor.
5.2
Selection of Study Population
Subjects will be evaluated to determine if they meet all of the inclusion criteria specified 
in Section 5.2.1 and none of the exclusion criteria specified in Section 5.2.2 of this 
protocol.  
5.2.1
Inclusion Criteria
1.
Subject must have successfully enrolled in and completed Protocol M06-806 
through Week 52.
2.
Subject must be a responder at any time point during the M06-806 study.

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M06-807 Protocol Amendment 7 for Poland
EudraCT 2007-006494-90
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3.
If female, subjects who are sexually active and are of child-bearing potential should 
be practicing an approved method of birth control throughout the study and for 
150 days after study drug administration.  Examples of approved methods of birth 
control include the following:
●
Condoms, sponge, foam, jellies, diaphragm or intrauterine device (IUD)
●
Oral, parenteral or intravaginal contraceptives
●
A vasectomized partner
4.
Subject of legal age, parent or legal guardian, as required, has voluntarily signed 
and dated an Institutional Review Board (IRB)/Independent Ethics Committee 
(IEC) approved informed consent form, after the nature of the study has been 
explained and the subject of legal age, subjects parent, or legal guardian, as 
required, has had the opportunity to ask questions.  Subjects will be included in all 
discussions, and if required, their signature on an assent form will be obtained.
5.
Parent or legal guardian of subject who is not of legal age, as required, must be 
willing to actively supervise storage and administration of study drug and to ensure 
that the time of each dose is accurately recorded in the subjects diary.
6.
If a subject of legal age, must be willing to actively store, administer, and 
accurately record study drug administration in the subject diary.
7.
Subject is judged to be in acceptable medical condition, as determined by the 
Principal Investigator based upon results of clinical and laboratory evaluations 
done throughout the preceding Crohns disease study M06-806.
5.2.2
Exclusion Criteria
A subject will be excluded from the study if he/she meets any of the following criteria: 
1.
For any reason, the subject is considered by the Investigator to be an unsuitable 
candidate for continuing therapy in the M06-807 study.

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M06-807 Protocol Amendment 7 for Poland
EudraCT 2007-006494-90
21
2.
Subject has abnormal laboratory or other test results that in the opinion of the 
Investigator will make the subject unsuitable to participate in this study.
3.
History of cancer or lymphoproliferative disease other than a successfully and 
completely treated cutaneous squamous cell or basal cell carcinoma or 
carcinoma-in-situ of the cervix.
4.
History of listeriosis, histoplasmosis, chronic or active hepatitis B infection, human 
immunodeficiency virus (HIV) infection, any immunodeficiency syndrome, central 
nervous system (CNS) demyelinating disease or active TB (receiving treatment or 
not receiving treatment).  Ongoing severe infections such as sepsis and 
opportunistic infections will be exclusionary.
5.
Subject with known, symptomatic obstructive strictures.
6.
Subject who is planning surgical bowel resection at any time point while enrolled 
in the study.
7.
Subject who has short bowel syndrome as determined by the Investigator.
8.
Subject who is currently receiving total parenteral nutrition (TPN).
9.
Subject who is unwilling to discontinue growth hormone prior to the first dose of 
open-label study drug at the Baseline visit of M06-807.
10.
Female subject who is pregnant or currently breast-feeding.
11.
Subject with a history of clinically significant drug or alcohol abuse in the last year.
12.
Subject with a poorly controlled medical condition such as: uncontrolled diabetes, 
recurrent infections, unstable ischemic heart disease, moderate to severe heart 
failure, recent cerebrovascular accidents or any other condition which, in the 
opinion of the Investigator or the Sponsor, will put the subject at risk by 
participation in the protocol.
13.
Subject with any prior exposure to Tysabri (natalizumab).
14.
Subject with a known hypersensitivity to the excipients of adalimumab as stated in 
the label.

Adalimumab
M06-807 Protocol Amendment 7 for Poland
EudraCT 2007-006494-90
22
15.
Subject with a previous history of dysplasia of the gastrointestinal tract.
16.
Subject is not in compliance with Section 5.2.3.
If there are any questions regarding inclusion and exclusion criteria and/or subject 
eligibility, contact the AbbVie Medical Monitor identified in Section 7.0.
5.2.3
Prior and Concomitant Therapy
5.2.3.1
Prior Therapy
Any medication (including over-the-counter medicines such as aspirin) that the subject is 
receiving during the study must be recorded in source documents and on the appropriate 
case report form (CRF) along with the reason for use, dates of administration and dosages.
Any vaccine administered to the subject during the study should be listed as a 
concomitant medication.  Subjects should continue on the recommended vaccination 
schedule; however, vaccinations with live vaccines are prohibited.  
Any medications captured in the M06-806 CRF(s) which are ongoing will be transcribed 
onto the M06-807 source documents and CRF(s).
If there are any questions regarding prior or concomitant therapy (ies), contact the AbbVie 
Medical Monitor identified in Section 7.0
In addition for patients age ≤ 30 with a reported malignancy adverse event, prior exposure 
to, or current use of, antineoplastics, or other drugs which have a risk of malignancy as 
stated in their label and other relevant dosing information to estimate total exposure will 
be collected in the source documents and appropriate CRF pages.  At the time of the 
reported malignancy adverse event, sites will be asked if any of the prior and concomitant 
medications contributed to the event.  Any medications used prior to the study will be 
captured on the appropriate CRF.  Information on the reason for use, date(s) of 
administration including start and end dates, highest maintained dose, dosage information 

Adalimumab
M06-807 Protocol Amendment 7 for Poland
EudraCT 2007-006494-90
23
including dose, route and frequency, and reason for stopping the medication will be 
collected in the source documents and appropriate CRF pages.
5.2.3.2
Concomitant Therapy
Adjustments of Crohn's related concomitant treatments, including Crohn's related 
antibiotics, are not allowed during the first 8 weeks of the M06-807 study, unless subject 
safety is at risk.
After Week 8, decreases in the dose or discontinuation of Crohn's related antibiotics or 
Crohn's related concomitant treatments are allowed according to the Investigators medical 
judgment.  These adjustments may be performed without prior discussion with the 
AbbVie Medical Monitor.  In addition, subjects may be able to initiate or reinitiate 
Crohn's related treatments, following eight (8) weeks of exposure to open-label 
adalimumab.  Therapeutic enemas and suppositories (not including those done in 
conjunction with routine colonoscopies) and total parenteral nutrition (TPN) during the 
study should be discussed with and approved by the Medical Monitor prior to use.
Setons are allowed as concomitant therapy in subjects with perianal fistulas.  Their use 
should be documented on the concomitant medications page of the CRF.
Growth hormone must be discontinued prior to the first dose of open-label study drug and 
subjects may not begin using it while participating in this study.
If a subject began to taper corticosteroids during the M06-806 study, they may continue 
this taper immediately upon enrollment into the M06-807 study.  Beginning at Week 8, 
subjects who are not in flare may begin corticosteroid taper according to the following 
schedule:
Tapering Schedule
Dose
Rate
Prednisone (or equivalent)
> 10 mg 
≤ 10 mg
5 mg/week 
2.5 mg/week
Budesonide
≤ 9 mg
3 mg/week

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M06-807 Protocol Amendment 7 for Poland
EudraCT 2007-006494-90
24
Subjects who are in flare or who flare after they have reduced or completely tapered their 
dose of corticosteroid may have their corticosteroid dose increased or restarted, at the 
discretion of the Investigator. 
5.2.3.3
Rescue Therapy
If the Investigator decides, during the study, that a subject requires rescue therapy other 
than that described in this protocol, the subject must be terminated from the study.  If 
possible, questions regarding the use of rescue therapy should be discussed with the 
Medical Monitor prior to use.
5.2.3.4
Prohibited Therapy
Live vaccines must not be given concurrently while on study drug and for 70 days after 
the last dose of study drug.
Infliximab and growth hormone use are prohibited during the study.  At the Baseline visit, 
any subject using Growth hormone must discontinue its use.
Tysabri (natalizumab), concurrent biological therapy, cyclosporine, tacrolimus, 
mycophenolate mofetil, Kineret® (anakinra), Orencia (abatacept), and any investigational 
agent are prohibited during the study (see Appendix L).
Concurrent use of budesonide and prednisone (or equivalent) is prohibited.
Subjects with any prior exposure to Tysabri (natalizumab) will be excluded.
5.3
Efficacy, and Safety Assessments/Variables
5.3.1
Efficacy and Safety Measurements Assessed and Flow 
Chart
Study procedures will be performed as summarized in the study schematic presented in 
Table 1.

Adalimumab
M06-807 Protocol Amendment 7 for Poland
EudraCT 2007-006494-90
25
Table 1.
Study Activities
Activity
Baseline
Week 4
Week 8
Week 12
Week 24
Week 36
Week 48
Week 60
Week 72
Week 84
Inclusion/exclusion criteria
X
Informed consent
X
Previous and concomitant 
medications
Xa
X
X
X
X
X
X
X
X
X
Urine pregnancy testb
Xa
X
X
X
X
X
X
X
X
X
Vital signsc
Xa
X
X
X
X
X
X
X
X
X
Physical exam
Xa
X
X
X
X
X
X
X
X
X
General LABd
Xa
X
X
X
X
X
X
X
X
X
TB testing (PPD or 
QuantiFERON-TB Gold)e
X
Urinalysisf
Xa
X
X
X
X
X
X
X
X
X
Erythrocyte sedimentation rate
Xa
X
X
X
X
X
X
X
X
X
CRP
Xa
X
X
X
ANA
Xa
X
Anti-dsDNAg
Xa
X
PCDAI
Xa
X
X
X
X
X
X
X
X
X
CDAIh
Xa
X
X
X
X
X
X
X
X
X
IMPACT III Questionnairei
Xa
X
X
X
X

Adalimumab
M06-807 Protocol Amendment 7 for Poland
EudraCT 2007-006494-90
26
Table 1.
Study Activities (Continued)
Activity
Baseline
Week 4
Week 8
Week 12
Week 24
Week 36
Week 48
Week 60
Week 72
Week 84
Unscheduled outpatient visits, 
emergency room visits and 
hospitalizations questionnaire
Xa
X
X
X
X
X
X
X
X
X
Work Productivity and 
Impairment Questionnaire:  
Crohn's Disease (WPAI – CD)
Xa
X
X
X
X
X
X
X
X
X
X-ray for bone agej
Xa
X
Serum bone markers
Xa
X
X
X
PK Blood Samplek
X
X
X
Anti-adalimumab blood levels 
(AAA)k
X
X
X
Adverse eventsl
Xa
X
X
X
X
X
X
X
X
X
Dispense study drug
Xa
X
X
X
X
X
X
X
X
X

Adalimumab
M06-807 Protocol Amendment 7 for Poland
EudraCT 2007-006494-90
27
Table 1.
Study Activities (Continued)
Activity
Week 96
Week 108
Week 120
Week 132 
Call
Week 144
Week 156 
Call
Week 168
Week 180 
Call
Week 192
Week 204 
Call
Inclusion/exclusion criteria
Informed consent
Previous and concomitant 
medications
X
X
X
X
X
X
X
X
X
X
Urine pregnancy testb
X
X
X
X
X
X
Vital signsc
X
X
X
X
X
X
Physical exam
X
X
X
X
X
X
General LABd
X
X
X
X
X
X
TB testing (PPD or 
QuantiFERON-TB Gold)e
X
X
X
Urinalysisf
X
X
X
X
X
X
Erythrocyte sedimentation rate
X
X
X
X
X
X
CRP
X
X
X
X
ANA
X
X
X
Anti-dsDNAg
X
X
X
PCDAI
X
X
X
X
X
X
CDAIh
X
X
X
X
X
X
IMPACT III Questionnairei
X
X
X
X
X

Adalimumab
M06-807 Protocol Amendment 7 for Poland
EudraCT 2007-006494-90
28
Table 1.
Study Activities (Continued)
Activity
Week 96
Week 108
Week 120
Week 132 
Call
Week 144
Week 156 
Call
Week 168
Week 180 
Call
Week 192
Week 204 
Call
Unscheduled outpatient visits, 
emergency room visits and 
hospitalizations questionnaire
X
X
X
X
X
X
X
X
X
X
Work Productivity and Impairment 
Questionnaire:  Crohn's Disease 
(WPAI – CD)
X
X
X
X
X
X
X-ray for bone agej
X
X
X
Serum bone markersj
X
X
X
X
X
PK Blood Samplek
X
X
X
X
X
Anti-adalimumab blood levels 
(AAA)k
X
X
X
X
X
Adverse eventsl
X
X
X
X
X
X
X
X
X
X
Dispense study drug
X
X
X
X
X
X

Adalimumab
M06-807 Protocol Amendment 7 for Poland
EudraCT 2007-006494-90
29
Table 1.
Study Activities (Continued)
Activity
Week 
216
Week 
228 
Call
Week 
240
Week 
252 
Call
Week 
264
Week 
276 
Call
Week 
288
Week 
300 
Call
Week 
312
Week 
324 
Call
Week 
336
Week 
348
Call
Week 360
Inclusion/exclusion criteria
Informed consent
Previous and concomitant 
medications
X
X
X
X
X
X
X
X
X
X
X
X
X
Urine pregnancy testb
X
X
X
X
X
X
X
Vital signsc
X
X
X
X
X
X
X
Physical exam
X
X
X
X
X
X
X
General LABd
X
X
X
X
X
X
X
TB testing (PPD or 
QuantiFERON-TB Gold)e
X
X
X
Urinalysisf
X
X
X
X
X
X
X
Erythrocyte sedimentation 
rate
X
X
X
X
X
X
X
CRP
X
X
X
X
X
X
ANA
X
Anti-dsDNAg
X
PCDAI
X
X
X
X
X
X
X
CDAIh
X
X
X
X
X
X
X
IMPACT III Questionnairei
X
X
X
X
X
X
X

Adalimumab
M06-807 Protocol Amendment 7 for Poland
EudraCT 2007-006494-90
30
Table 1.
Study Activities (Continued)
Activity
Week 
216
Week 
228 
Call
Week 
240
Week 
252 
Call
Week 
264
Week 
276 
Call
Week 
288
Week 
300 
Call
Week 
312
Week 
324 
Call
Week 
336
Week 
348
Call
Week 360
Unscheduled outpatient 
visits, emergency room 
visits and 
hospitalizations 
questionnaire
X
X
X
X
X
X
X
X
X
X
X
X
X
Work Productivity and 
Impairment 
Questionnaire:  Crohn's 
Disease (WPAI – CD)
X
X
X
X
X
X
X
X-ray for bone agej
X
X
X
Serum bone markersj
X
X
X
X
X
X
X
PK Blood Samplek
X
X
X
X
X
X
X
Anti-adalimumab blood 
levels (AAA)k
X
X
X
X
X
X
X
Adverse eventsl
X
X
X
X
X
X
X
X
X
X
X
X
X
Dispense study drug
X
X
X
X
X
X
X

Adalimumab
M06-807 Protocol Amendment 7 for Poland
EudraCT 2007-006494-90
31
Table 1.
Study Activities (Continued)
Activity
Week 372 Call
Week 384
Week 396 Call
Week 408/
Early Term
Unsched Visit
70-Day Follow-Up Call
Inclusion/exclusion criteria
Informed consent
Previous and concomitant medications
X
X
X
X
X
Urine pregnancy testb
X
X
X
Vital signsc
X
X
X
Physical exam
X
X
X
General LABd
X
X
X
TB testing (PPD or QuantiFERON-TB Gold)e
X
X
Urinalysisf
X
X
X
Erythrocyte sedimentation rate
X
X
X
CRP
X
X
X
ANA
X
Anti-dsDNAg
X
PCDAI
X
X
X
CDAIh
X
X
X
IMPACT III Questionnairei
X
X
X
Unscheduled outpatient visits, emergency room 
visits and hospitalizations questionnaire
X
X
X
X
X

Adalimumab
M06-807 Protocol Amendment 7 for Poland
EudraCT 2007-006494-90
32
Table 1.
Study Activities (Continued)
Activity
Week 372 Call
Week 384
Week 396 Call
Week 408/
Early Term
Unsched Visit
70-Day Follow Up Call
Work Productivity and Impairment 
Questionnaire:  Crohn's Disease (WPAI – CD)
X
X
X
X-ray for bone agej
X
Serum bone markersj
X
X
X
PK Blood Samplek
X
X
X
Anti-adalimumab blood levels (AAA)k
X
X
X
Adverse eventsl
X
X
X
X
X
X
Dispense study drug
X
Xm
a.
At the Baseline Visit, the following procedures will be completed as part of Week 52 of the M06-806 study.
b.
Performed on all females of child bearing potential – Urine pregnancy test at all study visits.
c.
Vital sign determinations of height, weight, sitting blood pressure, heart rate, respiratory rate, and body temperature will be obtained at each visit.
d.
Blood draws should be performed after questionnaire and vital signs determinations and before study drug administration.
e.
PPD or QuantiFERON-TB Gold testing at Weeks 48, 96, 144, 192, 240, 288, 336, 384 and 408/ET.  No annual TB test should be done at Week 408 or at ET if already done at 
Week 384 or later.
f.
Microscopic urinalysis will be performed at any visit if dipstick UA is abnormal (protein greater than a trace, blood greaterthan 5 – 10 Ery/ul, moderate or large ketone count 
or glucose greater than 50 mg/dL).
g.
If an ANA result is positive, anti-dsDNA will be performed automatically.
h.
For subjects who are age 13 or older at the M06-807 Baseline Visit, a CDAI will be completed at each visit.
i.
For subjects who are age 10 or older at the M06-807 Baseline Visit, an IMPACT III Assessment will be completed at Baseline, Weeks 12, 24, 48, 72, 108, 120, 144, 168, 192, 
216, 240, 264, 288, 312, 336, 360, 384, 408/ETC and unscheduled visits.
j.
If the height velocity is 0 and, in the opinion of the investigator, a subject is no longer growing, the x-ray for bone age and the determination of serum bone markers can be 
omitted.
k.
In addition to blood draws every 24 weeks, PK and AAA blood draws to be performed if subject meets flare criteria and dose escalated to ew dosing.

Adalimumab
M06-807 Protocol Amendment 7 for Poland
EudraCT 2007-006494-90
33
Table 1.
Study Activities (Continued)
l.
All AEs, including SAEs, will be captured throughout the study from the time that the subject signs the Informed Consent Form.  SAEs will be captured throughout the 70 day 
follow-up period (if applicable).
m.
If an unscheduled visit is performed to change the frequency or dose of study drug, study drug may be dispensed.

Adalimumab
M06-807 Protocol Amendment 7 for Poland
EudraCT 2007-006494-90
34
5.3.1.1
Study Procedures
The M06-806 Week 52 visit will serve as the Baseline visit for the M06-807 study.  The 
study procedures outlined in Table 1 are discussed in detail in this section, with the 
exception of the collection of AE information (discussed in Section 6.0).  All study data 
will be recorded in source documents and on the appropriate CRFs.  The site will call the 
subjects at Weeks 132, 156, 180, 204, 228, 252, 276, 300, 324, 348, 372 and 396 in order 
to collect any safety information from the subject as illustrated in Table 1.
The visit window for all scheduled visits is ± 7 days calculated from the Baseline visit of 
the M06-807 study.
Inclusion/Exclusion Criteria
A subject will be excluded from this study if he/she does not meet all inclusion criteria or 
meets any of the exclusion criteria of Protocol M06-807.
Informed Consent
A signed Informed Consent Form (ICF) will be obtained from a subject of legal age (in 
the state of residence) or from the parent or legal guardian (as appropriate)of a subject 
who is not of legal age before any study related procedures are undertaken or before any 
medications are discontinued for the purpose of this study.  Additionally, an informed 
consent will be required from those subjects who were not of legal age at the onset of this 
study but become of legal age during the course of the study.
In keeping with each institutions IRB requirements, an Informed Assent may also be 
required from pediatric subjects.  Pediatric subjects will be included in all discussions in 
order to obtain their signature on an assent form.  Details about how informed consent 
will be obtained and documented are provided in Section 9.3.
If an updated informed consent is approved after a subject has completed or terminated 
early from the study, but is within the 70-day follow-up window, the subject will not be 
required to return to the site for the purposes of signing the updated ICF.  The subject of 

Adalimumab
M06-807 Protocol Amendment 7 for Poland
EudraCT 2007-006494-90
35
legal age, parent or legal guardian (as appropriate) should be contacted regarding any 
changes and the documentation of the contact should be present in the subjects source.
Previous and Concomitant Medications
Changes in concomitant medications will be assessed at each study visit from Baseline 
through the Week 408/ET visit.  Concomitant medications that are taken prior to the 
first dose of study drug administration for this study will be captured in the subjects 
casebook from the previous study (M06-806).  They will not be required to be captured in 
the subjects casebook of the M06-807 study unless they were ongoing at the Week 52 
visit of the M06-806 study.  Ongoing concomitant medications from the M06-806 study 
will be transcribed into the subjects M06-807 casebook.
Subjects of legal age or the parent or guardian (as appropriate) of subjects who are not of 
legal age will be provided with a medication log (see Appendix O) to record all 
medications the subject takes throughout the study.  This log must be returned for review 
at every study visit.
Serum/Urine Pregnancy Test
All female subjects who are experiencing menses, are nearing sexual maturation (in the 
opinion of the Investigator), or who are of child-bearing potential, will undergo a urine 
pregnancy test at each visit.  Urine pregnancy tests will be performed locally by 
designated study personnel.  If a urine pregnancy test is positive, a serum pregnancy test 
must be performed by the central laboratory.  If the serum pregnancy test is positive, the 
subject will be removed from the study.  
A lactating or pregnant female will not be eligible for participation in this study.
TB Testing
For subjects with a negative test at Screening visit from parent study (Study M06-806), an 
annual PPD or QuantiFERON-TB Gold re-test will be required.  If one of the annual tests 

Adalimumab
M06-807 Protocol Amendment 7 for Poland
EudraCT 2007-006494-90
36
has a positive test result, the matter should be discussed with the medical monitor prior to 
starting any prophylaxis.
A PPD skin test (alternatively, also known as tuberculin skin test) must be placed or the 
QuantiFERON®-TB Gold test (or equivalent) must be performed for subjects with a 
negative test at Screening visit after the amended protocol is approved by IRB/IEC 
including those with a prior history of Bacille Calmette-Guérin (BCG) administration at 
the time the subject reaches one of the scheduled visits:  Weeks 48, 96, 144, 192, 240, 
288, 336 and 384.  TB testing should not be done at Week 408 or at the ET visit if a test 
was done at week 384 or later.
If the subject is experiencing signs or symptoms suspicious for TB or something has 
changed in the subject's medical history to warrant a repeat test before the next scheduled 
annual TB re-test, the case must be discussed with the AbbVie Medical Monitor.
For the PPD test:
●
The subject will be required to have the PPD test read by a licensed healthcare 
professional 48 to 72 hours after placement (or as per local guidelines), when 
the induration is maximal.  An induration (not erythema) of 5 mm or greater 
will be considered as PPD positive, irrespective of BCG status or local 
guidelines.  The absence of induration should be recorded, as "0 mm," not 
"negative."
●
If there are sites where the available testing materials are not accepted, an 
alternative tuberculin skin test may be substituted, but the method must be 
submitted and approved by AbbVie prior to use with study subjects.
●
If QuantiFERON®-TB Gold (or equivalent) result is indeterminate, the test 
should be repeated with a fresh blood sample.  If a repeat QuantiFERON®-TB 
Gold (or equivalent) result is indeterminate, this should be considered a 
positive test result and the case must be discussed with the AbbVie Medical 
Monitor.

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M06-807 Protocol Amendment 7 for Poland
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In the event both a PPD test and QuantiFERON-TB Gold test are performed, the result of 
the QuantiFERON-TB Gold test will supersede the result of the PPD test.
Newly initiated prophylactic treatment should be captured in the source documents and on 
the concomitant medications page in the CRF.  Prior therapy should be captured in the 
appropriate medical history CRF.
For sites participating in the Czech Republic, the following local requirements will also 
be applicable:
●
A pulmonologist will be responsible to obtain a detailed medical history with 
respect to TB exposure.  This information needs to include BCG vaccination, 
cohabitation with individuals who have had TB, and/or who reside or work in 
TB endemic locations.  The information obtained by the pulmonologist must 
be documented in the subject's source note, dated and signed by the 
pulmonologist.
●
A pulmonologist must review the results of the PPD skin test and the CXR and 
has to give his/her opinion about the eligibility of each subject to continue in 
the study.  This opinion must be documented in writing in the subject's source 
documents.
All subjects with a positive PPD need to be approved for continuation in the trial by both 
the Czech pulmonologist and the AbbVie Medical Monitor and all such subjects need to 
receive prophylaxis for latent TB.  Under no circumstances can a subject with a positive 
PPD result and no prior history of treatment for active or latent TB be allowed to continue 
in this trial.
Vital Signs
Vital sign determinations of sitting blood pressure, heart rate, respiratory rate, body 
temperature, weight and height will be obtained at each visit.  All measurements will be 
recorded in metric units when applicable. 

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Weight measurements will be obtained using the same measuring instrument at each visit 
and measured with subjects wearing only undergarments.  Height measurements will be 
obtained using the same measuring equipment at each visit and performed on subjects 
with their shoes taken off.
Physical Examination
A physical examination will be performed at each visit.  A count of the number of 
cutaneous fistulas draining upon gentle compression will be performed during each 
physical exam.30  Fistulas will be classified as abdominal or perianal/anal.
Physical exam abnormalities (including fistulas and fissures) noted by the Investigator 
will be evaluated and documented on the corresponding source documents.  Any new 
abnormalities or worsening of pre-existing conditions should be captured as AEs.
Clinical Laboratory Tests 
Samples will be obtained for the laboratory tests listed in Table 2 at all study visits.  
Blood draws should be performed after questionnaires (PCDAI, IMPACT III 
Questionnaire, etc.) and vital sign determinations during a study visit, and before study 
drug administration.
ICON central laboratory will be utilized to process and provide results for the general 
laboratory tests.  All abnormal laboratory test results that are considered clinically 
significant by the Investigator will be followed to a satisfactory resolution.
ICON will provide instructions regarding the collection, processing and shipping of these 
samples.

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Table 2.
Clinical Laboratory Tests
Hematologya
Clinical Chemistry
Urinalysisb
Serum Bone Markers
Hematocrit
Hemoglobin
Red Blood Cell (RBC) 
count
White Blood Cell 
(WBC) count
Neutrophils
Bands
Lymphocytes
Monocytes
Basophils
Eosinophils
Platelet count (estimate 
not acceptable)
Blood Urea Nitrogen 
(BUN)
Creatinine
Total bilirubin
Serum glutamic-pyruvic 
transaminase 
(SGPT/ALT)
Serum glutamic-
oxaloacetic
transaminase 
(SGOT/AST)
Alkaline phosphatase
Sodium
Potassium
Calcium
Inorganic phosphorus
Uric acid
Cholesterol
Total protein
Glucose
Triglycerides
Albumin
Specific gravity
Ketones
pH
Protein
Blood
Glucose
Osteocalcin
Bone-specific alkaline 
phosphatase (BSAP) 
bone resorption (Ntx)
a.
Basic hematology testing performed on instrumentation does not include band reporting.  When Hematology 
results reflex to a Manual Differential, if there is a band result over 5, it is reported.
b.
Microscopic urinalysis will be performed at any visits if dipstick UA is abnormal (protein greater than a trace, 
blood greater than 5 - 10 Ery/ul, moderate or large ketone count or glucose greater than 50 mg/dL).
Immunologic Laboratory Assessments  
CRP, adalimumab levels, anti-adalimumab antibody levels (AAA) and antinuclear 
antibody (ANA) assessments will be performed as indicated in Table 1.  If an ANA result 
is positive, anti-double-stranded DNA (anti-dsDNA) will be performed automatically.  All 
CRP, ANA, anti-dsDNA will be performed by the central laboratory.
Erythrocyte Sedimentation Rate (ESR) assessments will be performed at all visits as 
indicated in Table 1.  ESR assessments will be performed by the sites local laboratory.

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Markers of Bone Metabolism 
Serum markers of bone metabolism will be measured as indicated in Table 1.  The bone 
formation markers to be measured are osteocalcin, bone-specific alkaline phosphatase 
(BSAP), and bone resorption (Ntx).
Urinalysis
Urine will be assessed by dipstick at each visit (done locally).  All results, including 
abnormalities, will be captured in source documentation and on the appropriate CRF.  
If, at any visit, the dipstick UA results are abnormal, the central lab will perform a 
microscopic urinalysis.  Abnormal is defined as protein greater than a trace, blood greater 
than 5 - 10 Ery/ul, moderate or large ketone count or glucose greater than 50 mg/dL.
Pediatric Crohns Disease Activity Index (PCDAI)
The PCDAI score will be calculated at each visit.  When completing the PCDAI, the 
HCT, albumin, and ESR values will be utilized from the same study visit. 
An example of the PCDAI is located in Appendix G.  Instructions for completing the 
PCDAI score is located in Appendix H.
Crohns Disease Activity Index (CDAI)
At each visit, a CDAI score will be calculated for subjects who are age 13 or older at the 
M06-807 Baseline Visit.  The CDAI score will be calculated utilizing the subject diary 
and the HCT value from the same study visit.  A copy of the CDAI subject diary is 
located in Appendix H.
When completing question five (5) ("Taking Lomotil/Imodium/Loperamide/opiates for 
diarrhea, 0 = no, 1 = yes") on the CDAI, "no" should be answered if a subject is taking an 
opiate(s) solely for pain.

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For the CDAI questions regarding presence of anal fistulas and other fistulas, all fistulas 
detectable on physical examination (draining and non-draining) should be captured on the 
CDAI CRF page and calculated into the CDAI score.
The calculation of the CDAI score is in Appendix I.
IMPACT III Questionnaire
Subjects ≥ 10 years old at the Baseline visit of the M06-807 study will complete an 
IMPACT III questionnaire as indicated in Table 1.  A copy of the questionnaire is located 
in Appendix K. 
The IMPACT III will be recorded directly onto the CRF.  The completed CRF will be 
considered source documentation for this assessment.
Outcomes
The Unscheduled Outpatient Visits, Emergency Room Visits and Hospitalization 
Questionnaire and the Work Productivity and Activity Impairment Questionnaire:  
Crohn's Disease (WPAI-CD) will be completed at each visit except the Unscheduled Visit 
(Appendix N, Appendix T).
The subjects parent or legal guardian will complete the WPAI directly onto the CRF.  The 
completed CRF will be considered source documentation for this assessment.
If a subject is no longer taken care of by their parent or legal guardian, the WPAI-CD 
should not be completed (neither by the subject's parent or legal guardian nor by the 
subject himself/herself).
Bone Age
An x-ray of the wrist for the assessment of bone age will be obtained as indicated in 
Table 1.  Sites should use the Greulich and Pyle method for reading the x-ray.31  The x-ray 
report requires the signature of the radiologist who read the films.  The bone age that is 
determined by the x-ray should be recorded on the CRF.  

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Anthropometric Evaluations
Height and weight obtained at each visit will be used by AbbVie Data Management and 
Statistical groups for determination of BMI and "z" score (observed height velocity 
(cm/yr) - mean height velocity for age and sex (cm/yr)/SD of the mean) for height.
Adverse Events
Adverse events will be assessed at every study visit from Baseline through the 
Week 408/ET visit.  Any AEs, which are ongoing in the M06-806 study, will be 
transcribed onto the M06-807 source documents and CRF(s).
For those subjects who complete the study or terminate early, a phone call will be made 
70 days after the last dose of study drug to obtain follow-up information on any ongoing 
and any new AEs.  See Section 6.0 and Appendix M for additional information.
Study Drug Administration
At each study visit, the subject or their trained designated friend, family member or health 
care professional will perform study drug injections under the supervision of a trained 
medical professional to reinforce proper aseptic SC injection technique.  Subjects or a 
trained designated friend, family member or health care professional will perform 
injections of study drug in the subjects home during weeks they are not in for scheduled 
clinic visits.  Subjects may return to the study site for injections in between study visits if 
subject or a trained designated friend, family member or health care professional cannot 
inject the study medication.
Subjects will maintain a dosing diary for all study drug administered outside study visits, 
i.e., at home.  In the diary, the date, initials of the person administering the study drug, 
time study drug is administered, kit number and the dose administered will be recorded.  
Subjects must return this diary and it will be reviewed and verified for compliance at each 
visit by the research personnel at the study center.  All relevant dosing information will be 
retained by the study coordinator and transcribed onto a drug accountability form at each 
visit.  Additionally, any discernible departure from the protocol regarding study drug 

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administration will be recorded on source documents and appropriate drug accountability 
forms.  A sample of the Subject Dosing Diary is presented in Appendix P.
At all office visits subjects should be observed after study drug administration, until 
judged clinically stable by the study personnel.  If an anaphylactic reaction or other 
serious allergic reaction occurs, administration of study drug should be discontinued 
immediately and appropriate therapy initiated.  When dosing at home, subjects should be 
instructed to contact the site immediately with any signs or symptoms of a reaction.
The dosing dates, for all doses of study drug, should be calculated from the Baseline visit 
date.  The Baseline visit date for this study is 364 ± 7 days from the Baseline Visit date of 
M06-806.  A +/-3 day window is allowable for scheduled study dosing dates.
For subjects that deviate from this dosing window, every effort should be made to bring 
the subject back to the original dosing schedule as soon as possible.  For situations where 
bringing the subject back on the original dosing schedule will cause the dose to be out of 
the +/-3 day window, please contact the Medical Monitor for additional instructions.
Randomization and Assignment of Subject Numbers
All subjects will be centrally registered using an IVRS.  This is an open-label study; 
subjects will not be randomized.  The telephone number and call in directions for the 
IVRS will be provided to each site.  Subjects will keep their study subject number from 
the previous double-blind study (M06-806).
5.3.2
Drug Concentration Measurements
Blood samples for the assay of adalimumab and AAA serum concentrations will be 
collected at Baseline and every 24 weeks thereafter.  In addition, blood samples for 
adalimumab and AAA concentration analysis will also be collected if a subject meets flare 
criteria and dose escalated to ew dosing.  Study visits in which blood samples will be 
collected are listed in Table 1.  At each visit, blood samples will be collected prior to 
study drug administration at each visit.

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The time that each blood sample is collected will be recorded to the nearest minute in the 
source documents and on the appropriate CRF.
5.3.2.1
Collection of Samples for Analysis
Collection of Samples for Adalimumab Analysis
Blood samples for adalimumab analysis will be collected by venipuncture into 
appropriately labeled 4-mL evacuated serum collection tubes without gel separator at 
visits indicated in Table 1.  All samples will be obtained immediately prior to dosing at 
visits indicated in Table 1.  Sufficient blood will be collected to provide approximately 
2 mL serum.  Allow the blood to clot for 30 minutes at room temperature before 
centrifugation.
A minimum of 17 samples are planned to be collected per subject for the analysis of 
adalimumab concentrations.
For subjects who have a flare and require switching to higher dose or change dose to 
ew dosing, up to 2 additional samples are planned to be collected per subject for 
adalimumab analysis.
Collection of Samples for AAA Analysis
Blood samples for AAA assay will be collected by venipuncture into appropriately 
labeled 4-mL evacuated serum collection tubes without gel separator at visits indicated in 
Table 1.  All samples will be obtained immediately prior to dosing at visits indicated in 
Table 1.  Sufficient blood will be collected to provide approximately 2 mL serum.  Blood 
will be allowed to clot for 30 minutes at room temperature before centrifugation.
A minimum of 17 blood samples are planned to be collected per subject for AAA 
analysis.

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For subjects who have a flare and require switching to higher dose or change dose to 
ew dosing, up to 2 additional samples are planned to be collected per subject for AAA 
analysis.
5.3.2.2
Handling/Processing of Samples
The blood samples for adalimumab and AAA, assay will be centrifuged within 30 to 
60 minutes of collection to separate the serum.  The serum samples will be transferred 
using plastic pipettes into screw-capped polypropylene vials labeled with the type of 
sample (serum, SRM), the protocol number, subject number, the study week and the assay 
(PK-Adalimumab, AAA).  The serum samples will be frozen within 2 hours after 
collection and will remain frozen in a –20°C or colder until shipped.  Sites that do not 
have access to a –20°C or colder freezer will need to ship the samples the day they are 
collected.  (Detailed instructions provided in the ICON Laboratory Manual).
5.3.2.3
Disposition of Samples
The PK and AAA samples will be shipped to ICON with all other samples being shipped 
to ICON.  Refer to the ICON Lab Manual for further instruction.  Neither AbbVie nor 
ICON will supply dry ice for this study.  Study sites will identify a dry ice source and 
purchase the necessary dry ice.
5.3.2.4
Measurement Methods
Serum concentrations of adalimumab will be determined using a validated ELISA method 
under the supervision of the Drug Analysis Department at AbbVie.  Only serum samples 
that have adalimumab levels < 2.0 μg/mL will be selected for AAA concentration 
measurement.
Serum concentrations of AAA will be determined using a validated ELISA method under 
the supervision of the Drug Analysis Department at AbbVie.

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5.3.3
Efficacy Variables
Efficacy will be evaluated based on the proportion of subjects who maintain PCDAI 
clinical response at each visit.  Clinical response is defined as PCDAI decrease 
≥15 points from the M06-806 Baseline score.
Other measures of disease activity being assessed in this study will be summarized, 
including CDAI scores, IMPACT III scores, WPAI-CD Caregiver, z-score for height 
velocity, bone x-ray, serological markers of bone metabolism, healthcare resource 
utilization (unscheduled outpatient visits), adalimumab levels and anti-adalimumab levels 
(AAA).
5.3.4
Safety Variables
AEs, laboratory data, physical examinations and vital signs are the safety parameters and 
these will be assessed throughout the study.
Treatment-emergent events will be summarized and reported by treatment group and by 
AAA status (AAA+ versus AAA-).
5.3.5
Pharmacokinetic Variables
Serum concentrations of adalimumab and AAA will be determined from samples 
collected at the study visits listed in Table 1.
5.4
Removal of Subjects from Therapy or Assessment
5.4.1
Discontinuation of Individual Subjects
Subjects will be withdrawn from the study immediately if any of the following occur:  
●
Clinically significant abnormal laboratory results or AEs, which rule out 
continuation of the study drug, as determined by the Investigator and the 
Medical Monitor.
●
The Investigator believes it is in the best interest of the subject.
●
The subject or subjects legal guardian requests withdrawal from the study.

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●
Selection criteria violation was noted after the subject started study drug, as 
determined by the Medical Monitor (see Sections 5.2.1 and 5.2.2).
●
Introduction of prohibited medications or prohibited concomitant medication
dosages as determined by the Medical Monitor.
●
The subject is diagnosed with a malignancy except for localized 
non-melanoma skin cancer.  Discontinuation for carcinoma in-situ is at the 
discretion of the Investigator.
●
The subject is diagnosed with dysplasia of the gastrointestinal tract.
●
A female subject who becomes pregnant.
If the subject prematurely discontinues study drug use, the procedures outlined for the 
Week 408/ET Visit must be completed within 2 weeks of the last dose of study drug, and 
preferably prior to the initiation of another therapy.  These procedures should not interfere 
with the initiation of any new treatments or therapeutic modalities that the Investigator 
feels are necessary to treat the subjects condition.  Following discontinuation of the study 
drug, the subject will be treated in accordance with the Investigators best clinical 
judgment.
Subjects who prematurely discontinue from the study will not be replaced.  The date of 
last dose and reason for premature discontinuation will be recorded in the source 
document and on the appropriate CRF.
5.4.2
Discontinuation of Entire Study
AbbVie reserves the right to discontinue the study at any time and to remove all study 
materials from the site.  Possible reasons for termination of the study include, but are not 
limited to:
●
Safety concerns based on reported data
●
Unsatisfactory enrollment with respect to quantity or quality
●
Inaccurate or incomplete data collection
●
Falsification of records

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●
Failure to adhere to the protocol
5.4.3
Stopping Rules
An independent Data Monitoring Committee (DMC) will meet to discuss data from the 
study approximately every six (6) months or at a frequency determined by the DMC and 
render their recommendation for either the continuation of the study or an amendment to 
the study.  A Sponsor Steering Committee (SSC), composed of senior executives not 
directly participating in this study, will make final decisions based on DMC 
recommendations.
5.5
Treatments
5.5.1
Treatments Administered
Study drug will be provided as a SC injection solution in pre-filled syringes containing 
adalimumab 40 mg/0.8 mL or adalimumab 20 mg/0.4 mL or in vials containing 
adalimumab 40 mg/0.8mL.
Subjects who enroll into the study from blinded therapy in Study M06-806 will receive 
open-label therapy at a dose dependent on their body weight.  Subjects who weigh ≥40 kg 
will receive 40 mg eow of adalimumab, while subjects who weigh < 40 kg will receive 
20 mg eow of adalimumab.  Beginning from Week 8, subjects who have a disease flare 
may be switched to ew treatment at the same dose of adalimumab received while on eow 
treatment.
Subjects who enroll into the study from open-label therapy in Study M06-806 will 
continue to receive the same dose they were receiving (i.e., 40 mg ew or 20 mg ew) at the 
Week 52 visit of the M06-806 study.
Subjects who develop a flare while receiving ew open-label therapy or have a PCDAI 
score ≥ 15 points when compared to their Baseline (Week 52 of M06-806) PCDAI score 

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(regardless of study visit), may be discontinued from the study at the discretion of the 
Investigator.
Beginning from Week 8, the dose of adalimumab may be increased to 40 mg, at the 
discretion of the investigator, for subjects whose body weight has increased from < 40 kg 
to ≥ 40 kg from the study Baseline visit.  The site will enter the subject's body weight into 
the IVRS and the dose will be adjusted, if applicable.
The dose of adalimumab may be decreased to the next lower treatment level as applicable, 
at the discretion of the Investigator and prior approval from the medical monitor, for 
subjects whose body weight has decreased from ≥ 40 kg to < 40 kg from the previous 
visit.  The site will enter the subject's body weight into the IVRS and the dose will be 
adjusted, if applicable.
Subjects who responded to treatment defined as a) an improvement of at least 15 points in 
PCDAI compared to the last observation prior to dose escalation in patients who 
dose-escalated or b) an improvement of at least 15 points in PCDAI compared to Baseline 
of Study M06-806 in patients who did not dose-escalate) may have their dosage frequency 
decreased from ew to eow dosing.  The investigator should receive prior approval from 
the medical monitor before taking any action with regard to the dose frequency decrease.  
At least 8 weeks after dose frequency decrease, subjects who still responded to treatment 
(as defined above) may have their dosage decreased (subjects who weigh ≥ 40 kg will 
receive 20 mg eow of adalimumab, while subjects who weigh < 40 kg will receive 10 mg 
eow of adalimumab).  The investigator should receive prior approval from the medical 
monitor before taking any action with regard to dose decrease.
Subjects who experience a disease flare may re-increase their dosage or dose frequency to 
the next higher treatment level regardless of prior dose or dose frequency decrease. 
Simultaneous dose adjustment based on change of body weight as well as based on 
diseases status (response/flare) is prohibited.

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5.5.2
Identity of Investigational Product
The individual study drug information is presented in Table 3.  Pre-filled syringes (used 
for 40 mg/0.8 mL or 20 mg/0.4 mL doses) and 40 mg/0.8 mL vials (used for 10 mg dose) 
will be provided for this open-label clinical study.
Table 3.
Identity of Investigational Products
Study Drug
Formulation
Manufacturer
Adalimumab
40 mg/0.8 mL or 20 mg/0.4 mL
Adalimumab/Mannitol, Citric acid monohydrate, Sodium citrate, 
Disodium phosphate dihydrate, Sodium dihydrogen phosphate 
dihydrate, Sodium chloride, Polysorbate 80, Water for injections, 
Sodium hydroxide added as necessary to adjust pH
AbbVie/Abbott
Adalimumab
40 mg/0.8 mL (used for 10 mg dose)
Adalimumab/Mannitol, Citric acid monohydrate, Sodium citrate, 
Disodium phosphate dihydrate, Sodium dihydrogen phosphate 
dihydrate, Sodium chloride, Polysorbate 80, Water for injections, 
Sodium hydroxide added as necessary to adjust pH
AbbVie/Abbott
5.5.2.1
Packaging and Labeling
Two pre-filled syringes or vials will be provided in a dosing kit carton (see Table 4).  
Each kit will be labeled as required per country requirement.  Labels must remain affixed 
to the kit.
Detailed instructions and training for the administration of study supplies are provided in 
Appendix Q.
Table 4.
Study Drug Packaging and Administration
Open-label Pre-filled Syringes
Open-label kit cartons containing two pre-filled 
syringes of adalimumab 40 mg/0.8 mL.
Open-label kit cartons containing two pre-filled 
syringes of adalimumab 20 mg/0.4 mL.
Open-label Vials (used for 10 mg dose)
Open-label kit cartons containing two vials of adalimumab 40 mg/0.8 mL.

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5.5.2.2
Storage and Disposition of Study Drug
Pre-filled syringes and vials are to be stored protected from light at 2° to 8°C/36° to 46°F.  
DO NOT FREEZE.  A storage temperature log is to be maintained at the site to document 
proper storage conditions.  The refrigerator temperature must be recorded on every 
business day on a temperature log to record proper function.  Malfunctions must be 
reported to the sponsor immediately.  Study drug should be quarantined and not dispensed 
until AbbVie GPRD or AbbVie Temperature Excursion Management System (ATEMS) 
deems the medication as acceptable.  All clinical supplies must be stored and locked in a 
secure place until they are dispensed for subject use or are returned to AbbVie.
Investigational products are for investigational use only, and are to be used only within 
the context of this study.
5.5.3
Method of Assigning Subjects to Treatment Groups
This is an open-label study; all subjects will be receiving adalimumab.
All subjects will be centrally registered using an IVRS.  The telephone number and call-in 
directions for the IVRS will be provided to each site.  Subjects will keep their study 
subject number from the previous study (M06-806).
Study drug will be administered at the study visits summarized in Table 1 and detailed in 
Section 5.3.1.1.
5.5.4
Selection and Timing of Dose for Each Subject
Subjects who enroll into the study from blinded therapy in Study M06-806 will receive 
open-label therapy at a dose dependent on their body weight.  Subjects who weigh ≥40 kg 
will receive 40 mg eow of adalimumab, while subjects who weigh < 40 kg will receive 
20 mg eow of adalimumab.  Beginning from Week 8, subjects who have a disease flare 
may be switched to ew treatment at the same dose of adalimumab received while on eow 
treatment.

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Subjects who enroll into the study from open-label therapy in Study M06-806 will 
continue to receive the same dose they were receiving (i.e., 40 mg ew or 20 mg ew) at the 
Week 52 visit of the M06-806 study. 
Subjects who develop a flare while receiving ew open-label therapy or have a PCDAI 
score ≥ 15 points when compared to their Baseline (the Week 52 visit of the 
M06-806 study) PCDAI score (regardless of study visit), may be discontinued from the 
study at the discretion of the Investigator.
The dose of adalimumab may be decreased to the next lower treatment level as applicable 
at the discretion of the Investigator and prior approval from the medical monitor, for 
subjects whose body weight has decreased from ≥ 40 kg to < 40 kg from the previous 
visit.  The site will enter the subjects' body weight into the IVRS and the dose will be 
adjusted, if applicable.
Subjects who responded to treatment defined as a) an improvement of at least 15 points in 
PCDAI compared to the last observation prior to dose escalation in patients who 
dose-escalated or b) an improvement of at least 15 points in PCDAI compared to Baseline 
of Study M06-806 in patients who did not dose-escalate) may have their dosage frequency 
decreased from ew to eow dosing.  The investigator should receive prior approval from 
the medical monitor before taking any action with regard to the dose frequency decrease.  
At least 8 weeks after dose frequency decrease, subjects who still responded to treatment 
(as defined above) may have their dosage decreased (subjects who weigh ≥ 40 kg will 
receive 20 mg eow of adalimumab, while subjects who weigh < 40 kg will receive 10 mg 
eow of adalimumab).  The investigator should receive prior approval from the medical 
monitor before taking any action with regard to dose decrease.
Subjects who experience a disease flare may re-increase their dosage or dose frequency to 
the next higher treatment level regardless of prior dose or dose frequency decrease. 
Simultaneous dose adjustment based on change of body weight as well as based on 
diseases status (response/flare) is prohibited.

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The Baseline Visit date for this study should be 364 ± 7 days from Baseline Visit date of 
M06-806 study.  All clinic visits for the subject should be scheduled on the same day as 
the Baseline visit for this study.  For home administration of drug, subjects will be 
instructed to inject study drug on the same day of the week as their Baseline visit day.  
Subjects must inject within a +/-3 day window of this day.  If the subject is out of the 
dosing window, the Medical Monitor should be contacted to determine the timing of the 
next dose.  The subject must record all dosing information on the subject dosing diary 
(Appendix P).
5.5.5
Blinding
This is an open-label study.
5.5.6
Treatment Compliance
The Investigator or his/her designated representatives will administer study drug only to 
subjects enrolled in the study. 
In order to document compliance with the treatment regimen, all pre-filled syringes and 
vials will be counted and documented in source documents and on the appropriate drug 
accountability form.
5.5.7
Drug Accountability
The Investigator or designee will verify that study drug supplies are received intact, at the 
appropriate temperature, and in the correct amounts from the drug depot.  This will be 
documented by signing and dating the Proof of Receipt (POR) or similar document.  The 
original POR or similar document will be kept in the site files as a record of what was 
received.  An accurate running inventory of study drug will be kept by the site, and will 
include the kit number, lot number(s), the number of pre-filled syringes or vials 
dispensed, and the date study drug was dispensed for each subject.  An overall 
accountability of the study drug will be performed and verified by the Clinical Research 
Associate (CRA) throughout the study and at the site close-out visit.  All unused pre-filled 
syringes and vials will be inventoried and returned to an identified vendor for disposal as 

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designated by AbbVie.  A copy of the Drug Accountability Form, in accordance with 
instructions provided by the CRA, will also be included in the Returned Goods for 
disposal shipment.  A sample Drug Accountability Form is included in Appendix S.  A 
copy of the Drug Accountability Disposal Form, in accordance with instructions provided 
by the CRA, will also be included in the Pharmacy Binder provided to the site.
All used (expelled) pre-filled syringes and vials will be inventoried by the site and 
verified by the CRA.  The used syringes and vials will be discarded on site, using 
appropriate biohazard precautions.  CRAs and site staff will complete study drug 
accountability via study drug logs, source documents, verification of empty used syringe 
kit or vials boxes, subject diaries and by visually counting the syringes in the sharps 
container whenever possible.  Used sharps containers should never be opened.  Each 
subject will be given their own sharps disposal container to store expelled/used syringes.  
Sharps containers should be returned by the subject at each visit, for accountability and 
compliance purposes.  New containers will be issued to subjects as necessary.  Once the 
CRA has verified drug accountability at the site, the site staff and CRA will sign off that 
the expelled pre-filled syringes and used vials have been destroyed.
5.6
Discussion and Justification of Study Design
5.6.1
Discussion of Study Design and Choice of Control Groups
The design of this clinical study was chosen to demonstrate adalimumab as an effective 
therapy for maintaining clinical response in pediatric subjects with CD and to gather 
long-term safety and tolerability data in this subject population.
5.6.2
Appropriateness of Measurements
Standard statistical, clinical, and laboratory procedures will be utilized in this study.  All 
efficacy measurements in this study are standard for assessing disease activity in pediatric 
subjects with Crohns disease.  All clinical and laboratory procedures in this study are 
standard and generally accepted.

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5.6.3
Suitability of Subject Population
Pediatric subjects with CD who have participated in and successfully completed 
Protocol M06-806 through Week 52 and who meet all of the inclusion and none of the 
exclusion criteria are eligible for this study.
5.6.4
Selection of Doses in the Study
The results of the pivotal adalimumab adult CD maintenance trial M02-404, in 
conjunction with results from adalimumab CD Study M02-433, support a maintenance 
dose of adalimumab 40 mg eow.  Data also suggest that patients who lose response to 
adalimumab at 40 mg eow can be dose-escalated to 40 mg weekly with the potential of 
regaining clinical response.  The proposed dosing regimen for Study M06-807 before 
Amendment 4 was developed using an analogous approach as that studied in the adult CD 
population.  Population pharmacokinetic modeling of serum adalimumab concentration 
data from pediatric subjects with JRA was used to identify doses to be evaluated in the 
current study in children with CD before Amendment 4.  A model based on the JRA 
population was chosen because the body weight range would closely parallel that in a 
juvenile CD population.  Escalation to weekly dosing would provide average adalimumab 
concentrations at steady state about twice that observed with every other week dosing.  
However, these concentrations are within the range of systemic exposures that were safely 
studied in adult subjects with CD.
After completion of Study M06-806 and consideration of efficacy, safety and population 
pharmacokinetic results in conjunction with exposure-response modeling and simulation 
both the Low-Dose and High-Dose treatment provided evidence of efficacy and safety.  
Therefore, in order to minimize the systemic exposures to study drug to the lowest doses 
necessary in children with CD, Amendment 4 provides investigators with the option of 
dose de-escalation by reducing the dose or switching from ew to eow based on the clinical 
status of the individual patient.  In addition, since the 10 mg eow dose was efficacious in 
subjects weighing < 40 kg in Study M06-806 patients will have the option to be switched 

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to this dose based on their body weight and clinical status at the discretion of the 
investigator.
6.0
Complaints
A Complaint is any written, electronic, or oral communication that alleges deficiencies 
related to the physical characteristics, identity, quality, purity, potency, durability, 
reliability, safety, effectiveness, or performance of a product/device after it is released for 
distribution.
The investigational product in this trial contains both: 
●
Biologic compound(s) and
●
Device component(s) (pre-filled syringe)
Complaints associated with any component of this investigational product must be 
reported to the Sponsor (Section 6.2.2).  For adverse events, please refer to Sections 6.1 
through 6.1.6.  For product complaints, please refer to Section 6.2.
6.1
Medical Complaints
6.1.1
Definitions
6.1.1.1
Adverse Event
The Investigator will monitor each subject for clinical and laboratory evidence of AEs on 
a routine basis throughout the study.  The Investigator will assess and record any AE in 
detail including the date of onset, description, severity, time course, duration and 
outcome, relationship of the AE to study drug, an event diagnosis, if known, and any 
action(s) taken.  For SAEs not considered "probably related" to study drug, the 
Investigator must provide another cause of event.  For AEs to be considered sporadic, the 
events must be of similar nature and severity.  AEs, whether in response to a query, 
observed by site personnel, or reported spontaneously by the subject will be recorded in 
source documentation and on the appropriate CRF page.

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All AEs will be followed to a satisfactory conclusion.
An AE is defined as any untoward medical occurrence in a patient or clinical investigation 
subject administered a pharmaceutical product and which does not necessarily have a 
causal relationship with this treatment.  An AE can therefore be any unfavorable and 
unintended sign (including an abnormal laboratory finding), symptom, or disease 
temporally associated with the use of a medicinal (investigational) product, whether or not 
the event is considered causally related to the use of the product.
Such an event can result from use of the drug as stipulated in the protocol or labeling, as 
well as from accidental or intentional overdose, drug abuse, or drug withdrawal.  Any 
worsening of a pre-existing condition or illness is considered an AE.  Laboratory 
abnormalities and changes in vital signs are considered to be AEs only if they result in 
discontinuation from the study, necessitate therapeutic medical intervention, and/or if the 
Investigator considers them to be AEs.
An elective surgery/procedure scheduled to occur during a study will not be considered an 
AE if the surgery/procedure is being performed for a pre-existing condition and the 
surgery/procedure has been pre-planned prior to study entry.  However, if the pre-existing 
condition deteriorates unexpectedly during the study (e.g., surgery performed earlier than 
planned), then the deterioration of the condition for which the elective surgery/procedure 
is being done will be considered an AE.
6.1.1.2
Serious Adverse Events
If an AE meets any of the following criteria, it is to be reported to AbbVie as an SAE 
within 24 hours of the site being made aware of the SAE.  Additionally, if follow-up 
information is received, it must also be reported to AbbVie within 24 hours of being made 
aware of the information.

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Death of Subject
An event that results in the death of a subject.
Life-Threatening
An event that, in the opinion of the Investigator, will have resulted in 
immediate fatality if medical intervention had not been taken.  This does 
not include an event that will have been fatal if it had occurred in a 
more severe form.
Hospitalization
An event that results in an admission to the hospital for any length of 
time.  This does not include an emergency room visit or admission to an 
outpatient facility.
Prolongation of 
Hospitalization
An event that occurs while the study subject is hospitalized and 
prolongs the subjects hospital stay.
Congenital Anomaly
An anomaly detected at or after birth, or any anomaly that results in 
fetal loss.
Persistent or Significant 
Disability/Incapacity
An event that results in a condition that substantially interferes with the 
activities of daily living of a study subject.  Disability is not intended to 
include experiences of relatively minor medical significance such as 
headache, nausea, vomiting, diarrhea, influenza, and accidental trauma 
(e.g., sprained ankle).
Important Medical Event 
Requiring Medical or 
Surgical Intervention to 
Prevent Serious Outcome
An important medical event that may not be immediately 
life-threatening or result in death or hospitalization, but based on 
medical judgment may jeopardize the subject and may require medical 
or surgical intervention to prevent any of the outcomes listed above 
(i.e., death of subject, life threatening, hospitalization, prolongation of 
hospitalization, congenital anomaly, or persistent or significant 
disability/incapacity).  Examples of such events include allergic 
bronchospasm requiring intensive treatment in an emergency room or at 
home, blood dyscrasias or convulsions that do not result in inpatient 
hospitalization, or the development of drug dependency or drug abuse.
Spontaneous Abortion
Miscarriage experienced by study subject.
Elective Abortion
Elective abortion performed on study subject.
6.1.2
Adverse Event Severity
The Investigator will use the following definitions to rate the severity of each AE:
Mild
The AE is transient and easily tolerated by the subject.
Moderate
The AE causes the subject discomfort and interrupts the subjects usual 
activities.
Severe
The AE causes considerable interference with the subjects usual activities 
and may be incapacitating or life threatening.  

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6.1.3
Relationship to Study Drug
The Investigator will use the following definitions to assess the relationship of the AE to 
the use of study drug:  
Probably Related
An adverse event has a strong temporal relationship to study drug or recurs 
on re-challenge and an other cause of event is unlikely or significantly less 
likely.
Possibly Related
An AE has a strong temporal relationship to the study drug and an other 
cause of event is equally or less likely compared to the potential 
relationship to study drug.
Probably Not Related
An AE has little or no temporal relationship to the study drug and/or a more 
likely other cause of event exists.
Not Related
An AE is due to an underlying or concurrent illness or effect of another 
drug and is not related to the study drug (e.g., has no temporal relationship 
to study drug or has a much more likely other cause of event).
If an Investigators opinion of possibly, probably not, or not related to study drug for an 
SAE is given, an alternative cause of the event must be provided by the Investigator for 
the SAE.
6.1.4
Adverse Event Collection Period
All AEs reported from the time of informed consent until 5 half-lives (70 days), following 
discontinuation of study drug administration have elapsed will be collected, whether 
elicited or spontaneously reported by the subject.  In addition, SAEs will be collected 
from the time the subject or parent/legal guardian has signed the study-specific informed 
consent.
Adverse event information will be collected as shown in Figure 3.

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Figure 3.
Adverse Event Collection
SAEs and Non-serious AEs
Elicited and/or Spontaneously Reported
!
!
!
!
Consent 
Signed
Study Drug 
Start
Study Drug 
Stopped
70 Days After 
Study Drug 
Stopped
6.1.5
Adverse Event Reporting
In the event of a serious adverse event, and additionally, any non-serious event of 
malignancy in patients 30 years of age and younger, whether related to study drug or not, 
the physician will notify AbbVie Immunology Clinical Safety Management Team within 
24 hours of the physician becoming aware of the event by faxing or emailing the serious 
adverse event or nonserious event of malignancy in patients 30 years of age and younger 
forms to the Immunology Clinical Safety Team within 24 hours of being made aware of 
the adverse event.
To report a Serious Adverse Event (SAE):
AbbVie Safety Fax Number:  
Email:  
For SAE concerns, contact the Immunology Safety Team at:

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For any subject safety concerns, contact the physician listed below:
Primary Study Designated Physician:
Should in case of subject safety concerns or medical emergencies the Primary Study 
Designated Physician be unavailable, please call the following central back-up number:
Phone:  
6.1.5.1
Collection of Data Regarding Known Manifestations of the 
Disease Under Study
Flare, of Crohns disease events per study definition, are not required to be captured as 
AEs, but may be captured per Investigator discretion.  Additionally, CD pre-existing 
conditions will not be captured as AEs unless the condition has worsened or is considered
clinically significant in the opinion of the Investigator.
6.1.6
Pregnancy
Pregnancy in a study subject must be reported to AbbVie within 1 working day of the site 
becoming aware of the pregnancy.  Subjects who become pregnant during the study must 
be discontinued (Section 5.4.1).  Pregnancies will be collected from the date of the 
first dose through 150 days following the last dose of study drug.

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Information regarding a pregnancy occurrence in a study subject and the outcome of the 
pregnancy will be collected.
Pregnancy in a study subject is not considered an AE.  However, the medical outcome of 
an elective or a spontaneous abortion, stillbirth or congenital anomaly is considered a 
SAE, and must be reported to the sponsor with 24 hours of the site learning of the event.
6.2
Product Complaint
6.2.1
Definition
A Product Complaint is any Complaint (see Section 6.0 for the definition) related to the 
biologic or drug component of the product or to the medical device component(s).
For a product this may include, but is not limited to, damaged/broken product or 
packaging, product appearance whose color/markings do not match the labeling, labeling 
discrepancies/inadequacies in the labeling/instructions (example:  printing illegible), 
missing components/product, device not working properly, or packaging issues.
For medical devices, a product complaint also includes all deaths of a patient using the 
device, any illness, injury, or adverse event in the proximity of the device, an adverse 
event that could be a result of using the device, any event needing medical or surgical 
intervention including hospitalization while using the device and use errors.
Any information available to help in the determination of causality by the device to the 
events outlined directly above should be captured.
6.2.2
Reporting
Product Complaints concerning the investigational product and/or device must be reported 
to the Sponsor within 24 hours of the study site's knowledge of the event via the Product 
Complaint form.  Product Complaints occurring during the study will be followed-up to a 
satisfactory conclusion.  All follow-up information is to be reported to the Sponsor (or an 
authorized representative) and documented in source as required by the Sponsor.  Product 

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Complaints associated with adverse events will be reported in the study summary.  All 
other complaints will be monitored on an ongoing basis.
Product Complaints may require return of the product with the alleged complaint 
condition (syringe).  In instances where a return is requested, every effort should be made 
by the investigator to return the product within 30 days.  If returns cannot be 
accommodated within 30 days, the site will need to provide justification and an estimated 
date of return.
The description of the complaint is important for AbbVie in order to enable AbbVie to 
investigate and determine if any corrective actions are required.
7.0
Protocol Deviations
The investigator should not implement any deviation from the protocol without prior 
review and agreement by the Sponsor and in accordance with the IEC/IRB and local 
regulations, except when necessary to eliminate an immediate hazard to study subjects.  
When a deviation from the protocol is deemed necessary for an individual subject, the 
investigator must contact the following AbbVie representative:
For purposes of this protocol, reportable deviations are defined as:  
●
Subject entered into the study even though they did not satisfy entry criteria
●
Subject who developed withdrawal criteria during the study and was not 
withdrawn

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●
Subject who received wrong treatment or incorrect dose
●
Subject who received excluded concomitant treatment
Such contact must be made as soon as possible to permit a review by AbbVie to 
determine the impact of the deviation on the subject and/or the study.  Any significant 
protocol deviations affecting subject eligibility and/or safety must be reviewed and/or 
approved by the IEC/IRB and regulatory authorities, as applicable, prior to 
implementation.
8.0
Statistical Methods and Determination of Sample 
Size
8.1
Statistical and Analytical Plans
8.1.1
Analyzable Population
Efficacy analyses will be conducted in the intent-to-treat (ITT) population, which is 
defined as all subjects who received at least one dose of adalimumab in Study M06-807.  
The safety population consists of all subjects who received at least one dose of 
adalimumab in Study M06-807.
8.1.2
Planned Methods of Statistical Analysis
All statistical analyses are to be performed descriptively.  Descriptive summary statistics 
will be provided for the demographic and baseline characteristics, efficacy, and safety 
parameters.  Continuous variables will be summarized using the number of observation, 
mean, standard deviation, 1st quartile, median, 3rd quartile, minimum, and maximum; 
whereas discrete variables will be summarized using count and percentages. 
8.1.2.1
Demographics and Baseline Characteristics
Summary statistics for the demographic and baseline characteristics will be computed 
based on the Week 52 values (from double-blind Study M06-806).

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8.1.2.2
Efficacy Analysis
Summary statistics will be provided for each visit, based on observed data.  An additional 
summary will be provided for the last visit, using the last observation carried forward 
(LOCF).  That is, the subjects last non-missing, post-baseline value (i.e., post-Week 52 
M06-806 double-blind value) will be carried forward to the last visit.
8.1.3
Other Analyses
Efficacy will be analyzed for the following subgroups in the ITT population.
●
Sex [Male, Female]
●
Age [< 13 years, ≥13 years]
●
Race [White, Non-white]
●
Weight [< 40 kg, ≥ 40 kg]
●
Prior infliximab use [No, Yes]
●
Baseline CRP [< 1.0 mg/dL, ≥ 1.0 mg/dL]
●
Concomitant use of immunosuppressants and/or oral corticosteroids [No, Yes]
8.1.4
Safety Analyses
Safety analyses will be based on the safety population.  Treatment-emergent AEs will be 
summarized.  An overview of treatment-emergent AEs including AEs of special interest, 
such as AEs leading to death and AEs leading to premature discontinuation, AEs by 
(MedDRA® version 10.0 or later) preferred term and system organ class, AEs by 
maximum relationship to study drug, and AEs by maximum severity will be summarized.  
Treatment-emergent AEs are defined as new events that begin either on or after the 
first dose of the study drug and within 70 days after the last dose of the study drug.
Adverse events with missing or unknown severity will be categorized as severe.  Adverse 
events with missing or unknown relationship to study drug will be categorized as 
probably related.

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Adverse events that are reported more than 70 days after last study injection will be 
excluded from the summaries; however, all reported AEs will be included in the AE data 
listings.
For laboratory parameters, the normal range of the analyzing laboratory will be used and 
all values outside the normal range will be flagged and listed.  Additionally, descriptive 
statistics for the mean change from baseline to minimum (smallest) value, maximum 
(largest) value and final value during the study will be calculated for the continuous 
clinical laboratory parameters. 
Shift tables will be provided to cross-classify and tabulate subjects value from baseline to 
final value by the presence of clinically significant laboratory results.  Each subjects 
baseline value and final value will be flagged in reference to the normal range (low, 
normal, high) and also categorized as clinically non-significant (CTC grade < 3) or 
clinically significant (CTC grade ≥3).  Further details will be provided in the SAP.
8.1.4.1
Pharmacokinetic Analyses
Adalimumab trough serum concentrations will be summarized by treatment group at each 
time point using descriptive statistics including number of subjects, number of 
non missing observations (nnmiss), mean, median, standard deviation, coefficient of 
variation, minimum, and maximum.  The relationship between adalimumab 
concentrations and efficacy and/or safety variables may be explored.  Additional analysis 
may be performed.
8.1.5
Interim Analysis
There will be multiple planned interim analyses.  Details of the analyses will be described 
in the study SAPs.

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8.2
Determination of Sample Size
Subjects who successfully completed Study M06-806 through Week 52 may be eligible to 
participate in this study.  It is expected that approximately 70% (130) of subjects from the 
M06-806 study will enroll in this study.
8.3
Randomization Methods
All subjects will be centrally registered using an IVRS.  This is an open-label study; 
therefore, subjects will not be randomized before the study is initiated, the telephone 
number and call in directions for the IVRS will be provided to each site.  Subjects will 
keep their subject number from the previous study (M06-806).
9.0
Ethics
9.1
Independent Ethics Committee (IEC) or Institutional Review 
Board (IRB)
Good Clinical Practice (GCP) requires that the clinical protocol, any protocol 
amendments, the Investigators Brochure, the informed consent and all other forms of 
subject information related to the study (e.g., advertisements used to recruit subjects) and 
any other necessary documents be reviewed by an IEC/IRB.  IEC/IRB approval of the 
protocol, informed consent and subject information and/or advertising, as relevant, will be 
obtained prior to the authorization of drug shipment to a study site.
Any amendments to the protocol will require IEC/IRB approval prior to implementation 
of any changes made to the study design.  A list of the documents required prior to 
initiation of the study can be found in Appendix C.
Any SAEs that meet the reporting criteria, as dictated by local regulations, will be 
reported to both responsible Ethics Committees and Regulatory Agencies, as required by 
local regulations.  During the conduct of the study, the Investigator should promptly 
provide written reports (e.g., ICH Expedited Reports, and any additional reports required 
by local regulations) to the IEC/IRB of any changes that affect the conduct of the study 

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and/or increase the risk to subjects, unless otherwise submitted by the sponsor.  Written 
documentation of the submission to the IEC/IRB should also be provided to AbbVie.
9.2
Ethical Conduct of the Study
The study will be conducted in accordance with the protocol, International Conference on 
Harmonization (ICH) guidelines, applicable regulations and guidelines governing clinical 
trial conduct, and the ethical principles that have their origin in the Declaration of 
Helsinki.  Responsibilities of the clinical Investigator are specified in Appendix D.
9.3
Subject Information and Consent
Prior to any study-related procedures or discontinuation of any medications for this study, 
the Investigator or his/her representative will explain the nature of the study to the subject 
of legal age (in the state of residence) or to the parent or legal guardian (as appropriate) of 
a subject who is not of legal age and answer all questions regarding this study.  Subjects 
will be included in all discussions.
The ICF will be reviewed, signed and dated by the subject of legal age (in the state of 
residence) or by the parent or legal guardian (as appropriate) of a subject who is not of 
legal age, and the person who administered the informed consent. If a subject who was 
not of legal age at the onset of this study becomes of legal age during the course of the 
study, an informed consent will need to be obtained at that time.  Additionally, in keeping 
with each institutions IRB requirements an Informed Assent will also be obtained from 
the subject, as required.  
A copy of the signed ICF and Assent Form will be given to the subject and the subjects 
parent/legal guardian.  The original signed ICF and Assent Form will be placed in the 
subjects medical record.  An entry must also be made in the subjects dated source 
documents to confirm that informed consent was obtained prior to any study-related 
procedures and that the subject received a signed copy.

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If an updated informed consent is approved after a subject has completed or terminated 
early from the study, but is within the 70-day follow-up window, the subject will not be 
required to return to the site for the purposes of signing the updated ICF.  The subject of 
legal age, parent or legal guardian (as appropriate) should be contacted regarding any 
changes and the documentation of the contact should be present in the subjects source. 
10.0
Source Documents and Case Report Form 
Completion
10.1
Source Documents
Source documents are defined as original documents, data and records.  This may include 
hospital records, clinical and office charts, laboratory data/information, subjects diaries or 
evaluation checklists, pharmacy dispensing and other records, recorded data from 
automated instruments, microfiches, photographic negatives, microfilm or magnetic 
media, and/or x-rays.  Data collected during this study must be recorded on the 
appropriate source documents.
The Investigator(s)/institution(s) will permit study-related monitoring, audits, IEC/IRB 
review, and regulatory inspection(s), providing direct access to source data documents.
The IMPACT III questionnaire and the WPAI questionnaire will be recorded directly on 
the CRF(s) by the subject, parent or legal guardian (as appropriate) and these CRFs will 
be considered source data.
10.2
Case Report Forms
Case report forms will be supplied by AbbVie.  These forms will be used to transmit 
information collected during the study to AbbVie and regulatory authorities, as applicable.  
Case report forms must be completed for each subject enrolled in this study.  All case 
report forms must be legible and completed in indelible black ballpoint ink.  Any 
necessary corrections are to be made by drawing a single line through the incorrect entry 
and writing in the revision.  All revisions must be initialed and dated by the Investigator 
or his/her representative.  Data are not to be obliterated by blacking out, using correction 

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fluid or by erasing the original entry.  If the reason for the correction is not obvious, a 
brief explanation (e.g., transcription error) should accompany the change.  All information 
written on the case report forms must also be reflected in the subject source documents 
with the exception of the case report forms discussed above in Section 10.1.
The Principal Investigator will review the case report forms for completeness and 
accuracy and sign and date each set of case report forms where indicated.  The case report 
forms will be reviewed periodically for completeness, legibility and acceptability by 
AbbVie personnel (or their representatives).  AbbVie (or their representatives) will be 
allowed access to all source documents in order to verify case report form entries.
Once the original case report form has been removed from the site, all changes must be 
made via the appropriate change form specified by AbbVie.  The Principal Investigator 
will review the change form for completeness and accuracy and sign and date the change 
form where indicated.
11.0
Data Quality Assurance
Prior to the initiation of the study, an Investigators meeting will be held with AbbVie 
personnel, the Investigators and their study coordinators, the CROs project manager and 
the CRAs for the study.  This meeting will include a detailed discussion of the protocol, 
performance of study procedures, CRF and Subject Diary completion, and specimen 
collection methods.  In addition to or instead of the Investigators meeting, the study 
personnel at each site may be trained on the study procedures by a CRA at a study 
initiation visit and will be given a CRF completion workbook for reference.
The CRAs will monitor at each site throughout the study.  One hundred percent (100%) 
source document review will be performed against entries on the CRF and a quality 
assurance check will be performed to ensure that the Investigator is complying with the 
protocol and regulations.  In addition, after CRFs are retrieved by the CRA, a review of 
the data will be conducted by a physician and a clinical review team at AbbVie.

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All data hand entered in the database will be verified by a double-key entry procedure at 
AbbVie.  Any discrepancies will be reviewed against the hard copy CRF and corrected 
on-line.  After completion of the entry process, computer logic checks will be run to check 
for such items as inconsistent study dates and outlying laboratory values.  Any necessary 
corrections will be made to the database and documented via addenda, queries, source 
data clarification form or audit trail.  A manual review of selected line listings will also be 
performed at the end of the study.
Routine hematology, serum chemistry, and serology will be conducted using a central 
laboratory.  ESR analysis will be done at a local lab designated by the site.  The data from 
these analyses will be electronically transferred from the central laboratory to the study 
database.  Urinalysis will be completed locally.  If a microscopic urinalysis is necessary, 
this testing will be conducted using the central laboratory.  A final review of all laboratory 
results will be conducted by a physician and clinical review team at AbbVie.
Sites will provide AbbVie (or designate) with laboratory certifications (CAP and CLIA), 
CV of local lab director, and reference ranges for each local lab used.  The full name, 
address, phone number, and fax number for each local lab will also be included.
12.0
Use of Information and Publication
12.1
Use of Information
All information concerning adalimumab and AbbVie operations, such as AbbVie patent 
applications, formulas, manufacturing processes, basic scientific data, or formulation 
information, supplied by AbbVie and not previously published is considered confidential 
information.
The information developed during the conduct of this clinical study is also considered 
confidential and will be used by AbbVie in connection with the development of 
adalimumab.  This information may be disclosed as deemed necessary by AbbVie to other 
clinical Investigators, other pharmaceutical companies, to the FDA, and to other 
government agencies.  To allow for the use of the information derived from this clinical 

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study and to ensure complete and thorough analysis, the Investigator is obligated to 
provide AbbVie with complete test results and all data developed in this study and to 
provide direct access to source data/documents for study- related monitoring, audits, 
IEC/IRB review, and regulatory inspection.
This confidential information shall remain the sole property of AbbVie, shall not be 
disclosed to others without the written consent of AbbVie, and shall not be used except in 
the performance of this study.
The Investigator will maintain a confidential subject identification code list of all subjects 
enrolled in the study (by name and subject number).  This list will be maintained at the 
site and will not be retrieved by AbbVie.
12.2
Internet Sites
Information regarding this study may be posted on various internet web sites and will 
maximally include study name, number, general population to be enrolled, entrance 
qualifications, brief description of the study, study objectives, doses, accruing 
Investigators (upon their approval) and number of subjects to be enrolled.
13.0
Completion of the Study
The Investigator will conduct this study in compliance with the protocol, and will 
complete the study within the timeframe specified in the contract between the Investigator 
and AbbVie.  Continuation of the study beyond this time must be mutually agreed upon in 
writing by both the Investigator and AbbVie.  The Investigator will provide a summary of 
the study's outcome to the IEC/IRB following conclusion of the study, and will forward a 
copy of this summary to AbbVie or their designee.
AbbVie may terminate this study prematurely, either in its entirety or at individual sites, 
for reasonable cause provided that written notice is submitted a reasonable time in 
advance of the intended termination.  The Investigator may also terminate the study at 
their site for reasonable cause, after providing written notice to AbbVie a reasonable time 

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in advance of the intended termination.  Advance notice is not required by either party if 
the study is stopped due to safety concerns.  If AbbVie terminates the study for safety 
reasons, it will immediately notify the Investigator by telephone and subsequently provide 
written instructions for study termination.
AbbVie will select the signatory Investigator from the Investigators who participate in the 
study.  Selection criteria for this Investigator will include level of participation as well as 
significant knowledge of the clinical research, investigational drug and study protocol.  
The signatory Investigator for the study will review and sign the final study report in 
accordance with the European Agency for the Evaluation of Medicinal Products (EMEA) 
Guidance on Investigators Signature for Study Reports.
The Investigator will retain all essential documents until at least two years after the last 
approval of a marketing application in an ICH region and until there are no pending or 
contemplated marketing applications in an ICH region or at least two years have elapsed 
since the formal discontinuation of clinical development of the investigational product.  It 
is the responsibility of the sponsor to inform the Investigator/institution as to when these 
documents no longer need to be retained.
The end-of-study is defined as the date of the last subjects last scheduled visit or the 
actual date of follow-up contact, whichever is longer.

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14.0
Investigators Agreement
1.
I have received and reviewed the Investigator Brochure for Humira.
2.
I have read this protocol and agree that the study is ethical.
3.
I agree to conduct the study as outlined and in accordance with all applicable 
regulations and guidelines.
4.
I agree to maintain the confidentiality of all information received or developed in 
connection with this protocol.
Protocol Title:
A Multi-center, Open-label Study of the Human Anti-TNF 
Monoclonal Antibody Adalimumab to Evaluate the Efficacy and the 
Long-term Safety and Tolerability of Repeated Administration of 
Adalimumab in Pediatric Subjects with Crohn's Disease Who Have 
Demonstrated a Clinical Response in the M06-806 Study
Protocol Date:
26 May 2015
Signature of Principal Investigator
Date
Name of Principal Investigator (printed or typed)

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15.0
Reference List
1.
Hanauer SB, Sandborn W.  Management of Crohns disease in adults.  Am J 
Gastroenterol.  2001;96:635-43.
2.
Loftus Jr. EV.  Clinical epidemiology of inflammatory bowel disease:  Incidence, 
prevalence, and environmental influences.  Gastroenterology.  2004;126:1504-17.
3.
Seidman EG.  Recent advances in the diagnosis and treatment of pediatric 
inflammatory bowel disease.  Curr Gastroenterol Rep.  2000;2:248-52.
4.
Auvin S, Molinie F, Gower-Rousseau C, Brazier F, Merle V, Grandbastient B, 
et al.  Incidence, clinical presentation and location at diagnosis of pediatric 
inflammatory bowel disease:  a prospective population-based study in northern 
France (1988-1999).  J Pediatr Gastroenterol Nutr.  2005;41(1):49-55.
5.
Kugathasan S, Judd RH, Hoffmann RG, Heikenen J, Telega G, Khan F, et al.  
Epidemiologic and clinical characteristics of children with newly diagnosed 
inflammatory bowel disease in Wisconsin; a statewide population-based study.  
J Pediatr.  2003;143(4):525-31.
6.
Cosgrove M, Al-Atia RF, Jenkins HR.  The epidemiology of pediatric 
inflammatory bowel disease.  Arch Dis Child.  1996;74:460-1.
7.
Hassan K, Cowan FJ, Jenkins HR.  The incidence of childhood inflammatory 
bowel disease in Wales.  Eur J Pediatr.  2000;159:261-3.
8.
Barton JR, Gillon S, Ferguson A.  Incidence of inflammatory bowel disease in 
Scottish children between 1968 and 1983; marginal fall in ulcerative colitis, 
three-fold rise in Crohns Disease.  Gut.  1989;30:618-22.
9.
Sawczenko A, Sandhu BK, Logan RFA, et al.  Prospective survey of childhood 
inflammatory bowel disease in the British Isles.  Lancet.  2001;357:1093-4.
10.
Olafsdottir EJ, Fluge G, Haug K.  Chronic inflammatory bowel disease in children 
in western Norway.  J Pediatr Gastroenterol Nutr.  1989;8:454-8.

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11.
Lindberg E, Lindquist B, Holmquist L, Hildebrand H.  Inflammatory bowel disease 
in children and adolescents in Sweden (1984-1995).  J Pediatr Gastroenterol Nutr.  
2000;30:259-64.
12.
Hildebrand H, Finkel Y, Grahnquist L, Lindholm J, Ekbom A, Askling J.  
Changing pattern of paediatric inflammatory bowel disease in northern Stockholm 
1990-2001.  Gut.  2003;52:1432.
13.
Heyman MB, Kirshner BS, Gold BD, Ferry G, Baldassano R, Cohen SA, et al.  
Children with early onset inflammatory bowel disease (IBD):  analysis of a 
pediatric IBD consortium registry.  J Pediatr.  2005;146(1):35-40.
14.
Lindberg E, Lindquist B, Holmquist L, Hildebrand H.  Inflammatory bowel disease 
in children and adolescents in Sweden, 1984-1995.  J Pediatr Gastroenterol Nutr.  
2000;30(3):259-64.
15.
Sawczenko A, Sandhu BK.  Presenting features of inflammatory bowel disease in 
Great Britain and Ireland.  Arch Dis Child.  2003;88:995-1000.
16.
Griffiths AM.  Specificities of inflammatory bowel disease in childhood.  Best 
Pract Res Clin Gastroenterol.  2004;18(3):509-23.
17.
Griffiths AM, Nguyen P, Smith C, MacMillan JH, Sherman PM.  Growth and 
clinical course of children with Crohns disease.  Gut.  1993;34(7):939-43.
18.
Kanof ME, Lake AM, Bayless TM.  Decreased height velocity in children and 
adolescents before the diagnosis of Crohns disease.  Gastroenterology.  
1988;95(6):1523-7.
19.
Markowitz J, Grancher K, Rosa J, Aiges H, Daum F.  Growth failure in pediatric 
inflammatory bowel disease.  J Pediatr Gastroenterol Nutr.  1993;16(4):373-80.
20.
Kleinman RE, Baldassano RN, Caplan A, Griffiths AM, Heyman MB, 
Issenman RM, et al.  Nutrition support for pediatric patients with inflammatory 
bowel disease:  a clinical report of the North America Society for Pediatric 
Gastroenterology, Hepatology and Nutrition.  J Pediatr Gastroenterol Nutr.  
2004;39(1):15-27.

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21.
Gokhale R, Favus MJ, Karrison T, Sutton MM, Rich B, Kirshner BS.  Bone 
mineral density assessment in children with inflammatory bowel disease.  
Gastroenterology.  1998;114:902-11.
22.
Boot AM, Bouquet J, Krennings EP, de Muinck Keizer-Schrama SMPF.  Bone 
mineral density and nutritional status in children with chronic inflammatory bowel 
disease.  Gut.  1998;42:188-94.
23.
Ballinger AB, Savage MO, Sanderson IR.  Delayed puberty associated with 
Inflammatory bowel disease.  Pediatr Res.  2003;53:205-10.
24.
Harpavat M, Greenspan SL, OBrien C, Chang C-C, Bowen A, Keljo DJ.  Altered 
bone mass in children at diagnosis of Crohns disease:  a pilot study.  J Pediatr 
Gastroenterol Nutr.  2005;40:295-300.
25.
Hyams JS, Wyzga N, Kreutzer DL, Justinich CJ, Gronowicz GA.  Alterations in 
bone metabolism in children with inflammatory bowel disease:  an in vitro study.  
J Pediatr Gastroenterol Nutr.  1997;24(3):289-95.
26.
Hanauer S, Lukas M, MacIntosh D, Rutgeerts P, Sandborn W, Pollack P.  A 
randomized, double-blind, placebo-controlled trial of the human anti-TNF-α 
monoclonal antibody adalimumab for the induction of remission in patients with 
moderate to severely active Crohns disease.  Gastroenterology.  2004;127(1):332.
27.
Data on file at AbbVie.
28.
AbbVie Study DE038, Data on file.
29.
Humira® (adalimumab) [package insert].  North Chicago, IL:  AbbVie:  June 2006.
30.
Present DH, Rutgeerts P, Targan S, Hanauer SB, Mayer L, van Hogezand RA, 
et al.  Infliximab for the treatment of fistulas in patients with Crohns disease.  
N Eng J Med.  1999;340(18):1398-405.
31.
Greulich and Pyle Radiographic Atlas of Skeletal Development of the Hand and 
Wrist:  June 1959.
32.
Centers for Disease Control and Prevention.  Targeted tuberculin testing and 
treatment of latent tuberculosis infection.  MMWR 2006 April.

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Appendix A.
List of Abbreviations and Definition of Terms
Abbreviations
AAA
Anti-adalimumab antibody
AE
Adverse Event
ALT
Alanine Transaminase
ANA
Antinuclear antibody
AST
Aspartate transaminase
BMI
Body Mass Index
BSAP
Bone-specific alkaline phosphatase
BUN
Blood Urea Nitrogen
CD
Crohns disease
CDC
Center for Disease Control
CNS
Central Nervous Systems
CRA
Clinical Research Associate
CRF
Case Report Form
CRP
C-Reactive Protein
CTC
Common Toxicity Criteria
DMC
Data Monitoring Committee
DNA
Deoxyribonucleic acid
dsDNA
Double Stranded DNA
eow
Every other week
ESR
Erythrocyte sedimentation rate
ET
Early Termination
EU
European Union
ew
Every week
FDA
U.S. Food and Drug Administration
GCP
Good Clinical Practice
HCT
Hematocrit
HIV
Human immunodeficiency virus
ICH
International Conference on Harmonization
IEC
Independent Ethics Committee
IgG1
Immunoglobulin
ICF
Informed Consent Form

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IRB
Institutional Review Board
ITT
Intent-to Treat
IVRS
Interactive Voice Response System
JRA
Juvenile Rheumatoid Arthritis
LOCF
Last Observation Carried Forward
MTX
Methotrexate
Ntx 
N-telopeptide
OL
Open-Label
PCDAI
Pediatric Crohns Disease Activity Index
PK
Pharmacokinetics
POR
Proof of Receipt
RA
Rheumatoid Arthritis
SAE
Serious Adverse Event
SAP
Statistical analysis plan
SC
Subcutaneous
SSC
Sponsor Steering Committee
TB
Tuberculosis
TNF
Tumor Necrosis Factor
TPN
Total Parenteral Nutrition
US
United States
WPAI
Work Productivity and Activity Impairment Questionnaire
WPAI-CD
Work Productivity and Activity Impairment Questionnaire:  Crohns 
Disease

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Appendix B.
List of Protocol Signatories
Name
Title
Functional Area
Statistics
Pharmacokinetics
Clinical
Clinical
Clinical

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Appendix C.
Documents Required Prior to Initiation of the Study
As sponsor of a clinical study, AbbVie has an obligation to ensure that the study will be 
conducted by a qualified investigator with sufficient resources (of time, personnel, and 
physical facilities) to conduct the study and to ensure that the investigator understands and 
agrees to comply with Good Clinical Practices and applicable regulations, policies, and 
procedures.  Prior to the beginning of any clinical study, the investigator will be asked to 
provide the following documentation.
1.
A signed and dated Investigators agreement page for the study.
2.
A signed and dated Form FDA 1572 certifying the investigators agreement to 
comply with the appropriate regulations governing the conduct of the study.
A signed and dated Investigator Information and Agreement Form certifying the 
investigators agreement to comply with the appropriate (e.g., ICH GCP) 
regulations governing the conduct of the study.  These will be required only for 
sites that are recruited under this amendment, or when existing sites update study 
documentation.
3.
Current curriculum vitae for the investigator.  If subinvestigators will participate in 
the study, curriculum vitae for each.
4.
Requirements for the Independent Ethics Committee (IEC)/Institutional Review 
Board (IRB).
●
A copy of the signed and dated letter of approval of the IEC/IRB.  The letter 
must specify that both the protocol and informed consent form were approved 
(unless separate documentation that the informed consent was approved is 
provided).
●
A dated list containing the names and affiliations of the members of the 
IEC/IRB, or the institutions General Assurance Number.
●
If the investigator and/or subinvestigator is a member of the IEC/IRB, a letter 
stating that he/she did not participate in the review or approval of the protocol 
or informed consent form.

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5.
A specimen copy of the IEC/IRB-approved informed consent document to be used 
in the study.
6.
A list of reference ranges of values for all laboratory tests specified by the protocol 
for all laboratories utilized.
7.
A copy of the laboratory(ies) certification(s) or the authorization number of the 
certification(s), the name of the certifying authority, and the period of certification.
8.
Financial Disclosure Certification forms must be completed by each investigator 
and all subinvestigators identified on the Form FDA 1572 or Investigator 
Information and Agreement Form.  A Financial Disclosure, EU Consent, is 
required to be completed for each investigator and/or subinvestigator who is a 
resident of the European Union.

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Appendix D.
Responsibilities of the Clinical Investigator
Clinical research studies sponsored by AbbVie are subject to the regulations of the U.S. 
Food and Drug Administration (FDA).  The responsibilities imposed upon Investigators 
by the FDA are summarized in the "Statement of Investigator" (Form FDA 1572), which 
is a form letter addressed to the sponsor (AbbVie), summarizing the Investigators 
qualifications for the study and his/her willingness to follow FDA regulations with respect 
to the study.
In signing a Form FDA 1572, the Investigator agrees to assume the following 
responsibilities:  
1.
To conduct the study(ies) in accordance with the relevant, current protocol(s) and 
only make changes in a protocol after notifying AbbVie, except when necessary to 
protect the safety, rights, or welfare of subjects.
2.
To personally conduct or supervise the described investigation(s).
3.
To inform any subjects, or any persons used as controls, that the drugs are being 
used for investigational purposes and to ensure that the requirements relating to 
obtaining informed consent in 21 CFR Part 50 and Independent Ethics Committee 
(IEC)/Institutional Review Board (IRB) review and approval in 21 CFR Part 56 are 
met.
4.
To report to AbbVie adverse experiences that occur in the course of the 
investigation(s) in accordance with 21 CFR 312.64.
5.
To read and understand the information in the Investigators Brochure, including the
potential risks and side effects of the drug.
6.
To ensure that all associates, colleagues, and employees assisting in the conduct of 
the study(ies) are informed about their obligations in meeting the above 
commitments.
7.
To maintain adequate and accurate records of the conduct of the study and make 
those records available for inspection by representatives of AbbVie, the IEC/IRB 

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and/or the appropriate regulatory agency, and to retain all study-related documents 
until notification from AbbVie.  The Investigator must notify AbbVie when they 
are no longer able to retain the study related documents.
8.
To ensure that an IEC/IRB that complies with the requirements of 21 CFR Part 56 
will be responsible for the initial and continuing review and approval of the clinical 
investigation.
9.
To promptly report to the IEC/IRB all changes in the research activity and all 
unanticipated problems involving risks to human subjects or others (including 
submission of any Expedited Safety Reports received from AbbVie to the 
IEC/IRB), and to make no changes in the research without IEC/IRB approval, 
except where necessary to eliminate apparent immediate hazards to human 
subjects.
10.
To comply with all other requirements regarding the obligations of clinical 
Investigators and all other pertinent requirements in 21 CFR Part 312.

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Appendix E.
CDC Treatment of Tuberculosis Infection (Preventive Therapy)
Centers for Disease Control and Prevention
Tuberculosis Information
Treatment of Tuberculosis Infection (Preventive Therapy), Latent Tuberculosis
Infection (LBTI)32

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Appendix F.
Non-Drug Materials Provided to the Study Site(s)
Study sites will receive the following supplies prior to or during the study:
Tote Bags
Cooler
Sharps Containers
Ice Packs
CDAI subject diary
Dosing Diaries
Subject Medication Log
Self Injection Instructions
Dosing syringes, as applicable

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Appendix G.
Pediatric Crohns Disease Activity Index (PCDAI)
1.
Abdominal pain rating
- None
- Mild - Brief, does not interfere with activities
- Moderate/severe-Daily, longer lasting, affects activities, nocturnal
= 0 p
= 5 p
= 10 p
Score
2.
Stools (per day)
- 0–1 liquid stools, no blood
- Up to 2 semi-formed with small blood, or 2–5 liquid
- Gross bleeding, or ≥6 liquid, or nocturnal diarrhea
= 0 p
= 5 p
= 10 p
3.
Patient Functioning, General Well-Being
- No limitation of activities, well
- Occasional difficulty in maintaining age appropriate activities, below par
- Frequent limitation of activity, very poor
= 0 p
= 5 p
= 10 p
LABORATORY
Score
4.
HCT:  Male and female ≤10 years:
≥ 33
= 0 p
28-32
= 2.5 p
< 28
= 5 p
Male 11–14 years:
≥ 35
= 0 p
30-34
= 2.5 p
< 30
= 5 p
Female 11–19 years: ≥ 34= 0 p
29-33
= 2.5 p
< 29
= 5 p
Male 15–19 years:
≥ 37= 0 p
32-36
= 2.5 p
< 32
= 5 p
5.
ESR (mm/hr)
< 20
= 0 p
20-50
= 2.5 p
> 50
= 5 p
6.
Albumin (g/dL)
≥ 3.5
= 0 p
3.1-3.4 = 5 p
≤ 3.0
= 10 p

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EXAMINATION
Score
7.
Weight
- Weight gain or voluntary weight stable/loss
- Involuntary weight stable, weight loss 1–9%
- Weight loss ≥ 10%
= 0 p
= 5 p
= 10 p
8.
Height
Height velocity ≥ -1SD
Height velocity < -1SD, > -2SD
Height velocity ≤ -2SD
= 0 p
= 5 p
= 10 p
9.
Abdomen
- No tenderness, no mass
- Tenderness, or mass without tenderness
- Tenderness, involuntary guarding, definite mass
= 0 p
= 5 p
= 10 p
10. Perirectal disease
- None, asymptomatic tags
- 1–2 indolent fistula, scant drainage, no tenderness
- Active fistula, drainage, tenderness, or abscess
= 0 p
= 5 p
= 10 p
11. Extra-intestinal Manifestations
(Fever ≥ 38.5 for 3 days over past week, definite arthritis, uveitis, E. nodosum, 
P. gangrenosum)
- None
- One
- ≥ Two
= 0 p
= 5 p
= 10 p
TOTAL SCORE 
Pediatric Crohns Disease Activity Index (PCDAI)

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Appendix H.
PCDAI Users Guide and Guideline for Reference Weight and 
Reference Height
This guide is intended to help nurse coordinators and physicians complete the PCDAI in 
order to assess disease activity in children with Crohns disease participating in clinical 
trials.
History
All calculations are based upon a one-week (7 day) history recall of symptoms.  The 
history recall should be solicited from the subject and/or caregiver.
Item 1.  Abdominal pain
The descriptions in the PCDAI of "mild" and "moderate/severe" should be used to guide 
in scoring the pain.  Note that duration, effect on activities, and nocturnal occurrence 
separate moderate/severe from mild.  If pain varies in severity during the week, subject 
should be scored according to the most severe pain. However, mild pain should be present 
on at least two days to score 5 points rather than 0 points.
Item 2.  Stools
The intent is to score the stool pattern during the preceding week.
To facilitate scoring, first categorize the subject as having blood in the stool or not.
If there is no blood in the stool, score as follows:  
Formed stools or up to 1 loose stool daily = 0
2-5 liquid or very loose stools on 1 or more days = 5
6 or more liquid or very loose stools on 1 or more days or any nocturnal diarrhea = 10
If blood is present in the stool on any day during the past week, score as follows:  

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Small amounts of blood in stool (on toilet paper or small spots in stool, etc.) = 5
Any gross bleeding (large amounts on stool or colors the water in the toilet, etc.) = 10
Item 3.  Subject functioning, general well-being
If there is variation during the week, subject should be scored according to the most 
significant limitation of activity, even if it occurs during only one day of the week, as long 
as it is likely due to Crohns disease and not to an intercurrent illness.
Item 4.  Hematocrit
Hematocrit values should be rounded to a whole number prior to completing the 
calculation.  Numbers that fall between the range of 0.1-0.4 must be rounded down.   
Numbers that fall between the range of 0.5-0.9 must be rounded up.
Physical Examination
Item 7.  Weight (The intent is to assess the ability to normally maintain or gain weight)
Reference weight to be used for calculation of weight gain/loss during the study:
From Baseline to Week 408:  use weight from previous visit
Voluntary weight stable/loss means subject maintaining or losing weight on purpose.
Involuntary weight stable means subject wants to gain weight but cannot.
To calculate percentage weight loss use formula:  
Weight from previous visit – Current weight X 100 = % weight loss
Weight from previous visit

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Item 8.  Height
Reference height for calculation of height velocity
●
From Baseline to Week 24, use height from 6 months prior to Baseline
●
From Week 24 to Week 48, use height from Baseline visit
●
From Week 48 to Week 72, use height from Week 24
●
From Week 72 to Week 96, use height from Week 48
●
From Week 96 to Week 120, use height from Week 72
●
From Week 120 to Week 144, use height from Week 96
●
From Week 144 to Week 168, use height from Week 120
●
From Week 168 to Week 192, use height from Week 144
●
From Week 192 to Week 216, use height from Week 168
●
From Week 216 to Week 240, use height from Week 192
●
From Week 240 to Week 264, use height from Week 216
●
From Week 264 to Week 288, use height from Week 240
●
From Week 288 to Week 312, use height from Week 264
●
From Week 312 to Week 336, use height from Week 288
●
From Week 336 to Week 360, use height from Week 312
●
From Week 360 to Week 384, use height from Week 336
●
From Week 384 to Week 408, use height from Week 360
The intent is to assess the normalcy vs. impairment of the subjects recent linear growth.  
Note that post-pubertal subjects will score 0 points.  For subjects still growing, there are 
two options for scoring.  Method (a) is preferred.  Method (b) to be used if data required 
for (a) are unavailable.

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1.
Height velocity (cm/year), the most sensitive parameter, should be calculated as 
below:
Present height – Appropriate height measurement (from above) x 12 = Height velocity (cm/year)
        Interval (months) between heights
Using height velocity chart below, determine centile for height velocity.
2.
Scoring for the PCDAI:  
a.
Velocity less than "Minus 2 SD" scores 10 points.
b.
Velocity between "Minus 2 SD" and "Minus 1 SD" scores 5 points.
c.
Velocity greater than "Minus 1 SD" scores zero points.
*
Please note that subjects should score zero points if a subject is a female above 14.5 years of age or a male above 
17.5 years of age.

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Height Velocity Reference Values for Calculating the PCDAI (Males)
Height Velocity in cm per year (Males)
Age (years)
Minus 2SD
Minus 1SD
Mean
2.5
5.7
7.0
8.3
3
5.4
6.6
7.8
3.5
5.1
6.3
7.4
4
4.9
6.0
7.1
4.5
4.7
5.8
6.8
5
4.6
5.6
6.6
5.5
4.5
5.4
6.4
6
4.3
5.3
6.2
6.5
4.2
5.1
6.0
7
4.2
5.0
5.9
7.5
4.1
4.9
5.8
8
3.9
4.8
5.6
8.5
3.8
4.6
5.4
9
3.8
4.5
5.3
9.5
3.7
4.5
5.2
10
3.7
4.4
5.1
10.5
3.7
4.4
5.1
11
3.7
4.4
5.2
11.5
3.8
4.6
5.3
12
4.0
4.9
5.7
12.5
4.8
5.8
6.7
13
6.2
7.4
8.6
13.5
7.1
8.3
9.5
14
6.1
7.2
8.4
14.5
4.1
5.3
6.5
15
2.4
3.6
4.7
15.5
1.2
2.3
3.3
16
0.4
1.3
2.2
16.5
0.1
0.7
1.5
17
0.1
0.4
0.9
17.5
0.1
0.1
0.5

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Height Velocity Reference Values for Calculating the PCDAI (Females)
Height Velocity in cm per year (Females)
Age (years)
Minus 2SD
Minus 1SD
Mean
2.5
5.9
7.3
8.6
3
5.5
6.9
8.1
3.5
5.2
6.4
7.6
4
4.9
6.1
7.2
4.5
4.7
5.8
6.8
5
4.6
5.6
6.6
5.5
4.5
5.5
6.4
6
4.4
5.3
6.2
6.5
4.3
5.2
6.1
7
4.3
5.2
6.0
7.5
4.3
5.1
5.9
8
4.2
5.0
5.8
8.5
4.2
4.9
5.7
9
4.2
5.0
5.8
9.5
4.3
5.0
5.8
10
4.4
5.3
6.2
10.5
4.7
5.7
6.8
11
5.7
6.6
7.7
11.5
6.1
7.2
8.3
12
5.2
6.3
7.3
12.5
3.6
4.8
5.9
13
2.4
3.3
4.3
13.5
1.3
2.2
2.9
14
0.4
1.1
1.8
14.5
0.0
0.5
1.0

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Appendix I.
Crohns Disease Activity Index (CDAI)
Factor
Subtotal
1.
Number of liquid or very soft stools
(Record the frequency per day)
         __+___+___+___+___+___+___=___
Days: 1
    2      3      4 5      6
  7   Sum
X
2
2. Abdominal pain rating:
0 = none, 1 = mild, 2 = moderate, 
3 = severe
          __+___+___+___+___+___+___=___
Days: 1
    2      3      4 5      6
  7   Sum
X
5
3.
General well-being:
0 = generally well, 1 = slightly 
underpar, 2 = poor, 3 = very poor, 
4 = terrible
         __+___+___+___+___+___+___=___
Days: 1
    2      3      4 5      6
  7   Sum
X
7
4.
Number of 6 listed categories the 
subject now has:
Check all items that apply:
□  Arthritis/arthralgia
□  Iritis/uveitis
□  Erythema nodosum/ 
pyoderma gangrenosum/
aphthous stomatitis
□ Fissure, abscess and/or anal 
fistula (draining/non-draining)
□  Other cutaneous fistula 
(draining/non-draining) fistula
□  Fever over 100°F (37.8°C) during 
past week
                      ________
Record "0" if no categories checked
X
20
5.
Taking Lomotil/Imodium/ 
Loperamide/opiates for diarrhea 
0 = no, 1 = yes
________ X
30
6.
Abdominal mass
0 = none, 2 = questionable, 5 = defined
________ X
10
7.
Hematocrit:  ______
Male:
(47 - hematocrit) =
Female: (42 - hematocrit) = Subtotal ______
If hematocrit > normal, enter "0"
X
6
8.
Body weight:  __  __  __ . __ (kg)
Ideal weight for height:
  
  
 . 
 (kg)
100 x [1 - (Body wt/Ideal wt)] = 
Percent below ideal weight:  ______
If body wt > ideal wt, enter "0"
X
1
Total
*
Ideal weight is obtained from CDC growth charts.  The subtotal of box 8 should be rounded to a whole number.  
Numbers that fall between the range of .1-.4 must be rounded down.  Numbers that fall between the range of .5-.9 
must be rounded up.  To ensure consistency across all sites and to take into account the varying growth rates of 
subjects in this study, the IBW should be calculated at each visit.
*
Hematocrit values should be rounded to a whole number prior to completing the calculation in box 7 of the CDAI.  
Numbers that fall between the range of .1-.4 must be rounded down.  Numbers that fall between the range of .5-.9 
must be rounded up.

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Appendix J.
Subject CDAI Diary
Enter all values legibly using a black 
ballpoint pen.
Add item requested for each day.
Crohns Disease Activity Index
Subject Diary Card
Day
Date___
Day
Date___
Day
Date___
Day
Date___
Day
Date___
Day
Date___
Day
Date___
Number (total) of liquid or very soft 
stools per day.
Daily abdominal pain rating.
(0 = none, 1 = mild, 2 = moderate, 
3 = severe)
Daily rating of general well being.
(0 = well, 1 = slightly below par, 
2 = poor, 3 = very poor, 4 = terrible)
Subject Initials:___________ Subjects Signature:__________________________
Investigator or Designees Signature:______________________

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Question 1.
How much has your stomach been hurting you in the past two weeks?
□
□
□
□
□
Not at all
Hardly hurting 
at all
Hurting 
somewhat 
Hurting
quite a bit
Hurting
very much
Question 2. 
Taking medicines or tablets bothers you
□
□
□
□
□
Not at all
Hardly bothers 
at all
Bothers 
somewhat
Bothers 
quite a bit
Bothers
very much
Question 3.
How often has your inflammatory bowel disease prevented you from 
eating what you want in the past two weeks?
□
□
□
□
□
Never
Rarely
Sometimes
Often
Very often
Question 4.
How often have you been worrying about having a flare-up (increase of
symptoms) in the last two weeks?
□
□
□
□
□
Never
Rarely
Sometimes
Often
Very often
Question 5.
How much does it bother you that you have an illness that does not just go 
away?
□
□
□
□
□
Not at all
Hardly bothers 
at all
Bothers 
somewhat
Bothers quite a
bit
Bothers very 
much
Question 6.
How much energy did you have during the past two weeks?
□
□
□
□
□
Very much 
energy
Quite a bit of 
energy
Some energy
A little energy
No energy at 
all

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Question 7.
How do you feel about your weight?
□
□
□
□
□
I feel great 
about my 
weight
I feel good 
about my 
weight
I dont feel 
good or bad 
about my 
weight
I feel bad about 
my weight
I feel awful 
about my 
weight
Question 8.
How has your inflammatory bowel disease affected your family?
□
□
□
□
□
The effect has 
been great
The effect has 
been good
It has not 
affected our 
family
The effect has 
been bad
The effect has 
been awful
Question 9.
How often did you have to miss out on certain things (hobbies, play, 
parties) because of your inflammatory bowel disease in the past two weeks?
□
□
□
□
□
Never
Rarely
Sometimes
Often
Very often
Question 10.
How often have you been bothered by diarrhea (loose or frequent bowel 
movements) in the past two weeks?
□
□
□
□
□
Never
Rarely
Sometimes
Often
Very often
Question 11.
How often do you worry about health problems you might have in the 
future?
□
□
□
□
□
Never
Rarely
Sometimes
Often
Very often

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Question 12.
How often do you think it is unfair that you have inflammatory bowel 
disease?
□
□
□
□
□
Never
Rarely
Sometimes
Often
Very often
Question 13.
During the past two weeks, were you ever angry that you have 
inflammatory bowel disease?
□
□
□
□
□
Never
Rarely
Sometimes
Often
Very often
Question 14.
Do you think too many rules or limits are placed on you because of your 
inflammatory bowel disease?
□
□
□
□
□
Never
Rarely
Sometimes
Often
Very often
Question 15.
How do you feel about the way you look?
□
□
□
□
□
I think I look 
great
I think I look 
good
I dont think I 
look good or 
bad
I think I look 
bad
I think I look 
awful
Question 16.
Are you embarrassed because of your bowel condition?
□
□
□
□
□
Not at all
Hardly 
embarrassed at 
all
Embarrassed 
somewhat
Embarrassed 
quite a bit
Embarrassed 
very much
Question 17.
Did you have fun during the past two weeks?
□
□
□
□
□
Very often 
Often
Sometimes
Rarely
Never

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Question 18.
Is it harder to make friends because of your inflammatory bowel disease?
□
□
□
□
□
Not at all 
harder
A little harder
Quite a bit 
harder
Much harder
Very much 
harder
Question 19. How often do you worry about your stool (bowel movement) containing 
blood?
□
□
□
□
□
Never
Rarely
Sometimes
Often
Very often
Question 20.
Are you worried you cannot go out on a date or have a boyfriend or 
girlfriend because of your inflammatory bowel disease?
□
□
□
□
□
Not at all 
worried
Hardly worried 
at all
Worried 
somewhat
Worried quite 
a bit
Worried very 
much
Question 21.
How often did you feel sick to your stomach in the past two weeks?
□
□
□
□
□
Never
Rarely
Sometimes
Often
Very often
Question 22.
How do you feel about the tests you have to go through?
□
□
□
□
□
I do not mind 
them at all
I mind them a 
tiny bit
I mind them a 
little
I mind them a 
lot
I hate them
Question 23.
Do other children bully you or leave you out of things because of your 
inflammatory bowel disease or its treatment?
□
□
□
□
□
Never
Rarely
Sometimes
Often
Very often

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Question 24.
How often do you worry about having an operation?
□
□
□
□
□
Never
Rarely
Sometimes
Often
Very often
Question 25.
In the past two weeks how often were you afraid you may have an accident 
or not get to the toilet in time?
□
□
□
□
□
Never
Rarely
Sometimes
Often
Very often
Question 26.
Do you try to keep your inflammatory bowel disease a secret from other 
people?
□
□
□
□
□
No, I do not try 
at all
I dont try much
I try a little
I try hard
Yes, I try very 
hard
Question 27.
Does your inflammatory bowel disease make it difficult to travel or go on a 
holiday?
□
□
□
□
□
No, not 
difficult
A little 
difficult
Quite difficult
Very difficult
Yes, extremely 
difficult
Question 28.
How did you feel during the past two weeks?
□
□
□
□
□
Great
Good
Not good or 
bad
Bad
Awful
Question 29.
Are you happy with your life?
□
□
□
□
□
Yes, very 
happy
Happy
Not happy or 
unhappy
Unhappy
Very unhappy

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Question 30.
Do you feel there is someone you can talk to about your inflammatory 
bowel disease?
□
□
□
□
□
Always 
Often
Sometimes
Rarely
Never
Question 31.
How often did you have to pass gas in the past two weeks?
□
□
□
□
□
Never
Rarely
Sometimes
Often
Very often
Question 32.
How tired have you felt in the past two weeks?
□
□
□
□
□
Not at all tired
A little tired
Quite tired
Tired 
Very tired
Question 33.
How do you feel about your height?
□
□
□
□
□
I feel great 
about my 
height
I feel good 
about my 
height
I dont feel 
good or bad 
about my 
height
I feel bad 
about my 
height
I feel awful 
about my 
height
Question 34.
Does your inflammatory bowel disease get in the way of playing sports the 
way you would like to?
□
□
□
□
□
Never
Rarely
Sometimes
Often
Always
Question 35.
In the past two weeks how often were you able to go to school?  (If you are 
in the middle of a school break or the summer holidays, answer as if school was on)
□
□
□
□
□
Always 
Most days
Half the days
A few days
Never

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End of questionnaire
This completes the questionnaire.  Do you have anything else to add which you feel is 
important about having inflammatory bowel disease, or do you have any other 
remarks?  Please write them below.
_________________________________________________________
_________________________________________________________
_________________________________________________________

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Appendix L.
Excluded Medications
Cyclosporine
Tacrolimus
Therapeutic enemas and suppositories (not including those done in conjunction with 
routine colonoscopy)
Live vaccines
The combination of budesonide and prednisone (or equivalent)
Infliximab
Mycophenolate mofetil (MMF or CellCept®)
Growth Hormone
Kineret® (anakinra)
Tysabri (natalizumab)
Orencia (abatacept)
Concurrent biologic therapy
Any investigational agent
Any previous anti-TNF medication except infliximab before the M06-806 study 
(including adalimumab).

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Appendix M.
Day 70 Phone Call
Site Name/Number:  ________
Subject Number:  ________
Subject Initials:  ________
Please contact all Subjects 70 days following drug discontinuation.
Date of Call:  ____________
□     Lost to Follow-Up (Please check this box if subject was not willing to provide any follow-up 
information or you were unable to speak to the subject following at least one attempt).
□      No Events Reported
List any Adverse Events (AE) and/or Serious Adverse Events (SAE) that occurred since the subject was last 
seen in clinic for this study.  Please document all adverse events on a 500 AE CRF to be submitted to data 
management.  (Please report all SAEs to AbbVie within 24 hours of being made aware of the event.  
Follow-up information must also be reported within 24 hours of being made aware of the information.)
If events are listed above, your monitor will review and retrieve the appropriate CRF pages during 
their next visit.  Please fax this form to Clinipace Worldwide at (949) 809-6506.

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Appendix N.
Unscheduled Outpatient Visits, Emergency Room Visits and 
Hospitalizations
1.
Since the last study visit has the subject had any physician/health care visits for 
their Crohns disease other than the protocol required visits?
Yes ___
No  ___
If yes provide the following:
I.
Since the last visit, has the subject been seen by a physician for their Crohns 
Disease?
YES:_____
NO:_____
If YES, how many times:_______
II.
Since the last visit, has the subject been seen in the Emergency Room for their 
Crohns Disease?
YES:_____
NO:______
If YES, how many times:  _____
III. Since the last visit, has the subject been admitted to the hospital due to their 
Crohns Disease?
YES:_____
NO:______
If YES, how many times:_____
If YES, please indicate the total number of days in the hospital:_____

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Appendix O.
Subject Medication Log
Instructions:  As a participant in this study, it is also important to keep a record of all mediations you take (new and old) throughout the study.  Please take this 
sheet home with you and write down any medications you take during the study.  It will be VERY important that you bring this sheet back to your doctors office 
and speak with your doctor about everything you have written down.
Name of Medication
Date you took
first dose
Date you took
last dose
What dose of medicine 
did you take?
How often did you 
take the medicine?
Why did you take the 
medicine?

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Week 25 - Week 36
Subject Initials:  __________ Subject Study #:  ___________
Date
day/mm/yr
Day or 
Week #
Time of Study 
Drug 
Administration
Dose (mL) 
Administered
Kit #
Initials of Person 
Administering 
Study Medication
Comments
18/MAR/04
EXAMPLE
9:35 am
0.8
MM
none
Week 25
Week 26
Week 27
Week 28
Week 29
Week 30
Week 31
Week 32
Week 33
Week 34
Week 35
Week 36

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Week 241 - Week 263
Subject Initials:  __________ Subject Study #:  ___________
Date
day/mm/yr
Day or 
Week #
Time of Study 
Drug 
Administration
Dose (mL) 
Administered
Kit #
Initials of Person 
Administering 
Study Medication Comments
18/MAR/04
EXAMPLE
9:35 am
0.8
MM
none
Week 241
Week 242
Week 243
Week 244
Week 245
Week 246
Week 247
Week 248
Week 249
Week 250
Week 251
Week 252
Week 253
Week 254
Week 255
Week 256
Week 257
Week 258
Week 259
Week 260
Week 261
Week 262
Week 263
*
Week 263 dose will only be taken if on every-week dosing schedule.

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Week 313 - Week 335
Subject Initials:  __________ Subject Study #:  ___________
Date
day/mm/yr
Day or 
Week #
Time of Study 
Drug 
Administration
Dose (mL) 
Administered
Kit #
Initials of Person 
Administering 
Study Medication Comments
18/MAR/04
EXAMPLE
9:35 am
0.8
MM
none
Week 313
Week 314
Week 315
Week 316
Week 317
Week 318
Week 319
Week 320
Week 321
Week 322
Week 323
Week 324
Week 325
Week 326
Week 327
Week 328
Week 329
Week 330
Week 331
Week 332
Week 333
Week 334
Week 335
*
Week 335 dose will only be taken if on every-week dosing schedule.

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Appendix Q.
Self Injection Instructions
Subject Instructions
0.8 mL or 0.4 mL dose
(Administered as a single dose-prefilled syringe (PFS))
Protocol M06-807

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Tables of Contents
Dosing Schedule
General Information 
Injection Procedures

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Study Drug Dosing Schedule
Open-Label (PFS)
Subject Number:  _____________________________________
You will require subcutaneous (SC) injections throughout the study. 
Injections at scheduled study visits (Baseline, Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 
108, 120, 144, 168, 192, 216, 240, 264, 288, 312, 336, 360 and 384) will be done during 
your visit, at the doctors office.  On weeks between office visits, study drug will be 
self-administered at home by you or someone trained to give you the injections.
For 40 mg dose, one pre-filled syringe will contain 0.8 mL of liquid.  The total available 
dose is 0.8 mL.  The drug should be administered in one (1) SC injection, on the same day 
of the week for each dose.
For 20 mg dose, one pre-filled syringe will contain 0.4 mL of liquid.  The total available 
dose is 0.4 mL.  The drug should be administered in one (1) SC injection, on the same day 
of the week for each dose.
Please return all used and unused syringes to the clinic on your next visit.  Used syringes 
should be placed in the special sharps container provided.  All unused syringes should be 
returned in the original box.
If an injection is missed or something occurs where the full dose cannot be injected, 
contact your study center immediately for further instructions.  Please record any missed 
doses on your subject diary.
Remember to complete your dosing diary after each injection and to call the doctors office 
if you are having problems administering your study drug.

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General Information
PFS
●
Prefilled syringes will be labeled "adalimumab."
●
Store all adalimumab prefilled syringes in your refrigerator NOT in the 
freezer.  Should the syringes accidentally become frozen, call your study 
coordinator.
●
0.8 mL = 0.8 cc
●
Study drug should be taken at about the same time of day, on the same day of 
the week as directed by your study doctor.
●
USE A NEW SYRINGE EVERY INJECTION DAY.  There may be 
medication left in the syringe.  DO NOT RE-USE.
●
Save all study drugs.  Prefilled syringes (used and unused) must be returned 
to the study center at each visit.  Used syringes will be disposed of in a sharps 
container provided to you.
●
Whenever possible, have someone with you for at least 15 to 30 minutes after 
your injection.
●
Call your doctor IMMEDIATELY if you experience any itching, hives, 
shortness of breath, or any symptom that has you concerned.  If you are unable 
to reach your doctor or if you experience life-threatening symptoms call 911, 
or proceed to your nearest emergency room.

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Injection Procedures
PFS
1. Clean your workspace, gather your supplies, and wash your hands.
2. Identify the area on your abdomen or thigh (or upper 
arm if not self injecting).  Make sure the area you 
choose does not have any redness, tenderness, swelling, 
bruising, or psoriasis.  The area must also be at least 
2 cm (approximately 1 inch) away from the previous 
injection site.  IT IS VERY IMPORTANT TO 
CHANGE THE INJECTION SITE EVERY TIME!!!
3. Using a circular motion (starting at the injection site 
and moving outward) clean the selected injection site 
with an alcohol pad.  Allow skin to dry. 
4. Remove the needle cap.  Do not touch the needle.  
Expel any air bubbles from the syringe by tapping on 
the syringe.  If the needle becomes contaminated, 
discard all supplies and obtain a new syringe of study 
drug. 
5. Once the air is expelled from the syringe, the amount of 
solution in the syringe should be 0.8 mL.
6. Hold the syringe "like a dart" between your thumb and 
first finger close to the syringe/needle connection.

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PFS
7. With your other hand, pinch the skin around the 
injection site, forming a bulge in the skin.
8. Insert the needle into the skin at a 45-degree angle.  
Release pinched skin.
9.
GENTLY pull back on the syringe plunger.  If blood 
appears, withdraw needle - DO NOT INJECT!  
Contact your study center immediately for further 
instructions. 
10. Inject drug by pushing slowly on syringe plunger with 
thumb.
11. Remove needle while maintaining a 45-degree angle.
12. You may apply a Band-Aid over the injection site and 
apply gentle pressure, if necessary.  DO NOT RUB 
SITE.
13. DO NOT RECAP NEEDLE.  DO NOT SEPARATE THE NEEDLE FROM THE 
SYRINGE BEFORE DISPOSING.  Discard used syringes into Sharps Container.
EACH TIME THAT YOU GIVE YOURSELF AN INJECTION OF STUDY DRUG, 
REMEMBER TO RECORD THE INFORMATION ON YOUR SUBJECT DOSING 
DIARY.

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Self Injection Instructions
Subject Instructions
0.2 mL dose
Vials
Protocol M06-807

Adalimumab
M06-807 Protocol Amendment 7 for Poland
EudraCT 2007-006494-90
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Tables of Contents
Dosing Schedule
General Information 
Injection Procedures

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Study Drug Dosing Schedule
Vials
Subject Number:  _____________________________________
You will require subcutaneous (SC) injections throughout the study.
The injection for the visits at Weeks 4, 8, 12, 16, 20, 26, 32, 40, 48, 60, 72, 84, 96, 108, 
120, 144, 168, 192, 216, 240, 264, 288, 312, 336, 360 and 384 will be done during your 
visit at the doctor's office.  After Week 4, on weeks between office visits (i.e., Weeks 6, 
10, 14, etc.) study drug will be self-administered at home by you or someone trained to 
give you the injections.
The total dose is 0.2 mL.  The drug should be administered in one (1) SC injection, on the 
same day of the week for each dose.
For 10 mg dose, 0.2 mL of the solution is drawn from a vial containing adalimumab 
40 mg/0.8 mL solution.  The drug should be administered in one (1) SC injection, on the 
same day of the week for each dose.
Please return all used and unused vials to the clinic on your next visit.  Used syringes 
should be placed in the special sharps container provided.  All unused vials should be 
returned in the original box.
If an injection is missed or something occurs where the full dose cannot be injected, 
contact your study center immediately for further instructions.  Please record any missed 
doses on your subject diary.
Remember to complete your dosing sheet after each injection and to call the doctor's 
office if you are having problems administering your study medication.

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General Information
Vials
●
Vials will be labeled "adalimumab."
●
Store all adalimumab vials in your refrigerator NOT in the freezer.  Should the 
vials accidentally become frozen, call your study coordinator.
●
0.2 mL = 0.2 cc
●
Study drug should be taken at about the same time of day, on the same day of 
the week as directed by your study doctor.
●
USE A NEW VIAL EVERY INJECTION DAY.  There will be medication 
left in the vial.  DO NOT RE-USE.
●
Save all study drugs.  Vials (used and unused) must be returned to the study 
center at each visit.  Used vials and syringes will be disposed of in a sharps 
container provided to you.
●
Whenever possible, have someone with you for at least 15 to 30 minutes after 
your injection.
●
Call your doctor IMMEDIATELY if you experience any itching, hives, 
shortness of breath, or any symptom that has you concerned.  If you are unable 
to reach your doctor or if you experience life-threatening symptoms call 911, 
or proceed to your nearest emergency room.

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Injection Instructions 
Vials
Select a clean, well-lit, flat surface.
1.
Wash your hands thoroughly with soap and warm water.  It is important to keep 
your work surface as clean as possible.
2. Open carton.
3. Examine the carton and components in it to make sure they are complete.
●
One or two vials containing adalimumab
4. Remove the plastic cap from the vial.
5. Wipe the gray stopper with an alcohol swab and discard alcohol swab.
6. Place the vial upright on a hard, flat surface.
7. Choose an injection site on the upper thigh or abdomen.
8.
Prepare the injection site by wiping it thoroughly with a second alcohol swab.  Use 
a circular motion.

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9.
Remove the needle cover from the syringe.  (The needle is sterile, so be very 
careful not to touch the needle or allow it to touch any surface.)
10.
Draw the plunger on the syringe back.
11.
With the vial sitting on a hard, flat surface, insert needle straight down through the 
center of the gray stopper.  If the needle is correctly lined up, you should feel 
slight resistance and then a "pop" as the needle penetrates the center of the stopper. 
(Be careful not to insert the needle at an angle as this may cause the needle to 
bend.  If the needle is not correctly aligned, you will feel constant resistance as it 
penetrates the stopper and will not feel a "pop.")
12.
Push the plunger in forcing air into the vial.
13.
With the needle still in place, turn the vial upside down.  Keeping the vial at eye 
level, slowly pull the plunger back to draw the liquid into the syringe.  This will 
cause the bubbles to rise to the top of the syringe.  (As the liquid level in the vial 
drops, you may have to withdraw the needle partially to keep the tip of the needle 
in the liquid.)  Only 0.2 mL of the vial will be drawn into the syringe.
14.
With the needle still in the vial, check the syringe for air bubbles.  To remove any 
air bubbles, start by gently tapping the syringe.
15.
Slowly press the plunger to push any bubbles out of the syringe and into the vial.  
(If you accidentally push any liquid back into the vial, draw the liquid back into 
the syringe and check again for air bubbles.  It's okay for a small amount of liquid 
to remain in the vial.)
16.
Withdraw the needle from the vial, being careful not to touch it to any surface.

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Vials
17. Take the syringe in one hand.
18.
With your other hand, firmly pinch the skin around the cleaned injection site.  (Be 
careful not to touch the cleaned area.)
19.
Hold the syringe at about a 45-degree angle to the skin and use a quick, short 
motion to push the needle into the skin.
20. Once the needle is in, release the skin.

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Vials
21.
While firmly holding the syringe with one hand, use your other hand to slowly 
push the plunger and inject the adalimumab.  Only 0.2 mL of the vial will be 
injected.
22.
When the syringe is empty, remove the needle from the skin, being careful to keep 
it at the same 45-degree angle.
23.
Dispose of both the needle and syringe in a puncture-resistant container, or sharps 
container, which will be provided.
24.
You may want to press a cotton ball on the injection site for 10 seconds.  If there is 
some slight bleeding, you may choose to apply a small bandage.
25.
Return the vial into the original packaging.
26.
Place the medication kit back into the refrigerator.

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Vials
EACH TIME YOU RECEIVE AN INJECTION OF STUDY MEDICATION, 
REMEMBER TO RECORD THE INFORMATION ON YOUR DOSING SHEET.
GENERAL INFORMATION:
27.
ROTATING INJECTION SITES IS RECOMMENDED.  PLEASE DO NOT 
INJECT THE STUDY MEDICATION INTO A PRIOR SITE OF INJECTION.
28.
Store all of your drug in the refrigerator.  Should the vials become accidentally 
frozen or left out, call your study coordinator.  DO NOT USE THESE VIALS.
29.
If you forget to take the drug or make a mistake with an injection, please call your 
study coordinator.
30.
Please save all of your study medication, even if you skip a dose.  Please bring all 
used and unused vials back to the physician at your next study visit.
31.
There will be study medication remaining in the vials.  DO NOT USE THE 
MEDICATION LEFT IN THE VIAL.  Please return the vial along with the 
remaining study medication back to the physician at your next study visit.
32.
Specific side effects to watch for:  redness and swelling at the injection site.  
Please tell the study coordinator if you have any side effects from injecting the 
drug.

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Appendix R.
Standard Weights

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Appendix S.
Subject AbbVie Site Drug Accountability Form

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Appendix T.
Work Productivity and Activity Impairment Questionnaire: 
Crohns Disease (WPAI-CD) – Caregiver
The following questions ask about the effect of your childs Crohns disease on your ability 
to work and perform regular activities.  Please fill in the blanks or circle a number, as 
indicated.
1. Are you currently employed (working for pay)? _____ NO ___ YES
If NO, check "NO" and skip to question 6.
The next questions are about the past seven days, not including today.
2. During the past seven days, how many hours did you miss from work because of 
problems associated with your childs Crohns disease?  Include hours you missed on 
sick days, times you went in late, left early, etc., because of your childs Crohns 
disease.  Do not include time you missed for your child to participate in this study.
_____ HOURS
3. During the past seven days, how many hours did you miss from work because of any 
other reason, such as vacation, holidays, time off for your child to participate in this 
study?
_____ HOURS
4. During the past seven days, how many hours did you actually work?
_____ HOURS (If "0," skip to question 6.)

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5. During the past seven days, how much did your childs Crohns disease affect your 
productivity while you were working?
Think about days you were limited in the amount or kind of work you could do, days 
you accomplished less than you would like, or days you could not do your work as 
carefully as usual.  If your childs Crohns disease affected your work only a little, 
choose a low number.  Choose a high number if your childs Crohns disease affected 
your work a great deal.  
Consider only how much your childs Crohns disease affected 
your productivity while you were working.
My childs Crohns 
disease had no 
effect on my work
My childs Crohns 
disease completely 
prevented me from 
working
0
1
2
3
4
5
6
7
8
9
10
CIRCLE A NUMBER
6. During the past seven days, how much did your childs Crohns Disease affect your 
ability to do your regular daily activities, other than work at a job?
By regular activities, we mean the usual activities you do, such as work around the 
house, shopping, childcare, exercising, studying, etc.  Think about times you were 
limited in the amount or kind of activities you could do and times you accomplished 
less than you would like.  If your childs Crohns Disease affected your activities only a 
little, choose a low number.  Choose a high number if your childs Crohns Disease 
affected your activities a great deal.  
Consider only how much your childs Crohns disease affected your ability 
to do your regular daily activities, other than work at a job.
My childs Crohns 
disease had no 
effect on my 
daily activities
My childs Crohns 
disease completely 
prevented me from 
doing my daily 
activities
0
1
2
3
4
5
6
7
8
9
10
CIRCLE A NUMBER
WPAI:CD-Caregiver (US English)

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Appendix U.
Protocol Amendment:  List of Changes
The summary of changes is listed in Section 1.1.
Specific Protocol Changes:
Section 1.0  Title Page
"Emergency Contact:" previously read:
Emergency Contact:
Andreas Lazar, MD
Associate Medical Director
AbbVie Deutschland GmbH & Co. KG
Knollstrasse
Building 34, Room 214
67061 Ludwigshafen
Germany 
Office:
49 621 589 2679
Fax:
49 621 589 1288
Cell:
49 160 9725 4782
Email:
andreas.lazar@abbvie.com
Has been changed to read:
Emergency Contact:
Andreas Lazar, MD
Medical Director
AbbVie Deutschland GmbH & Co. KG
Knollstrasse
Building 34, Room 214
67061 Ludwigshafen
Germany 
Office:
49 621 589 2679
Fax:
49 621 589 1288
Cell:
49 160 9725 4782
Email:
andreas.lazar@abbvie.com
Section 5.1.  Overall Study Design and Plan:  Description
Eleventh paragraph, first sentence previously read:
The duration of the study could last up to 336 weeks (approximately 6.5 years).
Has been changed to read:
The duration of the study could last up to 408 weeks (approximately 8 years).

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Has been changed to read:

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Table 1.  Study Activities
Previously read:
Table 1.
Study Activities
Activity
Baseline
Week 4
Week 8
Week 12
Week 24
Week 36
Week 48
Week 60
Week 72
Week 84
Inclusion/exclusion criteria
X
Informed consent
X
Previous and concomitant 
medications
Xa
X
X
X
X
X
X
X
X
X
Urine pregnancy testb
Xa
X
X
X
X
X
X
X
X
X
Vital signsc
Xa
X
X
X
X
X
X
X
X
X
Physical exam
Xa
X
X
X
X
X
X
X
X
X
General LABd
Xa
X
X
X
X
X
X
X
X
X
TB testing (PPD or 
QuantiFERON-TB Gold)m
X
Urinalysise
Xa
X
X
X
X
X
X
X
X
X
Erythrocyte sedimentation rate
Xa
X
X
X
X
X
X
X
X
X
CRP
Xa
X
X
X
ANA
Xa
X
Anti-dsDNAf
Xa
X
PCDAI
Xa
X
X
X
X
X
X
X
X
X
CDAIg
Xa
X
X
X
X
X
X
X
X
X
IMPACT III Questionnaireh
Xa
X
X
X
X

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Activity
Baseline
Week 4
Week 8
Week 12
Week 24
Week 36
Week 48
Week 60
Week 72
Week 84
Unscheduled outpatient visits, 
emergency room visits and 
hospitalizations questionnaire
Xa
X
X
X
X
X
X
X
X
X
Work Productivity and 
Impairment Questionnaire:  
Crohn's Disease (WPAI – CD)
Xa
X
X
X
X
X
X
X
X
X
X-ray for bone agei
Xa
X
Serum bone markers
Xa
X
X
X
PK Blood Samplej
X
X
X
Anti-adalimumab blood levels 
(AAA)j
X
X
X
Adverse eventsk
Xa
X
X
X
X
X
X
X
X
X
Dispense study drug
Xa
X
X
X
X
X
X
X
X
X

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Activity
Week 96
Week 108
Week 120
Week 132 
Call
Week 144
Week 156 
Call
Week 168
Week 180 
Call
Week 192
Week 204 
Call
Inclusion/exclusion criteria
Informed consent
Previous and concomitant 
medications
X
X
X
X
X
X
X
X
X
X
Urine pregnancy testb
X
X
X
X
X
X
Vital signsc
X
X
X
X
X
X
Physical exam
X
X
X
X
X
X
General LABd
X
X
X
X
X
X
TB testing (PPD or 
QuantiFERON-TB Gold)m
X
X
X
Urinalysise
X
X
X
X
X
X
Erythrocyte sedimentation rate
X
X
X
X
X
X
CRP
X
X
X
X
ANA
X
X
X
Anti-dsDNAf
X
X
X
PCDAI
X
X
X
X
X
X
CDAIg
X
X
X
X
X
X
IMPACT III Questionnaireh
X
X
X
X
X

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Activity
Week 96
Week 108
Week 120
Week 132 
Call
Week 144
Week 156 
Call
Week 168
Week 180 
Call
Week 192
Week 204 
Call
Unscheduled outpatient visits, 
emergency room visits and 
hospitalizations questionnaire
X
X
X
X
X
X
X
X
X
X
Work Productivity and Impairment 
Questionnaire:  Crohn's Disease 
(WPAI – CD)
X
X
X
X
X
X
X-ray for bone agei
X
X
X
Serum bone markersi
X
X
X
X
X
PK Blood Samplej
X
X
X
X
X
Anti-adalimumab blood levels 
(AAA)j
X
X
X
X
X
Adverse eventsk
X
X
X
X
X
X
X
X
X
X
Dispense study drug
X
X
X
X
X
X

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Activity
Week 
216
Week 
228 
Call
Week 
240
Week 
252 
Call
Week 
264
Week 
276 
Call
Week 
288
Week 
300 
Call
Week 
312
Week 
324 
Call
Week 
336/ 
Early 
Term
Unsched 
Visit
70-Day 
Follow-up 
Call
Inclusion/exclusion criteria
Informed consent
Previous and concomitant 
medications
X
X
X
X
X
X
X
X
X
X
X
X
Urine pregnancy testb
X
X
X
X
X
X
X
Vital signsc
X
X
X
X
X
X
X
Physical exam
X
X
X
X
X
X
X
General LABd
X
X
X
X
X
X
X
TB testing (PPD or 
QuantiFERON-TB Gold)m
X
X
X
Urinalysise
X
X
X
X
X
X
X
Erythrocyte sedimentation 
rate
X
X
X
X
X
X
X
CRP
X
X
X
X
X
ANA
X
X
Anti-dsDNAf
X
X
PCDAI
X
X
X
X
X
X
X
CDAIg
X
X
X
X
X
X
X
IMPACT III Questionnaireh
X
X
X
X
X
X
X

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Activity
Week 
216
Week 
228 
Call
Week 
240
Week 
252 
Call
Week 
264
Week 
276 
Call
Week 
288
Week 
300 
Call
Week 
312
Week 
324 
Call
Week 
336/ 
Early 
Term
Unsched 
Visit
70-Day 
Follow-up 
Call
Unscheduled outpatient 
visits, emergency room 
visits and 
hospitalizations 
questionnaire
X
X
X
X
X
X
X
X
X
X
X
X
Work Productivity and 
Impairment 
Questionnaire:  Crohn's 
Disease (WPAI – CD)
X
X
X
X
X
X
X
X-ray for bone agei
X
X
Serum bone markersi
X
X
X
X
X
X
X
PK Blood Samplej
X
X
X
X
X
X
X
Anti-adalimumab blood 
levels (AAA)j
X
X
X
X
X
X
X
Adverse eventsk
X
X
X
X
X
X
X
X
X
X
X
X
X
Dispense study drug
X
X
X
X
X
Xl
a.
At the Baseline Visit, the following procedures will be completed as part of Week 52 of the M06-806 study.
b.
Performed on all females of child-bearing potential - Urine pregnancy test at all study visits.
c.
Vital sign determinations of height, weight, sitting blood pressure, heart rate, respiratory rate, and body temperature will be obtained at each visit.
d.
Blood draws should be performed after questionnaire and vital signs determinations and before study drug administration.
e.
Microscopic urinalysis will be performed at any visit if dipstick UA is abnormal (protein greater than a trace, blood greaterthan 5 - 10 Ery/ul, moderate or large ketone count 
or glucose greater than 50 mg/dL).
f.
If an ANA result is positive, anti-dsDNA will be performed automatically.
g.
For subjects who are age 13 or older at the M06-807 Baseline Visit, a CDAI will be completed at each visit.

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h.
For subjects who are age 10 or older at the M06-807 Baseline Visit, an IMPACT III Assessment will be completed at Baseline, Weeks 12, 24, 48, 72, 108, 120, 144, 168, 192, 
216, 240, 264, 288, 312 and 336/ET and unscheduled visits.
i.
If the height velocity is 0 and, in the opinion of the investigator, a subject is no longer growing, the x-ray for bone age and the determination of serum bone markers can be 
omitted.
j.
In addition to blood draws every 24 weeks, PK and AAA blood draws to be performed if subject meets flare criteria and dose escalated to ew dosing.
k.
All AEs, including SAEs, will be captured throughout the study from the time that the subject signs the Informed Consent Form.  SAEs will be captured throughout the 70 day 
follow-up period (if applicable).
l.
If an unscheduled visit is performed to change the frequency or dose of study drug, study drug may be dispensed.
m.
PPD or QuantiFERON-TB Gold testing at Weeks 48, 96, 144, 192, 240, 288 and 336.

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Has been changed to read:
Table 1.
Study Activities
Activity
Baseline
Week 4
Week 8
Week 12
Week 24
Week 36
Week 48
Week 60
Week 72
Week 84
Inclusion/exclusion criteria
X
Informed consent
X
Previous and concomitant 
medications
Xa
X
X
X
X
X
X
X
X
X
Urine pregnancy testb
Xa
X
X
X
X
X
X
X
X
X
Vital signsc
Xa
X
X
X
X
X
X
X
X
X
Physical exam
Xa
X
X
X
X
X
X
X
X
X
General LABd
Xa
X
X
X
X
X
X
X
X
X
TB testing (PPD or 
QuantiFERON-TB Gold)e
X
Urinalysisf
Xa
X
X
X
X
X
X
X
X
X
Erythrocyte sedimentation rate
Xa
X
X
X
X
X
X
X
X
X
CRP
Xa
X
X
X
ANA
Xa
X
Anti-dsDNAg
Xa
X
PCDAI
Xa
X
X
X
X
X
X
X
X
X
CDAIh
Xa
X
X
X
X
X
X
X
X
X
IMPACT III Questionnairei
Xa
X
X
X
X

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Activity
Baseline
Week 4
Week 8
Week 12
Week 24
Week 36
Week 48
Week 60
Week 72
Week 84
Unscheduled outpatient visits, 
emergency room visits and 
hospitalizations questionnaire
Xa
X
X
X
X
X
X
X
X
X
Work Productivity and 
Impairment Questionnaire:  
Crohn's Disease (WPAI – CD)
Xa
X
X
X
X
X
X
X
X
X
X-ray for bone agej
Xa
X
Serum bone markers
Xa
X
X
X
PK Blood Samplek
X
X
X
Anti-adalimumab blood levels 
(AAA)k
X
X
X
Adverse eventsl
Xa
X
X
X
X
X
X
X
X
X
Dispense study drug
Xa
X
X
X
X
X
X
X
X
X

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Activity
Week 96
Week 108
Week 120
Week 132 
Call
Week 144
Week 156 
Call
Week 168
Week 180 
Call
Week 192
Week 204 
Call
Inclusion/exclusion criteria
Informed consent
Previous and concomitant 
medications
X
X
X
X
X
X
X
X
X
X
Urine pregnancy testb
X
X
X
X
X
X
Vital signsc
X
X
X
X
X
X
Physical exam
X
X
X
X
X
X
General LABd
X
X
X
X
X
X
TB testing (PPD or 
QuantiFERON-TB Gold)e
X
X
X
Urinalysisf
X
X
X
X
X
X
Erythrocyte sedimentation rate
X
X
X
X
X
X
CRP
X
X
X
X
ANA
X
X
X
Anti-dsDNAg
X
X
X
PCDAI
X
X
X
X
X
X
CDAIh
X
X
X
X
X
X
IMPACT III Questionnairei
X
X
X
X
X

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Activity
Week 96
Week 108
Week 120
Week 132 
Call
Week 144
Week 156 
Call
Week 168
Week 180 
Call
Week 192
Week 204 
Call
Unscheduled outpatient visits, 
emergency room visits and 
hospitalizations questionnaire
X
X
X
X
X
X
X
X
X
X
Work Productivity and Impairment 
Questionnaire:  Crohn's Disease 
(WPAI – CD)
X
X
X
X
X
X
X-ray for bone agej
X
X
X
Serum bone markersj
X
X
X
X
X
PK Blood Samplek
X
X
X
X
X
Anti-adalimumab blood levels 
(AAA)k
X
X
X
X
X
Adverse eventsl
X
X
X
X
X
X
X
X
X
X
Dispense study drug
X
X
X
X
X
X

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Activity
Week 
216
Week 
228 
Call
Week 
240
Week 
252 
Call
Week 
264
Week 
276 
Call
Week 
288
Week 
300 
Call
Week 
312
Week 
324 
Call
Week 
336
Week 
348
Call
Week 360
Inclusion/exclusion criteria
Informed consent
Previous and concomitant 
medications
X
X
X
X
X
X
X
X
X
X
X
X
X
Urine pregnancy testb
X
X
X
X
X
X
X
Vital signsc
X
X
X
X
X
X
X
Physical exam
X
X
X
X
X
X
X
General LABd
X
X
X
X
X
X
X
TB testing (PPD or 
QuantiFERON-TB Gold)e
X
X
X
Urinalysisf
X
X
X
X
X
X
X
Erythrocyte sedimentation 
rate
X
X
X
X
X
X
X
CRP
X
X
X
X
X
X
ANA
X
Anti-dsDNAg
X
PCDAI
X
X
X
X
X
X
X
CDAIh
X
X
X
X
X
X
X
IMPACT III Questionnairei
X
X
X
X
X
X
X

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Activity
Week 
216
Week 
228 
Call
Week 
240
Week 
252 
Call
Week 
264
Week 
276 
Call
Week 
288
Week 
300 
Call
Week 
312
Week 
324 
Call
Week 
336
Week
348
Call
Week 360
Unscheduled outpatient 
visits, emergency room 
visits and 
hospitalizations 
questionnaire
X
X
X
X
X
X
X
X
X
X
X
X
X
Work Productivity and 
Impairment 
Questionnaire:  Crohn's 
Disease (WPAI – CD)
X
X
X
X
X
X
X
X-ray for bone agej
X
X
X
Serum bone markersj
X
X
X
X
X
X
X
PK Blood Samplek
X
X
X
X
X
X
X
Anti-adalimumab blood 
levels (AAA)k
X
X
X
X
X
X
X
Adverse eventsl
X
X
X
X
X
X
X
X
X
X
X
X
X
Dispense study drug
X
X
X
X
X
X
X

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Activity
Week 372 Call
Week 384
Week 396 Call
Week 408/
Early Term
Unsched Visit
70-Day Follow-Up Call
Inclusion/exclusion criteria
Informed consent
Previous and concomitant medications
X
X
X
X
X
Urine pregnancy testb
X
X
X
Vital signsc
X
X
X
Physical exam
X
X
X
General LABd
X
X
X
TB testing (PPD or QuantiFERON-TB Gold)e
X
X
Urinalysisf
X
X
X
Erythrocyte sedimentation rate
X
X
X
CRP
X
X
X
ANA
X
Anti-dsDNAg
X
PCDAI
X
X
X
CDAIh
X
X
X
IMPACT III Questionnairei
X
X
X
Unscheduled outpatient visits, emergency room 
visits and hospitalizations questionnaire
X
X
X
X
X

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Activity
Week 372 Call
Week 384
Week 396 Call
Week 408/
Early Term
Unsched Visit
70-Day Follow Up Call
Work Productivity and Impairment 
Questionnaire:  Crohn's Disease (WPAI – CD)
X
X
X
X-ray for bone agej
X
Serum bone markersj
X
X
X
PK Blood Samplek
X
X
X
Anti-adalimumab blood levels (AAA)k
X
X
X
Adverse eventsl
X
X
X
X
X
X
Dispense study drug
X
Xm
a.
At the Baseline Visit, the following procedures will be completed as part of Week 52 of the M06-806 study.
b.
Performed on all females of child bearing potential – Urine pregnancy test at all study visits.
c.
Vital sign determinations of height, weight, sitting blood pressure, heart rate, respiratory rate, and body temperature will be obtained at each visit.
d.
Blood draws should be performed after questionnaire and vital signs determinations and before study drug administration.
e.
PPD or QuantiFERON-TB Gold testing at Weeks 48, 96, 144, 192, 240, 288, 336, 384 and 408/ET.  No annual TB test should be done at Week 408 or at ET if already done at 
Week 384 or later.
f.
Microscopic urinalysis will be performed at any visit if dipstick UA is abnormal (protein greater than a trace, blood greaterthan 5 – 10 Ery/ul, moderate or large ketone count 
or glucose greater than 50 mg/dL).
g.
If an ANA result is positive, anti-dsDNA will be performed automatically.
h.
For subjects who are age 13 or older at the M06-807 Baseline Visit, a CDAI will be completed at each visit.
i.
For subjects who are age 10 or older at the M06-807 Baseline Visit, an IMPACT III Assessment will be completed at Baseline, Weeks 12, 24, 48, 72, 108, 120, 144, 168, 192, 
216, 240, 264, 288, 312, 336, 360, 384, 408/ETC and unscheduled visits.
j.
If the height velocity is 0 and, in the opinion of the investigator, a subject is no longer growing, the x-ray for bone age and the determination of serum bone markers can be 
omitted.
k.
In addition to blood draws every 24 weeks, PK and AAA blood draws to be performed if subject meets flare criteria and dose escalated to ew dosing.
l.
All AEs, including SAEs, will be captured throughout the study from the time that the subject signs the Informed Consent Form.  SAEs will be captured throughout the 70 day 
follow-up period (if applicable).

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m.
If an unscheduled visit is performed to change the frequency or dose of study drug, study drug may be dispensed.

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Section 5.3.1.1  Study Procedures
First paragraph, last sentence previously read:
The site will call the subjects at Weeks 132, 156, 180, 204, 228, 252, 276, 300 and 324 in 
order to collect any safety information from the subject as illustrated in Table 1.
Has been changed to read:
The site will call the subjects at Weeks 132, 156, 180, 204, 228, 252, 276, 300, 324, 348, 
372 and 396 in order to collect any safety information from the subject as illustrated in 
Table 1.
Section 5.3.1.1  Study Procedures
Subsection Previous and Concomitant Medications
First paragraph, first sentence previously read:
Changes in concomitant medications will be assessed at each study visit from Baseline 
through the Week 336/ET visit.
Has been changed to read:
Changes in concomitant medications will be assessed at each study visit from Baseline 
through the Week 408/ET visit.
Section 5.3.1.1  Study Procedures
Subsection TB Testing
Second paragraph previously read:
A PPD skin test (alternatively, also known as tuberculin skin test) must be placed or the 
QuantiFERON®-TB Gold test (or equivalent) must be performed for subjects with a 
negative test at Screening visit after the amended protocol is approved by IRB/IEC 
including those with a prior history of Bacille Calmette-Guérin (BCG) administration at 
the time the subject reaches one of the scheduled visits:  Weeks 48, 96, 144, 192, 240, 
288 and 336. 

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Has been changed to read:
A PPD skin test (alternatively, also known as tuberculin skin test) must be placed or the 
QuantiFERON®-TB Gold test (or equivalent) must be performed for subjects with a 
negative test at Screening visit after the amended protocol is approved by IRB/IEC 
including those with a prior history of Bacille Calmette-Guérin (BCG) administration at 
the time the subject reaches one of the scheduled visits:  Weeks 48, 96, 144, 192, 240, 
288, 336 and 384.  TB testing should not be done at Week 408 or at the ET visit if a test 
was done at week 384 or later.
Section 5.3.1.1  Study Procedures
Subsection Adverse Events
First paragraph, first sentence previously read:
Adverse events will be assessed at every study visit from Baseline through the 
Week 336/ET visit.
Has been changed to read:
Adverse events will be assessed at every study visit from Baseline through the 
Week 408/ET visit.  
Section 5.3.2.1  Collection of Samples for Analysis
Subsection Collection of Samples for Adalimumab Analysis
Second paragraph previously read:
A minimum of 14 samples are planned to be collected per subject for the analysis of 
adalimumab concentrations.
Has been changed to read:
A minimum of 17 samples are planned to be collected per subject for the analysis of 
adalimumab concentrations.

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Section 5.3.2.1  Collection of Samples for Analysis
Subsection Collection of Samples for AAA Analysis
Second paragraph previously read:
A minimum of 14 blood samples are planned to be collected per subject for AAA 
analysis.
Has been changed to read:
A minimum of 17 blood samples are planned to be collected per subject for AAA 
analysis.
Section 5.4.1  Discontinuation of Individual Subjects 
Second paragraph, first sentence previously read:
If the subject prematurely discontinues study drug use, the procedures outlined for the 
Week 336/ET Visit must be completed within 2 weeks of the last dose of study drug, and 
preferably prior to the initiation of another therapy.
Has been changed to read:
If the subject prematurely discontinues study drug use, the procedures outlined for the 
Week 408/ET Visit must be completed within 2 weeks of the last dose of study drug, and 
preferably prior to the initiation of another therapy.  

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Section 6.0  Complaints
Add:  new section number and text
6.0
Complaints 
A Complaint is any written, electronic, or oral communication that alleges deficiencies 
related to the physical characteristics, identity, quality, purity, potency, durability, 
reliability, safety, effectiveness, or performance of a product/device after it is released for 
distribution.
The investigational product in this trial contains both: 
●
Biologic compound(s) and
●
Device component(s) (pre-filled syringe, pen).
Complaints associated with any component of this investigational product must be 
reported to the Sponsor (Section 6.2.2).  For adverse events, please refer to Sections 6.1 
through 6.1.6.  For product complaints, please refer to Section 6.2.
Section 6.0 through 6.6
Section number and title previously read:
6.0 
Adverse Events
6.1
Definitions
6.1.1
Adverse Event
6.1.2
Serious Adverse Events
6.2
Adverse Event Severity
6.3
Relationship to Study Drug
6.4
Adverse Event Collection Period
6.5.1
Collection of Data Regarding Known Manifestations of the 
Disease Under Study

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6.6
Pregnancy
Has been changed to read:
6.0
Complaints
6.1
Medical Complaints
6.1.1
Definitions
6.1.1.1
Adverse Event
6.1.1.2
Serious Adverse Events
6.1.2
Adverse Event Severity
6.1.3
Relationship to Study Drug
6.1.4
Adverse Event Collection Period
6.1.5.1
Collection of Data Regarding Known Manifestations of the 
Disease Under Study
6.1.6
Pregnancy
Section 6.5  Adverse Event Reporting
Previously read:
6.5
Adverse Event Reporting
In the event of a serious adverse event, and additionally, any non-serious event of 
malignancy in patients 30 years of age and younger, whether related to study drug or not, 
the physician will notify AbbVie within 24 hours of the physician becoming aware of the 
event by faxing the serious adverse event or non-serious event of malignancy in patients 
30 years of age and younger forms to the Immunology Clinical Safety Team.

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For all sites:
For questions regarding SAEs, please contact:
Has been changed to read:
6.1.5
Adverse Event Reporting
In the event of a serious adverse event, and additionally, any non-serious event of 
malignancy in patients 30 years of age and younger, whether related to study drug or not, 
the physician will notify AbbVie Immunology Clinical Safety Management Team within 
24 hours of the physician becoming aware of the event by faxing or emailing the serious 
adverse event or nonserious event of malignancy in patients 30 years of age and younger 
forms to the Immunology Clinical Safety Team within 24 hours of being made aware of 
the adverse event.

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To report a Serious Adverse Event (SAE):
AbbVie Safety Fax Number:  
Email:  
For SAE concerns, contact the Immunology Safety Team at:
For any subject safety concerns, contact the physician listed below:
Primary Study Designated Physician:
Should in case of subject safety concerns or medical emergencies the Primary Study 
Designated Physician be unavailable, please call the following central back-up number:
Phone:  

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Section 6.2  Product Complaint
Add:  new section and text, renumber subsequent sections
6.2
Product Complaint 
6.2.1
Definition
A Product Complaint is any Complaint (see Section 6.0 for the definition) related to the 
biologic or drug component of the product or to the medical device component(s), if 
present (see below).
For a product this may include, but is not limited to, damaged/broken product or 
packaging, product appearance whose color/markings do not match the labeling, labeling 
discrepancies/inadequacies in the labeling/instructions (example:  printing illegible), 
missing components/product, device not working properly, or packaging issues.
For medical devices, a product complaint also includes all deaths of a patient using the 
device, any illness, injury, or adverse event in the proximity of the device, an adverse 
event that could be a result of using the device, any event needing medical or surgical 
intervention including hospitalization while using the device and use errors.
Any information available to help in the determination of causality by the device to the 
events outlined directly above should be captured.
6.2.2
Reporting
Product Complaints concerning the investigational product and/or device must be reported 
to the Sponsor within 24 hours of the study site's knowledge of the event via the Product 
Complaint form.  Product Complaints occurring during the study will be followed-up to a 
satisfactory conclusion.  All follow-up information is to be reported to the Sponsor (or an 
authorized representative) and documented in source as required by the Sponsor.  Product 
Complaints associated with adverse events will be reported in the study summary.  All 
other complaints will be monitored on an ongoing basis.

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Product Complaints may require return of the product with the alleged complaint 
condition (syringe, pen, etc.).  In instances where a return is requested, every effort should 
be made by the investigator to return the product within 30 days.  If returns cannot be 
accommodated within 30 days, the site will need to provide justification and an estimated 
date of return.
The description of the complaint is important for AbbVie in order to enable AbbVie to 
investigate and determine if any corrective actions are required.
Section 7.0  Protocol Deviations
Contact information following first paragraph previously read:
Has been changed to read:
Section 8.1.3  Other Analyses
Third bullet previously read:
●
Ethnicity [White, Non-white]

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Has been changed to read:
●
Race [White, Non-white]
Section 8.1.5  Interim Analysis
Previously read:
There will be one planned interim analysis.  Details of the analysis will be described in the 
study SAP.
Has been changed to read:
There will be multiple planned interim analyses.  Details of the analyses will be described 
in the study SAPs.
Appendix B.  List of Protocol Signatories
Previously read:
Name
Title
Functional Area
Statistics
Pharmacokinetics
Clinical
Clinical
Clinical
Has been changed to read:
Name
Title
Functional Area
Statistics
Pharmacokinetics
Clinical
Clinical
Clinical

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Appendix H.  PCDAI Users Guide and Guideline for Reference Weight and 
Reference Height
Subsection Physical Examination
Third paragraph previously read:
From Baseline to Week 336:  use weight from previous visit
Has been changed to read:
From Baseline to Week 408:  use weight from previous visit
Appendix H.  PCDAI Users Guide and Guideline for Reference Weight and 
Reference Height
Subsection Physical Examination
Heading "Item 8.  Height"
Add:  new bullet 15, 16 and 17
●
From Week 336 to Week 360, use height from Week 312
●
From Week 360 to Week 384, use height from Week 336
●
From Week 384 to Week 408, use height from Week 360
Appendix M.  Day 70 Phone Call
Last paragraph, last sentence previously read:
Please fax this form to Paragon at 
Has been changed to read:
Please fax this form to Clinipace Worldwide at 
Appendix P.  Subject Dosing Diary
Table:  Week 241 - Week 263
Last row previously read:
Date
day/mm/yr
Day or 
Week #
Time of Study 
Drug 
Administration
Dose (mL) 
Administered
Kit #
Initials of Person 
Administering 
Study Medication Comments
Week 263*

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Has been changed to read:
Date
day/mm/yr
Day or 
Week #
Time of Study 
Drug 
Administration
Dose (mL) 
Administered
Kit #
Initials of Person 
Administering 
Study Medication Comments
Week 263
Appendix P.  Subject Dosing Diary
Table:  Week 313 - Week 335
Row "Week 335*" previously read:
Date
day/mm/yr
Day or 
Week #
Time of Study 
Drug 
Administration
Dose (mL) 
Administered
Kit #
Initials of Person 
Administering 
Study Medication Comments
Week 335*
Has been changed to read:
Date
day/mm/yr
Day or 
Week #
Time of Study 
Drug 
Administration
Dose (mL) 
Administered
Kit #
Initials of Person 
Administering 
Study Medication Comments
Week 335

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Appendix P.  Subject Dosing Diary
Add table:  Week 336 - Week 360
Week 336 - Week 360
Subject Initials:  __________ Subject Study #:  ___________
Date
day/mm/yr
Day or 
Week #
Time of Study 
Drug 
Administration
Dose (mL) 
Administered
Kit #
Initials of Person 
Administering 
Study Medication Comments
18/MAR/04
EXAMPLE
9:35 am
0.8
MM
none
Week 336
Week 337
Week 338
Week 339
Week 340
Week 341
Week 342
Week 343
Week 344
Week 345
Week 346
Week 347
Week 348
Week 349
Week 350
Week 351
Week 352
Week 353
Week 354
Week 355
Week 356
Week 357
Week 358

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Appendix Q.  Self Injection Instructions
Subsection Study Drug Dosing Schedule
Open-Label (PFS)
Second paragraph, first sentence previously read:
Injections at scheduled study visits (Baseline, Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 
108, 120, 144, 168, 192, 216, 240, 264, 288 and 312) will be done during your visit, at the 
doctors office.
Has been changed to read:
Injections at scheduled study visits (Baseline, Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 
108, 120, 144, 168, 192, 216, 240, 264, 288, 312, 336, 360 and 384) will be done during 
your visit, at the doctors office.
Appendix Q.  Self Injection Instructions
Subsection Study Drug Dosing Schedule
Vials
Second paragraph, first sentence previously read:
The injection for the visits at Weeks 4, 8, 12, 16, 20, 26, 32, 40, 48, 60, 72, 84, 96, 108, 
120, 144, 168, 192, 216, 240, 264, 288 and 312 will be done during your visit at the 
doctor's office.
Has been changed to read:
The injection for the visits at Weeks 4, 8, 12, 16, 20, 26, 32, 40, 48, 60, 72, 84, 96, 108, 
120, 144, 168, 192, 216, 240, 264, 288, 312, 336, 360 and 384 will be done during your 
visit at the doctor's office.  

Adalimumab
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EudraCT 2007-006494-90
1
1.0
Title Page
CLINICAL TRIAL PROTOCOL M06-807
A Multi-center, Open-label Study of the Human 
Anti-TNF Monoclonal Antibody Adalimumab to 
Evaluate the Efficacy and the Long-term Safety and 
Tolerability of Repeated Administration of 
Adalimumab in Pediatric Subjects with 
Crohn's Disease Who Have Demonstrated a Clinical 
Response in the M06-806 Study
Incorporating Administrative Changes 1 and 2, 
Amendment 1, Administrative Changes 3, 4, 5, 6 and 
7 and Amendments 2, 3, 4, 5 and 6
AbbVie Number/ 
 Investigational Product:
Adalimumab
Date: 
12 April 2013
Development Phase:
3
Study Design: 
A multi-center, open-label safety and tolerability pediatric study in the 
United States, Canada and Europe.
EudraCT Number: 
2007-006494-90
Investigator:
Multicenter (Investigator information on file at AbbVie).
Sponsor:
European Union Countries:
AbbVie Deutschland GmbH & Co. KG 
Knollstrasse
67061 Ludwigshafen
Germany
Non European Union Countries:
AbbVie
1 North Waukegan Road
North Chicago, IL  60064
Emergency Contact:
This study will be conducted in compliance with the protocol, Good Clinical Practice and all other 
applicable regulatory requirements, including the archiving of essential documents.
Confidential Information
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.

Adalimumab
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EudraCT 2007-006494-90
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1.1
Protocol Amendment:  Summary of Changes
The purpose of this amendment is the following:
●
Administrative Change 7 was incorporated.
Rationale of Change:  To reflect that AbbVie, the research-based 
pharmaceutical company, will now be the Sponsor of this study.
●
Add subject visits through Week 336 throughout the protocol.
Rationale of Change:  Extension of this open-label study is necessary to allow 
for continued collection of long-term safety and efficacy information and 
provision for study to continue until local regulatory approval and 
reimbursement.
●
Section 3.0, Section 5.2.3.1 and Section 6.5 were revised to include additional 
anti-TNF information per Humira standards, and provided background 
information about enhanced data collection to understand the risks of 
malignancy in subjects 30 and younger.
Rationale:  AbbVie is participating in an FDA-requested, TNF inhibitor 
class wide exploration of the rare appearance of malignancy in patients who 
are 30 years old or younger at the time of diagnosis.
●
Section 5.2.3.2 Concomitant Therapy was revised to allow immunosuppressant 
to be started or restarted during the study.  In addition, a sentence regarding the 
use of therapeutic enemas, suppositories and total parenteral nutrition was 
added to encourage the investigator to discuss with the Medical Monitor prior 
to use.
Rationale of change:  Due to medical and ethical considerations.
●
Section 5.2.3.4 Prohibited Medication:  The use of therapeutic enemas and 
suppositories was removed.
Rationale of change:  Due to medical and ethical considerations.

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EudraCT 2007-006494-90
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●
Section 5.3.1.1 Study Procedures (Outcomes):  A clarification on the 
completion procedure of the Work Productivity and Activity Impairment 
Questionnaire:  Crohn's Disease (WPAI-CD):  Caregiver was added.
●
Section 5.3.2.1 Collection of samples for analysis:  A clarification on 
collecting samples for subjects that require switching or change dose was 
added.
●
Section 5.5.2.1 Packaging and Labeling was revised.
●
Section 6.6 Pregnancy:  The verbiage regarding the pregnancy registry was 
removed.
Rationale of change:  Registry is closed to Humira subjects, and is only 
enrolling in the comparator (non-Humira) arm.
An itemized list of all changes made to the protocol under this amendment can be found 
in Appendix U.

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2.0
Table of Contents
1.0
Title Page..................................................................................1
1.1
Protocol Amendment:  Summary of Changes ...........................................2
2.0
Table of Contents.....................................................................4
3.0
Introduction .............................................................................9
4.0
Study Objective......................................................................16
5.0
Investigational Plan...............................................................16
5.1
Overall Study Design and Plan:  Description ..........................................16
5.2
Selection of Study Population..................................................................21
5.2.1
Inclusion Criteria .....................................................................................21
5.2.2
Exclusion Criteria ....................................................................................22
5.2.3
Prior and Concomitant Therapy...............................................................24
5.2.3.1
Prior Therapy ...........................................................................................24
5.2.3.2
Concomitant Therapy...............................................................................25
5.2.3.3
Rescue Therapy........................................................................................26
5.2.3.4
Prohibited Therapy...................................................................................26
5.3
Efficacy, and Safety Assessments/Variables ...........................................27
5.3.1
Efficacy and Safety Measurements Assessed and Flow Chart ................27
5.3.1.1
Study Procedures .....................................................................................35
5.3.2
Drug Concentration Measurements .........................................................44
5.3.2.1
Collection of Samples for Analysis .........................................................45
5.3.2.2
Handling/Processing of Samples .............................................................46
5.3.2.3
Disposition of Samples ............................................................................46
5.3.2.4
Measurement Methods.............................................................................46
5.3.3
Efficacy Variables....................................................................................47
5.3.4
Safety Variables.......................................................................................47
5.3.5
Pharmacokinetic Variables ......................................................................47

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5.4
Removal of Subjects from Therapy or Assessment.................................47
5.4.1
Discontinuation of Individual Subjects....................................................47
5.4.2
Discontinuation of Entire Study...............................................................48
5.4.3
Stopping Rules.........................................................................................49
5.5
Treatments................................................................................................49
5.5.1
Treatments Administered.........................................................................49
5.5.2
Identity of Investigational Product...........................................................51
5.5.2.1
Packaging and Labeling...........................................................................51
5.5.2.2
Storage and Disposition of Study Drug ...................................................52
5.5.3
Method of Assigning Subjects to Treatment Groups...............................52
5.5.4
Selection and Timing of Dose for Each Subject......................................53
5.5.5
Blinding....................................................................................................54
5.5.6
Treatment Compliance.............................................................................54
5.5.7
Drug Accountability.................................................................................55
5.6
Discussion and Justification of Study Design..........................................56
5.6.1
Discussion of Study Design and Choice of Control Groups....................56
5.6.2
Appropriateness of Measurements...........................................................56
5.6.3
Suitability of Subject Population .............................................................56
5.6.4
Selection of Doses in the Study ...............................................................56
6.0
Adverse Events.......................................................................57
6.1
Definitions................................................................................................58
6.1.1
Adverse Event..........................................................................................58
6.1.2
Serious Adverse Events ...........................................................................58
6.2
Adverse Event Severity............................................................................59
6.3
Relationship to Study Drug......................................................................60
6.4
Adverse Event Collection Period.............................................................60
6.5
Adverse Event Reporting.........................................................................61

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6.5.1
Collection of Data Regarding Known Manifestations of the 
Disease Under Study................................................................................62
6.6
Pregnancy.................................................................................................62
7.0
Protocol Deviations................................................................62
8.0
Statistical Methods and Determination of Sample 
Size ..........................................................................................63
8.1
Statistical and Analytical Plans................................................................63
8.1.1
Analyzable Population.............................................................................63
8.1.2
Planned Methods of Statistical Analysis..................................................64
8.1.2.1
Demographics and Baseline Characteristics............................................64
8.1.2.2
Efficacy Analysis.....................................................................................64
8.1.3
Other Analyses.........................................................................................64
8.1.4
Safety Analyses........................................................................................65
8.1.4.1
Pharmacokinetic Analyses.......................................................................66
8.1.5
Interim Analysis.......................................................................................66
8.2
Determination of Sample Size .................................................................66
8.3
Randomization Methods ..........................................................................66
9.0
Ethics.......................................................................................66
9.1
Independent Ethics Committee (IEC) or Institutional Review 
Board (IRB) .............................................................................................66
9.2
Ethical Conduct of the Study...................................................................67
9.3
Subject Information and Consent.............................................................67
10.0
Source Documents and Case Report Form 
Completion .............................................................................68
10.1
Source Documents ...................................................................................68
10.2
Case Report Forms...................................................................................69
11.0
Data Quality Assurance ........................................................70
12.0
Use of Information and Publication.....................................71
12.1
Use of Information...................................................................................71

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12.2
Internet Sites ............................................................................................72
13.0
Completion of the Study .......................................................72
14.0
Investigators Agreement.......................................................74
15.0
Reference List ........................................................................75
List of Tables
Table 1.
Study Activities........................................................................................28
Table 2.
Clinical Laboratory Tests.........................................................................40
Table 3.
Identity of Investigational Products.........................................................51
Table 4.
Study Drug Packaging and Administration .............................................52
List of Figures
Figure 1.
Study Schematic.......................................................................................19
Figure 2.
Dosing Schematic After Amendment 4 ...................................................21
Figure 3.
Adverse Event Collection ........................................................................61
List of Appendices
Appendix A.
List of Abbreviations and Definition of Terms........................................79
Appendix B.
List of Protocol Signatories .....................................................................81
Appendix C.
Documents Required Prior to Initiation of the Study ..............................82
Appendix D.
Responsibilities of the Clinical Investigator............................................84
Appendix E.
CDC Treatment of Tuberculosis Infection (Preventive Therapy) ...........86
Appendix F.
Non-Drug Materials Provided to the Study Site(s)..................................88
Appendix G.
Pediatric Crohns Disease Activity Index (PCDAI)..................................89
Appendix H.
PCDAI Users Guide and Guideline for Reference Weight and 
Reference Height .....................................................................................91
Appendix I.
Crohns Disease Activity Index (CDAI)...................................................97

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Appendix J.
Subject CDAI Diary.................................................................................98
Appendix K.
IMPACT III Questionnaire......................................................................99
Appendix L.
Excluded Medications............................................................................107
Appendix M.
Day 70 Phone Call .................................................................................108
Appendix N.
Unscheduled Outpatient Visits, Emergency Room Visits and 
Hospitalizations......................................................................................109
Appendix O.
Subject Medication Log.........................................................................110
Appendix P.
Subject Dosing Diary.............................................................................111
Appendix Q.
Self Injection Instructions......................................................................132
Appendix R.
Standard Weights...................................................................................147
Appendix S.
Subject AbbVie Site Drug Accountability Form...................................149
Appendix T.
Work Productivity and Activity Impairment Questionnaire: 
Crohns Disease (WPAI-CD) – Caregiver..............................................150
Appendix U.
Protocol Amendment:  List of Changes.................................................152

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3.0
Introduction
Crohns Disease (CD) is a chronic, debilitating, and currently incurable inflammatory 
disease that can affect the entire digestive system as well as extraintestinal organs.  CD is 
primarily manifested by focal asymmetric, transmural, and occasionally, granulomatous 
inflammation affecting any segment of the gastrointestinal tract1 which can consist of 
mucosal edema, aphthous and linear ulcerations, asymmetrical narrowing and strictures.  
Noncaseating granulomas are virtually diagnostic in the correct clinical setting.  The most 
commonly involved area of the bowel is the small bowel, particularly the distal ileum, 
which is involved in 70% of cases often in combination with colitis, occurring in 50% of 
cases.  Extraintestinal manifestations can also occur, and include symptoms of joint, 
ocular and hepatic inflammation.  Genetic, geographic, ethnic, and environmental risk 
factors have all been described, but the basic etiology of the disease remains unknown.
The incidence in North America is similar to that in other western nations and is estimated 
from 3.1 to 14.6 cases per 100,000 person years and prevalence ranges from 26 to 
199 cases per 100,000 persons.2  The disease can affect persons of any age but the most 
common age of onset is in the second and third decades with a female preponderance.  
While predominantly a disease of adults, approximately 10% to 15% of CD cases are 
diagnosed before adulthood.3
In addition, the incidence of CD in patients less than 18 years of age appears to be 
increasing in both North America and Europe.4,5  Reported incidence rates range from 
1.2 to 4.9 per 100,000 persons in the UK, Europe, and North America6-12 with one study 
reporting an incidence of 4.6 per 100,000 persons in the United States.5  CD has been 
reported at all ages but is rare in early childhood.  In one study of patients with CD, 
17 years of age and younger, 9.1% of the patients were diagnosed before the age of 6.13  
In a second study of patients diagnosed with CD before the age of 15, 7.5% of the patients 
were under the age of 5.14
Despite obvious physiologic and development differences, the presentation of CD in the 
pediatric population is generally similar to that seen in older patients and is heterogeneous 

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with regard to anatomic localization and clinical severity.5,15,16  The unique aspect of this 
disease in children is its impact on nutrition and growth, with marked growth retardation 
being a prominent component of the disease in this age group.17-19  The use of accepted 
methodologies for assessing nutritional status, including the anthropometric measures of 
height, weight, triceps skin fold thickness and mid arm circumference as well as linear 
growth (height velocity and assessment of height velocity for chronological age "z-score") 
have documented the growth impairment that can occur in this age group, and also have 
been used to assess the efficacy of interventions.20  Profound impairment of bone 
formation and increased bone resorption are associated complications and are related to 
the effect of glucocorticoids,21,22 delayed puberty,22,23 decreased mobility,24 as well as to 
the effects of cytokines on bone formation.25
Initial symptoms are often subtle, and there is an average delay of almost six months 
between onset of symptoms and diagnosis.  The most common presentation is with 
abdominal pain, diarrhea, loss of appetite and weight loss.  However, isolated weight loss, 
anorexia, perianal disease and extraintestinal manifestations can occur in the absence of 
GI symptoms in a substantial number of patients.
The general approach to the treatment of CD in children is similar to adults with the goals 
being induction and maintenance of remission, prevention of relapse and hospitalizations, 
improved quality of life, and avoidance of disease and drug related complications.  
Restoration and/or preservation of normal growth and pubertal development are additional 
therapeutic goals.  The medical armamentarium is likewise similar to adults and includes 
induction of remission with corticosteroids, and ongoing maintenance therapy of 
immunomodulators, aminosalicylates and nutritional therapy.  Anti-tumor necrosis factor 
(TNF) therapy with infliximab has been evaluated for the therapy of CD in this age group 
as it has in adults.  The FDA and EMEA have recently approved Infliximab for use in 
children with CD.
Adalimumab is a recombinant human immunoglobulin (IgG1) monoclonal antibody 
exclusively containing human peptide sequences.  It is produced by recombinant 
deoxyribonucleic acid (DNA) technology in a mammalian cell expression system.  

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Adalimumab consists of 1330 amino acids and has a molecular weight of approximately 
148 kilodaltons.  It binds specifically with high affinity to the soluble and transmembrane 
forms of TNFα and inhibits the binding of TNFα with its receptors.
TNF is a naturally occurring cytokine that is involved in normal inflammatory and 
immune responses.  Elevated levels of TNF play an important role in pathologic 
inflammation.  Adalimumab binds specifically to TNF and neutralizes the biological 
function of TNF by blocking its interaction with the p55 and p75 cell surface TNF 
receptors.
Adalimumab was first approved for treatment of rheumatoid arthritis (RA) on 
31 Dec 2002 in the United States (US), on 08 Sep 2003 in the European Union (EU) and 
through August 2008 in a total of 76 countries.  Indication extensions to include treatment 
of psoriatic arthritis and early RA were granted in the EU on 01 Aug 2005 and in the US 
on 03 Oct 2005.  A further indication extension to include treatment of ankylosing 
spondylitis was approved in the EU on 01 Jun 2006 and was approved in the US on 
28 Jul 2006.  Adalimumab was approved for the treatment of Crohns disease in the United 
States on 27 Feb 2007, in the European Union on 04 Jun 2007 and in Canada on 
05 July 2007 for the adult population.  In December 2007 and January 2008, respectively, 
adalimumab was approved for the treatment of psoriasis in adult patients in the EU, 
Canada and USA.  Additionally, adalimumab was approved for the treatment of juvenile 
idiopathic arthritis in the USA in February 2008.
Adalimumab has been shown to be a safe and effective treatment of moderately to 
severely active Crohns disease.  In the CD development program, adalimumab was 
studied in over 1400 adult subjects in three pivotal studies (two induction studies and a 
maintenance study).
Study M02-403 was a multicenter, randomized, double-blind, placebo-controlled 
Phase 2/3 study to evaluate the efficacy and safety of adalimumab for the induction of 
remission in subjects with moderate to severe CD.26  A total of 299 subjects were 
randomized to receive one of four proposed induction treatment regimens (three active 

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treatment groups or placebo):  adalimumab 160 mg at Baseline (Week 0) followed by 
80 mg at Week 2, adalimumab 80 mg at Baseline followed by 40 mg at Week 2, 
adalimumab 40 mg at Baseline followed by 20 mg at Week 2 or placebo at Baseline and 
Week 2.  Eligible subjects could not have been previously treated with any anti TNF 
agent.  Only the group of subjects treated with adalimumab 160/80 mg had a statistically 
significantly greater remission rate at Week 4 (primary endpoint) compared to placebo 
(35.5% vs. 12.2%; p = 0.001).  In addition, statistically significantly greater proportions of 
subjects in the adalimumab 160/80 mg group than in the placebo group experienced 
clinical response CR-100 (48.7% and 24.3%, respectively) and clinical response CR-70 
(57.9% and 36.8%, respectively) at Week 4.
Study M04-691, a second induction study, was a multicenter, randomized, double-blind, 
placebo-controlled, Phase 3 study to evaluate the efficacy and safety of adalimumab as 
induction treatment for subjects with moderate to severe CD who either initially 
responded to administration of infliximab but stopped responding or were intolerant.27  
A total of 325 subjects were randomized to receive adalimumab 160/80 mg or placebo.  
Eligible subjects must have previously been treated with infliximab and discontinued use 
due to loss of response to or intolerance to infliximab therapy.  The proportion of subjects 
who achieved clinical remission at Week 4 (primary endpoint) was statistically 
significantly greater in the adalimumab 160/80 mg group compared to the placebo group 
(21.4% vs. 7.2%).  The proportion of subjects achieving clinical response CR-100 and 
CR-70 at Week 4 was statistically significantly greater in the adalimumab 160/80 mg 
group (38.4% and 51.6%, respectively) compared to the placebo group (24.7% and 
33.7%, respectively).
Study M02-404 was a multicenter, randomized, double-blind, placebo-controlled Phase 3 
study to assess the efficacy and safety of adalimumab for the maintenance of clinical 
remission in subjects with moderate to severe CD.27  A total of 854 subjects (both naïve to 
or previously treated with TNF antagonists [primarily infliximab]) were enrolled and 
received open-label adalimumab 80 mg at Baseline (Week 0) and adalimumab 40 mg at 
Week 2.  At Week 4, subjects were stratified by responder status (subjects who achieved 

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clinical response CR-70) and previous anti-TNF use and were randomized in a 1:1:1 ratio 
to one of three blinded treatment groups:  adalimumab 40 mg every week (ew), 
adalimumab 40 mg every other week (eow), or placebo.  Subjects who met clinical 
response CR-70 after Week 8 could be tapered from corticosteroids.
The proportion of Week 4 responders (N = 499) who achieved clinical remission at 
Weeks 26 and 56 (co-primary endpoint) were statistically significantly greater in the 
adalimumab 40 mg eow (39.5% and 36.0%, respectively) and 40 mg ew (46.5% and 
41.4%, respectively) groups compared to the placebo group (17.1% and 11.8%, 
respectively).  The differences between the adalimumab 40 mg eow and 
adalimumab 40 mg ew groups at both of these time points were not statistically 
significant.  The median time in first clinical remission was greater in the adalimumab 
40 mg eow group (378 days) compared to the placebo group (127 days).  The median time 
in remission could not be estimated in the adalimumab 40 mg ew group because more 
than 50% remained in clinical remission at the end of the study.  Approximately six times 
as many subjects treated with adalimumab maintenance therapy compared to placebo 
were able to discontinue corticosteroids for at least 90 days and achieve remission at 
Week 26 and Week 56.  Efficacy was independent of Baseline C-reactive protein (CRP), 
concomitant therapies, such as corticosteroids or immunosuppressants, or prior anti-TNF 
experience.  The adalimumab safety profile in CD was similar to that seen in the other 
rheumatologic populations previously studied, except for expected manifestations of CD.
Currently, there are two ongoing extension studies of adalimumab therapy in adult 
subjects with CD.  M04-690 trial is a long-term safety and tolerability study of repeated 
administration of adalimumab in adult subjects with CD who had previously participated 
in M02-404 or M04-691.  The other trial is a long-term open-label extension study 
following the initial first-year study period of the M02-433 study.
The efficacy and safety of adalimumab in children has recently been demonstrated in 
juvenile rheumatoid arthritis (JRA).28  One hundred and seventy-one pediatric patients 
(4 to 17 years of age) were initially enrolled into a 16-week open label segment and 
133 subjects continued in a 32-week double blind segment.  Clinically significant 

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improvements were noted in ACR30, ACR50 and ACR70 as well as other indices of 
arthritis activity.  Adverse events (AEs) were similar as those noted in adult RA patients.  
There were no deaths, malignancies, or opportunistic infections, including tuberculosis 
(TB).  Thirteen serious adverse events (SAEs) in 8 subjects were observed in the 16-week 
open label portion of the study.  These included 4 subjects with JRA, one patient with 
two episodes of leukopenia/neutropenia, and one case each of femur fracture, herpes 
simplex, and pneumonia.  Six SAEs were observed in 6 subjects (2 placebo, 
4 adalimumab) during the 32-week double blind portion (closed head injury, 
gastroduodenitis, retinal detachment, appendicitis, abdominal pain and urinary tract 
infection).  Infections, AEs at least possibly related to study drug, and injection site 
reactions were reported by similar proportions of patients in all treatment groups during 
the double-blind therapy (32 weeks).
Fatalities, serious infections, and sepsis have been reported with the use of TNF 
antagonists.  Many of the serious infections have occurred in subjects on concomitant 
immunosuppressive therapy that, in addition to their underlying immune disorder, could 
predispose them to infections.  TB has also been observed in subjects treated with TNF 
antagonists, including adalimumab.  The event rate for TB in the CD development 
program is consistent with the global adalimumab rate.29
TNF antagonists, including adalimumab, have been associated with cases of malignancy 
and demyelinating disease.  Serious allergic adverse reactions have been reported in RA 
subjects following subcutaneous (SC) administration of adalimumab; none were reported 
in the CD program.
A detailed discussion of the pre-clinical toxicology, metabolism, pharmacology, and 
safety experience can be found in the current Investigators Brochure.
The goal of this study is to demonstrate the efficacy of adalimumab in the maintenance of 
clinical response and to demonstrate the long-term safety and tolerability of repeated 
administration of adalimumab in pediatric subjects with Crohns disease.  The subject 
population will consist of subjects who participated in and successfully completed the 

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M06-806 study and who meet all the inclusion and none of the exclusion criteria of 
Protocol M06-807.  Qualifying subjects will administer open-label adalimumab by SC 
injection.  Subjects receiving every other weekly therapy who continue to have a disease 
flare or develop another flare may be switched to every week therapy at the investigators 
discretion.  Subjects receiving weekly therapy who continue to have a disease flare or 
develop another flare may be withdrawn from the study at the Investigators discretion.  
For a detailed description of the study please see Section 5.0.
Safety Information
In 2008 FDA issued an early communication about an ongoing safety review of TNF 
blockers and the development of lymphoma and other cancers in children and adolescents.
As of the December 2009 FDA Pediatric advisory committee, it was noted that in general, 
adverse events seen in studies submitted for the JIA indication were similar to those in the 
adult population, both in type and frequency.
Due to the relatively rare occurrence of these cancers, the limited number of pediatric 
patients treated with TNF blockers, and the possible role of other immunosuppressive 
therapies used concomitantly with TNF blockers, the FDA was unable at that time to fully 
characterize the strength of the association between using TNF blockers and developing a 
malignancy.  Product labeling for all anti-TNF agents now includes language regarding 
the risk of pediatric malignancies as requested by the FDA.
Furthermore, in November 2011 the FDA requested that all manufacturers of TNF 
inhibitors undertake a coordinated effort to better understand the risks for malignancies 
that develop in patients who are 30 years of age and younger at the time of diagnosis.  
Reporting requirements for these events can be found in Section 6.5 Adverse Event 
Reporting.  A detailed discussion of the pre-clinical toxicology, metabolism, 
pharmacology, and safety experience with adalimumab can be found in the current 
Investigator's Brochure.

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4.0
Study Objective
The objective of the study is to evaluate the long-term maintenance of clinical response, 
safety and tolerability of repeated administration of adalimumab in pediatric subjects with 
Crohns disease who participated in, and successfully completed, Protocol M06-806 
through Week 52 and who meet all the inclusion and none of the exclusion criteria of 
Protocol M06-807.
5.0
Investigational Plan
5.1
Overall Study Design and Plan:  Description
This study is a multi-center, open-label study of the human anti-TNF monoclonal 
antibody adalimumab.  Approximately 31 sites that have enrolled subjects in the M06-806 
clinical trial will participate in the M06-807 clinical trial.  Approximately 130 pediatric 
subjects were expected to enroll in this study; final enrollment was 100 subjects.  
The Week 52 visit from the M06-806 study will be the Baseline Visit for those subjects 
entering study M06-807.  The visit window for M06-806 Week 52 visit is 364 ± 7 days 
from the Baseline Visit date of M06-806.
Subjects may be allowed to enroll in the M06-807 study if they have participated in, and 
successfully completed Protocol M06-806 through Week 52.  A subject must be a 
responder at any time point during the M06-806 study.  A responder is defined as a 
subject who had a PCDAI score that was at least 15 points lower than the M06-806 
baseline score.
All subjects will be on open-label maintenance therapy.  Subjects who enroll into the 
study from blinded therapy in Study M06-806 will receive open-label therapy at a dose 
dependent on their body weight.  Subjects who weigh ≥ 40 kg at Baseline will receive 
40 mg eow of adalimumab, while subjects who weigh < 40 kg at Baseline will receive 
20 mg eow of adalimumab.  Beginning at Week 8, subjects who have a disease flare may 
be switched to ew treatment at the same dose of adalimumab received while on eow 

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treatment.  A disease flare is defined as an increase in the Pediatric Crohns Disease 
Activity Index (PCDAI) of ≥ 15 points when compared to the PCDAI score obtained at 
the subjects previous visit.
Subjects who enroll into the study from open-label therapy in Study M06-806 will 
continue to receive the same dose they were receiving (i.e. 40 mg ew or 20 mg ew) at the 
Week 52 visit of the M06-806 study. 
Subjects who develop a flare while receiving ew open-label therapy or have a PCDAI 
score ≥ 15 points when compared to their Baseline (the Week 52 visit of the M06-806 
study) PCDAI score (regardless of study visit), may be discontinued from the study at the 
discretion of the Investigator. 
Beginning from Week 8, the dose of adalimumab may be increased to 40 mg, at the 
discretion of the Investigator, for subjects whose body weight has increased from < 40 kg 
to ≥ 40 kg from the Baseline (Week 52 of the M06-806 Study) visit.  The site will enter 
the subjects body weight into the Interactive Voice Response System (IVRS) and the dose 
will be adjusted, if applicable. 
Reductions in concomitant therapy will be allowed for Crohns treatment related toxicities 
(e.g., leukopenia, anemia, neuropathy) of Grade 3 or higher.
Subjects may be allowed to decrease prednisone (or equivalent) and budesonide if 
qualifications are met (please see Section 5.2.3.2 for required timing and rate of taper).
Subjects may be allowed to adjust their Crohns specific concomitant medications as 
specified in Section 5.2.3.2.
The duration of the study could last up to 336 weeks (approximately 6.5 years).  Subjects 
who complete, or who early terminate from the study will be contacted 70 days after their 
last dose of study drug to obtain information on any ongoing and new AEs.  

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This study will conclude approximately 12 weeks after the following criteria have been 
satisfied:
●
Study drug receives country and local (if applicable) regulatory approval for 
pediatric Crohns Disease.
●
All applicable local reimbursement procedures are completed.
Sites will be notified once these criteria are met.
Following country and local (if applicable) regulatory approval and applicable local 
reimbursement approval of the study drug in a country, subjects should return to their next 
scheduled study visit as specified in the protocol.  The termination visit should be 
conducted in place of their regular scheduled study visit.  These subjects should be 
considered as having completed the study.
A schematic of the study design is shown in Figure 1 (prior to Amendment 4) and in 
Figure 2 (after Amendment 4).

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Figure 2.
Dosing Schematic After Amendment 4
F: 
Subjects who have a disease flare may be switched to the next higher treatment level.
R: 
Subjects who responded to their current treatment may be switched to the next lower treatment level at the 
discretion of the investigator after discussion with the medical monitor.  Response is defined as a) a ≥ 15 points 
decrease in PCDAI compared to the last observation prior to dose escalation in patients who dose-escalated or 
b) a ≥ 15 points decrease in PCDAI compared to Baseline of Study M06-806 in patients who did not 
dose-escalate.
BW: Subjects with an increase in body weight to ≥ 40 kg may increase their dose to the next higher level at the 
discretion of the investigator after discussion with the medical monitor.  Subjects with a decrease in body weight 
to < 40 kg may decrease their dose to the next lower level at the discretion of the investigator after discussion 
with the medical monitor.
5.2
Selection of Study Population
Subjects will be evaluated to determine if they meet all of the inclusion criteria specified 
in Section 5.2.1 and none of the exclusion criteria specified in Section 5.2.2 of this 
protocol.  
5.2.1
Inclusion Criteria
1.
Subject must have successfully enrolled in and completed Protocol M06-806 
through Week 52.

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2.
Subject must be a responder at any time point during the M06-806 study.
3.
If female, subjects who are sexually active and are of child-bearing potential should 
be practicing an approved method of birth control throughout the study and for 
150 days after study drug administration.  Examples of approved methods of birth 
control include the following:
●
Condoms, sponge, foam, jellies, diaphragm or intrauterine device (IUD)
●
Oral, parenteral or intravaginal contraceptives
●
A vasectomized partner
4.
Subject of legal age, parent or legal guardian, as required, has voluntarily signed 
and dated an Institutional Review Board (IRB)/Independent Ethics Committee 
(IEC) approved informed consent form, after the nature of the study has been 
explained and the subject of legal age, subjects parent, or legal guardian, as 
required, has had the opportunity to ask questions.  Subjects will be included in all 
discussions, and if required, their signature on an assent form will be obtained.
5.
Parent or legal guardian of subject who is not of legal age, as required, must be 
willing to actively supervise storage and administration of study drug and to ensure 
that the time of each dose is accurately recorded in the subjects diary.
6.
If a subject of legal age, must be willing to actively store, administer, and 
accurately record study drug administration in the subject diary.
7.
Subject is judged to be in acceptable medical condition, as determined by the 
Principal Investigator based upon results of clinical and laboratory evaluations 
done throughout the preceding Crohns disease study M06-806.
5.2.2
Exclusion Criteria
A subject will be excluded from the study if he/she meets any of the following criteria: 

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1.
For any reason, the subject is considered by the Investigator to be an unsuitable 
candidate for continuing therapy in the M06-807 study.
2.
Subject has abnormal laboratory or other test results that in the opinion of the 
Investigator will make the subject unsuitable to participate in this study.
3.
History of cancer or lymphoproliferative disease other than a successfully and 
completely treated cutaneous squamous cell or basal cell carcinoma or 
carcinoma-in-situ of the cervix.
4.
History of listeriosis, histoplasmosis, chronic or active hepatitis B infection, human 
immunodeficiency virus (HIV) infection, any immunodeficiency syndrome, central
nervous system (CNS) demyelinating disease or active TB (receiving treatment or 
not receiving treatment).  Ongoing severe infections such as sepsis and 
opportunistic infections will be exclusionary.
5.
Subject with known, symptomatic obstructive strictures.
6.
Subject who is planning surgical bowel resection at any time point while enrolled 
in the study.
7.
Subject who has short bowel syndrome as determined by the Investigator.
8.
Subject who is currently receiving total parenteral nutrition (TPN).
9.
Subject who is unwilling to discontinue growth hormone prior to the first dose of 
open-label study drug at the Baseline visit of M06-807.
10.
Female subject who is pregnant or currently breast-feeding.
11.
Subject with a history of clinically significant drug or alcohol abuse in the last year.

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12.
Subject with a poorly controlled medical condition such as: uncontrolled diabetes, 
recurrent infections, unstable ischemic heart disease, moderate to severe heart 
failure, recent cerebrovascular accidents or any other condition which, in the 
opinion of the Investigator or the Sponsor, will put the subject at risk by 
participation in the protocol.
13.
Subject with any prior exposure to Tysabri (natalizumab).
14.
Subject with a known hypersensitivity to the excipients of adalimumab as stated in 
the label.
15.
Subject with a previous history of dysplasia of the gastrointestinal tract.
16.
Subject is not in compliance with Section 5.2.3.
If there are any questions regarding inclusion and exclusion criteria and/or subject
eligibility, contact the AbbVie Medical Monitor identified in Section 7.0.
5.2.3
Prior and Concomitant Therapy
5.2.3.1
Prior Therapy
Any medication (including over-the-counter medicines such as aspirin) that the subject is 
receiving during the study must be recorded in source documents and on the appropriate 
case report form (CRF) along with the reason for use, dates of administration and dosages.
Any vaccine administered to the subject during the study should be listed as a 
concomitant medication.  Subjects should continue on the recommended vaccination 
schedule; however, vaccinations with live vaccines are prohibited.  
Any medications captured in the M06-806 CRF(s) which are ongoing will be transcribed 
onto the M06-807 source documents and CRF(s).

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If there are any questions regarding prior or concomitant therapy (ies), contact the AbbVie 
Medical Monitor identified in Section 7.0
In addition for patients age ≤ 30 with a reported malignancy adverse event, prior exposure 
to, or current use of, antineoplastics, or other drugs which have a risk of malignancy as 
stated in their label and other relevant dosing information to estimate total exposure will 
be collected in the source documents and appropriate CRF pages.  At the time of the 
reported malignancy adverse event, sites will be asked if any of the prior and concomitant 
medications contributed to the event.  Any medications used prior to the study will be 
captured on the appropriate CRF.  Information on the reason for use, date(s) of 
administration including start and end dates, highest maintained dose, dosage information 
including dose, route and frequency, and reason for stopping the medication will be 
collected in the source documents and appropriate CRF pages.
5.2.3.2
Concomitant Therapy
Adjustments of Crohn's related concomitant treatments, including Crohn's related 
antibiotics, are not allowed during the first 8 weeks of the M06-807 study, unless subject 
safety is at risk.
After Week 8, decreases in the dose or discontinuation of Crohn's related antibiotics or 
Crohn's related concomitant treatments are allowed according to the Investigators medical 
judgment.  These adjustments may be performed without prior discussion with the 
AbbVie Medical Monitor.  In addition, subjects may be able to initiate or reinitiate 
Crohn's related treatments, following eight (8) weeks of exposure to open-label 
adalimumab.  Therapeutic enemas and suppositories (not including those done in 
conjunction with routine colonoscopies) and total parenteral nutrition (TPN) during the 
study should be discussed with and approved by the Medical Monitor prior to use.
Setons are allowed as concomitant therapy in subjects with perianal fistulas.  Their use 
should be documented on the concomitant medications page of the CRF.

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Growth hormone must be discontinued prior to the first dose of open-label study drug and 
subjects may not begin using it while participating in this study.
If a subject began to taper corticosteroids during the M06-806 study, they may continue 
this taper immediately upon enrollment into the M06-807 study.  Beginning at Week 8, 
subjects who are not in flare may begin corticosteroid taper according to the following 
schedule:
Tapering Schedule
Dose
Rate
Prednisone (or equivalent)
> 10 mg 
≤ 10 mg 
5 mg/week 
2.5 mg/week
Budesonide
≤ 9 mg 
3 mg/week
Subjects who are in flare or who flare after they have reduced or completely tapered their 
dose of corticosteroid may have their corticosteroid dose increased or restarted, at the 
discretion of the Investigator. 
5.2.3.3
Rescue Therapy
If the Investigator decides, during the study, that a subject requires rescue therapy other 
than that described in this protocol, the subject must be terminated from the study.  If 
possible, questions regarding the use of rescue therapy should be discussed with the 
Medical Monitor prior to use.
5.2.3.4
Prohibited Therapy
Live vaccines must not be given concurrently while on study drug and for 70 days after 
the last dose of study drug.
Infliximab and growth hormone use are prohibited during the study.  At the Baseline visit, 
any subject using Growth hormone must discontinue its use.

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Tysabri (natalizumab), concurrent biological therapy, cyclosporine, tacrolimus, 
mycophenolate mofetil, Kineret® (anakinra), Orencia (abatacept), and any investigational 
agent are prohibited during the study (see Appendix L).
Concurrent use of budesonide and prednisone (or equivalent) is prohibited.
Subjects with any prior exposure to Tysabri (natalizumab) will be excluded.
5.3
Efficacy, and Safety Assessments/Variables
5.3.1
Efficacy and Safety Measurements Assessed and Flow 
Chart
Study procedures will be performed as summarized in the study schematic presented in 
Table 1.

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Table 1.
Study Activities
Activity
Baseline
Week 4
Week 8
Week 12
Week 24
Week 36
Week 48
Week 60
Week 72
Week 84
Inclusion/exclusion criteria
X
Informed consent
X
Previous and concomitant 
medications
Xa
X
X
X
X
X
X
X
X
X
Urine pregnancy testb
Xa
X
X
X
X
X
X
X
X
X
Vital signsc
Xa
X
X
X
X
X
X
X
X
X
Physical exam
Xa
X
X
X
X
X
X
X
X
X
General LABd
Xa
X
X
X
X
X
X
X
X
X
TB testing (PPD or 
QuantiFERON-TB Gold)m
X
Urinalysise
Xa
X
X
X
X
X
X
X
X
X
Erythrocyte sedimentation rate
Xa
X
X
X
X
X
X
X
X
X
CRP
Xa
X
X
X
ANA
Xa
X
Anti-dsDNAf
Xa
X
PCDAI
Xa
X
X
X
X
X
X
X
X
X
CDAIg
Xa
X
X
X
X
X
X
X
X
X
IMPACT III Questionnaireh
Xa
X
X
X
X

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Table 1.
Study Activities (Continued)
Activity
Baseline
Week 4
Week 8
Week 12
Week 24
Week 36
Week 48
Week 60
Week 72
Week 84
Unscheduled outpatient visits, 
emergency room visits and 
hospitalizations questionnaire
Xa
X
X
X
X
X
X
X
X
X
Work Productivity and 
Impairment Questionnaire:  
Crohn's Disease (WPAI – CD)
Xa
X
X
X
X
X
X
X
X
X
X-ray for bone agei
Xa
X
Serum bone markers
Xa
X
X
X
PK Blood Samplej
X
X
X
Anti-adalimumab blood levels 
(AAA)j
X
X
X
Adverse eventsk
Xa
X
X
X
X
X
X
X
X
X
Dispense study drug
Xa
X
X
X
X
X
X
X
X
X

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Table 1.
Study Activities (Continued)
Activity
Week 96
Week 108
Week 120
Week 132 
Call
Week 144
Week 156 
Call
Week 168
Week 180 
Call
Week 192
Week 204 
Call
Inclusion/exclusion criteria
Informed consent
Previous and concomitant 
medications
X
X
X
X
X
X
X
X
X
X
Urine pregnancy testb
X
X
X
X
X
X
Vital signsc
X
X
X
X
X
X
Physical exam
X
X
X
X
X
X
General LABd
X
X
X
X
X
X
TB testing (PPD or 
QuantiFERON-TB Gold)m
X
X
X
Urinalysise
X
X
X
X
X
X
Erythrocyte sedimentation rate
X
X
X
X
X
X
CRP
X
X
X
X
ANA
X
X
X
Anti-dsDNAf
X
X
X
PCDAI
X
X
X
X
X
X
CDAIg
X
X
X
X
X
X
IMPACT III Questionnaireh
X
X
X
X
X

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Table 1.
Study Activities (Continued)
Activity
Week 96
Week 108
Week 120
Week 132 
Call
Week 144
Week 156 
Call
Week 168
Week 180 
Call
Week 192
Week 204 
Call
Unscheduled outpatient visits, 
emergency room visits and 
hospitalizations questionnaire
X
X
X
X
X
X
X
X
X
X
Work Productivity and Impairment 
Questionnaire:  Crohn's Disease 
(WPAI – CD)
X
X
X
X
X
X
X-ray for bone agei
X
X
X
Serum bone markersi
X
X
X
X
X
PK Blood Samplej
X
X
X
X
X
Anti-adalimumab blood levels 
(AAA)j
X
X
X
X
X
Adverse eventsk
X
X
X
X
X
X
X
X
X
X
Dispense study drug
X
X
X
X
X
X

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32
Table 1.
Study Activities (Continued)
Activity
Week 
216
Week 
228 
Call
Week 
240
Week 
252 
Call
Week 
264
Week 
276 
Call
Week 
288
Week 
300
Call
Week 
312
Week 
324 
Call
Week 
336/ 
Early 
Term
Unsched 
Visit
70-Day 
Follow-up 
Call
Inclusion/exclusion criteria
Informed consent
Previous and concomitant 
medications
X
X
X
X
X
X
X
X
X
X
X
X
Urine pregnancy testb
X
X
X
X
X
X
X
Vital signsc
X
X
X
X
X
X
X
Physical exam
X
X
X
X
X
X
X
General LABd
X
X
X
X
X
X
X
TB testing (PPD or 
QuantiFERON-TB Gold)m
X
X
X
Urinalysise
X
X
X
X
X
X
X
Erythrocyte sedimentation 
rate
X
X
X
X
X
X
X
CRP
X
X
X
X
X
ANA
X
X
Anti-dsDNAf
X
X
PCDAI
X
X
X
X
X
X
X
CDAIg
X
X
X
X
X
X
X
IMPACT III Questionnaireh
X
X
X
X
X
X
X

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33
Table 1.
Study Activities (Continued)
Activity
Week 
216
Week 
228 
Call
Week 
240
Week 
252 
Call
Week 
264
Week 
276 
Call
Week 
288
Week 
300 
Call
Week 
312
Week 
324 
Call
Week 
336/ 
Early 
Term
Unsched 
Visit
70-Day 
Follow-up 
Call
Unscheduled outpatient 
visits, emergency room 
visits and 
hospitalizations 
questionnaire
X
X
X
X
X
X
X
X
X
X
X
X
Work Productivity and 
Impairment 
Questionnaire:  Crohn's 
Disease (WPAI – CD)
X
X
X
X
X
X
X
X-ray for bone agei
X
X
Serum bone markersi
X
X
X
X
X
X
X
PK Blood Samplej
X
X
X
X
X
X
X
Anti-adalimumab blood 
levels (AAA)j
X
X
X
X
X
X
X
Adverse eventsk
X
X
X
X
X
X
X
X
X
X
X
X
X
Dispense study drug
X
X
X
X
X
Xl
a.
At the Baseline Visit, the following procedures will be completed as part of Week 52 of the M06-806 study.
b.
Performed on all females of child-bearing potential - Urine pregnancy test at all study visits.
c.
Vital sign determinations of height, weight, sitting blood pressure, heart rate, respiratory rate, and body temperature will be obtained at each visit.
d.
Blood draws should be performed after questionnaire and vital signs determinations and before study drug administration.

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Table 1.
Study Activities (Continued)
e.
Microscopic urinalysis will be performed at any visit if dipstick UA is abnormal (protein greater than a trace, blood greater than 5 - 10 Ery/ul, moderate or large ketone count 
or glucose greater than 50 mg/dL).
f.
If an ANA result is positive, anti-dsDNA will be performed automatically.
g.
For subjects who are age 13 or older at the M06-807 Baseline Visit, a CDAI will be completed at each visit.
h.
For subjects who are age 10 or older at the M06-807 Baseline Visit, an IMPACT III Assessment will be completed at Baseline, Weeks 12, 24, 48, 72, 108, 120, 144, 168, 192, 
216, 240, 264, 288, 312 and 336/ET and unscheduled visits.
i.
If the height velocity is 0 and, in the opinion of the investigator, a subject is no longer growing, the x-ray for bone age and the determination of serum bone markers can be 
omitted.
j.
In addition to blood draws every 24 weeks, PK and AAA blood draws to be performed if subject meets flare criteria and dose escalated to ew dosing.
k.
All AEs, including SAEs, will be captured throughout the study from the time that the subject signs the Informed Consent Form.  SAEs will be captured throughout the 70 day 
follow-up period (if applicable).
l.
If an unscheduled visit is performed to change the frequency or dose of study drug, study drug may be dispensed.
m.
PPD or QuantiFERON-TB Gold testing at Weeks 48, 96, 144, 192, 240, 288 and 336.

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5.3.1.1
Study Procedures
The M06-806 Week 52 visit will serve as the Baseline visit for the M06-807 study.  The 
study procedures outlined in Table 1 are discussed in detail in this section, with the 
exception of the collection of AE information (discussed in Section 6.0).  All study data 
will be recorded in source documents and on the appropriate CRFs.  The site will call the 
subjects at Weeks 132, 156, 180, 204, 228, 252, 276, 300 and 324 in order to collect any 
safety information from the subject as illustrated in Table 1.
The visit window for all scheduled visits is ±7 days calculated from the Baseline visit of 
the M06-807 study.
Inclusion/Exclusion Criteria
A subject will be excluded from this study if he/she does not meet all inclusion criteria or 
meets any of the exclusion criteria of Protocol M06-807.
Informed Consent
A signed Informed Consent Form (ICF) will be obtained from a subject of legal age (in 
the state of residence) or from the parent or legal guardian (as appropriate)of a subject 
who is not of legal age before any study related procedures are undertaken or before any 
medications are discontinued for the purpose of this study.  Additionally, an informed 
consent will be required from those subjects who were not of legal age at the onset of this 
study but become of legal age during the course of the study.
In keeping with each institutions IRB requirements, an Informed Assent may also be 
required from pediatric subjects.  Pediatric subjects will be included in all discussions in 
order to obtain their signature on an assent form.  Details about how informed consent 
will be obtained and documented are provided in Section 9.3.
If an updated informed consent is approved after a subject has completed or terminated 
early from the study, but is within the 70-day follow-up window, the subject will not be 
required to return to the site for the purposes of signing the updated ICF.  The subject of 

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36
legal age, parent or legal guardian (as appropriate) should be contacted regarding any 
changes and the documentation of the contact should be present in the subjects source.
Previous and Concomitant Medications
Changes in concomitant medications will be assessed at each study visit from Baseline 
through the Week 336/ET visit.  Concomitant medications that are taken prior to the 
first dose of study drug administration for this study will be captured in the subjects 
casebook from the previous study (M06-806).  They will not be required to be captured in 
the subjects casebook of the M06-807 study unless they were ongoing at the Week 52 
visit of the M06-806 study.  Ongoing concomitant medications from the M06-806 study 
will be transcribed into the subjects M06-807 casebook.
Subjects of legal age or the parent or guardian (as appropriate) of subjects who are not of 
legal age will be provided with a medication log (see Appendix O) to record all 
medications the subject takes throughout the study.  This log must be returned for review 
at every study visit.
Serum/Urine Pregnancy Test
All female subjects who are experiencing menses, are nearing sexual maturation (in the 
opinion of the Investigator), or who are of child-bearing potential, will undergo a urine 
pregnancy test at each visit.  Urine pregnancy tests will be performed locally by 
designated study personnel.  If a urine pregnancy test is positive, a serum pregnancy test 
must be performed by the central laboratory.  If the serum pregnancy test is positive, the 
subject will be removed from the study.  
A lactating or pregnant female will not be eligible for participation in this study.
TB Testing
For subjects with a negative test at Screening visit from parent study (Study M06-806), an 
annual PPD or QuantiFERON-TB Gold re-test will be required.  If one of the annual tests 

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has a positive test result, the matter should be discussed with the medical monitor prior to 
starting any prophylaxis.
A PPD skin test (alternatively, also known as tuberculin skin test) must be placed or the 
QuantiFERON®-TB Gold test (or equivalent) must be performed for subjects with a 
negative test at Screening visit after the amended protocol is approved by IRB/IEC 
including those with a prior history of Bacille Calmette-Guérin (BCG) administration at 
the time the subject reaches one of the scheduled visits:  Weeks 48, 96, 144, 192, 240, 
288 and 336. 
If the subject is experiencing signs or symptoms suspicious for TB or something has 
changed in the subject's medical history to warrant a repeat test before the next scheduled 
annual TB re-test, the case must be discussed with the AbbVie Medical Monitor.
For the PPD test:
●
The subject will be required to have the PPD test read by a licensed healthcare 
professional 48 to 72 hours after placement (or as per local guidelines), when 
the induration is maximal.  An induration (not erythema) of 5 mm or greater 
will be considered as PPD positive, irrespective of BCG status or local 
guidelines.  The absence of induration should be recorded, as "0 mm," not 
"negative."
●
If there are sites where the available testing materials are not accepted, an 
alternative tuberculin skin test may be substituted, but the method must be 
submitted and approved by AbbVie prior to use with study subjects.
●
If QuantiFERON®-TB Gold (or equivalent) result is indeterminate, the test 
should be repeated with a fresh blood sample.  If a repeat QuantiFERON®-TB 
Gold (or equivalent) result is indeterminate, this should be considered a 
positive test result and the case must be discussed with the AbbVie Medical 
Monitor.
In the event both a PPD test and QuantiFERON-TB Gold test are performed, the result of 
the QuantiFERON-TB Gold test will supersede the result of the PPD test.

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Newly initiated prophylactic treatment should be captured in the source documents and on 
the concomitant medications page in the CRF.  Prior therapy should be captured in the 
appropriate medical history CRF.
For sites participating in the Czech Republic, the following local requirements will also 
be applicable:
●
A pulmonologist will be responsible to obtain a detailed medical history with 
respect to TB exposure.  This information needs to include BCG vaccination, 
cohabitation with individuals who have had TB, and/or who reside or work in 
TB endemic locations.  The information obtained by the pulmonologist must 
be documented in the subject's source note, dated and signed by the 
pulmonologist.
●
A pulmonologist must review the results of the PPD skin test and the CXR and 
has to give his/her opinion about the eligibility of each subject to continue in 
the study.  This opinion must be documented in writing in the subject's source 
documents.
All subjects with a positive PPD need to be approved for continuation in the trial by both 
the Czech pulmonologist and the AbbVie Medical Monitor and all such subjects need to 
receive prophylaxis for latent TB.  Under no circumstances can a subject with a positive 
PPD result and no prior history of treatment for active or latent TB be allowed to continue 
in this trial.
Vital Signs
Vital sign determinations of sitting blood pressure, heart rate, respiratory rate, body 
temperature, weight and height will be obtained at each visit.  All measurements will be 
recorded in metric units when applicable. 
Weight measurements will be obtained using the same measuring instrument at each visit 
and measured with subjects wearing only undergarments.  Height measurements will be 

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39
obtained using the same measuring equipment at each visit and performed on subjects 
with their shoes taken off.
Physical Examination
A physical examination will be performed at each visit.  A count of the number of 
cutaneous fistulas draining upon gentle compression will be performed during each 
physical exam.30  Fistulas will be classified as abdominal or perianal/anal.
Physical exam abnormalities (including fistulas and fissures) noted by the Investigator 
will be evaluated and documented on the corresponding source documents.  Any new 
abnormalities or worsening of pre-existing conditions should be captured as AEs.
Clinical Laboratory Tests 
Samples will be obtained for the laboratory tests listed in Table 2 at all study visits.  
Blood draws should be performed after questionnaires (PCDAI, IMPACT III 
Questionnaire, etc.) and vital sign determinations during a study visit, and before study 
drug administration.
ICON central laboratory will be utilized to process and provide results for the general 
laboratory tests.  All abnormal laboratory test results that are considered clinically 
significant by the Investigator will be followed to a satisfactory resolution.
ICON will provide instructions regarding the collection, processing and shipping of these 
samples.

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Table 2.
Clinical Laboratory Tests
Hematologya
Clinical Chemistry
Urinalysisb
Serum Bone Markers
Hematocrit
Hemoglobin
Red Blood Cell (RBC) 
count
White Blood Cell 
(WBC) count
Neutrophils
Bands
Lymphocytes
Monocytes
Basophils
Eosinophils
Platelet count (estimate 
not acceptable)
Blood Urea Nitrogen 
(BUN)
Creatinine
Total bilirubin
Serum glutamic-pyruvic 
transaminase 
(SGPT/ALT)
Serum glutamic-
oxaloacetic
transaminase 
(SGOT/AST)
Alkaline phosphatase
Sodium
Potassium
Calcium
Inorganic phosphorus
Uric acid
Cholesterol
Total protein
Glucose
Triglycerides
Albumin
Specific gravity
Ketones
pH
Protein
Blood
Glucose
Osteocalcin
Bone-specific alkaline 
phosphatase (BSAP) 
bone resorption (Ntx)
a.
Basic hematology testing performed on instrumentation does not include band reporting.  When Hematology 
results reflex to a Manual Differential, if there is a band result over 5, it is reported.
b.
Microscopic urinalysis will be performed at any visits if dipstick UA is abnormal (protein greater than a trace, 
blood greater than 5 - 10 Ery/ul, moderate or large ketone count or glucose greater than 50 mg/dL).
Immunologic Laboratory Assessments  
CRP, adalimumab levels, anti-adalimumab antibody levels (AAA) and antinuclear 
antibody (ANA) assessments will be performed as indicated in Table 1.  If an ANA result 
is positive, anti-double-stranded DNA (anti-dsDNA) will be performed automatically.  All 
CRP, ANA, anti-dsDNA will be performed by the central laboratory.
Erythrocyte Sedimentation Rate (ESR) assessments will be performed at all visits as 
indicated in Table 1.  ESR assessments will be performed by the sites local laboratory.

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41
Markers of Bone Metabolism 
Serum markers of bone metabolism will be measured as indicated in Table 1.  The bone 
formation markers to be measured are osteocalcin, bone-specific alkaline phosphatase 
(BSAP), and bone resorption (Ntx).
Urinalysis
Urine will be assessed by dipstick at each visit (done locally).  All results, including 
abnormalities, will be captured in source documentation and on the appropriate CRF.  
If, at any visit, the dipstick UA results are abnormal, the central lab will perform a 
microscopic urinalysis.  Abnormal is defined as protein greater than a trace, blood greater 
than 5 - 10 Ery/ul, moderate or large ketone count or glucose greater than 50 mg/dL.
Pediatric Crohns Disease Activity Index (PCDAI)
The PCDAI score will be calculated at each visit.  When completing the PCDAI, the 
HCT, albumin, and ESR values will be utilized from the same study visit. 
An example of the PCDAI is located in Appendix G.  Instructions for completing the 
PCDAI score is located in Appendix H.
Crohns Disease Activity Index (CDAI)
At each visit, a CDAI score will be calculated for subjects who are age 13 or older at the 
M06-807 Baseline Visit.  The CDAI score will be calculated utilizing the subject diary 
and the HCT value from the same study visit.  A copy of the CDAI subject diary is 
located in Appendix H.
When completing question five (5) ("Taking Lomotil/Imodium/Loperamide/opiates for 
diarrhea, 0 = no, 1 = yes") on the CDAI, "no" should be answered if a subject is taking an 
opiate(s) solely for pain.

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For the CDAI questions regarding presence of anal fistulas and other fistulas, all fistulas 
detectable on physical examination (draining and non-draining) should be captured on the 
CDAI CRF page and calculated into the CDAI score.
The calculation of the CDAI score is in Appendix I.
IMPACT III Questionnaire
Subjects ≥ 10 years old at the Baseline visit of the M06-807 study will complete an 
IMPACT III questionnaire as indicated in Table 1.  A copy of the questionnaire is located 
in Appendix K. 
The IMPACT III will be recorded directly onto the CRF.  The completed CRF will be 
considered source documentation for this assessment.
Outcomes
The Unscheduled Outpatient Visits, Emergency Room Visits and Hospitalization 
Questionnaire and the Work Productivity and Activity Impairment Questionnaire:  
Crohn's Disease (WPAI-CD) will be completed at each visit except the Unscheduled Visit 
(Appendix N, Appendix T).
The subjects parent or legal guardian will complete the WPAI directly onto the CRF.  The 
completed CRF will be considered source documentation for this assessment.
If a subject is no longer taken care of by their parent or legal guardian, the WPAI-CD 
should not be completed (neither by the subject's parent or legal guardian nor by the 
subject himself/herself).
Bone Age
An x-ray of the wrist for the assessment of bone age will be obtained as indicated in 
Table 1.  Sites should use the Greulich and Pyle method for reading the x-ray.31  The 
x-ray report requires the signature of the radiologist who read the films.  The bone age 
that is determined by the x-ray should be recorded on the CRF.  

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Anthropometric Evaluations
Height and weight obtained at each visit will be used by AbbVie Data Management and 
Statistical groups for determination of BMI and "z" score (observed height velocity 
(cm/yr) - mean height velocity for age and sex (cm/yr)/SD of the mean) for height.
Adverse Events
Adverse events will be assessed at every study visit from Baseline through the 
Week 336/ET visit.  Any AEs, which are ongoing in the M06-806 study, will be 
transcribed onto the M06-807 source documents and CRF(s).
For those subjects who complete the study or terminate early, a phone call will be made 
70 days after the last dose of study drug to obtain follow-up information on any ongoing 
and any new AEs.  See Section 6.0 and Appendix M for additional information.
Study Drug Administration
At each study visit, the subject or their trained designated friend, family member or health 
care professional will perform study drug injections under the supervision of a trained 
medical professional to reinforce proper aseptic SC injection technique.  Subjects or a 
trained designated friend, family member or health care professional will perform 
injections of study drug in the subjects home during weeks they are not in for scheduled 
clinic visits.  Subjects may return to the study site for injections in between study visits if 
subject or a trained designated friend, family member or health care professional cannot 
inject the study medication.
Subjects will maintain a dosing diary for all study drug administered outside study visits, 
i.e., at home.  In the diary, the date, initials of the person administering the study drug, 
time study drug is administered, kit number and the dose administered will be recorded.  
Subjects must return this diary and it will be reviewed and verified for compliance at each 
visit by the research personnel at the study center.  All relevant dosing information will be 
retained by the study coordinator and transcribed onto a drug accountability form at each 
visit.  Additionally, any discernible departure from the protocol regarding study drug 

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administration will be recorded on source documents and appropriate drug accountability 
forms.  A sample of the Subject Dosing Diary is presented in Appendix P.
At all office visits subjects should be observed after study drug administration, until 
judged clinically stable by the study personnel.  If an anaphylactic reaction or other 
serious allergic reaction occurs, administration of study drug should be discontinued 
immediately and appropriate therapy initiated.  When dosing at home, subjects should be 
instructed to contact the site immediately with any signs or symptoms of a reaction.
The dosing dates, for all doses of study drug, should be calculated from the Baseline visit 
date.  The Baseline visit date for this study is 364 ± 7 days from the Baseline Visit date of 
M06-806.  A +/-3 day window is allowable for scheduled study dosing dates.
For subjects that deviate from this dosing window, every effort should be made to bring 
the subject back to the original dosing schedule as soon as possible.  For situations where 
bringing the subject back on the original dosing schedule will cause the dose to be out of 
the +/-3 day window, please contact the Medical Monitor for additional instructions.
Randomization and Assignment of Subject Numbers
All subjects will be centrally registered using an IVRS.  This is an open-label study; 
subjects will not be randomized.  The telephone number and call in directions for the 
IVRS will be provided to each site.  Subjects will keep their study subject number from 
the previous double-blind study (M06-806).
5.3.2
Drug Concentration Measurements
Blood samples for the assay of adalimumab and AAA serum concentrations will be 
collected at Baseline and every 24 weeks thereafter.  In addition, blood samples for 
adalimumab and AAA concentration analysis will also be collected if a subject meets 
flare criteria and dose escalated to ew dosing.  Study visits in which blood samples will be 
collected are listed in Table 1.  At each visit, blood samples will be collected prior to 
study drug administration at each visit.

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The time that each blood sample is collected will be recorded to the nearest minute in the 
source documents and on the appropriate CRF.
5.3.2.1
Collection of Samples for Analysis
Collection of Samples for Adalimumab Analysis
Blood samples for adalimumab analysis will be collected by venipuncture into 
appropriately labeled 4-mL evacuated serum collection tubes without gel separator at 
visits indicated in Table 1.  All samples will be obtained immediately prior to dosing at 
visits indicated in Table 1.  Sufficient blood will be collected to provide approximately 
2 mL serum.  Allow the blood to clot for 30 minutes at room temperature before 
centrifugation.
A minimum of 14 samples are planned to be collected per subject for the analysis of 
adalimumab concentrations.
For subjects who have a flare and require switching to higher dose or change dose to 
ew dosing, up to 2 additional samples are planned to be collected per subject for 
adalimumab analysis.
Collection of Samples for AAA Analysis
Blood samples for AAA assay will be collected by venipuncture into appropriately 
labeled 4-mL evacuated serum collection tubes without gel separator at visits indicated in 
Table 1.  All samples will be obtained immediately prior to dosing at visits indicated in 
Table 1.  Sufficient blood will be collected to provide approximately 2 mL serum.  Blood 
will be allowed to clot for 30 minutes at room temperature before centrifugation.
A minimum of 14 blood samples are planned to be collected per subject for AAA 
analysis.

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For subjects who have a flare and require switching to higher dose or change dose to 
ew dosing, up to 2 additional samples are planned to be collected per subject for AAA 
analysis.
5.3.2.2
Handling/Processing of Samples
The blood samples for adalimumab and AAA, assay will be centrifuged within 30 to 
60 minutes of collection to separate the serum.  The serum samples will be transferred 
using plastic pipettes into screw-capped polypropylene vials labeled with the type of 
sample (serum, SRM), the protocol number, subject number, the study week and the assay 
(PK-Adalimumab, AAA).  The serum samples will be frozen within 2 hours after 
collection and will remain frozen in a –20°C or colder until shipped.  Sites that do not 
have access to a –20°C or colder freezer will need to ship the samples the day they are 
collected.  (Detailed instructions provided in the ICON Laboratory Manual).
5.3.2.3
Disposition of Samples
The PK and AAA samples will be shipped to ICON with all other samples being shipped 
to ICON.  Refer to the ICON Lab Manual for further instruction.  Neither AbbVie nor 
ICON will supply dry ice for this study.  Study sites will identify a dry ice source and 
purchase the necessary dry ice.
5.3.2.4
Measurement Methods
Serum concentrations of adalimumab will be determined using a validated ELISA method 
under the supervision of the Drug Analysis Department at AbbVie.  Only serum samples 
that have adalimumab levels < 2.0 μg/mL will be selected for AAA concentration 
measurement.
Serum concentrations of AAA will be determined using a validated ELISA method under 
the supervision of the Drug Analysis Department at AbbVie.

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5.3.3
Efficacy Variables
Efficacy will be evaluated based on the proportion of subjects who maintain PCDAI 
clinical response at each visit.  Clinical response is defined as PCDAI decrease 
≥15 points from the M06-806 Baseline score.
Other measures of disease activity being assessed in this study will be summarized, 
including CDAI scores, IMPACT III scores, WPAI-CD Caregiver, z-score for height 
velocity, bone x-ray, serological markers of bone metabolism, healthcare resource 
utilization (unscheduled outpatient visits), adalimumab levels and anti-adalimumab levels 
(AAA).
5.3.4
Safety Variables
AEs, laboratory data, physical examinations and vital signs are the safety parameters and 
these will be assessed throughout the study.
Treatment-emergent events will be summarized and reported by treatment group and by 
AAA status (AAA+ versus AAA-).
5.3.5
Pharmacokinetic Variables
Serum concentrations of adalimumab and AAA will be determined from samples 
collected at the study visits listed in Table 1.
5.4
Removal of Subjects from Therapy or Assessment
5.4.1
Discontinuation of Individual Subjects
Subjects will be withdrawn from the study immediately if any of the following occur:  
●
Clinically significant abnormal laboratory results or AEs, which rule out 
continuation of the study drug, as determined by the Investigator and the 
Medical Monitor.

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●
The Investigator believes it is in the best interest of the subject.
●
The subject or subjects legal guardian requests withdrawal from the study.
●
Selection criteria violation was noted after the subject started study drug, as 
determined by the Medical Monitor (see Sections 5.2.1 and 5.2.2).
●
Introduction of prohibited medications or prohibited concomitant medication 
dosages as determined by the Medical Monitor.
●
The subject is diagnosed with a malignancy except for localized 
non-melanoma skin cancer.  Discontinuation for carcinoma in-situ is at the 
discretion of the Investigator.
●
The subject is diagnosed with dysplasia of the gastrointestinal tract.
●
A female subject who becomes pregnant.
If the subject prematurely discontinues study drug use, the procedures outlined for the 
Week 336/ET Visit must be completed within 2 weeks of the last dose of study drug, and 
preferably prior to the initiation of another therapy.  These procedures should not interfere 
with the initiation of any new treatments or therapeutic modalities that the Investigator 
feels are necessary to treat the subjects condition.  Following discontinuation of the study 
drug, the subject will be treated in accordance with the Investigators best clinical 
judgment.
Subjects who prematurely discontinue from the study will not be replaced.  The date of 
last dose and reason for premature discontinuation will be recorded in the source 
document and on the appropriate CRF.
5.4.2
Discontinuation of Entire Study
AbbVie reserves the right to discontinue the study at any time and to remove all study 
materials from the site.  Possible reasons for termination of the study include, but are not 
limited to:

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●
Safety concerns based on reported data
●
Unsatisfactory enrollment with respect to quantity or quality
●
Inaccurate or incomplete data collection
●
Falsification of records
●
Failure to adhere to the protocol
5.4.3
Stopping Rules
An independent Data Monitoring Committee (DMC) will meet to discuss data from the 
study approximately every six (6) months or at a frequency determined by the DMC and 
render their recommendation for either the continuation of the study or an amendment to 
the study.  A Sponsor Steering Committee (SSC), composed of senior executives not 
directly participating in this study, will make final decisions based on DMC 
recommendations.
5.5
Treatments
5.5.1
Treatments Administered
Study drug will be provided as a SC injection solution in pre-filled syringes containing 
adalimumab 40 mg/0.8 mL or adalimumab 20 mg/0.4 mL or in vials containing 
adalimumab 40 mg/0.8mL.
Subjects who enroll into the study from blinded therapy in Study M06-806 will receive 
open-label therapy at a dose dependent on their body weight.  Subjects who weigh ≥40 kg 
will receive 40 mg eow of adalimumab, while subjects who weigh < 40 kg will receive 
20 mg eow of adalimumab.  Beginning from Week 8, subjects who have a disease flare 
may be switched to ew treatment at the same dose of adalimumab received while on eow 
treatment.

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Subjects who enroll into the study from open-label therapy in Study M06-806 will 
continue to receive the same dose they were receiving (i.e. 40 mg ew or 20 mg ew) at the 
Week 52 visit of the M06-806 study.
Subjects who develop a flare while receiving ew open-label therapy or have a PCDAI 
score ≥ 15 points when compared to their Baseline (Week 52 of M06-806) PCDAI score 
(regardless of study visit), may be discontinued from the study at the discretion of the 
Investigator.
Beginning from Week 8, the dose of adalimumab may be increased to 40 mg, at the 
discretion of the investigator, for subjects whose body weight has increased from < 40 kg 
to ≥ 40 kg from the study Baseline visit.  The site will enter the subject's body weight into 
the IVRS and the dose will be adjusted, if applicable.
The dose of adalimumab may be decreased to the next lower treatment level as applicable, 
at the discretion of the Investigator and prior approval from the medical monitor, for 
subjects whose body weight has decreased from ≥ 40 kg to < 40 kg from the previous 
visit.  The site will enter the subject's body weight into the IVRS and the dose will be 
adjusted, if applicable.
Subjects who responded to treatment defined as a) an improvement of at least 15 points in 
PCDAI compared to the last observation prior to dose escalation in patients who 
dose-escalated or b) an improvement of at least 15 points in PCDAI compared to Baseline 
of Study M06-806 in patients who did not dose-escalate) may have their dosage frequency 
decreased from ew to eow dosing.  The investigator should receive prior approval from 
the medical monitor before taking any action with regard to the dose frequency decrease.  
At least 8 weeks after dose frequency decrease, subjects who still responded to treatment 
(as defined above) may have their dosage decreased (subjects who weigh ≥ 40 kg will 
receive 20 mg eow of adalimumab, while subjects who weigh < 40 kg will receive 10 mg 
eow of adalimumab).  The investigator should receive prior approval from the medical 
monitor before taking any action with regard to dose decrease.

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Subjects who experience a disease flare may re-increase their dosage or dose frequency to 
the next higher treatment level regardless of prior dose or dose frequency decrease. 
Simultaneous dose adjustment based on change of body weight as well as based on 
diseases status (response/flare) is prohibited.
5.5.2
Identity of Investigational Product
The individual study drug information is presented in Table 3.  Pre-filled syringes (used 
for 40 mg/0.8 mL or 20 mg/0.4 mL doses) and 40 mg/0.8 mL vials (used for 10 mg dose) 
will be provided for this open-label clinical study.
Table 3.
Identity of Investigational Products
Study Drug
Formulation
Manufacturer
Adalimumab
40 mg/0.8 mL or 20 mg/0.4 mL
Adalimumab/Mannitol, Citric acid monohydrate, Sodium citrate, 
Disodium phosphate dihydrate, Sodium dihydrogen phosphate 
dihydrate, Sodium chloride, Polysorbate 80, Water for injections, 
Sodium hydroxide added as necessary to adjust pH
AbbVie/Abbott
Adalimumab
40 mg/0.8 mL (used for 10 mg dose)
Adalimumab/Mannitol, Citric acid monohydrate, Sodium citrate, 
Disodium phosphate dihydrate, Sodium dihydrogen phosphate 
dihydrate, Sodium chloride, Polysorbate 80, Water for injections, 
Sodium hydroxide added as necessary to adjust pH
AbbVie/Abbott
5.5.2.1
Packaging and Labeling
Two pre-filled syringes or vials will be provided in a dosing kit carton (see Table 4).  
Each kit will be labeled as required per country requirement.  Labels must remain affixed 
to the kit.
Detailed instructions and training for the administration of study supplies are provided in 
Appendix Q.

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Table 4.
Study Drug Packaging and Administration
Open-label Pre-filled Syringes
Open-label kit cartons containing two pre-filled 
syringes of adalimumab 40 mg/0.8 mL.
Open-label kit cartons containing two pre-filled 
syringes of adalimumab 20 mg/0.4 mL.
Open-label Vials (used for 10 mg dose)
Open-label kit cartons containing two vials of adalimumab 40 mg/0.8 mL.
5.5.2.2
Storage and Disposition of Study Drug
Pre-filled syringes and vials are to be stored protected from light at 2° to 8°C/36° to 46°F.  
DO NOT FREEZE.  A storage temperature log is to be maintained at the site to document 
proper storage conditions.  The refrigerator temperature must be recorded on every 
business day on a temperature log to record proper function.  Malfunctions must be 
reported to the sponsor immediately.  Study drug should be quarantined and not dispensed 
until AbbVie GPRD or Abbott Temperature Excursion Management System (ATEMS) 
deems the medication as acceptable.  All clinical supplies must be stored and locked in a 
secure place until they are dispensed for subject use or are returned to AbbVie.
Investigational products are for investigational use only, and are to be used only within 
the context of this study.
5.5.3
Method of Assigning Subjects to Treatment Groups
This is an open-label study; all subjects will be receiving adalimumab.
All subjects will be centrally registered using an IVRS.  The telephone number and call-in 
directions for the IVRS will be provided to each site.  Subjects will keep their study 
subject number from the previous study (M06-806).
Study drug will be administered at the study visits summarized in Table 1 and detailed in 
Section 5.3.1.1.

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5.5.4
Selection and Timing of Dose for Each Subject
Subjects who enroll into the study from blinded therapy in Study M06-806 will receive 
open-label therapy at a dose dependent on their body weight.  Subjects who weigh ≥40 kg 
will receive 40 mg eow of adalimumab, while subjects who weigh < 40 kg will receive 
20 mg eow of adalimumab.  Beginning from Week 8, subjects who have a disease flare 
may be switched to ew treatment at the same dose of adalimumab received while on eow 
treatment.
Subjects who enroll into the study from open-label therapy in Study M06-806 will 
continue to receive the same dose they were receiving (i.e., 40 mg ew or 20 mg ew) at the 
Week 52 visit of the M06-806 study. 
Subjects who develop a flare while receiving ew open-label therapy or have a PCDAI
score ≥ 15 points when compared to their Baseline (the Week 52 visit of the 
M06-806 study) PCDAI score (regardless of study visit), may be discontinued from the 
study at the discretion of the Investigator.
The dose of adalimumab may be decreased to the next lower treatment level as applicable 
at the discretion of the Investigator and prior approval from the medical monitor, for 
subjects whose body weight has decreased from ≥ 40 kg to < 40 kg from the previous 
visit.  The site will enter the subjects' body weight into the IVRS and the dose will be 
adjusted, if applicable.
Subjects who responded to treatment defined as a) an improvement of at least 15 points in 
PCDAI compared to the last observation prior to dose escalation in patients who 
dose-escalated or b) an improvement of at least 15 points in PCDAI compared to Baseline 
of Study M06-806 in patients who did not dose-escalate) may have their dosage frequency 
decreased from ew to eow dosing.  The investigator should receive prior approval from 
the medical monitor before taking any action with regard to the dose frequency decrease.  
At least 8 weeks after dose frequency decrease, subjects who still responded to treatment 
(as defined above) may have their dosage decreased (subjects who weigh ≥ 40 kg will 

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receive 20 mg eow of adalimumab, while subjects who weigh < 40 kg will receive 10 mg 
eow of adalimumab).  The investigator should receive prior approval from the medical 
monitor before taking any action with regard to dose decrease.
Subjects who experience a disease flare may re-increase their dosage or dose frequency to 
the next higher treatment level regardless of prior dose or dose frequency decrease. 
Simultaneous dose adjustment based on change of body weight as well as based on 
diseases status (response/flare) is prohibited.
The Baseline Visit date for this study should be 364 ± 7 days from Baseline Visit date of 
M06-806 study.  All clinic visits for the subject should be scheduled on the same day as 
the Baseline visit for this study.  For home administration of drug, subjects will be 
instructed to inject study drug on the same day of the week as their Baseline visit day.  
Subjects must inject within a +/-3 day window of this day.  If the subject is out of the 
dosing window, the Medical Monitor should be contacted to determine the timing of the 
next dose.  The subject must record all dosing information on the subject dosing diary 
(Appendix P).
5.5.5
Blinding
This is an open-label study.
5.5.6
Treatment Compliance
The Investigator or his/her designated representatives will administer study drug only to 
subjects enrolled in the study. 
In order to document compliance with the treatment regimen, all pre-filled syringes and 
vials will be counted and documented in source documents and on the appropriate drug 
accountability form.

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5.5.7
Drug Accountability
The Investigator or designee will verify that study drug supplies are received intact, at the 
appropriate temperature, and in the correct amounts from the drug depot.  This will be 
documented by signing and dating the Proof of Receipt (POR) or similar document.  The 
original POR or similar document will be kept in the site files as a record of what was 
received.  An accurate running inventory of study drug will be kept by the site, and will
include the kit number, lot number(s), the number of pre-filled syringes or vials 
dispensed, and the date study drug was dispensed for each subject.  An overall 
accountability of the study drug will be performed and verified by the Clinical Research 
Associate (CRA) throughout the study and at the site close-out visit.  All unused pre-filled 
syringes and vials will be inventoried and returned to an identified vendor for disposal as 
designated by AbbVie.  A copy of the Drug Accountability Form, in accordance with 
instructions provided by the CRA, will also be included in the Returned Goods for 
disposal shipment.  A sample Drug Accountability Form is included in Appendix S.  A 
copy of the Drug Accountability Disposal Form, in accordance with instructions provided 
by the CRA, will also be included in the Pharmacy Binder provided to the site.
All used (expelled) pre-filled syringes and vials will be inventoried by the site and 
verified by the CRA.  The used syringes and vials will be discarded on site, using 
appropriate biohazard precautions.  CRAs and site staff will complete study drug 
accountability via study drug logs, source documents, verification of empty used syringe 
kit or vials boxes, subject diaries and by visually counting the syringes in the sharps 
container whenever possible.  Used sharps containers should never be opened.  Each 
subject will be given their own sharps disposal container to store expelled/used syringes.  
Sharps containers should be returned by the subject at each visit, for accountability and 
compliance purposes.  New containers will be issued to subjects as necessary.  Once the 
CRA has verified drug accountability at the site, the site staff and CRA will sign off that 
the expelled pre-filled syringes and used vials have been destroyed.

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5.6
Discussion and Justification of Study Design
5.6.1
Discussion of Study Design and Choice of Control Groups
The design of this clinical study was chosen to demonstrate adalimumab as an effective 
therapy for maintaining clinical response in pediatric subjects with CD and to gather 
long-term safety and tolerability data in this subject population.
5.6.2
Appropriateness of Measurements
Standard statistical, clinical, and laboratory procedures will be utilized in this study.  All
efficacy measurements in this study are standard for assessing disease activity in pediatric 
subjects with Crohns disease.  All clinical and laboratory procedures in this study are 
standard and generally accepted.
5.6.3
Suitability of Subject Population
Pediatric subjects with CD who have participated in and successfully completed 
Protocol M06-806 through Week 52 and who meet all of the inclusion and none of the 
exclusion criteria are eligible for this study.
5.6.4
Selection of Doses in the Study
The results of the pivotal adalimumab adult CD maintenance trial M02-404, in 
conjunction with results from adalimumab CD Study M02-433, support a maintenance 
dose of adalimumab 40 mg eow.  Data also suggest that patients who lose response to 
adalimumab at 40 mg eow can be dose-escalated to 40 mg weekly with the potential of 
regaining clinical response.  The proposed dosing regimen for Study M06-807 before 
Amendment 4 was developed using an analogous approach as that studied in the adult CD 
population.  Population pharmacokinetic modeling of serum adalimumab concentration 
data from pediatric subjects with JRA was used to identify doses to be evaluated in the 
current study in children with CD before Amendment 4.  A model based on the JRA 
population was chosen because the body weight range would closely parallel that in a 

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juvenile CD population.  Escalation to weekly dosing would provide average adalimumab 
concentrations at steady state about twice that observed with every other week dosing.  
However, these concentrations are within the range of systemic exposures that were safely 
studied in adult subjects with CD.
After completion of Study M06-806 and consideration of efficacy, safety and population 
pharmacokinetic results in conjunction with exposure-response modeling and simulation 
both the Low-Dose and High-Dose treatment provided evidence of efficacy and safety.  
Therefore, in order to minimize the systemic exposures to study drug to the lowest doses 
necessary in children with CD, Amendment 4 provides investigators with the option of 
dose de-escalation by reducing the dose or switching from ew to eow based on the clinical 
status of the individual patient.  In addition, since the 10 mg eow dose was efficacious in 
subjects weighing < 40 kg in Study M06-806 patients will have the option to be switched 
to this dose based on their body weight and clinical status at the discretion of the 
investigator.
6.0
Adverse Events
The Investigator will monitor each subject for clinical and laboratory evidence of AEs on 
a routine basis throughout the study.  The Investigator will assess and record any AE in 
detail including the date of onset, description, severity, time course, duration and 
outcome, relationship of the AE to study drug, an event diagnosis, if known, and any 
action(s) taken.  For SAEs not considered "probably related" to study drug, the 
Investigator must provide another cause of event.  For AEs to be considered sporadic, the 
events must be of similar nature and severity.  AEs, whether in response to a query, 
observed by site personnel, or reported spontaneously by the subject will be recorded in 
source documentation and on the appropriate CRF page.
All AEs will be followed to a satisfactory conclusion.

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6.1
Definitions
6.1.1
Adverse Event
An AE is defined as any untoward medical occurrence in a patient or clinical investigation 
subject administered a pharmaceutical product and which does not necessarily have a 
causal relationship with this treatment.  An AE can therefore be any unfavorable and 
unintended sign (including an abnormal laboratory finding), symptom, or disease 
temporally associated with the use of a medicinal (investigational) product, whether or not 
the event is considered causally related to the use of the product.
Such an event can result from use of the drug as stipulated in the protocol or labeling, as 
well as from accidental or intentional overdose, drug abuse, or drug withdrawal.  Any 
worsening of a pre-existing condition or illness is considered an AE.  Laboratory 
abnormalities and changes in vital signs are considered to be AEs only if they result in 
discontinuation from the study, necessitate therapeutic medical intervention, and/or if the 
Investigator considers them to be AEs.
An elective surgery/procedure scheduled to occur during a study will not be considered an 
AE if the surgery/procedure is being performed for a pre-existing condition and the 
surgery/procedure has been pre-planned prior to study entry.  However, if the pre-existing 
condition deteriorates unexpectedly during the study (e.g., surgery performed earlier than 
planned), then the deterioration of the condition for which the elective surgery/procedure 
is being done will be considered an AE.
6.1.2
Serious Adverse Events
If an AE meets any of the following criteria, it is to be reported to AbbVie as an SAE 
within 24 hours of the site being made aware of the SAE.  Additionally, if follow-up 
information is received, it must also be reported to AbbVie within 24 hours of being made 
aware of the information.

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Death of Subject
An event that results in the death of a subject.
Life-Threatening
An event that, in the opinion of the Investigator, will have resulted in 
immediate fatality if medical intervention had not been taken.  This does 
not include an event that will have been fatal if it had occurred in a 
more severe form.
Hospitalization
An event that results in an admission to the hospital for any length of 
time.  This does not include an emergency room visit or admission to an 
outpatient facility.
Prolongation of 
Hospitalization
An event that occurs while the study subject is hospitalized and 
prolongs the subjects hospital stay.
Congenital Anomaly
An anomaly detected at or after birth, or any anomaly that results in 
fetal loss.
Persistent or Significant 
Disability/Incapacity
An event that results in a condition that substantially interferes with the 
activities of daily living of a study subject.  Disability is not intended to 
include experiences of relatively minor medical significance such as 
headache, nausea, vomiting, diarrhea, influenza, and accidental trauma 
(e.g., sprained ankle).
Important Medical Event 
Requiring Medical or 
Surgical Intervention to 
Prevent Serious Outcome
An important medical event that may not be immediately 
life-threatening or result in death or hospitalization, but based on 
medical judgment may jeopardize the subject and may require medical 
or surgical intervention to prevent any of the outcomes listed above 
(i.e., death of subject, life threatening, hospitalization, prolongation of 
hospitalization, congenital anomaly, or persistent or significant 
disability/incapacity).  Examples of such events include allergic 
bronchospasm requiring intensive treatment in an emergency room or at 
home, blood dyscrasias or convulsions that do not result in inpatient 
hospitalization, or the development of drug dependency or drug abuse.
Spontaneous Abortion
Miscarriage experienced by study subject.
Elective Abortion
Elective abortion performed on study subject.
6.2
Adverse Event Severity
The Investigator will use the following definitions to rate the severity of each AE:
Mild
The AE is transient and easily tolerated by the subject.
Moderate
The AE causes the subject discomfort and interrupts the subjects usual 
activities.
Severe
The AE causes considerable interference with the subjects usual activities 
and may be incapacitating or life threatening.  

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6.3
Relationship to Study Drug
The Investigator will use the following definitions to assess the relationship of the AE to 
the use of study drug:  
Probably Related
An adverse event has a strong temporal relationship to study drug or
recurs on re-challenge and an other cause of event is unlikely or 
significantly less likely.
Possibly Related
An AE has a strong temporal relationship to the study drug and an other 
cause of event is equally or less likely compared to the potential 
relationship to study drug.
Probably Not Related
An AE has little or no temporal relationship to the study drug and/or a 
more likely other cause of event exists.
Not Related
An AE is due to an underlying or concurrent illness or effect of another 
drug and is not related to the study drug (e.g., has no temporal 
relationship to study drug or has a much more likely other cause of 
event).
If an Investigators opinion of possibly, probably not, or not related to study drug for an 
SAE is given, an alternative cause of the event must be provided by the Investigator for 
the SAE.
6.4
Adverse Event Collection Period
All AEs reported from the time of informed consent until 5 half-lives (70 days), following 
discontinuation of study drug administration have elapsed will be collected, whether 
elicited or spontaneously reported by the subject.  In addition, SAEs will be collected 
from the time the subject or parent/legal guardian has signed the study-specific informed 
consent.
Adverse event information will be collected as shown in Figure 3.

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Figure 3.
Adverse Event Collection
SAEs and Non-serious AEs
Elicited and/or Spontaneously Reported
∀
∀
∀
∀
Consent 
Signed
Study Drug 
Start
Study Drug 
Stopped
70 Days After 
Study Drug 
Stopped
6.5
Adverse Event Reporting
In the event of a serious adverse event, and additionally, any non-serious event of 
malignancy in patients 30 years of age and younger, whether related to study drug or not, 
the physician will notify AbbVie within 24 hours of the physician becoming aware of the 
event by faxing the serious adverse event or non-serious event of malignancy in patients 
30 years of age and younger forms to the Immunology Clinical Safety Team.
For all sites:
For questions regarding SAEs, please contact:

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6.5.1
Collection of Data Regarding Known Manifestations of the 
Disease Under Study
Flare, of Crohns disease events per study definition, are not required to be captured as 
AEs, but may be captured per Investigator discretion.  Additionally, CD pre-existing 
conditions will not be captured as AEs unless the condition has worsened or is considered 
clinically significant in the opinion of the Investigator.
6.6
Pregnancy
Pregnancy in a study subject must be reported to AbbVie within 1 working day of the site 
becoming aware of the pregnancy.  Subjects who become pregnant during the study must 
be discontinued (Section 5.4.1).  Pregnancies will be collected from the date of the 
first dose through 150 days following the last dose of study drug.
Information regarding a pregnancy occurrence in a study subject and the outcome of the 
pregnancy will be collected.
Pregnancy in a study subject is not considered an AE.  However, the medical outcome of 
an elective or a spontaneous abortion, stillbirth or congenital anomaly is considered a 
SAE, and must be reported to the sponsor with 24 hours of the site learning of the event.
7.0
Protocol Deviations
The investigator should not implement any deviation from the protocol without prior 
review and agreement by the Sponsor and in accordance with the IEC/IRB and local 
regulations, except when necessary to eliminate an immediate hazard to study subjects.  
When a deviation from the protocol is deemed necessary for an individual subject, the 
investigator must contact the following AbbVie representative:

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For purposes of this protocol, reportable deviations are defined as:  
●
Subject entered into the study even though they did not satisfy entry criteria
●
Subject who developed withdrawal criteria during the study and was not 
withdrawn
●
Subject who received wrong treatment or incorrect dose
●
Subject who received excluded concomitant treatment
Such contact must be made as soon as possible to permit a review by AbbVie to 
determine the impact of the deviation on the subject and/or the study.  Any significant 
protocol deviations affecting subject eligibility and/or safety must be reviewed and/or 
approved by the IEC/IRB and regulatory authorities, as applicable, prior to 
implementation.
8.0
Statistical Methods and Determination of Sample 
Size
8.1
Statistical and Analytical Plans
8.1.1
Analyzable Population
Efficacy analyses will be conducted in the intent-to-treat (ITT) population, which is 
defined as all subjects who received at least one dose of adalimumab in Study M06-807.  

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The safety population consists of all subjects who received at least one dose of 
adalimumab in Study M06-807.
8.1.2
Planned Methods of Statistical Analysis
All statistical analyses are to be performed descriptively.  Descriptive summary statistics 
will be provided for the demographic and baseline characteristics, efficacy, and safety 
parameters.  Continuous variables will be summarized using the number of observation, 
mean, standard deviation, 1st quartile, median, 3rd quartile, minimum, and maximum; 
whereas discrete variables will be summarized using count and percentages. 
8.1.2.1
Demographics and Baseline Characteristics
Summary statistics for the demographic and baseline characteristics will be computed 
based on the Week 52 values (from double-blind Study M06-806).
8.1.2.2
Efficacy Analysis
Summary statistics will be provided for each visit, based on observed data.  An additional 
summary will be provided for the last visit, using the last observation carried forward 
(LOCF).  That is, the subjects last non-missing, post-baseline value (i.e., post-Week 52 
M06-806 double-blind value) will be carried forward to the last visit.
8.1.3
Other Analyses
Efficacy will be analyzed for the following subgroups in the ITT population.
●
Sex [Male, Female]
●
Age [< 13 years, ≥13 years]
●
Ethnicity [White, Non-white]
●
Weight [< 40 kg, ≥ 40 kg]
●
Prior infliximab use [No, Yes]

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●
Baseline CRP [< 1.0 mg/dL, ≥ 1.0 mg/dL]
●
Concomitant use of immunosuppressants and/or oral corticosteroids [No, Yes]
8.1.4
Safety Analyses
Safety analyses will be based on the safety population.  Treatment-emergent AEs will be 
summarized.  An overview of treatment-emergent AEs including AEs of special interest, 
such as AEs leading to death and AEs leading to premature discontinuation, AEs by 
(MedDRA® version 10.0 or later) preferred term and system organ class, AEs by 
maximum relationship to study drug, and AEs by maximum severity will be summarized.  
Treatment-emergent AEs are defined as new events that begin either on or after the 
first dose of the study drug and within 70 days after the last dose of the study drug.
Adverse events with missing or unknown severity will be categorized as severe.  Adverse 
events with missing or unknown relationship to study drug will be categorized as 
probably related.
Adverse events that are reported more than 70 days after last study injection will be 
excluded from the summaries; however, all reported AEs will be included in the AE data 
listings.
For laboratory parameters, the normal range of the analyzing laboratory will be used and 
all values outside the normal range will be flagged and listed.  Additionally, descriptive
statistics for the mean change from baseline to minimum (smallest) value, maximum 
(largest) value and final value during the study will be calculated for the continuous 
clinical laboratory parameters. 
Shift tables will be provided to cross-classify and tabulate subjects value from baseline to 
final value by the presence of clinically significant laboratory results.  Each subjects 
baseline value and final value will be flagged in reference to the normal range (low, 
normal, high) and also categorized as clinically non-significant (CTC grade < 3) or 
clinically significant (CTC grade ≥3).  Further details will be provided in the SAP.

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8.1.4.1
Pharmacokinetic Analyses
Adalimumab trough serum concentrations will be summarized by treatment group at each 
time point using descriptive statistics including number of subjects, number of 
non missing observations (nnmiss), mean, median, standard deviation, coefficient of 
variation, minimum, and maximum.  The relationship between adalimumab 
concentrations and efficacy and/or safety variables may be explored.  Additional analysis 
may be performed.
8.1.5
Interim Analysis
There will be one planned interim analysis.  Details of the analysis will be described in 
the study SAP.
8.2
Determination of Sample Size
Subjects who successfully completed Study M06-806 through Week 52 may be eligible to 
participate in this study.  It is expected that approximately 70% (130) of subjects from the 
M06-806 study will enroll in this study.
8.3
Randomization Methods
All subjects will be centrally registered using an IVRS.  This is an open-label study; 
therefore, subjects will not be randomized before the study is initiated, the telephone 
number and call in directions for the IVRS will be provided to each site.  Subjects will 
keep their subject number from the previous study (M06-806).
9.0
Ethics
9.1
Independent Ethics Committee (IEC) or Institutional Review 
Board (IRB)
Good Clinical Practice (GCP) requires that the clinical protocol, any protocol 
amendments, the Investigators Brochure, the informed consent and all other forms of 

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subject information related to the study (e.g., advertisements used to recruit subjects) and 
any other necessary documents be reviewed by an IEC/IRB.  IEC/IRB approval of the 
protocol, informed consent and subject information and/or advertising, as relevant, will be 
obtained prior to the authorization of drug shipment to a study site.
Any amendments to the protocol will require IEC/IRB approval prior to implementation 
of any changes made to the study design.  A list of the documents required prior to 
initiation of the study can be found in Appendix C.
Any SAEs that meet the reporting criteria, as dictated by local regulations, will be 
reported to both responsible Ethics Committees and Regulatory Agencies, as required by 
local regulations.  During the conduct of the study, the Investigator should promptly 
provide written reports (e.g., ICH Expedited Reports, and any additional reports required 
by local regulations) to the IEC/IRB of any changes that affect the conduct of the study 
and/or increase the risk to subjects, unless otherwise submitted by the sponsor.  Written 
documentation of the submission to the IEC/IRB should also be provided to AbbVie.
9.2
Ethical Conduct of the Study
The study will be conducted in accordance with the protocol, International Conference on 
Harmonization (ICH) guidelines, applicable regulations and guidelines governing clinical 
trial conduct, and the ethical principles that have their origin in the Declaration of 
Helsinki.  Responsibilities of the clinical Investigator are specified in Appendix D.
9.3
Subject Information and Consent
Prior to any study-related procedures or discontinuation of any medications for this study, 
the Investigator or his/her representative will explain the nature of the study to the subject 
of legal age (in the state of residence) or to the parent or legal guardian (as appropriate) of 
a subject who is not of legal age and answer all questions regarding this study.  Subjects 
will be included in all discussions.

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The ICF will be reviewed, signed and dated by the subject of legal age (in the state of 
residence) or by the parent or legal guardian (as appropriate) of a subject who is not of 
legal age, and the person who administered the informed consent.  If a subject who was 
not of legal age at the onset of this study becomes of legal age during the course of the 
study, an informed consent will need to be obtained at that time.  Additionally, in keeping 
with each institutions IRB requirements an Informed Assent will also be obtained from 
the subject, as required.  
A copy of the signed ICF and Assent Form will be given to the subject and the subjects 
parent/legal guardian.  The original signed ICF and Assent Form will be placed in the
subjects medical record.  An entry must also be made in the subjects dated source 
documents to confirm that informed consent was obtained prior to any study-related 
procedures and that the subject received a signed copy.
If an updated informed consent is approved after a subject has completed or terminated 
early from the study, but is within the 70-day follow-up window, the subject will not be 
required to return to the site for the purposes of signing the updated ICF.  The subject of 
legal age, parent or legal guardian (as appropriate) should be contacted regarding any 
changes and the documentation of the contact should be present in the subjects source. 
10.0
Source Documents and Case Report Form 
Completion
10.1
Source Documents
Source documents are defined as original documents, data and records.  This may include 
hospital records, clinical and office charts, laboratory data/information, subjects diaries or 
evaluation checklists, pharmacy dispensing and other records, recorded data from 
automated instruments, microfiches, photographic negatives, microfilm or magnetic 
media, and/or x-rays.  Data collected during this study must be recorded on the 
appropriate source documents.

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The Investigator(s)/institution(s) will permit study-related monitoring, audits, IEC/IRB 
review, and regulatory inspection(s), providing direct access to source data documents.
The IMPACT III questionnaire and the WPAI questionnaire will be recorded directly on 
the CRF(s) by the subject, parent or legal guardian (as appropriate) and these CRFs will 
be considered source data.
10.2
Case Report Forms
Case report forms will be supplied by AbbVie.  These forms will be used to transmit 
information collected during the study to AbbVie and regulatory authorities, as 
applicable.  Case report forms must be completed for each subject enrolled in this study.  
All case report forms must be legible and completed in indelible black ballpoint ink.  Any 
necessary corrections are to be made by drawing a single line through the incorrect entry 
and writing in the revision.  All revisions must be initialed and dated by the Investigator 
or his/her representative.  Data are not to be obliterated by blacking out, using correction 
fluid or by erasing the original entry.  If the reason for the correction is not obvious, a 
brief explanation (e.g., transcription error) should accompany the change.  All information 
written on the case report forms must also be reflected in the subject source documents 
with the exception of the case report forms discussed above in Section 10.1.
The Principal Investigator will review the case report forms for completeness and 
accuracy and sign and date each set of case report forms where indicated.  The case report 
forms will be reviewed periodically for completeness, legibility and acceptability by 
AbbVie personnel (or their representatives).  AbbVie (or their representatives) will be 
allowed access to all source documents in order to verify case report form entries.
Once the original case report form has been removed from the site, all changes must be 
made via the appropriate change form specified by AbbVie.  The Principal Investigator 
will review the change form for completeness and accuracy and sign and date the change 
form where indicated.

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11.0
Data Quality Assurance
Prior to the initiation of the study, an Investigators meeting will be held with AbbVie 
personnel, the Investigators and their study coordinators, the CROs project manager and 
the CRAs for the study.  This meeting will include a detailed discussion of the protocol, 
performance of study procedures, CRF and Subject Diary completion, and specimen 
collection methods.  In addition to or instead of the Investigators meeting, the study 
personnel at each site may be trained on the study procedures by a CRA at a study 
initiation visit and will be given a CRF completion workbook for reference.
The CRAs will monitor at each site throughout the study.  One hundred percent (100%) 
source document review will be performed against entries on the CRF and a quality 
assurance check will be performed to ensure that the Investigator is complying with the 
protocol and regulations.  In addition, after CRFs are retrieved by the CRA, a review of 
the data will be conducted by a physician and a clinical review team at AbbVie.
All data hand entered in the database will be verified by a double-key entry procedure at 
AbbVie.  Any discrepancies will be reviewed against the hard copy CRF and corrected 
on-line.  After completion of the entry process, computer logic checks will be run to
check for such items as inconsistent study dates and outlying laboratory values.  Any 
necessary corrections will be made to the database and documented via addenda, queries, 
source data clarification form or audit trail.  A manual review of selected line listings will 
also be performed at the end of the study.
Routine hematology, serum chemistry, and serology will be conducted using a central 
laboratory.  ESR analysis will be done at a local lab designated by the site.  The data from 
these analyses will be electronically transferred from the central laboratory to the study 
database.  Urinalysis will be completed locally.  If a microscopic urinalysis is necessary, 
this testing will be conducted using the central laboratory.  A final review of all laboratory 
results will be conducted by a physician and clinical review team at AbbVie.

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Sites will provide AbbVie (or designate) with laboratory certifications (CAP and CLIA), 
CV of local lab director, and reference ranges for each local lab used.  The full name, 
address, phone number, and fax number for each local lab will also be included.
12.0
Use of Information and Publication
12.1
Use of Information
All information concerning adalimumab and AbbVie operations, such as AbbVie patent 
applications, formulas, manufacturing processes, basic scientific data, or formulation 
information, supplied by AbbVie and not previously published is considered confidential 
information.
The information developed during the conduct of this clinical study is also considered 
confidential and will be used by AbbVie in connection with the development of 
adalimumab.  This information may be disclosed as deemed necessary by AbbVie to other 
clinical Investigators, other pharmaceutical companies, to the FDA, and to other 
government agencies.  To allow for the use of the information derived from this clinical 
study and to ensure complete and thorough analysis, the Investigator is obligated to 
provide AbbVie with complete test results and all data developed in this study and to 
provide direct access to source data/documents for study- related monitoring, audits, 
IEC/IRB review, and regulatory inspection.
This confidential information shall remain the sole property of AbbVie, shall not be 
disclosed to others without the written consent of AbbVie, and shall not be used except in 
the performance of this study.
The Investigator will maintain a confidential subject identification code list of all subjects 
enrolled in the study (by name and subject number).  This list will be maintained at the 
site and will not be retrieved by AbbVie.

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12.2
Internet Sites
Information regarding this study may be posted on various internet web sites and will 
maximally include study name, number, general population to be enrolled, entrance 
qualifications, brief description of the study, study objectives, doses, accruing 
Investigators (upon their approval) and number of subjects to be enrolled.
13.0
Completion of the Study
The Investigator will conduct this study in compliance with the protocol, and will 
complete the study within the timeframe specified in the contract between the Investigator 
and AbbVie.  Continuation of the study beyond this time must be mutually agreed upon in 
writing by both the Investigator and AbbVie.  The Investigator will provide a summary of 
the study's outcome to the IEC/IRB following conclusion of the study, and will forward a 
copy of this summary to AbbVie or their designee.
AbbVie may terminate this study prematurely, either in its entirety or at individual sites, 
for reasonable cause provided that written notice is submitted a reasonable time in 
advance of the intended termination.  The Investigator may also terminate the study at 
their site for reasonable cause, after providing written notice to AbbVie a reasonable time 
in advance of the intended termination.  Advance notice is not required by either party if 
the study is stopped due to safety concerns.  If AbbVie terminates the study for safety 
reasons, it will immediately notify the Investigator by telephone and subsequently provide 
written instructions for study termination.
AbbVie will select the signatory Investigator from the Investigators who participate in the 
study.  Selection criteria for this Investigator will include level of participation as well as 
significant knowledge of the clinical research, investigational drug and study protocol.  
The signatory Investigator for the study will review and sign the final study report in 
accordance with the European Agency for the Evaluation of Medicinal Products (EMEA) 
Guidance on Investigators Signature for Study Reports.

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The Investigator will retain all essential documents until at least two years after the last 
approval of a marketing application in an ICH region and until there are no pending or 
contemplated marketing applications in an ICH region or at least two years have elapsed 
since the formal discontinuation of clinical development of the investigational product.  It 
is the responsibility of the sponsor to inform the Investigator/institution as to when these 
documents no longer need to be retained.
The end-of-study is defined as the date of the last subjects last scheduled visit or the 
actual date of follow-up contact, whichever is longer.

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14.0
Investigators Agreement
1.
I have received and reviewed the Investigator Brochure for Humira.
2.
I have read this protocol and agree that the study is ethical.
3.
I agree to conduct the study as outlined and in accordance with all applicable 
regulations and guidelines.
4.
I agree to maintain the confidentiality of all information received or developed in 
connection with this protocol.
Protocol Title:
A Multi-center, Open-label Study of the Human Anti-TNF 
Monoclonal Antibody Adalimumab to Evaluate the Efficacy and the 
Long-term Safety and Tolerability of Repeated Administration of 
Adalimumab in Pediatric Subjects with Crohn's Disease Who Have
Demonstrated a Clinical Response in the M06-806 Study
Protocol Date:
12 April 2013
Signature of Principal Investigator
Date
Name of Principal Investigator (printed or typed)

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15.0
Reference List
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Hanauer SB, Sandborn W.  Management of Crohns disease in adults.  Am J 
Gastroenterol.  2001;96:635-43.
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Loftus Jr. EV.  Clinical epidemiology of inflammatory bowel disease:  Incidence, 
prevalence, and environmental influences.  Gastroenterology.  2004;126:1504-17.
3.
Seidman EG.  Recent advances in the diagnosis and treatment of pediatric 
inflammatory bowel disease.  Curr Gastroenterol Rep.  2000;2:248-52.
4.
Auvin S, Molinie F, Gower-Rousseau C, Brazier F, Merle V, Grandbastient B, 
et al.  Incidence, clinical presentation and location at diagnosis of pediatric 
inflammatory bowel disease:  a prospective population-based study in northern 
France (1988-1999).  J Pediatr Gastroenterol Nutr.  2005;41(1):49-55.
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Kugathasan S, Judd RH, Hoffmann RG, Heikenen J, Telega G, Khan F, et al.  
Epidemiologic and clinical characteristics of children with newly diagnosed 
inflammatory bowel disease in Wisconsin; a statewide population-based study.  
J Pediatr.  2003;143(4):525-31.
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Cosgrove M, Al-Atia RF, Jenkins HR.  The epidemiology of pediatric 
inflammatory bowel disease.  Arch Dis Child.  1996;74:460-1.
7.
Hassan K, Cowan FJ, Jenkins HR.  The incidence of childhood inflammatory 
bowel disease in Wales.  Eur J Pediatr.  2000;159:261-3.
8.
Barton JR, Gillon S, Ferguson A.  Incidence of inflammatory bowel disease in 
Scottish children between 1968 and 1983; marginal fall in ulcerative colitis, 
three-fold rise in Crohns Disease.  Gut.  1989;30:618-22.
9.
Sawczenko A, Sandhu BK, Logan RFA, et al.  Prospective survey of childhood 
inflammatory bowel disease in the British Isles.  Lancet.  2001;357:1093-4.
10.
Olafsdottir EJ, Fluge G, Haug K.  Chronic inflammatory bowel disease in children 
in western Norway.  J Pediatr Gastroenterol Nutr.  1989;8:454-8.

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11.
Lindberg E, Lindquist B, Holmquist L, Hildebrand H.  Inflammatory bowel disease 
in children and adolescents in Sweden (1984-1995).  J Pediatr Gastroenterol Nutr.  
2000;30:259-64.
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Hildebrand H, Finkel Y, Grahnquist L, Lindholm J, Ekbom A, Askling J.  
Changing pattern of paediatric inflammatory bowel disease in northern Stockholm 
1990-2001.  Gut.  2003;52:1432.
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Heyman MB, Kirshner BS, Gold BD, Ferry G, Baldassano R, Cohen SA, et al.  
Children with early onset inflammatory bowel disease (IBD):  analysis of a 
pediatric IBD consortium registry.  J Pediatr.  2005;146(1):35-40.
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Lindberg E, Lindquist B, Holmquist L, Hildebrand H.  Inflammatory bowel disease 
in children and adolescents in Sweden, 1984-1995.  J Pediatr Gastroenterol Nutr.  
2000;30(3):259-64.
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Sawczenko A, Sandhu BK.  Presenting features of inflammatory bowel disease in 
Great Britain and Ireland.  Arch Dis Child.  2003;88:995-1000.
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Griffiths AM.  Specificities of inflammatory bowel disease in childhood.  Best 
Pract Res Clin Gastroenterol.  2004;18(3):509-23.
17.
Griffiths AM, Nguyen P, Smith C, MacMillan JH, Sherman PM.  Growth and 
clinical course of children with Crohns disease.  Gut.  1993;34(7):939-43.
18.
Kanof ME, Lake AM, Bayless TM.  Decreased height velocity in children and 
adolescents before the diagnosis of Crohns disease.  Gastroenterology.  
1988;95(6):1523-7.
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Markowitz J, Grancher K, Rosa J, Aiges H, Daum F.  Growth failure in pediatric 
inflammatory bowel disease.  J Pediatr Gastroenterol Nutr.  1993;16(4):373-80.
20.
Kleinman RE, Baldassano RN, Caplan A, Griffiths AM, Heyman MB, 
Issenman RM, et al.  Nutrition support for pediatric patients with inflammatory 
bowel disease:  a clinical report of the North America Society for Pediatric 
Gastroenterology, Hepatology and Nutrition.  J Pediatr Gastroenterol Nutr.  
2004;39(1):15-27.

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21.
Gokhale R, Favus MJ, Karrison T, Sutton MM, Rich B, Kirshner BS.  Bone 
mineral density assessment in children with inflammatory bowel disease.  
Gastroenterology.  1998;114:902-11.
22.
Boot AM, Bouquet J, Krennings EP, de Muinck Keizer-Schrama SMPF.  Bone 
mineral density and nutritional status in children with chronic inflammatory bowel 
disease.  Gut.  1998;42:188-94.
23.
Ballinger AB, Savage MO, Sanderson IR.  Delayed puberty associated with 
Inflammatory bowel disease.  Pediatr Res.  2003;53:205-10.
24.
Harpavat M, Greenspan SL, OBrien C, Chang C-C, Bowen A, Keljo DJ.  Altered 
bone mass in children at diagnosis of Crohns disease:  a pilot study.  J Pediatr 
Gastroenterol Nutr.  2005;40:295-300.
25.
Hyams JS, Wyzga N, Kreutzer DL, Justinich CJ, Gronowicz GA.  Alterations in 
bone metabolism in children with inflammatory bowel disease:  an in vitro study.  
J Pediatr Gastroenterol Nutr.  1997;24(3):289-95.
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Hanauer S, Lukas M, MacIntosh D, Rutgeerts P, Sandborn W, Pollack P.  A 
randomized, double-blind, placebo-controlled trial of the human anti-TNF-α 
monoclonal antibody adalimumab for the induction of remission in patients with 
moderate to severely active Crohns disease.  Gastroenterology.  2004;127(1):332.
27.
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28.
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29.
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30.
Present DH, Rutgeerts P, Targan S, Hanauer SB, Mayer L, van Hogezand RA, 
et al.  Infliximab for the treatment of fistulas in patients with Crohns disease.  
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31.
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Wrist:  June 1959.
32.
Centers for Disease Control and Prevention.  Targeted tuberculin testing and 
treatment of latent tuberculosis infection.  MMWR 2006 April.

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Appendix A.
List of Abbreviations and Definition of Terms
Abbreviations
AAA
Anti-adalimumab antibody
AE
Adverse Event
ALT
Alanine Transaminase
ANA
Antinuclear antibody
AST
Aspartate transaminase
BMI
Body Mass Index
BSAP
Bone-specific alkaline phosphatase
BUN
Blood Urea Nitrogen
CD
Crohns disease
CDC
Center for Disease Control
CNS
Central Nervous Systems
CRA
Clinical Research Associate
CRF
Case Report Form
CRP
C-Reactive Protein
CTC
Common Toxicity Criteria
DMC
Data Monitoring Committee
DNA
Deoxyribonucleic acid
dsDNA
Double Stranded DNA
eow
Every other week
ESR
Erythrocyte sedimentation rate
ET
Early Termination
EU
European Union
ew
Every week
FDA
U.S. Food and Drug Administration
GCP
Good Clinical Practice
HCT
Hematocrit
HIV
Human immunodeficiency virus
ICH
International Conference on Harmonization
IEC
Independent Ethics Committee
IgG1
Immunoglobulin
ICF
Informed Consent Form

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IRB
Institutional Review Board
ITT
Intent-to Treat
IVRS
Interactive Voice Response System
JRA
Juvenile Rheumatoid Arthritis
LOCF
Last Observation Carried Forward
MTX
Methotrexate
Ntx 
N-telopeptide
OL
Open-Label
PCDAI
Pediatric Crohns Disease Activity Index
PK
Pharmacokinetics
POR
Proof of Receipt
RA
Rheumatoid Arthritis
SAE
Serious Adverse Event
SAP
Statistical analysis plan
SC
Subcutaneous
SSC
Sponsor Steering Committee
TB
Tuberculosis
TNF
Tumor Necrosis Factor
TPN
Total Parenteral Nutrition
US
United States
WPAI
Work Productivity and Activity Impairment Questionnaire
WPAI-CD
Work Productivity and Activity Impairment Questionnaire:  Crohns 
Disease

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Appendix B.
List of Protocol Signatories
Name
Title
Functional Area
Statistics
Pharmacokinetics
Clinical
Clinical
Clinical

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Appendix C.
Documents Required Prior to Initiation of the Study
As sponsor of a clinical study, AbbVie has an obligation to ensure that the study will be 
conducted by a qualified investigator with sufficient resources (of time, personnel, and 
physical facilities) to conduct the study and to ensure that the investigator understands and 
agrees to comply with Good Clinical Practices and applicable regulations, policies, and 
procedures.  Prior to the beginning of any clinical study, the investigator will be asked to 
provide the following documentation.
1.
A signed and dated Investigators agreement page for the study.
2.
A signed and dated Form FDA 1572 certifying the investigators agreement to 
comply with the appropriate regulations governing the conduct of the study.
A signed and dated Investigator Information and Agreement Form certifying the 
investigators agreement to comply with the appropriate (e.g., ICH GCP) 
regulations governing the conduct of the study.  These will be required only for 
sites that are recruited under this amendment, or when existing sites update study 
documentation.
3.
Current curriculum vitae for the investigator.  If subinvestigators will participate in 
the study, curriculum vitae for each.
4.
Requirements for the Independent Ethics Committee (IEC)/Institutional Review 
Board (IRB).
●
A copy of the signed and dated letter of approval of the IEC/IRB.  The letter 
must specify that both the protocol and informed consent form were approved 
(unless separate documentation that the informed consent was approved is 
provided).

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●
A dated list containing the names and affiliations of the members of the 
IEC/IRB, or the institutions General Assurance Number.
●
If the investigator and/or subinvestigator is a member of the IEC/IRB, a letter 
stating that he/she did not participate in the review or approval of the protocol 
or informed consent form.
5.
A specimen copy of the IEC/IRB-approved informed consent document to be used 
in the study.
6.
A list of reference ranges of values for all laboratory tests specified by the protocol 
for all laboratories utilized.
7.
A copy of the laboratory(ies) certification(s) or the authorization number of the 
certification(s), the name of the certifying authority, and the period of certification.
8.
Financial Disclosure Certification forms must be completed by each investigator 
and all subinvestigators identified on the Form FDA 1572 or Investigator 
Information and Agreement Form.  A Financial Disclosure, EU Consent, is 
required to be completed for each investigator and/or subinvestigator who is a 
resident of the European Union.

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Appendix D.
Responsibilities of the Clinical Investigator
Clinical research studies sponsored by AbbVie are subject to the regulations of the U.S. 
Food and Drug Administration (FDA).  The responsibilities imposed upon Investigators 
by the FDA are summarized in the "Statement of Investigator" (Form FDA 1572), which 
is a form letter addressed to the sponsor (AbbVie), summarizing the Investigators 
qualifications for the study and his/her willingness to follow FDA regulations with respect 
to the study.
In signing a Form FDA 1572, the Investigator agrees to assume the following 
responsibilities:  
1.
To conduct the study(ies) in accordance with the relevant, current protocol(s) and 
only make changes in a protocol after notifying AbbVie, except when necessary to 
protect the safety, rights, or welfare of subjects.
2.
To personally conduct or supervise the described investigation(s).
3.
To inform any subjects, or any persons used as controls, that the drugs are being 
used for investigational purposes and to ensure that the requirements relating to 
obtaining informed consent in 21 CFR Part 50 and Independent Ethics Committee 
(IEC)/Institutional Review Board (IRB) review and approval in 21 CFR Part 56 are 
met.
4.
To report to AbbVie adverse experiences that occur in the course of the 
investigation(s) in accordance with 21 CFR 312.64.
5.
To read and understand the information in the Investigators Brochure, including the 
potential risks and side effects of the drug.
6.
To ensure that all associates, colleagues, and employees assisting in the conduct of 
the study(ies) are informed about their obligations in meeting the above 
commitments.

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7.
To maintain adequate and accurate records of the conduct of the study and make 
those records available for inspection by representatives of AbbVie, the IEC/IRB 
and/or the appropriate regulatory agency, and to retain all study-related documents 
until notification from AbbVie.  The Investigator must notify AbbVie when they 
are no longer able to retain the study related documents.
8.
To ensure that an IEC/IRB that complies with the requirements of 21 CFR Part 56 
will be responsible for the initial and continuing review and approval of the clinical 
investigation.
9.
To promptly report to the IEC/IRB all changes in the research activity and all 
unanticipated problems involving risks to human subjects or others (including 
submission of any Expedited Safety Reports received from AbbVie to the 
IEC/IRB), and to make no changes in the research without IEC/IRB approval, 
except where necessary to eliminate apparent immediate hazards to human 
subjects.
10.
To comply with all other requirements regarding the obligations of clinical 
Investigators and all other pertinent requirements in 21 CFR Part 312.

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Appendix E.
CDC Treatment of Tuberculosis Infection (Preventive Therapy)
Centers for Disease Control and Prevention
Tuberculosis Information
Treatment of Tuberculosis Infection (Preventive Therapy), Latent Tuberculosis
Infection (LBTI)32

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Appendix F.
Non-Drug Materials Provided to the Study Site(s)
Study sites will receive the following supplies prior to or during the study:
Tote Bags
Cooler
Sharps Containers
Ice Packs
CDAI subject diary
Dosing Diaries
Subject Medication Log
Self Injection Instructions
Dosing syringes, as applicable

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Appendix G.
Pediatric Crohns Disease Activity Index (PCDAI)
1.
Abdominal pain rating
- None
- Mild - Brief, does not interfere with activities
- Moderate/severe-Daily, longer lasting, affects activities, nocturnal
= 0 p
= 5 p
= 10 p
Score
2.
Stools (per day)
- 0–1 liquid stools, no blood
- Up to 2 semi-formed with small blood, or 2–5 liquid
- Gross bleeding, or ≥6 liquid, or nocturnal diarrhea
= 0 p
= 5 p
= 10 p
3.
Patient Functioning, General Well-Being
- No limitation of activities, well
- Occasional difficulty in maintaining age appropriate activities, below par
- Frequent limitation of activity, very poor
= 0 p
= 5 p
= 10 p
LABORATORY
Score
4.
HCT:  Male and female ≤10 years:
≥ 33
= 0 p
28-32
= 2.5 p
< 28
= 5 p
Male 11–14 years:
≥ 35
= 0 p
30-34
= 2.5 p
< 30
= 5 p
Female 11–19 years: ≥ 34
= 0 p
29-33
= 2.5 p
< 29
= 5 p
Male 15–19 years:
≥ 37
= 0 p
32-36
= 2.5 p
< 32
= 5 p
5.
ESR (mm/hr)
< 20
= 0 p
20-50
= 2.5 p
> 50
= 5 p
6.
Albumin (g/dL)
≥ 3.5
= 0 p
3.1-3.4 = 5 p
≤ 3.0
= 10 p

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EXAMINATION
Score
7.
Weight
- Weight gain or voluntary weight stable/loss
- Involuntary weight stable, weight loss 1–9%
- Weight loss ≥ 10%
= 0 p
= 5 p
= 10 p
8.
Height
Height velocity ≥ -1SD
Height velocity < -1SD, > -2SD
Height velocity ≤ -2SD
= 0 p
= 5 p
= 10 p
9.
Abdomen
- No tenderness, no mass
- Tenderness, or mass without tenderness
- Tenderness, involuntary guarding, definite mass
= 0 p
= 5 p
= 10 p
10. Perirectal disease
- None, asymptomatic tags
- 1–2 indolent fistula, scant drainage, no tenderness
- Active fistula, drainage, tenderness, or abscess
= 0 p
= 5 p
= 10 p
11. Extra-intestinal Manifestations
(Fever ≥ 38.5 for 3 days over past week, definite arthritis, uveitis, E. nodosum, 
P. gangrenosum)
- None
- One
- ≥ Two
= 0 p
= 5 p
= 10 p
TOTAL SCORE 
Pediatric Crohns Disease Activity Index (PCDAI)

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Appendix H.
PCDAI Users Guide and Guideline for Reference Weight and 
Reference Height
This guide is intended to help nurse coordinators and physicians complete the PCDAI in 
order to assess disease activity in children with Crohns disease participating in clinical 
trials.
History
All calculations are based upon a one-week (7 day) history recall of symptoms.  The 
history recall should be solicited from the subject and/or caregiver.
Item 1.  Abdominal pain
The descriptions in the PCDAI of "mild" and "moderate/severe" should be used to guide 
in scoring the pain. Note that duration, effect on activities, and nocturnal occurrence 
separate moderate/severe from mild.  If pain varies in severity during the week, subject 
should be scored according to the most severe pain. However, mild pain should be present 
on at least two days to score 5 points rather than 0 points.
Item 2.  Stools
The intent is to score the stool pattern during the preceding week.
To facilitate scoring, first categorize the subject as having blood in the stool or not.
If there is no blood in the stool, score as follows:  
Formed stools or up to 1 loose stool daily = 0
2-5 liquid or very loose stools on 1 or more days = 5
6 or more liquid or very loose stools on 1 or more days or any nocturnal diarrhea = 10
If blood is present in the stool on any day during the past week, score as follows:  

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Small amounts of blood in stool (on toilet paper or small spots in stool, etc.) = 5
Any gross bleeding (large amounts on stool or colors the water in the toilet, etc.) = 10
Item 3.  Subject functioning, general well-being
If there is variation during the week, subject should be scored according to the most 
significant limitation of activity, even if it occurs during only one day of the week, as long 
as it is likely due to Crohns disease and not to an intercurrent illness.
Item 4.  Hematocrit
Hematocrit values should be rounded to a whole number prior to completing the 
calculation.  Numbers that fall between the range of 0.1-0.4 must be rounded down.   
Numbers that fall between the range of 0.5-0.9 must be rounded up.
Physical Examination
Item 7.  Weight (The intent is to assess the ability to normally maintain or gain weight)
Reference weight to be used for calculation of weight gain/loss during the study:
From Baseline to Week 336:  use weight from previous visit
Voluntary weight stable/loss means subject maintaining or losing weight on purpose.
Involuntary weight stable means subject wants to gain weight but cannot.
To calculate percentage weight loss use formula:  
Weight from previous visit – Current weight X 100 = % weight loss
Weight from previous visit

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Item 8.  Height
Reference height for calculation of height velocity
●
From Baseline to Week 24, use height from 6 months prior to Baseline
●
From Week 24 to Week 48, use height from Baseline visit
●
From Week 48 to Week 72, use height from Week 24
●
From Week 72 to Week 96, use height from Week 48
●
From Week 96 to Week 120, use height from Week 72
●
From Week 120 to Week 144, use height from Week 96
●
From Week 144 to Week 168, use height from Week 120
●
From Week 168 to Week 192, use height from Week 144
●
From Week 192 to Week 216, use height from Week 168
●
From Week 216 to Week 240, use height from Week 192
●
From Week 240 to Week 264, use height from Week 216
●
From Week 264 to Week 288, use height from Week 240
●
From Week 288 to Week 312, use height from Week 264
●
From Week 312 to Week 336, use height from Week 288
The intent is to assess the normalcy vs. impairment of the subjects recent linear growth.  
Note that post-pubertal subjects will score 0 points.  For subjects still growing, there are 
two options for scoring.  Method (a) is preferred.  Method (b) to be used if data required 
for (a) are unavailable.

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1.
Height velocity (cm/year), the most sensitive parameter, should be calculated as 
below:
Present height – Appropriate height measurement (from above) x 12 = Height velocity (cm/year)
        Interval (months) between heights
Using height velocity chart below, determine centile for height velocity.
2.
Scoring for the PCDAI:  
a.
Velocity less than "Minus 2 SD" scores 10 points.
b. Velocity between "Minus 2 SD" and "Minus 1 SD" scores 5 points.
c.
Velocity greater than "Minus 1 SD" scores zero points.
*
Please note that subjects should score zero points if a subject is a female above 14.5 years of age or a male above 
17.5 years of age.

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Height Velocity Reference Values for Calculating the PCDAI (Males)
Height Velocity in cm per year (Males)
Age (years)
Minus 2SD
Minus 1SD
Mean
2.5
5.7
7.0
8.3
3
5.4
6.6
7.8
3.5
5.1
6.3
7.4
4
4.9
6.0
7.1
4.5
4.7
5.8
6.8
5
4.6
5.6
6.6
5.5
4.5
5.4
6.4
6
4.3
5.3
6.2
6.5
4.2
5.1
6.0
7
4.2
5.0
5.9
7.5
4.1
4.9
5.8
8
3.9
4.8
5.6
8.5
3.8
4.6
5.4
9
3.8
4.5
5.3
9.5
3.7
4.5
5.2
10
3.7
4.4
5.1
10.5
3.7
4.4
5.1
11
3.7
4.4
5.2
11.5
3.8
4.6
5.3
12
4.0
4.9
5.7
12.5
4.8
5.8
6.7
13
6.2
7.4
8.6
13.5
7.1
8.3
9.5
14
6.1
7.2
8.4
14.5
4.1
5.3
6.5
15
2.4
3.6
4.7
15.5
1.2
2.3
3.3
16
0.4
1.3
2.2
16.5
0.1
0.7
1.5
17
0.1
0.4
0.9
17.5
0.1
0.1
0.5

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Height Velocity Reference Values for Calculating the PCDAI (Females)
Height Velocity in cm per year (Females)
Age (years)
Minus 2SD
Minus 1SD
Mean
2.5
5.9
7.3
8.6
3
5.5
6.9
8.1
3.5
5.2
6.4
7.6
4
4.9
6.1
7.2
4.5
4.7
5.8
6.8
5
4.6
5.6
6.6
5.5
4.5
5.5
6.4
6
4.4
5.3
6.2
6.5
4.3
5.2
6.1
7
4.3
5.2
6.0
7.5
4.3
5.1
5.9
8
4.2
5.0
5.8
8.5
4.2
4.9
5.7
9
4.2
5.0
5.8
9.5
4.3
5.0
5.8
10
4.4
5.3
6.2
10.5
4.7
5.7
6.8
11
5.7
6.6
7.7
11.5
6.1
7.2
8.3
12
5.2
6.3
7.3
12.5
3.6
4.8
5.9
13
2.4
3.3
4.3
13.5
1.3
2.2
2.9
14
0.4
1.1
1.8
14.5
0.0
0.5
1.0

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Appendix I.
Crohns Disease Activity Index (CDAI)
Factor
Subtotal
1.
Number of liquid or very soft stools
(Record the frequency per day)
         __+___+___+___+___+___+___=___
Days: 1
    2      3      4
5      6
  7   Sum
X
2
2. Abdominal pain rating:
0 = none, 1 = mild, 2 = moderate, 
3 = severe
          __+___+___+___+___+___+___=___
Days: 1
    2      3      4
5      6
  7   Sum
X
5
3.
General well-being:
0 = generally well, 1 = slightly 
underpar, 2 = poor, 3 = very poor, 
4 = terrible
         __+___+___+___+___+___+___=___
Days: 1
    2      3      4
5      6
  7   Sum
X
7
4.
Number of 6 listed categories the 
subject now has:
Check all items that apply:
□  Arthritis/arthralgia
□  Iritis/uveitis
□  Erythema nodosum/ 
pyoderma gangrenosum/
aphthous stomatitis
□  Fissure, abscess and/or anal 
fistula (draining/non-draining)
□  Other cutaneous fistula 
(draining/non-draining) fistula
□  Fever over 100°F (37.8°C) during 
past week
  
________
Record "0" if no categories checked
X
20
5.
Taking Lomotil/Imodium/ 
Loperamide/opiates for diarrhea 
0 = no, 1 = yes
________
X
30
6.
Abdominal mass
0 = none, 2 = questionable, 5 = defined
________
X
10
7.
Hematocrit:  ______
Male:
(47 - hematocrit) =
Female: (42 - hematocrit) = Subtotal ______
If hematocrit > normal, enter "0"
X
6
8.
Body weight:  __  __  __ . __ (kg)
Ideal weight for height:
__  __  __ . __ (kg)
100 x [1 - (Body wt/Ideal wt)] = 
Percent below ideal weight:  ______
If body wt > ideal wt, enter "0"
X
1
Total
*
Ideal weight is obtained from CDC growth charts.  The subtotal of box 8 should be rounded to a whole number.  
Numbers that fall between the range of .1-.4 must be rounded down.  Numbers that fall between the range of .5-.9 
must be rounded up.  To ensure consistency across all sites and to take into account the varying growth rates of
subjects in this study, the IBW should be calculated at each visit.
*
Hematocrit values should be rounded to a whole number prior to completing the calculation in box 7 of the CDAI.  
Numbers that fall between the range of .1-.4 must be rounded down.  Numbers that fall between the range of .5-.9 
must be rounded up.

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Appendix J.
Subject CDAI Diary
Crohns Disease Activity Index
Subject Diary Card
Enter all values legibly using a black 
ballpoint pen.
Add item requested for each day.
Day
Date___
Day
Date___
Day
Date___
Day
Date___
Day
Date___
Day
Date___
Day
Date___
Number (total) of liquid or very soft 
stools per day.
Daily abdominal pain rating.
(0 = none, 1 = mild, 2 = moderate, 
3 = severe)
Daily rating of general well being.
(0 = well, 1 = slightly below par, 
2 = poor, 3 = very poor, 4 = terrible)
Subject Initials:___________
Subjects Signature:__________________________
Investigator or Designees Signature:______________________

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Question 1.
How much has your stomach been hurting you in the past two weeks?
□
□
□
□
□
Not at all
Hardly hurting 
at all
Hurting 
somewhat 
Hurting
quite a bit
Hurting
very much
Question 2. 
Taking medicines or tablets bothers you
□
□
□
□
□
Not at all
Hardly bothers 
at all
Bothers 
somewhat
Bothers 
quite a bit
Bothers
very much
Question 3.
How often has your inflammatory bowel disease prevented you from 
eating what you want in the past two weeks?
□
□
□
□
□
Never
Rarely
Sometimes
Often
Very often
Question 4.
How often have you been worrying about having a flare-up (increase of
symptoms) in the last two weeks?
□
□
□
□
□
Never
Rarely
Sometimes
Often
Very often
Question 5.
How much does it bother you that you have an illness that does not just go 
away?
□
□
□
□
□
Not at all
Hardly bothers 
at all
Bothers 
somewhat
Bothers quite a
bit
Bothers very 
much
Question 6.
How much energy did you have during the past two weeks?
□
□
□
□
□
Very much 
energy
Quite a bit of 
energy
Some energy
A little energy
No energy at 
all

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Question 7.
How do you feel about your weight?
□
□
□
□
□
I feel great 
about my 
weight
I feel good 
about my 
weight
I dont feel 
good or bad 
about my 
weight
I feel bad about 
my weight
I feel awful 
about my 
weight
Question 8.
How has your inflammatory bowel disease affected your family?
□
□
□
□
□
The effect has 
been great
The effect has 
been good
It has not 
affected our 
family
The effect has 
been bad
The effect has 
been awful
Question 9.
How often did you have to miss out on certain things (hobbies, play, 
parties) because of your inflammatory bowel disease in the past two weeks?
□
□
□
□
□
Never
Rarely
Sometimes
Often
Very often
Question 10.
How often have you been bothered by diarrhea (loose or frequent bowel 
movements) in the past two weeks?
□
□
□
□
□
Never
Rarely
Sometimes
Often
Very often
Question 11.
How often do you worry about health problems you might have in the 
future?
□
□
□
□
□
Never
Rarely
Sometimes
Often
Very often

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Question 12.
How often do you think it is unfair that you have inflammatory bowel 
disease?
□
□
□
□
□
Never
Rarely
Sometimes
Often
Very often
Question 13.
During the past two weeks, were you ever angry that you have 
inflammatory bowel disease?
□
□
□
□
□
Never
Rarely
Sometimes
Often
Very often
Question 14.
Do you think too many rules or limits are placed on you because of your 
inflammatory bowel disease?
□
□
□
□
□
Never
Rarely
Sometimes
Often
Very often
Question 15.
How do you feel about the way you look?
□
□
□
□
□
I think I look 
great
I think I look 
good
I dont think I 
look good or 
bad
I think I look 
bad
I think I look 
awful
Question 16.
Are you embarrassed because of your bowel condition?
□
□
□
□
□
Not at all
Hardly 
embarrassed at 
all
Embarrassed 
somewhat
Embarrassed 
quite a bit
Embarrassed 
very much
Question 17.
Did you have fun during the past two weeks?
□
□
□
□
□
Very often 
Often
Sometimes
Rarely
Never

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Question 18.
Is it harder to make friends because of your inflammatory bowel disease?
□
□
□
□
□
Not at all 
harder
A little harder
Quite a bit 
harder
Much harder
Very much 
harder
Question 19. How often do you worry about your stool (bowel movement) containing 
blood?
□
□
□
□
□
Never
Rarely
Sometimes
Often
Very often
Question 20.
Are you worried you cannot go out on a date or have a boyfriend or 
girlfriend because of your inflammatory bowel disease?
□
□
□
□
□
Not at all 
worried
Hardly worried 
at all
Worried 
somewhat
Worried quite 
a bit
Worried very 
much
Question 21.
How often did you feel sick to your stomach in the past two weeks?
□
□
□
□
□
Never
Rarely
Sometimes
Often
Very often
Question 22.
How do you feel about the tests you have to go through?
□
□
□
□
□
I do not mind 
them at all
I mind them a 
tiny bit
I mind them a 
little
I mind them a 
lot
I hate them
Question 23.
Do other children bully you or leave you out of things because of your 
inflammatory bowel disease or its treatment?
□
□
□
□
□
Never
Rarely
Sometimes
Often
Very often

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Question 24.
How often do you worry about having an operation?
□
□
□
□
□
Never
Rarely
Sometimes
Often
Very often
Question 25.
In the past two weeks how often were you afraid you may have an accident 
or not get to the toilet in time?
□
□
□
□
□
Never
Rarely
Sometimes
Often
Very often
Question 26.
Do you try to keep your inflammatory bowel disease a secret from other 
people?
□
□
□
□
□
No, I do not try 
at all
I dont try much
I try a little
I try hard
Yes, I try very 
hard
Question 27.
Does your inflammatory bowel disease make it difficult to travel or go on a 
holiday?
□
□
□
□
□
No, not 
difficult
A little 
difficult
Quite difficult
Very difficult
Yes, extremely 
difficult
Question 28.
How did you feel during the past two weeks?
□
□
□
□
□
Great
Good
Not good or 
bad
Bad
Awful
Question 29.
Are you happy with your life?
□
□
□
□
□
Yes, very 
happy
Happy
Not happy or 
unhappy
Unhappy
Very unhappy

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Question 30.
Do you feel there is someone you can talk to about your inflammatory 
bowel disease?
□
□
□
□
□
Always 
Often
Sometimes
Rarely
Never
Question 31.
How often did you have to pass gas in the past two weeks?
□
□
□
□
□
Never
Rarely
Sometimes
Often
Very often
Question 32.
How tired have you felt in the past two weeks?
□
□
□
□
□
Not at all tired
A little tired
Quite tired
Tired 
Very tired
Question 33.
How do you feel about your height?
□
□
□
□
□
I feel great 
about my 
height
I feel good 
about my 
height
I dont feel 
good or bad 
about my 
height
I feel bad 
about my 
height
I feel awful 
about my 
height
Question 34.
Does your inflammatory bowel disease get in the way of playing sports the 
way you would like to?
□
□
□
□
□
Never
Rarely
Sometimes
Often
Always
Question 35.
In the past two weeks how often were you able to go to school?  (If you are 
in the middle of a school break or the summer holidays, answer as if school was on)
□
□
□
□
□
Always 
Most days
Half the days
A few days
Never

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End of questionnaire
This completes the questionnaire.  Do you have anything else to add which you feel is 
important about having inflammatory bowel disease, or do you have any other 
remarks?  Please write them below.
_________________________________________________________
_________________________________________________________
_________________________________________________________

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Appendix L.
Excluded Medications
Cyclosporine
Tacrolimus
Therapeutic enemas and suppositories (not including those done in conjunction with 
routine colonoscopy)
Live vaccines
The combination of budesonide and prednisone (or equivalent)
Infliximab
Mycophenolate mofetil (MMF or CellCept®)
Growth Hormone
Kineret® (anakinra)
Tysabri (natalizumab)
Orencia (abatacept)
Concurrent biologic therapy
Any investigational agent
Any previous anti-TNF medication except infliximab before the M06-806 study 
(including adalimumab).

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Appendix M.
Day 70 Phone Call
Site Name/Number:  ________
Subject Number:  ________
Subject Initials:  ________
Please contact all Subjects 70 days following drug discontinuation.
Date of Call:  ____________
□     Lost to Follow-Up (Please check this box if subject was not willing to provide any follow-up 
information or you were unable to speak to the subject following at least one attempt).
□      No Events Reported
List any Adverse Events (AE) and/or Serious Adverse Events (SAE) that occurred since the subject was last 
seen in clinic for this study.  Please document all adverse events on a 500 AE CRF to be submitted to data 
management.  (Please report all SAEs to AbbVie within 24 hours of being made aware of the event.  
Follow-up information must also be reported within 24 hours of being made aware of the information.).
If events are listed above, your monitor will review and retrieve the appropriate CRF pages during 
their next visit.  Please fax this form to Paragon at 

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Appendix N.
Unscheduled Outpatient Visits, Emergency Room Visits and 
Hospitalizations
1.
Since the last study visit has the subject had any physician/health care visits for 
their Crohns disease other than the protocol required visits?
Yes ___
No  ___
If yes provide the following:
I.
Since the last visit, has the subject been seen by a physician for their Crohns 
Disease?
YES:_____
NO:_____
If YES, how many times:_______
II.
Since the last visit, has the subject been seen in the Emergency Room for their 
Crohns Disease?
YES:_____
NO:______
If YES, how many times:  _____
III. Since the last visit, has the subject been admitted to the hospital due to their 
Crohns Disease?
YES:_____
NO:______
If YES, how many times:_____
If YES, please indicate the total number of days in the hospital:_____

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Appendix O.
Subject Medication Log
Instructions:  As a participant in this study, it is also important to keep a record of all mediations you take (new and old) throughout the study.  Please take this 
sheet home with you and write down any medications you take during the study.  It will be VERY important that you bring this sheet back to your doctors office 
and speak with your doctor about everything you have written down.
Name of Medication
Date you took
first dose
Date you took
last dose
What dose of medicine 
did you take?
How often did you 
take the medicine?
Why did you take the 
medicine?

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Week 25 - Week 36
Subject Initials:  __________
Subject Study #:  ___________
Date
day/mm/yr
Day or 
Week #
Time of Study 
Drug 
Administration
Dose (mL) 
Administered
Kit #
Initials of Person 
Administering 
Study Medication
Comments
18/MAR/04
EXAMPLE
9:35 am
0.8
MM
none
Week 25
Week 26
Week 27
Week 28
Week 29
Week 30
Week 31
Week 32
Week 33
Week 34
Week 35
Week 36

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Week 241 - Week 263
Subject Initials:  __________
Subject Study #:  ___________
Date
day/mm/yr
Day or 
Week #
Time of Study 
Drug 
Administration
Dose (mL) 
Administered
Kit #
Initials of Person 
Administering 
Study Medication
Comments
18/MAR/04
EXAMPLE
9:35 am
0.8
MM
none
Week 241
Week 242
Week 243
Week 244
Week 245
Week 246
Week 247
Week 248
Week 249
Week 250
Week 251
Week 252
Week 253
Week 254
Week 255
Week 256
Week 257
Week 258
Week 259
Week 260
Week 261
Week 262
Week 263*
*
Week 263 dose will only be taken if on every-week dosing schedule.

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Week 313 - Week 335
Subject Initials:  __________
Subject Study #:  ___________
Date
day/mm/yr
Day or 
Week #
Time of Study 
Drug 
Administration
Dose (mL) 
Administered
Kit #
Initials of Person 
Administering 
Study Medication
Comments
18/MAR/04
EXAMPLE
9:35 am
0.8
MM
none
Week 313
Week 314
Week 315
Week 316
Week 317
Week 318
Week 319
Week 320
Week 321
Week 322
Week 323
Week 324
Week 325
Week 326
Week 327
Week 328
Week 329
Week 330
Week 331
Week 332
Week 333
Week 334
Week 335*
*
Week 335 dose will only be taken if on every-week dosing schedule.

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Appendix Q.
Self Injection Instructions
Subject Instructions
0.8 mL or 0.4 mL dose
(Administered as a single dose-prefilled syringe (PFS))
Protocol M06-807

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Tables of Contents
Dosing Schedule
General Information 
Injection Procedures

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Study Drug Dosing Schedule
Open-Label (PFS)
Subject Number:  _____________________________________
You will require subcutaneous (SC) injections throughout the study. 
Injections at scheduled study visits (Baseline, Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 
108, 120, 144, 168, 192, 216, 240, 264, 288 and 312) will be done during your visit, at the 
doctors office.  On weeks between office visits, study drug will be self-administered at 
home by you or someone trained to give you the injections.
For 40 mg dose, one pre-filled syringe will contain 0.8 mL of liquid.  The total available 
dose is 0.8 mL.  The drug should be administered in one (1) SC injection, on the same day 
of the week for each dose.
For 20 mg dose, one pre-filled syringe will contain 0.4 mL of liquid.  The total available 
dose is 0.4 mL.  The drug should be administered in one (1) SC injection, on the same day 
of the week for each dose.
Please return all used and unused syringes to the clinic on your next visit.  Used syringes 
should be placed in the special sharps container provided.  All unused syringes should be 
returned in the original box.
If an injection is missed or something occurs where the full dose cannot be injected, 
contact your study center immediately for further instructions.  Please record any missed 
doses on your subject diary.
Remember to complete your dosing diary after each injection and to call the doctors office 
if you are having problems administering your study drug.

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General Information
PFS
●
Prefilled syringes will be labeled "adalimumab."
●
Store all adalimumab prefilled syringes in your refrigerator NOT in the 
freezer.  Should the syringes accidentally become frozen, call your study 
coordinator.
●
0.8 mL = 0.8 cc
●
Study drug should be taken at about the same time of day, on the same day of 
the week as directed by your study doctor.
●
USE A NEW SYRINGE EVERY INJECTION DAY.  There may be 
medication left in the syringe.  DO NOT RE-USE.
●
Save all study drugs.  Prefilled syringes (used and unused) must be returned 
to the study center at each visit.  Used syringes will be disposed of in a sharps 
container provided to you.
●
Whenever possible, have someone with you for at least 15 to 30 minutes after 
your injection.
●
Call your doctor IMMEDIATELY if you experience any itching, hives, 
shortness of breath, or any symptom that has you concerned.  If you are unable 
to reach your doctor or if you experience life-threatening symptoms call 911, 
or proceed to your nearest emergency room.

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Injection Procedures
PFS
1.
Clean your workspace, gather your supplies, and wash your hands.
2. Identify the area on your abdomen or thigh (or upper 
arm if not self injecting).  Make sure the area you 
choose does not have any redness, tenderness, swelling, 
bruising, or psoriasis.  The area must also be at least 
2 cm (approximately 1 inch) away from the previous 
injection site.  IT IS VERY IMPORTANT TO 
CHANGE THE INJECTION SITE EVERY TIME!!!
3. Using a circular motion (starting at the injection site 
and moving outward) clean the selected injection site 
with an alcohol pad.  Allow skin to dry. 
4. Remove the needle cap.  Do not touch the needle.  
Expel any air bubbles from the syringe by tapping on 
the syringe.  If the needle becomes contaminated, 
discard all supplies and obtain a new syringe of study 
drug. 
5. Once the air is expelled from the syringe, the amount of 
solution in the syringe should be 0.8 mL.
6. Hold the syringe "like a dart" between your thumb and 
first finger close to the syringe/needle connection.

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PFS
7. With your other hand, pinch the skin around the 
injection site, forming a bulge in the skin.
8. Insert the needle into the skin at a 45-degree angle.  
Release pinched skin.
9.
GENTLY pull back on the syringe plunger.  If blood 
appears, withdraw needle - DO NOT INJECT!  
Contact your study center immediately for further 
instructions. 
10. Inject drug by pushing slowly on syringe plunger with 
thumb.
11. Remove needle while maintaining a 45-degree angle.
12. You may apply a Band-Aid over the injection site and 
apply gentle pressure, if necessary.  DO NOT RUB 
SITE.
13.
DO NOT RECAP NEEDLE.  DO NOT SEPARATE THE NEEDLE FROM THE 
SYRINGE BEFORE DISPOSING.  Discard used syringes into Sharps Container.
EACH TIME THAT YOU GIVE YOURSELF AN INJECTION OF STUDY DRUG, 
REMEMBER TO RECORD THE INFORMATION ON YOUR SUBJECT DOSING 
DIARY.

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Self Injection Instructions
Subject Instructions
0.2 mL dose
Vials
Protocol M06-807

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Tables of Contents
Dosing Schedule
General Information 
Injection Procedures

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Study Drug Dosing Schedule
Vials
Subject Number:  _____________________________________
You will require subcutaneous (SC) injections throughout the study.
The injection for the visits at Weeks 4, 8, 12, 16, 20, 26, 32, 40, 48, 60, 72, 84, 96, 108, 
120, 144, 168, 192, 216, 240, 264, 288 and 312 will be done during your visit at the 
doctor's office.  After Week 4, on weeks between office visits (i.e., Weeks 6, 10, 14, etc.) 
study drug will be self-administered at home by you or someone trained to give you the 
injections.
The total dose is 0.2 mL.  The drug should be administered in one (1) SC injection, on the 
same day of the week for each dose.
For 10 mg dose, 0.2 mL of the solution is drawn from a vial containing adalimumab 
40 mg/0.8 mL solution.  The drug should be administered in one (1) SC injection, on the 
same day of the week for each dose.
Please return all used and unused vials to the clinic on your next visit.  Used syringes 
should be placed in the special sharps container provided.  All unused vials should be 
returned in the original box.
If an injection is missed or something occurs where the full dose cannot be injected, 
contact your study center immediately for further instructions.  Please record any missed 
doses on your subject diary.
Remember to complete your dosing sheet after each injection and to call the doctor's 
office if you are having problems administering your study medication.

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General Information
Vials
●
Vials will be labeled "adalimumab."
●
Store all adalimumab vials in your refrigerator NOT in the freezer.  Should the 
vials accidentally become frozen, call your study coordinator.
●
0.2 mL = 0.2 cc
●
Study drug should be taken at about the same time of day, on the same day of 
the week as directed by your study doctor.
●
USE A NEW VIAL EVERY INJECTION DAY.  There will be medication 
left in the vial.  DO NOT RE-USE.
●
Save all study drugs.  Vials (used and unused) must be returned to the study 
center at each visit.  Used vials and syringes will be disposed of in a sharps 
container provided to you.
●
Whenever possible, have someone with you for at least 15 to 30 minutes after 
your injection.
●
Call your doctor IMMEDIATELY if you experience any itching, hives, 
shortness of breath, or any symptom that has you concerned.  If you are unable 
to reach your doctor or if you experience life-threatening symptoms call 911, 
or proceed to your nearest emergency room.

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Injection Instructions 
Vials
Select a clean, well-lit, flat surface.
1.
Wash your hands thoroughly with soap and warm water.  It is important to keep 
your work surface as clean as possible.
2.
Open carton.
3.
Examine the carton and components in it to make sure they are complete.
●
One or two vials containing adalimumab
4.
Remove the plastic cap from the vial.
5.
Wipe the gray stopper with an alcohol swab and discard alcohol swab.
6.
Place the vial upright on a hard, flat surface.
7.
Choose an injection site on the upper thigh or abdomen.
8.
Prepare the injection site by wiping it thoroughly with a second alcohol swab.  Use 
a circular motion.

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9.
Remove the needle cover from the syringe.  (The needle is sterile, so be very 
careful not to touch the needle or allow it to touch any surface.)
10.
Draw the plunger on the syringe back.
11.
With the vial sitting on a hard, flat surface, insert needle straight down through the 
center of the gray stopper.  If the needle is correctly lined up, you should feel 
slight resistance and then a "pop" as the needle penetrates the center of the stopper.  
(Be careful not to insert the needle at an angle as this may cause the needle to 
bend.  If the needle is not correctly aligned, you will feel constant resistance as it 
penetrates the stopper and will not feel a "pop.")
12.
Push the plunger in forcing air into the vial.
13.
With the needle still in place, turn the vial upside down.  Keeping the vial at eye 
level, slowly pull the plunger back to draw the liquid into the syringe.  This will 
cause the bubbles to rise to the top of the syringe.  (As the liquid level in the vial 
drops, you may have to withdraw the needle partially to keep the tip of the needle 
in the liquid.)  Only 0.2 mL of the vial will be drawn into the syringe.
14.
With the needle still in the vial, check the syringe for air bubbles.  To remove any 
air bubbles, start by gently tapping the syringe.
15.
Slowly press the plunger to push any bubbles out of the syringe and into the vial.  
(If you accidentally push any liquid back into the vial, draw the liquid back into 
the syringe and check again for air bubbles.  It's okay for a small amount of liquid 
to remain in the vial.)
16.
Withdraw the needle from the vial, being careful not to touch it to any surface.

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Vials
17.
Take the syringe in one hand.
18.
With your other hand, firmly pinch the skin around the cleaned injection site.  (Be 
careful not to touch the cleaned area.)
19.
Hold the syringe at about a 45-degree angle to the skin and use a quick, short 
motion to push the needle into the skin.
20.
Once the needle is in, release the skin.

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Vials
21.
While firmly holding the syringe with one hand, use your other hand to slowly 
push the plunger and inject the adalimumab.  Only 0.2 mL of the vial will be 
injected.
22.
When the syringe is empty, remove the needle from the skin, being careful to keep 
it at the same 45-degree angle.
23.
Dispose of both the needle and syringe in a puncture-resistant container, or sharps 
container, which will be provided.
24.
You may want to press a cotton ball on the injection site for 10 seconds.  If there is 
some slight bleeding, you may choose to apply a small bandage.
25.
Return the vial into the original packaging.
26.
Place the medication kit back into the refrigerator.

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Vials
EACH TIME YOU RECEIVE AN INJECTION OF STUDY MEDICATION, 
REMEMBER TO RECORD THE INFORMATION ON YOUR DOSING SHEET.
GENERAL INFORMATION:
27.
ROTATING INJECTION SITES IS RECOMMENDED.  PLEASE DO NOT 
INJECT THE STUDY MEDICATION INTO A PRIOR SITE OF INJECTION.
28.
Store all of your drug in the refrigerator.  Should the vials become accidentally 
frozen or left out, call your study coordinator.  DO NOT USE THESE VIALS.
29.
If you forget to take the drug or make a mistake with an injection, please call your 
study coordinator.
30.
Please save all of your study medication, even if you skip a dose.  Please bring all 
used and unused vials back to the physician at your next study visit.
31.
There will be study medication remaining in the vials.  DO NOT USE THE 
MEDICATION LEFT IN THE VIAL.  Please return the vial along with the 
remaining study medication back to the physician at your next study visit.
32.
Specific side effects to watch for:  redness and swelling at the injection site.  
Please tell the study coordinator if you have any side effects from injecting the 
drug.

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Appendix R.
Standard Weights

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Appendix S.
Subject AbbVie Site Drug Accountability Form

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Appendix T.
Work Productivity and Activity Impairment Questionnaire: 
Crohns Disease (WPAI-CD) – Caregiver
The following questions ask about the effect of your childs Crohns disease on your ability 
to work and perform regular activities.  Please fill in the blanks or circle a number, as 
indicated.
1. Are you currently employed (working for pay)? _____ NO ___ YES
If NO, check "NO" and skip to question 6.
The next questions are about the past seven days, not including today.
2. During the past seven days, how many hours did you miss from work because of 
problems associated with your childs Crohns disease?  Include hours you missed on 
sick days, times you went in late, left early, etc., because of your childs Crohns 
disease.  Do not include time you missed for your child to participate in this study.
_____ HOURS
3. During the past seven days, how many hours did you miss from work because of any 
other reason, such as vacation, holidays, time off for your child to participate in this 
study?
_____ HOURS
4. During the past seven days, how many hours did you actually work?
_____ HOURS (If "0," skip to question 6.)

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5. During the past seven days, how much did your childs Crohns disease affect your 
productivity while you were working?
Think about days you were limited in the amount or kind of work you could do, days 
you accomplished less than you would like, or days you could not do your work as 
carefully as usual.  If your childs Crohns disease affected your work only a little, 
choose a low number.  Choose a high number if your childs Crohns disease affected 
your work a great deal.  
Consider only how much your childs Crohns disease affected 
your productivity while you were working.
My childs Crohns 
disease had no 
effect on my work
0
1
2
3
4
5
6
7
8
9
10
My childs Crohns 
disease completely 
prevented me from 
working
CIRCLE A NUMBER
6. During the past seven days, how much did your childs Crohns Disease affect your 
ability to do your regular daily activities, other than work at a job?
By regular activities, we mean the usual activities you do, such as work around the 
house, shopping, childcare, exercising, studying, etc.  Think about times you were 
limited in the amount or kind of activities you could do and times you accomplished 
less than you would like.  If your childs Crohns Disease affected your activities only a 
little, choose a low number.  Choose a high number if your childs Crohns Disease 
affected your activities a great deal.  
Consider only how much your childs Crohns disease affected your ability 
to do your regular daily activities, other than work at a job.
My childs Crohns 
disease had no 
effect on my 
daily activities
0
1
2
3
4
5
6
7
8
9
10
My childs Crohns 
disease completely
prevented me from 
doing my daily 
activities
CIRCLE A NUMBER
WPAI:CD-Caregiver (US English)

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Appendix U.
Protocol Amendment:  List of Changes
The summary of changes is listed in Section 1.1.
Specific Protocol Changes:
Section 1.0  Title Page
"Emergency Contact:" previously read:
Emergency Contact:
Has been changed to read:
Emergency Contact:
Section 3.0  Introduction
Add:  Safety Information
Safety Information
In 2008 FDA issued an early communication about an ongoing safety review of TNF 
blockers and the development of lymphoma and other cancers in children and adolescents.
As of the December 2009 FDA Pediatric advisory committee, it was noted that in general, 
adverse events seen in studies submitted for the JIA indication were similar to those in the 
adult population, both in type and frequency.

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Due to the relatively rare occurrence of these cancers, the limited number of pediatric 
patients treated with TNF blockers, and the possible role of other immunosuppressive 
therapies used concomitantly with TNF blockers, the FDA was unable at that time to fully 
characterize the strength of the association between using TNF blockers and developing a 
malignancy.  Product labeling for all anti-TNF agents now includes language regarding 
the risk of pediatric malignancies as requested by the FDA.
Furthermore, in November 2011 the FDA requested that all manufacturers of TNF 
inhibitors undertake a coordinated effort to better understand the risks for malignancies 
that develop in patients who are 30 years of age and younger at the time of diagnosis.  
Reporting requirements for these events can be found in Section 6.5 Adverse Event 
Reporting.  A detailed discussion of the pre-clinical toxicology, metabolism, 
pharmacology, and safety experience with adalimumab can be found in the current 
Investigator's Brochure.
Section 5.1  Overall Study Design and Plan:  Description
Eleventh paragraph, first sentence previously read:
The duration of the study could last up to 264 weeks (approximately 5 years).
Has been changed to read:
The duration of the study could last up to 336 weeks (approximately 6.5 years).

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including dose, route and frequency, and reason for stopping the medication will be 
collected in the source documents and appropriate CRF pages.
Section 5.2.3.2  Concomitant Therapy
Second paragraph previously read:
After Week 8, decreases in the dose or discontinuation of Crohns related antibiotics or 
Crohns related concomitant treatments are allowed according to the Investigators medical 
judgment.  These adjustments may be performed without prior discussion with the 
AbbVie Medical Monitor.  In addition, Subjects may be able to initiate or reinitiate 
Crohns related treatments, except immunosuppressants, following eight (8) weeks of 
exposure to open-label adalimumab.  Immunosuppressants may not be started or restarted 
during the study.
Has been changed to read:
After Week 8, decreases in the dose or discontinuation of Crohn's related antibiotics or 
Crohn's related concomitant treatments are allowed according to the Investigators medical 
judgment.  These adjustments may be performed without prior discussion with the 
AbbVie Medical Monitor.  In addition, subjects may be able to initiate or reinitiate 
Crohn's related treatments, following eight (8) weeks of exposure to open-label 
adalimumab.  Therapeutic enemas and suppositories (not including those done in 
conjunction with routine colonoscopies) and total parenteral nutrition (TPN) during the 
study should be discussed with and approved by the Medical Monitor prior to use.
Section 5.2.3.4  Prohibited Therapy
Third paragraph previously read:
Tysabri (natalizumab), concurrent biological therapy, cyclosporine, tacrolimus, 
mycophenolate mofetil, Kineret® (anakinra), Orencia (abatacept), therapeutic enemas and 
suppositories (not including those done in conjunction with routine colonoscopies) and 
any investigational agent are prohibited during the study (see Appendix L).

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Has been changed to read:
Tysabri (natalizumab), concurrent biological therapy, cyclosporine, tacrolimus, 
mycophenolate mofetil, Kineret® (anakinra), Orencia (abatacept), and any investigational 
agent are prohibited during the study (see Appendix L).

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Table 1.  Study Activities
Previously read:
Activity
Baseline
Week 4
Week 8
Week 12
Week 24
Week 36
Week 48
Week 60
Week 72
Week 84
Week 96
Week 108
Inclusion/exclusion criteria
X
Informed consent
X
Previous and concomitant 
medications
Xa
X
X
X
X
X
X
X
X
X
X
X
Urine pregnancy testb
Xa
X
X
X
X
X
X
X
X
X
X
X
Vital signsc
Xa
X
X
X
X
X
X
X
X
X
X
X
Physical exam
Xa
X
X
X
X
X
X
X
X
X
X
X
General LABd,m
Xa
X
X
X
X
X
X
X
X
X
X
X
Urinalysise
Xa
X
X
X
X
X
X
X
X
X
X
X
Erythrocyte sedimentation 
rate
Xa
X
X
X
X
X
X
X
X
X
X
X
CRP
Xa
X
X
X
X
ANA
Xa
X
X
Anti-dsDNAf
Xa
X
X
PCDAI
Xa
X
X
X
X
X
X
X
X
X
X
X
CDAIg
Xa
X
X
X
X
X
X
X
X
X
X
X
IMPACT III Questionnaireh
Xa
X
X
X
X
X

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Table 1.
Study Activities (Continued)
Activity
Baseline
Week 4
Week 8
Week 12
Week 24
Week 36
Week 48
Week 60
Week 72
Week 84
Week 96
Week 108
Unscheduled outpatient 
visits, emergency room 
visits and hospitalizations 
questionnaire
Xa
X
X
X
X
X
X
X
X
X
X
X
Work Productivity and 
Impairment Questionnaire:  
Crohns Disease (WPAI –
CD)
Xa
X
X
X
X
X
X
X
X
X
X
X
X-ray for bone agei
Xa
X
X
Serum bone markers
Xa
X
X
X
X
PK Blood Samplej
X
X
X
X
Anti-adalimumab blood 
levels (AAA)j
X
X
X
X
Adverse eventsk
Xa
X
X
X
X
X
X
X
X
X
X
X
Dispense study drug
Xa
X
X
X
X
X
X
X
X
X
X
X

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Table 1.
Study Activities (Continued)
Activity
Week 
120
Week 
132 
Call
Week 
144
Week 
156 
Call
Week 
168
Week 
180 
Call
Week 
192
Week 
204 
Call
Week 
216
Week 
228 
Call
Week 
240
Week 
252 
Call
Week 
264/ 
Early 
Term
Unsched 
Visit
70-Day 
Follow-up 
Call
Inclusion/exclusion 
criteria
Informed consent
Previous and 
concomitant medications
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Urine pregnancy testb
X
X
X
X
X
X
X
X
Vital signsc
X
X
X
X
X
X
X
X
Physical exam
X
X
X
X
X
X
X
X
General LABd,m
X
X
X
X
X
X
X
X
Urinalysise
X
X
X
X
X
X
X
X
Erythrocyte 
sedimentation rate
X
X
X
X
X
X
X
X
CRP
X
X
X
X
X
ANA
X
X
X
Anti-dsDNAf
X
X
X
PCDAI
X
X
X
X
X
X
X
X
CDAIg
X
X
X
X
X
X
X
X
IMPACT III 
Questionnaireh
X
X
X
X
X
X
X
X

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Table 1.
Study Activities (Continued)
Activity
Week 
120
Week 
132 
Call
Week 
144
Week 
156 
Call
Week 
168
Week 
180 
Call
Week 
192
Week 
204 
Call
Week 
216
Week 
228 
Call
Week 
240
Week 
252 
Call
Week 
264/ 
Early 
Term
Unsched 
Visit
70-Day 
Follow-up 
Call
Unscheduled outpatient 
visits, emergency room 
visits and 
hospitalizations 
questionnaire
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Work Productivity and 
Impairment 
Questionnaire:  Crohns 
Disease (WPAI – CD)
X
X
X
X
X
X
X
X
X-ray for bone agei
X
X
X
Serum bone markersi
X
X
X
X
X
X
X
X
PK Blood Samplej
X
X
X
X
X
X
X
X
Anti-adalimumab blood 
levels (AAA)j
X
X
X
X
X
X
X
X
Adverse eventsk
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Dispense study drug
X
X
X
X
X
X
Xl

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Has been changed to read:
Activity
Baseline
Week 4
Week 8
Week 12
Week 24
Week 36
Week 48
Week 60
Week 72
Week 84
Inclusion/exclusion criteria
X
Informed consent
X
Previous and concomitant 
medications
Xa
X
X
X
X
X
X
X
X
X
Urine pregnancy testb
Xa
X
X
X
X
X
X
X
X
X
Vital signsc
Xa
X
X
X
X
X
X
X
X
X
Physical exam
Xa
X
X
X
X
X
X
X
X
X
General LABd
Xa
X
X
X
X
X
X
X
X
X
TB testing (PPD or 
QuantiFERON-TB Gold)m
X
Urinalysise
Xa
X
X
X
X
X
X
X
X
X
Erythrocyte sedimentation rate
Xa
X
X
X
X
X
X
X
X
X
CRP
Xa
X
X
X
ANA
Xa
X
Anti-dsDNAf
Xa
X
PCDAI
Xa
X
X
X
X
X
X
X
X
X
CDAIg
Xa
X
X
X
X
X
X
X
X
X
IMPACT III Questionnaireh
Xa
X
X
X
X

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Table 1.
Study Activities (Continued)
Activity
Baseline
Week 4
Week 8
Week 12
Week 24
Week 36
Week 48
Week 60
Week 72
Week 84
Unscheduled outpatient visits, 
emergency room visits and 
hospitalizations questionnaire
Xa
X
X
X
X
X
X
X
X
X
Work Productivity and 
Impairment Questionnaire:  
Crohn's Disease (WPAI – CD)
Xa
X
X
X
X
X
X
X
X
X
X-ray for bone agei
Xa
X
Serum bone markers
Xa
X
X
X
PK Blood Samplej
X
X
X
Anti-adalimumab blood levels 
(AAA)j
X
X
X
Adverse eventsk
Xa
X
X
X
X
X
X
X
X
X
Dispense study drug
Xa
X
X
X
X
X
X
X
X
X

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Table 1.
Study Activities (Continued)
Activity
Week 96
Week 108
Week 120
Week 132 
Call
Week 144
Week 156 
Call
Week 168
Week 180 
Call
Week 192
Week 204 
Call
Inclusion/exclusion criteria
Informed consent
Previous and concomitant 
medications
X
X
X
X
X
X
X
X
X
X
Urine pregnancy testb
X
X
X
X
X
X
Vital signsc
X
X
X
X
X
X
Physical exam
X
X
X
X
X
X
General LABd
X
X
X
X
X
X
TB testing (PPD or 
QuantiFERON-TB Gold)m
X
X
X
Urinalysise
X
X
X
X
X
X
Erythrocyte sedimentation rate
X
X
X
X
X
X
CRP
X
X
X
X
ANA
X
X
X
Anti-dsDNAf
X
X
X
PCDAI
X
X
X
X
X
X
CDAIg
X
X
X
X
X
X
IMPACT III Questionnaireh
X
X
X
X
X

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Table 1.
Study Activities (Continued)
Activity
Week 96
Week 108
Week 120
Week 132 
Call
Week 144
Week 156 
Call
Week 168
Week 180 
Call
Week 192
Week 204 
Call
Unscheduled outpatient visits, 
emergency room visits and 
hospitalizations questionnaire
X
X
X
X
X
X
X
X
X
X
Work Productivity and Impairment 
Questionnaire:  Crohn's Disease 
(WPAI – CD)
X
X
X
X
X
X
X-ray for bone agei
X
X
X
Serum bone markersi
X
X
X
X
X
PK Blood Samplej
X
X
X
X
X
Anti-adalimumab blood levels 
(AAA)j
X
X
X
X
X
Adverse eventsk
X
X
X
X
X
X
X
X
X
X
Dispense study drug
X
X
X
X
X
X

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Table 1.
Study Activities (Continued)
Activity
Week 
216
Week 
228 
Call
Week 
240
Week 
252 
Call
Week 
264
Week 
276 
Call
Week 
288
Week 
300 
Call
Week 
312
Week 
324 
Call
Week 
336/ 
Early 
Term
Unsched 
Visit
70-Day 
Follow-up 
Call
Inclusion/exclusion criteria
Informed consent
Previous and concomitant 
medications
X
X
X
X
X
X
X
X
X
X
X
X
Urine pregnancy testb
X
X
X
X
X
X
X
Vital signsc
X
X
X
X
X
X
X
Physical exam
X
X
X
X
X
X
X
General LABd
X
X
X
X
X
X
X
TB testing (PPD or 
QuantiFERON-TB Gold)m
X
X
X
Urinalysise
X
X
X
X
X
X
X
Erythrocyte sedimentation 
rate
X
X
X
X
X
X
X
CRP
X
X
X
X
X
ANA
X
X
Anti-dsDNAf
X
X
PCDAI
X
X
X
X
X
X
X
CDAIg
X
X
X
X
X
X
X
IMPACT III Questionnaireh
X
X
X
X
X
X
X

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Table 1.
Study Activities (Continued)
Activity
Week 
216
Week 
228 
Call
Week 
240
Week 
252 
Call
Week 
264
Week 
276 
Call
Week 
288
Week 
300 
Call
Week 
312
Week 
324 
Call
Week 
336/ 
Early 
Term
Unsched 
Visit
70-Day 
Follow-up 
Call
Unscheduled outpatient 
visits, emergency room 
visits and 
hospitalizations 
questionnaire
X
X
X
X
X
X
X
X
X
X
X
X
Work Productivity and 
Impairment 
Questionnaire:  Crohn's 
Disease (WPAI – CD)
X
X
X
X
X
X
X
X-ray for bone agei
X
X
Serum bone markersi
X
X
X
X
X
X
X
PK Blood Samplej
X
X
X
X
X
X
X
Anti-adalimumab blood 
levels (AAA)j
X
X
X
X
X
X
X
Adverse eventsk
X
X
X
X
X
X
X
X
X
X
X
X
X
Dispense study drug
X
X
X
X
X
Xl

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Table 1.  Study Activities
Footnotes "h." and "m." previously read:
h.
For subjects who are age 10 or older at the M06-807 Baseline Visit, an IMPACT III Assessment will be completed 
at Baseline, Weeks 12, 24, 48, 72, 108, 120, 144, 168, 192, 216, 240, 264/ET and unscheduled visits.
m.
PPD or QuantiFERON-TB Gold testing at Weeks 48, 96, 144, 192 and 240.
Has been changed to read:
h.
For subjects who are age 10 or older at the M06-807 Baseline Visit, an IMPACT III Assessment will be completed 
at Baseline, Weeks 12, 24, 48, 72, 108, 120, 144, 168, 192, 216, 240, 264, 288, 312 and 336/ET and unscheduled 
visits.
m.
PPD or QuantiFERON-TB Gold testing at Weeks 48, 96, 144, 192, 240, 288 and 336.
Section 5.3.1.1  Study Procedures
First paragraph, last sentence previously read:
The site will call the subjects at Weeks 132, 156, 180, 204, 228 and 252 in order to collect 
any safety information from the subject as illustrated in Table 1.
Has been changed to read:
The site will call the subjects at Weeks 132, 156, 180, 204, 228, 252, 276, 300 and 324 in 
order to collect any safety information from the subject as illustrated in Table 1.
Section 5.3.1.1  Study Procedures
Subsection Previous and Concomitant Medications
First paragraph, first sentence previously read:
Changes in concomitant medications will be assessed at each study visit from Baseline 
through the Week 264/ET visit.
Has been changed to read:
Changes in concomitant medications will be assessed at each study visit from Baseline 
through the Week 336/ET visit.

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Section 5.3.1.1  Study Procedures
Subsection TB Testing
Second paragraph previously read:
A PPD skin test (alternatively, also known as tuberculin skin test) must be placed or the 
QuantiFERON®-TB Gold test (or equivalent) must be performed for subjects with a 
negative test at Screening visit after the amended protocol is approved by IRB/IEC 
including those with a prior history of Bacille Calmette-Guérin (BCG) administration at 
the time the subject reaches one of the scheduled visits:  Weeks 48, 96, 144, 192, and 240.
Has been changed to read:
A PPD skin test (alternatively, also known as tuberculin skin test) must be placed or the 
QuantiFERON®-TB Gold test (or equivalent) must be performed for subjects with a 
negative test at Screening visit after the amended protocol is approved by IRB/IEC 
including those with a prior history of Bacille Calmette-Guérin (BCG) administration at 
the time the subject reaches one of the scheduled visits:  Weeks 48, 96, 144, 192, 240, 288 
and 336. 
Section 5.3.1.1  Study Procedures
Subsection Outcomes
Add:  new last paragraph
If a subject is no longer taken care of by their parent or legal guardian, the WPAI-CD 
should not be completed (neither by the subject's parent or legal guardian nor by the 
subject himself/herself).  
Section 5.3.1.1  Study Procedures
Subsection Adverse Events
First paragraph, first sentence previously read:
Adverse events will be assessed at every study visit from Baseline through the 
Week 264/ET visit.

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Has been changed to read:
Adverse events will be assessed at every study visit from Baseline through the 
Week 336/ET visit.
Section 5.3.2.1  Collection of Samples for Analysis
Subsection Collection of Samples for Adalimumab Analysis
Last paragraph previously read:
A maximum of 13 samples are planned to be collected per subject for the analysis of 
adalimumab concentrations.
Has been changed to read:
A minimum of 14 samples are planned to be collected per subject for the analysis of 
adalimumab concentrations.
For subjects who have a flare and require switching to higher dose or change dose to 
ew dosing, up to 2 additional samples are planned to be collected per subject for 
adalimumab analysis.
Section 5.3.2.1  Collection of Samples for Analysis
Subsection Collection of Samples for AAA Analysis
Last paragraph previously read:
A maximum of 13 blood samples are planned to be collected per subject for AAA 
analysis.
Has been changed to read:
A minimum of 14 blood samples are planned to be collected per subject for AAA 
analysis.
For subjects who have a flare and require switching to higher dose or change dose to 
ew dosing, up to 2 additional samples are planned to be collected per subject for AAA 
analysis.

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Section 5.4.1  Discontinuation of Individual Subjects
Second paragraph, first sentence previously read:
If the subject prematurely discontinues study drug use, the procedures outlined for the 
Week 264/ET Visit must be completed within 2 weeks of the last dose of study drug, and 
preferably prior to the initiation of another therapy.
Has been changed to read:
If the subject prematurely discontinues study drug use, the procedures outlined for the 
Week 336/ET Visit must be completed within 2 weeks of the last dose of study drug, and 
preferably prior to the initiation of another therapy.
Section 5.5.2.1  Packaging and Labeling
Previously read:
The following information will appear on the pre-filled syringe, vial or carton labels:
●
Sponsor identification
●
Protocol number
●
Drug identification
●
Quantity of contents
●
Storage conditions
●
Dosing instructions
●
Kit number
●
Route of Administration
●
Excipients
●
Blank spaces to write the subjects identification number, initials, and date 
dispensed (as required)
●
Finishing lot #
●
Expiry Date (as required)

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Two pre-filled syringes or vials will be provided in a dosing kit carton (see Table 4).  
Detailed instructions and training for the administration of study supplies are provided in 
Appendix Q.
Has been changed to read:
Two pre-filled syringes or vials will be provided in a dosing kit carton (see Table 4).  
Each kit will be labeled as required per country requirement.  Labels must remain affixed 
to the kit.
Detailed instructions and training for the administration of study supplies are provided in 
Appendix Q.
Section 6.5 Adverse Event Reporting
First paragraph previously read:
In the event of an SAE, whether related to study drug or not, the investigator will notify 
one of the following people by faxing the appropriate SAE forms to one of the following 
people within 24 hours of the site being made aware of the SAE.
Has been changed to read:
In the event of an of a serious adverse event, and additionally, any non-serious event of 
malignancy in patients 30 years of age and younger, whether related to study drug or not, 
the physician will notify AbbVie within 24 hours of the physician becoming aware of the 
event by faxing the serious adverse event or non-serious event of malignancy in patients 
30 years of age and younger forms to the Immunology Clinical Safety Team.

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Section 6.5  Adverse Event Reporting
Last paragraph and in-text table previously read:
For questions regarding SAEs, please contact:
Has been changed to read:
For questions regarding SAEs, please contact:
Section 6.6.  Pregnancy
Previously read:
AbbVie must be notified within 1 working day of a sites learning if a female subject 
becomes pregnant during the study or within 150 days of receiving the last dose of study 
drug (see Section 6.5 for contact information).
Females who become pregnant during the study will be discontinued from study drug as 
described in Section 5.4.  Data regarding the outcome of any pregnancy occurring in a 

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study subject will be collected.  Upon notification of a pregnancy AbbVie will forward a 
form to the site, for the Investigator to complete and send back to AbbVie.  A 
second form will also be sent approximately 9 months from the date of notification to 
collect information on the outcome of the pregnancy.  This form will also need to be 
completed and sent back to AbbVie.
To monitor outcomes of pregnant women exposed to adalimumab, a pregnancy registry 
has been established for the United States, Canada and Puerto Rico.  Physicians in the 
United States are encouraged to register subjects by calling 
and/or 
provide this information to the subject.
Pregnancy in a study subject is not considered an AE.  However, the medical outcome of 
an elective or a spontaneous abortion, stillbirth or congenital anomaly is considered a 
SAE, and must be reported to the sponsor with 24 hours of the site learning of the event.
Has been changed to read:
Pregnancy in a study subject must be reported to AbbVie within 1 working day of the site 
becoming aware of the pregnancy.  Subjects who become pregnant during the study must 
be discontinued (Section 5.4.1).  Pregnancies will be collected from the date of the 
first dose through 150 days following the last dose of study drug.
Information regarding a pregnancy occurrence in a study subject and the outcome of the 
pregnancy will be collected.
Pregnancy in a study subject is not considered an AE.  However, the medical outcome of 
an elective or a spontaneous abortion, stillbirth or congenital anomaly is considered a 
SAE, and must be reported to the sponsor with 24 hours of the site learning of the event.

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Section 7.0  Protocol Deviations
In-text table previously read:
Has been changed to read:
Appendix B.  List of Protocol Signatories
Previously read:
Name
Title
Functional Area
Statistics
Clinical
Clinical
Clinical

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Has been changed to read:
Name
Title
Functional Area
Statistics
Pharmacokinetics
Clinical
Clinical
Clinical
Appendix H.  PCDAI Users Guide and Guideline for Reference Weight and 
Reference Height
Subsection Physical Examination
Third paragraph previously read:
From Baseline to Week 264:  use weight from previous visit
Has been changed to read:
From Baseline to Week 336:  use weight from previous visit
Appendix H.  PCDAI Users Guide and Guideline for Reference Weight and 
Reference Height
Subsection Physical Examination
Heading "Item.  Height"
Add:  new twelfth, thirteenth and last bullets
●
From Week 264 to Week 288, use height from Week 240
●
From Week 288 to Week 312, use height from Week 264
●
From Week 312 to Week 336, use height from Week 288

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Appendix P.  Subject Dosing Diary
Subsection "Week 313 - Week 335"
Add:  new subsection
Week 313 - Week 335
Subject Initials:  __________
Subject Study #:  ___________
Date
day/mm/yr
Day or 
Week #
Time of Study 
Drug 
Administration
Dose (mL) 
Administered
Kit #
Initials of Person 
Administering 
Study Medication
Comments
18/MAR/04
EXAMPLE
9:35 am
0.8
MM
none
Week 313
Week 314
Week 315
Week 316
Week 317
Week 318
Week 319
Week 320
Week 321
Week 322
Week 323
Week 324
Week 325
Week 326
Week 327
Week 328
Week 329
Week 330
Week 331
Week 332
Week 333
Week 334
Week 335*
*
Week 335 dose will only be taken if on every-week dosing schedule.

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Appendix Q  Self Injection Instructions
Subsection Study Drug Dosing Schedule
Open-Label (PFS)
Second paragraph previously read:
Injections at scheduled study visits (Baseline, Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 
108, 120, 144, 168, 192, 216 and 240) will be done during your visit, at the doctors office.  
On weeks between office visits, study drug will be self-administered at home by you or 
someone trained to give you the injections.
Has been changed to read:
Injections at scheduled study visits (Baseline, Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 
108, 120, 144, 168, 192, 216, 240, 264, 288 and 312) will be done during your visit, at the 
doctors office.  On weeks between office visits, study drug will be self-administered at 
home by you or someone trained to give you the injections.
Appendix Q  Self Injection Instructions
Subsection Study Drug Dosing Schedule
Vials
Second paragraph previously read:
The injection for the visits at Weeks 4, 8, 12, 16, 20, 26, 32, 40, 48, 60, 72, 84, 96, 108, 
120, 144, 168, 192, 216 and 240 will be done during your visit at the doctor's office.  
After Week 4, on weeks between office visits (i.e., Weeks 6, 10, 14, etc.) study drug will 
be self-administered at home by you or someone trained to give you the injections.
Has been changed to read:
The injection for the visits at Weeks 4, 8, 12, 16, 20, 26, 32, 40, 48, 60, 72, 84, 96, 108, 
120, 144, 168, 192, 216, 240, 264, 288 and 312 will be done during your visit at the 
doctor's office.  After Week 4, on weeks between office visits (i.e., Weeks 6, 10, 14, etc.) 
study drug will be self-administered at home by you or someone trained to give you the 
injections.

 
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1.0 
Title Page 
CLINICAL TRIAL PROTOCOL M06-807 
A Multi-center, Open-label Study of the Human 
Anti−TNF Monoclonal Antibody Adalimumab to 
Evaluate the Efficacy and the Long-term Safety and 
Tolerability of Repeated Administration of 
Adalimumab in Pediatric Subjects with 
Crohn's Disease Who Have Demonstrated a Clinical 
Response in the M06-806 Study 
Incorporating Administrative Changes 1 and 2, 
Amendment 1, Administrative Changes 3, 4, 5 and 6, 
and Amendments 2, 3, 4 and 5 
Abbott Number /  
 Investigational Product: 
 
Adalimumab 
Date:  
03 January 2012 
Development Phase: 
3 
Study Design:  
A multi-center, open-label safety and tolerability pediatric study in the 
United States, Canada and Europe. 
EudraCT Number:  
2007-006494-90 
Investigator: 
Multicenter (Investigator information on file at Abbott Laboratories). 
Sponsor: 
European Union Countries: 
Abbott GmbH & Co.KG  
Knollstrasse 50 
67061 Ludwigshafen, Germany 
Non European Union Countries: 
Abbott Laboratories, US  
100 Abbott Park Road 
Abbott Park, IL 60064 
Emergency Contact: 
This study will be conducted in compliance with the protocol, Good Clinical Practice and all other 
applicable regulatory requirements, including the archiving of essential documents. 
Confidential Information 
No use or disclosure outside Abbott is permitted without prior written authorization from Abbott. 

 
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1.1 
Protocol Amendment:  Summary of Changes 
The purpose of this amendment is to: 
● Add in regular TB testing language to protocol. 
Rationale of Change:  The FDA required a labeling change based on cases of 
reactivation of TB/occurrence of new TB infections in patients receiving 
Humira.  The USPI now says retest should be done "periodically" during 
therapy, without specifying the interval.  Based on the actual USPI and on 
literature search, annual TB rescreening was implemented as a reasonable 
interval. 
● Correct typo in the vial dosing instructions. 
 
An itemized list of all changes made to the protocol under this amendment can be found 
in Appendix U. 

 
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2.0 
Table of Contents 
1.0 
Title Page .................................................................................1 
1.1 
Protocol Amendment:  Summary of Changes...........................................2 
2.0 
Table of Contents....................................................................3 
3.0 
Introduction.............................................................................8 
4.0 
Study Objective .....................................................................14 
5.0 
Investigational Plan ..............................................................14 
5.1 
Overall Study Design and Plan:  Description..........................................14 
5.2 
Selection of Study Population .................................................................19 
5.2.1 
Inclusion Criteria.....................................................................................19 
5.2.2 
Exclusion Criteria....................................................................................20 
5.2.3 
Prior and Concomitant Therapy ..............................................................22 
5.2.3.1 
Prior Therapy...........................................................................................22 
5.2.3.2 
Concomitant Therapy..............................................................................23 
5.2.3.3 
Rescue Therapy .......................................................................................24 
5.2.3.4 
Prohibited Therapy ..................................................................................24 
5.3 
Efficacy, and Safety Assessments/Variables...........................................24 
5.3.1 
Efficacy and Safety Measurements Assessed and Flow Chart................24 
5.3.1.1 
Study Procedures.....................................................................................30 
5.3.2 
Drug Concentration Measurements.........................................................39 
5.3.2.1 
Collection of Samples for Analysis.........................................................40 
5.3.2.2 
Handling/Processing of Samples.............................................................40 
5.3.2.3 
Disposition of Samples............................................................................41 
5.3.2.4 
Measurement Methods ............................................................................41 
5.3.3 
Efficacy Variables ...................................................................................41 
5.3.4 
Safety Variables.......................................................................................42 
5.3.5 
Pharmacokinetic Variables......................................................................42 

 
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5.4 
Removal of Subjects from Therapy or Assessment ................................42 
5.4.1 
Discontinuation of Individual Subjects ...................................................42 
5.4.2 
Discontinuation of Entire Study ..............................................................43 
5.4.3 
Stopping Rules.........................................................................................43 
5.5 
Treatments ...............................................................................................44 
5.5.1 
Treatments Administered ........................................................................44 
5.5.2 
Identity of Investigational Product ..........................................................45 
5.5.2.1 
Packaging and Labeling ..........................................................................46 
5.5.2.2 
Storage and Disposition of Study Drug...................................................47 
5.5.3 
Method of Assigning Subjects to Treatment Groups ..............................47 
5.5.4 
Selection and Timing of Dose for Each Subject .....................................48 
5.5.5 
Blinding...................................................................................................49 
5.5.6 
Treatment Compliance ............................................................................49 
5.5.7 
Drug Accountability................................................................................50 
5.6 
Discussion and Justification of Study Design .........................................51 
5.6.1 
Discussion of Study Design and Choice of Control Groups...................51 
5.6.2 
Appropriateness of Measurements ..........................................................51 
5.6.3 
Suitability of Subject Population.............................................................51 
5.6.4 
Selection of Doses in the Study...............................................................51 
6.0 
Adverse Events......................................................................52 
6.1 
Definitions...............................................................................................53 
6.1.1 
Adverse Event .........................................................................................53 
6.1.2 
Serious Adverse Events...........................................................................53 
6.2 
Adverse Event Severity...........................................................................54 
6.3 
Relationship to Study Drug .....................................................................55 
6.4 
Adverse Event Collection Period ............................................................55 
6.5 
Adverse Event Reporting ........................................................................56 

 
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6.5.1 
Collection of Data Regarding Known Manifestations of the 
Disease Under Study ...............................................................................57 
6.6 
Pregnancy ................................................................................................57 
7.0 
Protocol Deviations...............................................................58 
8.0 
Statistical Methods and Determination of Sample 
Size..........................................................................................59 
8.1 
Statistical and Analytical Plans ...............................................................59 
8.1.1 
Analyzable Population.............................................................................59 
8.1.2 
Planned Methods of Statistical Analysis .................................................59 
8.1.2.1 
Demographics and Baseline Characteristics ...........................................59 
8.1.2.2 
Efficacy Analysis.....................................................................................59 
8.1.3 
Other Analyses ........................................................................................59 
8.1.4 
Safety Analyses .......................................................................................60 
8.1.4.1 
Pharmacokinetic Analyses.......................................................................61 
8.1.5 
Interim Analysis ......................................................................................61 
8.2 
Determination of Sample Size.................................................................61 
8.3 
Randomization Methods..........................................................................61 
9.0 
Ethics......................................................................................62 
9.1 
Independent Ethics Committee (IEC) or Institutional Review 
Board (IRB).............................................................................................62 
9.2 
Ethical Conduct of the Study...................................................................62 
9.3 
Subject Information and Consent ............................................................63 
10.0 
Source Documents and Case Report Form 
Completion.............................................................................64 
10.1 
Source Documents...................................................................................64 
10.2 
Case Report Forms ..................................................................................64 
11.0 
Data Quality Assurance........................................................65 
12.0 
Use of Information and Publication....................................66 
12.1 
Use of Information ..................................................................................66 

 
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12.2 
Internet Sites............................................................................................67 
13.0 
Completion of the Study.......................................................67 
14.0 
Investigators Agreement ......................................................69 
15.0 
Reference List........................................................................70 
 
List of Tables 
Table 1.  
Study Activities .......................................................................................25 
Table 2.  
Clinical Laboratory Tests ........................................................................35 
Table 3.  
Identity of Investigational Products.........................................................46 
Table 4.  
Study Drug Packaging and Administration.............................................47 
 
List of Figures 
Figure 1.  
Study Schematic ......................................................................................17 
Figure 2.  
Dosing Schematic After Amendment 4...................................................19 
Figure 3.  
Adverse Event Collection........................................................................56 
 
List of Appendices 
Appendix A.  
List of Abbreviations and Definition of Terms .......................................74 
Appendix B.  
List of Protocol Signatories.....................................................................76 
Appendix C.  
Documents Required Prior to Initiation of the Study..............................77 
Appendix D.  
Responsibilities of the Clinical Investigator............................................79 
Appendix E.  
CDC Treatment of Tuberculosis Infection (Preventive Therapy)...........81 
Appendix F.  
Non-Drug Materials Provided to the Study Site(s) .................................83 
Appendix G.  
Pediatric Crohns Disease Activity Index (PCDAI).................................84 
Appendix H.  
PCDAI Users Guide and Guideline for Reference Weight and 
Reference Height.....................................................................................86 
Appendix I.  
Crohns Disease Activity Index (CDAI) ..................................................92 
Appendix J.  
Subject CDAI Diary ................................................................................93 

 
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Appendix K.  
IMPACT III Questionnaire......................................................................94 
Appendix L.  
Excluded Medications ...........................................................................102 
Appendix M.  Day 70 Phone Call.................................................................................103 
Appendix N.  
Unscheduled Outpatient Visits, Emergency Room Visits and 
Hospitalizations .....................................................................................104 
Appendix O.  
Subject Medication Log ........................................................................105 
Appendix P.  
Subject Dosing Diary ............................................................................106 
Appendix Q.  
Self Injection Instructions......................................................................124 
Appendix R.  
Standard Weights...................................................................................139 
Appendix S.  
Subject Abbott Laboratories Site Drug Accountability Form...............141 
Appendix T.  
Work Productivity and Activity Impairment Questionnaire: 
Crohns Disease (WPAI-CD) - Caregiver ..............................................142 
Appendix U.  
Protocol Amendment:  List of Changes ................................................144 
 

 
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3.0 
Introduction 
Crohns Disease (CD) is a chronic, debilitating, and currently incurable inflammatory 
disease that can affect the entire digestive system as well as extraintestinal organs.  CD is 
primarily manifested by focal asymmetric, transmural, and occasionally, granulomatous 
inflammation affecting any segment of the gastrointestinal tract1 which can consist of 
mucosal edema, aphthous and linear ulcerations, asymmetrical narrowing and strictures.  
Noncaseating granulomas are virtually diagnostic in the correct clinical setting.  The most 
commonly involved area of the bowel is the small bowel, particularly the distal ileum, 
which is involved in 70% of cases often in combination with colitis, occurring in 50% of 
cases.  Extraintestinal manifestations can also occur, and include symptoms of joint, 
ocular and hepatic inflammation.  Genetic, geographic, ethnic, and environmental risk 
factors have all been described, but the basic etiology of the disease remains unknown. 
The incidence in North America is similar to that in other western nations and is 
estimated from 3.1 to 14.6 cases per 100,000 person years and prevalence ranges from 
26 to 199 cases per 100,000 persons.2  The disease can affect persons of any age but the 
most common age of onset is in the second and third decades with a female 
preponderance.  While predominantly a disease of adults, approximately 10% to 15% of 
CD cases are diagnosed before adulthood.3 
In addition, the incidence of CD in patients less than 18 years of age appears to be 
increasing in both North America and Europe.4,5  Reported incidence rates range from 
1.2 to 4.9 per 100,000 persons in the UK, Europe, and North America6-12 with one study 
reporting an incidence of 4.6 per 100,000 persons in the United States.5  CD has been 
reported at all ages but is rare in early childhood.  In one study of patients with CD, 
17 years of age and younger, 9.1% of the patients were diagnosed before the age of 6.13  
In a second study of patients diagnosed with CD before the age of 15, 7.5% of the 
patients were under the age of 5.14 
Despite obvious physiologic and development differences, the presentation of CD in the 
pediatric population is generally similar to that seen in older patients and is 

 
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heterogeneous with regard to anatomic localization and clinical severity.5,15,16  The 
unique aspect of this disease in children is its impact on nutrition and growth, with 
marked growth retardation being a prominent component of the disease in this age 
group.17-19  The use of accepted methodologies for assessing nutritional status, including 
the anthropometric measures of height, weight, triceps skin fold thickness and mid arm 
circumference as well as linear growth (height velocity and assessment of height velocity 
for chronological age "z-score") have documented the growth impairment that can occur 
in this age group, and also have been used to assess the efficacy of interventions.20  
Profound impairment of bone formation and increased bone resorption are associated 
complications and are related to the effect of glucocorticoids,21,22 delayed puberty,22,23 
decreased mobility,24 as well as to the effects of cytokines on bone formation.25 
Initial symptoms are often subtle, and there is an average delay of almost six months 
between onset of symptoms and diagnosis.  The most common presentation is with 
abdominal pain, diarrhea, loss of appetite and weight loss.  However, isolated weight 
loss, anorexia, perianal disease and extraintestinal manifestations can occur in the 
absence of GI symptoms in a substantial number of patients. 
The general approach to the treatment of CD in children is similar to adults with the goals 
being induction and maintenance of remission, prevention of relapse and hospitalizations, 
improved quality of life, and avoidance of disease and drug related complications.  
Restoration and/or preservation of normal growth and pubertal development are 
additional therapeutic goals.  The medical armamentarium is likewise similar to adults 
and includes induction of remission with corticosteroids, and ongoing maintenance 
therapy of immunomodulators, aminosalicylates and nutritional therapy.  Anti-tumor 
necrosis factor (TNF) therapy with infliximab has been evaluated for the therapy of CD 
in this age group as it has in adults.  The FDA and EMEA have recently approved 
Infliximab for use in children with CD. 
Adalimumab is a recombinant human immunoglobulin (IgG1) monoclonal antibody 
exclusively containing human peptide sequences.  It is produced by recombinant 
deoxyribonucleic acid (DNA) technology in a mammalian cell expression system.  

 
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Adalimumab consists of 1330 amino acids and has a molecular weight of approximately 
148 kilodaltons.  It binds specifically with high affinity to the soluble and transmembrane 
forms of TNFD and inhibits the binding of TNFD with its receptors. 
TNF is a naturally occurring cytokine that is involved in normal inflammatory and 
immune responses.  Elevated levels of TNF play an important role in pathologic 
inflammation.  Adalimumab binds specifically to TNF and neutralizes the biological 
function of TNF by blocking its interaction with the p55 and p75 cell surface TNF 
receptors. 
Adalimumab was first approved for treatment of rheumatoid arthritis (RA) on 
31 Dec 2002 in the United States (US), on 08 Sep 2003 in the European Union (EU) and 
through August 2008 in a total of 76 countries.  Indication extensions to include 
treatment of psoriatic arthritis and early RA were granted in the EU on 01 Aug 2005 and 
in the US on 03 Oct 2005.  A further indication extension to include treatment of 
ankylosing spondylitis was approved in the EU on 01 Jun 2006 and was approved in the 
US on 28 Jul 2006.  Adalimumab was approved for the treatment of Crohns disease in the 
United States on 27 Feb 2007, in the European Union on 04 Jun 2007 and in Canada on 
05 July 2007 for the adult population.  In December 2007 and January 2008, respectively, 
adalimumab was approved for the treatment of psoriasis in adult patients in the EU, 
Canada and USA.  Additionally, adalimumab was approved for the treatment of juvenile 
idiopathic arthritis in the USA in February 2008. 
Adalimumab has been shown to be a safe and effective treatment of moderately to 
severely active Crohns disease.  In the CD development program, adalimumab was 
studied in over 1400 adult subjects in three pivotal studies (two induction studies and a 
maintenance study). 
Study M02-403 was a multicenter, randomized, double-blind, placebo-controlled 
Phase 2/3 study to evaluate the efficacy and safety of adalimumab for the induction of 
remission in subjects with moderate to severe CD.26  A total of 299 subjects were 
randomized to receive one of four proposed induction treatment regimens (three active 

 
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treatment groups or placebo):  adalimumab 160 mg at Baseline (Week 0) followed by 
80 mg at Week 2, adalimumab 80 mg at Baseline followed by 40 mg at Week 2, 
adalimumab 40 mg at Baseline followed by 20 mg at Week 2 or placebo at Baseline and 
Week 2.  Eligible subjects could not have been previously treated with any anti TNF 
agent.  Only the group of subjects treated with adalimumab 160/80 mg had a statistically 
significantly greater remission rate at Week 4 (primary endpoint) compared to placebo 
(35.5% vs. 12.2%; p = 0.001).  In addition, statistically significantly greater proportions 
of subjects in the adalimumab 160/80 mg group than in the placebo group experienced 
clinical response CR-100 (48.7% and 24.3%, respectively) and clinical response CR-70 
(57.9% and 36.8%, respectively) at Week 4. 
Study M04-691, a second induction study, was a multicenter, randomized, double-blind, 
placebo-controlled, Phase 3 study to evaluate the efficacy and safety of adalimumab as 
induction treatment for subjects with moderate to severe CD who either initially 
responded to administration of infliximab but stopped responding or were intolerant.27  
A total of 325 subjects were randomized to receive adalimumab 160/80 mg or placebo.  
Eligible subjects must have previously been treated with infliximab and discontinued use 
due to loss of response to or intolerance to infliximab therapy.  The proportion of subjects 
who achieved clinical remission at Week 4 (primary endpoint) was statistically 
significantly greater in the adalimumab 160/80 mg group compared to the placebo group 
(21.4% vs. 7.2%).  The proportion of subjects achieving clinical response CR-100 and 
CR-70 at Week 4 was statistically significantly greater in the adalimumab 160/80 mg 
group (38.4% and 51.6%, respectively) compared to the placebo group (24.7% and 
33.7%, respectively). 
Study M02-404 was a multicenter, randomized, double-blind, placebo-controlled Phase 3 
study to assess the efficacy and safety of adalimumab for the maintenance of clinical 
remission in subjects with moderate to severe CD.27  A total of 854 subjects (both naïve 
to or previously treated with TNF antagonists [primarily infliximab]) were enrolled and 
received open-label adalimumab 80 mg at Baseline (Week 0) and adalimumab 40 mg at 
Week 2.  At Week 4, subjects were stratified by responder status (subjects who achieved 

 
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clinical response CR-70) and previous anti-TNF use and were randomized in a 1:1:1 ratio 
to one of three blinded treatment groups:  adalimumab 40 mg every week (ew), 
adalimumab 40 mg every other week (eow), or placebo.  Subjects who met clinical 
response CR-70 after Week 8 could be tapered from corticosteroids. 
The proportion of Week 4 responders (N = 499) who achieved clinical remission at 
Weeks 26 and 56 (co-primary endpoint) were statistically significantly greater in the 
adalimumab 40 mg eow (39.5% and 36.0%, respectively) and 40 mg ew (46.5% and 
41.4%, respectively) groups compared to the placebo group (17.1% and 11.8%, 
respectively).  The differences between the adalimumab 40 mg eow and 
adalimumab 40 mg ew groups at both of these time points were not statistically 
significant.  The median time in first clinical remission was greater in the adalimumab 
40 mg eow group (378 days) compared to the placebo group (127 days).  The median 
time in remission could not be estimated in the adalimumab 40 mg ew group because 
more than 50% remained in clinical remission at the end of the study.  Approximately six 
times as many subjects treated with adalimumab maintenance therapy compared to 
placebo were able to discontinue corticosteroids for at least 90 days and achieve 
remission at Week 26 and Week 56.  Efficacy was independent of Baseline C-reactive 
protein (CRP), concomitant therapies, such as corticosteroids or immunosuppressants, or 
prior anti-TNF experience.  The adalimumab safety profile in CD was similar to that seen 
in the other rheumatologic populations previously studied, except for expected 
manifestations of CD. 
Currently, there are two ongoing extension studies of adalimumab therapy in adult 
subjects with CD.  M04-690 trial is a long-term safety and tolerability study of repeated 
administration of adalimumab in adult subjects with CD who had previously participated 
in M02-404 or M04-691.  The other trial is a long-term open-label extension study 
following the initial first-year study period of the M02-433 study. 
The efficacy and safety of adalimumab in children has recently been demonstrated in 
juvenile rheumatoid arthritis (JRA).28  One hundred and seventy-one pediatric patients 
(4 to 17 years of age) were initially enrolled into a 16-week open label segment and 

 
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133 subjects continued in a 32-week double blind segment.  Clinically significant 
improvements were noted in ACR30, ACR50 and ACR70 as well as other indices of 
arthritis activity.  Adverse events (AEs) were similar as those noted in adult RA patients.  
There were no deaths, malignancies, or opportunistic infections, including tuberculosis 
(TB).  Thirteen serious adverse events (SAEs) in 8 subjects were observed in the 16-week 
open label portion of the study.  These included 4 subjects with JRA, one patient with 
two episodes of leukopenia/neutropenia, and one case each of femur fracture, herpes 
simplex, and pneumonia.  Six SAEs were observed in 6 subjects (2 placebo, 
4 adalimumab) during the 32-week double blind portion (closed head injury, 
gastroduodenitis, retinal detachment, appendicitis, abdominal pain and urinary tract 
infection).  Infections, AEs at least possibly related to study drug, and injection site 
reactions were reported by similar proportions of patients in all treatment groups during 
the double-blind therapy (32 weeks). 
Fatalities, serious infections, and sepsis have been reported with the use of TNF 
antagonists.  Many of the serious infections have occurred in subjects on concomitant 
immunosuppressive therapy that, in addition to their underlying immune disorder, could 
predispose them to infections.  TB has also been observed in subjects treated with TNF 
antagonists, including adalimumab.  The event rate for TB in the CD development 
program is consistent with the global adalimumab rate.29 
TNF antagonists, including adalimumab, have been associated with cases of malignancy 
and demyelinating disease.  Serious allergic adverse reactions have been reported in RA 
subjects following subcutaneous (SC) administration of adalimumab; none were reported 
in the CD program. 
A detailed discussion of the pre-clinical toxicology, metabolism, pharmacology, and 
safety experience can be found in the current Investigators Brochure. 
The goal of this study is to demonstrate the efficacy of adalimumab in the maintenance of 
clinical response and to demonstrate the long-term safety and tolerability of repeated 
administration of adalimumab in pediatric subjects with Crohns disease.  The subject 

 
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population will consist of subjects who participated in and successfully completed the 
M06-806 study and who meet all the inclusion and none of the exclusion criteria of 
Protocol M06-807.  Qualifying subjects will administer open-label adalimumab by SC 
injection.  Subjects receiving every other weekly therapy who continue to have a disease 
flare or develop another flare may be switched to every week therapy at the investigators 
discretion.  Subjects receiving weekly therapy who continue to have a disease flare or 
develop another flare may be withdrawn from the study at the Investigators discretion.  
For a detailed description of the study please see Section 5.0. 
4.0 
Study Objective 
The objective of the study is to evaluate the long-term maintenance of clinical response, 
safety and tolerability of repeated administration of adalimumab in pediatric subjects 
with Crohns disease who participated in, and successfully completed, Protocol M06-806 
through Week 52 and who meet all the inclusion and none of the exclusion criteria of 
Protocol M06-807. 
5.0 
Investigational Plan 
5.1 
Overall Study Design and Plan:  Description 
This study is a multi-center, open-label study of the human anti-TNF monoclonal 
antibody adalimumab.  Approximately 31 sites that have enrolled subjects in the 
M06-806 clinical trial will participate in the M06-807 clinical trial.  Approximately 
130 pediatric subjects were expected to enroll in this study; final enrollment was 
100 subjects.   
The Week 52 visit from the M06-806 study will be the Baseline Visit for those subjects 
entering study M06-807.  The visit window for M06-806 Week 52 visit is 364 ± 7 days 
from the Baseline Visit date of M06-806. 
Subjects may be allowed to enroll in the M06-807 study if they have participated in, and 
successfully completed Protocol M06-806 through Week 52.  A subject must be a 

 
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15 
responder at any time point during the M06-806 study.  A responder is defined as a 
subject who had a PCDAI score that was at least 15 points lower than the M06-806 
baseline score. 
All subjects will be on open-label maintenance therapy.  Subjects who enroll into the 
study from blinded therapy in Study M06-806 will receive open-label therapy at a dose 
dependent on their body weight.  Subjects who weigh t 40 kg at Baseline will receive 
40 mg eow of adalimumab, while subjects who weigh < 40 kg at Baseline will receive 
20 mg eow of adalimumab.  Beginning at Week 8, subjects who have a disease flare may 
be switched to ew treatment at the same dose of adalimumab received while on eow 
treatment.  A disease flare is defined as an increase in the Pediatric Crohns Disease 
Activity Index (PCDAI) of t 15 points when compared to the PCDAI score obtained at 
the subjects previous visit. 
Subjects who enroll into the study from open-label therapy in Study M06-806 will 
continue to receive the same dose they were receiving (i.e. 40 mg ew or 20 mg ew) at the 
Week 52 visit of the M06-806 study.  
Subjects who develop a flare while receiving ew open-label therapy or have a PCDAI 
score t 15 points when compared to their Baseline (the Week 52 visit of the M06-806 
study) PCDAI score (regardless of study visit), may be discontinued from the study at the 
discretion of the Investigator.  
Beginning from Week 8, the dose of adalimumab may be increased to 40 mg, at the 
discretion of the Investigator, for subjects whose body weight has increased from < 40 kg 
to t 40 kg from the Baseline (Week 52 of the M06-806 Study) visit.  The site will enter 
the subjects body weight into the Interactive Voice Response System (IVRS) and the 
dose will be adjusted, if applicable.  
Reductions in concomitant therapy will be allowed for Crohns treatment related toxicities 
(e.g., leukopenia, anemia, neuropathy) of Grade 3 or higher. 

 
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Subjects may be allowed to decrease prednisone (or equivalent) and budesonide if 
qualifications are met (please see Section 5.2.3.2 for required timing and rate of taper). 
Subjects may be allowed to adjust their Crohns specific concomitant medications as 
specified in Section 5.2.3.2. 
The duration of the study could last up to 264 weeks (approximately 5 years).  Subjects 
who complete, or who early terminate from the study will be contacted 70 days after their 
last dose of study drug to obtain information on any ongoing and new AEs.   
This study will conclude approximately 12 weeks after the following criteria have been 
satisfied: 
● Study drug receives country and local (if applicable) regulatory approval for 
pediatric Crohns Disease. 
● All applicable local reimbursement procedures are completed. 
 
Sites will be notified once these criteria are met. 
Following country and local (if applicable) regulatory approval and applicable local 
reimbursement approval of the study drug in a country, subjects should return to their 
next scheduled study visit as specified in the protocol.  The termination visit should be 
conducted in place of their regular scheduled study visit.  These subjects should be 
considered as having completed the study. 
A schematic of the study design is shown in Figure 1 (prior to Amendment 4) and in 
Figure 2 (after Amendment 4). 

 
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Figure 2.  
Dosing Schematic After Amendment 4 
 
F:  
Subjects who have a disease flare may be switched to the next higher treatment level. 
R:  
Subjects who responded to their current treatment may be switched to the next lower treatment level at the 
discretion of the investigator after discussion with the medical monitor.  Response is defined as a) a t 15 points 
decrease in PCDAI compared to the last observation prior to dose escalation in patients who dose-escalated or 
b) a t 15 points decrease in PCDAI compared to Baseline of Study M06-806 in patients who did not 
dose-escalate. 
BW: Subjects with an increase in body weight to t 40 kg may increase their dose to the next higher level at the 
discretion of the investigator after discussion with the medical monitor.  Subjects with a decrease in body weight 
to < 40 kg may decrease their dose to the next lower level at the discretion of the investigator after discussion 
with the medical monitor. 
 
5.2 
Selection of Study Population 
Subjects will be evaluated to determine if they meet all of the inclusion criteria specified 
in Section 5.2.1 and none of the exclusion criteria specified in Section 5.2.2 of this 
protocol.   
5.2.1 
Inclusion Criteria 
1. 
Subject must have successfully enrolled in and completed Protocol M06-806 
through Week 52. 
2. 
Subject must be a responder at any time point during the M06-806 study. 

 
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3. 
If female, subjects who are sexually active and are of child-bearing potential 
should be practicing an approved method of birth control throughout the study and 
for 150 days after study drug administration.  Examples of approved methods of 
birth control include the following: 
● Condoms, sponge, foam, jellies, diaphragm or intrauterine device (IUD) 
● Oral, parenteral or intravaginal contraceptives 
● A vasectomized partner 
4. 
Subject of legal age, parent or legal guardian, as required, has voluntarily signed 
and dated an Institutional Review Board (IRB)/Independent Ethics Committee 
(IEC) approved informed consent form, after the nature of the study has been 
explained and the subject of legal age, subjects parent, or legal guardian, as 
required, has had the opportunity to ask questions.  Subjects will be included in all 
discussions, and if required, their signature on an assent form will be obtained. 
5. 
Parent or legal guardian of subject who is not of legal age, as required, must be 
willing to actively supervise storage and administration of study drug and to 
ensure that the time of each dose is accurately recorded in the subjects diary. 
6. 
If a subject of legal age, must be willing to actively store, administer, and 
accurately record study drug administration in the subject diary. 
7. 
Subject is judged to be in acceptable medical condition, as determined by the 
Principal Investigator based upon results of clinical and laboratory evaluations 
done throughout the preceding Crohns disease study M06-806. 
 
5.2.2 
Exclusion Criteria 
A subject will be excluded from the study if he/she meets any of the following criteria:  
1. 
For any reason, the subject is considered by the Investigator to be an unsuitable 
candidate for continuing therapy in the M06-807 study. 

 
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2. 
Subject has abnormal laboratory or other test results that in the opinion of the 
Investigator will make the subject unsuitable to participate in this study. 
3. 
History of cancer or lymphoproliferative disease other than a successfully and 
completely treated cutaneous squamous cell or basal cell carcinoma or 
carcinoma − in-situ of the cervix. 
4. 
History of listeriosis, histoplasmosis, chronic or active hepatitis B infection, 
human immunodeficiency virus (HIV) infection, any immunodeficiency 
syndrome, central nervous system (CNS) demyelinating disease or active TB 
(receiving treatment or not receiving treatment).  Ongoing severe infections such 
as sepsis and opportunistic infections will be exclusionary. 
5. 
Subject with known, symptomatic obstructive strictures. 
6. 
Subject who is planning surgical bowel resection at any time point while enrolled 
in the study. 
7. 
Subject who has short bowel syndrome as determined by the Investigator. 
8. 
Subject who is currently receiving total parenteral nutrition (TPN). 
9. 
Subject who is unwilling to discontinue growth hormone prior to the first dose of 
open-label study drug at the Baseline visit of M06-807. 
10. 
Female subject who is pregnant or currently breast-feeding. 
11. 
Subject with a history of clinically significant drug or alcohol abuse in the last 
year. 

 
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12. 
Subject with a poorly controlled medical condition such as: uncontrolled diabetes, 
recurrent infections, unstable ischemic heart disease, moderate to severe heart 
failure, recent cerebrovascular accidents or any other condition which, in the 
opinion of the Investigator or the Sponsor, will put the subject at risk by 
participation in the protocol. 
13. 
Subject with any prior exposure to Tysabri (natalizumab). 
14. 
Subject with a known hypersensitivity to the excipients of adalimumab as stated in 
the label. 
15. 
Subject with a previous history of dysplasia of the gastrointestinal tract. 
16. 
Subject is not in compliance with Section 5.2.3. 
 
If there are any questions regarding inclusion and exclusion criteria and/or subject 
eligibility, contact the Abbott Laboratories Medical Monitor identified in Section 7.0. 
5.2.3 
Prior and Concomitant Therapy 
5.2.3.1 
Prior Therapy 
Any medication (including over-the-counter medicines such as aspirin) that the subject is 
receiving during the study must be recorded in source documents and on the appropriate 
case report form (CRF) along with the reason for use, dates of administration and 
dosages. 
Any vaccine administered to the subject during the study should be listed as a 
concomitant medication.  Subjects should continue on the recommended vaccination 
schedule; however, vaccinations with live vaccines are prohibited.   
Any medications captured in the M06-806 CRF(s) which are ongoing will be transcribed 
onto the M06-807 source documents and CRF(s). 

 
Adalimumab 
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23 
If there are any questions regarding prior or concomitant therapy (ies), contact the Abbott 
Laboratories Medical Monitor identified in Section 7.0 
5.2.3.2 
Concomitant Therapy 
Adjustments of Crohns related concomitant treatments, including Crohns related 
antibiotics, are not allowed during the first 8 weeks of the M06-807 study, unless subject 
safety is at risk. 
After Week 8, decreases in the dose or discontinuation of Crohns related antibiotics or 
Crohns related concomitant treatments are allowed according to the Investigators medical 
judgment.  These adjustments may be performed without prior discussion with the Abbott 
Medical Monitor.  In addition, Subjects may be able to initiate or reinitiate Crohns related 
treatments, except immunosuppressants, following eight (8) weeks of exposure to open-
label adalimumab.  Immunosuppressants may not be started or restarted during the study. 
Setons are allowed as concomitant therapy in subjects with perianal fistulas.  Their use 
should be documented on the concomitant medications page of the CRF. 
Growth hormone must be discontinued prior to the first dose of open-label study drug and 
Subjects may not begin using it while participating in this study. 
If a subject began to taper corticosteroids during the M06-806 study, they may continue 
this taper immediately upon enrollment into the M06-807 study.  Beginning at Week 8, 
subjects who are not in flare may begin corticosteroid taper according to the following 
schedule: 
Tapering Schedule 
Dose 
Rate 
Prednisone (or equivalent) 
> 10 mg 
d 10 mg  
5 mg/week 
2.5 mg/week 
Budesonide 
d 9 mg  
3 mg/week 
 

 
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24 
Subjects who are in flare or who flare after they have reduced or completely tapered their 
dose of corticosteroid may have their corticosteroid dose increased or restarted, at the 
discretion of the Investigator.  
5.2.3.3 
Rescue Therapy 
If the Investigator decides, during the study, that a subject requires rescue therapy other 
than that described in this protocol, the subject must be terminated from the study.  If 
possible, questions regarding the use of rescue therapy should be discussed with the 
Medical Monitor prior to use. 
5.2.3.4 
Prohibited Therapy 
Live vaccines must not be given concurrently while on study drug and for 70 days after 
the last dose of study drug. 
Infliximab and growth hormone use are prohibited during the study.  At the Baseline 
visit, any subject using Growth hormone must discontinue its use. 
Tysabri (natalizumab), concurrent biological therapy, cyclosporine, tacrolimus, 
mycophenolate mofetil, Kineret® (anakinra), Orencia (abatacept), therapeutic enemas and 
suppositories (not including those done in conjunction with routine colonoscopies) and 
any investigational agent are prohibited during the study (see Appendix L). 
Concurrent use of budesonide and prednisone (or equivalent) is prohibited. 
Subjects with any prior exposure to Tysabri (natalizumab) will be excluded. 
5.3 
Efficacy, and Safety Assessments/Variables 
5.3.1 
Efficacy and Safety Measurements Assessed and Flow 
Chart 
Study procedures will be performed as summarized in the study schematic presented in 
Table 1. 

 
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Table 1.  
Study Activities 
Activity 
Baseline 
Week 4 
Week 8 
Week 12 
Week 24 
Week 36 
Week 48 
Week 60 
Week 72 
Week 84 
Week 96 
Week 108
Inclusion/exclusion criteria 
X 
 
 
 
 
 
 
 
 
 
 
 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
 
 
Previous and concomitant 
medications 
Xa 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Urine pregnancy testb 
Xa 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Vital signsc 
Xa 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Physical exam 
Xa 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
General LABd,m 
Xa 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Urinalysise 
Xa 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Erythrocyte sedimentation 
rate 
Xa 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
CRP 
Xa 
 
 
 
X 
 
X 
 
X 
 
 
X 
ANA 
Xa 
 
 
X 
 
 
 
 
 
 
 
X 
Anti-dsDNAf 
Xa 
 
 
X 
 
 
 
 
 
 
 
X 
PCDAI 
Xa 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
CDAIg 
Xa 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
IMPACT III Questionnaireh 
Xa 
 
 
X 
X 
 
X 
 
X 
 
 
X 
 

 
Adalimumab 
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Table 1.  
Study Activities (Continued) 
Activity 
Baseline 
Week 4 
Week 8 
Week 12 
Week 24 
Week 36 
Week 48 
Week 60 
Week 72 
Week 84 
Week 96 
Week 108
Unscheduled outpatient 
visits, emergency room 
visits and hospitalizations 
questionnaire 
Xa 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Work Productivity and 
Impairment Questionnaire: 
Crohns Disease (WPAI − 
CD) 
Xa 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X-ray for bone agei 
Xa 
 
 
 
 
 
X 
 
 
 
 
X 
Serum bone markers 
Xa 
 
 
 
X 
 
X 
 
X 
 
 
X 
PK Blood Samplej 
 
 
 
 
X 
 
X 
 
X 
 
X 
 
Anti-adalimumab blood 
levels (AAA)j 
 
 
 
 
X 
 
X 
 
X 
 
X 
 
Adverse eventsk 
Xa 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Dispense study drug 
Xa 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 

 
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27 
Table 1.  
Study Activities (Continued) 
Activity 
Week 
120 
Week 
132 
Call 
Week 
144 
Week 
156 
Call 
Week 
168 
Week 
180 
Call 
Week 
192 
Week 
204 
Call 
Week 
216 
Week 
228 
Call 
Week 
240 
Week 
252 
Call 
Week 
264/ 
Early 
Term 
Unsched 
Visit 
70-Day 
Follow-up 
Call 
Inclusion/exclusion 
criteria 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Informed consent 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Previous and concomitant 
medications 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Urine pregnancy testb 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
 
Vital signsc 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
 
Physical exam 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
 
General LABd,m 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
 
Urinalysise 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
 
Erythrocyte 
sedimentation rate 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
 
CRP 
 
 
X 
 
X 
 
X 
 
X 
 
 
 
X 
 
 
ANA 
 
 
X 
 
 
 
X 
 
 
 
 
 
X 
 
 
Anti-dsDNAf 
 
 
X 
 
 
 
X 
 
 
 
 
 
X 
 
 
PCDAI 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
 
CDAIg 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
 
IMPACT III 
Questionnaireh 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
 
 

 
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Table 1.  
Study Activities (Continued) 
Activity 
Week 
120 
Week 
132 
Call 
Week 
144 
Week 
156 
Call 
Week 
168 
Week 
180 
Call 
Week 
192 
Week 
204 
Call 
Week 
216 
Week 
228 
Call 
Week 
240 
Week 
252 
Call 
Week 
264/ 
Early 
Term 
Unsched 
Visit 
70-Day 
Follow-up 
Call 
Unscheduled outpatient 
visits, emergency room 
visits and 
hospitalizations 
questionnaire 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Work Productivity and 
Impairment 
Questionnaire: Crohns 
Disease  (WPAI − CD) 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
 
X-ray for bone agei 
 
 
X 
 
 
 
X 
 
 
 
 
 
X 
 
 
Serum bone markersi 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
 
PK Blood Samplej 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
 
Anti-adalimumab blood 
levels (AAA)j 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
 
Adverse eventsk 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Dispense study drug 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
 
Xl 
 
 

 
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29 
Table 1.  
Study Activities (Continued) 
a. 
At the Baseline Visit, the following procedures will be completed as part of Week 52 of the M06-806 study. 
b. 
Performed on all females of child-bearing potential - Urine pregnancy test at all study visits. 
c. 
Vital sign determinations of height, weight, sitting blood pressure, heart rate, respiratory rate, and body temperature will be obtained at each visit. 
d. 
Blood draws should be performed after questionnaire and vital signs determinations and before study drug administration. 
e. 
Microscopic urinalysis will be performed at any visit if dipstick UA is abnormal (protein greater than a trace, blood greater than 5-10 Ery/ul, moderate or large ketone count 
or glucose greater than 50 mg/dL). 
f.  
If an ANA result is positive, anti-dsDNA will be performed automatically. 
g.  For subjects who are age 13 or older at the M06-807 Baseline Visit, a CDAI will be completed at each visit. 
h. 
For subjects who are age 10 or older at the M06-807 Baseline Visit, an IMPACT III Assessment will be completed at Baseline, Weeks 12, 24, 48, 72, 108, 120, 144, 168, 192, 
216, 240, 264/ET and unscheduled visits. 
i. 
If the height velocity is 0 and, in the opinion of the investigator, a subject is no longer growing, the x-ray for bone age and the determination of serum bone markers can be 
omitted. 
j. 
In addition to blood draws every 24 weeks, PK and AAA blood draws to be performed if subject meets flare criteria and dose escalated to ew dosing. 
k. 
All AEs, including SAEs, will be captured throughout the study from the time that the subject signs the Informed Consent Form.  SAEs will be captured throughout the 70 day 
follow-up period (if applicable). 
l. 
If an unscheduled visit is performed to change the frequency or dose of study drug, study drug may be dispensed. 
m. PPD or QuantiFERON-TB Gold testing at Weeks 48, 96, 144, 192 and 240. 
 
 

 
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5.3.1.1 
Study Procedures 
The M06-806 Week 52 visit will serve as the Baseline visit for the M06-807 study.  The 
study procedures outlined in Table 1 are discussed in detail in this section, with the 
exception of the collection of AE information (discussed in Section 6.0).  All study data 
will be recorded in source documents and on the appropriate CRFs.  The site will call the 
subjects at Weeks 132, 156, 180, 204, 228 and 252 in order to collect any safety 
information from the subject as illustrated in Table 1. 
The visit window for all scheduled visits is ±7 days calculated from the Baseline visit of 
the M06-807 study. 
Inclusion/Exclusion Criteria 
A subject will be excluded from this study if he/she does not meet all inclusion criteria or 
meets any of the exclusion criteria of Protocol M06-807. 
Informed Consent 
A signed Informed Consent Form (ICF) will be obtained from a subject of legal age (in 
the state of residence) or from the parent or legal guardian (as appropriate)of a subject 
who is not of legal age before any study related procedures are undertaken or before any 
medications are discontinued for the purpose of this study.  Additionally, an informed 
consent will be required from those subjects who were not of legal age at the onset of this 
study but become of legal age during the course of the study. 
In keeping with each institutions IRB requirements, an Informed Assent may also be 
required from pediatric subjects.  Pediatric subjects will be included in all discussions in 
order to obtain their signature on an assent form.  Details about how informed consent 
will be obtained and documented are provided in Section 9.3. 
If an updated informed consent is approved after a subject has completed or terminated 
early from the study, but is within the 70-day follow-up window, the subject will not be 
required to return to the site for the purposes of signing the updated ICF.  The subject of 

 
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31 
legal age, parent or legal guardian (as appropriate) should be contacted regarding any 
changes and the documentation of the contact should be present in the subjects source. 
Previous and Concomitant Medications 
Changes in concomitant medications will be assessed at each study visit from Baseline 
through the Week 264/ET visit.  Concomitant medications that are taken prior to the first 
dose of study drug administration for this study will be captured in the subjects casebook 
from the previous study (M06-806).  They will not be required to be captured in the 
subjects casebook of the M06-807 study unless they were ongoing at the Week 52 visit of 
the M06-806 study.  Ongoing concomitant medications from the M06-806 study will be 
transcribed into the subjects M06-807 casebook. 
Subjects of legal age or the parent or guardian (as appropriate) of subjects who are not of 
legal age will be provided with a medication log (see Appendix O) to record all 
medications the subject takes throughout the study.  This log must be returned for review 
at every study visit. 
Serum/Urine Pregnancy Test 
All female subjects who are experiencing menses, are nearing sexual maturation (in the 
opinion of the Investigator), or who are of child-bearing potential, will undergo a urine 
pregnancy test at each visit.  Urine pregnancy tests will be performed locally by 
designated study personnel.  If a urine pregnancy test is positive, a serum pregnancy test 
must be performed by the central laboratory.  If the serum pregnancy test is positive, the 
subject will be removed from the study.   
A lactating or pregnant female will not be eligible for participation in this study. 
TB Testing 
For subjects with a negative test at Screening visit from parent study (Study M06-806), 
an annual PPD or QuantiFERON-TB Gold re-test will be required.  If one of the annual 

 
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32 
tests has a positive test result, the matter should be discussed with the medical monitor 
prior to starting any prophylaxis. 
A PPD skin test (alternatively, also known as tuberculin skin test) must be placed or the 
QuantiFERON®-TB Gold test (or equivalent) must be performed for subjects with a 
negative test at Screening visit after the amended protocol is approved by IRB/IEC 
including those with a prior history of Bacille Calmette-Guérin (BCG) administration at 
the time the subject reaches one of the scheduled visits:  Weeks 48, 96, 144, 192, and 
240.  
If the subject is experiencing signs or symptoms suspicious for TB or something has 
changed in the subject's medical history to warrant a repeat test before the next scheduled 
annual TB re-test, the case must be discussed with the Abbott Medical Monitor. 
For the PPD test: 
● The subject will be required to have the PPD test read by a licensed healthcare 
professional 48 to 72 hours after placement (or as per local guidelines), when 
the induration is maximal.  An induration (not erythema) of 5 mm or greater 
will be considered as PPD positive, irrespective of BCG status or local 
guidelines.  The absence of induration should be recorded, as "0 mm," not 
"negative." 
● If there are sites where the available testing materials are not accepted, an 
alternative tuberculin skin test may be substituted, but the method must be 
submitted and approved by Abbott prior to use with study subjects. 
● If QuantiFERON®-TB Gold (or equivalent) result is indeterminate, the test 
should be repeated with a fresh blood sample.  If a repeat QuantiFERON®-TB 
Gold (or equivalent) result is indeterminate, this should be considered a 
positive test result and the case must be discussed with the Abbott Medical 
Monitor. 
 
In the event both a PPD test and QuantiFERON-TB Gold test are performed, the result of 
the QuantiFERON-TB Gold test will supersede the result of the PPD test. 

 
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33 
Newly initiated prophylactic treatment should be captured in the source documents and 
on the concomitant medications page in the CRF.  Prior therapy should be captured in the 
appropriate medical history CRF. 
For sites participating in the Czech Republic, the following local requirements will also 
be applicable: 
● A pulmonologist will be responsible to obtain a detailed medical history with 
respect to TB exposure.  This information needs to include BCG vaccination, 
cohabitation with individuals who have had TB, and/or who reside or work in 
TB endemic locations.  The information obtained by the pulmonologist must 
be documented in the subject's source note, dated and signed by the 
pulmonologist. 
● A pulmonologist must review the results of the PPD skin test and the CXR 
and has to give his/her opinion about the eligibility of each subject to continue 
in the study.  This opinion must be documented in writing in the subject's 
source documents. 
 
All subjects with a positive PPD need to be approved for continuation in the trial by both 
the Czech pulmonologist and the Abbott Medical Monitor and all such subjects need to 
receive prophylaxis for latent TB.  Under no circumstances can a subject with a positive 
PPD result and no prior history of treatment for active or latent TB be allowed to 
continue in this trial 
Vital Signs 
Vital sign determinations of sitting blood pressure, heart rate, respiratory rate, body 
temperature, weight and height will be obtained at each visit.  All measurements will be 
recorded in metric units when applicable.  
Weight measurements will be obtained using the same measuring instrument at each visit 
and measured with subjects wearing only undergarments.  Height measurements will be 

 
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34 
obtained using the same measuring equipment at each visit and performed on subjects 
with their shoes taken off. 
Physical Examination 
A physical examination will be performed at each visit.  A count of the number of 
cutaneous fistulas draining upon gentle compression will be performed during each 
physical exam.30  Fistulas will be classified as abdominal or perianal/anal. 
Physical exam abnormalities (including fistulas and fissures) noted by the Investigator 
will be evaluated and documented on the corresponding source documents.  Any new 
abnormalities or worsening of pre-existing conditions should be captured as AEs. 
Clinical Laboratory Tests  
Samples will be obtained for the laboratory tests listed in Table 2 at all study visits.  
Blood draws should be performed after questionnaires (PCDAI, IMPACT III 
Questionnaire, etc.) and vital sign determinations during a study visit, and before study 
drug administration. 
ICON central laboratory will be utilized to process and provide results for the general 
laboratory tests.  All abnormal laboratory test results that are considered clinically 
significant by the Investigator will be followed to a satisfactory resolution. 
ICON will provide instructions regarding the collection, processing and shipping of these 
samples. 

 
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35 
Table 2.  
Clinical Laboratory Tests  
Hematologya 
Clinical Chemistry 
Urinalysisb 
Serum Bone Markers 
Hematocrit 
Hemoglobin 
Red Blood Cell (RBC) 
count 
White Blood Cell 
(WBC) count 
Neutrophils 
Bands 
Lymphocytes 
Monocytes 
Basophils 
Eosinophils 
Platelet count (estimate 
not acceptable) 
Blood Urea Nitrogen 
(BUN) 
Creatinine 
Total bilirubin 
Serum glutamic-pyruvic  
 
transaminase 
(SGPT/ALT) 
Serum glutamic-
oxaloacetic 
 
transaminase 
(SGOT/AST) 
Alkaline phosphatase 
Sodium 
Potassium 
Calcium 
Inorganic phosphorus 
Uric acid 
Cholesterol 
Total protein 
Glucose 
Triglycerides 
Albumin 
Specific gravity 
Ketones 
pH 
Protein 
Blood 
Glucose 
Osteocalcin 
Bone-specific alkaline 
phosphatase (BSAP)  
bone resorption (Ntx) 
a. 
Basic hematology testing performed on instrumentation does not include band reporting.  When 
Hematology results reflex to a Manual Differential, if there is a band result over 5, it is reported. 
b. Microscopic urinalysis will be performed at any visits if dipstick UA is abnormal  (protein greater than 
a trace, blood greater than 5-10 Ery/ul, moderate or large ketone count or glucose greater than 
50 mg/dL). 
 
Immunologic Laboratory Assessments   
CRP, adalimumab levels, anti-adalimumab antibody levels (AAA) and antinuclear 
antibody (ANA) assessments will be performed as indicated in Table 1.  If an ANA result 
is positive, anti-double-stranded DNA (anti-dsDNA) will be performed automatically. All 
CRP, ANA, anti-dsDNA will be performed by the central laboratory. 

 
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Erythrocyte Sedimentation Rate (ESR) assessments will be performed at all visits as 
indicated in Table 1.  ESR assessments will be performed by the sites local laboratory. 
Markers of Bone Metabolism  
Serum markers of bone metabolism will be measured as indicated in Table 1.  The bone 
formation markers to be measured are osteocalcin, bone-specific alkaline phosphatase 
(BSAP), and bone resorption (Ntx). 
Urinalysis 
Urine will be assessed by dipstick at each visit (done locally).  All results, including 
abnormalities, will be captured in source documentation and on the appropriate CRF.  
If, at any visit, the dipstick UA results are abnormal, the central lab will perform a 
microscopic urinalysis.  Abnormal is defined as protein greater than a trace, blood greater 
than 5-10 Ery/ul, moderate or large ketone count or glucose greater than 50 mg/dL. 
Pediatric Crohns Disease Activity Index (PCDAI) 
The PCDAI score will be calculated at each visit.  When completing the PCDAI, the 
HCT, albumin, and ESR values will be utilized from the same study visit.  
An example of the PCDAI is located in Appendix G.  Instructions for completing the 
PCDAI score is located in Appendix H. 
Crohns Disease Activity Index (CDAI) 
At each visit, a CDAI score will be calculated for subjects who are age 13 or older at the 
M06-807 Baseline Visit.  The CDAI score will be calculated utilizing the subject diary 
and the HCT value from the same study visit.  A copy of the CDAI subject diary is 
located in Appendix H. 
When completing question five (5) ("Taking Lomotil/Imodium/Loperamide/opiates for 
diarrhea, 0 = no, 1 = yes") on the CDAI, "no" should be answered if a subject is taking an 
opiate(s) solely for pain. 

 
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For the CDAI questions regarding presence of anal fistulas and other fistulas, all fistulas 
detectable on physical examination (draining and non-draining) should be captured on the 
CDAI CRF page and calculated into the CDAI score. 
The calculation of the CDAI score is in Appendix I. 
IMPACT III Questionnaire 
Subjects t 10 years old at the Baseline visit of the M06-807 study will complete an 
IMPACT III questionnaire as indicated in Table 1.  A copy of the questionnaire is located 
in Appendix K.  
The IMPACT III will be recorded directly onto the CRF.  The completed CRF will be 
considered source documentation for this assessment. 
Outcomes 
The Unscheduled Outpatient Visits, Emergency Room Visits and Hospitalization 
Questionnaire and the Work Productivity and Activity Impairment Questionnaire:  
Crohns Disease (WPAI-CD) will be completed at each visit except the Unscheduled Visit 
(Appendix N, Appendix T). 
The subjects parent or legal guardian will complete the WPAI directly onto the CRF.  
The completed CRF will be considered source documentation for this assessment. 
Bone Age 
An x-ray of the wrist for the assessment of bone age will be obtained as indicated in 
Table 1.  Sites should use the Greulich and Pyle method for reading the x − ray.31  The 
x-ray report requires the signature of the radiologist who read the films.  The bone age 
that is determined by the x-ray should be recorded on the CRF.   

 
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Anthropometric Evaluations 
Height and weight obtained at each visit will be used by Abbott Data Management and 
Statistical groups for determination of BMI and "z" score (observed height velocity 
(cm/yr) - mean height velocity for age and sex (cm/yr) / SD of the mean) for height. 
Adverse Events 
Adverse events will be assessed at every study visit from Baseline through the 
Week 264/ET visit.  Any AEs, which are ongoing in the M06-806 study, will be 
transcribed onto the M06-807 source documents and CRF(s) 
For those subjects who complete the study or terminate early, a phone call will be made 
70 days after the last dose of study drug to obtain follow-up information on any ongoing 
and any new AEs. See Section 6.0 and Appendix M for additional information. 
Study Drug Administration 
At each study visit, the subject or their trained designated friend, family member or 
health care professional will perform study drug injections under the supervision of a 
trained medical professional to reinforce proper aseptic SC injection technique.  Subjects 
or a trained designated friend, family member or health care professional will perform 
injections of study drug in the subjects home during weeks they are not in for scheduled 
clinic visits.  Subjects may return to the study site for injections in between study visits if 
subject or a trained designated friend, family member or health care professional cannot 
inject the study medication. 
Subjects will maintain a dosing diary for all study drug administered outside study visits, 
i.e., at home.  In the diary, the date, initials of the person administering the study drug, 
time study drug is administered, kit number and the dose administered will be recorded.  
Subjects must return this diary and it will be reviewed and verified for compliance at 
each visit by the research personnel at the study center.  All relevant dosing information 
will be retained by the study coordinator and transcribed onto a drug accountability form 
at each visit.  Additionally, any discernible departure from the protocol regarding study 

 
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drug administration will be recorded on source documents and appropriate drug 
accountability forms.  A sample of the Subject Dosing Diary is presented in Appendix P. 
At all office visits subjects should be observed after study drug administration, until 
judged clinically stable by the study personnel.  If an anaphylactic reaction or other 
serious allergic reaction occurs, administration of study drug should be discontinued 
immediately and appropriate therapy initiated.  When dosing at home, subjects should be 
instructed to contact the site immediately with any signs or symptoms of a reaction. 
The dosing dates, for all doses of study drug, should be calculated from the Baseline visit 
date.  The Baseline visit date for this study is 364 ± 7 days from the Baseline Visit date of 
M06-806.  A +/- 3 day window is allowable for scheduled study dosing dates. 
For subjects that deviate from this dosing window, every effort should be made to bring 
the subject back to the original dosing schedule as soon as possible.  For situations where 
bringing the subject back on the original dosing schedule will cause the dose to be out of 
the +/- 3 day window, please contact the Medical Monitor for additional instructions. 
Randomization and Assignment of Subject Numbers 
All subjects will be centrally registered using an IVRS.  This is an open-label study; 
subjects will not be randomized.  The telephone number and call in directions for the 
IVRS will be provided to each site.  Subjects will keep their study subject number from 
the previous double-blind study (M06 − 806). 
5.3.2 
Drug Concentration Measurements 
Blood samples for the assay of adalimumab and AAA serum concentrations will be 
collected at Baseline and every 24 weeks thereafter.  In addition, blood samples for 
adalimumab and AAA concentration analysis will also be collected if a subject meets 
flare criteria and dose escalated to ew dosing.  Study visits in which blood samples will 
be collected are listed in Table 1.  At each visit, blood samples will be collected prior to 
study drug administration at each visit. 

 
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The time that each blood sample is collected will be recorded to the nearest minute in the 
source documents and on the appropriate CRF. 
5.3.2.1 
Collection of Samples for Analysis 
Collection of Samples for Adalimumab Analysis 
Blood samples for adalimumab analysis will be collected by venipuncture into 
appropriately labeled 4-mL evacuated serum collection tubes without gel separator at 
visits indicated in Table 1.  All samples will be obtained immediately prior to dosing at 
visits indicated in Table 1.  Sufficient blood will be collected to provide approximately 
2 mL serum.  Allow the blood to clot for 30 minutes at room temperature before 
centrifugation. 
A maximum of 13 samples are planned to be collected per subject for the analysis of 
adalimumab concentrations. 
Collection of Samples for AAA Analysis 
Blood samples for AAA assay will be collected by venipuncture into appropriately 
labeled 4-mL evacuated serum collection tubes without gel separator at visits indicated in 
Table 1.  All samples will be obtained immediately prior to dosing at visits indicated in 
Table 1. Sufficient blood will be collected to provide approximately 2 mL serum.  Blood 
will be allowed to clot for 30 minutes at room temperature before centrifugation. 
A maximum of 13 blood samples are planned to be collected per subject for AAA 
analysis. 
5.3.2.2 
Handling/Processing of Samples 
The blood samples for adalimumab and AAA, assay will be centrifuged within 30 to 
60 minutes of collection to separate the serum.  The serum samples will be transferred 
using plastic pipettes into screw-capped polypropylene vials labeled with the type of 
sample (serum, SRM), the protocol number, subject number, the study week and the 

 
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assay (PK-Adalimumab, AAA).  The serum samples will be frozen within 2 hours after 
collection and will remain frozen in a –20°C or colder until shipped.  Sites that do not 
have access to a −20°C or colder freezer will need to ship the samples the day they are 
collected.  (Detailed instructions provided in the ICON Laboratory Manual). 
5.3.2.3 
Disposition of Samples 
The PK and AAA samples will be shipped to ICON with all other samples being shipped 
to ICON.  Refer to the ICON Lab Manual for further instruction.  Neither Abbott nor 
ICON will supply dry ice for this study.  Study sites will identify a dry ice source and 
purchase the necessary dry ice. 
5.3.2.4 
Measurement Methods 
Serum concentrations of adalimumab will be determined using a validated ELISA 
method under the supervision of the Drug Analysis Department at Abbott Laboratories.  
Only serum samples that have adalimumab levels < 2.0 Pg/mL will be selected for AAA 
concentration measurement. 
Serum concentrations of AAA will be determined using a validated ELISA method under 
the supervision of the Drug Analysis Department at Abbott Laboratories. 
5.3.3 
Efficacy Variables 
Efficacy will be evaluated based on the proportion of subjects who maintain PCDAI 
clinical response at each visit.  Clinical response is defined as PCDAI decrease 
t 15 points from the M06-806 Baseline score. 
Other measures of disease activity being assessed in this study will be summarized, 
including CDAI scores, IMPACT III scores, WPAI-CD Caregiver, z-score for height 
velocity, bone x-ray, serological markers of bone metabolism, healthcare resource 
utilization (unscheduled outpatient visits), adalimumab levels and anti-adalimumab levels 
(AAA). 

 
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5.3.4 
Safety Variables 
AEs, laboratory data, physical examinations and vital signs are the safety parameters and 
these will be assessed throughout the study. 
Treatment-emergent events will be summarized and reported by treatment group and by 
AAA status (AAA+ versus AAA-). 
5.3.5 
Pharmacokinetic Variables 
Serum concentrations of adalimumab and AAA will be determined from samples 
collected at the study visits listed in Table 1. 
5.4 
Removal of Subjects from Therapy or Assessment 
5.4.1 
Discontinuation of Individual Subjects 
Subjects will be withdrawn from the study immediately if any of the following occur:   
● Clinically significant abnormal laboratory results or AEs, which rule out 
continuation of the study drug, as determined by the Investigator and the 
Medical Monitor. 
● The Investigator believes it is in the best interest of the subject. 
● The subject or subjects legal guardian requests withdrawal from the study. 
● Selection criteria violation was noted after the subject started study drug, as 
determined by the Medical Monitor (see Sections 5.2.1 and 5.2.2). 
● Introduction of prohibited medications or prohibited concomitant medication 
dosages as determined by the Medical Monitor. 
● The subject is diagnosed with a malignancy except for localized 
non − melanoma skin cancer.  Discontinuation for carcinoma in-situ is at the 
discretion of the Investigator. 
● The subject is diagnosed with dysplasia of the gastrointestinal tract. 
● A female subject who becomes pregnant. 
 

 
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If the subject prematurely discontinues study drug use, the procedures outlined for the 
Week 264/ET Visit must be completed within 2 weeks of the last dose of study drug, and 
preferably prior to the initiation of another therapy.  These procedures should not 
interfere with the initiation of any new treatments or therapeutic modalities that the 
Investigator feels are necessary to treat the subjects condition.  Following discontinuation 
of the study drug, the subject will be treated in accordance with the Investigators best 
clinical judgment. 
Subjects who prematurely discontinue from the study will not be replaced.  The date of 
last dose and reason for premature discontinuation will be recorded in the source 
document and on the appropriate CRF. 
5.4.2 
Discontinuation of Entire Study 
Abbott reserves the right to discontinue the study at any time and to remove all study 
materials from the site.  Possible reasons for termination of the study include, but are not 
limited to: 
● Safety concerns based on reported data 
● Unsatisfactory enrollment with respect to quantity or quality 
● Inaccurate or incomplete data collection 
● Falsification of records 
● Failure to adhere to the protocol 
 
5.4.3 
Stopping Rules 
An independent Data Monitoring Committee (DMC) will meet to discuss data from the 
study approximately every six (6) months or at a frequency determined by the DMC and 
render their recommendation for either the continuation of the study or an amendment to 
the study.  A Sponsor Steering Committee (SSC), composed of senior executives not 
directly participating in this study, will make final decisions based on DMC 
recommendations. 

 
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5.5 
Treatments 
5.5.1 
Treatments Administered 
Study drug will be provided as a SC injection solution in pre-filled syringes containing 
adalimumab 40 mg/0.8 mL or adalimumab 20 mg/0.4 mL or in vials containing 
adalimumab 40 mg/0.8mL. 
Subjects who enroll into the study from blinded therapy in Study M06-806 will receive 
open-label therapy at a dose dependent on their body weight.  Subjects who weigh 
t 40 kg will receive 40 mg eow of adalimumab, while subjects who weigh < 40 kg will 
receive 20 mg eow of adalimumab.  Beginning from Week 8, subjects who have a disease 
flare may be switched to ew treatment at the same dose of adalimumab received while on 
eow treatment. 
Subjects who enroll into the study from open-label therapy in Study M06-806 will 
continue to receive the same dose they were receiving (i.e. 40 mg ew or 20 mg ew) at the 
Week 52 visit of the M06-806 study. 
Subjects who develop a flare while receiving ew open-label therapy or have a PCDAI 
score t 15 points when compared to their Baseline (Week 52 of M06-806) PCDAI score 
(regardless of study visit), may be discontinued from the study at the discretion of the 
Investigator. 
Beginning from Week 8, the dose of adalimumab may be increased to 40 mg, at the 
discretion of the investigator, for subjects whose body weight has increased from < 40 kg 
to t 40 kg from the study Baseline visit.  The site will enter the subject's body weight into 
the IVRS and the dose will be adjusted, if applicable. 
The dose of adalimumab may be decreased to the next lower treatment level as 
applicable, at the discretion of the Investigator and prior approval from the medical 
monitor, for subjects whose body weight has decreased from t 40 kg to < 40 kg from the 

 
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previous visit.  The site will enter the subject's body weight into the IVRS and the dose 
will be adjusted, if applicable. 
Subjects who responded to treatment defined as a) an improvement of at least 15 points 
in PCDAI compared to the last observation prior to dose escalation in patients who 
dose-escalated or b) an improvement of at least 15 points in PCDAI compared to 
Baseline of Study M06-806 in patients who did not dose-escalate) may have their dosage 
frequency decreased from ew to eow dosing.  The investigator should receive prior 
approval from the medical monitor before taking any action with regard to the dose 
frequency decrease.  At least 8 weeks after dose frequency decrease, subjects who still 
responded to treatment (as defined above) may have their dosage decreased (subjects who 
weigh ≥ 40 kg will receive 20 mg eow of adalimumab, while subjects who weigh < 40 kg 
will receive 10 mg eow of adalimumab).  The investigator should receive prior approval 
from the medical monitor before taking any action with regard to dose decrease. 
Subjects who experience a disease flare may re-increase their dosage or dose frequency 
to the next higher treatment level regardless of prior dose or dose frequency decrease.  
Simultaneous dose adjustment based on change of body weight as well as based on 
diseases status (response/flare) is prohibited. 
5.5.2 
Identity of Investigational Product 
The individual study drug information is presented in Table 3.  Pre-filled syringes (used 
for 40 mg/0.8 mL or 20 mg/0.4 mL doses) and 40 mg/0.8 mL vials (used for 10 mg dose) 
will be provided for this open-label clinical study. 

 
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Table 3.  
Identity of Investigational Products  
Study Drug 
Formulation 
Manufacturer 
Adalimumab 
40 mg/0.8 mL or 20 mg/0.4 mL  
Adalimumab/Mannitol, Citric acid monohydrate, Sodium citrate, 
Disodium phosphate dihydrate, Sodium dihydrogen phosphate 
dihydrate, Sodium chloride, Polysorbate 80, Water for injections, 
Sodium hydroxide added as necessary to adjust pH 
Abbott 
Adalimumab 
40 mg/0.8 mL (used for 10 mg dose) 
Adalimumab/Mannitol, Citric acid monohydrate, Sodium citrate, 
Disodium phosphate dihydrate, Sodium dihydrogen phosphate 
dihydrate, Sodium chloride, Polysorbate 80, Water for injections, 
Sodium hydroxide added as necessary to adjust pH 
Abbott 
 
5.5.2.1 
Packaging and Labeling 
The following information will appear on the pre-filled syringe, vial or carton labels: 
● Sponsor identification 
● Protocol number 
● Drug identification 
● Quantity of contents 
● Storage conditions 
● Dosing instructions 
● Kit number 
● Route of Administration 
● Excipients 
● Blank spaces to write the subjects identification number, initials, and date 
dispensed (as required) 
● Finishing lot # 
● Expiry Date (as required) 
 

 
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Two pre-filled syringes or vials will be provided in a dosing kit carton (see Table 4).  
Detailed instructions and training for the administration of study supplies are provided in 
Appendix Q. 
Table 4.  
Study Drug Packaging and Administration 
Open-label Pre-filled Syringes 
Open-label kit cartons containing two pre-filled 
syringes of adalimumab 40 mg/0.8 mL. 
Open-label kit cartons containing two pre-filled 
syringes of adalimumab 20 mg/0.4 mL. 
Open-label Vials (used for 10 mg dose) 
Open-label kit cartons containing two vials of adalimumab 40 mg/0.8 mL. 
 
5.5.2.2 
Storage and Disposition of Study Drug 
Pre-filled syringes and vials are to be stored protected from light at 2° to 8°C/36° to 46°F.  
DO NOT FREEZE.  A storage temperature log is to be maintained at the site to document 
proper storage conditions.  The refrigerator temperature must be recorded on every 
business day on a temperature log to record proper function.  Malfunctions must be 
reported to the sponsor immediately.  Study drug should be quarantined and not 
dispensed until Abbott GPRD or Abbott Temperature Excursion Management System 
(ATEMS) deems the medication as acceptable.  All clinical supplies must be stored and 
locked in a secure place until they are dispensed for subject use or are returned to Abbott 
Laboratories. 
Investigational products are for investigational use only, and are to be used only within 
the context of this study. 
5.5.3 
Method of Assigning Subjects to Treatment Groups 
This is an open-label study; all subjects will be receiving adalimumab. 
All subjects will be centrally registered using an IVRS.  The telephone number and 
call − in directions for the IVRS will be provided to each site.  Subjects will keep their 
study subject number from the previous study (M06 − 806). 

 
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Study drug will be administered at the study visits summarized in Table 1 and detailed in 
Section 5.3.1.1. 
5.5.4 
Selection and Timing of Dose for Each Subject 
Subjects who enroll into the study from blinded therapy in Study M06-806 will receive 
open-label therapy at a dose dependent on their body weight.  Subjects who weigh 
t 40 kg will receive 40 mg eow of adalimumab, while subjects who weigh < 40 kg will 
receive 20 mg eow of adalimumab.  Beginning from Week 8, subjects who have a disease 
flare may be switched to ew treatment at the same dose of adalimumab received while on 
eow treatment. 
Subjects who enroll into the study from open-label therapy in Study M06-806 will 
continue to receive the same dose they were receiving (i.e., 40 mg ew or 20 mg ew) at the 
Week 52 visit of the M06-806 study.  
Subjects who develop a flare while receiving ew open-label therapy or have a PCDAI 
score t 15 points when compared to their Baseline (the Week 52 visit of the M06-806 
study) PCDAI score (regardless of study visit), may be discontinued from the study at the 
discretion of the Investigator. 
The dose of adalimumab may be decreased to the next lower treatment level as applicable 
at the discretion of the Investigator and prior approval from the medical monitor, for 
subjects whose body weight has decreased from t 40 kg to < 40 kg from the previous 
visit.  The site will enter the subjects' body weight into the IVRS and the dose will be 
adjusted, if applicable. 
Subjects who responded to treatment defined as a) an improvement of at least 15 points 
in PCDAI compared to the last observation prior to dose escalation in patients who 
dose-escalated or b) an improvement of at least 15 points in PCDAI compared to 
Baseline of Study M06-806 in patients who did not dose-escalate) may have their dosage 
frequency decreased from ew to eow dosing.  The investigator should receive prior 
approval from the medical monitor before taking any action with regard to the dose 

 
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frequency decrease.  At least 8 weeks after dose frequency decrease, subjects who still 
responded to treatment (as defined above) may have their dosage decreased (subjects who 
weigh t 40 kg will receive 20 mg eow of adalimumab, while subjects who weigh < 40 kg 
will receive 10 mg eow of adalimumab).  The investigator should receive prior approval 
from the medical monitor before taking any action with regard to dose decrease. 
Subjects who experience a disease flare may re-increase their dosage or dose frequency 
to the next higher treatment level regardless of prior dose or dose frequency decrease.  
Simultaneous dose adjustment based on change of body weight as well as based on 
diseases status (response/flare) is prohibited. 
The Baseline Visit date for this study should be 364 ± 7 days from Baseline Visit date of 
M06-806 study.  All clinic visits for the subject should be scheduled on the same day as 
the Baseline visit for this study.  For home administration of drug, subjects will be 
instructed to inject study drug on the same day of the week as their Baseline visit day.  
Subjects must inject within a +/-3 day window of this day.  If the subject is out of the 
dosing window, the Medical Monitor should be contacted to determine the timing of the 
next dose.  The subject must record all dosing information on the subject dosing diary 
(Appendix P). 
5.5.5 
Blinding 
This is an open-label study. 
5.5.6 
Treatment Compliance 
The Investigator or his/her designated representatives will administer study drug only to 
subjects enrolled in the study.  
In order to document compliance with the treatment regimen, all pre-filled syringes and 
vials will be counted and documented in source documents and on the appropriate drug 
accountability form. 

 
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5.5.7 
Drug Accountability 
The Investigator or designee will verify that study drug supplies are received intact, at the 
appropriate temperature, and in the correct amounts from the drug depot.  This will be 
documented by signing and dating the Proof of Receipt (POR) or similar document.  The 
original POR or similar document will be kept in the site files as a record of what was 
received.  An accurate running inventory of study drug will be kept by the site, and will 
include the kit number, lot number(s), the number of pre-filled syringes or vials 
dispensed, and the date study drug was dispensed for each subject.  An overall 
accountability of the study drug will be performed and verified by the Clinical Research 
Associate (CRA) throughout the study and at the site close-out visit.  All unused 
pre-filled syringes and vials will be inventoried and returned to an identified vendor for 
disposal as designated by Abbott Laboratories.  A copy of the Drug Accountability Form, 
in accordance with instructions provided by the CRA, will also be included in the 
Returned Goods for disposal shipment.  A sample Drug Accountability Form is included 
in Appendix S.  A copy of the Drug Accountability Disposal Form, in accordance with 
instructions provided by the CRA, will also be included in the Pharmacy Binder provided 
to the site. 
All used (expelled) pre-filled syringes and vials will be inventoried by the site and 
verified by the CRA.  The used syringes and vials will be discarded on site, using 
appropriate biohazard precautions.  CRAs and site staff will complete study drug 
accountability via study drug logs, source documents, verification of empty used syringe 
kit or vials boxes, subject diaries and by visually counting the syringes in the sharps 
container whenever possible.  Used sharps containers should never be opened.  Each 
subject will be given their own sharps disposal container to store expelled/used syringes.  
Sharps containers should be returned by the subject at each visit, for accountability and 
compliance purposes.  New containers will be issued to subjects as necessary.  Once the 
CRA has verified drug accountability at the site, the site staff and CRA will sign off that 
the expelled pre-filled syringes and used vials have been destroyed. 

 
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5.6 
Discussion and Justification of Study Design 
5.6.1 
Discussion of Study Design and Choice of Control Groups 
The design of this clinical study was chosen to demonstrate adalimumab as an effective 
therapy for maintaining clinical response in pediatric subjects with CD and to gather 
long-term safety and tolerability data in this subject population. 
5.6.2 
Appropriateness of Measurements 
Standard statistical, clinical, and laboratory procedures will be utilized in this study.  All 
efficacy measurements in this study are standard for assessing disease activity in pediatric 
subjects with Crohns disease.  All clinical and laboratory procedures in this study are 
standard and generally accepted. 
5.6.3 
Suitability of Subject Population 
Pediatric subjects with CD who have participated in and successfully completed Protocol 
M06-806 through Week 52 and who meet all of the inclusion and none of the exclusion 
criteria are eligible for this study. 
5.6.4 
Selection of Doses in the Study 
The results of the pivotal adalimumab adult CD maintenance trial M02-404, in 
conjunction with results from adalimumab CD Study M02-433, support a maintenance 
dose of adalimumab 40 mg eow.  Data also suggest that patients who lose response to 
adalimumab at 40 mg eow can be dose-escalated to 40 mg weekly with the potential of 
regaining clinical response.  The proposed dosing regimen for Study M06-807 before 
Amendment 4 was developed using an analogous approach as that studied in the adult 
CD population.  Population pharmacokinetic modeling of serum adalimumab 
concentration data from pediatric subjects with JRA was used to identify doses to be 
evaluated in the current study in children with CD before Amendment 4.  A model based 
on the JRA population was chosen because the body weight range would closely parallel 
that in a juvenile CD population.  Escalation to weekly dosing would provide average 

 
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adalimumab concentrations at steady state about twice that observed with every other 
week dosing.  However, these concentrations are within the range of systemic exposures 
that were safely studied in adult subjects with CD. 
After completion of Study M06-806 and consideration of efficacy, safety and population 
pharmacokinetic results in conjunction with exposure-response modeling and simulation 
both the Low-Dose and High-Dose treatment provided evidence of efficacy and safety.  
Therefore, in order to minimize the systemic exposures to study drug to the lowest doses 
necessary in children with CD, Amendment 4 provides investigators with the option of 
dose de-escalation by reducing the dose or switching from ew to eow based on the 
clinical status of the individual patient.  In addition, since the 10 mg eow dose was 
efficacious in subjects weighing < 40 kg in Study M06-806 patients will have the option 
to be switched to this dose based on their body weight and clinical status at the discretion 
of the investigator. 
6.0 
Adverse Events 
The Investigator will monitor each subject for clinical and laboratory evidence of AEs on 
a routine basis throughout the study.  The Investigator will assess and record any AE in 
detail including the date of onset, description, severity, time course, duration and 
outcome, relationship of the AE to study drug, an event diagnosis, if known, and any 
action(s) taken.  For SAEs not considered "probably related" to study drug, the 
Investigator must provide another cause of event.  For AEs to be considered sporadic, the 
events must be of similar nature and severity.  AEs, whether in response to a query, 
observed by site personnel, or reported spontaneously by the subject will be recorded in 
source documentation and on the appropriate CRF page. 
All AEs will be followed to a satisfactory conclusion. 

 
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6.1 
Definitions 
6.1.1 
Adverse Event 
An AE is defined as any untoward medical occurrence in a patient or clinical 
investigation subject administered a pharmaceutical product and which does not 
necessarily have a causal relationship with this treatment.  An AE can therefore be any 
unfavorable and unintended sign (including an abnormal laboratory finding), symptom, 
or disease temporally associated with the use of a medicinal (investigational) product, 
whether or not the event is considered causally related to the use of the product. 
Such an event can result from use of the drug as stipulated in the protocol or labeling, as 
well as from accidental or intentional overdose, drug abuse, or drug withdrawal.  Any 
worsening of a pre-existing condition or illness is considered an AE.  Laboratory 
abnormalities and changes in vital signs are considered to be AEs only if they result in 
discontinuation from the study, necessitate therapeutic medical intervention, and/or if the 
Investigator considers them to be AEs. 
An elective surgery/procedure scheduled to occur during a study will not be considered 
an AE if the surgery/procedure is being performed for a pre-existing condition and the 
surgery/procedure has been pre-planned prior to study entry.  However, if the pre-existing 
condition deteriorates unexpectedly during the study (e.g., surgery performed earlier than 
planned), then the deterioration of the condition for which the elective surgery/procedure 
is being done will be considered an AE. 
6.1.2 
Serious Adverse Events 
If an AE meets any of the following criteria, it is to be reported to Abbott as an SAE 
within 24 hours of the site being made aware of the SAE.  Additionally, if follow-up 
information is received, it must also be reported to Abbott within 24 hours of being made 
aware of the information. 

 
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Death of Subject 
An event that results in the death of a subject. 
Life-Threatening 
An event that, in the opinion of the Investigator, will have resulted in 
immediate fatality if medical intervention had not been taken.  This does 
not include an event that will have been fatal if it had occurred in a more 
severe form. 
Hospitalization 
An event that results in an admission to the hospital for any length of 
time.  This does not include an emergency room visit or admission to an 
outpatient facility. 
Prolongation of 
Hospitalization 
An event that occurs while the study subject is hospitalized and prolongs 
the subjects hospital stay. 
Congenital Anomaly 
An anomaly detected at or after birth, or any anomaly that results in fetal 
loss. 
Persistent or Significant 
Disability/Incapacity 
An event that results in a condition that substantially interferes with the 
activities of daily living of a study subject.  Disability is not intended to 
include experiences of relatively minor medical significance such as 
headache, nausea, vomiting, diarrhea, influenza, and accidental trauma 
(e.g., sprained ankle). 
Important Medical Event 
Requiring Medical or 
Surgical Intervention to 
Prevent Serious Outcome 
An important medical event that may not be immediately life-threatening 
or result in death or hospitalization, but based on medical judgment may 
jeopardize the subject and may require medical or surgical intervention to 
prevent any of the outcomes listed above (i.e., death of subject, life 
threatening, hospitalization, prolongation of hospitalization, congenital 
anomaly, or persistent or significant disability/incapacity).  Examples of 
such events include allergic bronchospasm requiring intensive treatment 
in an emergency room or at home, blood dyscrasias or convulsions that do 
not result in inpatient hospitalization, or the development of drug 
dependency or drug abuse. 
Spontaneous Abortion 
Miscarriage experienced by study subject. 
Elective Abortion 
Elective abortion performed on study subject. 
 
6.2 
Adverse Event Severity 
The Investigator will use the following definitions to rate the severity of each AE: 
Mild 
The AE is transient and easily tolerated by the subject. 
Moderate 
The AE causes the subject discomfort and interrupts the subjects usual 
activities. 
Severe 
The AE causes considerable interference with the subjects usual activities 
and may be incapacitating or life threatening.   
 

 
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6.3 
Relationship to Study Drug 
The Investigator will use the following definitions to assess the relationship of the AE to 
the use of study drug:   
Probably Related 
An adverse event has a strong temporal relationship to study drug or 
recurs on re-challenge and an other cause of event is unlikely or 
significantly less likely. 
Possibly Related 
An AE has a strong temporal relationship to the study drug and an other 
cause of event is equally or less likely compared to the potential 
relationship to study drug. 
Probably Not Related 
An AE has little or no temporal relationship to the study drug and/or a 
more likely other cause of event exists. 
Not Related 
An AE is due to an underlying or concurrent illness or effect of another 
drug and is not related to the study drug (e.g., has no temporal 
relationship to study drug or has a much more likely other cause of event). 
 
If an Investigators opinion of possibly, probably not, or not related to study drug for an 
SAE is given, an alternative cause of the event must be provided by the Investigator for 
the SAE. 
6.4 
Adverse Event Collection Period 
All AEs reported from the time of informed consent until 5 half-lives (70 days), 
following discontinuation of study drug administration have elapsed will be collected, 
whether elicited or spontaneously reported by the subject.  In addition, SAEs will be 
collected from the time the subject or parent/legal guardian has signed the study-specific 
informed consent. 
Adverse event information will be collected as shown in Figure 3. 

 
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Figure 3.  
Adverse Event Collection 
SAEs and Non-serious AEs 
Elicited and/or Spontaneously Reported 
_ 
 
_ 
 
_ 
 
_ 
Consent 
Signed 
 
Study Drug 
Start 
 
Study Drug 
Stopped 
 
70 Days After 
Study Drug 
Stopped 
 
6.5 
Adverse Event Reporting 
In the event of an SAE, whether related to study drug or not, the investigator will notify 
one of the following people by faxing the appropriate SAE forms to one of the following 
people within 24 hours of the site being made aware of the SAE. 
For all sites: 
 
 
For questions regarding SAEs, please contact: 

 
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6.5.1 
Collection of Data Regarding Known Manifestations of the 
Disease Under Study 
Flare, of Crohns disease events per study definition, are not required to be captured as 
AEs, but may be captured per Investigator discretion.  Additionally, CD pre-existing 
conditions will not be captured as AEs unless the condition has worsened or is considered 
clinically significant in the opinion of the Investigator. 
6.6 
Pregnancy 
Abbott Laboratories must be notified within 1 working day of a sites learning if a female 
subject becomes pregnant during the study or within 150 days of receiving the last dose 
of study drug (see Section 6.5 for contact information). 
Females who become pregnant during the study will be discontinued from study drug as 
described in Section 5.4.  Data regarding the outcome of any pregnancy occurring in a 
study subject will be collected.  Upon notification of a pregnancy Abbott will forward a 
form to the site, for the Investigator to complete and send back to Abbott.  A second form 
will also be sent approximately 9 months from the date of notification to collect 
information on the outcome of the pregnancy.  This form will also need to be completed 
and sent back to Abbott. 
To monitor outcomes of pregnant women exposed to adalimumab, a pregnancy registry 
has been established for the United States, Canada and Puerto Rico.  Physicians in the 
United States are encouraged to register subjects by calling 
and/or 
provide this information to the subject. 
Pregnancy in a study subject is not considered an AE.  However, the medical outcome of 
an elective or a spontaneous abortion, stillbirth or congenital anomaly is considered a 
SAE, and must be reported to the sponsor with 24 hours of the site learning of the event. 

 
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7.0 
Protocol Deviations 
The investigator should not implement any deviation from the protocol without prior 
review and agreement by the Sponsor and in accordance with the IEC/IRB and local 
regulations, except when necessary to eliminate an immediate hazard to study subjects.  
When a deviation from the protocol is deemed necessary for an individual subject, the 
investigator must contact the following Abbott representative: 
 
For purposes of this protocol, reportable deviations are defined as:   
● Subject entered into the study even though they did not satisfy entry criteria 
● Subject who developed withdrawal criteria during the study and was not 
withdrawn 
● Subject who received wrong treatment or incorrect dose 
● Subject who received excluded concomitant treatment 
 
Such contact must be made as soon as possible to permit a review by Abbott to determine 
the impact of the deviation on the subject and/or the study.  Any significant protocol 
deviations affecting subject eligibility and/or safety must be reviewed and/or approved by 
the IEC/IRB and regulatory authorities, as applicable, prior to implementation. 

 
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8.0 
Statistical Methods and Determination of Sample 
Size 
8.1 
Statistical and Analytical Plans 
8.1.1 
Analyzable Population 
Efficacy analyses will be conducted in the intent-to-treat (ITT) population, which is 
defined as all subjects who received at least one dose of adalimumab in Study M06-807.  
The safety population consists of all subjects who received at least one dose of 
adalimumab in Study M06-807. 
8.1.2 
Planned Methods of Statistical Analysis 
All statistical analyses are to be performed descriptively.  Descriptive summary statistics 
will be provided for the demographic and baseline characteristics, efficacy, and safety 
parameters.  Continuous variables will be summarized using the number of observation, 
mean, standard deviation, 1st quartile, median, 3rd quartile, minimum, and maximum; 
whereas discrete variables will be summarized using count and percentages.  
8.1.2.1 
Demographics and Baseline Characteristics 
Summary statistics for the demographic and baseline characteristics will be computed 
based on the Week 52 values (from double-blind Study M06-806). 
8.1.2.2 
Efficacy Analysis 
Summary statistics will be provided for each visit, based on observed data.  An additional 
summary will be provided for the last visit, using the last observation carried forward 
(LOCF).  That is, the subjects last non-missing, post-baseline value (i.e., post-Week 52 
M06-806 double-blind value) will be carried forward to the last visit. 
8.1.3 
Other Analyses 
Efficacy will be analyzed for the following subgroups in the ITT population. 

 
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● Sex [Male, Female] 
● Age [< 13 years, t 13 years] 
● Ethnicity [White, Non-white] 
● Weight [< 40 kg, t 40 kg] 
● Prior infliximab use [No, Yes] 
● Baseline CRP [< 1.0 mg/dL, t 1.0 mg/dL] 
● Concomitant use of immunosuppressants and/or oral corticosteroids [No, Yes] 
 
8.1.4 
Safety Analyses 
Safety analyses will be based on the safety population.  Treatment-emergent AEs will be 
summarized.  An overview of treatment-emergent AEs including AEs of special interest, 
such as AEs leading to death and AEs leading to premature discontinuation, AEs by 
(MedDRA® version 10.0 or later) preferred term and system organ class, AEs by 
maximum relationship to study drug, and AEs by maximum severity will be summarized.  
Treatment-emergent AEs are defined as new events that begin either on or after the first 
dose of the study drug and within 70 days after the last dose of the study drug. 
Adverse events with missing or unknown severity will be categorized as severe.  Adverse 
events with missing or unknown relationship to study drug will be categorized as 
probably related. 
Adverse events that are reported more than 70 days after last study injection will be 
excluded from the summaries; however, all reported AEs will be included in the AE data 
listings. 
For laboratory parameters, the normal range of the analyzing laboratory will be used and 
all values outside the normal range will be flagged and listed.  Additionally, descriptive 
statistics for the mean change from baseline to minimum (smallest) value, maximum 
(largest) value and final value during the study will be calculated for the continuous 
clinical laboratory parameters.  

 
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Shift tables will be provided to cross-classify and tabulate subjects value from baseline to 
final value by the presence of clinically significant laboratory results.  Each subjects 
baseline value and final value will be flagged in reference to the normal range (low, 
normal, high) and also categorized as clinically non-significant (CTC grade < 3) or 
clinically significant (CTC grade t 3).  Further details will be provided in the SAP. 
8.1.4.1 
Pharmacokinetic Analyses 
Adalimumab trough serum concentrations will be summarized by treatment group at each 
time point using descriptive statistics including number of subjects, number of non 
missing observations (nnmiss), mean, median, standard deviation, coefficient of 
variation, minimum, and maximum.  The relationship between adalimumab 
concentrations and efficacy and/or safety variables may be explored.  Additional analysis 
may be performed. 
8.1.5 
Interim Analysis 
There will be one planned interim analysis.  Details of the analysis will be described in 
the study SAP. 
8.2 
Determination of Sample Size 
Subjects who successfully completed Study M06-806 through Week 52 may be eligible 
to participate in this study. It is expected that approximately 70% (130) of subjects from 
the M06-806 study will enroll in this study. 
8.3 
Randomization Methods 
All subjects will be centrally registered using an IVRS.  This is an open-label study; 
therefore, subjects will not be randomized before the study is initiated, the telephone 
number and call in directions for the IVRS will be provided to each site.  Subjects will 
keep their subject number from the previous study (M06-806). 

 
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9.0 
Ethics 
9.1 
Independent Ethics Committee (IEC) or Institutional Review 
Board (IRB) 
Good Clinical Practice (GCP) requires that the clinical protocol, any protocol 
amendments, the Investigators Brochure, the informed consent and all other forms of 
subject information related to the study (e.g., advertisements used to recruit subjects) and 
any other necessary documents be reviewed by an IEC/IRB.  IEC/IRB approval of the 
protocol, informed consent and subject information and/or advertising, as relevant, will 
be obtained prior to the authorization of drug shipment to a study site. 
Any amendments to the protocol will require IEC/IRB approval prior to implementation 
of any changes made to the study design.  A list of the documents required prior to 
initiation of the study can be found in Appendix C. 
Any SAEs that meet the reporting criteria, as dictated by local regulations, will be 
reported to both responsible Ethics Committees and Regulatory Agencies, as required by 
local regulations.  During the conduct of the study, the Investigator should promptly 
provide written reports (e.g., ICH Expedited Reports, and any additional reports required 
by local regulations) to the IEC/IRB of any changes that affect the conduct of the study 
and/or increase the risk to subjects, unless otherwise submitted by the sponsor.  Written 
documentation of the submission to the IEC/IRB should also be provided to Abbott. 
9.2 
Ethical Conduct of the Study 
The study will be conducted in accordance with the protocol, International Conference on 
Harmonization (ICH) guidelines, applicable regulations and guidelines governing clinical 
trial conduct, and the ethical principles that have their origin in the Declaration of 
Helsinki.  Responsibilities of the clinical Investigator are specified in Appendix D. 

 
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9.3 
Subject Information and Consent 
Prior to any study-related procedures or discontinuation of any medications for this study, 
the Investigator or his/her representative will explain the nature of the study to the subject 
of legal age (in the state of residence) or to the parent or legal guardian (as appropriate) 
of a subject who is not of legal age and answer all questions regarding this study.  
Subjects will be included in all discussions. 
The ICF will be reviewed, signed and dated by the subject of legal age (in the state of 
residence) or by the parent or legal guardian (as appropriate) of a subject who is not of 
legal age, and the person who administered the informed consent.  If a subject who was 
not of legal age at the onset of this study becomes of legal age during the course of the 
study, an informed consent will need to be obtained at that time.  Additionally, in keeping 
with each institutions IRB requirements an Informed Assent will also be obtained from 
the subject, as required.   
A copy of the signed ICF and Assent Form will be given to the subject and the subjects 
parent/legal guardian.  The original signed ICF and Assent Form will be placed in the 
subjects medical record.  An entry must also be made in the subjects dated source 
documents to confirm that informed consent was obtained prior to any study-related 
procedures and that the subject received a signed copy. 
If an updated informed consent is approved after a subject has completed or terminated 
early from the study, but is within the 70-day follow-up window, the subject will not be 
required to return to the site for the purposes of signing the updated ICF.  The subject of 
legal age, parent or legal guardian (as appropriate) should be contacted regarding any 
changes and the documentation of the contact should be present in the subjects source.  

 
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10.0 
Source Documents and Case Report Form 
Completion 
10.1 
Source Documents 
Source documents are defined as original documents, data and records.  This may include 
hospital records, clinical and office charts, laboratory data/information, subjects diaries or 
evaluation checklists, pharmacy dispensing and other records, recorded data from 
automated instruments, microfiches, photographic negatives, microfilm or magnetic 
media, and/or x-rays.  Data collected during this study must be recorded on the 
appropriate source documents. 
The Investigator(s)/institution(s) will permit study-related monitoring, audits, IEC/IRB 
review, and regulatory inspection(s), providing direct access to source data documents. 
The IMPACT III questionnaire and the WPAI questionnaire will be recorded directly on 
the CRF(s) by the subject, parent or legal guardian (as appropriate) and these CRFs will 
be considered source data. 
10.2 
Case Report Forms 
Case report forms will be supplied by Abbott.  These forms will be used to transmit 
information collected during the study to Abbott and regulatory authorities, as applicable.  
Case report forms must be completed for each subject enrolled in this study.  All case 
report forms must be legible and completed in indelible black ballpoint ink.  Any 
necessary corrections are to be made by drawing a single line through the incorrect entry 
and writing in the revision.  All revisions must be initialed and dated by the Investigator 
or his/her representative.  Data are not to be obliterated by blacking out, using correction 
fluid or by erasing the original entry.  If the reason for the correction is not obvious, a 
brief explanation (e.g., transcription error) should accompany the change.  All 
information written on the case report forms must also be reflected in the subject source 
documents with the exception of the case report forms discussed above in Section 10.1. 

 
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The Principal Investigator will review the case report forms for completeness and 
accuracy and sign and date each set of case report forms where indicated.  The case 
report forms will be reviewed periodically for completeness, legibility and acceptability 
by Abbott personnel (or their representatives).  Abbott (or their representatives) will be 
allowed access to all source documents in order to verify case report form entries. 
Once the original case report form has been removed from the site, all changes must be 
made via the appropriate change form specified by Abbott.  The Principal Investigator 
will review the change form for completeness and accuracy and sign and date the change 
form where indicated. 
11.0 
Data Quality Assurance 
Prior to the initiation of the study, an Investigators meeting will be held with Abbott 
personnel, the Investigators and their study coordinators, the CROs project manager and 
the CRAs for the study.  This meeting will include a detailed discussion of the protocol, 
performance of study procedures, CRF and Subject Diary completion, and specimen 
collection methods.  In addition to or instead of the Investigators meeting, the study 
personnel at each site may be trained on the study procedures by a CRA at a study 
initiation visit and will be given a CRF completion workbook for reference. 
The CRAs will monitor at each site throughout the study.  One hundred percent (100%) 
source document review will be performed against entries on the CRF and a quality 
assurance check will be performed to ensure that the Investigator is complying with the 
protocol and regulations.  In addition, after CRFs are retrieved by the CRA, a review of 
the data will be conducted by a physician and a clinical review team at Abbott 
Laboratories. 
All data hand entered in the database will be verified by a double-key entry procedure at 
Abbott.  Any discrepancies will be reviewed against the hard copy CRF and corrected 
on-line. After completion of the entry process, computer logic checks will be run to check 
for such items as inconsistent study dates and outlying laboratory values.  Any necessary 

 
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corrections will be made to the database and documented via addenda, queries, source 
data clarification form or audit trail.  A manual review of selected line listings will also 
be performed at the end of the study. 
Routine hematology, serum chemistry, and serology will be conducted using a central 
laboratory.  ESR analysis will be done at a local lab designated by the site. The data from 
these analyses will be electronically transferred from the central laboratory to the study 
database.  Urinalysis will be completed locally.  If a microscopic urinalysis is necessary, 
this testing will be conducted using the central laboratory.  A final review of all 
laboratory results will be conducted by a physician and clinical review team at 
Abbott Laboratories. 
Sites will provide Abbott (or designate) with laboratory certifications (CAP and CLIA), 
CV of local lab director, and reference ranges for each local lab used.  The full name, 
address, phone number, and fax number for each local lab will also be included. 
12.0 
Use of Information and Publication 
12.1 
Use of Information 
All information concerning adalimumab and Abbott Laboratories operations, such as 
Abbott Laboratories patent applications, formulas, manufacturing processes, basic 
scientific data, or formulation information, supplied by Abbott Laboratories and not 
previously published is considered confidential information. 
The information developed during the conduct of this clinical study is also considered 
confidential and will be used by Abbott Laboratories in connection with the development 
of adalimumab.  This information may be disclosed as deemed necessary by 
Abbott Laboratories to other clinical Investigators, other pharmaceutical companies, to 
the FDA, and to other government agencies.  To allow for the use of the information 
derived from this clinical study and to ensure complete and thorough analysis, the 
Investigator is obligated to provide Abbott Laboratories with complete test results and all 

 
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data developed in this study and to provide direct access to source data/documents for 
study- related monitoring, audits, IEC/IRB review, and regulatory inspection. 
This confidential information shall remain the sole property of Abbott Laboratories, shall 
not be disclosed to others without the written consent of Abbott Laboratories, and shall 
not be used except in the performance of this study. 
The Investigator will maintain a confidential subject identification code list of all subjects 
enrolled in the study (by name and subject number).  This list will be maintained at the 
site and will not be retrieved by Abbott. 
12.2 
Internet Sites 
Information regarding this study may be posted on various internet web sites and will 
maximally include study name, number, general population to be enrolled, entrance 
qualifications, brief description of the study, study objectives, doses, accruing 
Investigators (upon their approval) and number of subjects to be enrolled. 
13.0 
Completion of the Study 
The Investigator will conduct this study in compliance with the protocol, and will 
complete the study within the timeframe specified in the contract between the 
Investigator and Abbott.  Continuation of the study beyond this time must be mutually 
agreed upon in writing by both the Investigator and Abbott.  The Investigator will 
provide a summary of the study's outcome to the IEC/IRB following conclusion of the 
study, and will forward a copy of this summary to Abbott or their designee. 
Abbott may terminate this study prematurely, either in its entirety or at individual sites, 
for reasonable cause provided that written notice is submitted a reasonable time in 
advance of the intended termination.  The Investigator may also terminate the study at 
their site for reasonable cause, after providing written notice to Abbott a reasonable time 
in advance of the intended termination.  Advance notice is not required by either party if 
the study is stopped due to safety concerns.  If Abbott terminates the study for safety 

 
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reasons, it will immediately notify the Investigator by telephone and subsequently 
provide written instructions for study termination. 
Abbott will select the signatory Investigator from the Investigators who participate in the 
study.  Selection criteria for this Investigator will include level of participation as well as 
significant knowledge of the clinical research, investigational drug and study protocol.  
The signatory Investigator for the study will review and sign the final study report in 
accordance with the European Agency for the Evaluation of Medicinal Products (EMEA) 
Guidance on Investigators Signature for Study Reports. 
The Investigator will retain all essential documents until at least two years after the last 
approval of a marketing application in an ICH region and until there are no pending or 
contemplated marketing applications in an ICH region or at least two years have elapsed 
since the formal discontinuation of clinical development of the investigational product.  It 
is the responsibility of the sponsor to inform the Investigator/institution as to when these 
documents no longer need to be retained. 
The end-of-study is defined as the date of the last subjects last scheduled visit or the 
actual date of follow-up contact, whichever is longer. 
 

 
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14.0 
Investigators Agreement 
1. I have received and reviewed the Investigator Brochure for Humira. 
2. I have read this protocol and agree that the study is ethical. 
3. I agree to conduct the study as outlined and in accordance with all applicable 
regulations and guidelines. 
4. I agree to maintain the confidentiality of all information received or developed in 
connection with this protocol. 
 
 
 
 
Protocol Title: 
A Multi-center, Open-label Study of the Human Anti-TNF 
Monoclonal Antibody Adalimumab to Evaluate the Efficacy and the 
Long-term Safety and Tolerability of Repeated Administration of 
Adalimumab in Pediatric Subjects with Crohn's Disease Who Have 
Demonstrated a Clinical Response in the M06-806 Study 
Protocol Date: 
03 January 2012 
 
 
 
 
 
 
Signature of Principal Investigator 
 
Date 
 
 
 
Name of Principal Investigator (printed or typed) 
 
 
 
 

 
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15.0 
Reference List 
1. 
Hanauer SB, Sandborn W.  Management of Crohns disease in adults.  Am J 
Gastroenterol 2001;96:635-43. 
2. 
Loftus Jr. EV.  Clinical epidemiology of inflammatory bowel disease: Incidence, 
prevalence, and environmental influences.  Gastroenterology 2004;126:1504-17. 
3. 
Seidman EG.  Recent advances in the diagnosis and treatment of pediatric 
inflammatory bowel disease.  Curr Gastroenterol Rep 2000;2:248-52. 
4. 
Auvin S, Molinie F, Gower-Rousseau C, Brazier F, Merle V, Grandbastient B, 
et al.  Incidence, clinical presentation and location at diagnosis of pediatric 
inflammatory bowel disease: a prospective population-based study in northern 
France (1988-1999).  J Pediatr Gastroenterol Nutr 2005;41(1):49-55. 
5. 
Kugathasan S, Judd RH, Hoffmann RG, Heikenen J, Telega G, Khan F, et al.  
Epidemiologic and clinical characteristics of children with newly diagnosed 
inflammatory bowel disease in Wisconsin; a statewide population-based study.  
J Pediatr 2003;143(4):525-31. 
6. 
Cosgrove M, Al-Atia RF, Jenkins HR.  The epidemiology of pediatric 
inflammatory bowel disease.  Arch Dis Child 1996;74:460-1. 
7. 
Hassan K, Cowan FJ, Jenkins HR.  The incidence of childhood inflammatory 
bowel disease in Wales.  Eur J Pediatr 2000;159:261-3. 
8. 
Barton JR, Gillon S, Ferguson A.  Incidence of inflammatory bowel disease in 
Scottish children between 1968 and 1983; marginal fall in ulcerative colitis, three-
fold rise in Crohns Disease.  Gut 1989;30:618-22. 
9. 
Sawczenko A, Sandhu BK, Logan RFA, et al.  Prospective survey of childhood 
inflammatory bowel disease in the British Isles.  Lancet 2001;357:1093-4. 

 
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10. 
Olafsdottir EJ, Fluge G, Haug K.  Chronic inflammatory bowel disease in children 
in western Norway.  J Pediatr Gastroenterol Nutr 1989;8:454-8. 
11. 
Lindberg E, Lindquist B, Holmquist L, Hildebrand H.  Inflammatory bowel 
disease in children and adolescents in Sweden (1984-1995).  J Pediatr 
Gastroenterol Nutr 2000;30:259-64. 
12. 
Hildebrand H, Finkel Y, Grahnquist L, Lindholm J, Ekbom A, Askling J.  
Changing pattern of paediatric inflammatory bowel disease in northern Stockholm 
1990-2001. Gut 2003;52:1432. 
13. 
Heyman MB, Kirshner BS, Gold BD, Ferry G, Baldassano R, Cohen SA, et al.  
Children with early onset inflammatory bowel disease (IBD): analysis of a 
pediatric IBD consortium registry.  J Pediatr 2005;146(1):35-40. 
14. 
Lindberg E, Lindquist B, Holmquist L, Hildebrand H.  Inflammatory bowel 
disease in children and adolescents in Sweden, 1984-1995.  J Pediatr Gastroenterol 
Nutr 2000;30(3):259-64. 
15. 
Sawczenko A, Sandhu BK.  Presenting features of inflammatory bowel disease in 
Great Britain and Ireland.  Arch Dis Child 2003;88:995-1000. 
16. 
Griffiths AM.  Specificities of inflammatory bowel disease in childhood.  Best 
Pract Res Clin Gastroenterol 2004;18(3):509-23. 
17. 
Griffiths AM, Nguyen P, Smith C, MacMillan JH, Sherman PM.  Growth and 
clinical course of children with Crohns disease.  Gut 1993;34(7):939-43. 
18. 
Kanof ME, Lake AM, Bayless TM.  Decreased height velocity in children and 
adolescents before the diagnosis of Crohns disease.  Gastroenterology 
1988;95(6):1523-7. 
19. 
Markowitz J, Grancher K, Rosa J, Aiges H, Daum F.  Growth failure in pediatric 
inflammatory bowel disease.  J Pediatr Gastroenterol Nutr 1993;16(4):373-80. 

 
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20. 
Kleinman RE, Baldassano RN, Caplan A, Griffiths AM, Heyman MB, 
Issenman RM, et al.  Nutrition support for pediatric patients with inflammatory 
bowel disease: a clinical report of the North America Society for Pediatric 
Gastroenterology, Hepatology and Nutrition.  J Pediatr Gastroenterol Nutr 
2004;39(1):15-27. 
21. 
Gokhale R, Favus MJ, Karrison T, Sutton MM, Rich B, Kirshner BS.  Bone 
mineral density assessment in children with inflammatory bowel disease.  
Gastroenterology 1998;114:902-11. 
22. 
Boot AM, Bouquet J, Krennings EP, de Muinck Keizer-Schrama SMPF.  Bone 
mineral density and nutritional status in children with chronic inflammatory bowel 
disease.  Gut 1998;42:188-94. 
23. 
Ballinger AB, Savage MO, Sanderson IR.  Delayed puberty associated with 
Inflammatory bowel disease.  Pediatr Res 2003;53:205-10. 
24. 
Harpavat M, Greenspan SL, OBrien C, Chang C-C, Bowen A, Keljo DJ.  Altered 
bone mass in children at diagnosis of Crohns disease: a pilot study.  J Pediatr 
Gastroenterol Nutr 2005;40:295-300. 
25. 
Hyams JS, Wyzga N, Kreutzer DL, Justinich CJ, Gronowicz GA.  Alterations in 
bone metabolism in children with inflammatory bowel disease: an in vitro study. 
J Pediatr Gastroenterol Nutr 1997;24(3):289-95. 
26. 
Hanauer S, Lukas M, MacIntosh D, Rutgeerts P, Sandborn W, Pollack P.  A 
randomized, double-blind, placebo-controlled trial of the human anti-TNF-D 
monoclonal antibody adalimumab for the induction of remission in patients with 
moderate to severely active Crohns disease.  Gastroenterology 2004;127(1):332. 
27. 
Data on file at Abbott Laboratories. 
28. 
Abbott Study DE038, Data on file. 

 
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29. 
Humira® (adalimumab) [package insert].  North Chicago, IL:  
Abbott Laboratories:  June 2006. 
30. 
Present DH, Rutgeerts P, Targan S, Hanauer SB, Mayer L, van Hogezand RA, 
et al.  Infliximab for the treatment of fistulas in patients with Crohns disease. 
N Eng J Med.  1999;340(18):1398-405. 
31. 
Greulich and Pyle Radiographic Atlas of Skeletal Development of the Hand and 
Wrist:  June 1959. 
32. 
Centers for Disease Control and Prevention.  Targeted tuberculin testing and 
treatment of latent tuberculosis infection.  MMWR 2006 April. 
 

 
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Appendix A.  
List of Abbreviations and Definition of Terms 
Abbreviations 
AAA 
Anti-adalimumab antibody 
AE 
Adverse Event 
ALT 
Alanine Transaminase 
ANA 
Antinuclear antibody 
AST 
Aspartate transaminase 
BMI 
Body Mass Index 
BSAP 
Bone-specific alkaline phosphatase 
BUN 
Blood Urea Nitrogen 
CD 
Crohns disease 
CDC 
Center for Disease Control 
CNS 
Central Nervous Systems 
CRA 
Clinical Research Associate 
CRF 
Case Report Form 
CRP 
C-Reactive Protein 
CTC 
Common Toxicity Criteria 
DMC 
Data Monitoring Committee 
DNA 
Deoxyribonucleic acid 
dsDNA 
Double Stranded DNA 
eow 
Every other week 
ESR 
Erythrocyte sedimentation rate 
ET 
Early Termination 
EU 
European Union 
ew 
Every week 
FDA 
U.S. Food and Drug Administration 
GCP 
Good Clinical Practice 
HCT 
Hematocrit 
HIV 
Human immunodeficiency virus 
ICH 
International Conference on Harmonization 
IEC 
Independent Ethics Committee 
IgG1 
Immunoglobulin 
ICF 
Informed Consent Form 

 
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IRB 
Institutional Review Board 
ITT 
Intent-to Treat 
IVRS 
Interactive Voice Response System 
JRA 
Juvenile Rheumatoid Arthritis 
LOCF 
Last Observation Carried Forward 
MTX 
Methotrexate 
Ntx  
N − telopeptide 
OL 
Open-Label 
PCDAI 
Pediatric Crohns Disease Activity Index 
PK 
Pharmacokinetics 
POR 
Proof of Receipt 
RA 
Rheumatoid Arthritis 
SAE 
Serious Adverse Event 
SAP 
Statistical analysis plan 
SC 
Subcutaneous 
SSC 
Sponsor Steering Committee 
TB 
Tuberculosis 
TNF 
Tumor Necrosis Factor 
TPN 
Total Parenteral Nutrition 
US 
United States 
WPAI 
Work Productivity and Activity Impairment Questionnaire 
WPAI-CD 
Work Productivity and Activity Impairment Questionnaire: Crohns 
Disease 
 

 
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Appendix B.  
List of Protocol Signatories 
Name 
Title 
Functional Area 
Statistics 
Clinical 
Clinical 
Clinical 
 

 
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Appendix C.  
Documents Required Prior to Initiation of the Study 
As sponsor of a clinical study, Abbott has an obligation to ensure that the study will be 
conducted by a qualified investigator with sufficient resources (of time, personnel, and 
physical facilities) to conduct the study and to ensure that the investigator understands 
and agrees to comply with Good Clinical Practices and applicable regulations, policies, 
and procedures.  Prior to the beginning of any clinical study, the investigator will be 
asked to provide the following documentation.  
1. 
A signed and dated Investigators agreement page for the study. 
2. 
A signed and dated Form FDA 1572 certifying the investigators agreement to 
comply with the appropriate regulations governing the conduct of the study. 
 
A signed and dated Investigator Information and Agreement Form certifying the 
investigators agreement to comply with the appropriate (e.g., ICH GCP) 
regulations governing the conduct of the study. These will be required only for 
sites that are recruited under this amendment, or when existing sites update study 
documentation. 
3. 
 Current curriculum vitae for the investigator.  If subinvestigators will participate 
in the study, curriculum vitae for each. 
4. 
Requirements for the Independent Ethics Committee (IEC)/Institutional Review 
Board (IRB). 
● A copy of the signed and dated letter of approval of the IEC/IRB.  The letter 
must specify that both the protocol and informed consent form were approved 
(unless separate documentation that the informed consent was approved is 
provided). 
● A dated list containing the names and affiliations of the members of the 
IEC/IRB, or the institutions General Assurance Number. 

 
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● If the investigator and/or subinvestigator is a member of the IEC/IRB, a letter 
stating that he/she did not participate in the review or approval of the protocol 
or informed consent form. 
5. 
A specimen copy of the IEC/IRB-approved informed consent document to be used 
in the study. 
6. 
A list of reference ranges of values for all laboratory tests specified by the protocol 
for all laboratories utilized. 
7. 
A copy of the laboratory(ies) certification(s) or the authorization number of the 
certification(s), the name of the certifying authority, and the period of certification. 
8. 
Financial Disclosure Certification forms must be completed by each investigator 
and all subinvestigators identified on the Form FDA 1572 or Investigator 
Information and Agreement Form.  A Financial Disclosure, EU Consent, is 
required to be completed for each investigator and/or subinvestigator who is a 
resident of the European Union 
 

 
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Appendix D.  
Responsibilities of the Clinical Investigator 
Clinical research studies sponsored by Abbott are subject to the regulations of the U.S. 
Food and Drug Administration (FDA).  The responsibilities imposed upon Investigators 
by the FDA are summarized in the "Statement of Investigator" (Form FDA 1572), which 
is a form letter addressed to the sponsor (Abbott), summarizing the Investigators 
qualifications for the study and his/her willingness to follow FDA regulations with 
respect to the study. 
In signing a Form FDA 1572, the Investigator agrees to assume the following 
responsibilities:   
1. 
To conduct the study(ies) in accordance with the relevant, current protocol(s) and 
only make changes in a protocol after notifying Abbott, except when necessary to 
protect the safety, rights, or welfare of subjects. 
2. 
To personally conduct or supervise the described investigation(s). 
3. 
To inform any subjects, or any persons used as controls, that the drugs are being 
used for investigational purposes and to ensure that the requirements relating to 
obtaining informed consent in 21 CFR Part 50 and Independent Ethics Committee 
(IEC)/Institutional Review Board (IRB) review and approval in 21 CFR Part 56 
are met. 
4. 
To report to Abbott adverse experiences that occur in the course of the 
investigation(s) in accordance with 21 CFR 312.64. 
5. 
To read and understand the information in the Investigators Brochure, including 
the potential risks and side effects of the drug. 
6. 
To ensure that all associates, colleagues, and employees assisting in the conduct of 
the study(ies) are informed about their obligations in meeting the above 
commitments. 

 
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7. 
To maintain adequate and accurate records of the conduct of the study and make 
those records available for inspection by representatives of Abbott, the IEC/IRB 
and/or the appropriate regulatory agency, and to retain all study-related documents 
until notification from Abbott.  The Investigator must notify Abbott when they are 
no longer able to retain the study related documents. 
8. 
To ensure that an IEC/IRB that complies with the requirements of 21 CFR Part 56 
will be responsible for the initial and continuing review and approval of the 
clinical investigation. 
9. 
To promptly report to the IEC/IRB all changes in the research activity and all 
unanticipated problems involving risks to human subjects or others (including 
submission of any Expedited Safety Reports received from Abbott to the 
IEC/IRB), and to make no changes in the research without IEC/IRB approval, 
except where necessary to eliminate apparent immediate hazards to human 
subjects. 
10. 
To comply with all other requirements regarding the obligations of clinical 
Investigators and all other pertinent requirements in 21 CFR Part 312. 
 

 
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Appendix E.  
CDC Treatment of Tuberculosis Infection (Preventive Therapy) 
Centers for Disease Control and Prevention 
Tuberculosis Information 
Treatment of Tuberculosis Infection (Preventive Therapy), Latent Tuberculosis 
Infection (LBTI)32 
 
 

 
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Appendix F.  
Non-Drug Materials Provided to the Study Site(s) 
Study sites will receive the following supplies prior to or during the study: 
Tote Bags 
Cooler 
Sharps Containers 
Ice Packs 
CDAI subject diary 
Dosing Diaries 
Subject Medication Log 
Self Injection Instructions 
Dosing syringes, as applicable 

 
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Appendix G.  
Pediatric Crohns Disease Activity Index (PCDAI) 
1. Abdominal pain rating 
 
- None 
 
- Mild - Brief, does not interfere with activities 
 
- Moderate/severe-Daily, longer lasting, affects activities, nocturnal 
 
= 0 p 
= 5 p 
= 10 p 
Score 
2. Stools (per day) 
 
- 0–1 liquid stools, no blood 
 
- Up to 2 semi-formed with small blood, or 2–5 liquid 
 
- Gross bleeding, or t 6 liquid, or nocturnal diarrhea 
 
= 0 p 
= 5 p 
= 10 p 
 
3. Patient Functioning, General Well-Being 
 
- No limitation of activities, well 
 
- Occasional difficulty in maintaining age appropriate activities, below par 
 
- Frequent limitation of activity, very poor 
 
= 0 p 
= 5 p 
= 10 p 
 
LABORATORY 
Score 
4. HCT: Male and female  d 10 years: 
 
 
t 33 
= 0 p 
 
 
28-32 
= 2.5 p 
 
 
< 28 
= 5 p 
 
Male 11–14 years: 
 
 
t35 
= 0 p 
 
 
30-34 
= 2.5 p 
 
 
<30 
= 5 p 
 
 
Female 11–19 years: t 34 
= 0 p 
 
 
29-33 
= 2.5 p 
 
 
< 29 
= 5 p 
 
Male 15–19 years: 
t37 
= 0 p 
 
 
32-36 
= 2.5 p 
 
 
<32 
= 5 p 
 
5. 
ESR (mm/hr) 
< 20 
= 0 p 
 
 
20-50 
= 2.5 p 
 
 
> 50 
= 5 p 
 
6. 
Albumin (g/dL) 
t 3.5 
= 0 p 
 
 
3.1-3.4 
= 5 p 
 
 
d 3.0 
= 10 p 
 

 
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EXAMINATION 
Score 
7. 
Weight 
- Weight gain or voluntary weight stable/loss 
 
 
- Involuntary weight stable, weight loss 1–9% 
 
 
- Weight loss t 10% 
= 0 p 
= 5 p 
= 10 p 
 
8. 
Height 
 
 
 
 
 
 
 
 
Height velocity t -1SD 
 
 
 
Height velocity < -1SD, > -2SD 
 
 
 
Height velocity d -2SD 
 
= 0 p 
= 5 p 
= 10 p 
 
9. 
Abdomen 
- No tenderness, no mass 
 
 
- Tenderness, or mass without tenderness 
 
 
- Tenderness, involuntary guarding, definite mass 
= 0 p 
= 5 p 
= 10 p 
 
10. Perirectal disease 
- None, asymptomatic tags 
 
 
- 1–2 indolent fistula, scant drainage, no tenderness 
 
 
- Active fistula, drainage, tenderness, or abscess 
= 0 p 
= 5 p 
= 10 p 
 
11. Extra-intestinal Manifestations 
 
(Fever t 38.5 for 3 days over past week, definite arthritis, uveitis, E. nodosum, 
P. gangrenosum) 
 
- None 
 
- One 
 
- t Two 
 
 
= 0 p 
= 5 p 
= 10 p 
 
TOTAL SCORE  
Pediatric Crohns Disease Activity Index (PCDAI) 
 
 

 
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Appendix H.  
PCDAI Users Guide and Guideline for Reference Weight and 
Reference Height 
This guide is intended to help nurse coordinators and physicians complete the PCDAI in 
order to assess disease activity in children with Crohns disease participating in clinical 
trials. 
History 
All calculations are based upon a one-week (7 day) history recall of symptoms.  The 
history recall should be solicited from the subject and/or caregiver. 
Item 1.  Abdominal pain 
The descriptions in the PCDAI of "mild" and "moderate/severe" should be used to guide 
in scoring the pain. Note that duration, effect on activities, and nocturnal occurrence 
separate moderate/severe from mild.  If pain varies in severity during the week, subject 
should be scored according to the most severe pain. However, mild pain should be 
present on at least two days to score 5 points rather than 0 points. 
Item 2.  Stools 
The intent is to score the stool pattern during the preceding week. 
To facilitate scoring, first categorize the subject as having blood in the stool or not. 
If there is no blood in the stool, score as follows:   
Formed stools or up to 1 loose stool daily = 0 
2-5 liquid or very loose stools on 1 or more days = 5 
6 or more liquid or very loose stools on 1 or more days or any nocturnal diarrhea = 10 

 
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If blood is present in the stool on any day during the past week, score as follows:   
Small amounts of blood in stool (on toilet paper or small spots in stool, etc.) = 5 
Any gross bleeding (large amounts on stool or colors the water in the toilet, etc.) = 10 
Item 3.  Subject functioning, general well-being 
If there is variation during the week, subject should be scored according to the most 
significant limitation of activity, even if it occurs during only one day of the week, as 
long as it is likely due to Crohns disease and not to an intercurrent illness. 
Item 4.  Hematocrit 
Hematocrit values should be rounded to a whole number prior to completing the 
calculation.   Numbers that fall between the range of 0.1-0.4 must be rounded down.   
Numbers that fall between the range of 0.5-0.9 must be rounded up. 
Physical Examination 
Item 7.  Weight (The intent is to assess the ability to normally maintain or gain weight) 
Reference weight to be used for calculation of weight gain/loss during the study: 
From Baseline to Week 264: use weight from previous visit 
Voluntary weight stable/loss means subject maintaining or losing weight on purpose. 
Involuntary weight stable means subject wants to gain weight but cannot. 
To calculate percentage weight loss use formula:   
Weight from previous visit – Current weight X 100 = % weight loss 
 
Weight from previous visit 

 
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Item 8.  Height 
Reference height for calculation of height velocity 
● From Baseline to Week 24, use height from 6 months prior to Baseline 
● From Week 24 to Week 48, use height from Baseline visit 
● From Week 48 to Week 72, use height from Week 24 
● From Week 72 to Week 96, use height from Week 48 
● From Week 96 to Week 120, use height from Week 72 
● From Week 120 to Week 144, use height from Week 96 
● From Week 144 to Week 168, use height from Week 120 
● From Week 168 to Week 192, use height from Week 144 
● From Week 192 to Week 216, use height from Week 168 
● From Week 216 to Week 240, use height from Week 192 
● From Week 240 to Week 264, use height from Week 216 
 
The intent is to assess the normalcy vs. impairment of the subjects recent linear growth.  
Note that post-pubertal subjects will score 0 points.  For subjects still growing, there are 
two options for scoring.  Method (a) is preferred.  Method (b) to be used if data required 
for (a) are unavailable. 
1. 
Height velocity (cm/year), the most sensitive parameter, should be calculated as 
below: 
Present height –  Appropriate height measurement (from above)  x  12  = Height velocity (cm/year) 
  
        Interval (months) between heights 
Using height velocity chart below, determine centile for height velocity. 

 
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2. 
Scoring for the PCDAI:   
a. Velocity less than "Minus 2 SD" scores 10 points. 
b. Velocity between "Minus 2 SD" and "Minus 1 SD" scores 5 points. 
c. Velocity greater than "Minus 1 SD" scores zero points. 
 
* 
Please note that subjects should score zero points if a subject is a female above 14.5 years of age or a 
male above 17.5 years of age. 
 

 
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Height Velocity Reference Values for Calculating the PCDAI (Males) 
 
Height Velocity in cm per year (Males) 
Age (years) 
Minus 2SD 
Minus 1SD 
Mean 
2.5 
5.7 
7.0 
8.3 
3 
5.4 
6.6 
7.8 
3.5 
5.1 
6.3 
7.4 
4 
4.9 
6.0 
7.1 
4.5 
4.7 
5.8 
6.8 
5 
4.6 
5.6 
6.6 
5.5 
4.5 
5.4 
6.4 
6 
4.3 
5.3 
6.2 
6.5 
4.2 
5.1 
6.0 
7 
4.2 
5.0 
5.9 
7.5 
4.1 
4.9 
5.8 
8 
3.9 
4.8 
5.6 
8.5 
3.8 
4.6 
5.4 
9 
3.8 
4.5 
5.3 
9.5 
3.7 
4.5 
5.2 
10 
3.7 
4.4 
5.1 
10.5 
3.7 
4.4 
5.1 
11 
3.7 
4.4 
5.2 
11.5 
3.8 
4.6 
5.3 
12 
4.0 
4.9 
5.7 
12.5 
4.8 
5.8 
6.7 
13 
6.2 
7.4 
8.6 
13.5 
7.1 
8.3 
9.5 
14 
6.1 
7.2 
8.4 
14.5 
4.1 
5.3 
6.5 
15 
2.4 
3.6 
4.7 
15.5 
1.2 
2.3 
3.3 
16 
0.4 
1.3 
2.2 
16.5 
0.1 
0.7 
1.5 
17 
0.1 
0.4 
0.9 
17.5 
0.1 
0.1 
0.5 
 

 
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Height Velocity Reference Values for Calculating the PCDAI (Females) 
 
Height Velocity in cm per year (Females) 
Age (years) 
Minus 2SD 
Minus 1SD 
Mean 
2.5 
5.9 
7.3 
8.6 
3 
5.5 
6.9 
8.1 
3.5 
5.2 
6.4 
7.6 
4 
4.9 
6.1 
7.2 
4.5 
4.7 
5.8 
6.8 
5 
4.6 
5.6 
6.6 
5.5 
4.5 
5.5 
6.4 
6 
4.4 
5.3 
6.2 
6.5 
4.3 
5.2 
6.1 
7 
4.3 
5.2 
6.0 
7.5 
4.3 
5.1 
5.9 
8 
4.2 
5.0 
5.8 
8.5 
4.2 
4.9 
5.7 
9 
4.2 
5.0 
5.8 
9.5 
4.3 
5.0 
5.8 
10 
4.4 
5.3 
6.2 
10.5 
4.7 
5.7 
6.8 
11 
5.7 
6.6 
7.7 
11.5 
6.1 
7.2 
8.3 
12 
5.2 
6.3 
7.3 
12.5 
3.6 
4.8 
5.9 
13 
2.4 
3.3 
4.3 
13.5 
1.3 
2.2 
2.9 
14 
0.4 
1.1 
1.8 
14.5 
0.0 
0.5 
1.0 
 

 
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Appendix I.  
Crohns Disease Activity Index (CDAI) 
 
 
 
Factor 
Subtotal 
1. Number of liquid or very soft stools
(Record the frequency per day) 
         __+___+___+___+___+___+___=___ 
Days: 1     2      3      4 
5      6 
  7   Sum 
X 
2 
 
2.  Abdominal pain rating: 
0=none, 1=mild, 2=moderate, 
3=severe 
          __+___+___+___+___+___+___=___ 
Days: 1     2      3      4 
5      6 
  7   Sum 
X 
5 
 
3. General well-being: 
0=generally well, 1=slightly 
underpar, 2=poor, 3=very poor, 
4=terrible 
         __+___+___+___+___+___+___=___ 
Days: 1     2      3      4 
5      6 
  7   Sum 
X 
7 
 
4. Number of 6 listed categories the 
subject now has: 
Check all items that apply: 
□  Arthritis/arthralgia 
□  Iritis/uveitis 
□  Erythema nodosum/  
 pyoderma gangrenosum/ 
 aphthous stomatitis 
□  Fissure, abscess and/or anal 
fistula (draining/non-draining) 
□  Other cutaneous fistula 
(draining/non-draining) fistula 
□  Fever over 100°F (37.8°C) during 
past week 
 
 
 
 
 
 
  
________ 
 
 
 
Record "0" if no categories checked 
X 
20 
 
5.   Taking Lomotil / Imodium / 
Loperamide /opiates for diarrhea  
0=no, 1=yes 
________ X 
30 
 
6.   Abdominal mass 
0=none, 2=questionable, 5=defined 
________ X 
10 
 
7.   Hematocrit: ______ 
Male: 
(47 - hematocrit) = 
Female: (42 - hematocrit) = Subtotal ______ 
If hematocrit > normal, enter "0" 
X 
6 
 
8.   Body weight: __  __  __ . __ (kg) 
Ideal weight for height: 
__  __  __ . __ (kg) 
100 x [1 - (Body wt/Ideal wt)] =  
Percent below ideal weight: ______ 
If body wt > ideal wt, enter "0" 
X 
1 
 
 
 
 
Total 
 
* 
Ideal weight is obtained from CDC growth charts.  The subtotal of box 8 should be rounded to a whole number.  
Numbers that fall between the range of .1-.4 must be rounded down.   Numbers that fall between the range of .5-.9 
must be rounded up.  To ensure consistency across all sites and to take into account the varying growth rates of 
subjects in this study, the IBW should be calculated at each visit. 
* 
Hematocrit values should be rounded to a whole number prior to completing the calculation in box 7 of the CDAI.   
Numbers that fall between the range of .1-.4 must be rounded down.   Numbers that fall between the range of .5-.9 
must be rounded up. 

 
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Appendix J.  
Subject CDAI Diary 
Crohns Disease Activity Index 
Subject Diary Card 
Enter all values legibly using a black 
ballpoint pen. 
Add item requested for each day. 
Day 
Date___ 
Day 
Date___ 
Day 
Date___ 
Day 
Date___ 
Day 
Date___ 
Day 
Date___ 
Day 
Date___ 
Number (total) of liquid or very soft 
stools per day. 
 
 
 
 
 
 
 
Daily abdominal pain rating. 
(0=none, 1=mild, 2=moderate, 3=severe) 
 
 
 
 
 
 
 
Daily rating of general well being. 
(0=well, 1=slightly below par, 2=poor, 
3=very poor, 4=terrible) 
 
 
 
 
 
 
 
Subject Initials:___________ 
Subjects Signature:__________________________ 
 
Investigator or Designees Signature:______________________ 

 
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Question 1. 
How much has your stomach been hurting you in the past two weeks? 
□ 
□ 
□ 
□ 
□ 
Not at all 
 Hardly hurting 
at all 
Hurting 
somewhat  
Hurting 
quite a bit 
Hurting 
very much 
 
Question 2.  
Taking medicines or tablets bothers you 
□ 
□ 
□ 
□ 
□ 
Not at all 
 Hardly bothers 
at all 
Bothers 
somewhat  
Bothers  
quite a bit 
Bothers 
very much 
 
Question 3. 
How often has your inflammatory bowel disease prevented you from 
eating what you want in the past two weeks? 
□ 
□ 
□ 
□ 
□ 
Never 
 Rarely 
Sometimes 
Often 
Very often 
 
Question 4. 
How often have you been worrying about having a flare-up (increase of 
symptoms) in the last two weeks? 
□ 
□ 
□ 
□ 
□ 
Never 
 Rarely 
Sometimes 
Often 
Very often 
 
Question 5. 
How much does it bother you that you have an illness that does not just go 
away? 
□ 
□ 
□ 
□ 
□ 
Not at all 
 Hardly bothers 
at all 
Bothers 
somewhat  
Bothers quite a 
bit 
Bothers very 
much 
 
Question 6. 
How much energy did you have during the past two weeks? 
□ 
□ 
□ 
□ 
□ 
Very much 
energy 
Quite a bit of 
energy 
Some energy 
 A little energy 
No energy at 
all  

 
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Question 7. 
How do you feel about your weight? 
□ 
□ 
□ 
□ 
□ 
I feel great 
about my 
weight 
I feel good 
about my 
weight 
I dont feel 
good or bad 
about my 
weight 
I feel bad about 
my weight 
I feel awful 
about my 
weight 
 
Question 8. 
How has your inflammatory bowel disease affected your family? 
□ 
□ 
□ 
□ 
□ 
The effect has 
been great 
The effect has 
been good 
It has not 
affected our 
family 
The effect has 
been bad 
The effect has 
been awful 
 
Question 9. 
How often did you have to miss out on certain things (hobbies, play, 
parties) because of your inflammatory bowel disease in the past two weeks? 
□ 
□ 
□ 
□ 
□ 
Never 
Rarely 
Sometimes 
Often 
Very often 
 
Question 10. How often have you been bothered by diarrhea (loose or frequent bowel 
movements) in the past two weeks? 
□ 
□ 
□ 
□ 
□ 
Never 
Rarely 
Sometimes 
Often 
Very often 
 
Question 11. How often do you worry about health problems you might have in the 
future? 
□ 
□ 
□ 
□ 
□ 
Never 
Rarely 
Sometimes 
Often 
Very often 
 

 
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Question 12. How often do you think it is unfair that you have inflammatory bowel 
disease? 
□ 
□ 
□ 
□ 
□ 
Never 
Rarely 
Sometimes 
Often 
Very often 
 
Question 13. During the past two weeks, were you ever angry that you have 
inflammatory bowel disease? 
□ 
□ 
□ 
□ 
□ 
Never 
Rarely 
Sometimes 
Often 
Very often 
 
Question 14. Do you think too many rules or limits are placed on you because of your 
inflammatory bowel disease? 
□ 
□ 
□ 
□ 
□ 
Never 
Rarely 
Sometimes 
Often 
Very often 
 
Question 15. How do you feel about the way you look? 
□ 
□ 
□ 
□ 
□ 
I think I look 
great 
I think I look 
good 
I dont think I 
look good or 
bad 
I think I look 
bad 
I think I look 
awful 
 
Question 16. Are you embarrassed because of your bowel condition? 
□ 
□ 
□ 
□ 
□ 
Not at all 
 Hardly 
embarrassed at 
all 
Embarrassed 
somewhat  
Embarrassed 
quite a bit 
Embarrassed 
very much 
 
Question 17. Did you have fun during the past two weeks? 
□ 
□ 
□ 
□ 
□ 
Very often 
Often 
Sometimes 
Rarely 
Never 

 
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Question 18. Is it harder to make friends because of your inflammatory bowel disease? 
□ 
□ 
□ 
□ 
□ 
Not at all 
harder 
 A little harder 
Quite a bit 
harder 
Much harder 
Very much 
harder 
 
Question 19.  How often do you worry about your stool (bowel movement) containing 
blood? 
□ 
□ 
□ 
□ 
□ 
Never 
Rarely 
Sometimes 
Often 
Very often 
 
Question 20. Are you worried you cannot go out on a date or have a boyfriend or 
girlfriend because of your inflammatory bowel disease? 
□ 
□ 
□ 
□ 
□ 
Not at all 
worried 
 Hardly 
worried at all 
Worried 
somewhat  
Worried quite a 
bit 
Worried very 
much 
 
Question 21. How often did you feel sick to your stomach in the past two weeks? 
□ 
□ 
□ 
□ 
□ 
Never 
Rarely 
Sometimes 
Often 
Very often 
 
Question 22. How do you feel about the tests you have to go through? 
□ 
□ 
□ 
□ 
□ 
I do not mind 
them at all 
I mind them a 
tiny bit 
I mind them a 
little 
I mind them a 
lot 
I hate them 
 
Question 23. Do other children bully you or leave you out of things because of your 
inflammatory bowel disease or its treatment? 
□ 
□ 
□ 
□ 
□ 
Never 
Rarely 
Sometimes 
Often 
Very often 

 
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Question 24. How often do you worry about having an operation? 
□ 
□ 
□ 
□ 
□ 
Never 
Rarely 
Sometimes 
Often 
Very often 
 
Question 25. In the past two weeks how often were you afraid you may have an 
accident or not get to the toilet in time? 
□ 
□ 
□ 
□ 
□ 
Never 
Rarely 
Sometimes 
Often 
Very often 
 
Question 26. Do you try to keep your inflammatory bowel disease a secret from other 
people? 
□ 
□ 
□ 
□ 
□ 
No, I do not try 
at all 
I dont try much I try a little 
I try hard 
Yes, I try very 
hard 
 
Question 27. Does your inflammatory bowel disease make it difficult to travel or go on 
a holiday? 
□ 
□ 
□ 
□ 
□ 
No, not 
difficult 
A little difficult
Quite difficult 
Very difficult 
Yes, extremely 
difficult 
 
Question 28.  How did you feel during the past two weeks? 
□ 
□ 
□ 
□ 
□ 
Great 
Good 
Not good or 
bad 
Bad  
Awful 
 
Question 29. Are you happy with your life? 
□ 
□ 
□ 
□ 
□ 
Yes, very 
happy 
Happy 
Not happy or 
unhappy 
Unhappy 
Very unhappy 

 
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Question 30. Do you feel there is someone you can talk to about your inflammatory 
bowel disease? 
□ 
□ 
□ 
□ 
□ 
Always  
Often  
Sometimes  
Rarely 
Never 
 
Question 31. How often did you have to pass gas in the past two weeks? 
□ 
□ 
□ 
□ 
□ 
Never 
Rarely 
Sometimes 
Often 
Very often 
 
Question 32. How tired have you felt in the past two weeks? 
□ 
□ 
□ 
□ 
□ 
Not at all tired 
 A little tired 
Quite tired 
Tired  
Very tired 
 
Question 33. How do you feel about your height? 
□ 
□ 
□ 
□ 
□ 
I feel great 
about my 
height 
I feel good 
about my 
height 
I dont feel 
good or bad 
about my 
height 
I feel bad about 
my height 
I feel awful 
about my 
height 
 
Question 34. Does your inflammatory bowel disease get in the way of playing sports the 
way you would like to? 
□ 
□ 
□ 
□ 
□ 
Never 
Rarely 
Sometimes 
Often 
Always 
 
Question 35. In the past two weeks how often were you able to go to school? (If you are 
in the middle of a school break or the summer holidays, answer as if school was on) 
□ 
□ 
□ 
□ 
□ 
Always  
Most days  
Half the days 
A few days 
Never 
 

 
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End of questionnaire 
This completes the questionnaire. Do you have anything else to add which you feel is 
important about having inflammatory bowel disease, or do you have any other 
remarks? Please write them below. 
 
_________________________________________________________ 
_________________________________________________________ 
_________________________________________________________ 

 
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Appendix L.  
Excluded Medications 
Cyclosporine 
Tacrolimus 
Therapeutic enemas and suppositories (not including those done in conjunction with 
routine colonoscopy) 
Live vaccines 
The combination of budesonide and prednisone (or equivalent) 
Infliximab 
Mycophenolate mofetil (MMF or CellCept® ) 
Growth Hormone 
Kineret® (anakinra) 
Tysabri (natalizumab) 
Orencia (abatacept) 
Concurrent biologic therapy 
Any investigational agent 
Any previous anti-TNF medication except infliximab before the M06-806 study 
(including adalimumab). 
 

 
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Appendix M.  
Day 70 Phone Call 
Site Name / Number: ________ 
Subject Number:________ 
Subject Initials:________ 
Please contact all Subjects 70 days following drug discontinuation. 
 
 
 
Date of Call: ____________ 
 
 
□     Lost to Follow-Up (Please check this box if subject was not willing to provide any follow-up 
information or you were unable to speak to the subject following at least one attempt). 
 
 
□      No Events Reported 
 
List any Adverse Events (AE) and/or Serious Adverse Events (SAE) that occurred since the subject was 
last seen in clinic for this study.  Please document all adverse events on a 500 AE CRF to be submitted to 
data management.  (Please report all SAEs to Abbott within 24 hours of being made aware of the event.  
Follow-up information must also be reported within 24 hours of being made aware of the information.). 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
If events are listed above, your monitor will review and retrieve the appropriate CRF pages during 
their next visit.  Please fax this form to Paragon at 
 
 

 
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Appendix N.  
Unscheduled Outpatient Visits, Emergency Room Visits and 
Hospitalizations 
1. 
Since the last study visit has the subject had any physician/health care visits for 
their Crohns disease other than the protocol required visits? 
Yes ___ 
No  ___ 
If yes provide the following: 
I. 
Since the last visit, has the subject been seen by a physician for their Crohns 
Disease? 
YES:_____ 
NO:_____ 
If YES, how many times:_______ 
 
 
II. Since the last visit, has the subject been seen in the Emergency Room for their 
Crohns Disease? 
YES:_____ 
NO:______ 
If YES, how many times:_____ 
III. Since the last visit, has the subject been admitted to the hospital due to their 
Crohns Disease? 
YES:_____ 
NO:______ 
If YES, how many times:_____ 
If YES, please indicate the total number of days in the hospital:_____ 
 
 

 
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Appendix O.  
Subject Medication Log 
Instructions:  As a participant in this study, it is also important to keep a record of all mediations you take (new and old) throughout the study.  Please take this 
sheet home with you and write down any medications you take during the study.  It will be VERY important that you bring this sheet back to your doctors office 
and speak with your doctor about everything you have written down. 
 
Name of Medication 
Date you took
first dose 
Date you took
last dose 
What dose of medicine 
did you take? 
How often did you 
take the medicine? 
Why did you take the 
medicine? 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
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Week 25 - Week 36 
Subject Initials: __________ 
Subject Study #: ___________ 
 
Date 
day/mm/yr 
Day or 
Week # 
Time of Study 
Drug 
Administration 
Dose (mL) 
Administered
Kit #
Initials of Person 
Administering 
Study Medication 
Comments 
18/MAR/04 EXAMPLE 
9:35 am 
0.8 
 
MM 
none 
 
Week 25 
 
 
 
 
 
 
Week 26 
 
 
 
 
 
 
Week 27 
 
 
 
 
 
 
Week 28 
 
 
 
 
 
 
Week 29 
 
 
 
 
 
 
Week 30 
 
 
 
 
 
 
Week 31 
 
 
 
 
 
 
Week 32 
 
 
 
 
 
 
Week 33 
 
 
 
 
 
 
Week 34 
 
 
 
 
 
 
Week 35 
 
 
 
 
 
 
Week 36 
 
 
 
 
 
 

 
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Week 241 - Week 263 
Subject Initials: __________ 
Subject Study #: ___________ 
 
Date 
day/mm/yr 
Day or 
Week # 
Time of Study 
Drug 
Administration 
Dose (mL) 
Administered
Kit #
Initials of Person 
Administering 
Study Medication Comments
18/MAR/04 
EXAMPLE 
9:35 am 
0.8 
 
MM 
none 
 
Week 241 
 
 
 
 
 
 
Week 242 
 
 
 
 
 
 
Week 243 
 
 
 
 
 
 
Week 244 
 
 
 
 
 
 
Week 245 
 
 
 
 
 
 
Week 246 
 
 
 
 
 
 
Week 247 
 
 
 
 
 
 
Week 248 
 
 
 
 
 
 
Week 249 
 
 
 
 
 
 
Week 250 
 
 
 
 
 
 
Week 251 
 
 
 
 
 
 
Week 252 
 
 
 
 
 
 
Week 253 
 
 
 
 
 
 
Week 254 
 
 
 
 
 
 
Week 255 
 
 
 
 
 
 
Week 256 
 
 
 
 
 
 
Week 257 
 
 
 
 
 
 
Week 258 
 
 
 
 
 
 
Week 259 
 
 
 
 
 
 
Week 260 
 
 
 
 
 
 
Week 261 
 
 
 
 
 
 
Week 262 
 
 
 
 
 
 
Week 263* 
 
 
 
 
 
* 
Week 263 dose will only be taken if on every-week dosing schedule. 
 

 
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Appendix Q.  
Self Injection Instructions 
 
 
Subject Instructions 
0.8 mL or 0.4 mL dose 
(Administered as a single dose-prefilled syringe (PFS)) 
 
Protocol M06-807 
 

 
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Tables of Contents 
Dosing Schedule 
General Information  
Injection Procedures 
 

 
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Study Drug Dosing Schedule 
Open-Label (PFS) 
Subject Number:_____________________________________ 
You will require subcutaneous (SC) injections throughout the study.  
Injections at scheduled study visits (Baseline, Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 
108, 120, 144, 168, 192, 216 and 240) will be done during your visit, at the doctors 
office.  On weeks between office visits, study drug will be self-administered at home by 
you or someone trained to give you the injections. 
For 40 mg dose, one pre-filled syringe will contain 0.8 mL of liquid.  The total available 
dose is 0.8 mL.  The drug should be administered in one (1) SC injection, on the same 
day of the week for each dose. 
For 20 mg dose, one pre-filled syringe will contain 0.4 mL of liquid.  The total available 
dose is 0.4 mL.  The drug should be administered in one (1) SC injection, on the same 
day of the week for each dose. 
Please return all used and unused syringes to the clinic on your next visit. Used syringes 
should be placed in the special sharps container provided. All unused syringes should be 
returned in the original box. 
If an injection is missed or something occurs where the full dose cannot be injected, 
contact your study center immediately for further instructions.  Please record any missed 
doses on your subject diary. 
Remember to complete your dosing diary after each injection and to call the doctors 
office if you are having problems administering your study drug. 

 
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General Information 
 
 
 
 
 
 
 
PFS 
● Prefilled syringes will be labeled "adalimumab." 
● Store all adalimumab prefilled syringes in your refrigerator NOT in the 
freezer.  Should the syringes accidentally become frozen, call your study 
coordinator. 
● 0.8 mL = 0.8 cc 
● Study drug should be taken at about the same time of day, on the same day of 
the week as directed by your study doctor. 
● USE A NEW SYRINGE EVERY INJECTION DAY.  There may be 
medication left in the syringe.  DO NOT RE-USE. 
● Save all study drugs.  Prefilled syringes (used and unused) must be returned 
to the study center at each visit.  Used syringes will be disposed of in a sharps 
container provided to you. 
● Whenever possible, have someone with you for at least 15 to 30 minutes after 
your injection. 
● Call your doctor IMMEDIATELY if you experience any itching, hives, 
shortness of breath, or any symptom that has you concerned.  If you are 
unable to reach your doctor or if you experience life-threatening symptoms 
call 911, or proceed to your nearest emergency room. 
 

 
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Injection Procedures 
 
 
 
 
 
 
 
PFS 
1. Clean your workspace, gather your supplies, and wash your hands. 
 
 
2. Identify the area on your abdomen or thigh (or upper arm 
if not self injecting).  Make sure the area you choose 
does not have any redness, tenderness, swelling, bruising, 
or psoriasis.  The area must also be at least 2 cm 
(approximately 1 inch) away from the previous injection 
site.  IT IS VERY IMPORTANT TO CHANGE THE 
INJECTION SITE EVERY TIME!!! 
 
 
3. Using a circular motion (starting at the injection site and 
moving outward) clean the selected injection site with 
an alcohol pad.  Allow skin to dry.  
4. Remove the needle cap. Do not touch the needle.  Expel 
any air bubbles from the syringe by tapping on the 
syringe.  If the needle becomes contaminated, discard 
all supplies and obtain a new syringe of study drug.  
5. Once the air is expelled from the syringe, the amount of 
solution in the syringe should be 0.8 mL. 
 
 
6.   Hold the syringe "like a dart" between your thumb and 
first finger close to the syringe/needle connection. 

 
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PFS 
 
7. With your other hand, pinch the skin around the 
injection site, forming a bulge in the skin. 
 
 
 
 
 
 
8. Insert the needle into the skin at a 45-degree angle. 
Release pinched skin. 
 
 
 
 
9. 
GENTLY pull back on the syringe plunger.  If blood 
appears, withdraw needle - DO NOT INJECT!  
Contact your study center immediately for further 
instructions.  
 
10. Inject drug by pushing slowly on syringe plunger with 
thumb. 
 
11. Remove needle while maintaining a 45-degree angle. 
 
12. You may apply a Band-Aid over the injection site and 
apply gentle pressure, if necessary.  DO NOT RUB 
SITE. 
 
13. 
DO NOT RECAP NEEDLE.  DO NOT SEPARATE THE NEEDLE FROM THE 
 
SYRINGE BEFORE DISPOSING.  Discard used syringes into Sharps Container. 
EACH TIME THAT YOU GIVE YOURSELF AN INJECTION OF STUDY DRUG, 
REMEMBER TO RECORD THE INFORMATION ON YOUR SUBJECT DOSING 
DIARY. 
 

 
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Self Injection Instructions 
 
Subject Instructions 
0.2 mL dose 
Vials 
Protocol M06-807 

 
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Tables of Contents 
Dosing Schedule 
General Information  
Injection Procedures 

 
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Study Drug Dosing Schedule 
Vials 
Subject Number:  _____________________________________ 
You will require subcutaneous (SC) injections throughout the study. 
The injection for the visits at Weeks 4, 8, 12, 16, 20, 26, 32, 40, 48, 60, 72, 84, 96, 108, 
120, 144, 168, 192, 216 and 240 will be done during your visit at the doctor's office.  
After Week 4, on weeks between office visits (i.e., Weeks 6, 10, 14, etc.) study drug will 
be self-administered at home by you or someone trained to give you the injections. 
The total dose is 0.2 mL.  The drug should be administered in one (1) SC injection, on the 
same day of the week for each dose. 
For 10 mg dose, 0.2 mL of the solution is drawn from a vial containing adalimumab 
40 mg/0.8 mL solution.  The drug should be administered in one (1) SC injection, on the 
same day of the week for each dose. 
Please return all used and unused vials to the clinic on your next visit.  Used syringes 
should be placed in the special sharps container provided.  All unused vials should be 
returned in the original box. 
If an injection is missed or something occurs where the full dose cannot be injected, 
contact your study center immediately for further instructions.  Please record any missed 
doses on your subject diary. 
Remember to complete your dosing sheet after each injection and to call the doctor's 
office if you are having problems administering your study medication. 

 
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General Information 
Vials 
● Vials will be labeled "adalimumab." 
● Store all adalimumab vials in your refrigerator NOT in the freezer.  Should the 
vials accidentally become frozen, call your study coordinator. 
● 0.2 mL = 0.2 cc 
● Study drug should be taken at about the same time of day, on the same day of 
the week as directed by your study doctor. 
● USE A NEW VIAL EVERY INJECTION DAY.  There will be medication 
left in the vial.  DO NOT RE-USE. 
● Save all study drugs.  Vials (used and unused) must be returned to the study 
center at each visit.  Used vials and syringes will be disposed of in a sharps 
container provided to you. 
● Whenever possible, have someone with you for at least 15 to 30 minutes after 
your injection. 
● Call your doctor IMMEDIATELY if you experience any itching, hives, 
shortness of breath, or any symptom that has you concerned.  If you are 
unable to reach your doctor or if you experience life-threatening symptoms 
call 911, or proceed to your nearest emergency room. 
 

 
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Injection Instructions  
Vials 
Select a clean, well-lit, flat surface. 
1. 
Wash your hands thoroughly with soap and warm water.  It is important to keep 
your work surface as clean as possible. 
2. 
Open carton. 
3. 
Examine the carton and components in it to make sure they are complete. 
● One or two vials containing adalimumab 
 
4. 
Remove the plastic cap from the vial. 
5. 
Wipe the gray stopper with an alcohol swab and discard alcohol swab. 
 
 
6. 
Place the vial upright on a hard, flat surface. 
7. 
Choose an injection site on the upper thigh or abdomen. 
8. 
Prepare the injection site by wiping it thoroughly with a second alcohol swab.  
Use a circular motion. 
 

 
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9. 
Remove the needle cover from the syringe.  (The needle is sterile, so be very 
careful not to touch the needle or allow it to touch any surface.) 
10. 
Draw the plunger on the syringe back. 
11. 
With the vial sitting on a hard, flat surface, insert needle straight down through 
the center of the gray stopper.  If the needle is correctly lined up, you should feel 
slight resistance and then a "pop" as the needle penetrates the center of the 
stopper.  (Be careful not to insert the needle at an angle as this may cause the 
needle to bend.  If the needle is not correctly aligned, you will feel constant 
resistance as it penetrates the stopper and will not feel a "pop.") 
12. 
Push the plunger in forcing air into the vial. 
13. 
With the needle still in place, turn the vial upside down.  Keeping the vial at eye 
level, slowly pull the plunger back to draw the liquid into the syringe.  This will 
cause the bubbles to rise to the top of the syringe.  (As the liquid level in the vial 
drops, you may have to withdraw the needle partially to keep the tip of the needle 
in the liquid.)  Only 0.2 mL of the vial will be drawn into the syringe. 
14. 
With the needle still in the vial, check the syringe for air bubbles.  To remove any 
air bubbles, start by gently tapping the syringe. 
15. 
Slowly press the plunger to push any bubbles out of the syringe and into the vial.  
(If you accidentally push any liquid back into the vial, draw the liquid back into 
the syringe and check again for air bubbles.  It's okay for a small amount of liquid 
to remain in the vial.) 
16. 
Withdraw the needle from the vial, being careful not to touch it to any surface. 

 
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Vials 
17. 
Take the syringe in one hand. 
 
 
18. 
With your other hand, firmly pinch the skin around the cleaned injection site.  (Be 
careful not to touch the cleaned area.) 
 
 
19. 
Hold the syringe at about a 45-degree angle to the skin and use a quick, short 
motion to push the needle into the skin. 
 
 
20. 
Once the needle is in, release the skin. 

 
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Vials 
21. 
While firmly holding the syringe with one hand, use your other hand to slowly 
push the plunger and inject the adalimumab.  Only 0.2 mL of the vial will be 
injected. 
 
 
22. 
When the syringe is empty, remove the needle from the skin, being careful to 
keep it at the same 45-degree angle. 
23. 
Dispose of both the needle and syringe in a puncture-resistant container, or sharps 
container, which will be provided. 
24. 
You may want to press a cotton ball on the injection site for 10 seconds.  If there 
is some slight bleeding, you may choose to apply a small bandage. 
25. 
Return the vial into the original packaging. 
26. 
Place the medication kit back into the refrigerator. 

 
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Vials 
EACH TIME YOU RECEIVE AN INJECTION OF STUDY MEDICATION, 
REMEMBER TO RECORD THE INFORMATION ON YOUR DOSING SHEET. 
GENERAL INFORMATION: 
27. 
ROTATING INJECTION SITES IS RECOMMENDED.  PLEASE DO NOT 
INJECT THE STUDY MEDICATION INTO A PRIOR SITE OF INJECTION. 
28. 
Store all of your drug in the refrigerator.  Should the vials become accidentally 
frozen or left out, call your study coordinator.  DO NOT USE THESE VIALS. 
29. 
If you forget to take the drug or make a mistake with an injection, please call your 
study coordinator. 
30. 
Please save all of your study medication, even if you skip a dose.  Please bring all 
used and unused vials back to the physician at your next study visit. 
31. 
There will be study medication remaining in the vials.  DO NOT USE THE 
MEDICATION LEFT IN THE VIAL.  Please return the vial along with the 
remaining study medication back to the physician at your next study visit. 
32. 
Specific side effects to watch for:  redness and swelling at the injection site.  
Please tell the study coordinator if you have any side effects from injecting the 
drug. 
 

 
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Appendix R.  
Standard Weights 
 
 

 
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Appendix S.  
Subject Abbott Laboratories Site Drug Accountability Form 
 

 
Adalimumab 
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Appendix T.  
Work Productivity and Activity Impairment Questionnaire: 
Crohns Disease (WPAI-CD) - Caregiver 
The following questions ask about the effect of your childs Crohns disease on your ability 
to work and perform regular activities.  Please fill in the blanks or circle a number, as 
indicated. 
1.  Are you currently employed (working for pay)?  
_____ NO ___ YES 
  If NO, check "NO" and skip to question 6. 
The next questions are about the past seven days, not including today. 
 
 
2. During the past seven days, how many hours did you miss from work because of 
problems associated with your childs Crohns disease?  Include hours you missed on 
sick days, times you went in late, left early, etc., because of your childs Crohns 
disease.  Do not include time you missed for your child to participate in this study. 
 
_____ HOURS 
 
3. During the past seven days, how many hours did you miss from work because of any 
other reason, such as vacation, holidays, time off for your child to participate in this 
study? 
 
_____HOURS 
 
4. During the past seven days, how many hours did you actually work? 
 
_____HOURS  (If "0," skip to question 6.) 
 

 
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5. During the past seven days, how much did your childs Crohns disease affect your 
productivity while you were working?   
 
Think about days you were limited in the amount or kind of work you could do, days 
you accomplished less than you would like, or days you could not do your work as 
carefully as usual.  If your childs Crohns disease affected your work only a little, 
choose a low number.  Choose a high number if your childs Crohns disease affected 
your work a great deal.   
Consider only how much your childs Crohns disease affected  
your productivity while you were working. 
 
 
 
 
 
 
 
 
 
 
 
My childs Crohns 
disease had no 
effect on my work 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
My childs Crohns 
disease completely 
prevented me from 
working 
CIRCLE A NUMBER 
6. During the past seven days, how much did your childs Crohns Disease affect your 
ability to do your regular daily activities, other than work at a job?   
 
By regular activities, we mean the usual activities you do, such as work around the 
house, shopping, childcare, exercising, studying, etc.  Think about times you were 
limited in the amount or kind of activities you could do and times you accomplished 
less than you would like.  If your childs Crohns Disease affected your activities only a 
little, choose a low number.  Choose a high number if your childs Crohns Disease 
affected your activities a great deal.   
 
Consider only how much your childs Crohns disease affected your ability  
to do your regular daily activities, other than work at a job. 
 
 
 
 
 
 
 
 
 
 
 
My childs Crohns 
disease had no 
effect on my daily 
activities 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
My childs Crohns 
disease completely 
prevented me from 
doing my daily 
activities 
 
 
                           
CIRCLE A NUMBER 
WPAI:CD-Caregiver (US English) 

 
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Appendix U.  
Protocol Amendment:  List of Changes 
The summary of changes is listed in Section 1.1. 
Specific Protocol Changes: 
Table 1.  Study Activities 
Add:  Footnote "m." 
m. PPD or QuantiFERON-TB Gold testing at Weeks 48, 96, 144, 192 and 240. 
 
Section 5.3.1.1  Study Procedures 
Add:  Subsection TB Testing 
TB Testing 
For subjects with a negative test at Screening visit from parent study (Study M06-806), 
an annual PPD or QuantiFERON-TB Gold re-test will be required.  If one of the annual 
tests has a positive test result, the matter should be discussed with the medical monitor 
prior to starting any prophylaxis. 
A PPD skin test (alternatively, also known as tuberculin skin test) must be placed or the 
QuantiFERON®-TB Gold test (or equivalent) must be performed for subjects with a 
negative test at Screening visit after the amended protocol is approved by IRB/IEC 
including those with a prior history of Bacille Calmette-Guérin (BCG) administration at 
the time the subject reaches one of the scheduled visits:  Weeks 48, 96, 144, 192, and 
240.  
If the subject is experiencing signs or symptoms suspicious for TB or something has 
changed in the subject's medical history to warrant a repeat test before the next scheduled 
annual TB re-test, the case must be discussed with the Abbott Medical Monitor. 
For the PPD test: 

 
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● The subject will be required to have the PPD test read by a licensed healthcare 
professional 48 to 72 hours after placement (or as per local guidelines), when 
the induration is maximal.  An induration (not erythema) of 5 mm or greater 
will be considered as PPD positive, irrespective of BCG status or local 
guidelines.  The absence of induration should be recorded, as "0 mm," not 
"negative." 
● If there are sites where the available testing materials are not accepted, an 
alternative tuberculin skin test may be substituted, but the method must be 
submitted and approved by Abbott prior to use with study subjects. 
● If QuantiFERON®-TB Gold (or equivalent) result is indeterminate, the test 
should be repeated with a fresh blood sample.  If a repeat QuantiFERON®-TB 
Gold (or equivalent) result is indeterminate, this should be considered a 
positive test result and the case must be discussed with the Abbott Medical 
Monitor. 
 
In the event both a PPD test and QuantiFERON-TB Gold test are performed, the result of 
the QuantiFERON-TB Gold test will supersede the result of the PPD test. 
Newly initiated prophylactic treatment should be captured in the source documents and 
on the concomitant medications page in the CRF.  Prior therapy should be captured in the 
appropriate medical history CRF. 
For sites participating in the Czech Republic, the following local requirements will also 
be applicable: 
● A pulmonologist will be responsible to obtain a detailed medical history with 
respect to TB exposure.  This information needs to include BCG vaccination, 
cohabitation with individuals who have had TB, and/or who reside or work in 
TB endemic locations.  The information obtained by the pulmonologist must 
be documented in the subject's source note, dated and signed by the 
pulmonologist. 

 
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● A pulmonologist must review the results of the PPD skin test and the CXR 
and has to give his/her opinion about the eligibility of each subject to continue 
in the study.  This opinion must be documented in writing in the subject's 
source documents. 
 
All subjects with a positive PPD need to be approved for continuation in the trial by both 
the Czech pulmonologist and the Abbott Medical Monitor and all such subjects need to 
receive prophylaxis for latent TB.  Under no circumstances can a subject with a positive 
PPD result and no prior history of treatment for active or latent TB be allowed to 
continue in this trial 
Appendix Q.  Self Injection Instructions 
Subsection "Injection Instructions" 
Item 21 previously read: 
While firmly holding the syringe with one hand, use your other hand to slowly push the 
plunger and inject the adalimumab.  For subjects that weigh t 40 kg, all 0.8 mL will be 
injected.  For subjects that weigh < 40 kg, only 0.4 mL of the vial will be injected. 
Has been changed to read: 
While firmly holding the syringe with one hand, use your other hand to slowly push the 
plunger and inject the adalimumab.  Only 0.2 mL of the vial will be injected. 
 

 
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1.0 
Title Page 
CLINICAL TRIAL PROTOCOL M06-807 
A Multi-center, Open-label Study of the Human 
Anti−TNF Monoclonal Antibody Adalimumab to 
Evaluate the Efficacy and the Long-term Safety and 
Tolerability of Repeated Administration of 
Adalimumab in Pediatric Subjects with 
Crohn's Disease Who Have Demonstrated a Clinical 
Response in the M06-806 Study 
Incorporating Administrative Changes 1 and 2, 
Amendment 1, Administrative Changes 3, 4, 5 and 6, 
and Amendments 2, 3 and 4 
Abbott Number /  
 Investigational Product: 
 
Adalimumab 
Date:  
29 June 2011 
Development Phase: 
3 
Study Design:  
A multi-center, open-label safety and tolerability pediatric study in the 
United States, Canada and Europe. 
EudraCT Number:  
2007-006494-90 
Investigator: 
Multicenter (Investigator information on file at Abbott Laboratories). 
Sponsor: 
European Union Countries: 
Abbott GmbH & Co.KG  
Knollstrasse 50 
67061 Ludwigshafen, Germany 
Non European Union Countries: 
Abbott Laboratories, US  
100 Abbott Park Road 
Abbott Park, IL 60064 
Emergency Contact: 
This study will be conducted in compliance with the protocol, Good Clinical Practice and all other 
applicable regulatory requirements, including the archiving of essential documents. 
Confidential Information 
No use or disclosure outside Abbott is permitted without prior written authorization from Abbott. 

 
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1.1 
Protocol Amendment:  Summary of Changes 
The purpose of this amendment is to: 
● Allow dose and frequency decrease in subjects who have responded well to 
treatment, allow dose adjustment due to weight loss and add 10 mg eow 
dosage. 
○ After completion of Study M06-806 and consideration of efficacy, safety 
and population pharmacokinetic results in conjunction with 
exposure-response modeling and simulation both the Low-Dose and 
High-Dose treatment provided evidence of efficacy and safety.  Therefore, 
in order to minimize the systemic exposures to study drug to the lowest 
doses necessary in children with CD, Amendment 4 provides investigators 
with the option of dose de-escalation by reducing the dose or dose 
frequency (i.e., switching from ew to eow) based on the clinical status of 
the individual patient.  In addition, since the 10 mg eow dose was 
efficacious in subjects weighing < 40 kg in Study M06-806 patients will 
have the option to be switched to this dose based on their body weight and 
clinical status at the discretion of the investigator. 
○ If subjects experience a flare after dose de-escalation, subjects also have 
an opportunity to re-escalate their dose back to the next higher treatment 
level. 
● Correct typographical errors. 
 
An itemized list of all changes made to the protocol under this amendment can be found 
in Appendix U. 

 
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2.0 
Table of Contents 
1.0 
Title Page .................................................................................1 
1.1 
Protocol Amendment:  Summary of Changes...........................................2 
2.0 
Table of Contents....................................................................3 
3.0 
Introduction.............................................................................8 
4.0 
Study Objective .....................................................................14 
5.0 
Investigational Plan ..............................................................14 
5.1 
Overall Study Design and Plan:  Description..........................................14 
5.2 
Selection of Study Population .................................................................19 
5.2.1 
Inclusion Criteria.....................................................................................19 
5.2.2 
Exclusion Criteria....................................................................................20 
5.2.3 
Prior and Concomitant Therapy ..............................................................22 
5.2.3.1 
Prior Therapy...........................................................................................22 
5.2.3.2 
Concomitant Therapy..............................................................................23 
5.2.3.3 
Rescue Therapy .......................................................................................24 
5.2.3.4 
Prohibited Therapy ..................................................................................24 
5.3 
Efficacy, and Safety Assessments/Variables...........................................24 
5.3.1 
Efficacy and Safety Measurements Assessed and Flow Chart................24 
5.3.1.1 
Study Procedures.....................................................................................30 
5.3.2 
Drug Concentration Measurements.........................................................37 
5.3.2.1 
Collection of Samples for Analysis.........................................................38 
5.3.2.2 
Handling/Processing of Samples.............................................................38 
5.3.2.3 
Disposition of Samples............................................................................39 
5.3.2.4 
Measurement Methods ............................................................................39 
5.3.3 
Efficacy Variables ...................................................................................39 
5.3.4 
Safety Variables.......................................................................................40 
5.3.5 
Pharmacokinetic Variables......................................................................40 

 
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5.4 
Removal of Subjects from Therapy or Assessment ................................40 
5.4.1 
Discontinuation of Individual Subjects ...................................................40 
5.4.2 
Discontinuation of Entire Study ..............................................................41 
5.4.3 
Stopping Rules.........................................................................................41 
5.5 
Treatments ...............................................................................................42 
5.5.1 
Treatments Administered ........................................................................42 
5.5.2 
Identity of Investigational Product ..........................................................43 
5.5.2.1 
Packaging and Labeling ..........................................................................44 
5.5.2.2 
Storage and Disposition of Study Drug...................................................45 
5.5.3 
Method of Assigning Subjects to Treatment Groups ..............................45 
5.5.4 
Selection and Timing of Dose for Each Subject .....................................46 
5.5.5 
Blinding...................................................................................................47 
5.5.6 
Treatment Compliance ............................................................................47 
5.5.7 
Drug Accountability................................................................................48 
5.6 
Discussion and Justification of Study Design .........................................49 
5.6.1 
Discussion of Study Design and Choice of Control Groups...................49 
5.6.2 
Appropriateness of Measurements ..........................................................49 
5.6.3 
Suitability of Subject Population.............................................................49 
5.6.4 
Selection of Doses in the Study...............................................................49 
6.0 
Adverse Events......................................................................50 
6.1 
Definitions...............................................................................................51 
6.1.1 
Adverse Event .........................................................................................51 
6.1.2 
Serious Adverse Events...........................................................................51 
6.2 
Adverse Event Severity...........................................................................52 
6.3 
Relationship to Study Drug .....................................................................53 
6.4 
Adverse Event Collection Period ............................................................53 
6.5 
Adverse Event Reporting ........................................................................54 

 
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6.5.1 
Collection of Data Regarding Known Manifestations of the 
Disease Under Study ...............................................................................55 
6.6 
Pregnancy ................................................................................................55 
7.0 
Protocol Deviations...............................................................56 
8.0 
Statistical Methods and Determination of Sample 
Size..........................................................................................57 
8.1 
Statistical and Analytical Plans ...............................................................57 
8.1.1 
Analyzable Population.............................................................................57 
8.1.2 
Planned Methods of Statistical Analysis .................................................57 
8.1.2.1 
Demographics and Baseline Characteristics ...........................................57 
8.1.2.2 
Efficacy Analysis.....................................................................................57 
8.1.3 
Other Analyses ........................................................................................57 
8.1.4 
Safety Analyses .......................................................................................58 
8.1.4.1 
Pharmacokinetic Analyses.......................................................................59 
8.1.5 
Interim Analysis ......................................................................................59 
8.2 
Determination of Sample Size.................................................................59 
8.3 
Randomization Methods..........................................................................59 
9.0 
Ethics......................................................................................60 
9.1 
Independent Ethics Committee (IEC) or Institutional Review 
Board (IRB).............................................................................................60 
9.2 
Ethical Conduct of the Study...................................................................60 
9.3 
Subject Information and Consent ............................................................61 
10.0 
Source Documents and Case Report Form 
Completion.............................................................................62 
10.1 
Source Documents...................................................................................62 
10.2 
Case Report Forms ..................................................................................62 
11.0 
Data Quality Assurance........................................................63 
12.0 
Use of Information and Publication....................................64 
12.1 
Use of Information ..................................................................................64 

 
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12.2 
Internet Sites............................................................................................65 
13.0 
Completion of the Study.......................................................65 
14.0 
Investigators Agreement ......................................................67 
15.0 
Reference List........................................................................68 
 
List of Tables 
Table 1.  
Study Activities .......................................................................................25 
Table 2.  
Clinical Laboratory Tests ........................................................................33 
Table 3.  
Identity of Investigational Products.........................................................44 
Table 4.  
Study Drug Packaging and Administration.............................................45 
 
List of Figures 
Figure 1.  
Study Schematic ......................................................................................17 
Figure 2.  
Dosing Schematic After Amendment 4...................................................19 
Figure 3.  
Adverse Event Collection........................................................................54 
 
List of Appendices 
Appendix A.  
List of Abbreviations and Definition of Terms .......................................72 
Appendix B.  
List of Protocol Signatories.....................................................................74 
Appendix C.  
Documents Required Prior to Initiation of the Study..............................75 
Appendix D.  
Responsibilities of the Clinical Investigator............................................77 
Appendix E.  
CDC Treatment of Tuberculosis Infection (Preventive Therapy)...........79 
Appendix F.  
Non-Drug Materials Provided to the Study Site(s) .................................81 
Appendix G.  
Pediatric Crohns Disease Activity Index (PCDAI).................................82 
Appendix H.  
PCDAI Users Guide and Guideline for Reference Weight and 
Reference Height.....................................................................................84 
Appendix I.  
Crohns Disease Activity Index (CDAI) ..................................................90 
Appendix J.  
Subject CDAI Diary ................................................................................91 

 
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Appendix K.  
IMPACT III Questionnaire......................................................................92 
Appendix L.  
Excluded Medications ...........................................................................100 
Appendix M.  Day 70 Phone Call.................................................................................101 
Appendix N.  
Unscheduled Outpatient Visits, Emergency Room Visits and 
Hospitalizations .....................................................................................102 
Appendix O.  
Subject Medication Log ........................................................................103 
Appendix P.  
Subject Dosing Diary ............................................................................104 
Appendix Q.  
Self Injection Instructions......................................................................122 
Appendix R.  
Standard Weights...................................................................................137 
Appendix S.  
Subject Abbott Laboratories Site Drug Accountability Form...............139 
Appendix T.  
Work Productivity and Activity Impairment Questionnaire: 
Crohns Disease (WPAI-CD) - Caregiver ..............................................140 
Appendix U.  
Protocol Amendment:  List of Changes ................................................142 
 

 
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3.0 
Introduction 
Crohns Disease (CD) is a chronic, debilitating, and currently incurable inflammatory 
disease that can affect the entire digestive system as well as extraintestinal organs.  CD is 
primarily manifested by focal asymmetric, transmural, and occasionally, granulomatous 
inflammation affecting any segment of the gastrointestinal tract1 which can consist of 
mucosal edema, aphthous and linear ulcerations, asymmetrical narrowing and strictures.  
Noncaseating granulomas are virtually diagnostic in the correct clinical setting.  The most 
commonly involved area of the bowel is the small bowel, particularly the distal ileum, 
which is involved in 70% of cases often in combination with colitis, occurring in 50% of 
cases.  Extraintestinal manifestations can also occur, and include symptoms of joint, 
ocular and hepatic inflammation.  Genetic, geographic, ethnic, and environmental risk 
factors have all been described, but the basic etiology of the disease remains unknown. 
The incidence in North America is similar to that in other western nations and is 
estimated from 3.1 to 14.6 cases per 100,000 person years and prevalence ranges from 
26 to 199 cases per 100,000 persons.2  The disease can affect persons of any age but the 
most common age of onset is in the second and third decades with a female 
preponderance.  While predominantly a disease of adults, approximately 10% to 15% of 
CD cases are diagnosed before adulthood.3 
In addition, the incidence of CD in patients less than 18 years of age appears to be 
increasing in both North America and Europe.4,5  Reported incidence rates range from 
1.2 to 4.9 per 100,000 persons in the UK, Europe, and North America6-12 with one study 
reporting an incidence of 4.6 per 100,000 persons in the United States.5  CD has been 
reported at all ages but is rare in early childhood.  In one study of patients with CD, 
17 years of age and younger, 9.1% of the patients were diagnosed before the age of 6.13  
In a second study of patients diagnosed with CD before the age of 15, 7.5% of the 
patients were under the age of 5.14 
Despite obvious physiologic and development differences, the presentation of CD in the 
pediatric population is generally similar to that seen in older patients and is 

 
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heterogeneous with regard to anatomic localization and clinical severity.5,15,16  The 
unique aspect of this disease in children is its impact on nutrition and growth, with 
marked growth retardation being a prominent component of the disease in this age 
group.17-19  The use of accepted methodologies for assessing nutritional status, including 
the anthropometric measures of height, weight, triceps skin fold thickness and mid arm 
circumference as well as linear growth (height velocity and assessment of height velocity 
for chronological age "z-score") have documented the growth impairment that can occur 
in this age group, and also have been used to assess the efficacy of interventions.20  
Profound impairment of bone formation and increased bone resorption are associated 
complications and are related to the effect of glucocorticoids,21,22 delayed puberty,22,23 
decreased mobility,24 as well as to the effects of cytokines on bone formation.25 
Initial symptoms are often subtle, and there is an average delay of almost six months 
between onset of symptoms and diagnosis.  The most common presentation is with 
abdominal pain, diarrhea, loss of appetite and weight loss.  However, isolated weight 
loss, anorexia, perianal disease and extraintestinal manifestations can occur in the 
absence of GI symptoms in a substantial number of patients. 
The general approach to the treatment of CD in children is similar to adults with the goals 
being induction and maintenance of remission, prevention of relapse and hospitalizations, 
improved quality of life, and avoidance of disease and drug related complications.  
Restoration and/or preservation of normal growth and pubertal development are 
additional therapeutic goals.  The medical armamentarium is likewise similar to adults 
and includes induction of remission with corticosteroids, and ongoing maintenance 
therapy of immunomodulators, aminosalicylates and nutritional therapy.  Anti-tumor 
necrosis factor (TNF) therapy with infliximab has been evaluated for the therapy of CD 
in this age group as it has in adults.  The FDA and EMEA have recently approved 
Infliximab for use in children with CD. 
Adalimumab is a recombinant human immunoglobulin (IgG1) monoclonal antibody 
exclusively containing human peptide sequences.  It is produced by recombinant 
deoxyribonucleic acid (DNA) technology in a mammalian cell expression system.  

 
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Adalimumab consists of 1330 amino acids and has a molecular weight of approximately 
148 kilodaltons.  It binds specifically with high affinity to the soluble and transmembrane 
forms of TNFD and inhibits the binding of TNFD with its receptors. 
TNF is a naturally occurring cytokine that is involved in normal inflammatory and 
immune responses.  Elevated levels of TNF play an important role in pathologic 
inflammation.  Adalimumab binds specifically to TNF and neutralizes the biological 
function of TNF by blocking its interaction with the p55 and p75 cell surface TNF 
receptors. 
Adalimumab was first approved for treatment of rheumatoid arthritis (RA) on 
31 Dec 2002 in the United States (US), on 08 Sep 2003 in the European Union (EU) and 
through August 2008 in a total of 76 countries.  Indication extensions to include 
treatment of psoriatic arthritis and early RA were granted in the EU on 01 Aug 2005 and 
in the US on 03 Oct 2005.  A further indication extension to include treatment of 
ankylosing spondylitis was approved in the EU on 01 Jun 2006 and was approved in the 
US on 28 Jul 2006.  Adalimumab was approved for the treatment of Crohns disease in the 
United States on 27 Feb 2007, in the European Union on 04 Jun 2007 and in Canada on 
05 July 2007 for the adult population.  In December 2007 and January 2008, respectively, 
adalimumab was approved for the treatment of psoriasis in adult patients in the EU, 
Canada and USA.  Additionally, adalimumab was approved for the treatment of juvenile 
idiopathic arthritis in the USA in February 2008. 
Adalimumab has been shown to be a safe and effective treatment of moderately to 
severely active Crohns disease.  In the CD development program, adalimumab was 
studied in over 1400 adult subjects in three pivotal studies (two induction studies and a 
maintenance study). 
Study M02-403 was a multicenter, randomized, double-blind, placebo-controlled 
Phase 2/3 study to evaluate the efficacy and safety of adalimumab for the induction of 
remission in subjects with moderate to severe CD.26  A total of 299 subjects were 
randomized to receive one of four proposed induction treatment regimens (three active 

 
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treatment groups or placebo):  adalimumab 160 mg at Baseline (Week 0) followed by 
80 mg at Week 2, adalimumab 80 mg at Baseline followed by 40 mg at Week 2, 
adalimumab 40 mg at Baseline followed by 20 mg at Week 2 or placebo at Baseline and 
Week 2.  Eligible subjects could not have been previously treated with any anti TNF 
agent.  Only the group of subjects treated with adalimumab 160/80 mg had a statistically 
significantly greater remission rate at Week 4 (primary endpoint) compared to placebo 
(35.5% vs. 12.2%; p = 0.001).  In addition, statistically significantly greater proportions 
of subjects in the adalimumab 160/80 mg group than in the placebo group experienced 
clinical response CR-100 (48.7% and 24.3%, respectively) and clinical response CR-70 
(57.9% and 36.8%, respectively) at Week 4. 
Study M04-691, a second induction study, was a multicenter, randomized, double-blind, 
placebo-controlled, Phase 3 study to evaluate the efficacy and safety of adalimumab as 
induction treatment for subjects with moderate to severe CD who either initially 
responded to administration of infliximab but stopped responding or were intolerant.27  
A total of 325 subjects were randomized to receive adalimumab 160/80 mg or placebo.  
Eligible subjects must have previously been treated with infliximab and discontinued use 
due to loss of response to or intolerance to infliximab therapy.  The proportion of subjects 
who achieved clinical remission at Week 4 (primary endpoint) was statistically 
significantly greater in the adalimumab 160/80 mg group compared to the placebo group 
(21.4% vs. 7.2%).  The proportion of subjects achieving clinical response CR-100 and 
CR-70 at Week 4 was statistically significantly greater in the adalimumab 160/80 mg 
group (38.4% and 51.6%, respectively) compared to the placebo group (24.7% and 
33.7%, respectively). 
Study M02-404 was a multicenter, randomized, double-blind, placebo-controlled Phase 3 
study to assess the efficacy and safety of adalimumab for the maintenance of clinical 
remission in subjects with moderate to severe CD.27  A total of 854 subjects (both naïve 
to or previously treated with TNF antagonists [primarily infliximab]) were enrolled and 
received open-label adalimumab 80 mg at Baseline (Week 0) and adalimumab 40 mg at 
Week 2.  At Week 4, subjects were stratified by responder status (subjects who achieved 

 
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clinical response CR-70) and previous anti-TNF use and were randomized in a 1:1:1 ratio 
to one of three blinded treatment groups:  adalimumab 40 mg every week (ew), 
adalimumab 40 mg every other week (eow), or placebo.  Subjects who met clinical 
response CR-70 after Week 8 could be tapered from corticosteroids. 
The proportion of Week 4 responders (N = 499) who achieved clinical remission at 
Weeks 26 and 56 (co-primary endpoint) were statistically significantly greater in the 
adalimumab 40 mg eow (39.5% and 36.0%, respectively) and 40 mg ew (46.5% and 
41.4%, respectively) groups compared to the placebo group (17.1% and 11.8%, 
respectively).  The differences between the adalimumab 40 mg eow and 
adalimumab 40 mg ew groups at both of these time points were not statistically 
significant.  The median time in first clinical remission was greater in the adalimumab 
40 mg eow group (378 days) compared to the placebo group (127 days).  The median 
time in remission could not be estimated in the adalimumab 40 mg ew group because 
more than 50% remained in clinical remission at the end of the study.  Approximately six 
times as many subjects treated with adalimumab maintenance therapy compared to 
placebo were able to discontinue corticosteroids for at least 90 days and achieve 
remission at Week 26 and Week 56.  Efficacy was independent of Baseline C-reactive 
protein (CRP), concomitant therapies, such as corticosteroids or immunosuppressants, or 
prior anti-TNF experience.  The adalimumab safety profile in CD was similar to that seen 
in the other rheumatologic populations previously studied, except for expected 
manifestations of CD. 
Currently, there are two ongoing extension studies of adalimumab therapy in adult 
subjects with CD.  M04-690 trial is a long-term safety and tolerability study of repeated 
administration of adalimumab in adult subjects with CD who had previously participated 
in M02-404 or M04-691.  The other trial is a long-term open-label extension study 
following the initial first-year study period of the M02-433 study. 
The efficacy and safety of adalimumab in children has recently been demonstrated in 
juvenile rheumatoid arthritis (JRA).28  One hundred and seventy-one pediatric patients 
(4 to 17 years of age) were initially enrolled into a 16-week open label segment and 

 
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13 
133 subjects continued in a 32-week double blind segment.  Clinically significant 
improvements were noted in ACR30, ACR50 and ACR70 as well as other indices of 
arthritis activity.  Adverse events (AEs) were similar as those noted in adult RA patients.  
There were no deaths, malignancies, or opportunistic infections, including tuberculosis 
(TB).  Thirteen serious adverse events (SAEs) in 8 subjects were observed in the 16-week 
open label portion of the study.  These included 4 subjects with JRA, one patient with 
two episodes of leukopenia/neutropenia, and one case each of femur fracture, herpes 
simplex, and pneumonia.  Six SAEs were observed in 6 subjects (2 placebo, 
4 adalimumab) during the 32-week double blind portion (closed head injury, 
gastroduodenitis, retinal detachment, appendicitis, abdominal pain and urinary tract 
infection).  Infections, AEs at least possibly related to study drug, and injection site 
reactions were reported by similar proportions of patients in all treatment groups during 
the double-blind therapy (32 weeks). 
Fatalities, serious infections, and sepsis have been reported with the use of TNF 
antagonists.  Many of the serious infections have occurred in subjects on concomitant 
immunosuppressive therapy that, in addition to their underlying immune disorder, could 
predispose them to infections.  TB has also been observed in subjects treated with TNF 
antagonists, including adalimumab.  The event rate for TB in the CD development 
program is consistent with the global adalimumab rate.29 
TNF antagonists, including adalimumab, have been associated with cases of malignancy 
and demyelinating disease.  Serious allergic adverse reactions have been reported in RA 
subjects following subcutaneous (SC) administration of adalimumab; none were reported 
in the CD program. 
A detailed discussion of the pre-clinical toxicology, metabolism, pharmacology, and 
safety experience can be found in the current Investigators Brochure. 
The goal of this study is to demonstrate the efficacy of adalimumab in the maintenance of 
clinical response and to demonstrate the long-term safety and tolerability of repeated 
administration of adalimumab in pediatric subjects with Crohns disease.  The subject 

 
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population will consist of subjects who participated in and successfully completed the 
M06-806 study and who meet all the inclusion and none of the exclusion criteria of 
Protocol M06-807.  Qualifying subjects will administer open-label adalimumab by SC 
injection.  Subjects receiving every other weekly therapy who continue to have a disease 
flare or develop another flare may be switched to every week therapy at the investigators 
discretion.  Subjects receiving weekly therapy who continue to have a disease flare or 
develop another flare may be withdrawn from the study at the Investigators discretion.  
For a detailed description of the study please see Section 5.0. 
4.0 
Study Objective 
The objective of the study is to evaluate the long-term maintenance of clinical response, 
safety and tolerability of repeated administration of adalimumab in pediatric subjects 
with Crohns disease who participated in, and successfully completed, Protocol M06-806 
through Week 52 and who meet all the inclusion and none of the exclusion criteria of 
Protocol M06-807. 
5.0 
Investigational Plan 
5.1 
Overall Study Design and Plan:  Description 
This study is a multi-center, open-label study of the human anti-TNF monoclonal 
antibody adalimumab.  Approximately 31 sites that have enrolled subjects in the 
M06-806 clinical trial will participate in the M06-807 clinical trial.  Approximately 
130 pediatric subjects were expected to enroll in this study; final enrollment was 
100 subjects.   
The Week 52 visit from the M06-806 study will be the Baseline Visit for those subjects 
entering study M06-807.  The visit window for M06-806 Week 52 visit is 364 ± 7 days 
from the Baseline Visit date of M06-806. 
Subjects may be allowed to enroll in the M06-807 study if they have participated in, and 
successfully completed Protocol M06-806 through Week 52.  A subject must be a 

 
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responder at any time point during the M06-806 study.  A responder is defined as a 
subject who had a PCDAI score that was at least 15 points lower than the M06-806 
baseline score. 
All subjects will be on open-label maintenance therapy.  Subjects who enroll into the 
study from blinded therapy in Study M06-806 will receive open-label therapy at a dose 
dependent on their body weight.  Subjects who weigh t 40 kg at Baseline will receive 
40 mg eow of adalimumab, while subjects who weigh < 40 kg at Baseline will receive 
20 mg eow of adalimumab.  Beginning at Week 8, subjects who have a disease flare may 
be switched to ew treatment at the same dose of adalimumab received while on eow 
treatment.  A disease flare is defined as an increase in the Pediatric Crohns Disease 
Activity Index (PCDAI) of t 15 points when compared to the PCDAI score obtained at 
the subjects previous visit. 
Subjects who enroll into the study from open-label therapy in Study M06-806 will 
continue to receive the same dose they were receiving (i.e. 40 mg ew or 20 mg ew) at the 
Week 52 visit of the M06-806 study.  
Subjects who develop a flare while receiving ew open-label therapy or have a PCDAI 
score t 15 points when compared to their Baseline (the Week 52 visit of the M06-806 
study) PCDAI score (regardless of study visit), may be discontinued from the study at the 
discretion of the Investigator.  
Beginning from Week 8, the dose of adalimumab may be increased to 40 mg, at the 
discretion of the Investigator, for subjects whose body weight has increased from < 40 kg 
to t 40 kg from the Baseline (Week 52 of the M06-806 Study) visit.  The site will enter 
the subjects body weight into the Interactive Voice Response System (IVRS) and the 
dose will be adjusted, if applicable.  
Reductions in concomitant therapy will be allowed for Crohns treatment related toxicities 
(e.g., leukopenia, anemia, neuropathy) of Grade 3 or higher. 

 
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Subjects may be allowed to decrease prednisone (or equivalent) and budesonide if 
qualifications are met (please see Section 5.2.3.2 for required timing and rate of taper). 
Subjects may be allowed to adjust their Crohns specific concomitant medications as 
specified in Section 5.2.3.2. 
The duration of the study could last up to 264 weeks (approximately 5 years).  Subjects 
who complete, or who early terminate from the study will be contacted 70 days after their 
last dose of study drug to obtain information on any ongoing and new AEs.   
This study will conclude approximately 12 weeks after the following criteria have been 
satisfied: 
● Study drug receives country and local (if applicable) regulatory approval for 
pediatric Crohns Disease. 
● All applicable local reimbursement procedures are completed. 
 
Sites will be notified once these criteria are met. 
Following country and local (if applicable) regulatory approval and applicable local 
reimbursement approval of the study drug in a country, subjects should return to their 
next scheduled study visit as specified in the protocol.  The termination visit should be 
conducted in place of their regular scheduled study visit.  These subjects should be 
considered as having completed the study. 
A schematic of the study design is shown in Figure 1 (prior to Amendment 4) and in 
Figure 2 (after Amendment 4). 

 
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Figure 2.  
Dosing Schematic After Amendment 4 
 
F:  
Subjects who have a disease flare may be switched to the next higher treatment level. 
R:  
Subjects who responded to their current treatment may be switched to the next lower treatment level at the 
discretion of the investigator after discussion with the medical monitor.  Response is defined as a) a t 15 points 
decrease in PCDAI compared to the last observation prior to dose escalation in patients who dose-escalated or 
b) a t 15 points decrease in PCDAI compared to Baseline of Study M06-806 in patients who did not 
dose-escalate. 
BW: Subjects with an increase in body weight to t 40 kg may increase their dose to the next higher level at the 
discretion of the investigator after discussion with the medical monitor.  Subjects with a decrease in body weight 
to < 40 kg may decrease their dose to the next lower level at the discretion of the investigator after discussion 
with the medical monitor. 
 
5.2 
Selection of Study Population 
Subjects will be evaluated to determine if they meet all of the inclusion criteria specified 
in Section 5.2.1 and none of the exclusion criteria specified in Section 5.2.2 of this 
protocol.   
5.2.1 
Inclusion Criteria 
1. 
Subject must have successfully enrolled in and completed Protocol M06-806 
through Week 52. 
2. 
Subject must be a responder at any time point during the M06-806 study. 

 
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3. 
If female, subjects who are sexually active and are of child-bearing potential 
should be practicing an approved method of birth control throughout the study and 
for 150 days after study drug administration.  Examples of approved methods of 
birth control include the following: 
● Condoms, sponge, foam, jellies, diaphragm or intrauterine device (IUD) 
● Oral, parenteral or intravaginal contraceptives 
● A vasectomized partner 
4. 
Subject of legal age, parent or legal guardian, as required, has voluntarily signed 
and dated an Institutional Review Board (IRB)/Independent Ethics Committee 
(IEC) approved informed consent form, after the nature of the study has been 
explained and the subject of legal age, subjects parent, or legal guardian, as 
required, has had the opportunity to ask questions.  Subjects will be included in all 
discussions, and if required, their signature on an assent form will be obtained. 
5. 
Parent or legal guardian of subject who is not of legal age, as required, must be 
willing to actively supervise storage and administration of study drug and to 
ensure that the time of each dose is accurately recorded in the subjects diary. 
6. 
If a subject of legal age, must be willing to actively store, administer, and 
accurately record study drug administration in the subject diary. 
7. 
Subject is judged to be in acceptable medical condition, as determined by the 
Principal Investigator based upon results of clinical and laboratory evaluations 
done throughout the preceding Crohns disease study M06-806. 
 
5.2.2 
Exclusion Criteria 
A subject will be excluded from the study if he/she meets any of the following criteria:  
1. 
For any reason, the subject is considered by the Investigator to be an unsuitable 
candidate for continuing therapy in the M06-807 study. 

 
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2. 
Subject has abnormal laboratory or other test results that in the opinion of the 
Investigator will make the subject unsuitable to participate in this study. 
3. 
History of cancer or lymphoproliferative disease other than a successfully and 
completely treated cutaneous squamous cell or basal cell carcinoma or 
carcinoma − in-situ of the cervix. 
4. 
History of listeriosis, histoplasmosis, chronic or active hepatitis B infection, 
human immunodeficiency virus (HIV) infection, any immunodeficiency 
syndrome, central nervous system (CNS) demyelinating disease or active TB 
(receiving treatment or not receiving treatment).  Ongoing severe infections such 
as sepsis and opportunistic infections will be exclusionary. 
5. 
Subject with known, symptomatic obstructive strictures. 
6. 
Subject who is planning surgical bowel resection at any time point while enrolled 
in the study. 
7. 
Subject who has short bowel syndrome as determined by the Investigator. 
8. 
Subject who is currently receiving total parenteral nutrition (TPN). 
9. 
Subject who is unwilling to discontinue growth hormone prior to the first dose of 
open-label study drug at the Baseline visit of M06-807. 
10. 
Female subject who is pregnant or currently breast-feeding. 
11. 
Subject with a history of clinically significant drug or alcohol abuse in the last 
year. 
12. 
Subject with a poorly controlled medical condition such as: uncontrolled diabetes, 
recurrent infections, unstable ischemic heart disease, moderate to severe heart 
failure, recent cerebrovascular accidents or any other condition which, in the 

 
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opinion of the Investigator or the Sponsor, will put the subject at risk by 
participation in the protocol. 
13. 
Subject with any prior exposure to Tysabri (natalizumab). 
14. 
Subject with a known hypersensitivity to the excipients of adalimumab as stated in 
the label. 
15. 
Subject with a previous history of dysplasia of the gastrointestinal tract. 
16. 
Subject is not in compliance with Section 5.2.3. 
 
If there are any questions regarding inclusion and exclusion criteria and/or subject 
eligibility, contact the Abbott Laboratories Medical Monitor identified in Section 7.0. 
5.2.3 
Prior and Concomitant Therapy 
5.2.3.1 
Prior Therapy 
Any medication (including over-the-counter medicines such as aspirin) that the subject is 
receiving during the study must be recorded in source documents and on the appropriate 
case report form (CRF) along with the reason for use, dates of administration and 
dosages. 
Any vaccine administered to the subject during the study should be listed as a 
concomitant medication.  Subjects should continue on the recommended vaccination 
schedule; however, vaccinations with live vaccines are prohibited.   
Any medications captured in the M06-806 CRF(s) which are ongoing will be transcribed 
onto the M06-807 source documents and CRF(s). 
If there are any questions regarding prior or concomitant therapy (ies), contact the Abbott 
Laboratories Medical Monitor identified in Section 7.0 

 
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5.2.3.2 
Concomitant Therapy 
Adjustments of Crohns related concomitant treatments, including Crohns related 
antibiotics, are not allowed during the first 8 weeks of the M06-807 study, unless subject 
safety is at risk. 
After Week 8, decreases in the dose or discontinuation of Crohns related antibiotics or 
Crohns related concomitant treatments are allowed according to the Investigators medical 
judgment.  These adjustments may be performed without prior discussion with the Abbott 
Medical Monitor.  In addition, Subjects may be able to initiate or reinitiate Crohns related 
treatments, except immunosuppressants, following eight (8) weeks of exposure to open-
label adalimumab.  Immunosuppressants may not be started or restarted during the study. 
Setons are allowed as concomitant therapy in subjects with perianal fistulas.  Their use 
should be documented on the concomitant medications page of the CRF. 
Growth hormone must be discontinued prior to the first dose of open-label study drug and 
Subjects may not begin using it while participating in this study. 
If a subject began to taper corticosteroids during the M06-806 study, they may continue 
this taper immediately upon enrollment into the M06-807 study.  Beginning at Week 8, 
subjects who are not in flare may begin corticosteroid taper according to the following 
schedule: 
Tapering Schedule 
Dose 
Rate 
Prednisone (or equivalent) 
> 10 mg 
d 10 mg  
5 mg/week 
2.5 mg/week 
Budesonide 
d 9 mg  
3 mg/week 
 
Subjects who are in flare or who flare after they have reduced or completely tapered their 
dose of corticosteroid may have their corticosteroid dose increased or restarted, at the 
discretion of the Investigator.  

 
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5.2.3.3 
Rescue Therapy 
If the Investigator decides, during the study, that a subject requires rescue therapy other 
than that described in this protocol, the subject must be terminated from the study.  If 
possible, questions regarding the use of rescue therapy should be discussed with the 
Medical Monitor prior to use. 
5.2.3.4 
Prohibited Therapy 
Live vaccines must not be given concurrently while on study drug and for 70 days after 
the last dose of study drug. 
Infliximab and growth hormone use are prohibited during the study.  At the Baseline 
visit, any subject using Growth hormone must discontinue its use. 
Tysabri (natalizumab), concurrent biological therapy, cyclosporine, tacrolimus, 
mycophenolate mofetil, Kineret® (anakinra), Orencia (abatacept), therapeutic enemas and 
suppositories (not including those done in conjunction with routine colonoscopies) and 
any investigational agent are prohibited during the study (see Appendix L). 
Concurrent use of budesonide and prednisone (or equivalent) is prohibited. 
Subjects with any prior exposure to Tysabri (natalizumab) will be excluded. 
5.3 
Efficacy, and Safety Assessments/Variables 
5.3.1 
Efficacy and Safety Measurements Assessed and Flow 
Chart 
Study procedures will be performed as summarized in the study schematic presented in 
Table 1. 
 

 
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Table 1.  
Study Activities 
Activity 
Baseline 
Week 4 
Week 8 
Week 12 
Week 24 
Week 36 
Week 48 
Week 60 
Week 72 
Week 84 
Week 96 
Week 108
Inclusion/exclusion criteria 
X 
 
 
 
 
 
 
 
 
 
 
 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
 
 
Previous and concomitant 
medications 
Xa 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Urine pregnancy testb 
Xa 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Vital signsc 
Xa 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Physical exam 
Xa 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
General LABd 
Xa 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Urinalysise 
Xa 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Erythrocyte sedimentation 
rate 
Xa 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
CRP 
Xa 
 
 
 
X 
 
X 
 
X 
 
 
X 
ANA 
Xa 
 
 
X 
 
 
 
 
 
 
 
X 
Anti-dsDNAf 
Xa 
 
 
X 
 
 
 
 
 
 
 
X 
PCDAI 
Xa 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
CDAIg 
Xa 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
IMPACT III Questionnaireh 
Xa 
 
 
X 
X 
 
X 
 
X 
 
 
X 
 

 
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Table 1.  
Study Activities (Continued) 
Activity 
Baseline 
Week 4 
Week 8 
Week 12 
Week 24 
Week 36 
Week 48 
Week 60 
Week 72 
Week 84 
Week 96 
Week 108
Unscheduled outpatient 
visits, emergency room 
visits and hospitalizations 
questionnaire 
Xa 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Work Productivity and 
Impairment Questionnaire: 
Crohns Disease (WPAI − 
CD) 
Xa 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X-ray for bone agei 
Xa 
 
 
 
 
 
X 
 
 
 
 
X 
Serum bone markers 
Xa 
 
 
 
X 
 
X 
 
X 
 
 
X 
PK Blood Samplej 
 
 
 
 
X 
 
X 
 
X 
 
X 
 
Anti-adalimumab blood 
levels (AAA)j 
 
 
 
 
X 
 
X 
 
X 
 
X 
 
Adverse eventsk 
Xa 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Dispense study drug 
Xa 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 

 
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27 
Table 1.  
Study Activities (Continued) 
Activity 
Week 
120 
Week 
132 
Call 
Week 
144 
Week 
156 
Call 
Week 
168 
Week 
180 
Call 
Week 
192 
Week 
204 
Call 
Week 
216 
Week 
228 
Call 
Week 
240 
Week 
252 
Call 
Week 
264/ 
Early 
Term 
Unsched 
Visit 
70-Day 
Follow-up 
Call 
Inclusion/exclusion 
criteria 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Informed consent 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Previous and concomitant 
medications 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Urine pregnancy testb 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
 
Vital signsc 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
 
Physical exam 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
 
General LABd 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
 
Urinalysise 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
 
Erythrocyte 
sedimentation rate 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
 
CRP 
 
 
X 
 
X 
 
X 
 
X 
 
 
 
X 
 
 
ANA 
 
 
X 
 
 
 
X 
 
 
 
 
 
X 
 
 
Anti-dsDNAf 
 
 
X 
 
 
 
X 
 
 
 
 
 
X 
 
 
PCDAI 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
 
CDAIg 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
 
IMPACT III 
Questionnaireh 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
 
 

 
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Table 1.  
Study Activities (Continued) 
Activity 
Week 
120 
Week 
132 
Call 
Week 
144 
Week 
156 
Call 
Week 
168 
Week 
180 
Call 
Week 
192 
Week 
204 
Call 
Week 
216 
Week 
228 
Call 
Week 
240 
Week 
252 
Call 
Week 
264/ 
Early 
Term 
Unsched 
Visit 
70-Day 
Follow-up 
Call 
Unscheduled outpatient 
visits, emergency room 
visits and 
hospitalizations 
questionnaire 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Work Productivity and 
Impairment 
Questionnaire: Crohns 
Disease  (WPAI − CD) 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
 
X-ray for bone agei 
 
 
X 
 
 
 
X 
 
 
 
 
 
X 
 
 
Serum bone markersi 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
 
PK Blood Samplej 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
 
Anti-adalimumab blood 
levels (AAA)j 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
 
Adverse eventsk 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Dispense study drug 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
 
Xl 
 
 

 
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Table 1.  
Study Activities (Continued) 
a. 
At the Baseline Visit, the following procedures will be completed as part of Week 52 of the M06-806 study. 
b. 
Performed on all females of child-bearing potential - Urine pregnancy test at all study visits. 
c. 
Vital sign determinations of height, weight, sitting blood pressure, heart rate, respiratory rate, and body temperature will be obtained at each visit. 
d. 
Blood draws should be performed after questionnaire and vital signs determinations and before study drug administration. 
e. 
Microscopic urinalysis will be performed at any visit if dipstick UA is abnormal (protein greater than a trace, blood greater than 5-10 Ery/ul, moderate or large ketone count 
or glucose greater than 50 mg/dL). 
f.  
If an ANA result is positive, anti-dsDNA will be performed automatically. 
g.  For subjects who are age 13 or older at the M06-807 Baseline Visit, a CDAI will be completed at each visit. 
h. 
For subjects who are age 10 or older at the M06-807 Baseline Visit, an IMPACT III Assessment will be completed at Baseline, Weeks 12, 24, 48, 72, 108, 120, 144, 168, 192, 
216, 240, 264/ET and unscheduled visits. 
i. 
If the height velocity is 0 and, in the opinion of the investigator, a subject is no longer growing, the x-ray for bone age and the determination of serum bone markers can be 
omitted. 
j. 
In addition to blood draws every 24 weeks, PK and AAA blood draws to be performed if subject meets flare criteria and dose escalated to ew dosing. 
k. 
All AEs, including SAEs, will be captured throughout the study from the time that the subject signs the Informed Consent Form.  SAEs will be captured throughout the 70 day 
follow-up period (if applicable). 
l. 
If an unscheduled visit is performed to change the frequency or dose of study drug, study drug may be dispensed. 
 
 

 
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5.3.1.1 
Study Procedures 
The M06-806 Week 52 visit will serve as the Baseline visit for the M06-807 study.  The 
study procedures outlined in Table 1 are discussed in detail in this section, with the 
exception of the collection of AE information (discussed in Section 6.0).  All study data 
will be recorded in source documents and on the appropriate CRFs.  The site will call the 
subjects at Weeks 132, 156, 180, 204, 228 and 252 in order to collect any safety 
information from the subject as illustrated in Table 1. 
The visit window for all scheduled visits is ±7 days calculated from the Baseline visit of 
the M06-807 study. 
Inclusion/Exclusion Criteria 
A subject will be excluded from this study if he/she does not meet all inclusion criteria or 
meets any of the exclusion criteria of Protocol M06-807. 
Informed Consent 
A signed Informed Consent Form (ICF) will be obtained from a subject of legal age (in 
the state of residence) or from the parent or legal guardian (as appropriate)of a subject 
who is not of legal age before any study related procedures are undertaken or before any 
medications are discontinued for the purpose of this study.  Additionally, an informed 
consent will be required from those subjects who were not of legal age at the onset of this 
study but become of legal age during the course of the study. 
In keeping with each institutions IRB requirements, an Informed Assent may also be 
required from pediatric subjects.  Pediatric subjects will be included in all discussions in 
order to obtain their signature on an assent form.  Details about how informed consent 
will be obtained and documented are provided in Section 9.3. 
If an updated informed consent is approved after a subject has completed or terminated 
early from the study, but is within the 70-day follow-up window, the subject will not be 
required to return to the site for the purposes of signing the updated ICF.  The subject of 

 
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31 
legal age, parent or legal guardian (as appropriate) should be contacted regarding any 
changes and the documentation of the contact should be present in the subjects source. 
Previous and Concomitant Medications 
Changes in concomitant medications will be assessed at each study visit from Baseline 
through the Week 264/ET visit.  Concomitant medications that are taken prior to the first 
dose of study drug administration for this study will be captured in the subjects casebook 
from the previous study (M06-806).  They will not be required to be captured in the 
subjects casebook of the M06-807 study unless they were ongoing at the Week 52 visit of 
the M06-806 study.  Ongoing concomitant medications from the M06-806 study will be 
transcribed into the subjects M06-807 casebook. 
Subjects of legal age or the parent or guardian (as appropriate) of subjects who are not of 
legal age will be provided with a medication log (see Appendix O) to record all 
medications the subject takes throughout the study.  This log must be returned for review 
at every study visit. 
Serum/Urine Pregnancy Test 
All female subjects who are experiencing menses, are nearing sexual maturation (in the 
opinion of the Investigator), or who are of child-bearing potential, will undergo a urine 
pregnancy test at each visit.  Urine pregnancy tests will be performed locally by 
designated study personnel.  If a urine pregnancy test is positive, a serum pregnancy test 
must be performed by the central laboratory.  If the serum pregnancy test is positive, the 
subject will be removed from the study.   
A lactating or pregnant female will not be eligible for participation in this study. 
Vital Signs 
Vital sign determinations of sitting blood pressure, heart rate, respiratory rate, body 
temperature, weight and height will be obtained at each visit.  All measurements will be 
recorded in metric units when applicable.  

 
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Weight measurements will be obtained using the same measuring instrument at each visit 
and measured with subjects wearing only undergarments.  Height measurements will be 
obtained using the same measuring equipment at each visit and performed on subjects 
with their shoes taken off. 
Physical Examination 
A physical examination will be performed at each visit.  A count of the number of 
cutaneous fistulas draining upon gentle compression will be performed during each 
physical exam.30  Fistulas will be classified as abdominal or perianal/anal. 
Physical exam abnormalities (including fistulas and fissures) noted by the Investigator 
will be evaluated and documented on the corresponding source documents.  Any new 
abnormalities or worsening of pre-existing conditions should be captured as AEs. 
Clinical Laboratory Tests  
Samples will be obtained for the laboratory tests listed in Table 2 at all study visits.  
Blood draws should be performed after questionnaires (PCDAI, IMPACT III 
Questionnaire, etc.) and vital sign determinations during a study visit, and before study 
drug administration. 
ICON central laboratory will be utilized to process and provide results for the general 
laboratory tests.  All abnormal laboratory test results that are considered clinically 
significant by the Investigator will be followed to a satisfactory resolution. 
ICON will provide instructions regarding the collection, processing and shipping of these 
samples. 

 
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Table 2.  
Clinical Laboratory Tests  
Hematologya 
Clinical Chemistry 
Urinalysisb 
Serum Bone Markers 
Hematocrit 
Hemoglobin 
Red Blood Cell (RBC) 
count 
White Blood Cell 
(WBC) count 
Neutrophils 
Bands 
Lymphocytes 
Monocytes 
Basophils 
Eosinophils 
Platelet count (estimate 
not acceptable) 
Blood Urea Nitrogen 
(BUN) 
Creatinine 
Total bilirubin 
Serum glutamic-pyruvic  
 
transaminase 
(SGPT/ALT) 
Serum glutamic-
oxaloacetic 
 
transaminase 
(SGOT/AST) 
Alkaline phosphatase 
Sodium 
Potassium 
Calcium 
Inorganic phosphorus 
Uric acid 
Cholesterol 
Total protein 
Glucose 
Triglycerides 
Albumin 
Specific gravity 
Ketones 
pH 
Protein 
Blood 
Glucose 
Osteocalcin 
Bone-specific alkaline 
phosphatase (BSAP)  
bone resorption (Ntx) 
a. 
Basic hematology testing performed on instrumentation does not include band reporting.  When 
Hematology results reflex to a Manual Differential, if there is a band result over 5, it is reported. 
b. Microscopic urinalysis will be performed at any visits if dipstick UA is abnormal  (protein greater than 
a trace, blood greater than 5-10 Ery/ul, moderate or large ketone count or glucose greater than 
50 mg/dL). 
 
Immunologic Laboratory Assessments   
CRP, adalimumab levels, anti-adalimumab antibody levels (AAA) and antinuclear 
antibody (ANA) assessments will be performed as indicated in Table 1.  If an ANA result 
is positive, anti-double-stranded DNA (anti-dsDNA) will be performed automatically. All 
CRP, ANA, anti-dsDNA will be performed by the central laboratory. 

 
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Erythrocyte Sedimentation Rate (ESR) assessments will be performed at all visits as 
indicated in Table 1.  ESR assessments will be performed by the sites local laboratory. 
Markers of Bone Metabolism  
Serum markers of bone metabolism will be measured as indicated in Table 1.  The bone 
formation markers to be measured are osteocalcin, bone-specific alkaline phosphatase 
(BSAP), and bone resorption (Ntx). 
Urinalysis 
Urine will be assessed by dipstick at each visit (done locally).  All results, including 
abnormalities, will be captured in source documentation and on the appropriate CRF.  
If, at any visit, the dipstick UA results are abnormal, the central lab will perform a 
microscopic urinalysis.  Abnormal is defined as protein greater than a trace, blood greater 
than 5-10 Ery/ul, moderate or large ketone count or glucose greater than 50 mg/dL. 
Pediatric Crohns Disease Activity Index (PCDAI) 
The PCDAI score will be calculated at each visit.  When completing the PCDAI, the 
HCT, albumin, and ESR values will be utilized from the same study visit.  
An example of the PCDAI is located in Appendix G.  Instructions for completing the 
PCDAI score is located in Appendix H. 
Crohns Disease Activity Index (CDAI) 
At each visit, a CDAI score will be calculated for subjects who are age 13 or older at the 
M06-807 Baseline Visit.  The CDAI score will be calculated utilizing the subject diary 
and the HCT value from the same study visit.  A copy of the CDAI subject diary is 
located in Appendix H. 
When completing question five (5) ("Taking Lomotil/Imodium/Loperamide/opiates for 
diarrhea, 0 = no, 1 = yes") on the CDAI, "no" should be answered if a subject is taking an 
opiate(s) solely for pain. 

 
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For the CDAI questions regarding presence of anal fistulas and other fistulas, all fistulas 
detectable on physical examination (draining and non-draining) should be captured on the 
CDAI CRF page and calculated into the CDAI score. 
The calculation of the CDAI score is in Appendix I. 
IMPACT III Questionnaire 
Subjects t 10 years old at the Baseline visit of the M06-807 study will complete an 
IMPACT III questionnaire as indicated in Table 1.  A copy of the questionnaire is located 
in Appendix K.  
The IMPACT III will be recorded directly onto the CRF.  The completed CRF will be 
considered source documentation for this assessment. 
Outcomes 
The Unscheduled Outpatient Visits, Emergency Room Visits and Hospitalization 
Questionnaire and the Work Productivity and Activity Impairment Questionnaire:  
Crohns Disease (WPAI-CD) will be completed at each visit except the Unscheduled Visit 
(Appendix N, Appendix T). 
The subjects parent or legal guardian will complete the WPAI directly onto the CRF.  
The completed CRF will be considered source documentation for this assessment. 
Bone Age 
An x-ray of the wrist for the assessment of bone age will be obtained as indicated in 
Table 1.  Sites should use the Greulich and Pyle method for reading the x − ray.31  The 
x-ray report requires the signature of the radiologist who read the films.  The bone age 
that is determined by the x-ray should be recorded on the CRF.   

 
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Anthropometric Evaluations 
Height and weight obtained at each visit will be used by Abbott Data Management and 
Statistical groups for determination of BMI and "z" score (observed height velocity 
(cm/yr) - mean height velocity for age and sex (cm/yr) / SD of the mean) for height. 
Adverse Events 
Adverse events will be assessed at every study visit from Baseline through the 
Week 264/ET visit.  Any AEs, which are ongoing in the M06-806 study, will be 
transcribed onto the M06-807 source documents and CRF(s) 
For those subjects who complete the study or terminate early, a phone call will be made 
70 days after the last dose of study drug to obtain follow-up information on any ongoing 
and any new AEs. See Section 6.0 and Appendix M for additional information. 
Study Drug Administration 
At each study visit, the subject or their trained designated friend, family member or 
health care professional will perform study drug injections under the supervision of a 
trained medical professional to reinforce proper aseptic SC injection technique.  Subjects 
or a trained designated friend, family member or health care professional will perform 
injections of study drug in the subjects home during weeks they are not in for scheduled 
clinic visits.  Subjects may return to the study site for injections in between study visits if 
subject or a trained designated friend, family member or health care professional cannot 
inject the study medication. 
Subjects will maintain a dosing diary for all study drug administered outside study visits, 
i.e., at home.  In the diary, the date, initials of the person administering the study drug, 
time study drug is administered, kit number and the dose administered will be recorded.  
Subjects must return this diary and it will be reviewed and verified for compliance at 
each visit by the research personnel at the study center.  All relevant dosing information 
will be retained by the study coordinator and transcribed onto a drug accountability form 
at each visit.  Additionally, any discernible departure from the protocol regarding study 

 
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drug administration will be recorded on source documents and appropriate drug 
accountability forms.  A sample of the Subject Dosing Diary is presented in Appendix P. 
At all office visits subjects should be observed after study drug administration, until 
judged clinically stable by the study personnel.  If an anaphylactic reaction or other 
serious allergic reaction occurs, administration of study drug should be discontinued 
immediately and appropriate therapy initiated.  When dosing at home, subjects should be 
instructed to contact the site immediately with any signs or symptoms of a reaction. 
The dosing dates, for all doses of study drug, should be calculated from the Baseline visit 
date.  The Baseline visit date for this study is 364 ± 7 days from the Baseline Visit date of 
M06-806.  A +/- 3 day window is allowable for scheduled study dosing dates. 
For subjects that deviate from this dosing window, every effort should be made to bring 
the subject back to the original dosing schedule as soon as possible.  For situations where 
bringing the subject back on the original dosing schedule will cause the dose to be out of 
the +/- 3 day window, please contact the Medical Monitor for additional instructions. 
Randomization and Assignment of Subject Numbers 
All subjects will be centrally registered using an IVRS.  This is an open-label study; 
subjects will not be randomized.  The telephone number and call in directions for the 
IVRS will be provided to each site.  Subjects will keep their study subject number from 
the previous double-blind study (M06 − 806). 
5.3.2 
Drug Concentration Measurements 
Blood samples for the assay of adalimumab and AAA serum concentrations will be 
collected at Baseline and every 24 weeks thereafter.  In addition, blood samples for 
adalimumab and AAA concentration analysis will also be collected if a subject meets 
flare criteria and dose escalated to ew dosing.  Study visits in which blood samples will 
be collected are listed in Table 1.  At each visit, blood samples will be collected prior to 
study drug administration at each visit. 

 
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The time that each blood sample is collected will be recorded to the nearest minute in the 
source documents and on the appropriate CRF. 
5.3.2.1 
Collection of Samples for Analysis 
Collection of Samples for Adalimumab Analysis 
Blood samples for adalimumab analysis will be collected by venipuncture into 
appropriately labeled 4-mL evacuated serum collection tubes without gel separator at 
visits indicated in Table 1.  All samples will be obtained immediately prior to dosing at 
visits indicated in Table 1.  Sufficient blood will be collected to provide approximately 
2 mL serum.  Allow the blood to clot for 30 minutes at room temperature before 
centrifugation. 
A maximum of 13 samples are planned to be collected per subject for the analysis of 
adalimumab concentrations. 
Collection of Samples for AAA Analysis 
Blood samples for AAA assay will be collected by venipuncture into appropriately 
labeled 4-mL evacuated serum collection tubes without gel separator at visits indicated in 
Table 1.  All samples will be obtained immediately prior to dosing at visits indicated in 
Table 1. Sufficient blood will be collected to provide approximately 2 mL serum.  Blood 
will be allowed to clot for 30 minutes at room temperature before centrifugation. 
A maximum of 13 blood samples are planned to be collected per subject for AAA 
analysis. 
5.3.2.2 
Handling/Processing of Samples 
The blood samples for adalimumab and AAA, assay will be centrifuged within 30 to 
60 minutes of collection to separate the serum.  The serum samples will be transferred 
using plastic pipettes into screw-capped polypropylene vials labeled with the type of 
sample (serum, SRM), the protocol number, subject number, the study week and the 

 
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assay (PK-Adalimumab, AAA).  The serum samples will be frozen within 2 hours after 
collection and will remain frozen in a –20°C or colder until shipped.  Sites that do not 
have access to a −20°C or colder freezer will need to ship the samples the day they are 
collected.  (Detailed instructions provided in the ICON Laboratory Manual). 
5.3.2.3 
Disposition of Samples 
The PK and AAA samples will be shipped to ICON with all other samples being shipped 
to ICON.  Refer to the ICON Lab Manual for further instruction.  Neither Abbott nor 
ICON will supply dry ice for this study.  Study sites will identify a dry ice source and 
purchase the necessary dry ice. 
5.3.2.4 
Measurement Methods 
Serum concentrations of adalimumab will be determined using a validated ELISA 
method under the supervision of the Drug Analysis Department at Abbott Laboratories.  
Only serum samples that have adalimumab levels < 2.0 Pg/mL will be selected for AAA 
concentration measurement. 
Serum concentrations of AAA will be determined using a validated ELISA method under 
the supervision of the Drug Analysis Department at Abbott Laboratories. 
5.3.3 
Efficacy Variables 
Efficacy will be evaluated based on the proportion of subjects who maintain PCDAI 
clinical response at each visit.  Clinical response is defined as PCDAI decrease 
t 15 points from the M06-806 Baseline score. 
Other measures of disease activity being assessed in this study will be summarized, 
including CDAI scores, IMPACT III scores, WPAI-CD Caregiver, z-score for height 
velocity, bone x-ray, serological markers of bone metabolism, healthcare resource 
utilization (unscheduled outpatient visits), adalimumab levels and anti-adalimumab levels 
(AAA). 

 
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5.3.4 
Safety Variables 
AEs, laboratory data, physical examinations and vital signs are the safety parameters and 
these will be assessed throughout the study. 
Treatment-emergent events will be summarized and reported by treatment group and by 
AAA status (AAA+ versus AAA-). 
5.3.5 
Pharmacokinetic Variables 
Serum concentrations of adalimumab and AAA will be determined from samples 
collected at the study visits listed in Table 1. 
5.4 
Removal of Subjects from Therapy or Assessment 
5.4.1 
Discontinuation of Individual Subjects 
Subjects will be withdrawn from the study immediately if any of the following occur:   
● Clinically significant abnormal laboratory results or AEs, which rule out 
continuation of the study drug, as determined by the Investigator and the 
Medical Monitor. 
● The Investigator believes it is in the best interest of the subject. 
● The subject or subjects legal guardian requests withdrawal from the study. 
● Selection criteria violation was noted after the subject started study drug, as 
determined by the Medical Monitor (see Sections 5.2.1 and 5.2.2). 
● Introduction of prohibited medications or prohibited concomitant medication 
dosages as determined by the Medical Monitor. 
● The subject is diagnosed with a malignancy except for localized 
non − melanoma skin cancer.  Discontinuation for carcinoma in-situ is at the 
discretion of the Investigator. 
● The subject is diagnosed with dysplasia of the gastrointestinal tract. 
● A female subject who becomes pregnant. 
 

 
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If the subject prematurely discontinues study drug use, the procedures outlined for the 
Week 264/ET Visit must be completed within 2 weeks of the last dose of study drug, and 
preferably prior to the initiation of another therapy.  These procedures should not 
interfere with the initiation of any new treatments or therapeutic modalities that the 
Investigator feels are necessary to treat the subjects condition.  Following discontinuation 
of the study drug, the subject will be treated in accordance with the Investigators best 
clinical judgment. 
Subjects who prematurely discontinue from the study will not be replaced.  The date of 
last dose and reason for premature discontinuation will be recorded in the source 
document and on the appropriate CRF. 
5.4.2 
Discontinuation of Entire Study 
Abbott reserves the right to discontinue the study at any time and to remove all study 
materials from the site.  Possible reasons for termination of the study include, but are not 
limited to: 
● Safety concerns based on reported data 
● Unsatisfactory enrollment with respect to quantity or quality 
● Inaccurate or incomplete data collection 
● Falsification of records 
● Failure to adhere to the protocol 
 
5.4.3 
Stopping Rules 
An independent Data Monitoring Committee (DMC) will meet to discuss data from the 
study approximately every six (6) months or at a frequency determined by the DMC and 
render their recommendation for either the continuation of the study or an amendment to 
the study.  A Sponsor Steering Committee (SSC), composed of senior executives not 
directly participating in this study, will make final decisions based on DMC 
recommendations. 

 
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5.5 
Treatments 
5.5.1 
Treatments Administered 
Study drug will be provided as a SC injection solution in pre-filled syringes containing 
adalimumab 40 mg/0.8 mL or adalimumab 20 mg/0.4 mL or in vials containing 
adalimumab 40 mg/0.8mL. 
Subjects who enroll into the study from blinded therapy in Study M06-806 will receive 
open-label therapy at a dose dependent on their body weight.  Subjects who weigh 
t 40 kg will receive 40 mg eow of adalimumab, while subjects who weigh < 40 kg will 
receive 20 mg eow of adalimumab.  Beginning from Week 8, subjects who have a disease 
flare may be switched to ew treatment at the same dose of adalimumab received while on 
eow treatment. 
Subjects who enroll into the study from open-label therapy in Study M06-806 will 
continue to receive the same dose they were receiving (i.e. 40 mg ew or 20 mg ew) at the 
Week 52 visit of the M06-806 study. 
Subjects who develop a flare while receiving ew open-label therapy or have a PCDAI 
score t 15 points when compared to their Baseline (Week 52 of M06-806) PCDAI score 
(regardless of study visit), may be discontinued from the study at the discretion of the 
Investigator. 
Beginning from Week 8, the dose of adalimumab may be increased to 40 mg, at the 
discretion of the investigator, for subjects whose body weight has increased from < 40 kg 
to t 40 kg from the study Baseline visit.  The site will enter the subject's body weight into 
the IVRS and the dose will be adjusted, if applicable. 
The dose of adalimumab may be decreased to the next lower treatment level as 
applicable, at the discretion of the Investigator and prior approval from the medical 
monitor, for subjects whose body weight has decreased from t 40 kg to < 40 kg from the 

 
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previous visit.  The site will enter the subject's body weight into the IVRS and the dose 
will be adjusted, if applicable. 
Subjects who responded to treatment defined as a) an improvement of at least 15 points 
in PCDAI compared to the last observation prior to dose escalation in patients who 
dose-escalated or b) an improvement of at least 15 points in PCDAI compared to 
Baseline of Study M06-806 in patients who did not dose-escalate) may have their dosage 
frequency decreased from ew to eow dosing.  The investigator should receive prior 
approval from the medical monitor before taking any action with regard to the dose 
frequency decrease.  At least 8 weeks after dose frequency decrease, subjects who still 
responded to treatment (as defined above) may have their dosage decreased (subjects who 
weigh ≥ 40 kg will receive 20 mg eow of adalimumab, while subjects who weigh < 40 kg 
will receive 10 mg eow of adalimumab).  The investigator should receive prior approval 
from the medical monitor before taking any action with regard to dose decrease. 
Subjects who experience a disease flare may re-increase their dosage or dose frequency 
to the next higher treatment level regardless of prior dose or dose frequency decrease.  
Simultaneous dose adjustment based on change of body weight as well as based on 
diseases status (response/flare) is prohibited. 
5.5.2 
Identity of Investigational Product 
The individual study drug information is presented in Table 3.  Pre-filled syringes (used 
for 40 mg/0.8 mL or 20 mg/0.4 mL doses) and 40 mg/0.8 mL vials (used for 10 mg dose) 
will be provided for this open-label clinical study. 

 
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Table 3.  
Identity of Investigational Products  
Study Drug 
Formulation 
Manufacturer 
Adalimumab 
40 mg/0.8 mL or 20 mg/0.4 mL  
Adalimumab/Mannitol, Citric acid monohydrate, Sodium citrate, 
Disodium phosphate dihydrate, Sodium dihydrogen phosphate 
dihydrate, Sodium chloride, Polysorbate 80, Water for injections, 
Sodium hydroxide added as necessary to adjust pH 
Abbott 
Adalimumab 
40 mg/0.8 mL (used for 10 mg dose) 
Adalimumab/Mannitol, Citric acid monohydrate, Sodium citrate, 
Disodium phosphate dihydrate, Sodium dihydrogen phosphate 
dihydrate, Sodium chloride, Polysorbate 80, Water for injections, 
Sodium hydroxide added as necessary to adjust pH 
Abbott 
 
5.5.2.1 
Packaging and Labeling 
The following information will appear on the pre-filled syringe, vial or carton labels: 
● Sponsor identification 
● Protocol number 
● Drug identification 
● Quantity of contents 
● Storage conditions 
● Dosing instructions 
● Kit number 
● Route of Administration 
● Excipients 
● Blank spaces to write the subjects identification number, initials, and date 
dispensed (as required) 
● Finishing lot # 
● Expiry Date (as required) 
 

 
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Two pre-filled syringes or vials will be provided in a dosing kit carton (see Table 4).  
Detailed instructions and training for the administration of study supplies are provided in 
Appendix Q. 
Table 4.  
Study Drug Packaging and Administration 
Open-label Pre-filled Syringes 
Open-label kit cartons containing two pre-filled 
syringes of adalimumab 40 mg/0.8 mL. 
Open-label kit cartons containing two pre-filled 
syringes of adalimumab 20 mg/0.4 mL. 
Open-label Vials (used for 10 mg dose) 
Open-label kit cartons containing two vials of adalimumab 40 mg/0.8 mL. 
 
5.5.2.2 
Storage and Disposition of Study Drug 
Pre-filled syringes and vials are to be stored protected from light at 2° to 8°C/36° to 46°F.  
DO NOT FREEZE.  A storage temperature log is to be maintained at the site to document 
proper storage conditions.  The refrigerator temperature must be recorded on every 
business day on a temperature log to record proper function.  Malfunctions must be 
reported to the sponsor immediately.  Study drug should be quarantined and not 
dispensed until Abbott GPRD or Abbott Temperature Excursion Management System 
(ATEMS) deems the medication as acceptable.  All clinical supplies must be stored and 
locked in a secure place until they are dispensed for subject use or are returned to Abbott 
Laboratories. 
Investigational products are for investigational use only, and are to be used only within 
the context of this study. 
5.5.3 
Method of Assigning Subjects to Treatment Groups 
This is an open-label study; all subjects will be receiving adalimumab. 
All subjects will be centrally registered using an IVRS.  The telephone number and 
call − in directions for the IVRS will be provided to each site.  Subjects will keep their 
study subject number from the previous study (M06 − 806). 

 
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Study drug will be administered at the study visits summarized in Table 1 and detailed in 
Section 5.3.1.1. 
5.5.4 
Selection and Timing of Dose for Each Subject 
Subjects who enroll into the study from blinded therapy in Study M06-806 will receive 
open-label therapy at a dose dependent on their body weight.  Subjects who weigh 
t 40 kg will receive 40 mg eow of adalimumab, while subjects who weigh < 40 kg will 
receive 20 mg eow of adalimumab.  Beginning from Week 8, subjects who have a disease 
flare may be switched to ew treatment at the same dose of adalimumab received while on 
eow treatment. 
Subjects who enroll into the study from open-label therapy in Study M06-806 will 
continue to receive the same dose they were receiving (i.e., 40 mg ew or 20 mg ew) at the 
Week 52 visit of the M06-806 study.  
Subjects who develop a flare while receiving ew open-label therapy or have a PCDAI 
score t 15 points when compared to their Baseline (the Week 52 visit of the M06-806 
study) PCDAI score (regardless of study visit), may be discontinued from the study at the 
discretion of the Investigator. 
The dose of adalimumab may be decreased to the next lower treatment level as applicable 
at the discretion of the Investigator and prior approval from the medical monitor, for 
subjects whose body weight has decreased from t 40 kg to < 40 kg from the previous 
visit.  The site will enter the subjects' body weight into the IVRS and the dose will be 
adjusted, if applicable. 
Subjects who responded to treatment defined as a) an improvement of at least 15 points 
in PCDAI compared to the last observation prior to dose escalation in patients who 
dose-escalated or b) an improvement of at least 15 points in PCDAI compared to 
Baseline of Study M06-806 in patients who did not dose-escalate) may have their dosage 
frequency decreased from ew to eow dosing.  The investigator should receive prior 
approval from the medical monitor before taking any action with regard to the dose 

 
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frequency decrease.  At least 8 weeks after dose frequency decrease, subjects who still 
responded to treatment (as defined above) may have their dosage decreased (subjects who 
weigh t 40 kg will receive 20 mg eow of adalimumab, while subjects who weigh < 40 kg 
will receive 10 mg eow of adalimumab).  The investigator should receive prior approval 
from the medical monitor before taking any action with regard to dose decrease. 
Subjects who experience a disease flare may re-increase their dosage or dose frequency 
to the next higher treatment level regardless of prior dose or dose frequency decrease.  
Simultaneous dose adjustment based on change of body weight as well as based on 
diseases status (response/flare) is prohibited. 
The Baseline Visit date for this study should be 364 ± 7 days from Baseline Visit date of 
M06-806 study.  All clinic visits for the subject should be scheduled on the same day as 
the Baseline visit for this study.  For home administration of drug, subjects will be 
instructed to inject study drug on the same day of the week as their Baseline visit day.  
Subjects must inject within a +/-3 day window of this day.  If the subject is out of the 
dosing window, the Medical Monitor should be contacted to determine the timing of the 
next dose.  The subject must record all dosing information on the subject dosing diary 
(Appendix P). 
5.5.5 
Blinding 
This is an open-label study. 
5.5.6 
Treatment Compliance 
The Investigator or his/her designated representatives will administer study drug only to 
subjects enrolled in the study.  
In order to document compliance with the treatment regimen, all pre-filled syringes and 
vials will be counted and documented in source documents and on the appropriate drug 
accountability form. 

 
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5.5.7 
Drug Accountability 
The Investigator or designee will verify that study drug supplies are received intact, at the 
appropriate temperature, and in the correct amounts from the drug depot.  This will be 
documented by signing and dating the Proof of Receipt (POR) or similar document.  The 
original POR or similar document will be kept in the site files as a record of what was 
received.  An accurate running inventory of study drug will be kept by the site, and will 
include the kit number, lot number(s), the number of pre-filled syringes or vials 
dispensed, and the date study drug was dispensed for each subject.  An overall 
accountability of the study drug will be performed and verified by the Clinical Research 
Associate (CRA) throughout the study and at the site close-out visit.  All unused 
pre-filled syringes and vials will be inventoried and returned to an identified vendor for 
disposal as designated by Abbott Laboratories.  A copy of the Drug Accountability Form, 
in accordance with instructions provided by the CRA, will also be included in the 
Returned Goods for disposal shipment.  A sample Drug Accountability Form is included 
in Appendix S.  A copy of the Drug Accountability Disposal Form, in accordance with 
instructions provided by the CRA, will also be included in the Pharmacy Binder provided 
to the site. 
All used (expelled) pre-filled syringes and vials will be inventoried by the site and 
verified by the CRA.  The used syringes and vials will be discarded on site, using 
appropriate biohazard precautions.  CRAs and site staff will complete study drug 
accountability via study drug logs, source documents, verification of empty used syringe 
kit or vials boxes, subject diaries and by visually counting the syringes in the sharps 
container whenever possible.  Used sharps containers should never be opened.  Each 
subject will be given their own sharps disposal container to store expelled/used syringes.  
Sharps containers should be returned by the subject at each visit, for accountability and 
compliance purposes.  New containers will be issued to subjects as necessary.  Once the 
CRA has verified drug accountability at the site, the site staff and CRA will sign off that 
the expelled pre-filled syringes and used vials have been destroyed. 

 
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5.6 
Discussion and Justification of Study Design 
5.6.1 
Discussion of Study Design and Choice of Control Groups 
The design of this clinical study was chosen to demonstrate adalimumab as an effective 
therapy for maintaining clinical response in pediatric subjects with CD and to gather 
long-term safety and tolerability data in this subject population. 
5.6.2 
Appropriateness of Measurements 
Standard statistical, clinical, and laboratory procedures will be utilized in this study.  All 
efficacy measurements in this study are standard for assessing disease activity in pediatric 
subjects with Crohns disease.  All clinical and laboratory procedures in this study are 
standard and generally accepted. 
5.6.3 
Suitability of Subject Population 
Pediatric subjects with CD who have participated in and successfully completed Protocol 
M06-806 through Week 52 and who meet all of the inclusion and none of the exclusion 
criteria are eligible for this study. 
5.6.4 
Selection of Doses in the Study 
The results of the pivotal adalimumab adult CD maintenance trial M02-404, in 
conjunction with results from adalimumab CD Study M02-433, support a maintenance 
dose of adalimumab 40 mg eow.  Data also suggest that patients who lose response to 
adalimumab at 40 mg eow can be dose-escalated to 40 mg weekly with the potential of 
regaining clinical response.  The proposed dosing regimen for Study M06-807 before 
Amendment 4 was developed using an analogous approach as that studied in the adult 
CD population.  Population pharmacokinetic modeling of serum adalimumab 
concentration data from pediatric subjects with JRA was used to identify doses to be 
evaluated in the current study in children with CD before Amendment 4.  A model based 
on the JRA population was chosen because the body weight range would closely parallel 
that in a juvenile CD population.  Escalation to weekly dosing would provide average 

 
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adalimumab concentrations at steady state about twice that observed with every other 
week dosing.  However, these concentrations are within the range of systemic exposures 
that were safely studied in adult subjects with CD. 
After completion of Study M06-806 and consideration of efficacy, safety and population 
pharmacokinetic results in conjunction with exposure-response modeling and simulation 
both the Low-Dose and High-Dose treatment provided evidence of efficacy and safety.  
Therefore, in order to minimize the systemic exposures to study drug to the lowest doses 
necessary in children with CD, Amendment 4 provides investigators with the option of 
dose de-escalation by reducing the dose or switching from ew to eow based on the 
clinical status of the individual patient.  In addition, since the 10 mg eow dose was 
efficacious in subjects weighing < 40 kg in Study M06-806 patients will have the option 
to be switched to this dose based on their body weight and clinical status at the discretion 
of the investigator. 
6.0 
Adverse Events 
The Investigator will monitor each subject for clinical and laboratory evidence of AEs on 
a routine basis throughout the study.  The Investigator will assess and record any AE in 
detail including the date of onset, description, severity, time course, duration and 
outcome, relationship of the AE to study drug, an event diagnosis, if known, and any 
action(s) taken.  For SAEs not considered "probably related" to study drug, the 
Investigator must provide another cause of event.  For AEs to be considered sporadic, the 
events must be of similar nature and severity.  AEs, whether in response to a query, 
observed by site personnel, or reported spontaneously by the subject will be recorded in 
source documentation and on the appropriate CRF page. 
All AEs will be followed to a satisfactory conclusion. 

 
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6.1 
Definitions 
6.1.1 
Adverse Event 
An AE is defined as any untoward medical occurrence in a patient or clinical 
investigation subject administered a pharmaceutical product and which does not 
necessarily have a causal relationship with this treatment.  An AE can therefore be any 
unfavorable and unintended sign (including an abnormal laboratory finding), symptom, 
or disease temporally associated with the use of a medicinal (investigational) product, 
whether or not the event is considered causally related to the use of the product. 
Such an event can result from use of the drug as stipulated in the protocol or labeling, as 
well as from accidental or intentional overdose, drug abuse, or drug withdrawal.  Any 
worsening of a pre-existing condition or illness is considered an AE.  Laboratory 
abnormalities and changes in vital signs are considered to be AEs only if they result in 
discontinuation from the study, necessitate therapeutic medical intervention, and/or if the 
Investigator considers them to be AEs. 
An elective surgery/procedure scheduled to occur during a study will not be considered 
an AE if the surgery/procedure is being performed for a pre-existing condition and the 
surgery/procedure has been pre-planned prior to study entry.  However, if the pre-existing 
condition deteriorates unexpectedly during the study (e.g., surgery performed earlier than 
planned), then the deterioration of the condition for which the elective surgery/procedure 
is being done will be considered an AE. 
6.1.2 
Serious Adverse Events 
If an AE meets any of the following criteria, it is to be reported to Abbott as an SAE 
within 24 hours of the site being made aware of the SAE.  Additionally, if follow-up 
information is received, it must also be reported to Abbott within 24 hours of being made 
aware of the information. 

 
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Death of Subject 
An event that results in the death of a subject. 
Life-Threatening 
An event that, in the opinion of the Investigator, will have resulted in 
immediate fatality if medical intervention had not been taken.  This does 
not include an event that will have been fatal if it had occurred in a more 
severe form. 
Hospitalization 
An event that results in an admission to the hospital for any length of 
time.  This does not include an emergency room visit or admission to an 
outpatient facility. 
Prolongation of 
Hospitalization 
An event that occurs while the study subject is hospitalized and prolongs 
the subjects hospital stay. 
Congenital Anomaly 
An anomaly detected at or after birth, or any anomaly that results in fetal 
loss. 
Persistent or Significant 
Disability/Incapacity 
An event that results in a condition that substantially interferes with the 
activities of daily living of a study subject.  Disability is not intended to 
include experiences of relatively minor medical significance such as 
headache, nausea, vomiting, diarrhea, influenza, and accidental trauma 
(e.g., sprained ankle). 
Important Medical Event 
Requiring Medical or 
Surgical Intervention to 
Prevent Serious Outcome 
An important medical event that may not be immediately life-threatening 
or result in death or hospitalization, but based on medical judgment may 
jeopardize the subject and may require medical or surgical intervention to 
prevent any of the outcomes listed above (i.e., death of subject, life 
threatening, hospitalization, prolongation of hospitalization, congenital 
anomaly, or persistent or significant disability/incapacity).  Examples of 
such events include allergic bronchospasm requiring intensive treatment 
in an emergency room or at home, blood dyscrasias or convulsions that do 
not result in inpatient hospitalization, or the development of drug 
dependency or drug abuse. 
Spontaneous Abortion 
Miscarriage experienced by study subject. 
Elective Abortion 
Elective abortion performed on study subject. 
 
6.2 
Adverse Event Severity 
The Investigator will use the following definitions to rate the severity of each AE: 
Mild 
The AE is transient and easily tolerated by the subject. 
Moderate 
The AE causes the subject discomfort and interrupts the subjects usual 
activities. 
Severe 
The AE causes considerable interference with the subjects usual activities 
and may be incapacitating or life threatening.   
 

 
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6.3 
Relationship to Study Drug 
The Investigator will use the following definitions to assess the relationship of the AE to 
the use of study drug:   
Probably Related 
An adverse event has a strong temporal relationship to study drug or 
recurs on re-challenge and an other cause of event is unlikely or 
significantly less likely. 
Possibly Related 
An AE has a strong temporal relationship to the study drug and an other 
cause of event is equally or less likely compared to the potential 
relationship to study drug. 
Probably Not Related 
An AE has little or no temporal relationship to the study drug and/or a 
more likely other cause of event exists. 
Not Related 
An AE is due to an underlying or concurrent illness or effect of another 
drug and is not related to the study drug (e.g., has no temporal 
relationship to study drug or has a much more likely other cause of event). 
 
If an Investigators opinion of possibly, probably not, or not related to study drug for an 
SAE is given, an alternative cause of the event must be provided by the Investigator for 
the SAE. 
6.4 
Adverse Event Collection Period 
All AEs reported from the time of informed consent until 5 half-lives (70 days), 
following discontinuation of study drug administration have elapsed will be collected, 
whether elicited or spontaneously reported by the subject.  In addition, SAEs will be 
collected from the time the subject or parent/legal guardian has signed the study-specific 
informed consent. 
Adverse event information will be collected as shown in Figure 3. 

 
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Figure 3.  
Adverse Event Collection 
SAEs and Non-serious AEs 
Elicited and/or Spontaneously Reported 
_ 
 
_ 
 
_ 
 
_ 
Consent 
Signed 
 
Study Drug 
Start 
 
Study Drug 
Stopped 
 
70 Days After 
Study Drug 
Stopped 
 
6.5 
Adverse Event Reporting 
In the event of an SAE, whether related to study drug or not, the investigator will notify 
one of the following people by faxing the appropriate SAE forms to one of the following 
people within 24 hours of the site being made aware of the SAE. 
For all sites: 
 
 
For questions regarding SAEs, please contact: 
 

 
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6.5.1 
Collection of Data Regarding Known Manifestations of the 
Disease Under Study 
Flare, of Crohns disease events per study definition, are not required to be captured as 
AEs, but may be captured per Investigator discretion.  Additionally, CD pre-existing 
conditions will not be captured as AEs unless the condition has worsened or is considered 
clinically significant in the opinion of the Investigator. 
6.6 
Pregnancy 
Abbott Laboratories must be notified within 1 working day of a sites learning if a female 
subject becomes pregnant during the study or within 150 days of receiving the last dose 
of study drug (see Section 6.5 for contact information). 
Females who become pregnant during the study will be discontinued from study drug as 
described in Section 5.4.  Data regarding the outcome of any pregnancy occurring in a 
study subject will be collected.  Upon notification of a pregnancy Abbott will forward a 
form to the site, for the Investigator to complete and send back to Abbott.  A second form 
will also be sent approximately 9 months from the date of notification to collect 
information on the outcome of the pregnancy.  This form will also need to be completed 
and sent back to Abbott. 
To monitor outcomes of pregnant women exposed to adalimumab, a pregnancy registry 
has been established for the United States, Canada and Puerto Rico.  Physicians in the 
United States are encouraged to register subjects by calling 
and/or 
provide this information to the subject. 
Pregnancy in a study subject is not considered an AE.  However, the medical outcome of 
an elective or a spontaneous abortion, stillbirth or congenital anomaly is considered a 
SAE, and must be reported to the sponsor with 24 hours of the site learning of the event. 

 
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7.0 
Protocol Deviations 
The investigator should not implement any deviation from the protocol without prior 
review and agreement by the Sponsor and in accordance with the IEC/IRB and local 
regulations, except when necessary to eliminate an immediate hazard to study subjects.  
When a deviation from the protocol is deemed necessary for an individual subject, the 
investigator must contact the following Abbott representative: 
 
For purposes of this protocol, reportable deviations are defined as:   
● Subject entered into the study even though they did not satisfy entry criteria 
● Subject who developed withdrawal criteria during the study and was not 
withdrawn 
● Subject who received wrong treatment or incorrect dose 
● Subject who received excluded concomitant treatment 
 
Such contact must be made as soon as possible to permit a review by Abbott to determine 
the impact of the deviation on the subject and/or the study.  Any significant protocol 
deviations affecting subject eligibility and/or safety must be reviewed and/or approved by 
the IEC/IRB and regulatory authorities, as applicable, prior to implementation. 

 
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8.0 
Statistical Methods and Determination of Sample 
Size 
8.1 
Statistical and Analytical Plans 
8.1.1 
Analyzable Population 
Efficacy analyses will be conducted in the intent-to-treat (ITT) population, which is 
defined as all subjects who received at least one dose of adalimumab in Study M06-807.  
The safety population consists of all subjects who received at least one dose of 
adalimumab in Study M06-807. 
8.1.2 
Planned Methods of Statistical Analysis 
All statistical analyses are to be performed descriptively.  Descriptive summary statistics 
will be provided for the demographic and baseline characteristics, efficacy, and safety 
parameters.  Continuous variables will be summarized using the number of observation, 
mean, standard deviation, 1st quartile, median, 3rd quartile, minimum, and maximum; 
whereas discrete variables will be summarized using count and percentages.  
8.1.2.1 
Demographics and Baseline Characteristics 
Summary statistics for the demographic and baseline characteristics will be computed 
based on the Week 52 values (from double-blind Study M06-806). 
8.1.2.2 
Efficacy Analysis 
Summary statistics will be provided for each visit, based on observed data.  An additional 
summary will be provided for the last visit, using the last observation carried forward 
(LOCF).  That is, the subjects last non-missing, post-baseline value (i.e., post-Week 52 
M06-806 double-blind value) will be carried forward to the last visit. 
8.1.3 
Other Analyses 
Efficacy will be analyzed for the following subgroups in the ITT population. 

 
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● Sex [Male, Female] 
● Age [< 13 years, t 13 years] 
● Ethnicity [White, Non-white] 
● Weight [< 40 kg, t 40 kg] 
● Prior infliximab use [No, Yes] 
● Baseline CRP [< 1.0 mg/dL, t 1.0 mg/dL] 
● Concomitant use of immunosuppressants and/or oral corticosteroids [No, Yes] 
 
8.1.4 
Safety Analyses 
Safety analyses will be based on the safety population.  Treatment-emergent AEs will be 
summarized.  An overview of treatment-emergent AEs including AEs of special interest, 
such as AEs leading to death and AEs leading to premature discontinuation, AEs by 
(MedDRA® version 10.0 or later) preferred term and system organ class, AEs by 
maximum relationship to study drug, and AEs by maximum severity will be summarized.  
Treatment-emergent AEs are defined as new events that begin either on or after the first 
dose of the study drug and within 70 days after the last dose of the study drug. 
Adverse events with missing or unknown severity will be categorized as severe.  Adverse 
events with missing or unknown relationship to study drug will be categorized as 
probably related. 
Adverse events that are reported more than 70 days after last study injection will be 
excluded from the summaries; however, all reported AEs will be included in the AE data 
listings. 
For laboratory parameters, the normal range of the analyzing laboratory will be used and 
all values outside the normal range will be flagged and listed.  Additionally, descriptive 
statistics for the mean change from baseline to minimum (smallest) value, maximum 
(largest) value and final value during the study will be calculated for the continuous 
clinical laboratory parameters.  

 
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Shift tables will be provided to cross-classify and tabulate subjects value from baseline to 
final value by the presence of clinically significant laboratory results.  Each subjects 
baseline value and final value will be flagged in reference to the normal range (low, 
normal, high) and also categorized as clinically non-significant (CTC grade < 3) or 
clinically significant (CTC grade t 3).  Further details will be provided in the SAP. 
8.1.4.1 
Pharmacokinetic Analyses 
Adalimumab trough serum concentrations will be summarized by treatment group at each 
time point using descriptive statistics including number of subjects, number of non 
missing observations (nnmiss), mean, median, standard deviation, coefficient of 
variation, minimum, and maximum.  The relationship between adalimumab 
concentrations and efficacy and/or safety variables may be explored.  Additional analysis 
may be performed. 
8.1.5 
Interim Analysis 
There will be one planned interim analysis.  Details of the analysis will be described in 
the study SAP. 
8.2 
Determination of Sample Size 
Subjects who successfully completed Study M06-806 through Week 52 may be eligible 
to participate in this study. It is expected that approximately 70% (130) of subjects from 
the M06-806 study will enroll in this study. 
8.3 
Randomization Methods 
All subjects will be centrally registered using an IVRS.  This is an open-label study; 
therefore, subjects will not be randomized before the study is initiated, the telephone 
number and call in directions for the IVRS will be provided to each site.  Subjects will 
keep their subject number from the previous study (M06-806). 

 
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9.0 
Ethics 
9.1 
Independent Ethics Committee (IEC) or Institutional Review 
Board (IRB) 
Good Clinical Practice (GCP) requires that the clinical protocol, any protocol 
amendments, the Investigators Brochure, the informed consent and all other forms of 
subject information related to the study (e.g., advertisements used to recruit subjects) and 
any other necessary documents be reviewed by an IEC/IRB.  IEC/IRB approval of the 
protocol, informed consent and subject information and/or advertising, as relevant, will 
be obtained prior to the authorization of drug shipment to a study site. 
Any amendments to the protocol will require IEC/IRB approval prior to implementation 
of any changes made to the study design.  A list of the documents required prior to 
initiation of the study can be found in Appendix C. 
Any SAEs that meet the reporting criteria, as dictated by local regulations, will be 
reported to both responsible Ethics Committees and Regulatory Agencies, as required by 
local regulations.  During the conduct of the study, the Investigator should promptly 
provide written reports (e.g., ICH Expedited Reports, and any additional reports required 
by local regulations) to the IEC/IRB of any changes that affect the conduct of the study 
and/or increase the risk to subjects, unless otherwise submitted by the sponsor.  Written 
documentation of the submission to the IEC/IRB should also be provided to Abbott. 
9.2 
Ethical Conduct of the Study 
The study will be conducted in accordance with the protocol, International Conference on 
Harmonization (ICH) guidelines, applicable regulations and guidelines governing clinical 
trial conduct, and the ethical principles that have their origin in the Declaration of 
Helsinki.  Responsibilities of the clinical Investigator are specified in Appendix D. 

 
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9.3 
Subject Information and Consent 
Prior to any study-related procedures or discontinuation of any medications for this study, 
the Investigator or his/her representative will explain the nature of the study to the subject 
of legal age (in the state of residence) or to the parent or legal guardian (as appropriate) 
of a subject who is not of legal age and answer all questions regarding this study.  
Subjects will be included in all discussions. 
The ICF will be reviewed, signed and dated by the subject of legal age (in the state of 
residence) or by the parent or legal guardian (as appropriate) of a subject who is not of 
legal age, and the person who administered the informed consent.  If a subject who was 
not of legal age at the onset of this study becomes of legal age during the course of the 
study, an informed consent will need to be obtained at that time.  Additionally, in keeping 
with each institutions IRB requirements an Informed Assent will also be obtained from 
the subject, as required.   
A copy of the signed ICF and Assent Form will be given to the subject and the subjects 
parent/legal guardian.  The original signed ICF and Assent Form will be placed in the 
subjects medical record.  An entry must also be made in the subjects dated source 
documents to confirm that informed consent was obtained prior to any study-related 
procedures and that the subject received a signed copy. 
If an updated informed consent is approved after a subject has completed or terminated 
early from the study, but is within the 70-day follow-up window, the subject will not be 
required to return to the site for the purposes of signing the updated ICF.  The subject of 
legal age, parent or legal guardian (as appropriate) should be contacted regarding any 
changes and the documentation of the contact should be present in the subjects source.  

 
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10.0 
Source Documents and Case Report Form 
Completion 
10.1 
Source Documents 
Source documents are defined as original documents, data and records.  This may include 
hospital records, clinical and office charts, laboratory data/information, subjects diaries or 
evaluation checklists, pharmacy dispensing and other records, recorded data from 
automated instruments, microfiches, photographic negatives, microfilm or magnetic 
media, and/or x-rays.  Data collected during this study must be recorded on the 
appropriate source documents. 
The Investigator(s)/institution(s) will permit study-related monitoring, audits, IEC/IRB 
review, and regulatory inspection(s), providing direct access to source data documents. 
The IMPACT III questionnaire and the WPAI questionnaire will be recorded directly on 
the CRF(s) by the subject, parent or legal guardian (as appropriate) and these CRFs will 
be considered source data. 
10.2 
Case Report Forms 
Case report forms will be supplied by Abbott.  These forms will be used to transmit 
information collected during the study to Abbott and regulatory authorities, as applicable.  
Case report forms must be completed for each subject enrolled in this study.  All case 
report forms must be legible and completed in indelible black ballpoint ink.  Any 
necessary corrections are to be made by drawing a single line through the incorrect entry 
and writing in the revision.  All revisions must be initialed and dated by the Investigator 
or his/her representative.  Data are not to be obliterated by blacking out, using correction 
fluid or by erasing the original entry.  If the reason for the correction is not obvious, a 
brief explanation (e.g., transcription error) should accompany the change.  All 
information written on the case report forms must also be reflected in the subject source 
documents with the exception of the case report forms discussed above in Section 10.1. 

 
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The Principal Investigator will review the case report forms for completeness and 
accuracy and sign and date each set of case report forms where indicated.  The case 
report forms will be reviewed periodically for completeness, legibility and acceptability 
by Abbott personnel (or their representatives).  Abbott (or their representatives) will be 
allowed access to all source documents in order to verify case report form entries. 
Once the original case report form has been removed from the site, all changes must be 
made via the appropriate change form specified by Abbott.  The Principal Investigator 
will review the change form for completeness and accuracy and sign and date the change 
form where indicated. 
11.0 
Data Quality Assurance 
Prior to the initiation of the study, an Investigators meeting will be held with Abbott 
personnel, the Investigators and their study coordinators, the CROs project manager and 
the CRAs for the study.  This meeting will include a detailed discussion of the protocol, 
performance of study procedures, CRF and Subject Diary completion, and specimen 
collection methods.  In addition to or instead of the Investigators meeting, the study 
personnel at each site may be trained on the study procedures by a CRA at a study 
initiation visit and will be given a CRF completion workbook for reference. 
The CRAs will monitor at each site throughout the study.  One hundred percent (100%) 
source document review will be performed against entries on the CRF and a quality 
assurance check will be performed to ensure that the Investigator is complying with the 
protocol and regulations.  In addition, after CRFs are retrieved by the CRA, a review of 
the data will be conducted by a physician and a clinical review team at Abbott 
Laboratories. 
All data hand entered in the database will be verified by a double-key entry procedure at 
Abbott.  Any discrepancies will be reviewed against the hard copy CRF and corrected on-
line. After completion of the entry process, computer logic checks will be run to check 
for such items as inconsistent study dates and outlying laboratory values.  Any necessary 

 
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corrections will be made to the database and documented via addenda, queries, source 
data clarification form or audit trail.  A manual review of selected line listings will also 
be performed at the end of the study. 
Routine hematology, serum chemistry, and serology will be conducted using a central 
laboratory.  ESR analysis will be done at a local lab designated by the site. The data from 
these analyses will be electronically transferred from the central laboratory to the study 
database.  Urinalysis will be completed locally.  If a microscopic urinalysis is necessary, 
this testing will be conducted using the central laboratory.  A final review of all 
laboratory results will be conducted by a physician and clinical review team at 
Abbott Laboratories. 
Sites will provide Abbott (or designate) with laboratory certifications (CAP and CLIA), 
CV of local lab director, and reference ranges for each local lab used.  The full name, 
address, phone number, and fax number for each local lab will also be included. 
12.0 
Use of Information and Publication 
12.1 
Use of Information 
All information concerning adalimumab and Abbott Laboratories operations, such as 
Abbott Laboratories patent applications, formulas, manufacturing processes, basic 
scientific data, or formulation information, supplied by Abbott Laboratories and not 
previously published is considered confidential information. 
The information developed during the conduct of this clinical study is also considered 
confidential and will be used by Abbott Laboratories in connection with the development 
of adalimumab.  This information may be disclosed as deemed necessary by 
Abbott Laboratories to other clinical Investigators, other pharmaceutical companies, to 
the FDA, and to other government agencies.  To allow for the use of the information 
derived from this clinical study and to ensure complete and thorough analysis, the 
Investigator is obligated to provide Abbott Laboratories with complete test results and all 

 
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data developed in this study and to provide direct access to source data/documents for 
study- related monitoring, audits, IEC/IRB review, and regulatory inspection. 
This confidential information shall remain the sole property of Abbott Laboratories, shall 
not be disclosed to others without the written consent of Abbott Laboratories, and shall 
not be used except in the performance of this study. 
The Investigator will maintain a confidential subject identification code list of all subjects 
enrolled in the study (by name and subject number).  This list will be maintained at the 
site and will not be retrieved by Abbott. 
12.2 
Internet Sites 
Information regarding this study may be posted on various internet web sites and will 
maximally include study name, number, general population to be enrolled, entrance 
qualifications, brief description of the study, study objectives, doses, accruing 
Investigators (upon their approval) and number of subjects to be enrolled. 
13.0 
Completion of the Study 
The Investigator will conduct this study in compliance with the protocol, and will 
complete the study within the timeframe specified in the contract between the 
Investigator and Abbott.  Continuation of the study beyond this time must be mutually 
agreed upon in writing by both the Investigator and Abbott.  The Investigator will 
provide a summary of the study's outcome to the IEC/IRB following conclusion of the 
study, and will forward a copy of this summary to Abbott or their designee. 
Abbott may terminate this study prematurely, either in its entirety or at individual sites, 
for reasonable cause provided that written notice is submitted a reasonable time in 
advance of the intended termination.  The Investigator may also terminate the study at 
their site for reasonable cause, after providing written notice to Abbott a reasonable time 
in advance of the intended termination.  Advance notice is not required by either party if 
the study is stopped due to safety concerns.  If Abbott terminates the study for safety 

 
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reasons, it will immediately notify the Investigator by telephone and subsequently 
provide written instructions for study termination. 
Abbott will select the signatory Investigator from the Investigators who participate in the 
study.  Selection criteria for this Investigator will include level of participation as well as 
significant knowledge of the clinical research, investigational drug and study protocol.  
The signatory Investigator for the study will review and sign the final study report in 
accordance with the European Agency for the Evaluation of Medicinal Products (EMEA) 
Guidance on Investigators Signature for Study Reports. 
The Investigator will retain all essential documents until at least two years after the last 
approval of a marketing application in an ICH region and until there are no pending or 
contemplated marketing applications in an ICH region or at least two years have elapsed 
since the formal discontinuation of clinical development of the investigational product.  It 
is the responsibility of the sponsor to inform the Investigator/institution as to when these 
documents no longer need to be retained. 
The end-of-study is defined as the date of the last subjects last scheduled visit or the 
actual date of follow-up contact, whichever is longer. 
 

 
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14.0 
Investigators Agreement 
1. I have received and reviewed the Investigator Brochure for Humira. 
2. I have read this protocol and agree that the study is ethical. 
3. I agree to conduct the study as outlined and in accordance with all applicable 
regulations and guidelines. 
4. I agree to maintain the confidentiality of all information received or developed in 
connection with this protocol. 
 
 
 
 
Protocol Title: 
A Multi-center, Open-label Study of the Human Anti-TNF 
Monoclonal Antibody Adalimumab to Evaluate the Efficacy and the 
Long-term Safety and Tolerability of Repeated Administration of 
Adalimumab in Pediatric Subjects with Crohn's Disease Who Have 
Demonstrated a Clinical Response in the M06-806 Study 
Protocol Date: 
29 June 2011 
 
 
 
 
 
 
Signature of Principal Investigator 
 
Date 
 
 
 
Name of Principal Investigator (printed or typed) 
 
 
 
 

 
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15.0 
Reference List 
1. 
Hanauer SB, Sandborn W.  Management of Crohns disease in adults.  Am J 
Gastroenterol 2001;96:635-43. 
2. 
Loftus Jr. EV.  Clinical epidemiology of inflammatory bowel disease: Incidence, 
prevalence, and environmental influences.  Gastroenterology 2004;126:1504-17. 
3. 
Seidman EG.  Recent advances in the diagnosis and treatment of pediatric 
inflammatory bowel disease.  Curr Gastroenterol Rep 2000;2:248-52. 
4. 
Auvin S, Molinie F, Gower-Rousseau C, Brazier F, Merle V, Grandbastient B, 
et al.  Incidence, clinical presentation and location at diagnosis of pediatric 
inflammatory bowel disease: a prospective population-based study in northern 
France (1988-1999).  J Pediatr Gastroenterol Nutr 2005;41(1):49-55. 
5. 
Kugathasan S, Judd RH, Hoffmann RG, Heikenen J, Telega G, Khan F, et al.  
Epidemiologic and clinical characteristics of children with newly diagnosed 
inflammatory bowel disease in Wisconsin; a statewide population-based study.  
J Pediatr 2003;143(4):525-31. 
6. 
Cosgrove M, Al-Atia RF, Jenkins HR.  The epidemiology of pediatric 
inflammatory bowel disease.  Arch Dis Child 1996;74:460-1. 
7. 
Hassan K, Cowan FJ, Jenkins HR.  The incidence of childhood inflammatory 
bowel disease in Wales.  Eur J Pediatr 2000;159:261-3. 
8. 
Barton JR, Gillon S, Ferguson A.  Incidence of inflammatory bowel disease in 
Scottish children between 1968 and 1983; marginal fall in ulcerative colitis, three-
fold rise in Crohns Disease.  Gut 1989;30:618-22. 
9. 
Sawczenko A, Sandhu BK, Logan RFA, et al.  Prospective survey of childhood 
inflammatory bowel disease in the British Isles.  Lancet 2001;357:1093-4. 

 
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10. 
Olafsdottir EJ, Fluge G, Haug K.  Chronic inflammatory bowel disease in children 
in western Norway.  J Pediatr Gastroenterol Nutr 1989;8:454-8. 
11. 
Lindberg E, Lindquist B, Holmquist L, Hildebrand H.  Inflammatory bowel 
disease in children and adolescents in Sweden (1984-1995).  J Pediatr 
Gastroenterol Nutr 2000;30:259-64. 
12. 
Hildebrand H, Finkel Y, Grahnquist L, Lindholm J, Ekbom A, Askling J.  
Changing pattern of paediatric inflammatory bowel disease in northern Stockholm 
1990-2001. Gut 2003;52:1432. 
13. 
Heyman MB, Kirshner BS, Gold BD, Ferry G, Baldassano R, Cohen SA, et al.  
Children with early onset inflammatory bowel disease (IBD): analysis of a 
pediatric IBD consortium registry.  J Pediatr 2005;146(1):35-40. 
14. 
Lindberg E, Lindquist B, Holmquist L, Hildebrand H.  Inflammatory bowel 
disease in children and adolescents in Sweden, 1984-1995.  J Pediatr Gastroenterol 
Nutr 2000;30(3):259-64. 
15. 
Sawczenko A, Sandhu BK.  Presenting features of inflammatory bowel disease in 
Great Britain and Ireland.  Arch Dis Child 2003;88:995-1000. 
16. 
Griffiths AM.  Specificities of inflammatory bowel disease in childhood.  Best 
Pract Res Clin Gastroenterol 2004;18(3):509-23. 
17. 
Griffiths AM, Nguyen P, Smith C, MacMillan JH, Sherman PM.  Growth and 
clinical course of children with Crohns disease.  Gut 1993;34(7):939-43. 
18. 
Kanof ME, Lake AM, Bayless TM.  Decreased height velocity in children and 
adolescents before the diagnosis of Crohns disease.  Gastroenterology 
1988;95(6):1523-7. 
19. 
Markowitz J, Grancher K, Rosa J, Aiges H, Daum F.  Growth failure in pediatric 
inflammatory bowel disease.  J Pediatr Gastroenterol Nutr 1993;16(4):373-80. 

 
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20. 
Kleinman RE, Baldassano RN, Caplan A, Griffiths AM, Heyman MB, 
Issenman RM, et al.  Nutrition support for pediatric patients with inflammatory 
bowel disease: a clinical report of the North America Society for Pediatric 
Gastroenterology, Hepatology and Nutrition.  J Pediatr Gastroenterol Nutr 
2004;39(1):15-27. 
21. 
Gokhale R, Favus MJ, Karrison T, Sutton MM, Rich B, Kirshner BS.  Bone 
mineral density assessment in children with inflammatory bowel disease.  
Gastroenterology 1998;114:902-11. 
22. 
Boot AM, Bouquet J, Krennings EP, de Muinck Keizer-Schrama SMPF.  Bone 
mineral density and nutritional status in children with chronic inflammatory bowel 
disease.  Gut 1998;42:188-94. 
23. 
Ballinger AB, Savage MO, Sanderson IR.  Delayed puberty associated with 
Inflammatory bowel disease.  Pediatr Res 2003;53:205-10. 
24. 
Harpavat M, Greenspan SL, OBrien C, Chang C-C, Bowen A, Keljo DJ.  Altered 
bone mass in children at diagnosis of Crohns disease: a pilot study.  J Pediatr 
Gastroenterol Nutr 2005;40:295-300. 
25. 
Hyams JS, Wyzga N, Kreutzer DL, Justinich CJ, Gronowicz GA.  Alterations in 
bone metabolism in children with inflammatory bowel disease: an in vitro study. 
J Pediatr Gastroenterol Nutr 1997;24(3):289-95. 
26. 
Hanauer S, Lukas M, MacIntosh D, Rutgeerts P, Sandborn W, Pollack P.  A 
randomized, double-blind, placebo-controlled trial of the human anti-TNF-D 
monoclonal antibody adalimumab for the induction of remission in patients with 
moderate to severely active Crohns disease.  Gastroenterology 2004;127(1):332. 
27. 
Data on file at Abbott Laboratories. 
28. 
Abbott Study DE038, Data on file. 

 
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29. 
Humira® (adalimumab) [package insert].  North Chicago, IL:  
Abbott Laboratories:  June 2006. 
30. 
Present DH, Rutgeerts P, Targan S, Hanauer SB, Mayer L, van Hogezand RA, 
et al.  Infliximab for the treatment of fistulas in patients with Crohns disease. 
N Eng J Med.  1999;340(18):1398-405. 
31. 
Greulich and Pyle Radiographic Atlas of Skeletal Development of the Hand and 
Wrist:  June 1959. 
32. 
Centers for Disease Control and Prevention.  Targeted tuberculin testing and 
treatment of latent tuberculosis infection.  MMWR 2006 April. 
 

 
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Appendix A.  
List of Abbreviations and Definition of Terms 
Abbreviations 
AAA 
Anti-adalimumab antibody 
AE 
Adverse Event 
ALT 
Alanine Transaminase 
ANA 
Antinuclear antibody 
AST 
Aspartate transaminase 
BMI 
Body Mass Index 
BSAP 
Bone-specific alkaline phosphatase 
BUN 
Blood Urea Nitrogen 
CD 
Crohns disease 
CDC 
Center for Disease Control 
CNS 
Central Nervous Systems 
CRA 
Clinical Research Associate 
CRF 
Case Report Form 
CRP 
C-Reactive Protein 
CTC 
Common Toxicity Criteria 
DMC 
Data Monitoring Committee 
DNA 
Deoxyribonucleic acid 
dsDNA 
Double Stranded DNA 
eow 
Every other week 
ESR 
Erythrocyte sedimentation rate 
ET 
Early Termination 
EU 
European Union 
ew 
Every week 
FDA 
U.S. Food and Drug Administration 
GCP 
Good Clinical Practice 
HCT 
Hematocrit 
HIV 
Human immunodeficiency virus 
ICH 
International Conference on Harmonization 
IEC 
Independent Ethics Committee 
IgG1 
Immunoglobulin 
ICF 
Informed Consent Form 

 
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IRB 
Institutional Review Board 
ITT 
Intent-to Treat 
IVRS 
Interactive Voice Response System 
JRA 
Juvenile Rheumatoid Arthritis 
LOCF 
Last Observation Carried Forward 
MTX 
Methotrexate 
Ntx  
N − telopeptide 
OL 
Open-Label 
PCDAI 
Pediatric Crohns Disease Activity Index 
PK 
Pharmacokinetics 
POR 
Proof of Receipt 
RA 
Rheumatoid Arthritis 
SAE 
Serious Adverse Event 
SAP 
Statistical analysis plan 
SC 
Subcutaneous 
SSC 
Sponsor Steering Committee 
TB 
Tuberculosis 
TNF 
Tumor Necrosis Factor 
TPN 
Total Parenteral Nutrition 
US 
United States 
WPAI 
Work Productivity and Activity Impairment Questionnaire 
WPAI-CD 
Work Productivity and Activity Impairment Questionnaire: Crohns 
Disease 
 

 
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Appendix B.  
List of Protocol Signatories 
Name 
Title 
Functional Area 
Statistics 
Clinical 
Clinical 
Clinical 
 

 
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Appendix C.  
Documents Required Prior to Initiation of the Study 
As sponsor of a clinical study, Abbott has an obligation to ensure that the study will be 
conducted by a qualified investigator with sufficient resources (of time, personnel, and 
physical facilities) to conduct the study and to ensure that the investigator understands 
and agrees to comply with Good Clinical Practices and applicable regulations, policies, 
and procedures.  Prior to the beginning of any clinical study, the investigator will be 
asked to provide the following documentation.  
1. 
A signed and dated Investigators agreement page for the study. 
2. 
A signed and dated Form FDA 1572 certifying the investigators agreement to 
comply with the appropriate regulations governing the conduct of the study. 
 
A signed and dated Investigator Information and Agreement Form certifying the 
investigators agreement to comply with the appropriate (e.g., ICH GCP) 
regulations governing the conduct of the study. These will be required only for 
sites that are recruited under this amendment, or when existing sites update study 
documentation. 
3. 
 Current curriculum vitae for the investigator.  If subinvestigators will participate 
in the study, curriculum vitae for each. 
4. 
Requirements for the Independent Ethics Committee (IEC)/Institutional Review 
Board (IRB). 
● A copy of the signed and dated letter of approval of the IEC/IRB.  The letter 
must specify that both the protocol and informed consent form were approved 
(unless separate documentation that the informed consent was approved is 
provided). 
● A dated list containing the names and affiliations of the members of the 
IEC/IRB, or the institutions General Assurance Number. 

 
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● If the investigator and/or subinvestigator is a member of the IEC/IRB, a letter 
stating that he/she did not participate in the review or approval of the protocol 
or informed consent form. 
5. 
A specimen copy of the IEC/IRB-approved informed consent document to be used 
in the study. 
6. 
A list of reference ranges of values for all laboratory tests specified by the protocol 
for all laboratories utilized. 
7. 
A copy of the laboratory(ies) certification(s) or the authorization number of the 
certification(s), the name of the certifying authority, and the period of certification. 
8. 
Financial Disclosure Certification forms must be completed by each investigator 
and all subinvestigators identified on the Form FDA 1572 or Investigator 
Information and Agreement Form.  A Financial Disclosure, EU Consent, is 
required to be completed for each investigator and/or subinvestigator who is a 
resident of the European Union 
 

 
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Appendix D.  
Responsibilities of the Clinical Investigator 
Clinical research studies sponsored by Abbott are subject to the regulations of the U.S. 
Food and Drug Administration (FDA).  The responsibilities imposed upon Investigators 
by the FDA are summarized in the "Statement of Investigator" (Form FDA 1572), which 
is a form letter addressed to the sponsor (Abbott), summarizing the Investigators 
qualifications for the study and his/her willingness to follow FDA regulations with 
respect to the study. 
In signing a Form FDA 1572, the Investigator agrees to assume the following 
responsibilities:   
1. 
To conduct the study(ies) in accordance with the relevant, current protocol(s) and 
only make changes in a protocol after notifying Abbott, except when necessary to 
protect the safety, rights, or welfare of subjects. 
2. 
To personally conduct or supervise the described investigation(s). 
3. 
To inform any subjects, or any persons used as controls, that the drugs are being 
used for investigational purposes and to ensure that the requirements relating to 
obtaining informed consent in 21 CFR Part 50 and Independent Ethics Committee 
(IEC)/Institutional Review Board (IRB) review and approval in 21 CFR Part 56 
are met. 
4. 
To report to Abbott adverse experiences that occur in the course of the 
investigation(s) in accordance with 21 CFR 312.64. 
5. 
To read and understand the information in the Investigators Brochure, including 
the potential risks and side effects of the drug. 
6. 
To ensure that all associates, colleagues, and employees assisting in the conduct of 
the study(ies) are informed about their obligations in meeting the above 
commitments. 

 
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7. 
To maintain adequate and accurate records of the conduct of the study and make 
those records available for inspection by representatives of Abbott, the IEC/IRB 
and/or the appropriate regulatory agency, and to retain all study-related documents 
until notification from Abbott.  The Investigator must notify Abbott when they are 
no longer able to retain the study related documents. 
8. 
To ensure that an IEC/IRB that complies with the requirements of 21 CFR Part 56 
will be responsible for the initial and continuing review and approval of the 
clinical investigation. 
9. 
To promptly report to the IEC/IRB all changes in the research activity and all 
unanticipated problems involving risks to human subjects or others (including 
submission of any Expedited Safety Reports received from Abbott to the 
IEC/IRB), and to make no changes in the research without IEC/IRB approval, 
except where necessary to eliminate apparent immediate hazards to human 
subjects. 
10. 
To comply with all other requirements regarding the obligations of clinical 
Investigators and all other pertinent requirements in 21 CFR Part 312. 
 

 
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Appendix E.  
CDC Treatment of Tuberculosis Infection (Preventive Therapy) 
Centers for Disease Control and Prevention 
Tuberculosis Information 
Treatment of Tuberculosis Infection (Preventive Therapy), Latent Tuberculosis 
Infection (LBTI)32 
 
 

 
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Appendix F.  
Non-Drug Materials Provided to the Study Site(s) 
Study sites will receive the following supplies prior to or during the study: 
Tote Bags 
Cooler 
Sharps Containers 
Ice Packs 
CDAI subject diary 
Dosing Diaries 
Subject Medication Log 
Self Injection Instructions 
Dosing syringes, as applicable 

 
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Appendix G.  
Pediatric Crohns Disease Activity Index (PCDAI) 
1. Abdominal pain rating 
 
- None 
 
- Mild - Brief, does not interfere with activities 
 
- Moderate/severe-Daily, longer lasting, affects activities, nocturnal 
 
= 0 p 
= 5 p 
= 10 p 
Score 
2. Stools (per day) 
 
- 0–1 liquid stools, no blood 
 
- Up to 2 semi-formed with small blood, or 2–5 liquid 
 
- Gross bleeding, or t 6 liquid, or nocturnal diarrhea 
 
= 0 p 
= 5 p 
= 10 p 
 
3. Patient Functioning, General Well-Being 
 
- No limitation of activities, well 
 
- Occasional difficulty in maintaining age appropriate activities, below par 
 
- Frequent limitation of activity, very poor 
 
= 0 p 
= 5 p 
= 10 p 
 
LABORATORY 
Score 
4. HCT: Male and female  d 10 years: 
 
 
t 33 
= 0 p 
 
 
28-32 
= 2.5 p 
 
 
< 28 
= 5 p 
 
Male 11–14 years: 
 
 
t35 
= 0 p 
 
 
30-34 
= 2.5 p 
 
 
<30 
= 5 p 
 
 
Female 11–19 years: t 34 
= 0 p 
 
 
29-33 
= 2.5 p 
 
 
< 29 
= 5 p 
 
Male 15–19 years: 
t37 
= 0 p 
 
 
32-36 
= 2.5 p 
 
 
<32 
= 5 p 
 
5. 
ESR (mm/hr) 
< 20 
= 0 p 
 
 
20-50 
= 2.5 p 
 
 
> 50 
= 5 p 
 
6. 
Albumin (g/dL) 
t 3.5 
= 0 p 
 
 
3.1-3.4 
= 5 p 
 
 
d 3.0 
= 10 p 
 

 
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EXAMINATION 
Score 
7. 
Weight 
- Weight gain or voluntary weight stable/loss 
 
 
- Involuntary weight stable, weight loss 1–9% 
 
 
- Weight loss t 10% 
= 0 p 
= 5 p 
= 10 p 
 
8. 
Height 
 
 
 
 
 
 
 
 
Height velocity t -1SD 
 
 
 
Height velocity < -1SD, > -2SD 
 
 
 
Height velocity d -2SD 
 
= 0 p 
= 5 p 
= 10 p 
 
9. 
Abdomen 
- No tenderness, no mass 
 
 
- Tenderness, or mass without tenderness 
 
 
- Tenderness, involuntary guarding, definite mass 
= 0 p 
= 5 p 
= 10 p 
 
10. Perirectal disease 
- None, asymptomatic tags 
 
 
- 1–2 indolent fistula, scant drainage, no tenderness 
 
 
- Active fistula, drainage, tenderness, or abscess 
= 0 p 
= 5 p 
= 10 p 
 
11. Extra-intestinal Manifestations 
 
(Fever t 38.5 for 3 days over past week, definite arthritis, uveitis, E. nodosum, 
P. gangrenosum) 
 
- None 
 
- One 
 
- t Two 
 
 
= 0 p 
= 5 p 
= 10 p 
 
TOTAL SCORE  
Pediatric Crohns Disease Activity Index (PCDAI) 
 
 

 
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Appendix H.  
PCDAI Users Guide and Guideline for Reference Weight and 
Reference Height 
This guide is intended to help nurse coordinators and physicians complete the PCDAI in 
order to assess disease activity in children with Crohns disease participating in clinical 
trials. 
History 
All calculations are based upon a one-week (7 day) history recall of symptoms.  The 
history recall should be solicited from the subject and/or caregiver. 
Item 1.  Abdominal pain 
The descriptions in the PCDAI of "mild" and "moderate/severe" should be used to guide 
in scoring the pain. Note that duration, effect on activities, and nocturnal occurrence 
separate moderate/severe from mild.  If pain varies in severity during the week, subject 
should be scored according to the most severe pain. However, mild pain should be 
present on at least two days to score 5 points rather than 0 points. 
Item 2.  Stools 
The intent is to score the stool pattern during the preceding week. 
To facilitate scoring, first categorize the subject as having blood in the stool or not. 
If there is no blood in the stool, score as follows:   
Formed stools or up to 1 loose stool daily = 0 
2-5 liquid or very loose stools on 1 or more days = 5 
6 or more liquid or very loose stools on 1 or more days or any nocturnal diarrhea = 10 

 
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If blood is present in the stool on any day during the past week, score as follows:   
Small amounts of blood in stool (on toilet paper or small spots in stool, etc.) = 5 
Any gross bleeding (large amounts on stool or colors the water in the toilet, etc.) = 10 
Item 3.  Subject functioning, general well-being 
If there is variation during the week, subject should be scored according to the most 
significant limitation of activity, even if it occurs during only one day of the week, as 
long as it is likely due to Crohns disease and not to an intercurrent illness. 
Item 4.  Hematocrit 
Hematocrit values should be rounded to a whole number prior to completing the 
calculation.   Numbers that fall between the range of 0.1-0.4 must be rounded down.   
Numbers that fall between the range of 0.5-0.9 must be rounded up. 
Physical Examination 
Item 7.  Weight (The intent is to assess the ability to normally maintain or gain weight) 
Reference weight to be used for calculation of weight gain/loss during the study: 
From Baseline to Week 264: use weight from previous visit 
Voluntary weight stable/loss means subject maintaining or losing weight on purpose. 
Involuntary weight stable means subject wants to gain weight but cannot. 
To calculate percentage weight loss use formula:   
Weight from previous visit – Current weight X 100 = % weight loss 
 
Weight from previous visit 

 
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Item 8.  Height 
Reference height for calculation of height velocity 
● From Baseline to Week 24, use height from 6 months prior to Baseline 
● From Week 24 to Week 48, use height from Baseline visit 
● From Week 48 to Week 72, use height from Week 24 
● From Week 72 to Week 96, use height from Week 48 
● From Week 96 to Week 120, use height from Week 72 
● From Week 120 to Week 144, use height from Week 96 
● From Week 144 to Week 168, use height from Week 120 
● From Week 168 to Week 192, use height from Week 144 
● From Week 192 to Week 216, use height from Week 168 
● From Week 216 to Week 240, use height from Week 192 
● From Week 240 to Week 264, use height from Week 216 
 
The intent is to assess the normalcy vs. impairment of the subjects recent linear growth.  
Note that post-pubertal subjects will score 0 points.  For subjects still growing, there are 
two options for scoring.  Method (a) is preferred.  Method (b) to be used if data required 
for (a) are unavailable. 
1. 
Height velocity (cm/year), the most sensitive parameter, should be calculated as 
below: 
Present height –  Appropriate height measurement (from above)  x  12  = Height velocity (cm/year) 
  
        Interval (months) between heights 
Using height velocity chart below, determine centile for height velocity. 

 
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2. 
Scoring for the PCDAI:   
a. Velocity less than "Minus 2 SD" scores 10 points. 
b. Velocity between "Minus 2 SD" and "Minus 1 SD" scores 5 points. 
c. Velocity greater than "Minus 1 SD" scores zero points. 
 
* 
Please note that subjects should score zero points if a subject is a female above 14.5 years of age or a 
male above 17.5 years of age. 
 

 
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Height Velocity Reference Values for Calculating the PCDAI (Males) 
 
Height Velocity in cm per year (Males) 
Age (years) 
Minus 2SD 
Minus 1SD 
Mean 
2.5 
5.7 
7.0 
8.3 
3 
5.4 
6.6 
7.8 
3.5 
5.1 
6.3 
7.4 
4 
4.9 
6.0 
7.1 
4.5 
4.7 
5.8 
6.8 
5 
4.6 
5.6 
6.6 
5.5 
4.5 
5.4 
6.4 
6 
4.3 
5.3 
6.2 
6.5 
4.2 
5.1 
6.0 
7 
4.2 
5.0 
5.9 
7.5 
4.1 
4.9 
5.8 
8 
3.9 
4.8 
5.6 
8.5 
3.8 
4.6 
5.4 
9 
3.8 
4.5 
5.3 
9.5 
3.7 
4.5 
5.2 
10 
3.7 
4.4 
5.1 
10.5 
3.7 
4.4 
5.1 
11 
3.7 
4.4 
5.2 
11.5 
3.8 
4.6 
5.3 
12 
4.0 
4.9 
5.7 
12.5 
4.8 
5.8 
6.7 
13 
6.2 
7.4 
8.6 
13.5 
7.1 
8.3 
9.5 
14 
6.1 
7.2 
8.4 
14.5 
4.1 
5.3 
6.5 
15 
2.4 
3.6 
4.7 
15.5 
1.2 
2.3 
3.3 
16 
0.4 
1.3 
2.2 
16.5 
0.1 
0.7 
1.5 
17 
0.1 
0.4 
0.9 
17.5 
0.1 
0.1 
0.5 
 

 
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Height Velocity Reference Values for Calculating the PCDAI (Females) 
 
Height Velocity in cm per year (Females) 
Age (years) 
Minus 2SD 
Minus 1SD 
Mean 
2.5 
5.9 
7.3 
8.6 
3 
5.5 
6.9 
8.1 
3.5 
5.2 
6.4 
7.6 
4 
4.9 
6.1 
7.2 
4.5 
4.7 
5.8 
6.8 
5 
4.6 
5.6 
6.6 
5.5 
4.5 
5.5 
6.4 
6 
4.4 
5.3 
6.2 
6.5 
4.3 
5.2 
6.1 
7 
4.3 
5.2 
6.0 
7.5 
4.3 
5.1 
5.9 
8 
4.2 
5.0 
5.8 
8.5 
4.2 
4.9 
5.7 
9 
4.2 
5.0 
5.8 
9.5 
4.3 
5.0 
5.8 
10 
4.4 
5.3 
6.2 
10.5 
4.7 
5.7 
6.8 
11 
5.7 
6.6 
7.7 
11.5 
6.1 
7.2 
8.3 
12 
5.2 
6.3 
7.3 
12.5 
3.6 
4.8 
5.9 
13 
2.4 
3.3 
4.3 
13.5 
1.3 
2.2 
2.9 
14 
0.4 
1.1 
1.8 
14.5 
0.0 
0.5 
1.0 
 

 
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Appendix I.  
Crohns Disease Activity Index (CDAI) 
 
 
 
Factor 
Subtotal 
1. Number of liquid or very soft stools
(Record the frequency per day) 
         __+___+___+___+___+___+___=___ 
Days: 1     2      3      4 
5      6 
  7   Sum 
X 
2 
 
2.  Abdominal pain rating: 
0=none, 1=mild, 2=moderate, 
3=severe 
          __+___+___+___+___+___+___=___ 
Days: 1     2      3      4 
5      6 
  7   Sum 
X 
5 
 
3. General well-being: 
0=generally well, 1=slightly 
underpar, 2=poor, 3=very poor, 
4=terrible 
         __+___+___+___+___+___+___=___ 
Days: 1     2      3      4 
5      6 
  7   Sum 
X 
7 
 
4. Number of 6 listed categories the 
subject now has: 
Check all items that apply: 
□  Arthritis/arthralgia 
□  Iritis/uveitis 
□  Erythema nodosum/  
 pyoderma gangrenosum/ 
 aphthous stomatitis 
□  Fissure, abscess and/or anal 
fistula (draining/non-draining) 
□  Other cutaneous fistula 
(draining/non-draining) fistula 
□  Fever over 100°F (37.8°C) during 
past week 
 
 
 
 
 
 
  
________ 
 
 
 
Record "0" if no categories checked 
X 
20 
 
5.   Taking Lomotil / Imodium / 
Loperamide /opiates for diarrhea  
0=no, 1=yes 
________ X 
30 
 
6.   Abdominal mass 
0=none, 2=questionable, 5=defined 
________ X 
10 
 
7.   Hematocrit: ______ 
Male: 
(47 - hematocrit) = 
Female: (42 - hematocrit) = Subtotal ______ 
If hematocrit > normal, enter "0" 
X 
6 
 
8.   Body weight: __  __  __ . __ (kg) 
Ideal weight for height: 
__  __  __ . __ (kg) 
100 x [1 - (Body wt/Ideal wt)] =  
Percent below ideal weight: ______ 
If body wt > ideal wt, enter "0" 
X 
1 
 
 
 
 
Total 
 
* 
Ideal weight is obtained from CDC growth charts.  The subtotal of box 8 should be rounded to a whole number.  
Numbers that fall between the range of .1-.4 must be rounded down.   Numbers that fall between the range of .5-.9 
must be rounded up.  To ensure consistency across all sites and to take into account the varying growth rates of 
subjects in this study, the IBW should be calculated at each visit. 
* 
Hematocrit values should be rounded to a whole number prior to completing the calculation in box 7 of the CDAI.   
Numbers that fall between the range of .1-.4 must be rounded down.   Numbers that fall between the range of .5-.9 
must be rounded up. 

 
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Appendix J.  
Subject CDAI Diary 
Crohns Disease Activity Index 
Subject Diary Card 
Enter all values legibly using a black 
ballpoint pen. 
Add item requested for each day. 
Day 
Date___ 
Day 
Date___ 
Day 
Date___ 
Day 
Date___ 
Day 
Date___ 
Day 
Date___ 
Day 
Date___ 
Number (total) of liquid or very soft 
stools per day. 
 
 
 
 
 
 
 
Daily abdominal pain rating. 
(0=none, 1=mild, 2=moderate, 3=severe) 
 
 
 
 
 
 
 
Daily rating of general well being. 
(0=well, 1=slightly below par, 2=poor, 
3=very poor, 4=terrible) 
 
 
 
 
 
 
 
Subject Initials:___________ 
Subjects Signature:__________________________ 
 
Investigator or Designees Signature:______________________ 

 
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Question 1. 
How much has your stomach been hurting you in the past two weeks? 
□ 
□ 
□ 
□ 
□ 
Not at all 
 Hardly hurting 
at all 
Hurting 
somewhat  
Hurting 
quite a bit 
Hurting 
very much 
 
Question 2.  
Taking medicines or tablets bothers you 
□ 
□ 
□ 
□ 
□ 
Not at all 
 Hardly bothers 
at all 
Bothers 
somewhat  
Bothers  
quite a bit 
Bothers 
very much 
 
Question 3. 
How often has your inflammatory bowel disease prevented you from 
eating what you want in the past two weeks? 
□ 
□ 
□ 
□ 
□ 
Never 
 Rarely 
Sometimes 
Often 
Very often 
 
Question 4. 
How often have you been worrying about having a flare-up (increase of 
symptoms) in the last two weeks? 
□ 
□ 
□ 
□ 
□ 
Never 
 Rarely 
Sometimes 
Often 
Very often 
 
Question 5. 
How much does it bother you that you have an illness that does not just go 
away? 
□ 
□ 
□ 
□ 
□ 
Not at all 
 Hardly bothers 
at all 
Bothers 
somewhat  
Bothers quite a 
bit 
Bothers very 
much 
 
Question 6. 
How much energy did you have during the past two weeks? 
□ 
□ 
□ 
□ 
□ 
Very much 
energy 
Quite a bit of 
energy 
Some energy 
 A little energy 
No energy at 
all  

 
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Question 7. 
How do you feel about your weight? 
□ 
□ 
□ 
□ 
□ 
I feel great 
about my 
weight 
I feel good 
about my 
weight 
I dont feel 
good or bad 
about my 
weight 
I feel bad about 
my weight 
I feel awful 
about my 
weight 
 
Question 8. 
How has your inflammatory bowel disease affected your family? 
□ 
□ 
□ 
□ 
□ 
The effect has 
been great 
The effect has 
been good 
It has not 
affected our 
family 
The effect has 
been bad 
The effect has 
been awful 
 
Question 9. 
How often did you have to miss out on certain things (hobbies, play, 
parties) because of your inflammatory bowel disease in the past two weeks? 
□ 
□ 
□ 
□ 
□ 
Never 
Rarely 
Sometimes 
Often 
Very often 
 
Question 10. How often have you been bothered by diarrhea (loose or frequent bowel 
movements) in the past two weeks? 
□ 
□ 
□ 
□ 
□ 
Never 
Rarely 
Sometimes 
Often 
Very often 
 
Question 11. How often do you worry about health problems you might have in the 
future? 
□ 
□ 
□ 
□ 
□ 
Never 
Rarely 
Sometimes 
Often 
Very often 
 

 
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Question 12. How often do you think it is unfair that you have inflammatory bowel 
disease? 
□ 
□ 
□ 
□ 
□ 
Never 
Rarely 
Sometimes 
Often 
Very often 
 
Question 13. During the past two weeks, were you ever angry that you have 
inflammatory bowel disease? 
□ 
□ 
□ 
□ 
□ 
Never 
Rarely 
Sometimes 
Often 
Very often 
 
Question 14. Do you think too many rules or limits are placed on you because of your 
inflammatory bowel disease? 
□ 
□ 
□ 
□ 
□ 
Never 
Rarely 
Sometimes 
Often 
Very often 
 
Question 15. How do you feel about the way you look? 
□ 
□ 
□ 
□ 
□ 
I think I look 
great 
I think I look 
good 
I dont think I 
look good or 
bad 
I think I look 
bad 
I think I look 
awful 
 
Question 16. Are you embarrassed because of your bowel condition? 
□ 
□ 
□ 
□ 
□ 
Not at all 
 Hardly 
embarrassed at 
all 
Embarrassed 
somewhat  
Embarrassed 
quite a bit 
Embarrassed 
very much 
 
Question 17. Did you have fun during the past two weeks? 
□ 
□ 
□ 
□ 
□ 
Very often 
Often 
Sometimes 
Rarely 
Never 

 
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Question 18. Is it harder to make friends because of your inflammatory bowel disease? 
□ 
□ 
□ 
□ 
□ 
Not at all 
harder 
 A little harder 
Quite a bit 
harder 
Much harder 
Very much 
harder 
 
Question 19.  How often do you worry about your stool (bowel movement) containing 
blood? 
□ 
□ 
□ 
□ 
□ 
Never 
Rarely 
Sometimes 
Often 
Very often 
 
Question 20. Are you worried you cannot go out on a date or have a boyfriend or 
girlfriend because of your inflammatory bowel disease? 
□ 
□ 
□ 
□ 
□ 
Not at all 
worried 
 Hardly 
worried at all 
Worried 
somewhat  
Worried quite a 
bit 
Worried very 
much 
 
Question 21. How often did you feel sick to your stomach in the past two weeks? 
□ 
□ 
□ 
□ 
□ 
Never 
Rarely 
Sometimes 
Often 
Very often 
 
Question 22. How do you feel about the tests you have to go through? 
□ 
□ 
□ 
□ 
□ 
I do not mind 
them at all 
I mind them a 
tiny bit 
I mind them a 
little 
I mind them a 
lot 
I hate them 
 
Question 23. Do other children bully you or leave you out of things because of your 
inflammatory bowel disease or its treatment? 
□ 
□ 
□ 
□ 
□ 
Never 
Rarely 
Sometimes 
Often 
Very often 

 
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Question 24. How often do you worry about having an operation? 
□ 
□ 
□ 
□ 
□ 
Never 
Rarely 
Sometimes 
Often 
Very often 
 
Question 25. In the past two weeks how often were you afraid you may have an 
accident or not get to the toilet in time? 
□ 
□ 
□ 
□ 
□ 
Never 
Rarely 
Sometimes 
Often 
Very often 
 
Question 26. Do you try to keep your inflammatory bowel disease a secret from other 
people? 
□ 
□ 
□ 
□ 
□ 
No, I do not try 
at all 
I dont try much I try a little 
I try hard 
Yes, I try very 
hard 
 
Question 27. Does your inflammatory bowel disease make it difficult to travel or go on 
a holiday? 
□ 
□ 
□ 
□ 
□ 
No, not 
difficult 
A little difficult
Quite difficult 
Very difficult 
Yes, extremely 
difficult 
 
Question 28.  How did you feel during the past two weeks? 
□ 
□ 
□ 
□ 
□ 
Great 
Good 
Not good or 
bad 
Bad  
Awful 
 
Question 29. Are you happy with your life? 
□ 
□ 
□ 
□ 
□ 
Yes, very 
happy 
Happy 
Not happy or 
unhappy 
Unhappy 
Very unhappy 

 
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Question 30. Do you feel there is someone you can talk to about your inflammatory 
bowel disease? 
□ 
□ 
□ 
□ 
□ 
Always  
Often  
Sometimes  
Rarely 
Never 
 
Question 31. How often did you have to pass gas in the past two weeks? 
□ 
□ 
□ 
□ 
□ 
Never 
Rarely 
Sometimes 
Often 
Very often 
 
Question 32. How tired have you felt in the past two weeks? 
□ 
□ 
□ 
□ 
□ 
Not at all tired 
 A little tired 
Quite tired 
Tired  
Very tired 
 
Question 33. How do you feel about your height? 
□ 
□ 
□ 
□ 
□ 
I feel great 
about my 
height 
I feel good 
about my 
height 
I dont feel 
good or bad 
about my 
height 
I feel bad about 
my height 
I feel awful 
about my 
height 
 
Question 34. Does your inflammatory bowel disease get in the way of playing sports the 
way you would like to? 
□ 
□ 
□ 
□ 
□ 
Never 
Rarely 
Sometimes 
Often 
Always 
 
Question 35. In the past two weeks how often were you able to go to school? (If you are 
in the middle of a school break or the summer holidays, answer as if school was on) 
□ 
□ 
□ 
□ 
□ 
Always  
Most days  
Half the days 
A few days 
Never 
 

 
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End of questionnaire 
This completes the questionnaire. Do you have anything else to add which you feel is 
important about having inflammatory bowel disease, or do you have any other 
remarks? Please write them below. 
 
_________________________________________________________ 
_________________________________________________________ 
_________________________________________________________ 

 
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Appendix L.  
Excluded Medications 
Cyclosporine 
Tacrolimus 
Therapeutic enemas and suppositories (not including those done in conjunction with 
routine colonoscopy) 
Live vaccines 
The combination of budesonide and prednisone (or equivalent) 
Infliximab 
Mycophenolate mofetil (MMF or CellCept® ) 
Growth Hormone 
Kineret® (anakinra) 
Tysabri (natalizumab) 
Orencia (abatacept) 
Concurrent biologic therapy 
Any investigational agent 
Any previous anti-TNF medication except infliximab before the M06-806 study 
(including adalimumab). 
 

 
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Appendix M.  
Day 70 Phone Call 
Site Name / Number: ________ 
Subject Number:________ 
Subject Initials:________ 
Please contact all Subjects 70 days following drug discontinuation. 
 
 
 
Date of Call: ____________ 
 
 
□     Lost to Follow-Up (Please check this box if subject was not willing to provide any follow-up 
information or you were unable to speak to the subject following at least one attempt). 
 
 
□      No Events Reported 
 
List any Adverse Events (AE) and/or Serious Adverse Events (SAE) that occurred since the subject was 
last seen in clinic for this study.  Please document all adverse events on a 500 AE CRF to be submitted to 
data management.  (Please report all SAEs to Abbott within 24 hours of being made aware of the event.  
Follow-up information must also be reported within 24 hours of being made aware of the information.). 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
If events are listed above, your monitor will review and retrieve the appropriate CRF pages during 
their next visit.  Please fax this form to Paragon at 
 
 

 
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Appendix N.  
Unscheduled Outpatient Visits, Emergency Room Visits and 
Hospitalizations 
1. 
Since the last study visit has the subject had any physician/health care visits for 
their Crohns disease other than the protocol required visits? 
Yes ___ 
No  ___ 
If yes provide the following: 
I. 
Since the last visit, has the subject been seen by a physician for their Crohns 
Disease? 
YES:_____ 
NO:_____ 
If YES, how many times:_______ 
 
 
II. Since the last visit, has the subject been seen in the Emergency Room for their 
Crohns Disease? 
YES:_____ 
NO:______ 
If YES, how many times:_____ 
III. Since the last visit, has the subject been admitted to the hospital due to their 
Crohns Disease? 
YES:_____ 
NO:______ 
If YES, how many times:_____ 
If YES, please indicate the total number of days in the hospital:_____ 
 
 

 
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Appendix O.  
Subject Medication Log 
Instructions:  As a participant in this study, it is also important to keep a record of all mediations you take (new and old) throughout the study.  Please take this 
sheet home with you and write down any medications you take during the study.  It will be VERY important that you bring this sheet back to your doctors office 
and speak with your doctor about everything you have written down. 
 
Name of Medication 
Date you took
first dose 
Date you took
last dose 
What dose of medicine 
did you take? 
How often did you 
take the medicine? 
Why did you take the 
medicine? 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
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Week 25 - Week 36 
Subject Initials: __________ 
Subject Study #: ___________ 
 
Date 
day/mm/yr 
Day or 
Week # 
Time of Study 
Drug 
Administration 
Dose (mL) 
Administered
Kit #
Initials of Person 
Administering 
Study Medication 
Comments 
18/MAR/04 EXAMPLE 
9:35 am 
0.8 
 
MM 
none 
 
Week 25 
 
 
 
 
 
 
Week 26 
 
 
 
 
 
 
Week 27 
 
 
 
 
 
 
Week 28 
 
 
 
 
 
 
Week 29 
 
 
 
 
 
 
Week 30 
 
 
 
 
 
 
Week 31 
 
 
 
 
 
 
Week 32 
 
 
 
 
 
 
Week 33 
 
 
 
 
 
 
Week 34 
 
 
 
 
 
 
Week 35 
 
 
 
 
 
 
Week 36 
 
 
 
 
 
 

 
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Week 241 - Week 263 
Subject Initials: __________ 
Subject Study #: ___________ 
 
Date 
day/mm/yr 
Day or 
Week # 
Time of Study 
Drug 
Administration 
Dose (mL) 
Administered
Kit #
Initials of Person 
Administering 
Study Medication Comments
18/MAR/04 
EXAMPLE 
9:35 am 
0.8 
 
MM 
none 
 
Week 241 
 
 
 
 
 
 
Week 242 
 
 
 
 
 
 
Week 243 
 
 
 
 
 
 
Week 244 
 
 
 
 
 
 
Week 245 
 
 
 
 
 
 
Week 246 
 
 
 
 
 
 
Week 247 
 
 
 
 
 
 
Week 248 
 
 
 
 
 
 
Week 249 
 
 
 
 
 
 
Week 250 
 
 
 
 
 
 
Week 251 
 
 
 
 
 
 
Week 252 
 
 
 
 
 
 
Week 253 
 
 
 
 
 
 
Week 254 
 
 
 
 
 
 
Week 255 
 
 
 
 
 
 
Week 256 
 
 
 
 
 
 
Week 257 
 
 
 
 
 
 
Week 258 
 
 
 
 
 
 
Week 259 
 
 
 
 
 
 
Week 260 
 
 
 
 
 
 
Week 261 
 
 
 
 
 
 
Week 262 
 
 
 
 
 
 
Week 263* 
 
 
 
 
 
* 
Week 263 dose will only be taken if on every-week dosing schedule. 
 

 
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Appendix Q.  
Self Injection Instructions 
 
 
Subject Instructions 
0.8 mL or 0.4 mL dose 
(Administered as a single dose-prefilled syringe (PFS)) 
 
Protocol M06-807 
 

 
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Tables of Contents 
Dosing Schedule 
General Information  
Injection Procedures 
 

 
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Study Drug Dosing Schedule 
Open-Label (PFS) 
Subject Number:_____________________________________ 
You will require subcutaneous (SC) injections throughout the study.  
Injections at scheduled study visits (Baseline, Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 
108, 120, 144, 168, 192, 216 and 240) will be done during your visit, at the doctors 
office.  On weeks between office visits, study drug will be self-administered at home by 
you or someone trained to give you the injections. 
For 40 mg dose, one pre-filled syringe will contain 0.8 mL of liquid.  The total available 
dose is 0.8 mL.  The drug should be administered in one (1) SC injection, on the same 
day of the week for each dose. 
For 20 mg dose, one pre-filled syringe will contain 0.4 mL of liquid.  The total available 
dose is 0.4 mL.  The drug should be administered in one (1) SC injection, on the same 
day of the week for each dose. 
Please return all used and unused syringes to the clinic on your next visit. Used syringes 
should be placed in the special sharps container provided. All unused syringes should be 
returned in the original box. 
If an injection is missed or something occurs where the full dose cannot be injected, 
contact your study center immediately for further instructions.  Please record any missed 
doses on your subject diary. 
Remember to complete your dosing diary after each injection and to call the doctors 
office if you are having problems administering your study drug. 

 
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General Information 
 
 
 
 
 
 
 
PFS 
● Prefilled syringes will be labeled "adalimumab." 
● Store all adalimumab prefilled syringes in your refrigerator NOT in the 
freezer.  Should the syringes accidentally become frozen, call your study 
coordinator. 
● 0.8 mL = 0.8 cc 
● Study drug should be taken at about the same time of day, on the same day of 
the week as directed by your study doctor. 
● USE A NEW SYRINGE EVERY INJECTION DAY.  There may be 
medication left in the syringe.  DO NOT RE-USE. 
● Save all study drugs.  Prefilled syringes (used and unused) must be returned 
to the study center at each visit.  Used syringes will be disposed of in a sharps 
container provided to you. 
● Whenever possible, have someone with you for at least 15 to 30 minutes after 
your injection. 
● Call your doctor IMMEDIATELY if you experience any itching, hives, 
shortness of breath, or any symptom that has you concerned.  If you are 
unable to reach your doctor or if you experience life-threatening symptoms 
call 911, or proceed to your nearest emergency room. 
 

 
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Injection Procedures 
 
 
 
 
 
 
 
PFS 
1. Clean your workspace, gather your supplies, and wash your hands. 
 
 
2. Identify the area on your abdomen or thigh (or upper arm 
if not self injecting).  Make sure the area you choose 
does not have any redness, tenderness, swelling, bruising, 
or psoriasis.  The area must also be at least 2 cm 
(approximately 1 inch) away from the previous injection 
site.  IT IS VERY IMPORTANT TO CHANGE THE 
INJECTION SITE EVERY TIME!!! 
 
 
3. Using a circular motion (starting at the injection site and 
moving outward) clean the selected injection site with 
an alcohol pad.  Allow skin to dry.  
4. Remove the needle cap. Do not touch the needle.  Expel 
any air bubbles from the syringe by tapping on the 
syringe.  If the needle becomes contaminated, discard 
all supplies and obtain a new syringe of study drug.  
5. Once the air is expelled from the syringe, the amount of 
solution in the syringe should be 0.8 mL. 
 
 
6.   Hold the syringe "like a dart" between your thumb and 
first finger close to the syringe/needle connection. 

 
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PFS 
 
7. With your other hand, pinch the skin around the 
injection site, forming a bulge in the skin. 
 
 
 
 
 
 
8. Insert the needle into the skin at a 45-degree angle. 
Release pinched skin. 
 
 
 
 
9. 
GENTLY pull back on the syringe plunger.  If blood 
appears, withdraw needle - DO NOT INJECT!  
Contact your study center immediately for further 
instructions.  
 
10. Inject drug by pushing slowly on syringe plunger with 
thumb. 
 
11. Remove needle while maintaining a 45-degree angle. 
 
12. You may apply a Band-Aid over the injection site and 
apply gentle pressure, if necessary.  DO NOT RUB 
SITE. 
 
13. 
DO NOT RECAP NEEDLE.  DO NOT SEPARATE THE NEEDLE FROM THE 
 
SYRINGE BEFORE DISPOSING.  Discard used syringes into Sharps Container. 
EACH TIME THAT YOU GIVE YOURSELF AN INJECTION OF STUDY DRUG, 
REMEMBER TO RECORD THE INFORMATION ON YOUR SUBJECT DOSING 
DIARY. 
 

 
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Self Injection Instructions 
 
Subject Instructions 
0.2 mL dose 
Vials 
Protocol M06-807 

 
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Tables of Contents 
Dosing Schedule 
General Information  
Injection Procedures 

 
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Study Drug Dosing Schedule 
Vials 
Subject Number:  _____________________________________ 
You will require subcutaneous (SC) injections throughout the study. 
The injection for the visits at Weeks 4, 8, 12, 16, 20, 26, 32, 40, 48, 60, 72, 84, 96, 108, 
120, 144, 168, 192, 216 and 240 will be done during your visit at the doctor's office.  
After Week 4, on weeks between office visits (i.e., Weeks 6, 10, 14, etc.) study drug will 
be self-administered at home by you or someone trained to give you the injections. 
The total dose is 0.2 mL.  The drug should be administered in one (1) SC injection, on the 
same day of the week for each dose. 
For 10 mg dose, 0.2 mL of the solution is drawn from a vial containing adalimumab 
40 mg/0.8 mL solution.  The drug should be administered in one (1) SC injection, on the 
same day of the week for each dose. 
Please return all used and unused vials to the clinic on your next visit.  Used syringes 
should be placed in the special sharps container provided.  All unused vials should be 
returned in the original box. 
If an injection is missed or something occurs where the full dose cannot be injected, 
contact your study center immediately for further instructions.  Please record any missed 
doses on your subject diary. 
Remember to complete your dosing sheet after each injection and to call the doctor's 
office if you are having problems administering your study medication. 

 
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General Information 
Vials 
● Vials will be labeled "adalimumab." 
● Store all adalimumab vials in your refrigerator NOT in the freezer.  Should the 
vials accidentally become frozen, call your study coordinator. 
● 0.2 mL = 0.2 cc 
● Study drug should be taken at about the same time of day, on the same day of 
the week as directed by your study doctor. 
● USE A NEW VIAL EVERY INJECTION DAY.  There will be medication 
left in the vial.  DO NOT RE-USE. 
● Save all study drugs.  Vials (used and unused) must be returned to the study 
center at each visit.  Used vials and syringes will be disposed of in a sharps 
container provided to you. 
● Whenever possible, have someone with you for at least 15 to 30 minutes after 
your injection. 
● Call your doctor IMMEDIATELY if you experience any itching, hives, 
shortness of breath, or any symptom that has you concerned.  If you are 
unable to reach your doctor or if you experience life-threatening symptoms 
call 911, or proceed to your nearest emergency room. 
 

 
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Injection Instructions  
Vials 
Select a clean, well-lit, flat surface. 
1. 
Wash your hands thoroughly with soap and warm water.  It is important to keep 
your work surface as clean as possible. 
2. 
Open carton. 
3. 
Examine the carton and components in it to make sure they are complete. 
● One or two vials containing adalimumab 
 
4. 
Remove the plastic cap from the vial. 
5. 
Wipe the gray stopper with an alcohol swab and discard alcohol swab. 
 
 
6. 
Place the vial upright on a hard, flat surface. 
7. 
Choose an injection site on the upper thigh or abdomen. 
8. 
Prepare the injection site by wiping it thoroughly with a second alcohol swab.  
Use a circular motion. 
 

 
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9. 
Remove the needle cover from the syringe.  (The needle is sterile, so be very 
careful not to touch the needle or allow it to touch any surface.) 
10. 
Draw the plunger on the syringe back. 
11. 
With the vial sitting on a hard, flat surface, insert needle straight down through 
the center of the gray stopper.  If the needle is correctly lined up, you should feel 
slight resistance and then a "pop" as the needle penetrates the center of the 
stopper.  (Be careful not to insert the needle at an angle as this may cause the 
needle to bend.  If the needle is not correctly aligned, you will feel constant 
resistance as it penetrates the stopper and will not feel a "pop.") 
12. 
Push the plunger in forcing air into the vial. 
13. 
With the needle still in place, turn the vial upside down.  Keeping the vial at eye 
level, slowly pull the plunger back to draw the liquid into the syringe.  This will 
cause the bubbles to rise to the top of the syringe.  (As the liquid level in the vial 
drops, you may have to withdraw the needle partially to keep the tip of the needle 
in the liquid.)  Only 0.2 mL of the vial will be drawn into the syringe. 
14. 
With the needle still in the vial, check the syringe for air bubbles.  To remove any 
air bubbles, start by gently tapping the syringe. 
15. 
Slowly press the plunger to push any bubbles out of the syringe and into the vial.  
(If you accidentally push any liquid back into the vial, draw the liquid back into 
the syringe and check again for air bubbles.  It's okay for a small amount of liquid 
to remain in the vial.) 
16. 
Withdraw the needle from the vial, being careful not to touch it to any surface. 

 
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Vials 
17. 
Take the syringe in one hand. 
 
 
18. 
With your other hand, firmly pinch the skin around the cleaned injection site.  (Be 
careful not to touch the cleaned area.) 
 
 
19. 
Hold the syringe at about a 45-degree angle to the skin and use a quick, short 
motion to push the needle into the skin. 
 
 
20. 
Once the needle is in, release the skin. 

 
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Vials 
21. 
While firmly holding the syringe with one hand, use your other hand to slowly 
push the plunger and inject the adalimumab.  For subjects that weigh t 40 kg, all 
0.8 mL will be injected.  For subjects that weigh < 40 kg, only 0.4 mL of the vial 
will be injected. 
 
 
22. 
When the syringe is empty, remove the needle from the skin, being careful to 
keep it at the same 45-degree angle. 
23. 
Dispose of both the needle and syringe in a puncture-resistant container, or sharps 
container, which will be provided. 
24. 
You may want to press a cotton ball on the injection site for 10 seconds.  If there 
is some slight bleeding, you may choose to apply a small bandage. 
25. 
Return the vial into the original packaging. 
26. 
Place the medication kit back into the refrigerator. 

 
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Vials 
EACH TIME YOU RECEIVE AN INJECTION OF STUDY MEDICATION, 
REMEMBER TO RECORD THE INFORMATION ON YOUR DOSING SHEET. 
GENERAL INFORMATION: 
27. 
ROTATING INJECTION SITES IS RECOMMENDED.  PLEASE DO NOT 
INJECT THE STUDY MEDICATION INTO A PRIOR SITE OF INJECTION. 
28. 
Store all of your drug in the refrigerator.  Should the vials become accidentally 
frozen or left out, call your study coordinator.  DO NOT USE THESE VIALS. 
29. 
If you forget to take the drug or make a mistake with an injection, please call your 
study coordinator. 
30. 
Please save all of your study medication, even if you skip a dose.  Please bring all 
used and unused vials back to the physician at your next study visit. 
31. 
There will be study medication remaining in the vials.  DO NOT USE THE 
MEDICATION LEFT IN THE VIAL.  Please return the vial along with the 
remaining study medication back to the physician at your next study visit. 
32. 
Specific side effects to watch for:  redness and swelling at the injection site.  
Please tell the study coordinator if you have any side effects from injecting the 
drug. 
 

 
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Appendix R.  
Standard Weights 
 
 

 
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Appendix S.  
Subject Abbott Laboratories Site Drug Accountability Form 
 

 
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Appendix T.  
Work Productivity and Activity Impairment Questionnaire: 
Crohns Disease (WPAI-CD) - Caregiver 
The following questions ask about the effect of your childs Crohns disease on your ability 
to work and perform regular activities.  Please fill in the blanks or circle a number, as 
indicated. 
1.  Are you currently employed (working for pay)?  
_____ NO ___ YES 
  If NO, check "NO" and skip to question 6. 
The next questions are about the past seven days, not including today. 
 
 
2. During the past seven days, how many hours did you miss from work because of 
problems associated with your childs Crohns disease?  Include hours you missed on 
sick days, times you went in late, left early, etc., because of your childs Crohns 
disease.  Do not include time you missed for your child to participate in this study. 
 
_____ HOURS 
 
3. During the past seven days, how many hours did you miss from work because of any 
other reason, such as vacation, holidays, time off for your child to participate in this 
study? 
 
_____HOURS 
 
4. During the past seven days, how many hours did you actually work? 
 
_____HOURS  (If "0," skip to question 6.) 
 

 
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5. During the past seven days, how much did your childs Crohns disease affect your 
productivity while you were working?   
 
Think about days you were limited in the amount or kind of work you could do, days 
you accomplished less than you would like, or days you could not do your work as 
carefully as usual.  If your childs Crohns disease affected your work only a little, 
choose a low number.  Choose a high number if your childs Crohns disease affected 
your work a great deal.   
Consider only how much your childs Crohns disease affected  
your productivity while you were working. 
 
 
 
 
 
 
 
 
 
 
 
My childs Crohns 
disease had no 
effect on my work 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
My childs Crohns 
disease completely 
prevented me from 
working 
CIRCLE A NUMBER 
6. During the past seven days, how much did your childs Crohns Disease affect your 
ability to do your regular daily activities, other than work at a job?   
 
By regular activities, we mean the usual activities you do, such as work around the 
house, shopping, childcare, exercising, studying, etc.  Think about times you were 
limited in the amount or kind of activities you could do and times you accomplished 
less than you would like.  If your childs Crohns Disease affected your activities only a 
little, choose a low number.  Choose a high number if your childs Crohns Disease 
affected your activities a great deal.   
 
Consider only how much your childs Crohns disease affected your ability  
to do your regular daily activities, other than work at a job. 
 
 
 
 
 
 
 
 
 
 
 
My childs Crohns 
disease had no 
effect on my daily 
activities 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
My childs Crohns 
disease completely 
prevented me from 
doing my daily 
activities 
 
 
                           
CIRCLE A NUMBER 
WPAI:CD-Caregiver (US English) 

 
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Appendix U.  
Protocol Amendment:  List of Changes 
The summary of changes is listed in Section 1.1. 
Specific Protocol Changes: 
Section 5.1  Overall Study Design and Plan:  Description 
Fifteenth paragraph previously read: 
A schematic of the study design is shown in Figure 1. 
Has been changed to read: 
A schematic of the study design is shown in Figure 1 (prior to Amendment 4) and in 
Figure 3 (after Amendment 4). 
Figure 2.  Dosing Schematic After Amendment 4 
Add:  new figure 
 
F:  
Subjects who have a disease flare may be switched to the next higher treatment level. 
R:  
Subjects who responded to their current treatment may be switched to the next lower treatment level at the 
discretion of the investigator after discussion with the medical monitor.  Response is defined as a) a t 15 points 
decrease in PCDAI compared to the last observation prior to dose escalation in patients who dose-escalated or 
b) a t 15 points decrease in PCDAI compared to Baseline of Study M06-806 in patients who did not 
dose-escalate. 

 
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BW: Subjects with an increase in body weight to t 40 kg may increase their dose to the next higher level at the 
discretion of the investigator after discussion with the medical monitor.  Subjects with a decrease in body weight 
to < 40 kg may decrease their dose to the next lower level at the discretion of the investigator after discussion 
with the medical monitor. 
 
Table 1.  Study Activities 
Table note "l." previously read: 
l. 
If an unscheduled visit is performed to change the frequency of study drug from OL eow to OL ew, study drug 
may be dispensed. 
 
Has been changed to read: 
l. 
If an unscheduled visit is performed to change the frequency or dose of study drug, study drug may be dispensed. 
 
Section 5.5.1  Treatments Administered 
First paragraph previously read: 
All study drug will be provided as a SC injection solution in pre-filled syringes 
containing adalimumab 40 mg/0.8 mL or adalimumab 20 mg/0.4 mL. 
Has been changed to read: 
Study drug will be provided as a SC injection solution in pre-filled syringes containing 
adalimumab 40 mg/0.8 mL or adalimumab 20 mg/0.4 mL or in vials containing 
adalimumab 40 mg/0.8mL. 
Section 5.5.1  Treatments Administered 
Add:  new sixth, seventh, eighth and ninth paragraph 
The dose of adalimumab may be decreased to the next lower treatment level as 
applicable, at the discretion of the Investigator and prior approval from the medical 
monitor, for subjects whose body weight has decreased from t 40 kg to < 40 kg from the 
previous visit.  The site will enter the subject's body weight into the IVRS and the dose 
will be adjusted, if applicable. 
Subjects who responded to treatment defined as (a) an improvement of at least 15 points 
in PCDAI compared to the last observation prior to dose escalation in patients who 

 
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dose-escalated or b) an improvement of at least 15 points in PCDAI compared to 
Baseline of Study M06-806 in patients who did not dose-escalate) may have their dosage 
frequency decreased from ew to eow dosing.  The investigator should receive prior 
approval from the medical monitor before taking any action with regard to the dose 
frequency decrease.  At least 8 weeks after dose frequency decrease, subjects who still 
responded to treatment (as defined above) may have their dosage decreased (subjects who 
weigh ≥ 40 kg will receive 20 mg eow of adalimumab, while subjects who weigh < 40 kg 
will receive 10 mg eow of adalimumab).  The investigator should receive prior approval 
from the medical monitor before taking any action with regard to dose decrease. 
Subjects who experience a disease flare may re-increase their dosage or dose frequency 
to the next higher treatment level regardless of prior dose or dose frequency decrease.  
Simultaneous dose adjustment based on change of body weight as well as based on 
diseases status (response/flare) is prohibited. 
Section 5.5.2  Identity of Investigational Product 
First paragraph, second sentence previously read: 
Pre-filled syringes will be provided for this open-label clinical study. 
Has been changed to read: 
Pre-filled syringes (used for 40 mg/0.8 mL or 20 mg/0.4 mL doses) and 40 mg/0.8 mL 
vials (used for 10 mg dose) will be provided for this open-label clinical study. 
Table 3.  Identity of Investigational Products 
Previously read: 
Study Drug 
Formulation 
Manufacturer 
Adalimumab 
40 mg/0.8 mL or 20 mg/0.4 mL  
Adalimumab/Mannitol, Citric acid monohydrate, Sodium citrate, 
Disodium phosphate dihydrate, Sodium dihydrogen phosphate 
dihydrate, Sodium chloride, Polysorbate 80, Water for injections, 
Sodium hydroxide added as necessary to adjust pH 
Abbott 
 

 
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Has been changed to read: 
Study Drug 
Formulation 
Manufacturer 
Adalimumab 
40 mg/0.8 mL or 20 mg/0.4 mL  
Adalimumab/Mannitol, Citric acid monohydrate, Sodium citrate, 
Disodium phosphate dihydrate, Sodium dihydrogen phosphate 
dihydrate, Sodium chloride, Polysorbate 80, Water for injections, 
Sodium hydroxide added as necessary to adjust pH 
Abbott 
Adalimumab 
40 mg/0.8 mL (used for 10 mg dose) 
Adalimumab/Mannitol, Citric acid monohydrate, Sodium citrate, 
Disodium phosphate dihydrate, Sodium dihydrogen phosphate 
dihydrate, Sodium chloride, Polysorbate 80, Water for injections, 
Sodium hydroxide added as necessary to adjust pH 
Abbott 
 
Section 5.5.2.1  Packaging and Labeling 
Second paragraph previously read: 
The following information will appear on the pre-filled syringe or carton labels: 
Has been changed to read: 
The following information will appear on the pre-filled syringe, vial or carton labels: 
Section 5.5.2.1  Packaging and Labeling 
First paragraph previously read: 
Two pre-filled syringes will be provided in a dosing kit carton (see Table 4). 
Has been changed to read: 
Two pre-filled syringes or vials will be provided in a dosing kit carton (see Table 4). 
Table 4.  Study Drug Packaging and Administration 
Previously read: 
Open-label Pre-filled Syringes 
Open-label kit cartons containing two pre-filled 
syringes of adalimumab 40 mg/0.8 mL. 
Open-label kit cartons containing two pre-filled 
syringes of adalimumab 20 mg/0.4 mL. 
 

 
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Has been changed to read: 
Open-label Pre-filled Syringes 
Open-label kit cartons containing two pre-filled 
syringes of adalimumab 40 mg/0.8 mL. 
Open-label kit cartons containing two pre-filled 
syringes of adalimumab 20 mg/0.4 mL. 
Open-label Vials (used for 10 mg dose) 
Open-label kit cartons containing two vials of adalimumab 40 mg/0.8 mL. 
 
Section 5.5.2.2  Storage and Disposition of Study Drug 
First paragraph, first sentence previously read: 
Pre-filled syringes are to be stored protected from light at 2° to 8°C/ 36° to 46°F. 
Has been changed to read: 
Pre-filled syringes and vials are to be stored protected from light at 2° to 8°C/36° to 46°F. 
Section 5.5.4  Selection and Timing of Dose for Each Subject 
Add:  new fourth, fifth, sixth, and seventh paragraph 
The dose of adalimumab may be decreased to the next lower treatment level as applicable 
at the discretion of the investigator and prior approval from the medical monitor, for 
subjects whose body weight has decreased from t 40 kg to < 40 kg from the previous 
visit.  The site will enter the subjects' body weight into the IVRS and the dose will be 
adjusted, if applicable. 
Subjects who responded to treatment defined as a) an improvement of at least 15 points 
in PCDAI compared to the last observation prior to dose escalation in patients who 
dose-escalated or b) an improvement of at least 15 points in PCDAI compared to 
Baseline of Study M06-806 in patients who did not dose-escalate) may have their dosage 
frequency decreased from ew to eow dosing.  The investigator should receive prior 
approval from the medical monitor before taking any action with regard to the dose 
frequency decrease.  At least 8 weeks after dose frequency decrease, subjects who still 
responded to treatment (as defined above) may have their dosage decreased (subjects who 
weigh t 40 kg will receive 20 mg eow of adalimumab, while subjects who weigh < 40 kg 

 
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will receive 10 mg eow of adalimumab).  The investigator should receive prior approval 
from the medical monitor before taking any action with regard to dose decrease. 
Subjects who experience a disease flare may re-increase their dosage or dose frequency 
to the next higher treatment level regardless of prior dose or dose frequency decrease.  
Simultaneous dose adjustment based on change of body weight as well as based on 
diseases status (response/flare) is prohibited. 
Section 5.5.6  Treatment Compliance 
Second paragraph previously read: 
In order to document compliance with the treatment regimen, all pre-filled syringes will 
be counted and documented in source documents and on the appropriate drug 
accountability form. 
Has been changed to read: 
In order to document compliance with the treatment regimen, all pre-filled syringes and 
vials will be counted and documented in source documents and on the appropriate drug 
accountability form. 
Section 5.5.7  Drug Accountability 
First paragraph, fourth sentence previously read: 
An accurate running inventory of study drug will be kept by the site, and will include the 
kit number, lot number(s), the number of pre-filled syringes dispensed, and the date study 
drug was dispensed for each subject. 
Has been changed to read: 
An accurate running inventory of study drug will be kept by the site, and will include the 
kit number, lot number(s), the number of pre-filled syringes or vials dispensed, and the 
date study drug was dispensed for each subject. 

 
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Section 5.5.7  Drug Accountability 
First paragraph, sixth sentence previously read: 
All unused pre-filled syringes will be inventoried and returned to an identified vendor for 
disposal as designated by Abbott Laboratories. 
Has been changed to read: 
All unused pre-filled syringes and vials will be inventoried and returned to an identified 
vendor for disposal as designated by Abbott Laboratories. 
Section 5.5.7  Drug Accountability 
Second paragraph previously read: 
All used (expelled) pre-filled syringes will be inventoried by the site and verified by the 
CRA.  The used syringes will be discarded on site, using appropriate biohazard 
precautions.  CRAs and site staff will complete study drug accountability via study drug 
logs, source documents, verification of empty used syringe kit boxes, subject diaries and 
by visually counting the syringes in the sharps container whenever possible.  Used sharps 
containers should never be opened.  Each subject will be given their own sharps disposal 
container to store expelled syringes.  Sharps containers should be returned by the subject 
at each visit, for accountability and compliance purposes.  New containers will be issued 
to subjects as necessary.  Once the CRA has verified drug accountability at the site, the 
site staff and CRA will sign off that the expelled pre-filled syringes have been destroyed. 
Has been changed to read: 
All used (expelled) pre-filled syringes and vials will be inventoried by the site and 
verified by the CRA.  The used syringes and vials will be discarded on site, using 
appropriate biohazard precautions.  CRAs and site staff will complete study drug 
accountability via study drug logs, source documents, verification of empty used syringe 
kit or vials boxes, subject diaries and by visually counting the syringes in the sharps 
container whenever possible.  Used sharps containers should never be opened.  Each 
subject will be given their own sharps disposal container to store expelled/used syringes.  

 
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Sharps containers should be returned by the subject at each visit, for accountability and 
compliance purposes.  New containers will be issued to subjects as necessary.  Once the 
CRA has verified drug accountability at the site, the site staff and CRA will sign off that 
the expelled pre-filled syringes and used vials have been destroyed. 
Section 5.6.4  Selection of Doses in the Study 
Previously read: 
The results of the pivotal adalimumab adult CD maintenance trial M02-404, in 
conjunction with results from adalimumab CD Study M02-433, support a maintenance 
dose of adalimumab 40 mg eow.  Data also suggest that patients who lose response to 
adalimumab at 40 mg eow can be dose-escalated to 40 mg weekly with the potential of 
regaining clinical response.  The proposed dosing regimen for Study M06-807 was 
developed using an analogous approach as that studied in the adult CD population.  
Population pharmacokinetic modeling of serum adalimumab concentration data from 
pediatric subjects with JRA was used to identify doses to be evaluated in the current 
study in children with CD.  A model based on the JRA population was chosen because 
the body weight range will closely parallel that in a juvenile CD population.  Escalation 
to weekly dosing will provide average adalimumab concentrations at steady state about 
twice that observed with every other week dosing.  However, these concentrations are 
within the range of systemic exposures that were safely studied in adult subjects with CD. 
Has been changed to read: 
The results of the pivotal adalimumab adult CD maintenance trial M02-404, in 
conjunction with results from adalimumab CD Study M02-433, support a maintenance 
dose of adalimumab 40 mg eow.  Data also suggest that patients who lose response to 
adalimumab at 40 mg eow can be dose-escalated to 40 mg weekly with the potential of 
regaining clinical response.  The proposed dosing regimen for Study M06-807 before 
Amendment 4 was developed using an analogous approach as that studied in the adult 
CD population.  Population pharmacokinetic modeling of serum adalimumab 
concentration data from pediatric subjects with JRA was used to identify doses to be 
evaluated in the current study in children with CD before Amendment 4.  A model based 

 
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on the JRA population was chosen because the body weight range would closely parallel 
that in a juvenile CD population.  Escalation to weekly dosing would provide average 
adalimumab concentrations at steady state about twice that observed with every other 
week dosing.  However, these concentrations are within the range of systemic exposures 
that were safely studied in adult subjects with CD. 
After completion of Study M06-806 and consideration of efficacy, safety and population 
pharmacokinetic results in conjunction with exposure-response modeling and simulation 
both the Low-Dose and High-Dose treatment provided evidence of efficacy and safety.  
Therefore, in order to minimize the systemic exposures to study drug to the lowest doses 
necessary in children with CD, Amendment 4 provides investigators with the option of 
dose de-escalation by reducing the dose or switching from ew to eow based on the 
clinical status of the individual patient.  In addition, since the 10 mg eow dose was 
efficacious in subjects weighing < 40 kg in Study M06-806 patients will have the option 
to be switched to this dose based on their body weight and clinical status at the discretion 
of the investigator. 
Section 8.1.1  Analyzable Population 
Delete:  second sentence 
In order to evaluate the impact of major protocol violations / deviations on the results of 
the study, additional analyses may be performed on the per-protocol population, which 
excludes all subjects with major protocol deviations.   
Section 8.1.2.2  Primary Efficacy Analysis 
Section title previously read: 
Primary Efficacy Analysis 
Has been changed to read: 
Efficacy Analysis 

 
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Section 8.1.3  Other Analyses 
First paragraph previously read: 
The primary endpoint will be analyzed for the following subgroups in the ITT population. 
Has been changed to read: 
Efficacy will be analyzed for the following subgroups in the ITT population. 
Section 8.1.4  Safety Analyses 
First paragraph, second sentence previously read: 
Treatment-emergent, and post − treatment AEs will be summarized.   
Has been changed to read: 
Treatment-emergent AEs will be summarized.   
Appendix B.  List of Protocol Signatories 
Previously read: 
Name 
Title 
Functional Area 
Statistics 
Clinical 
Clinical 
Clinical 
 
Has been changed to read: 
Name 
Title 
Functional Area 
Statistics 
Clinical 
Clinical 
Clinical 
 

 
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Appendix F.  Non-Drug Materials Provided to the Study Site(s) 
Add:  new ninth item following first paragraph 
Dosing syringes, as applicable 
Appendix Q.  Self Injection Instructions 
Previously read: 
 

 
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Has been changed to read: 
 
 
Subject Instructions 
0.8 mL or 0.4 mL dose 
(Administered as a single dose-prefilled syringe (PFS)) 
 
Protocol M06-807 
 

 
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Tables of Contents 
Dosing Schedule 
General Information  
Injection Procedures 
 

 
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Study Drug Dosing Schedule 
Open-Label (PFS) 
Subject Number:_____________________________________ 
You will require subcutaneous (SC) injections throughout the study.  
Injections at scheduled study visits (Baseline, Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 
108, 120, 144, 168, 192, 216 and 240) will be done during your visit, at the doctors 
office.  On weeks between office visits, study drug will be self-administered at home by 
you or someone trained to give you the injections. 
For 40 mg dose, one pre-filled syringe will contain 0.8 mL of liquid.  The total available 
dose is 0.8 mL.  The drug should be administered in one (1) SC injection, on the same 
day of the week for each dose. 
For 20 mg dose, one pre-filled syringe will contain 0.4 mL of liquid.  The total available 
dose is 0.4 mL.  The drug should be administered in one (1) SC injection, on the same 
day of the week for each dose. 
Please return all used and unused syringes to the clinic on your next visit. Used syringes 
should be placed in the special sharps container provided. All unused syringes should be 
returned in the original box. 
If an injection is missed or something occurs where the full dose cannot be injected, 
contact your study center immediately for further instructions.  Please record any missed 
doses on your subject diary. 
Remember to complete your dosing diary after each injection and to call the doctors 
office if you are having problems administering your study drug. 

 
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General Information 
 
 
 
 
 
 
 
PFS 
● Prefilled syringes will be labeled "adalimumab." 
● Store all adalimumab prefilled syringes in your refrigerator NOT in the 
freezer.  Should the syringes accidentally become frozen, call your study 
coordinator. 
● 0.8 mL = 0.8 cc 
● Study drug should be taken at about the same time of day, on the same day of 
the week as directed by your study doctor. 
● USE A NEW SYRINGE EVERY INJECTION DAY.  There may be 
medication left in the syringe.  DO NOT RE-USE. 
● Save all study drugs.  Prefilled syringes (used and unused) must be returned 
to the study center at each visit.  Used syringes will be disposed of in a sharps 
container provided to you. 
● Whenever possible, have someone with you for at least 15 to 30 minutes after 
your injection. 
● Call your doctor IMMEDIATELY if you experience any itching, hives, 
shortness of breath, or any symptom that has you concerned.  If you are 
unable to reach your doctor or if you experience life-threatening symptoms 
call 911, or proceed to your nearest emergency room. 
 

 
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Injection Procedures 
 
 
 
 
 
 
 
PFS 
1. Clean your workspace, gather your supplies, and wash your hands. 
 
 
2. Identify the area on your abdomen or thigh (or upper arm 
if not self injecting).  Make sure the area you choose 
does not have any redness, tenderness, swelling, bruising, 
or psoriasis.  The area must also be at least 2 cm 
(approximately 1 inch) away from the previous injection 
site.  IT IS VERY IMPORTANT TO CHANGE THE 
INJECTION SITE EVERY TIME!!! 
 
 
3. Using a circular motion (starting at the injection site and 
moving outward) clean the selected injection site with 
an alcohol pad.  Allow skin to dry.  
4. Remove the needle cap. Do not touch the needle.  Expel 
any air bubbles from the syringe by tapping on the 
syringe.  If the needle becomes contaminated, discard 
all supplies and obtain a new syringe of study drug.  
5. Once the air is expelled from the syringe, the amount of 
solution in the syringe should be 0.8 mL. 
 
 
6.   Hold the syringe "like a dart" between your thumb and 
first finger close to the syringe/needle connection. 

 
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PFS 
 
7. With your other hand, pinch the skin around the 
injection site, forming a bulge in the skin. 
 
 
 
 
 
 
8. Insert the needle into the skin at a 45-degree angle. 
Release pinched skin. 
 
 
 
 
9. 
GENTLY pull back on the syringe plunger.  If blood 
appears, withdraw needle - DO NOT INJECT!  
Contact your study center immediately for further 
instructions.  
 
10. Inject drug by pushing slowly on syringe plunger with 
thumb. 
 
11. Remove needle while maintaining a 45-degree angle. 
 
12. You may apply a Band-Aid over the injection site and 
apply gentle pressure, if necessary.  DO NOT RUB 
SITE. 
 
13. 
DO NOT RECAP NEEDLE.  DO NOT SEPARATE THE NEEDLE FROM THE 
 
SYRINGE BEFORE DISPOSING.  Discard used syringes into Sharps Container. 
EACH TIME THAT YOU GIVE YOURSELF AN INJECTION OF STUDY DRUG, 
REMEMBER TO RECORD THE INFORMATION ON YOUR SUBJECT DOSING 
DIARY. 
 

 
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Self Injection Instructions 
 
Subject Instructions 
0.2 mL dose 
Vials 
Protocol M06-807 

 
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Tables of Contents 
Dosing Schedule 
General Information  
Injection Procedures 

 
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Study Drug Dosing Schedule 
Vials 
Subject Number:  _____________________________________ 
You will require subcutaneous (SC) injections throughout the study. 
The injection for the visits at Weeks 4, 8, 12, 16, 20, 26, 32, 40, 48, 60, 72, 84, 96, 108, 
120, 144, 168, 192, 216 and 240 will be done during your visit at the doctor's office.  
After Week 4, on weeks between office visits (i.e., Weeks 6, 10, 14 etc.) study drug will 
be self-administered at home by you or someone trained to give you the injections. 
The total dose is 0.2 mL.  The drug should be administered in one (1) SC injection, on the 
same day of the week for each dose. 
For 10 mg dose, 0.2 mL of the solution is drawn from a vial containing adalimumab 
40 mg/0.8 mL solution.  The drug should be administered in one (1) SC injection, on the 
same day of the week for each dose. 
Please return all used and unused vials to the clinic on your next visit.  Used syringes 
should be placed in the special sharps container provided.  All unused vials should be 
returned in the original box. 
If an injection is missed or something occurs where the full dose cannot be injected, 
contact your study center immediately for further instructions.  Please record any missed 
doses on your subject diary. 
Remember to complete your dosing sheet after each injection and to call the doctor's 
office if you are having problems administering your study medication. 

 
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General Information 
Vials 
● Vials will be labeled "adalimumab." 
● Store all adalimumab vials in your refrigerator NOT in the freezer.  Should the 
vials accidentally become frozen, call your study coordinator. 
● 0.2 mL = 0.2 cc 
● Study drug should be taken at about the same time of day, on the same day of 
the week as directed by your study doctor. 
● USE A NEW VIAL EVERY INJECTION DAY.  There will be medication 
left in the vial.  DO NOT RE-USE. 
● Save all study drugs.  Vials (used and unused) must be returned to the study 
center at each visit.  Used vials and syringes will be disposed of in a sharps 
container provided to you. 
● Whenever possible, have someone with you for at least 15 to 30 minutes after 
your injection. 
● Call your doctor IMMEDIATELY if you experience any itching, hives, 
shortness of breath, or any symptom that has you concerned.  If you are 
unable to reach your doctor or if you experience life-threatening symptoms 
call 911, or proceed to your nearest emergency room. 
 

 
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Injection Instructions  
Vials 
Select a clean, well-lit, flat surface. 
1. 
Wash your hands thoroughly with soap and warm water.  It is important to keep 
your work surface as clean as possible. 
2. 
Open carton. 
3. 
Examine the carton and components in it to make sure they are complete. 
● One or two vials containing adalimumab 
 
4. 
Remove the plastic cap from the vial. 
5. 
Wipe the gray stopper with an alcohol swab and discard alcohol swab. 
 
 
6. 
Place the vial upright on a hard, flat surface. 
7. 
Choose an injection site on the upper thigh or abdomen. 
8. 
Prepare the injection site by wiping it thoroughly with a second alcohol swab.  
Use a circular motion. 
 

 
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9. 
Remove the needle cover from the syringe.  (The needle is sterile, so be very 
careful not to touch the needle or allow it to touch any surface.) 
10. 
Draw the plunger on the syringe back. 
11. 
With the vial sitting on a hard, flat surface, insert needle straight down through 
the center of the gray stopper.  If the needle is correctly lined up, you should feel 
slight resistance and then a "pop" as the needle penetrates the center of the 
stopper.  (Be careful not to insert the needle at an angle as this may cause the 
needle to bend.  If the needle is not correctly aligned, you will feel constant 
resistance as it penetrates the stopper and will not feel a "pop.") 
12. 
Push the plunger in forcing air into the vial. 
13. 
With the needle still in place, turn the vial upside down.  Keeping the vial at eye 
level, slowly pull the plunger back to draw the liquid into the syringe.  This will 
cause the bubbles to rise to the top of the syringe.  (As the liquid level in the vial 
drops, you may have to withdraw the needle partially to keep the tip of the needle 
in the liquid.)  Only 0.2 mL of the vial will be drawn into the syringe. 
14. 
With the needle still in the vial, check the syringe for air bubbles.  To remove any 
air bubbles, start by gently tapping the syringe. 
15. 
Slowly press the plunger to push any bubbles out of the syringe and into the vial.  
(If you accidentally push any liquid back into the vial, draw the liquid back into 
the syringe and check again for air bubbles.  It's okay for a small amount of liquid 
to remain in the vial.) 
16. 
Withdraw the needle from the vial, being careful not to touch it to any surface. 

 
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Vials 
17. 
Take the syringe in one hand. 
 
 
18. 
With your other hand, firmly pinch the skin around the cleaned injection site.  (Be 
careful not to touch the cleaned area.) 
 
 
19. 
Hold the syringe at about a 45-degree angle to the skin and use a quick, short 
motion to push the needle into the skin. 
 
 
20. 
Once the needle is in, release the skin. 

 
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Vials 
21. 
While firmly holding the syringe with one hand, use your other hand to slowly 
push the plunger and inject the adalimumab.  For subjects that weigh t 40 kg, all 
0.8 mL will be injected.  For subjects that weigh < 40 kg, only 0.4 mL of the vial 
will be inject. 
 
 
22. 
When the syringe is empty, remove the needle from the skin, being careful to 
keep it at the same 45-degree angle. 
23. 
Dispose of both the needle and syringe in a puncture-resistant container, or sharps 
container, which will be provided. 
24. 
You may want to press a cotton ball on the injection site for 10 seconds.  If there 
is some slight bleeding, you may choose to apply a small bandage. 
25. 
Return the vial into the original packaging. 
26. 
Place the medication kit back into the refrigerator. 

 
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Vials 
EACH TIME YOU RECEIVE AN INJECTION OF STUDY MEDICATION, 
REMEMBER TO RECORD THE INFORMATION ON YOUR DOSING SHEET. 
GENERAL INFORMATION: 
27. 
ROTATING INJECTION SITES IS RECOMMENDED.  PLEASE DO NOT 
INJECT THE STUDY MEDICATION INTO A PRIOR SITE OF INJECTION. 
28. 
Store all of your drug in the refrigerator.  Should the vials become accidentally 
frozen or left out, call your study coordinator.  DO NOT USE THESE VIALS. 
29. 
If you forget to take the drug or make a mistake with an injection, please call your 
study coordinator. 
30. 
Please save all of your study medication, even if you skip a dose.  Please bring all 
used and unused vials back to the physician at your next study visit. 
31. 
There will be study medication remaining in the vials.  DO NOT USE THE 
MEDICATION LEFT IN THE VIAL.  Please return the vial along with the 
remaining study medication back to the physician at your next study visit. 
32. 
Specific side effects to watch for:  redness and swelling at the injection site.  
Please tell the study coordinator if you have any side effects from injecting the 
drug. 
 

 
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1.0 
Title Page 
CLINICAL TRIAL PROTOCOL M06-807 
A Multi-center, Open-label Study of the Human 
Anti−TNF Monoclonal Antibody Adalimumab to 
Evaluate the Efficacy and the Long-term Safety and 
Tolerability of Repeated Administration of 
Adalimumab in Pediatric Subjects with 
Crohn's Disease Who Have Demonstrated a Clinical 
Response in the M06-806 Study 
Incorporating Administrative Changes 1 and 2, 
Amendment 1, Administrative Changes 3, 4, 5 and 6, 
and Amendments 2 and 3 
Abbott Number /  
 Investigational Product: 
 
Adalimumab 
Date:  
14 December 2010 
Development Phase: 
3 
Study Design:  
A multi-center, open-label safety and tolerability pediatric study in the 
United States, Canada and Europe. 
EudraCT Number:  
2007-006494-90 
Investigator: 
Multicenter (Investigator information on file at Abbott Laboratories). 
Sponsor: 
European Union Countries: 
Abbott GmbH & Co.KG  
Knollstrasse 50 
67061 Ludwigshafen, Germany 
Non European Union Countries: 
Abbott Laboratories, US  
100 Abbott Park Road 
Abbott Park, IL 60064 
Emergency Contact: 
This study will be conducted in compliance with the protocol, Good Clinical Practice and all other 
applicable regulatory requirements, including the archiving of essential documents. 
Confidential Information 
No use or disclosure outside Abbott is permitted without prior written authorization from Abbott. 

 
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1.1 
Protocol Amendment:  Summary of Changes 
The purpose of this amendment is to: 
● Include interim analysis. 
● Clarify that the x-ray for bone age will not be performed at the unscheduled 
visit. 
● Add a statement allowing the investigator to omit the x-ray for bone age and 
the determination of serum bone markers if the subject is no longer growing. 
● Correct typographical errors. 
 
An itemized list of all changes made to the protocol under this amendment can be found 
in Appendix U. 

 
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2.0 
Table of Contents 
1.0 
Title Page .................................................................................1 
1.1 
Protocol Amendment:  Summary of Changes...........................................2 
2.0 
Table of Contents....................................................................3 
3.0 
Introduction.............................................................................8 
4.0 
Study Objective .....................................................................14 
5.0 
Investigational Plan ..............................................................14 
5.1 
Overall Study Design and Plan:  Description..........................................14 
5.2 
Selection of Study Population .................................................................18 
5.2.1 
Inclusion Criteria.....................................................................................18 
5.2.2 
Exclusion Criteria....................................................................................19 
5.2.3 
Prior and Concomitant Therapy ..............................................................21 
5.2.3.1 
Prior Therapy...........................................................................................21 
5.2.3.2 
Concomitant Therapy..............................................................................22 
5.2.3.3 
Rescue Therapy .......................................................................................23 
5.2.3.4 
Prohibited Therapy ..................................................................................23 
5.3 
Efficacy, and Safety Assessments/Variables...........................................23 
5.3.1 
Efficacy and Safety Measurements Assessed and Flow Chart................23 
5.3.1.1 
Study Procedures.....................................................................................29 
5.3.2 
Drug Concentration Measurements.........................................................36 
5.3.2.1 
Collection of Samples for Analysis.........................................................37 
5.3.2.2 
Handling/Processing of Samples.............................................................37 
5.3.2.3 
Disposition of Samples............................................................................38 
5.3.2.4 
Measurement Methods ............................................................................38 
5.3.3 
Efficacy Variables ...................................................................................38 
5.3.4 
Safety Variables.......................................................................................39 
5.3.5 
Pharmacokinetic Variables......................................................................39 

 
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5.4 
Removal of Subjects from Therapy or Assessment ................................39 
5.4.1 
Discontinuation of Individual Subjects ...................................................39 
5.4.2 
Discontinuation of Entire Study ..............................................................40 
5.4.3 
Stopping Rules.........................................................................................40 
5.5 
Treatments ...............................................................................................41 
5.5.1 
Treatments Administered ........................................................................41 
5.5.2 
Identity of Investigational Product ..........................................................41 
5.5.2.1 
Packaging and Labeling ..........................................................................42 
5.5.2.2 
Storage and Disposition of Study Drug...................................................43 
5.5.3 
Method of Assigning Subjects to Treatment Groups ..............................43 
5.5.4 
Selection and Timing of Dose for Each Subject .....................................44 
5.5.5 
Blinding...................................................................................................44 
5.5.6 
Treatment Compliance ............................................................................45 
5.5.7 
Drug Accountability................................................................................45 
5.6 
Discussion and Justification of Study Design .........................................46 
5.6.1 
Discussion of Study Design and Choice of Control Groups...................46 
5.6.2 
Appropriateness of Measurements ..........................................................46 
5.6.3 
Suitability of Subject Population.............................................................46 
5.6.4 
Selection of Doses in the Study...............................................................46 
6.0 
Adverse Events......................................................................47 
6.1 
Definitions...............................................................................................47 
6.1.1 
Adverse Event .........................................................................................47 
6.1.2 
Serious Adverse Events...........................................................................48 
6.2 
Adverse Event Severity...........................................................................49 
6.3 
Relationship to Study Drug .....................................................................49 
6.4 
Adverse Event Collection Period ............................................................50 
6.5 
Adverse Event Reporting ........................................................................50 

 
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6.5.1 
Collection of Data Regarding Known Manifestations of the 
Disease Under Study ...............................................................................51 
6.6 
Pregnancy ................................................................................................51 
7.0 
Protocol Deviations...............................................................52 
8.0 
Statistical Methods and Determination of Sample 
Size..........................................................................................53 
8.1 
Statistical and Analytical Plans ...............................................................53 
8.1.1 
Analyzable Population.............................................................................53 
8.1.2 
Planned Methods of Statistical Analysis .................................................53 
8.1.2.1 
Demographics and Baseline Characteristics ...........................................54 
8.1.2.2 
Primary Efficacy Analysis.......................................................................54 
8.1.3 
Other Analyses ........................................................................................54 
8.1.4 
Safety Analyses .......................................................................................54 
8.1.4.1 
Pharmacokinetic Analyses.......................................................................55 
8.1.5 
Interim Analysis ......................................................................................56 
8.2 
Determination of Sample Size.................................................................56 
8.3 
Randomization Methods..........................................................................56 
9.0 
Ethics......................................................................................56 
9.1 
Independent Ethics Committee (IEC) or Institutional Review 
Board (IRB).............................................................................................56 
9.2 
Ethical Conduct of the Study...................................................................57 
9.3 
Subject Information and Consent ............................................................57 
10.0 
Source Documents and Case Report Form 
Completion.............................................................................58 
10.1 
Source Documents...................................................................................58 
10.2 
Case Report Forms ..................................................................................58 
11.0 
Data Quality Assurance........................................................59 
12.0 
Use of Information and Publication....................................60 
12.1 
Use of Information ..................................................................................60 

 
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12.2 
Internet Sites............................................................................................61 
13.0 
Completion of the Study.......................................................61 
14.0 
Investigators Agreement ......................................................63 
15.0 
Reference List........................................................................64 
 
List of Tables 
Table 1.  
Study Activities .......................................................................................24 
Table 2.  
Clinical Laboratory Tests ........................................................................32 
Table 3.  
Identity of Investigational Products.........................................................42 
Table 4.  
Study Drug Packaging and Administration.............................................43 
 
List of Figures 
Figure 1.  
Study Schematic ......................................................................................17 
Figure 2.  
Adverse Event Collection........................................................................50 
 
List of Appendices 
Appendix A.  
List of Abbreviations and Definition of Terms .......................................68 
Appendix B.  
List of Protocol Signatories.....................................................................70 
Appendix C.  
Documents Required Prior to Initiation of the Study..............................71 
Appendix D.  
Responsibilities of the Clinical Investigator............................................73 
Appendix E.  
CDC Treatment of Tuberculosis Infection (Preventive Therapy)...........75 
Appendix F.  
Non-Drug Materials Provided to the Study Site(s) .................................77 
Appendix G.  
Pediatric Crohns Disease Activity Index (PCDAI).................................78 
Appendix H.  
PCDAI Users Guide and Guideline for Reference Weight and 
Reference Height.....................................................................................80 
Appendix I.  
Crohns Disease Activity Index (CDAI) ..................................................86 
Appendix J.  
Subject CDAI Diary ................................................................................87 
Appendix K.  
IMPACT III Questionnaire......................................................................88 

 
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Appendix L.  
Excluded Medications .............................................................................96 
Appendix M.  Day 70 Phone Call...................................................................................97 
Appendix N.  
Unscheduled Outpatient Visits, Emergency Room Visits and 
Hospitalizations .......................................................................................98 
Appendix O.  
Subject Medication Log ..........................................................................99 
Appendix P.  
Subject Dosing Diary ............................................................................100 
Appendix Q.  
Self Injection Instructions......................................................................118 
Appendix R.  
Standard Weights...................................................................................124 
Appendix S.  
Subject Abbott Laboratories Site Drug Accountability Form...............126 
Appendix T.  
Work Productivity and Activity Impairment Questionnaire: 
Crohns Disease (WPAI-CD) - Caregiver ..............................................127 
Appendix U.  
Protocol Amendment:  List of Changes ................................................129 
 

 
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3.0 
Introduction 
Crohns Disease (CD) is a chronic, debilitating, and currently incurable inflammatory 
disease that can affect the entire digestive system as well as extraintestinal organs.  CD is 
primarily manifested by focal asymmetric, transmural, and occasionally, granulomatous 
inflammation affecting any segment of the gastrointestinal tract1 which can consist of 
mucosal edema, aphthous and linear ulcerations, asymmetrical narrowing and strictures.  
Noncaseating granulomas are virtually diagnostic in the correct clinical setting.  The most 
commonly involved area of the bowel is the small bowel, particularly the distal ileum, 
which is involved in 70% of cases often in combination with colitis, occurring in 50% of 
cases.  Extraintestinal manifestations can also occur, and include symptoms of joint, 
ocular and hepatic inflammation.  Genetic, geographic, ethnic, and environmental risk 
factors have all been described, but the basic etiology of the disease remains unknown. 
The incidence in North America is similar to that in other western nations and is 
estimated from 3.1 to 14.6 cases per 100,000 person years and prevalence ranges from 
26 to 199 cases per 100,000 persons.2  The disease can affect persons of any age but the 
most common age of onset is in the second and third decades with a female 
preponderance.  While predominantly a disease of adults, approximately 10% to 15% of 
CD cases are diagnosed before adulthood.3 
In addition, the incidence of CD in patients less than 18 years of age appears to be 
increasing in both North America and Europe.4,5  Reported incidence rates range from 
1.2 to 4.9 per 100,000 persons in the UK, Europe, and North America6-12 with one study 
reporting an incidence of 4.6 per 100,000 persons in the United States.5  CD has been 
reported at all ages but is rare in early childhood.  In one study of patients with CD, 
17 years of age and younger, 9.1% of the patients were diagnosed before the age of 6.13  
In a second study of patients diagnosed with CD before the age of 15, 7.5% of the 
patients were under the age of 5.14 
Despite obvious physiologic and development differences, the presentation of CD in the 
pediatric population is generally similar to that seen in older patients and is 

 
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heterogeneous with regard to anatomic localization and clinical severity.5,15,16  The 
unique aspect of this disease in children is its impact on nutrition and growth, with 
marked growth retardation being a prominent component of the disease in this age 
group.17-19  The use of accepted methodologies for assessing nutritional status, including 
the anthropometric measures of height, weight, triceps skin fold thickness and mid arm 
circumference as well as linear growth (height velocity and assessment of height velocity 
for chronological age "z-score") have documented the growth impairment that can occur 
in this age group, and also have been used to assess the efficacy of interventions.20  
Profound impairment of bone formation and increased bone resorption are associated 
complications and are related to the effect of glucocorticoids,21,22 delayed puberty,22,23 
decreased mobility,24 as well as to the effects of cytokines on bone formation.25 
Initial symptoms are often subtle, and there is an average delay of almost six months 
between onset of symptoms and diagnosis.  The most common presentation is with 
abdominal pain, diarrhea, loss of appetite and weight loss.  However, isolated weight 
loss, anorexia, perianal disease and extraintestinal manifestations can occur in the 
absence of GI symptoms in a substantial number of patients. 
The general approach to the treatment of CD in children is similar to adults with the goals 
being induction and maintenance of remission, prevention of relapse and hospitalizations, 
improved quality of life, and avoidance of disease and drug related complications.  
Restoration and/or preservation of normal growth and pubertal development are 
additional therapeutic goals.  The medical armamentarium is likewise similar to adults 
and includes induction of remission with corticosteroids, and ongoing maintenance 
therapy of immunomodulators, aminosalicylates and nutritional therapy.  Anti-tumor 
necrosis factor (TNF) therapy with infliximab has been evaluated for the therapy of CD 
in this age group as it has in adults.  The FDA and EMEA have recently approved 
Infliximab for use in children with CD. 
Adalimumab is a recombinant human immunoglobulin (IgG1) monoclonal antibody 
exclusively containing human peptide sequences.  It is produced by recombinant 
deoxyribonucleic acid (DNA) technology in a mammalian cell expression system.  

 
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Adalimumab consists of 1330 amino acids and has a molecular weight of approximately 
148 kilodaltons.  It binds specifically with high affinity to the soluble and transmembrane 
forms of TNFD and inhibits the binding of TNFD with its receptors. 
TNF is a naturally occurring cytokine that is involved in normal inflammatory and 
immune responses.  Elevated levels of TNF play an important role in pathologic 
inflammation.  Adalimumab binds specifically to TNF and neutralizes the biological 
function of TNF by blocking its interaction with the p55 and p75 cell surface TNF 
receptors. 
Adalimumab was first approved for treatment of rheumatoid arthritis (RA) on 
31 Dec 2002 in the United States (US), on 08 Sep 2003 in the European Union (EU) and 
through August 2008 in a total of 76 countries.  Indication extensions to include 
treatment of psoriatic arthritis and early RA were granted in the EU on 01 Aug 2005 and 
in the US on 03 Oct 2005.  A further indication extension to include treatment of 
ankylosing spondylitis was approved in the EU on 01 Jun 2006 and was approved in the 
US on 28 Jul 2006.  Adalimumab was approved for the treatment of Crohns disease in the 
United States on 27 Feb 2007, in the European Union on 04 Jun 2007 and in Canada on 
05 July 2007 for the adult population.  In December 2007 and January 2008, respectively, 
adalimumab was approved for the treatment of psoriasis in adult patients in the EU, 
Canada and USA.  Additionally, adalimumab was approved for the treatment of juvenile 
idiopathic arthritis in the USA in February 2008. 
Adalimumab has been shown to be a safe and effective treatment of moderately to 
severely active Crohns disease.  In the CD development program, adalimumab was 
studied in over 1400 adult subjects in three pivotal studies (two induction studies and a 
maintenance study). 
Study M02-403 was a multicenter, randomized, double-blind, placebo-controlled 
Phase 2/3 study to evaluate the efficacy and safety of adalimumab for the induction of 
remission in subjects with moderate to severe CD.26  A total of 299 subjects were 
randomized to receive one of four proposed induction treatment regimens (three active 

 
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treatment groups or placebo):  adalimumab 160 mg at Baseline (Week 0) followed by 
80 mg at Week 2, adalimumab 80 mg at Baseline followed by 40 mg at Week 2, 
adalimumab 40 mg at Baseline followed by 20 mg at Week 2 or placebo at Baseline and 
Week 2.  Eligible subjects could not have been previously treated with any anti TNF 
agent.  Only the group of subjects treated with adalimumab 160/80 mg had a statistically 
significantly greater remission rate at Week 4 (primary endpoint) compared to placebo 
(35.5% vs. 12.2%; p = 0.001).  In addition, statistically significantly greater proportions 
of subjects in the adalimumab 160/80 mg group than in the placebo group experienced 
clinical response CR-100 (48.7% and 24.3%, respectively) and clinical response CR-70 
(57.9% and 36.8%, respectively) at Week 4. 
Study M04-691, a second induction study, was a multicenter, randomized, double-blind, 
placebo-controlled, Phase 3 study to evaluate the efficacy and safety of adalimumab as 
induction treatment for subjects with moderate to severe CD who either initially 
responded to administration of infliximab but stopped responding or were intolerant.27  
A total of 325 subjects were randomized to receive adalimumab 160/80 mg or placebo.  
Eligible subjects must have previously been treated with infliximab and discontinued use 
due to loss of response to or intolerance to infliximab therapy.  The proportion of subjects 
who achieved clinical remission at Week 4 (primary endpoint) was statistically 
significantly greater in the adalimumab 160/80 mg group compared to the placebo group 
(21.4% vs. 7.2%).  The proportion of subjects achieving clinical response CR-100 and 
CR-70 at Week 4 was statistically significantly greater in the adalimumab 160/80 mg 
group (38.4% and 51.6%, respectively) compared to the placebo group (24.7% and 
33.7%, respectively). 
Study M02-404 was a multicenter, randomized, double-blind, placebo-controlled Phase 3 
study to assess the efficacy and safety of adalimumab for the maintenance of clinical 
remission in subjects with moderate to severe CD.27  A total of 854 subjects (both naïve 
to or previously treated with TNF antagonists [primarily infliximab]) were enrolled and 
received open-label adalimumab 80 mg at Baseline (Week 0) and adalimumab 40 mg at 
Week 2.  At Week 4, subjects were stratified by responder status (subjects who achieved 

 
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clinical response CR-70) and previous anti-TNF use and were randomized in a 1:1:1 ratio 
to one of three blinded treatment groups:  adalimumab 40 mg every week (ew), 
adalimumab 40 mg every other week (eow), or placebo.  Subjects who met clinical 
response CR-70 after Week 8 could be tapered from corticosteroids. 
The proportion of Week 4 responders (N = 499) who achieved clinical remission at 
Weeks 26 and 56 (co-primary endpoint) were statistically significantly greater in the 
adalimumab 40 mg eow (39.5% and 36.0%, respectively) and 40 mg ew (46.5% and 
41.4%, respectively) groups compared to the placebo group (17.1% and 11.8%, 
respectively).  The differences between the adalimumab 40 mg eow and 
adalimumab 40 mg ew groups at both of these time points were not statistically 
significant.  The median time in first clinical remission was greater in the adalimumab 
40 mg eow group (378 days) compared to the placebo group (127 days).  The median 
time in remission could not be estimated in the adalimumab 40 mg ew group because 
more than 50% remained in clinical remission at the end of the study.  Approximately six 
times as many subjects treated with adalimumab maintenance therapy compared to 
placebo were able to discontinue corticosteroids for at least 90 days and achieve 
remission at Week 26 and Week 56.  Efficacy was independent of Baseline C-reactive 
protein (CRP), concomitant therapies, such as corticosteroids or immunosuppressants, or 
prior anti-TNF experience.  The adalimumab safety profile in CD was similar to that seen 
in the other rheumatologic populations previously studied, except for expected 
manifestations of CD. 
Currently, there are two ongoing extension studies of adalimumab therapy in adult 
subjects with CD.  M04-690 trial is a long-term safety and tolerability study of repeated 
administration of adalimumab in adult subjects with CD who had previously participated 
in M02-404 or M04-691.  The other trial is a long-term open-label extension study 
following the initial first-year study period of the M02-433 study. 
The efficacy and safety of adalimumab in children has recently been demonstrated in 
juvenile rheumatoid arthritis (JRA).28  One hundred and seventy-one pediatric patients 
(4 to 17 years of age) were initially enrolled into a 16-week open label segment and 

 
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133 subjects continued in a 32-week double blind segment.  Clinically significant 
improvements were noted in ACR30, ACR50 and ACR70 as well as other indices of 
arthritis activity.  Adverse events (AEs) were similar as those noted in adult RA patients.  
There were no deaths, malignancies, or opportunistic infections, including tuberculosis 
(TB).  Thirteen serious adverse events (SAEs) in 8 subjects were observed in the 16-week 
open label portion of the study.  These included 4 subjects with JRA, one patient with 
two episodes of leukopenia/neutropenia, and one case each of femur fracture, herpes 
simplex, and pneumonia.  Six SAEs were observed in 6 subjects (2 placebo, 
4 adalimumab) during the 32-week double blind portion (closed head injury, 
gastroduodenitis, retinal detachment, appendicitis, abdominal pain and urinary tract 
infection).  Infections, AEs at least possibly related to study drug, and injection site 
reactions were reported by similar proportions of patients in all treatment groups during 
the double-blind therapy (32 weeks). 
Fatalities, serious infections, and sepsis have been reported with the use of TNF 
antagonists.  Many of the serious infections have occurred in subjects on concomitant 
immunosuppressive therapy that, in addition to their underlying immune disorder, could 
predispose them to infections.  TB has also been observed in subjects treated with TNF 
antagonists, including adalimumab.  The event rate for TB in the CD development 
program is consistent with the global adalimumab rate.29 
TNF antagonists, including adalimumab, have been associated with cases of malignancy 
and demyelinating disease.  Serious allergic adverse reactions have been reported in RA 
subjects following subcutaneous (SC) administration of adalimumab; none were reported 
in the CD program. 
A detailed discussion of the pre-clinical toxicology, metabolism, pharmacology, and 
safety experience can be found in the current Investigators Brochure. 
The goal of this study is to demonstrate the efficacy of adalimumab in the maintenance of 
clinical response and to demonstrate the long-term safety and tolerability of repeated 
administration of adalimumab in pediatric subjects with Crohns disease.  The subject 

 
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population will consist of subjects who participated in and successfully completed the 
M06-806 study and who meet all the inclusion and none of the exclusion criteria of 
Protocol M06-807.  Qualifying subjects will administer open-label adalimumab by SC 
injection.  Subjects receiving every other weekly therapy who continue to have a disease 
flare or develop another flare may be switched to every week therapy at the investigators 
discretion.  Subjects receiving weekly therapy who continue to have a disease flare or 
develop another flare may be withdrawn from the study at the Investigators discretion.  
For a detailed description of the study please see Section 5.0. 
4.0 
Study Objective 
The objective of the study is to evaluate the long-term maintenance of clinical response, 
safety and tolerability of repeated administration of adalimumab in pediatric subjects 
with Crohns disease who participated in, and successfully completed, Protocol M06-806 
through Week 52 and who meet all the inclusion and none of the exclusion criteria of 
Protocol M06-807. 
5.0 
Investigational Plan 
5.1 
Overall Study Design and Plan:  Description 
This study is a multi-center, open-label study of the human anti-TNF monoclonal 
antibody adalimumab.  Approximately 31 sites that have enrolled subjects in the 
M06-806 clinical trial will participate in the M06-807 clinical trial.  Approximately 
130 pediatric subjects were expected to enroll in this study; final enrollment was 
100 subjects.   
The Week 52 visit from the M06-806 study will be the Baseline Visit for those subjects 
entering study M06-807.  The visit window for M06-806 Week 52 visit is 364 ± 7 days 
from the Baseline Visit date of M06-806. 
Subjects may be allowed to enroll in the M06-807 study if they have participated in, and 
successfully completed Protocol M06-806 through Week 52.  A subject must be a 

 
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responder at any time point during the M06-806 study.  A responder is defined as a 
subject who had a PCDAI score that was at least 15 points lower than the M06-806 
baseline score. 
All subjects will be on open-label maintenance therapy.  Subjects who enroll into the 
study from blinded therapy in Study M06-806 will receive open-label therapy at a dose 
dependent on their body weight.  Subjects who weigh t 40 kg at Baseline will receive 
40 mg eow of adalimumab, while subjects who weigh < 40 kg at Baseline will receive 
20 mg eow of adalimumab.  Beginning at Week 8, subjects who have a disease flare may 
be switched to ew treatment at the same dose of adalimumab received while on eow 
treatment.  A disease flare is defined as an increase in the Pediatric Crohns Disease 
Activity Index (PCDAI) of t 15 points when compared to the PCDAI score obtained at 
the subjects previous visit. 
Subjects who enroll into the study from open-label therapy in Study M06-806 will 
continue to receive the same dose they were receiving (i.e. 40 mg ew or 20 mg ew) at the 
Week 52 visit of the M06-806 study.  
Subjects who develop a flare while receiving ew open-label therapy or have a PCDAI 
score t 15 points when compared to their Baseline (the Week 52 visit of the M06-806 
study) PCDAI score (regardless of study visit), may be discontinued from the study at the 
discretion of the Investigator.  
Beginning from Week 8, the dose of adalimumab may be increased to 40 mg, at the 
discretion of the Investigator, for subjects whose body weight has increased from < 40 kg 
to t 40 kg from the Baseline (Week 52 of the M06-806 Study) visit.  The site will enter 
the subjects body weight into the Interactive Voice Response System (IVRS) and the 
dose will be adjusted, if applicable.  
Reductions in concomitant therapy will be allowed for Crohns treatment related toxicities 
(e.g., leukopenia, anemia, neuropathy) of Grade 3 or higher. 

 
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Subjects may be allowed to decrease prednisone (or equivalent) and budesonide if 
qualifications are met (please see Section 5.2.3.2 for required timing and rate of taper). 
Subjects may be allowed to adjust their Crohns specific concomitant medications as 
specified in Section 5.2.3.2. 
The duration of the study could last up to 264 weeks (approximately 5 years).  Subjects 
who complete, or who early terminate from the study will be contacted 70 days after their 
last dose of study drug to obtain information on any ongoing and new AEs.   
This study will conclude approximately 12 weeks after the following criteria have been 
satisfied: 
● Study drug receives country and local (if applicable) regulatory approval for 
pediatric Crohns Disease. 
● All applicable local reimbursement procedures are completed. 
 
Sites will be notified once these criteria are met. 
Following country and local (if applicable) regulatory approval and applicable local 
reimbursement approval of the study drug in a country, subjects should return to their 
next scheduled study visit as specified in the protocol.  The termination visit should be 
conducted in place of their regular scheduled study visit.  These subjects should be 
considered as having completed the study. 
A schematic of the study design is shown in Figure 1. 

 
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3. 
If female, subjects who are sexually active and are of child-bearing potential 
should be practicing an approved method of birth control throughout the study and 
for 150 days after study drug administration.  Examples of approved methods of 
birth control include the following: 
● Condoms, sponge, foam, jellies, diaphragm or intrauterine device (IUD) 
● Oral, parenteral or intravaginal contraceptives 
● A vasectomized partner 
4. 
Subject of legal age, parent or legal guardian, as required, has voluntarily signed 
and dated an Institutional Review Board (IRB)/Independent Ethics Committee 
(IEC) approved informed consent form, after the nature of the study has been 
explained and the subject of legal age, subjects parent, or legal guardian, as 
required, has had the opportunity to ask questions.  Subjects will be included in all 
discussions, and if required, their signature on an assent form will be obtained. 
5. 
Parent or legal guardian of subject who is not of legal age, as required, must be 
willing to actively supervise storage and administration of study drug and to 
ensure that the time of each dose is accurately recorded in the subjects diary. 
6. 
If a subject of legal age, must be willing to actively store, administer, and 
accurately record study drug administration in the subject diary. 
7. 
Subject is judged to be in acceptable medical condition, as determined by the 
Principal Investigator based upon results of clinical and laboratory evaluations 
done throughout the preceding Crohns disease study M06-806. 
 
5.2.2 
Exclusion Criteria 
A subject will be excluded from the study if he/she meets any of the following criteria:  
1. 
For any reason, the subject is considered by the Investigator to be an unsuitable 
candidate for continuing therapy in the M06-807 study. 

 
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2. 
Subject has abnormal laboratory or other test results that in the opinion of the 
Investigator will make the subject unsuitable to participate in this study. 
3. 
History of cancer or lymphoproliferative disease other than a successfully and 
completely treated cutaneous squamous cell or basal cell carcinoma or 
carcinoma − in-situ of the cervix. 
4. 
History of listeriosis, histoplasmosis, chronic or active hepatitis B infection, 
human immunodeficiency virus (HIV) infection, any immunodeficiency 
syndrome, central nervous system (CNS) demyelinating disease or active TB 
(receiving treatment or not receiving treatment).  Ongoing severe infections such 
as sepsis and opportunistic infections will be exclusionary. 
5. 
Subject with known, symptomatic obstructive strictures. 
6. 
Subject who is planning surgical bowel resection at any time point while enrolled 
in the study. 
7. 
Subject who has short bowel syndrome as determined by the Investigator. 
8. 
Subject who is currently receiving total parenteral nutrition (TPN). 
9. 
Subject who is unwilling to discontinue growth hormone prior to the first dose of 
open-label study drug at the Baseline visit of M06-807. 
10. 
Female subject who is pregnant or currently breast-feeding. 
11. 
Subject with a history of clinically significant drug or alcohol abuse in the last 
year. 
12. 
Subject with a poorly controlled medical condition such as: uncontrolled diabetes, 
recurrent infections, unstable ischemic heart disease, moderate to severe heart 
failure, recent cerebrovascular accidents or any other condition which, in the 

 
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opinion of the Investigator or the Sponsor, will put the subject at risk by 
participation in the protocol. 
13. 
Subject with any prior exposure to Tysabri (natalizumab). 
14. 
Subject with a known hypersensitivity to the excipients of adalimumab as stated in 
the label. 
15. 
Subject with a previous history of dysplasia of the gastrointestinal tract. 
16. 
Subject is not in compliance with Section 5.2.3. 
 
If there are any questions regarding inclusion and exclusion criteria and/or subject 
eligibility, contact the Abbott Laboratories Medical Monitor identified in Section 7.0. 
5.2.3 
Prior and Concomitant Therapy 
5.2.3.1 
Prior Therapy 
Any medication (including over-the-counter medicines such as aspirin) that the subject is 
receiving during the study must be recorded in source documents and on the appropriate 
case report form (CRF) along with the reason for use, dates of administration and 
dosages. 
Any vaccine administered to the subject during the study should be listed as a 
concomitant medication.  Subjects should continue on the recommended vaccination 
schedule; however, vaccinations with live vaccines are prohibited.   
Any medications captured in the M06-806 CRF(s) which are ongoing will be transcribed 
onto the M06-807 source documents and CRF(s). 
If there are any questions regarding prior or concomitant therapy (ies), contact the Abbott 
Laboratories Medical Monitor identified in Section 7.0 

 
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5.2.3.2 
Concomitant Therapy 
Adjustments of Crohns related concomitant treatments, including Crohns related 
antibiotics, are not allowed during the first 8 weeks of the M06-807 study, unless subject 
safety is at risk. 
After Week 8, decreases in the dose or discontinuation of Crohns related antibiotics or 
Crohns related concomitant treatments are allowed according to the Investigators medical 
judgment.  These adjustments may be performed without prior discussion with the Abbott 
Medical Monitor.  In addition, Subjects may be able to initiate or reinitiate Crohns related 
treatments, except immunosuppressants, following eight (8) weeks of exposure to open-
label adalimumab.  Immunosuppressants may not be started or restarted during the study. 
Setons are allowed as concomitant therapy in subjects with perianal fistulas.  Their use 
should be documented on the concomitant medications page of the CRF. 
Growth hormone must be discontinued prior to the first dose of open-label study drug and 
Subjects may not begin using it while participating in this study. 
If a subject began to taper corticosteroids during the M06-806 study, they may continue 
this taper immediately upon enrollment into the M06-807 study.  Beginning at Week 8, 
subjects who are not in flare may begin corticosteroid taper according to the following 
schedule: 
Tapering Schedule 
Dose 
Rate 
Prednisone (or equivalent) 
> 10 mg 
d 10 mg  
5 mg/week 
2.5 mg/week 
Budesonide 
d 9 mg  
3 mg/week 
 
Subjects who are in flare or who flare after they have reduced or completely tapered their 
dose of corticosteroid may have their corticosteroid dose increased or restarted, at the 
discretion of the Investigator.  

 
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5.2.3.3 
Rescue Therapy 
If the Investigator decides, during the study, that a subject requires rescue therapy other 
than that described in this protocol, the subject must be terminated from the study.  If 
possible, questions regarding the use of rescue therapy should be discussed with the 
Medical Monitor prior to use. 
5.2.3.4 
Prohibited Therapy 
Live vaccines must not be given concurrently while on study drug and for 70 days after 
the last dose of study drug. 
Infliximab and growth hormone use are prohibited during the study.  At the Baseline 
visit, any subject using Growth hormone must discontinue its use. 
Tysabri (natalizumab), concurrent biological therapy, cyclosporine, tacrolimus, 
mycophenolate mofetil, Kineret® (anakinra), Orencia (abatacept), therapeutic enemas and 
suppositories (not including those done in conjunction with routine colonoscopies) and 
any investigational agent are prohibited during the study (see Appendix L). 
Concurrent use of budesonide and prednisone (or equivalent) is prohibited. 
Subjects with any prior exposure to Tysabri (natalizumab) will be excluded. 
5.3 
Efficacy, and Safety Assessments/Variables 
5.3.1 
Efficacy and Safety Measurements Assessed and Flow 
Chart 
Study procedures will be performed as summarized in the study schematic presented in 
Table 1. 
 

 
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Table 1.  
Study Activities 
Activity 
Baseline 
Week 4 
Week 8 
Week 12 
Week 24 
Week 36 
Week 48 
Week 60 
Week 72 
Week 84 
Week 96 
Week 108
Inclusion/exclusion criteria 
X 
 
 
 
 
 
 
 
 
 
 
 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
 
 
Previous and concomitant 
medications 
Xa 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Urine pregnancy testb 
Xa 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Vital signsc 
Xa 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Physical exam 
Xa 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
General LABd 
Xa 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Urinalysise 
Xa 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Erythrocyte sedimentation 
rate 
Xa 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
CRP 
Xa 
 
 
 
X 
 
X 
 
X 
 
 
X 
ANA 
Xa 
 
 
X 
 
 
 
 
 
 
 
X 
Anti-dsDNAf 
Xa 
 
 
X 
 
 
 
 
 
 
 
X 
PCDAI 
Xa 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
CDAIg 
Xa 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
IMPACT III Questionnaireh 
Xa 
 
 
X 
X 
 
X 
 
X 
 
 
X 
 

 
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Table 1.  
Study Activities (Continued) 
Activity 
Baseline 
Week 4 
Week 8 
Week 12 
Week 24 
Week 36 
Week 48 
Week 60 
Week 72 
Week 84 
Week 96 
Week 108
Unscheduled outpatient 
visits, emergency room 
visits and hospitalizations 
questionnaire 
Xa 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Work Productivity and 
Impairment Questionnaire: 
Crohns Disease (WPAI − 
CD) 
Xa 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X-ray for bone agei 
Xa 
 
 
 
 
 
X 
 
 
 
 
X 
Serum bone markers 
Xa 
 
 
 
X 
 
X 
 
X 
 
 
X 
PK Blood Samplej 
 
 
 
 
X 
 
X 
 
X 
 
X 
 
Anti-adalimumab blood 
levels (AAA)j 
 
 
 
 
X 
 
X 
 
X 
 
X 
 
Adverse eventsk 
Xa 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Dispense study drug 
Xa 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 

 
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Table 1.  
Study Activities (Continued) 
Activity 
Week 
120 
Week 
132 
Call 
Week 
144 
Week 
156 
Call 
Week 
168 
Week 
180 
Call 
Week 
192 
Week 
204 
Call 
Week 
216 
Week 
228 
Call 
Week 
240 
Week 
252 
Call 
Week 
264/ 
Early 
Term 
Unsched 
Visit 
70-Day 
Follow-up 
Call 
Inclusion/exclusion 
criteria 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Informed consent 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Previous and concomitant 
medications 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Urine pregnancy testb 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
 
Vital signsc 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
 
Physical exam 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
 
General LABd 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
 
Urinalysise 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
 
Erythrocyte 
sedimentation rate 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
 
CRP 
 
 
X 
 
X 
 
X 
 
X 
 
 
 
X 
 
 
ANA 
 
 
X 
 
 
 
X 
 
 
 
 
 
X 
 
 
Anti-dsDNAf 
 
 
X 
 
 
 
X 
 
 
 
 
 
X 
 
 
PCDAI 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
 
CDAIg 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
 
IMPACT III 
Questionnaireh 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
 
 

 
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Table 1.  
Study Activities (Continued) 
Activity 
Week 
120 
Week 
132 
Call 
Week 
144 
Week 
156 
Call 
Week 
168 
Week 
180 
Call 
Week 
192 
Week 
204 
Call 
Week 
216 
Week 
228 
Call 
Week 
240 
Week 
252 
Call 
Week 
264/ 
Early 
Term 
Unsched 
Visit 
70-Day 
Follow-up 
Call 
Unscheduled outpatient 
visits, emergency room 
visits and 
hospitalizations 
questionnaire 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Work Productivity and 
Impairment 
Questionnaire: Crohns 
Disease  (WPAI − CD) 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
 
X-ray for bone agei 
 
 
X 
 
 
 
X 
 
 
 
 
 
X 
 
 
Serum bone markersi 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
 
PK Blood Samplej 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
 
Anti-adalimumab blood 
levels (AAA)j 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
 
Adverse eventsk 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Dispense study drug 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
 
Xl 
 
 

 
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Table 1.  
Study Activities (Continued) 
a. 
At the Baseline Visit, the following procedures will be completed as part of Week 52 of the M06-806 study. 
b. 
Performed on all females of child-bearing potential - Urine pregnancy test at all study visits. 
c. 
Vital sign determinations of height, weight, sitting blood pressure, heart rate, respiratory rate, and body temperature will be obtained at each visit. 
d. 
Blood draws should be performed after questionnaire and vital signs determinations and before study drug administration. 
e. 
Microscopic urinalysis will be performed at any visit if dipstick UA is abnormal (protein greater than a trace, blood greater than 5-10 Ery/ul, moderate or large ketone count 
or glucose greater than 50 mg/dL). 
f.  
If an ANA result is positive, anti-dsDNA will be performed automatically. 
g.  For subjects who are age 13 or older at the M06-807 Baseline Visit, a CDAI will be completed at each visit. 
h. 
For subjects who are age 10 or older at the M06-807 Baseline Visit, an IMPACT III Assessment will be completed at Baseline, Weeks 12, 24, 48, 72, 108, 120, 144, 168, 192, 
216, 240, 264/ET and unscheduled visits. 
i. 
If the height velocity is 0 and, in the opinion of the investigator, a subject is no longer growing, the x-ray for bone age and the determination of serum bone markers can be 
omitted. 
j. 
In addition to blood draws every 24 weeks, PK and AAA blood draws to be performed if subject meets flare criteria and dose escalated to ew dosing. 
k. 
All AEs, including SAEs, will be captured throughout the study from the time that the subject signs the Informed Consent Form.  SAEs will be captured throughout the 70 day 
follow-up period (if applicable). 
l. 
If an unscheduled visit is performed to change the frequency of study drug from OL eow to OL ew, study drug may be dispensed. 
 
 

 
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5.3.1.1 
Study Procedures 
The M06-806 Week 52 visit will serve as the Baseline visit for the M06-807 study.  The 
study procedures outlined in Table 1 are discussed in detail in this section, with the 
exception of the collection of AE information (discussed in Section 6.0).  All study data 
will be recorded in source documents and on the appropriate CRFs.  The site will call the 
subjects at Weeks 132, 156, 180, 204, 228 and 252 in order to collect any safety 
information from the subject as illustrated in Table 1. 
The visit window for all scheduled visits is ±7 days calculated from the Baseline visit of 
the M06-807 study. 
Inclusion/Exclusion Criteria 
A subject will be excluded from this study if he/she does not meet all inclusion criteria or 
meets any of the exclusion criteria of Protocol M06-807. 
Informed Consent 
A signed Informed Consent Form (ICF) will be obtained from a subject of legal age (in 
the state of residence) or from the parent or legal guardian (as appropriate)of a subject 
who is not of legal age before any study related procedures are undertaken or before any 
medications are discontinued for the purpose of this study.  Additionally, an informed 
consent will be required from those subjects who were not of legal age at the onset of this 
study but become of legal age during the course of the study. 
In keeping with each institutions IRB requirements, an Informed Assent may also be 
required from pediatric subjects.  Pediatric subjects will be included in all discussions in 
order to obtain their signature on an assent form.  Details about how informed consent 
will be obtained and documented are provided in Section 9.3. 
If an updated informed consent is approved after a subject has completed or terminated 
early from the study, but is within the 70-day follow-up window, the subject will not be 
required to return to the site for the purposes of signing the updated ICF.  The subject of 

 
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30 
legal age, parent or legal guardian (as appropriate) should be contacted regarding any 
changes and the documentation of the contact should be present in the subjects source. 
Previous and Concomitant Medications 
Changes in concomitant medications will be assessed at each study visit from Baseline 
through the Week 264/ET visit.  Concomitant medications that are taken prior to the first 
dose of study drug administration for this study will be captured in the subjects casebook 
from the previous study (M06-806).  They will not be required to be captured in the 
subjects casebook of the M06-807 study unless they were ongoing at the Week 52 visit of 
the M06-806 study.  Ongoing concomitant medications from the M06-806 study will be 
transcribed into the subjects M06-807 casebook. 
Subjects of legal age or the parent or guardian (as appropriate) of subjects who are not of 
legal age will be provided with a medication log (see Appendix O) to record all 
medications the subject takes throughout the study.  This log must be returned for review 
at every study visit. 
Serum/Urine Pregnancy Test 
All female subjects who are experiencing menses, are nearing sexual maturation (in the 
opinion of the Investigator), or who are of child-bearing potential, will undergo a urine 
pregnancy test at each visit.  Urine pregnancy tests will be performed locally by 
designated study personnel.  If a urine pregnancy test is positive, a serum pregnancy test 
must be performed by the central laboratory.  If the serum pregnancy test is positive, the 
subject will be removed from the study.   
A lactating or pregnant female will not be eligible for participation in this study. 
Vital Signs 
Vital sign determinations of sitting blood pressure, heart rate, respiratory rate, body 
temperature, weight and height will be obtained at each visit.  All measurements will be 
recorded in metric units when applicable.  

 
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Weight measurements will be obtained using the same measuring instrument at each visit 
and measured with subjects wearing only undergarments.  Height measurements will be 
obtained using the same measuring equipment at each visit and performed on subjects 
with their shoes taken off. 
Physical Examination 
A physical examination will be performed at each visit.  A count of the number of 
cutaneous fistulas draining upon gentle compression will be performed during each 
physical exam.30  Fistulas will be classified as abdominal or perianal/anal. 
Physical exam abnormalities (including fistulas and fissures) noted by the Investigator 
will be evaluated and documented on the corresponding source documents.  Any new 
abnormalities or worsening of pre-existing conditions should be captured as AEs. 
Clinical Laboratory Tests  
Samples will be obtained for the laboratory tests listed in Table 2 at all study visits.  
Blood draws should be performed after questionnaires (PCDAI, IMPACT III 
Questionnaire, etc.) and vital sign determinations during a study visit, and before study 
drug administration. 
ICON central laboratory will be utilized to process and provide results for the general 
laboratory tests.  All abnormal laboratory test results that are considered clinically 
significant by the Investigator will be followed to a satisfactory resolution. 
ICON will provide instructions regarding the collection, processing and shipping of these 
samples. 

 
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Table 2.  
Clinical Laboratory Tests  
Hematologya 
Clinical Chemistry 
Urinalysisb 
Serum Bone Markers 
Hematocrit 
Hemoglobin 
Red Blood Cell (RBC) 
count 
White Blood Cell 
(WBC) count 
Neutrophils 
Bands 
Lymphocytes 
Monocytes 
Basophils 
Eosinophils 
Platelet count (estimate 
not acceptable) 
Blood Urea Nitrogen 
(BUN) 
Creatinine 
Total bilirubin 
Serum glutamic-pyruvic  
 
transaminase 
(SGPT/ALT) 
Serum glutamic-
oxaloacetic 
 
transaminase 
(SGOT/AST) 
Alkaline phosphatase 
Sodium 
Potassium 
Calcium 
Inorganic phosphorus 
Uric acid 
Cholesterol 
Total protein 
Glucose 
Triglycerides 
Albumin 
Specific gravity 
Ketones 
pH 
Protein 
Blood 
Glucose 
Osteocalcin 
Bone-specific alkaline 
phosphatase (BSAP)  
bone resorption (Ntx) 
a. 
Basic hematology testing performed on instrumentation does not include band reporting.  When 
Hematology results reflex to a Manual Differential, if there is a band result over 5, it is reported. 
b. Microscopic urinalysis will be performed at any visits if dipstick UA is abnormal  (protein greater than 
a trace, blood greater than 5-10 Ery/ul, moderate or large ketone count or glucose greater than 
50 mg/dL). 
 
Immunologic Laboratory Assessments   
CRP, adalimumab levels, anti-adalimumab antibody levels (AAA) and antinuclear 
antibody (ANA) assessments will be performed as indicated in Table 1.  If an ANA result 
is positive, anti-double-stranded DNA (anti-dsDNA) will be performed automatically. All 
CRP, ANA, anti-dsDNA will be performed by the central laboratory. 

 
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33 
Erythrocyte Sedimentation Rate (ESR) assessments will be performed at all visits as 
indicated in Table 1.  ESR assessments will be performed by the sites local laboratory. 
Markers of Bone Metabolism  
Serum markers of bone metabolism will be measured as indicated in Table 1.  The bone 
formation markers to be measured are osteocalcin, bone-specific alkaline phosphatase 
(BSAP), and bone resorption (Ntx). 
Urinalysis 
Urine will be assessed by dipstick at each visit (done locally).  All results, including 
abnormalities, will be captured in source documentation and on the appropriate CRF.  
If, at any visit, the dipstick UA results are abnormal, the central lab will perform a 
microscopic urinalysis.  Abnormal is defined as protein greater than a trace, blood greater 
than 5-10 Ery/ul, moderate or large ketone count or glucose greater than 50 mg/dL. 
Pediatric Crohns Disease Activity Index (PCDAI) 
The PCDAI score will be calculated at each visit.  When completing the PCDAI, the 
HCT, albumin, and ESR values will be utilized from the same study visit.  
An example of the PCDAI is located in Appendix G.  Instructions for completing the 
PCDAI score is located in Appendix H. 
Crohns Disease Activity Index (CDAI) 
At each visit, a CDAI score will be calculated for subjects who are age 13 or older at the 
M06-807 Baseline Visit.  The CDAI score will be calculated utilizing the subject diary 
and the HCT value from the same study visit.  A copy of the CDAI subject diary is 
located in Appendix H. 
When completing question five (5) ("Taking Lomotil/Imodium/Loperamide/opiates for 
diarrhea, 0 = no, 1 = yes") on the CDAI, "no" should be answered if a subject is taking an 
opiate(s) solely for pain. 

 
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For the CDAI questions regarding presence of anal fistulas and other fistulas, all fistulas 
detectable on physical examination (draining and non-draining) should be captured on the 
CDAI CRF page and calculated into the CDAI score. 
The calculation of the CDAI score is in Appendix I. 
IMPACT III Questionnaire 
Subjects t 10 years old at the Baseline visit of the M06-807 study will complete an 
IMPACT III questionnaire as indicated in Table 1.  A copy of the questionnaire is located 
in Appendix K.  
The IMPACT III will be recorded directly onto the CRF.  The completed CRF will be 
considered source documentation for this assessment. 
Outcomes 
The Unscheduled Outpatient Visits, Emergency Room Visits and Hospitalization 
Questionnaire and the Work Productivity and Activity Impairment Questionnaire:  
Crohns Disease (WPAI-CD) will be completed at each visit except the Unscheduled Visit 
(Appendix N, Appendix T). 
The subjects parent or legal guardian will complete the WPAI directly onto the CRF.  
The completed CRF will be considered source documentation for this assessment. 
Bone Age 
An x-ray of the wrist for the assessment of bone age will be obtained as indicated in 
Table 1.  Sites should use the Greulich and Pyle method for reading the x − ray.31  The 
x-ray report requires the signature of the radiologist who read the films.  The bone age 
that is determined by the x-ray should be recorded on the CRF.   

 
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Anthropometric Evaluations 
Height and weight obtained at each visit will be used by Abbott Data Management and 
Statistical groups for determination of BMI and "z" score (observed height velocity 
(cm/yr) - mean height velocity for age and sex (cm/yr) / SD of the mean) for height. 
Adverse Events 
Adverse events will be assessed at every study visit from Baseline through the 
Week 264/ET visit.  Any AEs, which are ongoing in the M06-806 study, will be 
transcribed onto the M06-807 source documents and CRF(s) 
For those subjects who complete the study or terminate early, a phone call will be made 
70 days after the last dose of study drug to obtain follow-up information on any ongoing 
and any new AEs. See Section 6.0 and Appendix M for additional information. 
Study Drug Administration 
At each study visit, the subject or their trained designated friend, family member or 
health care professional will perform study drug injections under the supervision of a 
trained medical professional to reinforce proper aseptic SC injection technique.  Subjects 
or a trained designated friend, family member or health care professional will perform 
injections of study drug in the subjects home during weeks they are not in for scheduled 
clinic visits.  Subjects may return to the study site for injections in between study visits if 
subject or a trained designated friend, family member or health care professional cannot 
inject the study medication. 
Subjects will maintain a dosing diary for all study drug administered outside study visits, 
i.e., at home.  In the diary, the date, initials of the person administering the study drug, 
time study drug is administered, kit number and the dose administered will be recorded.  
Subjects must return this diary and it will be reviewed and verified for compliance at 
each visit by the research personnel at the study center.  All relevant dosing information 
will be retained by the study coordinator and transcribed onto a drug accountability form 
at each visit.  Additionally, any discernible departure from the protocol regarding study 

 
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drug administration will be recorded on source documents and appropriate drug 
accountability forms.  A sample of the Subject Dosing Diary is presented in Appendix P. 
At all office visits subjects should be observed after study drug administration, until 
judged clinically stable by the study personnel.  If an anaphylactic reaction or other 
serious allergic reaction occurs, administration of study drug should be discontinued 
immediately and appropriate therapy initiated.  When dosing at home, subjects should be 
instructed to contact the site immediately with any signs or symptoms of a reaction. 
The dosing dates, for all doses of study drug, should be calculated from the Baseline visit 
date.  The Baseline visit date for this study is 364 ± 7 days from the Baseline Visit date of 
M06-806.  A +/- 3 day window is allowable for scheduled study dosing dates. 
For subjects that deviate from this dosing window, every effort should be made to bring 
the subject back to the original dosing schedule as soon as possible.  For situations where 
bringing the subject back on the original dosing schedule will cause the dose to be out of 
the +/- 3 day window, please contact the Medical Monitor for additional instructions. 
Randomization and Assignment of Subject Numbers 
All subjects will be centrally registered using an IVRS.  This is an open-label study; 
subjects will not be randomized.  The telephone number and call in directions for the 
IVRS will be provided to each site.  Subjects will keep their study subject number from 
the previous double-blind study (M06 − 806). 
5.3.2 
Drug Concentration Measurements 
Blood samples for the assay of adalimumab and AAA serum concentrations will be 
collected at Baseline and every 24 weeks thereafter.  In addition, blood samples for 
adalimumab and AAA concentration analysis will also be collected if a subject meets 
flare criteria and dose escalated to ew dosing.  Study visits in which blood samples will 
be collected are listed in Table 1.  At each visit, blood samples will be collected prior to 
study drug administration at each visit. 

 
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The time that each blood sample is collected will be recorded to the nearest minute in the 
source documents and on the appropriate CRF. 
5.3.2.1 
Collection of Samples for Analysis 
Collection of Samples for Adalimumab Analysis 
Blood samples for adalimumab analysis will be collected by venipuncture into 
appropriately labeled 4-mL evacuated serum collection tubes without gel separator at 
visits indicated in Table 1.  All samples will be obtained immediately prior to dosing at 
visits indicated in Table 1.  Sufficient blood will be collected to provide approximately 
2 mL serum.  Allow the blood to clot for 30 minutes at room temperature before 
centrifugation. 
A maximum of 13 samples are planned to be collected per subject for the analysis of 
adalimumab concentrations. 
Collection of Samples for AAA Analysis 
Blood samples for AAA assay will be collected by venipuncture into appropriately 
labeled 4-mL evacuated serum collection tubes without gel separator at visits indicated in 
Table 1.  All samples will be obtained immediately prior to dosing at visits indicated in 
Table 1. Sufficient blood will be collected to provide approximately 2 mL serum.  Blood 
will be allowed to clot for 30 minutes at room temperature before centrifugation. 
A maximum of 13 blood samples are planned to be collected per subject for AAA 
analysis. 
5.3.2.2 
Handling/Processing of Samples 
The blood samples for adalimumab and AAA, assay will be centrifuged within 30 to 
60 minutes of collection to separate the serum.  The serum samples will be transferred 
using plastic pipettes into screw-capped polypropylene vials labeled with the type of 
sample (serum, SRM), the protocol number, subject number, the study week and the 

 
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assay (PK-Adalimumab, AAA).  The serum samples will be frozen within 2 hours after 
collection and will remain frozen in a –20°C or colder until shipped.  Sites that do not 
have access to a −20°C or colder freezer will need to ship the samples the day they are 
collected.  (Detailed instructions provided in the ICON Laboratory Manual). 
5.3.2.3 
Disposition of Samples 
The PK and AAA samples will be shipped to ICON with all other samples being shipped 
to ICON.  Refer to the ICON Lab Manual for further instruction.  Neither Abbott nor 
ICON will supply dry ice for this study.  Study sites will identify a dry ice source and 
purchase the necessary dry ice. 
5.3.2.4 
Measurement Methods 
Serum concentrations of adalimumab will be determined using a validated ELISA 
method under the supervision of the Drug Analysis Department at Abbott Laboratories.  
Only serum samples that have adalimumab levels < 2.0 Pg/mL will be selected for AAA 
concentration measurement. 
Serum concentrations of AAA will be determined using a validated ELISA method under 
the supervision of the Drug Analysis Department at Abbott Laboratories. 
5.3.3 
Efficacy Variables 
Efficacy will be evaluated based on the proportion of subjects who maintain PCDAI 
clinical response at each visit.  Clinical response is defined as PCDAI decrease 
t 15 points from the M06-806 Baseline score. 
Other measures of disease activity being assessed in this study will be summarized, 
including CDAI scores, IMPACT III scores, WPAI-CD Caregiver, z-score for height 
velocity, bone x-ray, serological markers of bone metabolism, healthcare resource 
utilization (unscheduled outpatient visits), adalimumab levels and anti-adalimumab levels 
(AAA). 

 
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5.3.4 
Safety Variables 
AEs, laboratory data, physical examinations and vital signs are the safety parameters and 
these will be assessed throughout the study. 
Treatment-emergent events will be summarized and reported by treatment group and by 
AAA status (AAA+ versus AAA-). 
5.3.5 
Pharmacokinetic Variables 
Serum concentrations of adalimumab and AAA will be determined from samples 
collected at the study visits listed in Table 1. 
5.4 
Removal of Subjects from Therapy or Assessment 
5.4.1 
Discontinuation of Individual Subjects 
Subjects will be withdrawn from the study immediately if any of the following occur:   
● Clinically significant abnormal laboratory results or AEs, which rule out 
continuation of the study drug, as determined by the Investigator and the 
Medical Monitor. 
● The Investigator believes it is in the best interest of the subject. 
● The subject or subjects legal guardian requests withdrawal from the study. 
● Selection criteria violation was noted after the subject started study drug, as 
determined by the Medical Monitor (see Sections 5.2.1 and 5.2.2). 
● Introduction of prohibited medications or prohibited concomitant medication 
dosages as determined by the Medical Monitor. 
● The subject is diagnosed with a malignancy except for localized 
non − melanoma skin cancer.  Discontinuation for carcinoma in-situ is at the 
discretion of the Investigator. 
● The subject is diagnosed with dysplasia of the gastrointestinal tract. 
● A female subject who becomes pregnant. 
 

 
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If the subject prematurely discontinues study drug use, the procedures outlined for the 
Week 264/ET Visit must be completed within 2 weeks of the last dose of study drug, and 
preferably prior to the initiation of another therapy.  These procedures should not 
interfere with the initiation of any new treatments or therapeutic modalities that the 
Investigator feels are necessary to treat the subjects condition.  Following discontinuation 
of the study drug, the subject will be treated in accordance with the Investigators best 
clinical judgment. 
Subjects who prematurely discontinue from the study will not be replaced.  The date of 
last dose and reason for premature discontinuation will be recorded in the source 
document and on the appropriate CRF. 
5.4.2 
Discontinuation of Entire Study 
Abbott reserves the right to discontinue the study at any time and to remove all study 
materials from the site.  Possible reasons for termination of the study include, but are not 
limited to: 
● Safety concerns based on reported data 
● Unsatisfactory enrollment with respect to quantity or quality 
● Inaccurate or incomplete data collection 
● Falsification of records 
● Failure to adhere to the protocol 
 
5.4.3 
Stopping Rules 
An independent Data Monitoring Committee (DMC) will meet to discuss data from the 
study approximately every six (6) months or at a frequency determined by the DMC and 
render their recommendation for either the continuation of the study or an amendment to 
the study.  A Sponsor Steering Committee (SSC), composed of senior executives not 
directly participating in this study, will make final decisions based on DMC 
recommendations. 

 
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5.5 
Treatments 
5.5.1 
Treatments Administered 
All study drug will be provided as a SC injection solution in pre-filled syringes 
containing adalimumab 40 mg/0.8 mL or adalimumab 20 mg/0.4 mL. 
Subjects who enroll into the study from blinded therapy in Study M06-806 will receive 
open-label therapy at a dose dependent on their body weight.  Subjects who weigh t 40 
kg will receive 40 mg eow of adalimumab, while subjects who weigh < 40 kg will 
receive 20 mg eow of adalimumab.  Beginning from Week 8, subjects who have a disease 
flare may be switched to ew treatment at the same dose of adalimumab received while on 
eow treatment. 
Subjects who enroll into the study from open-label therapy in Study M06-806 will 
continue to receive the same dose they were receiving (i.e. 40 mg ew or 20 mg ew) at the 
Week 52 visit of the M06-806 study. 
Subjects who develop a flare while receiving ew open-label therapy or have a PCDAI 
score t 15 points when compared to their Baseline (Week 52 of M06-806) PCDAI score 
(regardless of study visit), may be discontinued from the study at the discretion of the 
Investigator. 
Beginning from Week 8, the dose of adalimumab may be increased to 40 mg, at the 
discretion of the Investigator, for subjects whose body weight has increased from < 40 kg 
to t 40 kg from the study Baseline visit.  The site will enter the subjects body weight into 
the IVRS and the dose will be adjusted, if applicable. 
5.5.2 
Identity of Investigational Product 
The individual study drug information is presented in Table 3.  Pre-filled syringes will be 
provided for this open-label clinical study. 

 
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Table 3.  
Identity of Investigational Products  
Study Drug 
Formulation 
Manufacturer 
Adalimumab 
40 mg/0.8 mL or 20 mg/0.4 mL  
Adalimumab/Mannitol, Citric acid monohydrate, Sodium citrate, 
Disodium phosphate dihydrate, Sodium dihydrogen phosphate 
dihydrate, Sodium chloride, Polysorbate 80, Water for injections, 
Sodium hydroxide added as necessary to adjust pH 
Abbott 
 
5.5.2.1 
Packaging and Labeling 
The following information will appear on the pre-filled syringe or carton labels: 
● Sponsor identification 
● Protocol number 
● Drug identification 
● Quantity of contents 
● Storage conditions 
● Dosing instructions 
● Kit number 
● Route of Administration 
● Excipients 
● Blank spaces to write the subjects identification number, initials, and date 
dispensed (as required) 
● Finishing lot # 
● Expiry Date (as required) 
 
Two pre-filled syringes will be provided in a dosing kit carton (see Table 4).  Detailed 
instructions and training for the administration of study supplies are provided in 
Appendix Q. 

 
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Table 4.  
Study Drug Packaging and Administration 
Open-label Pre-filled Syringes 
Open-label kit cartons containing two pre-filled 
syringes of adalimumab 40 mg/0.8 mL. 
Open-label kit cartons containing two pre-filled 
syringes of adalimumab 20 mg/0.4 mL. 
 
5.5.2.2 
Storage and Disposition of Study Drug 
Pre-filled syringes are to be stored protected from light at 2° to 8°C/ 36° to 46°F.  
DO NOT FREEZE.  A storage temperature log is to be maintained at the site to document 
proper storage conditions.  The refrigerator temperature must be recorded on every 
business day on a temperature log to record proper function.  Malfunctions must be 
reported to the sponsor immediately.  Study drug should be quarantined and not 
dispensed until Abbott GPRD or Abbott Temperature Excursion Management System 
(ATEMS) deems the medication as acceptable.  All clinical supplies must be stored and 
locked in a secure place until they are dispensed for subject use or are returned to Abbott 
Laboratories. 
Investigational products are for investigational use only, and are to be used only within 
the context of this study. 
5.5.3 
Method of Assigning Subjects to Treatment Groups 
This is an open-label study; all subjects will be receiving adalimumab. 
All subjects will be centrally registered using an IVRS.  The telephone number and 
call − in directions for the IVRS will be provided to each site.  Subjects will keep their 
study subject number from the previous study (M06 − 806). 
Study drug will be administered at the study visits summarized in Table 1 and detailed in 
Section 5.3.1.1. 

 
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5.5.4 
Selection and Timing of Dose for Each Subject 
Subjects who enroll into the study from blinded therapy in Study M06-806 will receive 
open-label therapy at a dose dependent on their body weight.  Subjects who weigh 
t 40 kg will receive 40 mg eow of adalimumab, while subjects who weigh < 40 kg will 
receive 20 mg eow of adalimumab.  Beginning from Week 8, subjects who have a disease 
flare may be switched to ew treatment at the same dose of adalimumab received while on 
eow treatment. 
Subjects who enroll into the study from open-label therapy in Study M06-806 will 
continue to receive the same dose they were receiving (i.e., 40 mg ew or 20 mg ew) at the 
Week 52 visit of the M06-806 study.  
Subjects who develop a flare while receiving ew open-label therapy or have a PCDAI 
score t 15 points when compared to their Baseline (the Week 52 visit of the M06-806 
study) PCDAI score (regardless of study visit), may be discontinued from the study at the 
discretion of the Investigator.  
The Baseline Visit date for this study should be 364 ± 7 days from Baseline Visit date of 
M06-806 study.  All clinic visits for the subject should be scheduled on the same day as 
the Baseline visit for this study.  For home administration of drug, subjects will be 
instructed to inject study drug on the same day of the week as their Baseline visit day.  
Subjects must inject within a +/-3 day window of this day.  If the subject is out of the 
dosing window, the Medical Monitor should be contacted to determine the timing of the 
next dose.  The subject must record all dosing information on the subject dosing diary 
(Appendix P). 
5.5.5 
Blinding 
This is an open-label study. 

 
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5.5.6 
Treatment Compliance 
The Investigator or his/her designated representatives will administer study drug only to 
subjects enrolled in the study.  
In order to document compliance with the treatment regimen, all pre-filled syringes will 
be counted and documented in source documents and on the appropriate drug 
accountability form. 
5.5.7 
Drug Accountability 
The Investigator or designee will verify that study drug supplies are received intact, at the 
appropriate temperature, and in the correct amounts from the drug depot.  This will be 
documented by signing and dating the Proof of Receipt (POR) or similar document.  The 
original POR or similar document will be kept in the site files as a record of what was 
received.  An accurate running inventory of study drug will be kept by the site, and will 
include the kit number, lot number(s), the number of pre-filled syringes dispensed, and 
the date study drug was dispensed for each subject.  An overall accountability of the 
study drug will be performed and verified by the Clinical Research Associate (CRA) 
throughout the study and at the site close-out visit.  All unused pre-filled syringes will be 
inventoried and returned to an identified vendor for disposal as designated by Abbott 
Laboratories.  A copy of the Drug Accountability Form, in accordance with instructions 
provided by the CRA, will also be included in the Returned Goods for disposal shipment.  
A sample Drug Accountability Form is included in Appendix S.  A copy of the Drug 
Accountability Disposal Form, in accordance with instructions provided by the CRA, will 
also be included in the Pharmacy Binder provided to the site. 
All used (expelled) pre-filled syringes will be inventoried by the site and verified by the 
CRA.  The used syringes will be discarded on site, using appropriate biohazard 
precautions.  CRAs and site staff will complete study drug accountability via study drug 
logs, source documents, verification of empty used syringe kit boxes, subject diaries and 
by visually counting the syringes in the sharps container whenever possible.  Used sharps 
containers should never be opened.  Each subject will be given their own sharps disposal 

 
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container to store expelled syringes.  Sharps containers should be returned by the subject 
at each visit, for accountability and compliance purposes.  New containers will be issued 
to subjects as necessary.  Once the CRA has verified drug accountability at the site, the 
site staff and CRA will sign off that the expelled pre-filled syringes have been destroyed. 
5.6 
Discussion and Justification of Study Design 
5.6.1 
Discussion of Study Design and Choice of Control Groups 
The design of this clinical study was chosen to demonstrate adalimumab as an effective 
therapy for maintaining clinical response in pediatric subjects with CD and to gather 
long-term safety and tolerability data in this subject population. 
5.6.2 
Appropriateness of Measurements 
Standard statistical, clinical, and laboratory procedures will be utilized in this study.  All 
efficacy measurements in this study are standard for assessing disease activity in pediatric 
subjects with Crohns disease.  All clinical and laboratory procedures in this study are 
standard and generally accepted. 
5.6.3 
Suitability of Subject Population 
Pediatric subjects with CD who have participated in and successfully completed Protocol 
M06-806 through Week 52 and who meet all of the inclusion and none of the exclusion 
criteria are eligible for this study. 
5.6.4 
Selection of Doses in the Study 
The results of the pivotal adalimumab adult CD maintenance trial M02-404, in 
conjunction with results from adalimumab CD Study M02-433, support a maintenance 
dose of adalimumab 40 mg eow.  Data also suggest that patients who lose response to 
adalimumab at 40 mg eow can be dose-escalated to 40 mg weekly with the potential of 
regaining clinical response.  The proposed dosing regimen for Study M06-807 was 
developed using an analogous approach as that studied in the adult CD population. 
Population pharmacokinetic modeling of serum adalimumab concentration data from 

 
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pediatric subjects with JRA was used to identify doses to be evaluated in the current 
study in children with CD.  A model based on the JRA population was chosen because 
the body weight range will closely parallel that in a juvenile CD population.  Escalation 
to weekly dosing will provide average adalimumab concentrations at steady state about 
twice that observed with every other week dosing.  However, these concentrations are 
within the range of systemic exposures that were safely studied in adult subjects with CD. 
6.0 
Adverse Events 
The Investigator will monitor each subject for clinical and laboratory evidence of AEs on 
a routine basis throughout the study.  The Investigator will assess and record any AE in 
detail including the date of onset, description, severity, time course, duration and 
outcome, relationship of the AE to study drug, an event diagnosis, if known, and any 
action(s) taken.  For SAEs not considered "probably related" to study drug, the 
Investigator must provide another cause of event.  For AEs to be considered sporadic, the 
events must be of similar nature and severity.  AEs, whether in response to a query, 
observed by site personnel, or reported spontaneously by the subject will be recorded in 
source documentation and on the appropriate CRF page. 
All AEs will be followed to a satisfactory conclusion. 
6.1 
Definitions 
6.1.1 
Adverse Event 
An AE is defined as any untoward medical occurrence in a patient or clinical 
investigation subject administered a pharmaceutical product and which does not 
necessarily have a causal relationship with this treatment.  An AE can therefore be any 
unfavorable and unintended sign (including an abnormal laboratory finding), symptom, 
or disease temporally associated with the use of a medicinal (investigational) product, 
whether or not the event is considered causally related to the use of the product. 

 
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Such an event can result from use of the drug as stipulated in the protocol or labeling, as 
well as from accidental or intentional overdose, drug abuse, or drug withdrawal.  Any 
worsening of a pre-existing condition or illness is considered an AE.  Laboratory 
abnormalities and changes in vital signs are considered to be AEs only if they result in 
discontinuation from the study, necessitate therapeutic medical intervention, and/or if the 
Investigator considers them to be AEs. 
An elective surgery/procedure scheduled to occur during a study will not be considered 
an AE if the surgery/procedure is being performed for a pre-existing condition and the 
surgery/procedure has been pre-planned prior to study entry.  However, if the pre-existing 
condition deteriorates unexpectedly during the study (e.g., surgery performed earlier than 
planned), then the deterioration of the condition for which the elective surgery/procedure 
is being done will be considered an AE. 
6.1.2 
Serious Adverse Events 
If an AE meets any of the following criteria, it is to be reported to Abbott as an SAE 
within 24 hours of the site being made aware of the SAE.  Additionally, if follow-up 
information is received, it must also be reported to Abbott within 24 hours of being made 
aware of the information. 
Death of Subject 
An event that results in the death of a subject. 
Life-Threatening 
An event that, in the opinion of the Investigator, will have resulted in 
immediate fatality if medical intervention had not been taken.  This does 
not include an event that will have been fatal if it had occurred in a more 
severe form. 
Hospitalization 
An event that results in an admission to the hospital for any length of 
time.  This does not include an emergency room visit or admission to an 
outpatient facility. 
Prolongation of 
Hospitalization 
An event that occurs while the study subject is hospitalized and prolongs 
the subjects hospital stay. 
Congenital Anomaly 
An anomaly detected at or after birth, or any anomaly that results in fetal 
loss. 

 
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Persistent or Significant 
Disability/Incapacity 
An event that results in a condition that substantially interferes with the 
activities of daily living of a study subject.  Disability is not intended to 
include experiences of relatively minor medical significance such as 
headache, nausea, vomiting, diarrhea, influenza, and accidental trauma 
(e.g., sprained ankle). 
Important Medical Event 
Requiring Medical or 
Surgical Intervention to 
Prevent Serious Outcome 
An important medical event that may not be immediately life-threatening 
or result in death or hospitalization, but based on medical judgment may 
jeopardize the subject and may require medical or surgical intervention to 
prevent any of the outcomes listed above (i.e., death of subject, life 
threatening, hospitalization, prolongation of hospitalization, congenital 
anomaly, or persistent or significant disability/incapacity).  Examples of 
such events include allergic bronchospasm requiring intensive treatment 
in an emergency room or at home, blood dyscrasias or convulsions that do 
not result in inpatient hospitalization, or the development of drug 
dependency or drug abuse. 
Spontaneous Abortion 
Miscarriage experienced by study subject. 
Elective Abortion 
Elective abortion performed on study subject. 
 
6.2 
Adverse Event Severity 
The Investigator will use the following definitions to rate the severity of each AE: 
Mild 
The AE is transient and easily tolerated by the subject. 
Moderate 
The AE causes the subject discomfort and interrupts the subjects usual 
activities. 
Severe 
The AE causes considerable interference with the subjects usual activities 
and may be incapacitating or life threatening.   
 
6.3 
Relationship to Study Drug 
The Investigator will use the following definitions to assess the relationship of the AE to 
the use of study drug:   
Probably Related 
An adverse event has a strong temporal relationship to study drug or 
recurs on re-challenge and an other cause of event is unlikely or 
significantly less likely. 
Possibly Related 
An AE has a strong temporal relationship to the study drug and an other 
cause of event is equally or less likely compared to the potential 
relationship to study drug. 

 
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Probably Not Related 
An AE has little or no temporal relationship to the study drug and/or a 
more likely other cause of event exists. 
Not Related 
An AE is due to an underlying or concurrent illness or effect of another 
drug and is not related to the study drug (e.g., has no temporal 
relationship to study drug or has a much more likely other cause of event). 
 
If an Investigators opinion of possibly, probably not, or not related to study drug for an 
SAE is given, an alternative cause of the event must be provided by the Investigator for 
the SAE. 
6.4 
Adverse Event Collection Period 
All AEs reported from the time of informed consent until 5 half-lives (70 days), 
following discontinuation of study drug administration have elapsed will be collected, 
whether elicited or spontaneously reported by the subject.  In addition, SAEs will be 
collected from the time the subject or parent/legal guardian has signed the study-specific 
informed consent. 
Adverse event information will be collected as shown in Figure 2. 
Figure 2.  
Adverse Event Collection 
SAEs and Non-serious AEs 
Elicited and/or Spontaneously Reported 
_ 
 
_ 
 
_ 
 
_ 
Consent 
Signed 
 
Study Drug 
Start 
 
Study Drug 
Stopped 
 
70 Days After 
Study Drug 
Stopped 
 
6.5 
Adverse Event Reporting 
In the event of an SAE, whether related to study drug or not, the investigator will notify 
one of the following people by faxing the appropriate SAE forms to one of the following 
people within 24 hours of the site being made aware of the SAE. 

 
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For all sites: 
 
 
For questions regarding SAEs, please contact: 
 
6.5.1 
Collection of Data Regarding Known Manifestations of the 
Disease Under Study 
Flare, of Crohns disease events per study definition, are not required to be captured as 
AEs, but may be captured per Investigator discretion.  Additionally, CD pre-existing 
conditions will not be captured as AEs unless the condition has worsened or is considered 
clinically significant in the opinion of the Investigator. 
6.6 
Pregnancy 
Abbott Laboratories must be notified within 1 working day of a sites learning if a female 
subject becomes pregnant during the study or within 150 days of receiving the last dose 
of study drug (see Section 6.5 for contact information). 

 
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Females who become pregnant during the study will be discontinued from study drug as 
described in Section 5.4.  Data regarding the outcome of any pregnancy occurring in a 
study subject will be collected.  Upon notification of a pregnancy Abbott will forward a 
form to the site, for the Investigator to complete and send back to Abbott.  A second form 
will also be sent approximately 9 months from the date of notification to collect 
information on the outcome of the pregnancy.  This form will also need to be completed 
and sent back to Abbott. 
To monitor outcomes of pregnant women exposed to adalimumab, a pregnancy registry 
has been established for the United States, Canada and Puerto Rico.  Physicians in the 
United States are encouraged to register subjects by calling 
and/or 
provide this information to the subject. 
Pregnancy in a study subject is not considered an AE.  However, the medical outcome of 
an elective or a spontaneous abortion, stillbirth or congenital anomaly is considered a 
SAE, and must be reported to the sponsor with 24 hours of the site learning of the event. 
7.0 
Protocol Deviations 
The investigator should not implement any deviation from the protocol without prior 
review and agreement by the Sponsor and in accordance with the IEC/IRB and local 
regulations, except when necessary to eliminate an immediate hazard to study subjects.  
When a deviation from the protocol is deemed necessary for an individual subject, the 
investigator must contact the following Abbott representative: 
 
 

 
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For purposes of this protocol, reportable deviations are defined as:   
● Subject entered into the study even though they did not satisfy entry criteria 
● Subject who developed withdrawal criteria during the study and was not 
withdrawn 
● Subject who received wrong treatment or incorrect dose 
● Subject who received excluded concomitant treatment 
 
Such contact must be made as soon as possible to permit a review by Abbott to determine 
the impact of the deviation on the subject and/or the study.  Any significant protocol 
deviations affecting subject eligibility and/or safety must be reviewed and/or approved by 
the IEC/IRB and regulatory authorities, as applicable, prior to implementation. 
8.0 
Statistical Methods and Determination of Sample 
Size 
8.1 
Statistical and Analytical Plans 
8.1.1 
Analyzable Population 
Efficacy analyses will be conducted in the intent-to-treat (ITT) population, which is 
defined as all subjects who received at least one dose of adalimumab in Study M06-807.  
In order to evaluate the impact of major protocol violations / deviations on the results of 
the study, additional analyses may be performed on the per-protocol population, which 
excludes all subjects with major protocol deviations.  The safety population consists of all 
subjects who received at least one dose of adalimumab in Study M06-807. 
8.1.2 
Planned Methods of Statistical Analysis 
All statistical analyses are to be performed descriptively.  Descriptive summary statistics 
will be provided for the demographic and baseline characteristics, efficacy, and safety 
parameters.  Continuous variables will be summarized using the number of observation, 

 
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mean, standard deviation, 1st quartile, median, 3rd quartile, minimum, and maximum; 
whereas discrete variables will be summarized using count and percentages.  
8.1.2.1 
Demographics and Baseline Characteristics 
Summary statistics for the demographic and baseline characteristics will be computed 
based on the Week 52 values (from double-blind study M06-806). 
8.1.2.2 
Primary Efficacy Analysis 
Summary statistics will be provided for each visit, based on observed data.  An additional 
summary will be provided for the last visit, using the last observation carried forward 
(LOCF).  That is, the subjects last non-missing, post-baseline value (i.e., post-Week 52 
M06-806 double-blind value) will be carried forward to the last visit. 
8.1.3 
Other Analyses 
The primary endpoint will be analyzed for the following subgroups in the ITT population. 
● Sex [Male, Female] 
● Age [< 13 years, t 13 years] 
● Ethnicity [White, Non-white] 
● Weight [< 40 kg, t 40 kg] 
● Prior infliximab use [No, Yes] 
● Baseline CRP [< 1.0 mg/dL, t 1.0 mg/dL] 
● Concomitant use of immunosuppressants and/or oral corticosteroids [No, Yes] 
 
8.1.4 
Safety Analyses 
Safety analyses will be based on the safety population.  Treatment-emergent, and 
post − treatment AEs will be summarized.  An overview of treatment-emergent AEs 
including AEs of special interest, such as AEs leading to death and AEs leading to 
premature discontinuation, AEs by (MedDRA® version 10.0 or later) preferred term and 

 
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system organ class, AEs by maximum relationship to study drug, and AEs by maximum 
severity will be summarized.  Treatment-emergent AEs are defined as new events that 
begin either on or after the first dose of the study drug and within 70 days after the last 
dose of the study drug. 
Adverse events with missing or unknown severity will be categorized as severe.  Adverse 
events with missing or unknown relationship to study drug will be categorized as 
probably related. 
Adverse events that are reported more than 70 days after last study injection will be 
excluded from the summaries; however, all reported AEs will be included in the AE data 
listings. 
For laboratory parameters, the normal range of the analyzing laboratory will be used and 
all values outside the normal range will be flagged and listed.  Additionally, descriptive 
statistics for the mean change from baseline to minimum (smallest) value, maximum 
(largest) value and final value during the study will be calculated for the continuous 
clinical laboratory parameters.  
Shift tables will be provided to cross-classify and tabulate subjects value from baseline to 
final value by the presence of clinically significant laboratory results.  Each subjects 
baseline value and final value will be flagged in reference to the normal range (low, 
normal, high) and also categorized as clinically non-significant (CTC grade < 3) or 
clinically significant (CTC grade t 3).  Further details will be provided in the SAP. 
8.1.4.1 
Pharmacokinetic Analyses 
Adalimumab trough serum concentrations will be summarized by treatment group at each 
time point using descriptive statistics including number of subjects, number of non 
missing observations (nnmiss), mean, median, standard deviation, coefficient of 
variation, minimum, and maximum.  The relationship between adalimumab 
concentrations and efficacy and/or safety variables may be explored.  Additional analysis 
may be performed. 

 
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8.1.5 
Interim Analysis 
There will be one planned interim analysis.  Details of the analysis will be described in 
the study SAP. 
8.2 
Determination of Sample Size 
Subjects who successfully completed Study M06-806 through Week 52 may be eligible 
to participate in this study. It is expected that approximately 70% (130) of subjects from 
the M06-806 study will enroll in this study. 
8.3 
Randomization Methods 
All subjects will be centrally registered using an IVRS.  This is an open-label study; 
therefore, subjects will not be randomized before the study is initiated, the telephone 
number and call in directions for the IVRS will be provided to each site.  Subjects will 
keep their subject number from the previous study (M06-806). 
9.0 
Ethics 
9.1 
Independent Ethics Committee (IEC) or Institutional Review 
Board (IRB) 
Good Clinical Practice (GCP) requires that the clinical protocol, any protocol 
amendments, the Investigators Brochure, the informed consent and all other forms of 
subject information related to the study (e.g., advertisements used to recruit subjects) and 
any other necessary documents be reviewed by an IEC/IRB.  IEC/IRB approval of the 
protocol, informed consent and subject information and/or advertising, as relevant, will 
be obtained prior to the authorization of drug shipment to a study site. 
Any amendments to the protocol will require IEC/IRB approval prior to implementation 
of any changes made to the study design.  A list of the documents required prior to 
initiation of the study can be found in Appendix C. 

 
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Any SAEs that meet the reporting criteria, as dictated by local regulations, will be 
reported to both responsible Ethics Committees and Regulatory Agencies, as required by 
local regulations.  During the conduct of the study, the Investigator should promptly 
provide written reports (e.g., ICH Expedited Reports, and any additional reports required 
by local regulations) to the IEC/IRB of any changes that affect the conduct of the study 
and/or increase the risk to subjects, unless otherwise submitted by the sponsor.  Written 
documentation of the submission to the IEC/IRB should also be provided to Abbott. 
9.2 
Ethical Conduct of the Study 
The study will be conducted in accordance with the protocol, International Conference on 
Harmonization (ICH) guidelines, applicable regulations and guidelines governing clinical 
trial conduct, and the ethical principles that have their origin in the Declaration of 
Helsinki.  Responsibilities of the clinical Investigator are specified in Appendix D. 
9.3 
Subject Information and Consent 
Prior to any study-related procedures or discontinuation of any medications for this study, 
the Investigator or his/her representative will explain the nature of the study to the subject 
of legal age (in the state of residence) or to the parent or legal guardian (as appropriate) 
of a subject who is not of legal age and answer all questions regarding this study.  
Subjects will be included in all discussions. 
The ICF will be reviewed, signed and dated by the subject of legal age (in the state of 
residence) or by the parent or legal guardian (as appropriate) of a subject who is not of 
legal age, and the person who administered the informed consent.  If a subject who was 
not of legal age at the onset of this study becomes of legal age during the course of the 
study, an informed consent will need to be obtained at that time.  Additionally, in keeping 
with each institutions IRB requirements an Informed Assent will also be obtained from 
the subject, as required.   
A copy of the signed ICF and Assent Form will be given to the subject and the subjects 
parent/legal guardian.  The original signed ICF and Assent Form will be placed in the 

 
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subjects medical record.  An entry must also be made in the subjects dated source 
documents to confirm that informed consent was obtained prior to any study-related 
procedures and that the subject received a signed copy. 
If an updated informed consent is approved after a subject has completed or terminated 
early from the study, but is within the 70-day follow-up window, the subject will not be 
required to return to the site for the purposes of signing the updated ICF.  The subject of 
legal age, parent or legal guardian (as appropriate) should be contacted regarding any 
changes and the documentation of the contact should be present in the subjects source.  
10.0 
Source Documents and Case Report Form 
Completion 
10.1 
Source Documents 
Source documents are defined as original documents, data and records.  This may include 
hospital records, clinical and office charts, laboratory data/information, subjects diaries or 
evaluation checklists, pharmacy dispensing and other records, recorded data from 
automated instruments, microfiches, photographic negatives, microfilm or magnetic 
media, and/or x-rays.  Data collected during this study must be recorded on the 
appropriate source documents. 
The Investigator(s)/institution(s) will permit study-related monitoring, audits, IEC/IRB 
review, and regulatory inspection(s), providing direct access to source data documents. 
The IMPACT III questionnaire and the WPAI questionnaire will be recorded directly on 
the CRF(s) by the subject, parent or legal guardian (as appropriate) and these CRFs will 
be considered source data. 
10.2 
Case Report Forms 
Case report forms will be supplied by Abbott.  These forms will be used to transmit 
information collected during the study to Abbott and regulatory authorities, as applicable.  
Case report forms must be completed for each subject enrolled in this study.  All case 

 
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report forms must be legible and completed in indelible black ballpoint ink.  Any 
necessary corrections are to be made by drawing a single line through the incorrect entry 
and writing in the revision.  All revisions must be initialed and dated by the Investigator 
or his/her representative.  Data are not to be obliterated by blacking out, using correction 
fluid or by erasing the original entry.  If the reason for the correction is not obvious, a 
brief explanation (e.g., transcription error) should accompany the change.  All 
information written on the case report forms must also be reflected in the subject source 
documents with the exception of the case report forms discussed above in Section 10.1. 
The Principal Investigator will review the case report forms for completeness and 
accuracy and sign and date each set of case report forms where indicated.  The case 
report forms will be reviewed periodically for completeness, legibility and acceptability 
by Abbott personnel (or their representatives).  Abbott (or their representatives) will be 
allowed access to all source documents in order to verify case report form entries. 
Once the original case report form has been removed from the site, all changes must be 
made via the appropriate change form specified by Abbott.  The Principal Investigator 
will review the change form for completeness and accuracy and sign and date the change 
form where indicated. 
11.0 
Data Quality Assurance 
Prior to the initiation of the study, an Investigators meeting will be held with Abbott 
personnel, the Investigators and their study coordinators, the CROs project manager and 
the CRAs for the study.  This meeting will include a detailed discussion of the protocol, 
performance of study procedures, CRF and Subject Diary completion, and specimen 
collection methods.  In addition to or instead of the Investigators meeting, the study 
personnel at each site may be trained on the study procedures by a CRA at a study 
initiation visit and will be given a CRF completion workbook for reference. 
The CRAs will monitor at each site throughout the study.  One hundred percent (100%) 
source document review will be performed against entries on the CRF and a quality 

 
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assurance check will be performed to ensure that the Investigator is complying with the 
protocol and regulations.  In addition, after CRFs are retrieved by the CRA, a review of 
the data will be conducted by a physician and a clinical review team at Abbott 
Laboratories. 
All data hand entered in the database will be verified by a double-key entry procedure at 
Abbott.  Any discrepancies will be reviewed against the hard copy CRF and corrected on-
line. After completion of the entry process, computer logic checks will be run to check 
for such items as inconsistent study dates and outlying laboratory values.  Any necessary 
corrections will be made to the database and documented via addenda, queries, source 
data clarification form or audit trail.  A manual review of selected line listings will also 
be performed at the end of the study. 
Routine hematology, serum chemistry, and serology will be conducted using a central 
laboratory.  ESR analysis will be done at a local lab designated by the site. The data from 
these analyses will be electronically transferred from the central laboratory to the study 
database.  Urinalysis will be completed locally.  If a microscopic urinalysis is necessary, 
this testing will be conducted using the central laboratory.  A final review of all 
laboratory results will be conducted by a physician and clinical review team at 
Abbott Laboratories. 
Sites will provide Abbott (or designate) with laboratory certifications (CAP and CLIA), 
CV of local lab director, and reference ranges for each local lab used.  The full name, 
address, phone number, and fax number for each local lab will also be included. 
12.0 
Use of Information and Publication 
12.1 
Use of Information 
All information concerning adalimumab and Abbott Laboratories operations, such as 
Abbott Laboratories patent applications, formulas, manufacturing processes, basic 
scientific data, or formulation information, supplied by Abbott Laboratories and not 
previously published is considered confidential information. 

 
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The information developed during the conduct of this clinical study is also considered 
confidential and will be used by Abbott Laboratories in connection with the development 
of adalimumab.  This information may be disclosed as deemed necessary by 
Abbott Laboratories to other clinical Investigators, other pharmaceutical companies, to 
the FDA,  and to other government agencies.  To allow for the use of the information 
derived from this clinical study and to ensure complete and thorough analysis, the 
Investigator is obligated to provide Abbott Laboratories with complete test results and all 
data developed in this study and to provide direct access to source data/documents for 
study- related monitoring, audits, IEC/IRB review, and regulatory inspection. 
This confidential information shall remain the sole property of Abbott Laboratories, shall 
not be disclosed to others without the written consent of Abbott Laboratories, and shall 
not be used except in the performance of this study. 
The Investigator will maintain a confidential subject identification code list of all subjects 
enrolled in the study (by name and subject number).  This list will be maintained at the 
site and will not be retrieved by Abbott. 
12.2 
Internet Sites 
Information regarding this study may be posted on various internet web sites and will 
maximally include study name, number, general population to be enrolled, entrance 
qualifications, brief description of the study, study objectives, doses, accruing 
Investigators (upon their approval) and number of subjects to be enrolled. 
13.0 
Completion of the Study 
The Investigator will conduct this study in compliance with the protocol, and will 
complete the study within the timeframe specified in the contract between the 
Investigator and Abbott.  Continuation of the study beyond this time must be mutually 
agreed upon in writing by both the Investigator and Abbott.  The Investigator will 
provide a summary of the studys outcome to the IEC/IRB following conclusion of the 
study, and will forward a copy of this summary to Abbott or their designee. 

 
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Abbott may terminate this study prematurely, either in its entirety or at individual sites, 
for reasonable cause provided that written notice is submitted a reasonable time in 
advance of the intended termination.  The Investigator may also terminate the study at 
their site for reasonable cause, after providing written notice to Abbott a reasonable time 
in advance of the intended termination.  Advance notice is not required by either party if 
the study is stopped due to safety concerns.  If Abbott terminates the study for safety 
reasons, it will immediately notify the Investigator by telephone and subsequently 
provide written instructions for study termination. 
Abbott will select the signatory Investigator from the Investigators who participate in the 
study.  Selection criteria for this Investigator will include level of participation as well as 
significant knowledge of the clinical research, investigational drug and study protocol.  
The signatory Investigator for the study will review and sign the final study report in 
accordance with the European Agency for the Evaluation of Medicinal Products (EMEA) 
Guidance on Investigators Signature for Study Reports. 
The Investigator will retain all essential documents until at least two years after the last 
approval of a marketing application in an ICH region and until there are no pending or 
contemplated marketing applications in an ICH region or at least two years have elapsed 
since the formal discontinuation of clinical development of the investigational product.  It 
is the responsibility of the sponsor to inform the Investigator/institution as to when these 
documents no longer need to be retained. 
The end-of-study is defined as the date of the last subjects last scheduled visit or the 
actual date of follow-up contact, whichever is longer. 
 

 
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14.0 
Investigators Agreement 
1. I have received and reviewed the Investigator Brochure for Humira. 
2. I have read this protocol and agree that the study is ethical. 
3. I agree to conduct the study as outlined and in accordance with all applicable 
regulations and guidelines. 
4. I agree to maintain the confidentiality of all information received or developed in 
connection with this protocol. 
 
 
 
 
Protocol Title: 
A Multi-center, Open-label Study of the Human Anti-TNF 
Monoclonal Antibody Adalimumab to Evaluate the Efficacy and the 
Long-term Safety and Tolerability of Repeated Administration of 
Adalimumab in Pediatric Subjects with Crohn's Disease Who Have 
Demonstrated a Clinical Response in the M06-806 Study 
Protocol Date: 
14 December 2010 
 
 
 
 
 
 
Signature of Principal Investigator 
 
Date 
 
 
 
Name of Principal Investigator (printed or typed) 
 
 
 
 

 
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15.0 
Reference List 
1. 
Hanauer SB, Sandborn W.  Management of Crohns disease in adults.  Am J 
Gastroenterol 2001;96:635-43. 
2. 
Loftus Jr. EV.  Clinical epidemiology of inflammatory bowel disease: Incidence, 
prevalence, and environmental influences.  Gastroenterology 2004;126:1504-17. 
3. 
Seidman EG.  Recent advances in the diagnosis and treatment of pediatric 
inflammatory bowel disease.  Curr Gastroenterol Rep 2000;2:248-52. 
4. 
Auvin S, Molinie F, Gower-Rousseau C, Brazier F, Merle V, Grandbastient B, 
et al.  Incidence, clinical presentation and location at diagnosis of pediatric 
inflammatory bowel disease: a prospective population-based study in northern 
France (1988-1999).  J Pediatr Gastroenterol Nutr 2005;41(1):49-55. 
5. 
Kugathasan S, Judd RH, Hoffmann RG, Heikenen J, Telega G, Khan F, et al.  
Epidemiologic and clinical characteristics of children with newly diagnosed 
inflammatory bowel disease in Wisconsin; a statewide population-based study.  
J Pediatr 2003;143(4):525-31. 
6. 
Cosgrove M, Al-Atia RF, Jenkins HR.  The epidemiology of pediatric 
inflammatory bowel disease.  Arch Dis Child 1996;74:460-1. 
7. 
Hassan K, Cowan FJ, Jenkins HR.  The incidence of childhood inflammatory 
bowel disease in Wales.  Eur J Pediatr 2000;159:261-3. 
8. 
Barton JR, Gillon S, Ferguson A.  Incidence of inflammatory bowel disease in 
Scottish children between 1968 and 1983; marginal fall in ulcerative colitis, three-
fold rise in Crohns Disease.  Gut 1989;30:618-22. 
9. 
Sawczenko A, Sandhu BK, Logan RFA, et al.  Prospective survey of childhood 
inflammatory bowel disease in the British Isles.  Lancet 2001;357:1093-4. 

 
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10. 
Olafsdottir EJ, Fluge G, Haug K.  Chronic inflammatory bowel disease in children 
in western Norway.  J Pediatr Gastroenterol Nutr 1989;8:454-8. 
11. 
Lindberg E, Lindquist B, Holmquist L, Hildebrand H.  Inflammatory bowel 
disease in children and adolescents in Sweden (1984-1995).  J Pediatr 
Gastroenterol Nutr 2000;30:259-64. 
12. 
Hildebrand H, Finkel Y, Grahnquist L, Lindholm J, Ekbom A, Askling J.  
Changing pattern of paediatric inflammatory bowel disease in northern Stockholm 
1990-2001. Gut 2003;52:1432. 
13. 
Heyman MB, Kirshner BS, Gold BD, Ferry G, Baldassano R, Cohen SA, et al.  
Children with early onset inflammatory bowel disease (IBD): analysis of a 
pediatric IBD consortium registry.  J Pediatr 2005;146(1):35-40. 
14. 
Lindberg E, Lindquist B, Holmquist L, Hildebrand H.  Inflammatory bowel 
disease in children and adolescents in Sweden, 1984-1995.  J Pediatr Gastroenterol 
Nutr 2000;30(3):259-64. 
15. 
Sawczenko A, Sandhu BK.  Presenting features of inflammatory bowel disease in 
Great Britain and Ireland.  Arch Dis Child 2003;88:995-1000. 
16. 
Griffiths AM.  Specificities of inflammatory bowel disease in childhood.  Best 
Pract Res Clin Gastroenterol 2004;18(3):509-23. 
17. 
Griffiths AM, Nguyen P, Smith C, MacMillan JH, Sherman PM.  Growth and 
clinical course of children with Crohns disease.  Gut 1993;34(7):939-43. 
18. 
Kanof ME, Lake AM, Bayless TM.  Decreased height velocity in children and 
adolescents before the diagnosis of Crohns disease.  Gastroenterology 
1988;95(6):1523-7. 
19. 
Markowitz J, Grancher K, Rosa J, Aiges H, Daum F.  Growth failure in pediatric 
inflammatory bowel disease.  J Pediatr Gastroenterol Nutr 1993;16(4):373-80. 

 
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20. 
Kleinman RE, Baldassano RN, Caplan A, Griffiths AM, Heyman MB, 
Issenman RM, et al.  Nutrition support for pediatric patients with inflammatory 
bowel disease: a clinical report of the North America Society for Pediatric 
Gastroenterology, Hepatology and Nutrition.  J Pediatr Gastroenterol Nutr 
2004;39(1):15-27. 
21. 
Gokhale R, Favus MJ, Karrison T, Sutton MM, Rich B, Kirshner BS.  Bone 
mineral density assessment in children with inflammatory bowel disease.  
Gastroenterology 1998;114:902-11. 
22. 
Boot AM, Bouquet J, Krennings EP, de Muinck Keizer-Schrama SMPF.  Bone 
mineral density and nutritional status in children with chronic inflammatory bowel 
disease.  Gut 1998;42:188-94. 
23. 
Ballinger AB, Savage MO, Sanderson IR.  Delayed puberty associated with 
Inflammatory bowel disease.  Pediatr Res 2003;53:205-10. 
24. 
Harpavat M, Greenspan SL, OBrien C, Chang C-C, Bowen A, Keljo DJ.  Altered 
bone mass in children at diagnosis of Crohns disease: a pilot study.  J Pediatr 
Gastroenterol Nutr 2005;40:295-300. 
25. 
Hyams JS, Wyzga N, Kreutzer DL, Justinich CJ, Gronowicz GA.  Alterations in 
bone metabolism in children with inflammatory bowel disease: an in vitro study. 
J Pediatr Gastroenterol Nutr 1997;24(3):289-95. 
26. 
Hanauer S, Lukas M, MacIntosh D, Rutgeerts P, Sandborn W, Pollack P.  A 
randomized, double-blind, placebo-controlled trial of the human anti-TNF-D 
monoclonal antibody adalimumab for the induction of remission in patients with 
moderate to severely active Crohns disease.  Gastroenterology 2004;127(1):332. 
27. 
Data on file at Abbott Laboratories. 
28. 
Abbott Study DE038, Data on file. 

 
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29. 
Humira® (adalimumab) [package insert].  North Chicago, IL:  
Abbott Laboratories:  June 2006. 
30. 
Present DH, Rutgeerts P, Targan S, Hanauer SB, Mayer L, van Hogezand RA, 
et al.  Infliximab for the treatment of fistulas in patients with Crohns disease. 
N Eng J Med.  1999;340(18):1398-405. 
31. 
Greulich and Pyle Radiographic Atlas of Skeletal Development of the Hand and 
Wrist:  June 1959. 
32. 
Centers for Disease Control and Prevention.  Targeted tuberculin testing and 
treatment of latent tuberculosis infection.  MMWR 2006 April. 
 

 
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Appendix A.  
List of Abbreviations and Definition of Terms 
Abbreviations 
AAA 
Anti-adalimumab antibody 
AE 
Adverse Event 
ALT 
Alanine Transaminase 
ANA 
Antinuclear antibody 
AST 
Aspartate transaminase 
BMI 
Body Mass Index 
BSAP 
Bone-specific alkaline phosphatase 
BUN 
Blood Urea Nitrogen 
CD 
Crohns disease 
CDC 
Center for Disease Control 
CNS 
Central Nervous Systems 
CRA 
Clinical Research Associate 
CRF 
Case Report Form 
CRP 
C-Reactive Protein 
CTC 
Common Toxicity Criteria 
DMC 
Data Monitoring Committee 
DNA 
Deoxyribonucleic acid 
dsDNA 
Double Stranded DNA 
eow 
Every other week 
ESR 
Erythrocyte sedimentation rate 
ET 
Early Termination 
EU 
European Union 
ew 
Every week 
FDA 
U.S. Food and Drug Administration 
GCP 
Good Clinical Practice 
HCT 
Hematocrit 
HIV 
Human immunodeficiency virus 
ICH 
International Conference on Harmonization 
IEC 
Independent Ethics Committee 
IgG1 
Immunoglobulin 
ICF 
Informed Consent Form 

 
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IRB 
Institutional Review Board 
ITT 
Intent-to Treat 
IVRS 
Interactive Voice Response System 
JRA 
Juvenile Rheumatoid Arthritis 
LOCF 
Last Observation Carried Forward 
MTX 
Methotrexate 
Ntx  
N − telopeptide 
OL 
Open-Label 
PCDAI 
Pediatric Crohns Disease Activity Index 
PK 
Pharmacokinetics 
POR 
Proof of Receipt 
RA 
Rheumatoid Arthritis 
SAE 
Serious Adverse Event 
SAP 
Statistical analysis plan 
SC 
Subcutaneous 
SSC 
Sponsor Steering Committee 
TB 
Tuberculosis 
TNF 
Tumor Necrosis Factor 
TPN 
Total Parenteral Nutrition 
US 
United States 
WPAI 
Work Productivity and Activity Impairment Questionnaire 
WPAI-CD 
Work Productivity and Activity Impairment Questionnaire: Crohns 
Disease 
 

 
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Appendix B.  
List of Protocol Signatories 
Name 
Title 
Functional Area 
Statistics 
Clinical 
Clinical 
Clinical 
 

 
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Appendix C.  
Documents Required Prior to Initiation of the Study 
As sponsor of a clinical study, Abbott has an obligation to ensure that the study will be 
conducted by a qualified investigator with sufficient resources (of time, personnel, and 
physical facilities) to conduct the study and to ensure that the investigator understands 
and agrees to comply with Good Clinical Practices and applicable regulations, policies, 
and procedures.  Prior to the beginning of any clinical study, the investigator will be 
asked to provide the following documentation.  
1. 
A signed and dated Investigators agreement page for the study. 
2. 
A signed and dated Form FDA 1572 certifying the investigators agreement to 
comply with the appropriate regulations governing the conduct of the study. 
 
A signed and dated Investigator Information and Agreement Form certifying the 
investigators agreement to comply with the appropriate (e.g., ICH GCP) 
regulations governing the conduct of the study. These will be required only for 
sites that are recruited under this amendment, or when existing sites update study 
documentation. 
3. 
 Current curriculum vitae for the investigator.  If subinvestigators will participate 
in the study, curriculum vitae for each. 
4. 
Requirements for the Independent Ethics Committee (IEC)/Institutional Review 
Board (IRB). 
● A copy of the signed and dated letter of approval of the IEC/IRB.  The letter 
must specify that both the protocol and informed consent form were approved 
(unless separate documentation that the informed consent was approved is 
provided). 
● A dated list containing the names and affiliations of the members of the 
IEC/IRB, or the institutions General Assurance Number. 

 
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● If the investigator and/or subinvestigator is a member of the IEC/IRB, a letter 
stating that he/she did not participate in the review or approval of the protocol 
or informed consent form. 
5. 
A specimen copy of the IEC/IRB-approved informed consent document to be used 
in the study. 
6. 
A list of reference ranges of values for all laboratory tests specified by the protocol 
for all laboratories utilized. 
7. 
A copy of the laboratory(ies) certification(s) or the authorization number of the 
certification(s), the name of the certifying authority, and the period of certification. 
8. 
Financial Disclosure Certification forms must be completed by each investigator 
and all subinvestigators identified on the Form FDA 1572 or Investigator 
Information and Agreement Form.  A Financial Disclosure, EU Consent, is 
required to be completed for each investigator and/or subinvestigator who is a 
resident of the European Union 
 

 
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Appendix D.  
Responsibilities of the Clinical Investigator 
Clinical research studies sponsored by Abbott are subject to the regulations of the U.S. 
Food and Drug Administration (FDA).  The responsibilities imposed upon Investigators 
by the FDA are summarized in the "Statement of Investigator" (Form FDA 1572), which 
is a form letter addressed to the sponsor (Abbott), summarizing the Investigators 
qualifications for the study and his/her willingness to follow FDA regulations with 
respect to the study. 
In signing a Form FDA 1572, the Investigator agrees to assume the following 
responsibilities:   
1. 
To conduct the study(ies) in accordance with the relevant, current protocol(s) and 
only make changes in a protocol after notifying Abbott, except when necessary to 
protect the safety, rights, or welfare of subjects. 
2. 
To personally conduct or supervise the described investigation(s). 
3. 
To inform any subjects, or any persons used as controls, that the drugs are being 
used for investigational purposes and to ensure that the requirements relating to 
obtaining informed consent in 21 CFR Part 50 and Independent Ethics Committee 
(IEC)/Institutional Review Board (IRB) review and approval in 21 CFR Part 56 
are met. 
4. 
To report to Abbott adverse experiences that occur in the course of the 
investigation(s) in accordance with 21 CFR 312.64. 
5. 
To read and understand the information in the Investigators Brochure, including 
the potential risks and side effects of the drug. 
6. 
To ensure that all associates, colleagues, and employees assisting in the conduct of 
the study(ies) are informed about their obligations in meeting the above 
commitments. 

 
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7. 
To maintain adequate and accurate records of the conduct of the study and make 
those records available for inspection by representatives of Abbott, the IEC/IRB 
and/or the appropriate regulatory agency, and to retain all study-related documents 
until notification from Abbott.  The Investigator must notify Abbott when they are 
no longer able to retain the study related documents. 
8. 
To ensure that an IEC/IRB that complies with the requirements of 21 CFR Part 56 
will be responsible for the initial and continuing review and approval of the 
clinical investigation. 
9. 
To promptly report to the IEC/IRB all changes in the research activity and all 
unanticipated problems involving risks to human subjects or others (including 
submission of any Expedited Safety Reports received from Abbott to the 
IEC/IRB), and to make no changes in the research without IEC/IRB approval, 
except where necessary to eliminate apparent immediate hazards to human 
subjects. 
10. 
To comply with all other requirements regarding the obligations of clinical 
Investigators and all other pertinent requirements in 21 CFR Part 312. 
 

 
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Appendix E.  
CDC Treatment of Tuberculosis Infection (Preventive Therapy) 
Centers for Disease Control and Prevention 
Tuberculosis Information 
Treatment of Tuberculosis Infection (Preventive Therapy), Latent Tuberculosis 
Infection (LBTI)32 
 
 

 
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Appendix F.  
Non-Drug Materials Provided to the Study Site(s) 
Study sites will receive the following supplies prior to or during the study: 
Tote Bags 
Cooler 
Sharps Containers 
Ice Packs 
CDAI subject diary 
Dosing Diaries 
Subject Medication Log 
Self Injection Instructions 

 
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Appendix G.  
Pediatric Crohns Disease Activity Index (PCDAI) 
1. Abdominal pain rating 
 
- None 
 
- Mild - Brief, does not interfere with activities 
 
- Moderate/severe-Daily, longer lasting, affects activities, nocturnal 
 
= 0 p 
= 5 p 
= 10 p 
Score 
2. Stools (per day) 
 
- 0–1 liquid stools, no blood 
 
- Up to 2 semi-formed with small blood, or 2–5 liquid 
 
- Gross bleeding, or t 6 liquid, or nocturnal diarrhea 
 
= 0 p 
= 5 p 
= 10 p 
 
3. Patient Functioning, General Well-Being 
 
- No limitation of activities, well 
 
- Occasional difficulty in maintaining age appropriate activities, below par 
 
- Frequent limitation of activity, very poor 
 
= 0 p 
= 5 p 
= 10 p 
 
LABORATORY 
Score 
4. HCT: Male and female  d 10 years: 
 
 
t 33 
= 0 p 
 
 
28-32 
= 2.5 p 
 
 
< 28 
= 5 p 
 
Male 11–14 years: 
 
 
t35 
= 0 p 
 
 
30-34 
= 2.5 p 
 
 
<30 
= 5 p 
 
 
Female 11–19 years: t 34 
= 0 p 
 
 
29-33 
= 2.5 p 
 
 
< 29 
= 5 p 
 
Male 15–19 years: 
t37 
= 0 p 
 
 
32-36 
= 2.5 p 
 
 
<32 
= 5 p 
 
5. 
ESR (mm/hr) 
< 20 
= 0 p 
 
 
20-50 
= 2.5 p 
 
 
> 50 
= 5 p 
 
6. 
Albumin (g/dL) 
t 3.5 
= 0 p 
 
 
3.1-3.4 
= 5 p 
 
 
d 3.0 
= 10 p 
 

 
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EXAMINATION 
Score 
7. 
Weight 
- Weight gain or voluntary weight stable/loss 
 
 
- Involuntary weight stable, weight loss 1–9% 
 
 
- Weight loss t 10% 
= 0 p 
= 5 p 
= 10 p 
 
8. 
Height 
 
 
 
 
 
 
 
 
Height velocity t -1SD 
 
 
 
Height velocity < -1SD, > -2SD 
 
 
 
Height velocity d -2SD 
 
= 0 p 
= 5 p 
= 10 p 
 
9. 
Abdomen 
- No tenderness, no mass 
 
 
- Tenderness, or mass without tenderness 
 
 
- Tenderness, involuntary guarding, definite mass 
= 0 p 
= 5 p 
= 10 p 
 
10. Perirectal disease 
- None, asymptomatic tags 
 
 
- 1–2 indolent fistula, scant drainage, no tenderness 
 
 
- Active fistula, drainage, tenderness, or abscess 
= 0 p 
= 5 p 
= 10 p 
 
11. Extra-intestinal Manifestations 
 
(Fever t 38.5 for 3 days over past week, definite arthritis, uveitis, E. nodosum, 
P. gangrenosum) 
 
- None 
 
- One 
 
- t Two 
 
 
= 0 p 
= 5 p 
= 10 p 
 
TOTAL SCORE  
Pediatric Crohns Disease Activity Index (PCDAI) 
 
 

 
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Appendix H.  
PCDAI Users Guide and Guideline for Reference Weight and 
Reference Height 
This guide is intended to help nurse coordinators and physicians complete the PCDAI in 
order to assess disease activity in children with Crohns disease participating in clinical 
trials. 
History 
All calculations are based upon a one-week (7 day) history recall of symptoms.  The 
history recall should be solicited from the subject and/or caregiver. 
Item 1.  Abdominal pain 
The descriptions in the PCDAI of "mild" and "moderate/severe" should be used to guide 
in scoring the pain. Note that duration, effect on activities, and nocturnal occurrence 
separate moderate/severe from mild.  If pain varies in severity during the week, subject 
should be scored according to the most severe pain. However, mild pain should be 
present on at least two days to score 5 points rather than 0 points. 
Item 2.  Stools 
The intent is to score the stool pattern during the preceding week. 
To facilitate scoring, first categorize the subject as having blood in the stool or not. 
If there is no blood in the stool, score as follows:   
Formed stools or up to 1 loose stool daily = 0 
2-5 liquid or very loose stools on 1 or more days = 5 
6 or more liquid or very loose stools on 1 or more days or any nocturnal diarrhea = 10 

 
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If blood is present in the stool on any day during the past week, score as follows:   
Small amounts of blood in stool (on toilet paper or small spots in stool, etc.) = 5 
Any gross bleeding (large amounts on stool or colors the water in the toilet, etc.) = 10 
Item 3.  Subject functioning, general well-being 
If there is variation during the week, subject should be scored according to the most 
significant limitation of activity, even if it occurs during only one day of the week, as 
long as it is likely due to Crohns disease and not to an intercurrent illness. 
Item 4.  Hematocrit 
Hematocrit values should be rounded to a whole number prior to completing the 
calculation.   Numbers that fall between the range of 0.1-0.4 must be rounded down.   
Numbers that fall between the range of 0.5-0.9 must be rounded up. 
Physical Examination 
Item 7.  Weight (The intent is to assess the ability to normally maintain or gain weight) 
Reference weight to be used for calculation of weight gain/loss during the study: 
From Baseline to Week 264: use weight from previous visit 
Voluntary weight stable/loss means subject maintaining or losing weight on purpose. 
Involuntary weight stable means subject wants to gain weight but cannot. 
To calculate percentage weight loss use formula:   
Weight from previous visit – Current weight X 100 = % weight loss 
 
Weight from previous visit 

 
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Item 8.  Height 
Reference height for calculation of height velocity 
● From Baseline to Week 24, use height from 6 months prior to Baseline 
● From Week 24 to Week 48, use height from Baseline visit 
● From Week 48 to Week 72, use height from Week 24 
● From Week 72 to Week 96, use height from Week 48 
● From Week 96 to Week 120, use height from Week 72 
● From Week 120 to Week 144, use height from Week 96 
● From Week 144 to Week 168, use height from Week 120 
● From Week 168 to Week 192, use height from Week 144 
● From Week 192 to Week 216, use height from Week 168 
● From Week 216 to Week 240, use height from Week 192 
● From Week 240 to Week 264, use height from Week 216 
 
The intent is to assess the normalcy vs. impairment of the subjects recent linear growth.  
Note that post-pubertal subjects will score 0 points.  For subjects still growing, there are 
two options for scoring.  Method (a) is preferred.  Method (b) to be used if data required 
for (a) are unavailable. 
1. 
Height velocity (cm/year), the most sensitive parameter, should be calculated as 
below: 
Present height –  Appropriate height measurement (from above)  x  12  = Height velocity (cm/year) 
  
        Interval (months) between heights 
Using height velocity chart below, determine centile for height velocity. 

 
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2. 
Scoring for the PCDAI:   
a. Velocity less than "Minus 2 SD" scores 10 points. 
b. Velocity between "Minus 2 SD" and "Minus 1 SD" scores 5 points. 
c. Velocity greater than "Minus 1 SD" scores zero points. 
 
* 
Please note that subjects should score zero points if a subject is a female above 14.5 years of age or a 
male above 17.5 years of age. 
 

 
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Height Velocity Reference Values for Calculating the PCDAI (Males) 
 
Height Velocity in cm per year (Males) 
Age (years) 
Minus 2SD 
Minus 1SD 
Mean 
2.5 
5.7 
7.0 
8.3 
3 
5.4 
6.6 
7.8 
3.5 
5.1 
6.3 
7.4 
4 
4.9 
6.0 
7.1 
4.5 
4.7 
5.8 
6.8 
5 
4.6 
5.6 
6.6 
5.5 
4.5 
5.4 
6.4 
6 
4.3 
5.3 
6.2 
6.5 
4.2 
5.1 
6.0 
7 
4.2 
5.0 
5.9 
7.5 
4.1 
4.9 
5.8 
8 
3.9 
4.8 
5.6 
8.5 
3.8 
4.6 
5.4 
9 
3.8 
4.5 
5.3 
9.5 
3.7 
4.5 
5.2 
10 
3.7 
4.4 
5.1 
10.5 
3.7 
4.4 
5.1 
11 
3.7 
4.4 
5.2 
11.5 
3.8 
4.6 
5.3 
12 
4.0 
4.9 
5.7 
12.5 
4.8 
5.8 
6.7 
13 
6.2 
7.4 
8.6 
13.5 
7.1 
8.3 
9.5 
14 
6.1 
7.2 
8.4 
14.5 
4.1 
5.3 
6.5 
15 
2.4 
3.6 
4.7 
15.5 
1.2 
2.3 
3.3 
16 
0.4 
1.3 
2.2 
16.5 
0.1 
0.7 
1.5 
17 
0.1 
0.4 
0.9 
17.5 
0.1 
0.1 
0.5 
 

 
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Height Velocity Reference Values for Calculating the PCDAI (Females) 
 
Height Velocity in cm per year (Females) 
Age (years) 
Minus 2SD 
Minus 1SD 
Mean 
2.5 
5.9 
7.3 
8.6 
3 
5.5 
6.9 
8.1 
3.5 
5.2 
6.4 
7.6 
4 
4.9 
6.1 
7.2 
4.5 
4.7 
5.8 
6.8 
5 
4.6 
5.6 
6.6 
5.5 
4.5 
5.5 
6.4 
6 
4.4 
5.3 
6.2 
6.5 
4.3 
5.2 
6.1 
7 
4.3 
5.2 
6.0 
7.5 
4.3 
5.1 
5.9 
8 
4.2 
5.0 
5.8 
8.5 
4.2 
4.9 
5.7 
9 
4.2 
5.0 
5.8 
9.5 
4.3 
5.0 
5.8 
10 
4.4 
5.3 
6.2 
10.5 
4.7 
5.7 
6.8 
11 
5.7 
6.6 
7.7 
11.5 
6.1 
7.2 
8.3 
12 
5.2 
6.3 
7.3 
12.5 
3.6 
4.8 
5.9 
13 
2.4 
3.3 
4.3 
13.5 
1.3 
2.2 
2.9 
14 
0.4 
1.1 
1.8 
14.5 
0.0 
0.5 
1.0 
 

 
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Appendix I.  
Crohns Disease Activity Index (CDAI) 
 
 
 
Factor 
Subtotal 
1. Number of liquid or very soft stools
(Record the frequency per day) 
         __+___+___+___+___+___+___=___ 
Days: 1     2      3      4 
5      6 
  7   Sum 
X 
2 
 
2.  Abdominal pain rating: 
0=none, 1=mild, 2=moderate, 
3=severe 
          __+___+___+___+___+___+___=___ 
Days: 1     2      3      4 
5      6 
  7   Sum 
X 
5 
 
3. General well-being: 
0=generally well, 1=slightly 
underpar, 2=poor, 3=very poor, 
4=terrible 
         __+___+___+___+___+___+___=___ 
Days: 1     2      3      4 
5      6 
  7   Sum 
X 
7 
 
4. Number of 6 listed categories the 
subject now has: 
Check all items that apply: 
□  Arthritis/arthralgia 
□  Iritis/uveitis 
□  Erythema nodosum/  
 pyoderma gangrenosum/ 
 aphthous stomatitis 
□  Fissure, abscess and/or anal 
fistula (draining/non-draining) 
□  Other cutaneous fistula 
(draining/non-draining) fistula 
□  Fever over 100°F (37.8°C) during 
past week 
 
 
 
 
 
 
  
________ 
 
 
 
Record "0" if no categories checked 
X 
20 
 
5.   Taking Lomotil / Imodium / 
Loperamide /opiates for diarrhea  
0=no, 1=yes 
________ X 
30 
 
6.   Abdominal mass 
0=none, 2=questionable, 5=defined 
________ X 
10 
 
7.   Hematocrit: ______ 
Male: 
(47 - hematocrit) = 
Female: (42 - hematocrit) = Subtotal ______ 
If hematocrit > normal, enter "0" 
X 
6 
 
8.   Body weight: __  __  __ . __ (kg) 
Ideal weight for height: 
__  __  __ . __ (kg) 
100 x [1 - (Body wt/Ideal wt)] =  
Percent below ideal weight: ______ 
If body wt > ideal wt, enter "0" 
X 
1 
 
 
 
 
Total 
 
* 
Ideal weight is obtained from CDC growth charts.  The subtotal of box 8 should be rounded to a whole number.  
Numbers that fall between the range of .1-.4 must be rounded down.   Numbers that fall between the range of .5-.9 
must be rounded up.  To ensure consistency across all sites and to take into account the varying growth rates of 
subjects in this study, the IBW should be calculated at each visit. 
* 
Hematocrit values should be rounded to a whole number prior to completing the calculation in box 7 of the CDAI.   
Numbers that fall between the range of .1-.4 must be rounded down.   Numbers that fall between the range of .5-.9 
must be rounded up. 

 
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Appendix J.  
Subject CDAI Diary 
Crohns Disease Activity Index 
Subject Diary Card 
Enter all values legibly using a black 
ballpoint pen. 
Add item requested for each day. 
Day 
Date___ 
Day 
Date___ 
Day 
Date___ 
Day 
Date___ 
Day 
Date___ 
Day 
Date___ 
Day 
Date___ 
Number (total) of liquid or very soft 
stools per day. 
 
 
 
 
 
 
 
Daily abdominal pain rating. 
(0=none, 1=mild, 2=moderate, 3=severe) 
 
 
 
 
 
 
 
Daily rating of general well being. 
(0=well, 1=slightly below par, 2=poor, 
3=very poor, 4=terrible) 
 
 
 
 
 
 
 
Subject Initials:___________ 
Subjects Signature:__________________________ 
 
Investigator or Designees Signature:______________________ 

 
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Question 1. 
How much has your stomach been hurting you in the past two weeks? 
□ 
□ 
□ 
□ 
□ 
Not at all 
 Hardly hurting 
at all 
Hurting 
somewhat  
Hurting 
quite a bit 
Hurting 
very much 
 
Question 2.  
Taking medicines or tablets bothers you 
□ 
□ 
□ 
□ 
□ 
Not at all 
 Hardly bothers 
at all 
Bothers 
somewhat  
Bothers  
quite a bit 
Bothers 
very much 
 
Question 3. 
How often has your inflammatory bowel disease prevented you from 
eating what you want in the past two weeks? 
□ 
□ 
□ 
□ 
□ 
Never 
 Rarely 
Sometimes 
Often 
Very often 
 
Question 4. 
How often have you been worrying about having a flare-up (increase of 
symptoms) in the last two weeks? 
□ 
□ 
□ 
□ 
□ 
Never 
 Rarely 
Sometimes 
Often 
Very often 
 
Question 5. 
How much does it bother you that you have an illness that does not just go 
away? 
□ 
□ 
□ 
□ 
□ 
Not at all 
 Hardly bothers 
at all 
Bothers 
somewhat  
Bothers quite a 
bit 
Bothers very 
much 
 
Question 6. 
How much energy did you have during the past two weeks? 
□ 
□ 
□ 
□ 
□ 
Very much 
energy 
Quite a bit of 
energy 
Some energy 
 A little energy 
No energy at 
all  

 
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Question 7. 
How do you feel about your weight? 
□ 
□ 
□ 
□ 
□ 
I feel great 
about my 
weight 
I feel good 
about my 
weight 
I dont feel 
good or bad 
about my 
weight 
I feel bad about 
my weight 
I feel awful 
about my 
weight 
 
Question 8. 
How has your inflammatory bowel disease affected your family? 
□ 
□ 
□ 
□ 
□ 
The effect has 
been great 
The effect has 
been good 
It has not 
affected our 
family 
The effect has 
been bad 
The effect has 
been awful 
 
Question 9. 
How often did you have to miss out on certain things (hobbies, play, 
parties) because of your inflammatory bowel disease in the past two weeks? 
□ 
□ 
□ 
□ 
□ 
Never 
Rarely 
Sometimes 
Often 
Very often 
 
Question 10. How often have you been bothered by diarrhea (loose or frequent bowel 
movements) in the past two weeks? 
□ 
□ 
□ 
□ 
□ 
Never 
Rarely 
Sometimes 
Often 
Very often 
 
Question 11. How often do you worry about health problems you might have in the 
future? 
□ 
□ 
□ 
□ 
□ 
Never 
Rarely 
Sometimes 
Often 
Very often 
 

 
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Question 12. How often do you think it is unfair that you have inflammatory bowel 
disease? 
□ 
□ 
□ 
□ 
□ 
Never 
Rarely 
Sometimes 
Often 
Very often 
 
Question 13. During the past two weeks, were you ever angry that you have 
inflammatory bowel disease? 
□ 
□ 
□ 
□ 
□ 
Never 
Rarely 
Sometimes 
Often 
Very often 
 
Question 14. Do you think too many rules or limits are placed on you because of your 
inflammatory bowel disease? 
□ 
□ 
□ 
□ 
□ 
Never 
Rarely 
Sometimes 
Often 
Very often 
 
Question 15. How do you feel about the way you look? 
□ 
□ 
□ 
□ 
□ 
I think I look 
great 
I think I look 
good 
I dont think I 
look good or 
bad 
I think I look 
bad 
I think I look 
awful 
 
Question 16. Are you embarrassed because of your bowel condition? 
□ 
□ 
□ 
□ 
□ 
Not at all 
 Hardly 
embarrassed at 
all 
Embarrassed 
somewhat  
Embarrassed 
quite a bit 
Embarrassed 
very much 
 
Question 17. Did you have fun during the past two weeks? 
□ 
□ 
□ 
□ 
□ 
Very often 
Often 
Sometimes 
Rarely 
Never 

 
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Question 18. Is it harder to make friends because of your inflammatory bowel disease? 
□ 
□ 
□ 
□ 
□ 
Not at all 
harder 
 A little harder 
Quite a bit 
harder 
Much harder 
Very much 
harder 
 
Question 19.  How often do you worry about your stool (bowel movement) containing 
blood? 
□ 
□ 
□ 
□ 
□ 
Never 
Rarely 
Sometimes 
Often 
Very often 
 
Question 20. Are you worried you cannot go out on a date or have a boyfriend or 
girlfriend because of your inflammatory bowel disease? 
□ 
□ 
□ 
□ 
□ 
Not at all 
worried 
 Hardly 
worried at all 
Worried 
somewhat  
Worried quite a 
bit 
Worried very 
much 
 
Question 21. How often did you feel sick to your stomach in the past two weeks? 
□ 
□ 
□ 
□ 
□ 
Never 
Rarely 
Sometimes 
Often 
Very often 
 
Question 22. How do you feel about the tests you have to go through? 
□ 
□ 
□ 
□ 
□ 
I do not mind 
them at all 
I mind them a 
tiny bit 
I mind them a 
little 
I mind them a 
lot 
I hate them 
 
Question 23. Do other children bully you or leave you out of things because of your 
inflammatory bowel disease or its treatment? 
□ 
□ 
□ 
□ 
□ 
Never 
Rarely 
Sometimes 
Often 
Very often 

 
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Question 24. How often do you worry about having an operation? 
□ 
□ 
□ 
□ 
□ 
Never 
Rarely 
Sometimes 
Often 
Very often 
 
Question 25. In the past two weeks how often were you afraid you may have an 
accident or not get to the toilet in time? 
□ 
□ 
□ 
□ 
□ 
Never 
Rarely 
Sometimes 
Often 
Very often 
 
Question 26. Do you try to keep your inflammatory bowel disease a secret from other 
people? 
□ 
□ 
□ 
□ 
□ 
No, I do not try 
at all 
I dont try much I try a little 
I try hard 
Yes, I try very 
hard 
 
Question 27. Does your inflammatory bowel disease make it difficult to travel or go on 
a holiday? 
□ 
□ 
□ 
□ 
□ 
No, not 
difficult 
A little difficult
Quite difficult 
Very difficult 
Yes, extremely 
difficult 
 
Question 28.  How did you feel during the past two weeks? 
□ 
□ 
□ 
□ 
□ 
Great 
Good 
Not good or 
bad 
Bad  
Awful 
 
Question 29. Are you happy with your life? 
□ 
□ 
□ 
□ 
□ 
Yes, very 
happy 
Happy 
Not happy or 
unhappy 
Unhappy 
Very unhappy 

 
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Question 30. Do you feel there is someone you can talk to about your inflammatory 
bowel disease? 
□ 
□ 
□ 
□ 
□ 
Always  
Often  
Sometimes  
Rarely 
Never 
 
Question 31. How often did you have to pass gas in the past two weeks? 
□ 
□ 
□ 
□ 
□ 
Never 
Rarely 
Sometimes 
Often 
Very often 
 
Question 32. How tired have you felt in the past two weeks? 
□ 
□ 
□ 
□ 
□ 
Not at all tired 
 A little tired 
Quite tired 
Tired  
Very tired 
 
Question 33. How do you feel about your height? 
□ 
□ 
□ 
□ 
□ 
I feel great 
about my 
height 
I feel good 
about my 
height 
I dont feel 
good or bad 
about my 
height 
I feel bad about 
my height 
I feel awful 
about my 
height 
 
Question 34. Does your inflammatory bowel disease get in the way of playing sports the 
way you would like to? 
□ 
□ 
□ 
□ 
□ 
Never 
Rarely 
Sometimes 
Often 
Always 
 
Question 35. In the past two weeks how often were you able to go to school? (If you are 
in the middle of a school break or the summer holidays, answer as if school was on) 
□ 
□ 
□ 
□ 
□ 
Always  
Most days  
Half the days 
A few days 
Never 
 

 
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End of questionnaire 
This completes the questionnaire. Do you have anything else to add which you feel is 
important about having inflammatory bowel disease, or do you have any other 
remarks? Please write them below. 
 
_________________________________________________________ 
_________________________________________________________ 
_________________________________________________________ 

 
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Appendix L.  
Excluded Medications 
Cyclosporine 
Tacrolimus 
Therapeutic enemas and suppositories (not including those done in conjunction with 
routine colonoscopy) 
Live vaccines 
The combination of budesonide and prednisone (or equivalent) 
Infliximab 
Mycophenolate mofetil (MMF or CellCept® ) 
Growth Hormone 
Kineret® (anakinra) 
Tysabri (natalizumab) 
Orencia (abatacept) 
Concurrent biologic therapy 
Any investigational agent 
Any previous anti-TNF medication except infliximab before the M06-806 study 
(including adalimumab). 
 

 
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Appendix M.  
Day 70 Phone Call 
Site Name / Number: ________ 
Subject Number:________ 
Subject Initials:________ 
Please contact all Subjects 70 days following drug discontinuation. 
 
 
 
Date of Call: ____________ 
 
 
□     Lost to Follow-Up (Please check this box if subject was not willing to provide any follow-up 
information or you were unable to speak to the subject following at least one attempt). 
 
 
□      No Events Reported 
 
List any Adverse Events (AE) and/or Serious Adverse Events (SAE) that occurred since the subject was 
last seen in clinic for this study.  Please document all adverse events on a 500 AE CRF to be submitted to 
data management.  (Please report all SAEs to Abbott within 24 hours of being made aware of the event.  
Follow-up information must also be reported within 24 hours of being made aware of the information.). 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
If events are listed above, your monitor will review and retrieve the appropriate CRF pages during 
their next visit.  Please fax this form to Paragon at 
 
 

 
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Appendix N.  
Unscheduled Outpatient Visits, Emergency Room Visits and 
Hospitalizations 
1. 
Since the last study visit has the subject had any physician/health care visits for 
their Crohns disease other than the protocol required visits? 
Yes ___ 
No  ___ 
If yes provide the following: 
I. 
Since the last visit, has the subject been seen by a physician for their Crohns 
Disease? 
YES:_____ 
NO:_____ 
If YES, how many times:_______ 
 
 
II. Since the last visit, has the subject been seen in the Emergency Room for their 
Crohns Disease? 
YES:_____ 
NO:______ 
If YES, how many times:_____ 
III. Since the last visit, has the subject been admitted to the hospital due to their 
Crohns Disease? 
YES:_____ 
NO:______ 
If YES, how many times:_____ 
If YES, please indicate the total number of days in the hospital:_____ 
 
 

 
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Appendix O.  
Subject Medication Log 
Instructions:  As a participant in this study, it is also important to keep a record of all mediations you take (new and old) throughout the study.  Please take this 
sheet home with you and write down any medications you take during the study.  It will be VERY important that you bring this sheet back to your doctors office 
and speak with your doctor about everything you have written down. 
 
Name of Medication 
Date you took
first dose 
Date you took
last dose 
What dose of medicine 
did you take? 
How often did you 
take the medicine? 
Why did you take the 
medicine? 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
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Week 25 - Week 36 
Subject Initials: __________ 
Subject Study #: ___________ 
 
Date 
day/mm/yr 
Day or 
Week # 
Time of Study 
Drug 
Administration 
Dose (mL) 
Administered
Kit #
Initials of Person 
Administering 
Study Medication 
Comments 
18/MAR/04 EXAMPLE 
9:35 am 
0.8 
 
MM 
none 
 
Week 25 
 
 
 
 
 
 
Week 26 
 
 
 
 
 
 
Week 27 
 
 
 
 
 
 
Week 28 
 
 
 
 
 
 
Week 29 
 
 
 
 
 
 
Week 30 
 
 
 
 
 
 
Week 31 
 
 
 
 
 
 
Week 32 
 
 
 
 
 
 
Week 33 
 
 
 
 
 
 
Week 34 
 
 
 
 
 
 
Week 35 
 
 
 
 
 
 
Week 36 
 
 
 
 
 
 

 
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Week 241 - Week 263 
Subject Initials: __________ 
Subject Study #: ___________ 
 
Date 
day/mm/yr 
Day or 
Week # 
Time of Study 
Drug 
Administration 
Dose (mL) 
Administered
Kit #
Initials of Person 
Administering 
Study Medication Comments
18/MAR/04 
EXAMPLE 
9:35 am 
0.8 
 
MM 
none 
 
Week 241 
 
 
 
 
 
 
Week 242 
 
 
 
 
 
 
Week 243 
 
 
 
 
 
 
Week 244 
 
 
 
 
 
 
Week 245 
 
 
 
 
 
 
Week 246 
 
 
 
 
 
 
Week 247 
 
 
 
 
 
 
Week 248 
 
 
 
 
 
 
Week 249 
 
 
 
 
 
 
Week 250 
 
 
 
 
 
 
Week 251 
 
 
 
 
 
 
Week 252 
 
 
 
 
 
 
Week 253 
 
 
 
 
 
 
Week 254 
 
 
 
 
 
 
Week 255 
 
 
 
 
 
 
Week 256 
 
 
 
 
 
 
Week 257 
 
 
 
 
 
 
Week 258 
 
 
 
 
 
 
Week 259 
 
 
 
 
 
 
Week 260 
 
 
 
 
 
 
Week 261 
 
 
 
 
 
 
Week 262 
 
 
 
 
 
 
Week 263* 
 
 
 
 
 
* 
Week 263 dose will only be taken if on every-week dosing schedule. 
 

 
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118 
Appendix Q.  
Self Injection Instructions 
 
 
Subject Instructions 
0.8 mL or 0.4 mL dose 
(Administered as a single dose-prefilled syringe (PFS)) 
 
Protocol M06-807 
 

 
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119 
Tables of Contents 
Dosing Schedule 
General Information & Supplies 
Injection Procedures 
 

 
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120 
Study Drug Dosing Schedule 
Open-Label (PFS) 
Subject Number:_____________________________________ 
You will require subcutaneous (SC) injections throughout the study.  
Injections at scheduled study visits (Baseline, Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 
108, 120, 144, 168, 192, 216 and 240) will be done during your visit, at the doctors 
office.  On weeks between office visits, study drug will be self-administered at home by 
you or someone trained to give you the injections. 
One pre-filled syringe will contain 0.8 mL of liquid.  The total available dose is 0.8 mL. 
The drug should be administered in one (1) SC injection, on the same day of the week for 
each dose. 
Please return all used and unused syringes to the clinic on your next visit. Used syringes 
should be placed in the special sharps container provided. All unused syringes should be 
returned in the original box. 
If an injection is missed or something occurs where the full dose cannot be injected, 
contact your study center immediately for further instructions. Please record any missed 
doses on your subject diary. 
Remember to complete your dosing diary after each injection and to call the doctors 
office if you are having problems administering your study drug. 

 
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121 
General Information 
 
 
 
 
 
 
 
PFS 
● Prefilled syringes will be labeled "adalimumab." 
● Store all adalimumab prefilled syringes in your refrigerator NOT in the 
freezer.  Should the syringes accidentally become frozen, call your study 
coordinator. 
● 0.8 mL = 0.8 cc 
● Study drug should be taken at about the same time of day, on the same day of 
the week as directed by your study doctor. 
● USE A NEW SYRINGE EVERY INJECTION DAY. There may be 
medication left in the syringe. DO NOT RE-USE. 
● Save all study drugs. Prefilled syringes (used and unused) must be returned 
to the study center at each visit. Used syringes will be disposed of in a sharps 
container provided to you. 
● Whenever possible, have someone with you for at least 15 to 30 minutes after 
your injection. 
● Call your doctor IMMEDIATELY if you experience any itching, hives, 
shortness of breath, or any symptom that has you concerned. If you are unable 
to reach your doctor or if you experience life-threatening symptoms call 911, 
or proceed to your nearest emergency room. 
 

 
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122 
Injection Procedures 
 
 
 
 
 
 
 
PFS 
1. Clean your workspace, gather your supplies, and wash your hands. 
 
 
2. Identify the area on your abdomen or thigh (or upper arm 
if not self injecting). Make sure the area you choose does 
not have any redness, tenderness, swelling, bruising, or 
psoriasis. The area must also be at least 2 cm 
(approximately 1 inch) away from the previous injection 
site. IT IS VERY IMPORTANT TO CHANGE THE 
INJECTION SITE EVERY TIME!!! 
 
 
3. Using a circular motion (starting at the injection site and 
moving outward) clean the selected injection site with 
an alcohol pad. Allow skin to dry.  
4. Remove the needle cap. Do not touch the needle. Expel 
any air bubbles from the syringe by tapping on the 
syringe. If the needle becomes contaminated, discard all 
supplies and obtain a new syringe of study drug.  
5. Once the air is expelled from the syringe, the amount of 
solution in the syringe should be 0.8 mL. 
 
 
6.   Hold the syringe "like a dart" between your thumb and 
first finger close to the syringe/needle connection. 

 
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123 
 
 
 
 
 
 
 
 
PFS 
 
7. With your other hand, pinch the skin around the 
injection site, forming a bulge in the skin. 
 
 
 
 
 
 
8. Insert the needle into the skin at a 45-degree angle. 
Release pinched skin. 
 
 
 
 
9. 
GENTLY pull back on the syringe plunger. If blood 
appears, withdraw needle - DO NOT INJECT! Contact 
your study center immediately for further instructions. 
 
10. Inject drug by pushing slowly on syringe plunger with 
thumb. 
 
11. Remove needle while maintaining a 45-degree angle. 
 
12. You may apply a Band-Aid over the injection site and 
apply gentle pressure, if necessary. DO NOT RUB 
SITE. 
 
13. 
DO NOT RECAP NEEDLE. DO NOT SEPARATE THE NEEDLE FROM THE 
 
SYRINGE BEFORE DISPOSING. Discard used syringes into Sharps Container. 
EACH TIME THAT YOU GIVE YOURSELF AN INJECTION OF STUDY DRUG, 
REMEMBER TO RECORD THE INFORMATION ON YOUR SUBJECT DOSING 
DIARY. 
 

 
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Appendix R.  
Standard Weights 
 
 

 
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EudraCT 2007-006494-90 
 
 
125 
 
 

 
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126 
Appendix S.  
Subject Abbott Laboratories Site Drug Accountability Form 
 

 
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127 
Appendix T.  
Work Productivity and Activity Impairment Questionnaire: 
Crohns Disease (WPAI-CD) - Caregiver 
The following questions ask about the effect of your childs Crohns disease on your ability 
to work and perform regular activities.  Please fill in the blanks or circle a number, as 
indicated. 
1.  Are you currently employed (working for pay)?  
_____ NO ___ YES 
  If NO, check "NO" and skip to question 6. 
The next questions are about the past seven days, not including today. 
 
 
2. During the past seven days, how many hours did you miss from work because of 
problems associated with your childs Crohns disease?  Include hours you missed on 
sick days, times you went in late, left early, etc., because of your childs Crohns 
disease.  Do not include time you missed for your child to participate in this study. 
 
_____ HOURS 
 
3. During the past seven days, how many hours did you miss from work because of any 
other reason, such as vacation, holidays, time off for your child to participate in this 
study? 
 
_____HOURS 
 
4. During the past seven days, how many hours did you actually work? 
 
_____HOURS  (If "0," skip to question 6.) 
 

 
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128 
5. During the past seven days, how much did your childs Crohns disease affect your 
productivity while you were working?   
 
Think about days you were limited in the amount or kind of work you could do, days 
you accomplished less than you would like, or days you could not do your work as 
carefully as usual.  If your childs Crohns disease affected your work only a little, 
choose a low number.  Choose a high number if your childs Crohns disease affected 
your work a great deal.   
Consider only how much your childs Crohns disease affected  
your productivity while you were working. 
 
 
 
 
 
 
 
 
 
 
 
My childs Crohns 
disease had no 
effect on my work 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
My childs Crohns 
disease completely 
prevented me from 
working 
CIRCLE A NUMBER 
6. During the past seven days, how much did your childs Crohns Disease affect your 
ability to do your regular daily activities, other than work at a job?   
 
By regular activities, we mean the usual activities you do, such as work around the 
house, shopping, childcare, exercising, studying, etc.  Think about times you were 
limited in the amount or kind of activities you could do and times you accomplished 
less than you would like.  If your childs Crohns Disease affected your activities only a 
little, choose a low number.  Choose a high number if your childs Crohns Disease 
affected your activities a great deal.   
 
Consider only how much your childs Crohns disease affected your ability  
to do your regular daily activities, other than work at a job. 
 
 
 
 
 
 
 
 
 
 
 
My childs Crohns 
disease had no 
effect on my daily 
activities 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
My childs Crohns 
disease completely 
prevented me from 
doing my daily 
activities 
 
 
                           
CIRCLE A NUMBER 
WPAI:CD-Caregiver (US English) 

 
Adalimumab 
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133 
Table 1.  Study Activities  
Previously read: 
Activity 
Baseline 
Week 4 
Week 8 
Week 12 
Week 24 
Week 36 
Week 48 
Week 60 
Week 72 
Week 84 
Week 96 
Week 108
Inclusion/exclusion criteria 
X 
 
 
 
 
 
 
 
 
 
 
 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
 
 
Previous and concomitant 
medications 
Xa 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Urine pregnancy testb 
Xa 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Vital signsc 
Xa 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Physical exam 
Xa 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
General LABd 
Xa 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Urinalysise 
Xa 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Erythrocyte sedimentation 
rate 
Xa 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
CRP 
Xa 
 
 
 
X 
 
X 
 
X 
 
 
X 
ANA 
Xa 
 
 
X 
 
 
 
 
 
 
 
X 
Anti-dsDNAf 
Xa 
 
 
X 
 
 
 
 
 
 
 
X 
PCDAI 
Xa 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
CDAIg 
Xa 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
IMPACT III Questionnaireh 
Xa 
 
 
X 
X 
 
X 
 
X 
 
 
X 
 

 
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134 
Table 1.  
Study Activities (Continued) 
Activity 
Baseline 
Week 4 
Week 8 
Week 12 
Week 24 
Week 36 
Week 48 
Week 60 
Week 72 
Week 84 
Week 96 
Week 108
Unscheduled outpatient 
visits, emergency room 
visits and hospitalizations 
questionnaire 
Xa 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Work Productivity and 
Impairment Questionnaire: 
Crohns Disease (WPAI − 
CD) 
Xa 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X-ray for bone age 
Xa 
 
 
 
 
 
X 
 
 
 
 
X 
Serum bone markers 
Xa 
 
 
 
X 
 
X 
 
X 
 
 
X 
PK Blood Sample 
 
 
 
 
X 
 
X 
 
X 
 
X 
 
Anti-adalimumab blood 
levels (AAA) 
 
 
 
 
X 
 
X 
 
X 
 
X 
 
Adverse eventsi 
Xa 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Dispense study drug 
Xa 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 

 
Adalimumab 
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135 
Table 1.  
Study Activities (Continued) 
Activity 
Week 
120 
Week 
132 
Call 
Week 
144 
Week 
156 
Call 
Week 
168 
Week 
180 
Call 
Week 
192 
Week 
204 
Call 
Week 
216 
Week 
228 
Call 
Week 
240 
Week 
252 
Call 
Week 
264/ 
Early 
Term 
Unsched 
Visit 
70-Day 
Follow-up 
Call 
Inclusion/exclusion 
criteria 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Informed consent 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Previous and concomitant 
medications 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Urine pregnancy testb 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
 
Vital signsc 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
 
Physical exam 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
 
General LABd 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
 
Urinalysise 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
 
Erythrocyte 
sedimentation rate 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
 
CRP 
 
 
X 
 
X 
 
X 
 
X 
 
 
 
X 
 
 
ANA 
 
 
X 
 
 
 
X 
 
 
 
 
 
X 
 
 
Anti-dsDNAf 
 
 
X 
 
 
 
X 
 
 
 
 
 
X 
 
 
PCDAI 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
 
CDAIg 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
 
IMPACT III 
Questionnaireh 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
 

 
Adalimumab 
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136 
Table 1.  
Study Activities (Continued) 
Activity 
Week 
120 
Week 
132 
Call 
Week 
144 
Week 
156 
Call 
Week 
168 
Week 
180 
Call 
Week 
192 
Week 
204 
Call 
Week 
216 
Week 
228 
Call 
Week 
240 
Week 
252 
Call 
Week 
264/ 
Early 
Term 
Unsched 
Visit 
70-Day 
Follow-up 
Call 
Unscheduled outpatient 
visits, emergency room 
visits and 
hospitalizations 
questionnaire 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Work Productivity and 
Impairment 
Questionnaire: Crohns 
Disease  (WPAI − CD) 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
 
X-ray for bone age 
 
 
X 
 
 
 
X 
 
 
 
 
 
X 
X 
 
Serum bone markers 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
 
PK Blood Samplei 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
 
Anti-adalimumab blood 
levels (AAA)i 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
 
Adverse eventsj 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Dispense study drug 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
 
Xk 
 
 

 
Adalimumab 
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137 
Table 1.  
Study Activities (Continued) 
a. 
At the Baseline Visit, the following procedures will be completed as part of Week 52 of the M06-806 study. 
b. 
Performed on all females of child-bearing potential - Urine pregnancy test at all study visits. 
c. 
Vital sign determinations of height, weight, sitting blood pressure, heart rate, respiratory rate, and body temperature will be obtained at each visit. 
d. 
Blood draws should be performed after questionnaire and vital signs determinations and before study drug administration. 
e. 
Microscopic urinalysis will be performed at any visit if dipstick UA is abnormal (protein greater than a trace, blood greater than 5-10 Ery/ul, moderate or large ketone count 
or glucose greater than 50 mg/dL). 
f.  
If an ANA result is positive, anti-dsDNA will be performed automatically. 
g.  For subjects who are age 13 or older at the M06-807 Baseline Visit, a CDAI will be completed at each visit. 
h. 
For subjects who are age 10 or older at the M06-807 Baseline Visit, an IMPACT III Assessment will be completed at Baseline, Weeks 12, 24, 48, 72, 108, 144, 168, 192, 216, 
240 and 264/ET. 
i. 
In addition to blood draws every 24 weeks, PK and AAA blood draws to be performed if subject meets flare criteria and dose escalated to ew dosing. 
j. 
All AEs, including SAEs, will be captured throughout the study from the time that the subject signs the Informed Consent Form. SAEs will be captured throughout the 70 day 
follow-up period (if applicable). 
k. 
If an unscheduled visit is performed to change the frequency of study drug from OL eow to OL ew, study drug may be dispensed. 
 

 
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138 
Has been changed to read: 
Activity 
Baseline 
Week 4 
Week 8 
Week 12 
Week 24 
Week 36 
Week 48 
Week 60 
Week 72 
Week 84 
Week 96 
Week 108
Inclusion/exclusion criteria 
X 
 
 
 
 
 
 
 
 
 
 
 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
 
 
Previous and concomitant 
medications 
Xa 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Urine pregnancy testb 
Xa 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Vital signsc 
Xa 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Physical exam 
Xa 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
General LABd 
Xa 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Urinalysise 
Xa 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Erythrocyte sedimentation 
rate 
Xa 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
CRP 
Xa 
 
 
 
X 
 
X 
 
X 
 
 
X 
ANA 
Xa 
 
 
X 
 
 
 
 
 
 
 
X 
Anti-dsDNAf 
Xa 
 
 
X 
 
 
 
 
 
 
 
X 
PCDAI 
Xa 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
CDAIg 
Xa 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
IMPACT III Questionnaireh 
Xa 
 
 
X 
X 
 
X 
 
X 
 
 
X 
 

 
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139 
Table 1.  
Study Activities (Continued) 
Activity 
Baseline 
Week 4 
Week 8 
Week 12 
Week 24 
Week 36 
Week 48 
Week 60 
Week 72 
Week 84 
Week 96 
Week 108
Unscheduled outpatient 
visits, emergency room 
visits and hospitalizations 
questionnaire 
Xa 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Work Productivity and 
Impairment Questionnaire: 
Crohns Disease (WPAI − 
CD) 
Xa 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X-ray for bone agei 
Xa 
 
 
 
 
 
X 
 
 
 
 
X 
Serum bone markers 
Xa 
 
 
 
X 
 
X 
 
X 
 
 
X 
PK Blood Samplej 
 
 
 
 
X 
 
X 
 
X 
 
X 
 
Anti-adalimumab blood 
levels (AAA)j 
 
 
 
 
X 
 
X 
 
X 
 
X 
 
Adverse eventsk 
Xa 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Dispense study drug 
Xa 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 

 
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Table 1.  
Study Activities (Continued) 
Activity 
Week 
120 
Week 
132 
Call 
Week 
144 
Week 
156 
Call 
Week 
168 
Week 
180 
Call 
Week 
192 
Week 
204 
Call 
Week 
216 
Week 
228 
Call 
Week 
240 
Week 
252 
Call 
Week 
264/ 
Early 
Term 
Unsched 
Visit 
70-Day 
Follow-up 
Call 
Inclusion/exclusion 
criteria 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Informed consent 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Previous and concomitant 
medications 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Urine pregnancy testb 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
 
Vital signsc 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
 
Physical exam 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
 
General LABd 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
 
Urinalysise 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
 
Erythrocyte 
sedimentation rate 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
 
CRP 
 
 
X 
 
X 
 
X 
 
X 
 
 
 
X 
 
 
ANA 
 
 
X 
 
 
 
X 
 
 
 
 
 
X 
 
 
Anti-dsDNAf 
 
 
X 
 
 
 
X 
 
 
 
 
 
X 
 
 
PCDAI 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
 
CDAIg 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
 
IMPACT III 
Questionnaireh 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
 

 
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Table 1.  
Study Activities (Continued) 
Activity 
Week 
120 
Week 
132 
Call 
Week 
144 
Week 
156 
Call 
Week 
168 
Week 
180 
Call 
Week 
192 
Week 
204 
Call 
Week 
216 
Week 
228 
Call 
Week 
240 
Week 
252 
Call 
Week 
264/ 
Early 
Term 
Unsched 
Visit 
70-Day 
Follow-up 
Call 
Unscheduled outpatient 
visits, emergency room 
visits and 
hospitalizations 
questionnaire 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Work Productivity and 
Impairment 
Questionnaire: Crohns 
Disease  (WPAI − CD) 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
 
X-ray for bone agei 
 
 
X 
 
 
 
X 
 
 
 
 
 
X 
 
 
Serum bone markersi 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
 
PK Blood Samplej 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
 
Anti-adalimumab blood 
levels (AAA)j 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
 
Adverse eventsk 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Dispense study drug 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
 
Xl 
 
 

 
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Table 1.  
Study Activities (Continued) 
a. 
At the Baseline Visit, the following procedures will be completed as part of Week 52 of the M06-806 study. 
b. 
Performed on all females of child-bearing potential - Urine pregnancy test at all study visits. 
c. 
Vital sign determinations of height, weight, sitting blood pressure, heart rate, respiratory rate, and body temperature will be obtained at each visit. 
d. 
Blood draws should be performed after questionnaire and vital signs determinations and before study drug administration. 
e. 
Microscopic urinalysis will be performed at any visit if dipstick UA is abnormal (protein greater than a trace, blood greater than 5-10 Ery/ul, moderate or large ketone count 
or glucose greater than 50 mg/dL). 
f.  
If an ANA result is positive, anti-dsDNA will be performed automatically. 
g.  For subjects who are age 13 or older at the M06-807 Baseline Visit, a CDAI will be completed at each visit. 
h. 
For subjects who are age 10 or older at the M06-807 Baseline Visit, an IMPACT III Assessment will be completed at Baseline, Weeks 12, 24, 48, 72, 108, 120, 144, 168, 192, 
216, 240, 264/ET and unscheduled visits. 
i. 
If the height velocity is 0 and, in the opinion of the investigator, a subject is no longer growing, the x-ray for bone age and the determination of serum bone markers can be 
omitted. 
j. 
In addition to blood draws every 24 weeks, PK and AAA blood draws to be performed if subject meets flare criteria and dose escalated to ew dosing. 
k. 
All AEs, including SAEs, will be captured throughout the study from the time that the subject signs the Informed Consent Form.  SAEs will be captured throughout the 70 day 
follow-up period (if applicable). 
l. 
If an unscheduled visit is performed to change the frequency of study drug from OL eow to OL ew, study drug may be dispensed. 
 
 

 
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Section 5.3.2  Drug Concentration Measurements 
First paragraph, fourth sentence previously read: 
At each visit, blood samples will be collect prior to study drug administration at each 
visit. 
Has been changed to read: 
At each visit, blood samples will be collected prior to study drug administration at each 
visit. 
Section 8.1.5  Interim Analysis 
Previously read: 
There are no planned interim analyses. 
Has been changed to read: 
There will be one planned interim analysis.  Details of the analysis will be described in 
the study SAP. 
Appendix B.  List of Protocol Signatories 
Previously read: 
Name 
Title 
Functional Area 
Statistics 
Clinical 
Clinical 
Clinical 
 

 
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Has been changed to read: 
Name 
Title 
Functional Area 
Statistics 
Clinical 
Clinical 
Clinical 
 
Appendix P.  Subject Dosing Diary 
Diary "Week 241 - Week 263" 
Footnote previously read: 
*  Week 259 dose will only be taken if on every-week dosing schedule. 
Has been changed to read: 
*  Week 263 dose will only be taken if on every-week dosing schedule. 

 
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1.0 
Title Page 
CLINICAL TRIAL PROTOCOL M06-807 
A Multi-center, Open-label Study of the Human 
Anti−TNF Monoclonal Antibody Adalimumab to 
Evaluate the Efficacy and the Long-term Safety and 
Tolerability of Repeated Administration of 
Adalimumab in Pediatric Subjects with 
Crohn's Disease Who Have Demonstrated a Clinical 
Response in the M06-806 Study 
Incorporating Administrative Changes 1 and 2, 
Amendment 1, Administrative Changes 3, 4, 5 and 6, 
and Amendment 2 
Abbott Number /  
 Investigational Product: 
 
Adalimumab 
Date:  
26 August 2010 
Development Phase: 
3 
Study Design:  
A multi-center, open-label safety and tolerability pediatric study in the 
United States, Canada and Europe. 
EudraCT Number:  
2007-006494-90 
Investigator: 
Multicenter (Investigator information on file at Abbott Laboratories). 
Sponsor: 
European Union Countries: 
Abbott GmbH & Co.KG  
Knollstrasse 50 
67061 Ludwigshafen  Germany 
Non European Union Countries: 
Abbott Laboratories, US  
100 Abbott Park Road 
Abbott Park  IL 60064 
Emergency Contact: 
This study will be conducted in compliance with the protocol, Good Clinical Practice and all other 
applicable regulatory requirements, including the archiving of essential documents. 
Confidential Information 
No use or disclosure outside Abbott is permitted without prior written authorization from Abbott. 

 
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1.1 
Protocol Amendment:  Summary of Changes 
The purpose of this amendment is to: 
● Add blood sample collections for adalimumab concentration and 
anti-adalimumab antibody (AAA) assays.  PK and AAA was analyzed as part 
of Study M06-806.  Additional PK and AAA collection from long-term 
treatment in these subjects will be used for further analysis of 
pharmacokinetic and safety data in pediatric CD patients. 
● Change the stopping criteria for study based on discussion and 
recommendation by the DMC members.  Stoppage of the study will be 
assessed at each meeting by the DMC but there will be no stringent criteria 
since the subjects are no longer blinded (due to completion of M06-806 
study). 
● Add subject visits through Week 264 and provision for study to continue until 
local regulatory approval.  Extension of this open-label study is necessary to 
allow for continued collection of long-term safety and efficacy information on 
these pediatric CD subjects. 
● Incorporate Administrative Changes 3 through 6 into this protocol. 
● Added new required template for protocol signatories (Appendix B). 
 
An itemized list of all changes made to the protocol under this amendment can be found 
in Appendix U. 

 
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2.0 
Table of Contents 
1.0 
Title Page .................................................................................1 
1.1 
Protocol Amendment:  Summary of Changes...........................................2 
2.0 
Table of Contents....................................................................3 
3.0 
Introduction.............................................................................8 
4.0 
Study Objective .....................................................................14 
5.0 
Investigational Plan ..............................................................14 
5.1 
Overall Study Design and Plan:  Description..........................................14 
5.2 
Selection of Study Population .................................................................18 
5.2.1 
Inclusion Criteria.....................................................................................18 
5.2.2 
Exclusion Criteria....................................................................................19 
5.2.3 
Prior and Concomitant Therapy ..............................................................21 
5.2.3.1 
Prior Therapy...........................................................................................21 
5.2.3.2 
Concomitant Therapy..............................................................................22 
5.2.3.3 
Rescue Therapy .......................................................................................23 
5.2.3.4 
Prohibited Therapy ..................................................................................23 
5.3 
Efficacy, and Safety Assessments/Variables...........................................23 
5.3.1 
Efficacy and Safety Measurements Assessed and Flow Chart................23 
5.3.1.1 
Study Procedures.....................................................................................29 
5.3.2 
Drug Concentration Measurements.........................................................36 
5.3.2.1 
Collection of Samples for Analysis.........................................................37 
5.3.2.2 
Handling/Processing of Samples.............................................................37 
5.3.2.3 
Disposition of Samples............................................................................38 
5.3.2.4 
Measurement Methods ............................................................................38 
5.3.3 
Efficacy Variables ...................................................................................38 
5.3.4 
Safety Variables.......................................................................................39 
5.3.5 
Pharmacokinetic Variables......................................................................39 

 
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5.4 
Removal of Subjects from Therapy or Assessment ................................39 
5.4.1 
Discontinuation of Individual Subjects ...................................................39 
5.4.2 
Discontinuation of Entire Study ..............................................................40 
5.4.3 
Stopping Rules.........................................................................................40 
5.5 
Treatments ...............................................................................................41 
5.5.1 
Treatments Administered ........................................................................41 
5.5.2 
Identity of Investigational Product ..........................................................41 
5.5.2.1 
Packaging and Labeling ..........................................................................42 
5.5.2.2 
Storage and Disposition of Study Drug...................................................43 
5.5.3 
Method of Assigning Subjects to Treatment Groups ..............................43 
5.5.4 
Selection and Timing of Dose for Each Subject .....................................44 
5.5.5 
Blinding...................................................................................................44 
5.5.6 
Treatment Compliance ............................................................................45 
5.5.7 
Drug Accountability................................................................................45 
5.6 
Discussion and Justification of Study Design .........................................46 
5.6.1 
Discussion of Study Design and Choice of Control Groups...................46 
5.6.2 
Appropriateness of Measurements ..........................................................46 
5.6.3 
Suitability of Subject Population.............................................................46 
5.6.4 
Selection of Doses in the Study...............................................................46 
6.0 
Adverse Events......................................................................47 
6.1 
Definitions...............................................................................................47 
6.1.1 
Adverse Event .........................................................................................47 
6.1.2 
Serious Adverse Events...........................................................................48 
6.2 
Adverse Event Severity...........................................................................49 
6.3 
Relationship to Study Drug .....................................................................49 
6.4 
Adverse Event Collection Period ............................................................50 
6.5 
Adverse Event Reporting ........................................................................50 

 
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6.5.1 
Collection of Data Regarding Known Manifestations of the 
Disease Under Study ...............................................................................51 
6.6 
Pregnancy ................................................................................................51 
7.0 
Protocol Deviations...............................................................52 
8.0 
Statistical Methods and Determination of Sample 
Size..........................................................................................53 
8.1 
Statistical and Analytical Plans ...............................................................53 
8.1.1 
Analyzable Population.............................................................................53 
8.1.2 
Planned Methods of Statistical Analysis .................................................53 
8.1.2.1 
Demographics and Baseline Characteristics ...........................................54 
8.1.2.2 
Primary Efficacy Analysis.......................................................................54 
8.1.3 
Other Analyses ........................................................................................54 
8.1.4 
Safety Analyses .......................................................................................54 
8.1.4.1 
Pharmacokinetic Analyses.......................................................................55 
8.1.5 
Interim Analysis ......................................................................................56 
8.2 
Determination of Sample Size.................................................................56 
8.3 
Randomization Methods..........................................................................56 
9.0 
Ethics......................................................................................56 
9.1 
Independent Ethics Committee (IEC) or Institutional Review 
Board (IRB).............................................................................................56 
9.2 
Ethical Conduct of the Study...................................................................57 
9.3 
Subject Information and Consent ............................................................57 
10.0 
Source Documents and Case Report Form 
Completion.............................................................................58 
10.1 
Source Documents...................................................................................58 
10.2 
Case Report Forms ..................................................................................58 
11.0 
Data Quality Assurance........................................................59 
12.0 
Use of Information and Publication....................................60 
12.1 
Use of Information ..................................................................................60 

 
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12.2 
Internet Sites............................................................................................61 
13.0 
Completion of the Study.......................................................61 
14.0 
Investigator's Agreement .....................................................63 
15.0 
Reference List........................................................................64 
 
List of Tables 
Table 1.  
Study Activities .......................................................................................24 
Table 2.  
Clinical Laboratory Tests ........................................................................32 
Table 3.  
Identity of Investigational Products.........................................................42 
Table 4.  
Study Drug Packaging and Administration.............................................43 
 
List of Figures 
Figure 1.  
Study Schematic ......................................................................................17 
Figure 2.  
Adverse Event Collection........................................................................50 
 
List of Appendices 
Appendix A.  
List of Abbreviations and Definition of Terms .......................................68 
Appendix B.  
List of Protocol Signatories.....................................................................70 
Appendix C.  
Documents Required Prior to Initiation of the Study..............................71 
Appendix D.  
Responsibilities of the Clinical Investigator............................................73 
Appendix E.  
CDC Treatment of Tuberculosis Infection (Preventive Therapy)...........75 
Appendix F.  
Non-Drug Materials Provided to the Study Site(s) .................................77 
Appendix G.  
Pediatric Crohn's Disease Activity Index (PCDAI) ................................78 
Appendix H.  
PCDAI User's Guide and Guideline for Reference Weight and 
Reference Height.....................................................................................80 
Appendix I.  
Crohn's Disease Activity Index (CDAI)..................................................86 
Appendix J.  
Subject CDAI Diary ................................................................................87 
Appendix K.  
IMPACT III Questionnaire......................................................................88 

 
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Appendix L.  
Excluded Medications .............................................................................96 
Appendix M.  Day 70 Phone Call...................................................................................97 
Appendix N.  
Unscheduled Outpatient Visits, Emergency Room Visits and 
Hospitalizations .......................................................................................98 
Appendix O.  
Subject Medication Log ..........................................................................99 
Appendix P.  
Subject Dosing Diary ............................................................................100 
Appendix Q.  
Self Injection Instructions......................................................................118 
Appendix R.  
Standard Weights...................................................................................124 
Appendix S.  
Subject Abbott Laboratories Site Drug Accountability Form...............126 
Appendix T.  
Work Productivity and Activity Impairment Questionnaire: 
Crohn's Disease (WPAI-CD) - Caregiver..............................................127 
Appendix U.  
Protocol Amendment:  List of Changes ................................................129 
 

 
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8 
3.0 
Introduction 
Crohn's Disease (CD) is a chronic, debilitating, and currently incurable inflammatory 
disease that can affect the entire digestive system as well as extraintestinal organs.  CD is 
primarily manifested by focal asymmetric, transmural, and occasionally, granulomatous 
inflammation affecting any segment of the gastrointestinal tract1 which can consist of 
mucosal edema, aphthous and linear ulcerations, asymmetrical narrowing and strictures.  
Noncaseating granulomas are virtually diagnostic in the correct clinical setting.  The most 
commonly involved area of the bowel is the small bowel, particularly the distal ileum, 
which is involved in 70% of cases often in combination with colitis, occurring in 50% of 
cases.  Extraintestinal manifestations can also occur, and include symptoms of joint, 
ocular and hepatic inflammation.  Genetic, geographic, ethnic, and environmental risk 
factors have all been described, but the basic etiology of the disease remains unknown. 
The incidence in North America is similar to that in other western nations and is 
estimated from 3.1 to 14.6 cases per 100,000 person years and prevalence ranges from 
26 to 199 cases per 100,000 persons.2  The disease can affect persons of any age but the 
most common age of onset is in the second and third decades with a female 
preponderance.  While predominantly a disease of adults, approximately 10% to 15% of 
CD cases are diagnosed before adulthood.3 
In addition, the incidence of CD in patients less than 18 years of age appears to be 
increasing in both North America and Europe.4,5  Reported incidence rates range from 
1.2 to 4.9 per 100,000 persons in the UK, Europe, and North America6-12 with one study 
reporting an incidence of 4.6 per 100,000 persons in the United States.5  CD has been 
reported at all ages but is rare in early childhood.  In one study of patients with CD, 
17 years of age and younger, 9.1% of the patients were diagnosed before the age of 6.13  
In a second study of patients diagnosed with CD before the age of 15, 7.5% of the 
patients were under the age of 5.14 
Despite obvious physiologic and development differences, the presentation of CD in the 
pediatric population is generally similar to that seen in older patients and is 

 
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9 
heterogeneous with regard to anatomic localization and clinical severity.5,15,16  The 
unique aspect of this disease in children is its impact on nutrition and growth, with 
marked growth retardation being a prominent component of the disease in this age 
group.17-19  The use of accepted methodologies for assessing nutritional status, including 
the anthropometric measures of height, weight, triceps skin fold thickness and mid arm 
circumference as well as linear growth (height velocity and assessment of height velocity 
for chronological age "z-score") have documented the growth impairment that can occur 
in this age group, and also have been used to assess the efficacy of interventions.20  
Profound impairment of bone formation and increased bone resorption are associated 
complications and are related to the effect of glucocorticoids,21,22 delayed puberty,22,23 
decreased mobility,24 as well as to the effects of cytokines on bone formation.25 
Initial symptoms are often subtle, and there is an average delay of almost six months 
between onset of symptoms and diagnosis.  The most common presentation is with 
abdominal pain, diarrhea, loss of appetite and weight loss.  However, isolated weight 
loss, anorexia, perianal disease and extraintestinal manifestations can occur in the 
absence of GI symptoms in a substantial number of patients. 
The general approach to the treatment of CD in children is similar to adults with the goals 
being induction and maintenance of remission, prevention of relapse and hospitalizations, 
improved quality of life, and avoidance of disease and drug related complications.  
Restoration and/or preservation of normal growth and pubertal development are 
additional therapeutic goals.  The medical armamentarium is likewise similar to adults 
and includes induction of remission with corticosteroids, and ongoing maintenance 
therapy of immunomodulators, aminosalicylates and nutritional therapy.  Anti-tumor 
necrosis factor (TNF) therapy with infliximab has been evaluated for the therapy of CD 
in this age group as it has in adults.  The FDA and EMEA have recently approved 
Infliximab for use in children with CD. 
Adalimumab is a recombinant human immunoglobulin (IgG1) monoclonal antibody 
exclusively containing human peptide sequences.  It is produced by recombinant 
deoxyribonucleic acid (DNA) technology in a mammalian cell expression system.  

 
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10 
Adalimumab consists of 1330 amino acids and has a molecular weight of approximately 
148 kilodaltons.  It binds specifically with high affinity to the soluble and transmembrane 
forms of TNFD and inhibits the binding of TNFD with its receptors. 
TNF is a naturally occurring cytokine that is involved in normal inflammatory and 
immune responses.  Elevated levels of TNF play an important role in pathologic 
inflammation.  Adalimumab binds specifically to TNF and neutralizes the biological 
function of TNF by blocking its interaction with the p55 and p75 cell surface TNF 
receptors. 
Adalimumab was first approved for treatment of rheumatoid arthritis (RA) on 
31 Dec 2002 in the United States (US), on 08 Sep 2003 in the European Union (EU) and 
through August 2008 in a total of 76 countries.  Indication extensions to include 
treatment of psoriatic arthritis and early RA were granted in the EU on 01 Aug 2005 and 
in the US on 03 Oct 2005.  A further indication extension to include treatment of 
ankylosing spondylitis was approved in the EU on 01 Jun 2006 and was approved in the 
US on 28 Jul 2006.  Adalimumab was approved for the treatment of Crohn's disease in 
the United States on 27 Feb 2007, in the European Union on 04 Jun 2007 and in Canada 
on 05 July 2007 for the adult population.  In December 2007 and January 2008, 
respectively, adalimumab was approved for the treatment of psoriasis in adult patients in 
the EU, Canada and USA.  Additionally, adalimumab was approved for the treatment of 
juvenile idiopathic arthritis in the USA in February 2008. 
Adalimumab has been shown to be a safe and effective treatment of moderately to 
severely active Crohn's disease.  In the CD development program, adalimumab was 
studied in over 1400 adult subjects in three pivotal studies (two induction studies and a 
maintenance study). 
Study M02-403 was a multicenter, randomized, double-blind, placebo-controlled 
Phase 2/3 study to evaluate the efficacy and safety of adalimumab for the induction of 
remission in subjects with moderate to severe CD.26  A total of 299 subjects were 
randomized to receive one of four proposed induction treatment regimens (three active 

 
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11 
treatment groups or placebo):  adalimumab 160 mg at Baseline (Week 0) followed by 
80 mg at Week 2, adalimumab 80 mg at Baseline followed by 40 mg at Week 2, 
adalimumab 40 mg at Baseline followed by 20 mg at Week 2 or placebo at Baseline and 
Week 2.  Eligible subjects could not have been previously treated with any anti TNF 
agent.  Only the group of subjects treated with adalimumab 160/80 mg had a statistically 
significantly greater remission rate at Week 4 (primary endpoint) compared to placebo 
(35.5% vs. 12.2%; p = 0.001).  In addition, statistically significantly greater proportions 
of subjects in the adalimumab 160/80 mg group than in the placebo group experienced 
clinical response CR-100 (48.7% and 24.3%, respectively) and clinical response CR-70 
(57.9% and 36.8%, respectively) at Week 4. 
Study M04-691, a second induction study, was a multicenter, randomized, double-blind, 
placebo-controlled, Phase 3 study to evaluate the efficacy and safety of adalimumab as 
induction treatment for subjects with moderate to severe CD who either initially 
responded to administration of infliximab but stopped responding or were intolerant.27  
A total of 325 subjects were randomized to receive adalimumab 160/80 mg or placebo.  
Eligible subjects must have previously been treated with infliximab and discontinued use 
due to loss of response to or intolerance to infliximab therapy.  The proportion of subjects 
who achieved clinical remission at Week 4 (primary endpoint) was statistically 
significantly greater in the adalimumab 160/80 mg group compared to the placebo group 
(21.4% vs. 7.2%).  The proportion of subjects achieving clinical response CR-100 and 
CR-70 at Week 4 was statistically significantly greater in the adalimumab 160/80 mg 
group (38.4% and 51.6%, respectively) compared to the placebo group (24.7% and 
33.7%, respectively). 
Study M02-404 was a multicenter, randomized, double-blind, placebo-controlled Phase 3 
study to assess the efficacy and safety of adalimumab for the maintenance of clinical 
remission in subjects with moderate to severe CD.27  A total of 854 subjects (both naïve 
to or previously treated with TNF antagonists [primarily infliximab]) were enrolled and 
received open-label adalimumab 80 mg at Baseline (Week 0) and adalimumab 40 mg at 
Week 2.  At Week 4, subjects were stratified by responder status (subjects who achieved 

 
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12 
clinical response CR-70) and previous anti-TNF use and were randomized in a 1:1:1 ratio 
to one of three blinded treatment groups:  adalimumab 40 mg every week (ew), 
adalimumab 40 mg every other week (eow), or placebo.  Subjects who met clinical 
response CR-70 after Week 8 could be tapered from corticosteroids. 
The proportion of Week 4 responders (N = 499) who achieved clinical remission at 
Weeks 26 and 56 (co-primary endpoint) were statistically significantly greater in the 
adalimumab 40 mg eow (39.5% and 36.0%, respectively) and 40 mg ew (46.5% and 
41.4%, respectively) groups compared to the placebo group (17.1% and 11.8%, 
respectively).  The differences between the adalimumab 40 mg eow and 
adalimumab 40 mg ew groups at both of these time points were not statistically 
significant.  The median time in first clinical remission was greater in the adalimumab 
40 mg eow group (378 days) compared to the placebo group (127 days).  The median 
time in remission could not be estimated in the adalimumab 40 mg ew group because 
more than 50% remained in clinical remission at the end of the study.  Approximately six 
times as many subjects treated with adalimumab maintenance therapy compared to 
placebo were able to discontinue corticosteroids for at least 90 days and achieve 
remission at Week 26 and Week 56.  Efficacy was independent of Baseline C-reactive 
protein (CRP), concomitant therapies, such as corticosteroids or immunosuppressants, or 
prior anti-TNF experience.  The adalimumab safety profile in CD was similar to that seen 
in the other rheumatologic populations previously studied, except for expected 
manifestations of CD. 
Currently, there are two ongoing extension studies of adalimumab therapy in adult 
subjects with CD.  M04-690 trial is a long-term safety and tolerability study of repeated 
administration of adalimumab in adult subjects with CD who had previously participated 
in M02-404 or M04-691.  The other trial is a long-term open-label extension study 
following the initial first-year study period of the M02-433 study. 
The efficacy and safety of adalimumab in children has recently been demonstrated in 
juvenile rheumatoid arthritis (JRA).28  One hundred and seventy-one pediatric patients 
(4 to 17 years of age) were initially enrolled into a 16-week open label segment and 

 
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133 subjects continued in a 32-week double blind segment.  Clinically significant 
improvements were noted in ACR30, ACR50 and ACR70 as well as other indices of 
arthritis activity.  Adverse events (AEs) were similar as those noted in adult RA patients.  
There were no deaths, malignancies, or opportunistic infections, including tuberculosis 
(TB).  Thirteen serious adverse events (SAEs) in 8 subjects were observed in the 16-week 
open label portion of the study.  These included 4 subjects with JRA, one patient with 
two episodes of leukopenia/neutropenia, and one case each of femur fracture, herpes 
simplex, and pneumonia.  Six SAEs were observed in 6 subjects (2 placebo, 
4 adalimumab) during the 32-week double blind portion (closed head injury, 
gastroduodenitis, retinal detachment, appendicitis, abdominal pain and urinary tract 
infection).  Infections, AEs at least possibly related to study drug, and injection site 
reactions were reported by similar proportions of patients in all treatment groups during 
the double-blind therapy (32 weeks). 
Fatalities, serious infections, and sepsis have been reported with the use of TNF 
antagonists.  Many of the serious infections have occurred in subjects on concomitant 
immunosuppressive therapy that, in addition to their underlying immune disorder, could 
predispose them to infections.  TB has also been observed in subjects treated with TNF 
antagonists, including adalimumab.  The event rate for TB in the CD development 
program is consistent with the global adalimumab rate.29 
TNF antagonists, including adalimumab, have been associated with cases of malignancy 
and demyelinating disease.  Serious allergic adverse reactions have been reported in RA 
subjects following subcutaneous (SC) administration of adalimumab; none were reported 
in the CD program. 
A detailed discussion of the pre-clinical toxicology, metabolism, pharmacology, and 
safety experience can be found in the current Investigator's Brochure. 
The goal of this study is to demonstrate the efficacy of adalimumab in the maintenance of 
clinical response and to demonstrate the long-term safety and tolerability of repeated 
administration of adalimumab in pediatric subjects with Crohn's disease.  The subject 

 
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population will consist of subjects who participated in and successfully completed the 
M06-806 study and who meet all the inclusion and none of the exclusion criteria of 
Protocol M06-807.  Qualifying subjects will administer open-label adalimumab by SC 
injection.  Subjects receiving every other weekly therapy who continue to have a disease 
flare or develop another flare may be switched to every week therapy at the investigator's 
discretion.  Subjects receiving weekly therapy who continue to have a disease flare or 
develop another flare may be withdrawn from the study at the Investigator's discretion.  
For a detailed description of the study please see Section 5.0. 
4.0 
Study Objective 
The objective of the study is to evaluate the long-term maintenance of clinical response, 
safety and tolerability of repeated administration of adalimumab in pediatric subjects 
with Crohn's disease who participated in, and successfully completed, Protocol M06-806 
through Week 52 and who meet all the inclusion and none of the exclusion criteria of 
Protocol M06-807. 
5.0 
Investigational Plan 
5.1 
Overall Study Design and Plan:  Description 
This study is a multi-center, open-label study of the human anti-TNF monoclonal 
antibody adalimumab.  Approximately 31 sites that have enrolled subjects in the 
M06-806 clinical trial will participate in the M06-807 clinical trial.  Approximately 
130 pediatric subjects were expected to enroll in this study; final enrollment was 
100 subjects.   
The Week 52 visit from the M06-806 study will be the Baseline Visit for those subjects 
entering study M06-807.  The visit window for M06-806 Week 52 visit is 364 ± 7 days 
from the Baseline Visit date of M06-806. 
Subjects may be allowed to enroll in the M06-807 study if they have participated in, and 
successfully completed Protocol M06-806 through Week 52.  A subject must be a 

 
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responder at any time point during the M06-806 study.  A responder is defined as a 
subject who had a PCDAI score that was at least 15 points lower than the M06-806 
baseline score. 
All subjects will be on open-label maintenance therapy.  Subjects who enroll into the 
study from blinded therapy in Study M06-806 will receive open-label therapy at a dose 
dependent on their body weight.  Subjects who weigh t 40 kg at Baseline will receive 
40 mg eow of adalimumab, while subjects who weigh < 40 kg at Baseline will receive 
20 mg eow of adalimumab.  Beginning at Week 8, subjects who have a disease flare may 
be switched to ew treatment at the same dose of adalimumab received while on eow 
treatment.  A disease flare is defined as an increase in the Pediatric Crohn's Disease 
Activity Index (PCDAI) of t 15 points when compared to the PCDAI score obtained at 
the subject's previous visit. 
Subjects who enroll into the study from open-label therapy in Study M06-806 will 
continue to receive the same dose they were receiving (i.e. 40 mg ew or 20 mg ew) at the 
Week 52 visit of the M06-806 study.  
Subjects who develop a flare while receiving ew open-label therapy or have a PCDAI 
score t 15 points when compared to their Baseline (the Week 52 visit of the M06-806 
study) PCDAI score (regardless of study visit), may be discontinued from the study at the 
discretion of the Investigator.  
Beginning from Week 8, the dose of adalimumab may be increased to 40 mg, at the 
discretion of the Investigator, for subjects whose body weight has increased from < 40 kg 
to t 40 kg from the Baseline (Week 52 of the M06-806 Study) visit.  The site will enter 
the subjects' body weight into the Interactive Voice Response System (IVRS) and the 
dose will be adjusted, if applicable.  
Reductions in concomitant therapy will be allowed for Crohn's treatment related 
toxicities (e.g., leukopenia, anemia, neuropathy) of Grade 3 or higher. 

 
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Subjects may be allowed to decrease prednisone (or equivalent) and budesonide if 
qualifications are met (please see Section 5.2.3.2 for required timing and rate of taper). 
Subjects may be allowed to adjust their Crohn's specific concomitant medications as 
specified in Section 5.2.3.2. 
The duration of the study could last up to 264 weeks (approximately 5 years).  Subjects 
who complete, or who early terminate from the study will be contacted 70 days after their 
last dose of study drug to obtain information on any ongoing and new AEs.   
This study will conclude approximately 12 weeks after the following criteria have been 
satisfied: 
● Study drug receives country and local (if applicable) regulatory approval for 
pediatric Crohn's Disease. 
● All applicable local reimbursement procedures are completed. 
 
Sites will be notified once these criteria are met. 
Following country and local (if applicable) regulatory approval and applicable local 
reimbursement approval of the study drug in a country, subjects should return to their 
next scheduled study visit as specified in the protocol.  The termination visit should be 
conducted in place of their regular scheduled study visit.  These subjects should be 
considered as having completed the study. 
A schematic of the study design is shown in Figure 1. 

 
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3. 
If female, subjects who are sexually active and are of child-bearing potential 
should be practicing an approved method of birth control throughout the study and 
for 150 days after study drug administration.  Examples of approved methods of 
birth control include the following: 
● Condoms, sponge, foam, jellies, diaphragm or intrauterine device (IUD) 
● Oral, parenteral or intravaginal contraceptives 
● A vasectomized partner 
4. 
Subject of legal age, parent or legal guardian, as required, has voluntarily signed 
and dated an Institutional Review Board (IRB)/Independent Ethics Committee 
(IEC) approved informed consent form, after the nature of the study has been 
explained and the subject of legal age, subject's parent, or legal guardian, as 
required, has had the opportunity to ask questions.  Subjects will be included in all 
discussions, and if required, their signature on an assent form will be obtained. 
5. 
Parent or legal guardian of subject who is not of legal age, as required, must be 
willing to actively supervise storage and administration of study drug and to 
ensure that the time of each dose is accurately recorded in the subject's diary. 
6. 
If a subject of legal age, must be willing to actively store, administer, and 
accurately record study drug administration in the subject diary. 
7. 
Subject is judged to be in acceptable medical condition, as determined by the 
Principal Investigator based upon results of clinical and laboratory evaluations 
done throughout the preceding Crohn's disease study M06-806. 
 
5.2.2 
Exclusion Criteria 
A subject will be excluded from the study if he/she meets any of the following criteria:  
1. 
For any reason, the subject is considered by the Investigator to be an unsuitable 
candidate for continuing therapy in the M06-807 study. 

 
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2. 
Subject has abnormal laboratory or other test results that in the opinion of the 
Investigator will make the subject unsuitable to participate in this study. 
3. 
History of cancer or lymphoproliferative disease other than a successfully and 
completely treated cutaneous squamous cell or basal cell carcinoma or 
carcinoma − in-situ of the cervix. 
4. 
History of listeriosis, histoplasmosis, chronic or active hepatitis B infection, 
human immunodeficiency virus (HIV) infection, any immunodeficiency 
syndrome, central nervous system (CNS) demyelinating disease or active TB 
(receiving treatment or not receiving treatment).  Ongoing severe infections such 
as sepsis and opportunistic infections will be exclusionary. 
5. 
Subject with known, symptomatic obstructive strictures. 
6. 
Subject who is planning surgical bowel resection at any time point while enrolled 
in the study. 
7. 
Subject who has short bowel syndrome as determined by the Investigator. 
8. 
Subject who is currently receiving total parenteral nutrition (TPN). 
9. 
Subject who is unwilling to discontinue growth hormone prior to the first dose of 
open-label study drug at the Baseline visit of M06-807. 
10. 
Female subject who is pregnant or currently breast-feeding. 
11. 
Subject with a history of clinically significant drug or alcohol abuse in the last 
year. 
12. 
Subject with a poorly controlled medical condition such as: uncontrolled diabetes, 
recurrent infections, unstable ischemic heart disease, moderate to severe heart 
failure, recent cerebrovascular accidents or any other condition which, in the 

 
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opinion of the Investigator or the Sponsor, will put the subject at risk by 
participation in the protocol. 
13. 
Subject with any prior exposure to Tysabri (natalizumab). 
14. 
Subject with a known hypersensitivity to the excipients of adalimumab as stated in 
the label. 
15. 
Subject with a previous history of dysplasia of the gastrointestinal tract. 
16. 
Subject is not in compliance with Section 5.2.3. 
 
If there are any questions regarding inclusion and exclusion criteria and/or subject 
eligibility, contact the Abbott Laboratories Medical Monitor identified in Section 7.0. 
5.2.3 
Prior and Concomitant Therapy 
5.2.3.1 
Prior Therapy 
Any medication (including over-the-counter medicines such as aspirin) that the subject is 
receiving during the study must be recorded in source documents and on the appropriate 
case report form (CRF) along with the reason for use, dates of administration and 
dosages. 
Any vaccine administered to the subject during the study should be listed as a 
concomitant medication.  Subjects should continue on the recommended vaccination 
schedule; however, vaccinations with live vaccines are prohibited.   
Any medications captured in the M06-806 CRF(s) which are ongoing will be transcribed 
onto the M06-807 source documents and CRF(s). 
If there are any questions regarding prior or concomitant therapy (ies), contact the Abbott 
Laboratories Medical Monitor identified in Section 7.0 

 
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5.2.3.2 
Concomitant Therapy 
Adjustments of Crohn's related concomitant treatments, including Crohn's related 
antibiotics, are not allowed during the first 8 weeks of the M06-807 study, unless subject 
safety is at risk. 
After Week 8, decreases in the dose or discontinuation of Crohn's related antibiotics or 
Crohn's related concomitant treatments are allowed according to the Investigator's 
medical judgment.  These adjustments may be performed without prior discussion with 
the Abbott Medical Monitor.  In addition, Subjects may be able to initiate or reinitiate 
Crohn's related treatments, except immunosuppressants, following eight (8) weeks of 
exposure to open-label adalimumab.  Immunosuppressants may not be started or restarted 
during the study. 
Setons are allowed as concomitant therapy in subjects with perianal fistulas.  Their use 
should be documented on the concomitant medications page of the CRF. 
Growth hormone must be discontinued prior to the first dose of open-label study drug and 
Subjects may not begin using it while participating in this study. 
If a subject began to taper corticosteroids during the M06-806 study, they may continue 
this taper immediately upon enrollment into the M06-807 study.  Beginning at Week 8, 
subjects who are not in flare may begin corticosteroid taper according to the following 
schedule: 
Tapering Schedule 
Dose 
Rate 
Prednisone (or equivalent) 
> 10 mg 
d 10 mg  
5 mg/week 
2.5 mg/week 
Budesonide 
d 9 mg  
3 mg/week 
 
Subjects who are in flare or who flare after they have reduced or completely tapered their 
dose of corticosteroid may have their corticosteroid dose increased or restarted, at the 
discretion of the Investigator.  

 
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5.2.3.3 
Rescue Therapy 
If the Investigator decides, during the study, that a subject requires rescue therapy other 
than that described in this protocol, the subject must be terminated from the study.  If 
possible, questions regarding the use of rescue therapy should be discussed with the 
Medical Monitor prior to use. 
5.2.3.4 
Prohibited Therapy 
Live vaccines must not be given concurrently while on study drug and for 70 days after 
the last dose of study drug. 
Infliximab and growth hormone use are prohibited during the study.  At the Baseline 
visit, any subject using Growth hormone must discontinue its use. 
Tysabri (natalizumab), concurrent biological therapy, cyclosporine, tacrolimus, 
mycophenolate mofetil, Kineret® (anakinra), Orencia (abatacept), therapeutic enemas and 
suppositories (not including those done in conjunction with routine colonoscopies) and 
any investigational agent are prohibited during the study (see Appendix L). 
Concurrent use of budesonide and prednisone (or equivalent) is prohibited. 
Subjects with any prior exposure to Tysabri (natalizumab) will be excluded. 
5.3 
Efficacy, and Safety Assessments/Variables 
5.3.1 
Efficacy and Safety Measurements Assessed and Flow 
Chart 
Study procedures will be performed as summarized in the study schematic presented in 
Table 1. 
 

 
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Table 1.  
Study Activities 
Activity 
Baseline 
Week 4 
Week 8 
Week 12 
Week 24 
Week 36 
Week 48 
Week 60 
Week 72 
Week 84 
Week 96 
Week 108
Inclusion/exclusion criteria 
X 
 
 
 
 
 
 
 
 
 
 
 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
 
 
Previous and concomitant 
medications 
Xa 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Urine pregnancy testb 
Xa 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Vital signsc 
Xa 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Physical exam 
Xa 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
General LABd 
Xa 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Urinalysise 
Xa 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Erythrocyte sedimentation 
rate 
Xa 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
CRP 
Xa 
 
 
 
X 
 
X 
 
X 
 
 
X 
ANA 
Xa 
 
 
X 
 
 
 
 
 
 
 
X 
Anti-dsDNAf 
Xa 
 
 
X 
 
 
 
 
 
 
 
X 
PCDAI 
Xa 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
CDAIg 
Xa 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
IMPACT III Questionnaireh 
Xa 
 
 
X 
X 
 
X 
 
X 
 
 
X 
 

 
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Table 1.  
Study Activities (Continued) 
Activity 
Baseline 
Week 4 
Week 8 
Week 12 
Week 24 
Week 36 
Week 48 
Week 60 
Week 72 
Week 84 
Week 96 
Week 108
Unscheduled outpatient 
visits, emergency room 
visits and hospitalizations 
questionnaire 
Xa 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Work Productivity and 
Impairment Questionnaire: 
Crohn's Disease (WPAI − 
CD) 
Xa 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X-ray for bone age 
Xa 
 
 
 
 
 
X 
 
 
 
 
X 
Serum bone markers 
Xa 
 
 
 
X 
 
X 
 
X 
 
 
X 
PK Blood Sample 
 
 
 
 
X 
 
X 
 
X 
 
X 
 
Anti-adalimumab blood 
levels (AAA) 
 
 
 
 
X 
 
X 
 
X 
 
X 
 
Adverse eventsi 
Xa 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Dispense study drug 
Xa 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 

 
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Table 1.  
Study Activities (Continued) 
Activity 
Week 
120 
Week 
132 
Call 
Week 
144 
Week 
156 
Call 
Week 
168 
Week 
180 
Call 
Week 
192 
Week 
204 
Call 
Week 
216 
Week 
228 
Call 
Week 
240 
Week 
252 
Call 
Week 
264/ 
Early 
Term 
Unsched 
Visit 
70-Day 
Follow-up 
Call 
Inclusion/exclusion 
criteria 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Informed consent 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Previous and concomitant 
medications 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Urine pregnancy testb 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
 
Vital signsc 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
 
Physical exam 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
 
General LABd 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
 
Urinalysise 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
 
Erythrocyte 
sedimentation rate 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
 
CRP 
 
 
X 
 
X 
 
X 
 
X 
 
 
 
X 
 
 
ANA 
 
 
X 
 
 
 
X 
 
 
 
 
 
X 
 
 
Anti-dsDNAf 
 
 
X 
 
 
 
X 
 
 
 
 
 
X 
 
 
PCDAI 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
 
CDAIg 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
 
IMPACT III 
Questionnaireh 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
 
 

 
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Table 1.  
Study Activities (Continued) 
Activity 
Week 
120 
Week 
132 
Call 
Week 
144 
Week 
156 
Call 
Week 
168 
Week 
180 
Call 
Week 
192 
Week 
204 
Call 
Week 
216 
Week 
228 
Call 
Week 
240 
Week 
252 
Call 
Week 
264/ 
Early 
Term 
Unsched 
Visit 
70-Day 
Follow-up 
Call 
Unscheduled outpatient 
visits, emergency room 
visits and 
hospitalizations 
questionnaire 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Work Productivity and 
Impairment 
Questionnaire: Crohn's 
Disease  (WPAI − CD) 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
 
X-ray for bone age 
 
 
X 
 
 
 
X 
 
 
 
 
 
X 
X 
 
Serum bone markers 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
 
PK Blood Samplei 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
 
Anti-adalimumab blood 
levels (AAA)i 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
 
Adverse eventsj 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Dispense study drug 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
 
Xk 
 
 

 
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Table 1.  
Study Activities (Continued) 
a. 
At the Baseline Visit, the following procedures will be completed as part of Week 52 of the M06-806 study. 
b. 
Performed on all females of child-bearing potential - Urine pregnancy test at all study visits. 
c. 
Vital sign determinations of height, weight, sitting blood pressure, heart rate, respiratory rate, and body temperature will be obtained at each visit. 
d. 
Blood draws should be performed after questionnaire and vital signs determinations and before study drug administration. 
e. 
Microscopic urinalysis will be performed at any visit if dipstick UA is abnormal (protein greater than a trace, blood greater than 5-10 Ery/ul, moderate or large ketone count 
or glucose greater than 50 mg/dL). 
f.  
If an ANA result is positive, anti-dsDNA will be performed automatically. 
g.  For subjects who are age 13 or older at the M06-807 Baseline Visit, a CDAI will be completed at each visit. 
h. 
For subjects who are age 10 or older at the M06-807 Baseline Visit, an IMPACT III Assessment will be completed at Baseline, Weeks 12, 24, 48, 72, 108, 144, 168, 192, 216, 
240 and 264/ET. 
i. 
In addition to blood draws every 24 weeks, PK and AAA blood draws to be performed if subject meets flare criteria and dose escalated to ew dosing. 
j. 
All AEs, including SAEs, will be captured throughout the study from the time that the subject signs the Informed Consent Form. SAEs will be captured throughout the 70 day 
follow-up period (if applicable). 
k. 
If an unscheduled visit is performed to change the frequency of study drug from OL eow to OL ew, study drug may be dispensed. 
 
 

 
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5.3.1.1 
Study Procedures 
The M06-806 Week 52 visit will serve as the Baseline visit for the M06-807 study.  The 
study procedures outlined in Table 1 are discussed in detail in this section, with the 
exception of the collection of AE information (discussed in Section 6.0).  All study data 
will be recorded in source documents and on the appropriate CRFs.  The site will call the 
subjects at Weeks 132, 156, 180, 204, 228 and 252 in order to collect any safety 
information from the subject as illustrated in Table 1. 
The visit window for all scheduled visits is ±7 days calculated from the Baseline visit of 
the M06-807 study. 
Inclusion/Exclusion Criteria 
A subject will be excluded from this study if he/she does not meet all inclusion criteria or 
meets any of the exclusion criteria of Protocol M06-807. 
Informed Consent 
A signed Informed Consent Form (ICF) will be obtained from a subject of legal age (in 
the state of residence) or from the parent or legal guardian (as appropriate)of a subject 
who is not of legal age before any study related procedures are undertaken or before any 
medications are discontinued for the purpose of this study.  Additionally, an informed 
consent will be required from those subjects who were not of legal age at the onset of this 
study but become of legal age during the course of the study. 
In keeping with each institution's IRB requirements, an Informed Assent may also be 
required from pediatric subjects.  Pediatric subjects will be included in all discussions in 
order to obtain their signature on an assent form.  Details about how informed consent 
will be obtained and documented are provided in Section 9.3. 
If an updated informed consent is approved after a subject has completed or terminated 
early from the study, but is within the 70-day follow-up window, the subject will not be 
required to return to the site for the purposes of signing the updated ICF.  The subject of 

 
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legal age, parent or legal guardian (as appropriate) should be contacted regarding any 
changes and the documentation of the contact should be present in the subject's source. 
Previous and Concomitant Medications 
Changes in concomitant medications will be assessed at each study visit from Baseline 
through the Week 264/ET visit.  Concomitant medications that are taken prior to the first 
dose of study drug administration for this study will be captured in the subject's casebook 
from the previous study (M06-806).  They will not be required to be captured in the 
subject's casebook of the M06-807 study unless they were ongoing at the Week 52 visit 
of the M06-806 study.  Ongoing concomitant medications from the M06-806 study will 
be transcribed into the subject's M06-807 casebook. 
Subjects of legal age or the parent or guardian (as appropriate) of subjects who are not of 
legal age will be provided with a medication log (see Appendix O) to record all 
medications the subject takes throughout the study.  This log must be returned for review 
at every study visit. 
Serum/Urine Pregnancy Test 
All female subjects who are experiencing menses, are nearing sexual maturation (in the 
opinion of the Investigator), or who are of child-bearing potential, will undergo a urine 
pregnancy test at each visit.  Urine pregnancy tests will be performed locally by 
designated study personnel.  If a urine pregnancy test is positive, a serum pregnancy test 
must be performed by the central laboratory.  If the serum pregnancy test is positive, the 
subject will be removed from the study.   
A lactating or pregnant female will not be eligible for participation in this study. 
Vital Signs 
Vital sign determinations of sitting blood pressure, heart rate, respiratory rate, body 
temperature, weight and height will be obtained at each visit.  All measurements will be 
recorded in metric units when applicable.  

 
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Weight measurements will be obtained using the same measuring instrument at each visit 
and measured with subjects wearing only undergarments.  Height measurements will be 
obtained using the same measuring equipment at each visit and performed on subjects 
with their shoes taken off. 
Physical Examination 
A physical examination will be performed at each visit.  A count of the number of 
cutaneous fistulas draining upon gentle compression will be performed during each 
physical exam.30  Fistulas will be classified as abdominal or perianal/anal. 
Physical exam abnormalities (including fistulas and fissures) noted by the Investigator 
will be evaluated and documented on the corresponding source documents.  Any new 
abnormalities or worsening of pre-existing conditions should be captured as AEs. 
Clinical Laboratory Tests  
Samples will be obtained for the laboratory tests listed in Table 2 at all study visits.  
Blood draws should be performed after questionnaires (PCDAI, IMPACT III 
Questionnaire, etc.) and vital sign determinations during a study visit, and before study 
drug administration. 
ICON central laboratory will be utilized to process and provide results for the general 
laboratory tests.  All abnormal laboratory test results that are considered clinically 
significant by the Investigator will be followed to a satisfactory resolution. 
ICON will provide instructions regarding the collection, processing and shipping of these 
samples. 

 
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Table 2.  
Clinical Laboratory Tests  
Hematologya 
Clinical Chemistry 
Urinalysisb 
Serum Bone Markers 
Hematocrit 
Hemoglobin 
Red Blood Cell (RBC) 
count 
White Blood Cell 
(WBC) count 
Neutrophils 
Bands 
Lymphocytes 
Monocytes 
Basophils 
Eosinophils 
Platelet count (estimate 
not acceptable) 
Blood Urea Nitrogen 
(BUN) 
Creatinine 
Total bilirubin 
Serum glutamic-pyruvic  
 
transaminase 
(SGPT/ALT) 
Serum glutamic-
oxaloacetic 
 
transaminase 
(SGOT/AST) 
Alkaline phosphatase 
Sodium 
Potassium 
Calcium 
Inorganic phosphorus 
Uric acid 
Cholesterol 
Total protein 
Glucose 
Triglycerides 
Albumin 
Specific gravity 
Ketones 
pH 
Protein 
Blood 
Glucose 
Osteocalcin 
Bone-specific alkaline 
phosphatase (BSAP)  
bone resorption (Ntx) 
a. 
Basic hematology testing performed on instrumentation does not include band reporting.  When 
Hematology results reflex to a Manual Differential, if there is a band result over 5, it is reported. 
b. Microscopic urinalysis will be performed at any visits if dipstick UA is abnormal  (protein greater than 
a trace, blood greater than 5-10 Ery/ul, moderate or large ketone count or glucose greater than 
50 mg/dL). 
 
Immunologic Laboratory Assessments   
CRP, adalimumab levels, anti-adalimumab antibody levels (AAA) and antinuclear 
antibody (ANA) assessments will be performed as indicated in Table 1.  If an ANA result 
is positive, anti-double-stranded DNA (anti-dsDNA) will be performed automatically. All 
CRP, ANA, anti-dsDNA will be performed by the central laboratory. 

 
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Erythrocyte Sedimentation Rate (ESR) assessments will be performed at all visits as 
indicated in Table 1.  ESR assessments will be performed by the site's local laboratory. 
Markers of Bone Metabolism  
Serum markers of bone metabolism will be measured as indicated in Table 1.  The bone 
formation markers to be measured are osteocalcin, bone-specific alkaline phosphatase 
(BSAP), and bone resorption (Ntx). 
Urinalysis 
Urine will be assessed by dipstick at each visit (done locally).  All results, including 
abnormalities, will be captured in source documentation and on the appropriate CRF.  
If, at any visit, the dipstick UA results are abnormal, the central lab will perform a 
microscopic urinalysis.  Abnormal is defined as protein greater than a trace, blood greater 
than 5-10 Ery/ul, moderate or large ketone count or glucose greater than 50 mg/dL. 
Pediatric Crohn's Disease Activity Index (PCDAI) 
The PCDAI score will be calculated at each visit.  When completing the PCDAI, the 
HCT, albumin, and ESR values will be utilized from the same study visit.  
An example of the PCDAI is located in Appendix G.  Instructions for completing the 
PCDAI score is located in Appendix H. 
Crohn's Disease Activity Index (CDAI) 
At each visit, a CDAI score will be calculated for subjects who are age 13 or older at the 
M06-807 Baseline Visit.  The CDAI score will be calculated utilizing the subject diary 
and the HCT value from the same study visit.  A copy of the CDAI subject diary is 
located in Appendix H. 
When completing question five (5) ("Taking Lomotil/Imodium/Loperamide/opiates for 
diarrhea, 0 = no, 1 = yes") on the CDAI, "no" should be answered if a subject is taking an 
opiate(s) solely for pain. 

 
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For the CDAI questions regarding presence of anal fistulas and other fistulas, all fistulas 
detectable on physical examination (draining and non-draining) should be captured on the 
CDAI CRF page and calculated into the CDAI score. 
The calculation of the CDAI score is in Appendix I. 
IMPACT III Questionnaire 
Subjects t 10 years old at the Baseline visit of the M06-807 study will complete an 
IMPACT III questionnaire as indicated in Table 1.  A copy of the questionnaire is located 
in Appendix K.  
The IMPACT III will be recorded directly onto the CRF.  The completed CRF will be 
considered source documentation for this assessment. 
Outcomes 
The Unscheduled Outpatient Visits, Emergency Room Visits and Hospitalization 
Questionnaire and the Work Productivity and Activity Impairment Questionnaire:  
Crohn's Disease (WPAI-CD) will be completed at each visit except the Unscheduled 
Visit (Appendix N, Appendix T). 
The subject's parent or legal guardian will complete the WPAI directly onto the CRF.  
The completed CRF will be considered source documentation for this assessment. 
Bone Age 
An x-ray of the wrist for the assessment of bone age will be obtained as indicated in 
Table 1.  Sites should use the Greulich and Pyle method for reading the x − ray.31  The 
x-ray report requires the signature of the radiologist who read the films.  The bone age 
that is determined by the x-ray should be recorded on the CRF.   

 
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Anthropometric Evaluations 
Height and weight obtained at each visit will be used by Abbott Data Management and 
Statistical groups for determination of BMI and "z" score (observed height velocity 
(cm/yr) - mean height velocity for age and sex (cm/yr) / SD of the mean) for height. 
Adverse Events 
Adverse events will be assessed at every study visit from Baseline through the 
Week 264/ET visit.  Any AEs, which are ongoing in the M06-806 study, will be 
transcribed onto the M06-807 source documents and CRF(s) 
For those subjects who complete the study or terminate early, a phone call will be made 
70 days after the last dose of study drug to obtain follow-up information on any ongoing 
and any new AEs. See Section 6.0 and Appendix M for additional information. 
Study Drug Administration 
At each study visit, the subject or their trained designated friend, family member or 
health care professional will perform study drug injections under the supervision of a 
trained medical professional to reinforce proper aseptic SC injection technique.  Subjects 
or a trained designated friend, family member or health care professional will perform 
injections of study drug in the subject's home during weeks they are not in for scheduled 
clinic visits.  Subjects may return to the study site for injections in between study visits if 
subject or a trained designated friend, family member or health care professional cannot 
inject the study medication. 
Subjects will maintain a dosing diary for all study drug administered outside study visits, 
i.e., at home.  In the diary, the date, initials of the person administering the study drug, 
time study drug is administered, kit number and the dose administered will be recorded.  
Subjects must return this diary and it will be reviewed and verified for compliance at 
each visit by the research personnel at the study center.  All relevant dosing information 
will be retained by the study coordinator and transcribed onto a drug accountability form 
at each visit.  Additionally, any discernible departure from the protocol regarding study 

 
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drug administration will be recorded on source documents and appropriate drug 
accountability forms.  A sample of the Subject Dosing Diary is presented in Appendix P. 
At all office visits subjects should be observed after study drug administration, until 
judged clinically stable by the study personnel.  If an anaphylactic reaction or other 
serious allergic reaction occurs, administration of study drug should be discontinued 
immediately and appropriate therapy initiated.  When dosing at home, subjects should be 
instructed to contact the site immediately with any signs or symptoms of a reaction. 
The dosing dates, for all doses of study drug, should be calculated from the Baseline visit 
date.  The Baseline visit date for this study is 364 ± 7 days from the Baseline Visit date of 
M06-806.  A +/- 3 day window is allowable for scheduled study dosing dates. 
For subjects that deviate from this dosing window, every effort should be made to bring 
the subject back to the original dosing schedule as soon as possible.  For situations where 
bringing the subject back on the original dosing schedule will cause the dose to be out of 
the +/- 3 day window, please contact the Medical Monitor for additional instructions. 
Randomization and Assignment of Subject Numbers 
All subjects will be centrally registered using an IVRS.  This is an open-label study; 
subjects will not be randomized.  The telephone number and call in directions for the 
IVRS will be provided to each site.  Subjects will keep their study subject number from 
the previous double-blind study (M06 − 806). 
5.3.2 
Drug Concentration Measurements 
Blood samples for the assay of adalimumab and AAA serum concentrations will be 
collected at Baseline and every 24 weeks thereafter.  In addition, blood samples for 
adalimumab and AAA concentration analysis will also be collected if a subject meets 
flare criteria and dose escalated to ew dosing.  Study visits in which blood samples will 
be collected are listed in Table 1.  At each visit, blood samples will be collect prior to 
study drug administration at each visit. 

 
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The time that each blood sample is collected will be recorded to the nearest minute in the 
source documents and on the appropriate CRF. 
5.3.2.1 
Collection of Samples for Analysis 
Collection of Samples for Adalimumab Analysis 
Blood samples for adalimumab analysis will be collected by venipuncture into 
appropriately labeled 4-mL evacuated serum collection tubes without gel separator at 
visits indicated in Table 1.  All samples will be obtained immediately prior to dosing at 
visits indicated in Table 1.  Sufficient blood will be collected to provide approximately 
2 mL serum.  Allow the blood to clot for 30 minutes at room temperature before 
centrifugation. 
A maximum of 13 samples are planned to be collected per subject for the analysis of 
adalimumab concentrations. 
Collection of Samples for AAA Analysis 
Blood samples for AAA assay will be collected by venipuncture into appropriately 
labeled 4-mL evacuated serum collection tubes without gel separator at visits indicated in 
Table 1.  All samples will be obtained immediately prior to dosing at visits indicated in 
Table 1. Sufficient blood will be collected to provide approximately 2 mL serum.  Blood 
will be allowed to clot for 30 minutes at room temperature before centrifugation. 
A maximum of 13 blood samples are planned to be collected per subject for AAA 
analysis. 
5.3.2.2 
Handling/Processing of Samples 
The blood samples for adalimumab and AAA, assay will be centrifuged within 30 to 
60 minutes of collection to separate the serum.  The serum samples will be transferred 
using plastic pipettes into screw-capped polypropylene vials labeled with the type of 
sample (serum, SRM), the protocol number, subject number, the study week and the 

 
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assay (PK-Adalimumab, AAA).  The serum samples will be frozen within 2 hours after 
collection and will remain frozen in a –20°C or colder until shipped.  Sites that do not 
have access to a −20°C or colder freezer will need to ship the samples the day they are 
collected.  (Detailed instructions provided in the ICON Laboratory Manual). 
5.3.2.3 
Disposition of Samples 
The PK and AAA samples will be shipped to ICON with all other samples being shipped 
to ICON.  Refer to the ICON Lab Manual for further instruction.  Neither Abbott nor 
ICON will supply dry ice for this study.  Study sites will identify a dry ice source and 
purchase the necessary dry ice. 
5.3.2.4 
Measurement Methods 
Serum concentrations of adalimumab will be determined using a validated ELISA 
method under the supervision of the Drug Analysis Department at Abbott Laboratories.  
Only serum samples that have adalimumab levels < 2.0 Pg/mL will be selected for AAA 
concentration measurement. 
Serum concentrations of AAA will be determined using a validated ELISA method under 
the supervision of the Drug Analysis Department at Abbott Laboratories. 
5.3.3 
Efficacy Variables 
Efficacy will be evaluated based on the proportion of subjects who maintain PCDAI 
clinical response at each visit.  Clinical response is defined as PCDAI decrease 
t 15 points from the M06-806 Baseline score. 
Other measures of disease activity being assessed in this study will be summarized, 
including CDAI scores, IMPACT III scores, WPAI-CD Caregiver, z-score for height 
velocity, bone x-ray, serological markers of bone metabolism, healthcare resource 
utilization (unscheduled outpatient visits), adalimumab levels and anti-adalimumab levels 
(AAA). 

 
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5.3.4 
Safety Variables 
AEs, laboratory data, physical examinations and vital signs are the safety parameters and 
these will be assessed throughout the study. 
Treatment-emergent events will be summarized and reported by treatment group and by 
AAA status (AAA+ versus AAA-). 
5.3.5 
Pharmacokinetic Variables 
Serum concentrations of adalimumab and AAA will be determined from samples 
collected at the study visits listed in Table 1. 
5.4 
Removal of Subjects from Therapy or Assessment 
5.4.1 
Discontinuation of Individual Subjects 
Subjects will be withdrawn from the study immediately if any of the following occur:   
● Clinically significant abnormal laboratory results or AEs, which rule out 
continuation of the study drug, as determined by the Investigator and the 
Medical Monitor. 
● The Investigator believes it is in the best interest of the subject. 
● The subject or subject's legal guardian requests withdrawal from the study. 
● Selection criteria violation was noted after the subject started study drug, as 
determined by the Medical Monitor (see Sections 5.2.1 and 5.2.2). 
● Introduction of prohibited medications or prohibited concomitant medication 
dosages as determined by the Medical Monitor. 
● The subject is diagnosed with a malignancy except for localized 
non − melanoma skin cancer.  Discontinuation for carcinoma in-situ is at the 
discretion of the Investigator. 
● The subject is diagnosed with dysplasia of the gastrointestinal tract. 
● A female subject who becomes pregnant. 
 

 
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If the subject prematurely discontinues study drug use, the procedures outlined for the 
Week 264/ET Visit must be completed within 2 weeks of the last dose of study drug, and 
preferably prior to the initiation of another therapy.  These procedures should not 
interfere with the initiation of any new treatments or therapeutic modalities that the 
Investigator feels are necessary to treat the subject's condition.  Following 
discontinuation of the study drug, the subject will be treated in accordance with the 
Investigator's best clinical judgment. 
Subjects who prematurely discontinue from the study will not be replaced.  The date of 
last dose and reason for premature discontinuation will be recorded in the source 
document and on the appropriate CRF. 
5.4.2 
Discontinuation of Entire Study 
Abbott reserves the right to discontinue the study at any time and to remove all study 
materials from the site.  Possible reasons for termination of the study include, but are not 
limited to: 
● Safety concerns based on reported data 
● Unsatisfactory enrollment with respect to quantity or quality 
● Inaccurate or incomplete data collection 
● Falsification of records 
● Failure to adhere to the protocol 
 
5.4.3 
Stopping Rules 
An independent Data Monitoring Committee (DMC) will meet to discuss data from the 
study approximately every six (6) months or at a frequency determined by the DMC and 
render their recommendation for either the continuation of the study or an amendment to 
the study.  A Sponsor Steering Committee (SSC), composed of senior executives not 
directly participating in this study, will make final decisions based on DMC 
recommendations. 

 
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5.5 
Treatments 
5.5.1 
Treatments Administered 
All study drug will be provided as a SC injection solution in pre-filled syringes 
containing adalimumab 40 mg/0.8 mL or adalimumab 20 mg/0.4 mL. 
Subjects who enroll into the study from blinded therapy in Study M06-806 will receive 
open-label therapy at a dose dependent on their body weight.  Subjects who weigh t 40 
kg will receive 40 mg eow of adalimumab, while subjects who weigh < 40 kg will 
receive 20 mg eow of adalimumab.  Beginning from Week 8, subjects who have a disease 
flare may be switched to ew treatment at the same dose of adalimumab received while on 
eow treatment. 
Subjects who enroll into the study from open-label therapy in Study M06-806 will 
continue to receive the same dose they were receiving (i.e. 40 mg ew or 20 mg ew) at the 
Week 52 visit of the M06-806 study. 
Subjects who develop a flare while receiving ew open-label therapy or have a PCDAI 
score t 15 points when compared to their Baseline (Week 52 of M06-806) PCDAI score 
(regardless of study visit), may be discontinued from the study at the discretion of the 
Investigator. 
Beginning from Week 8, the dose of adalimumab may be increased to 40 mg, at the 
discretion of the Investigator, for subjects whose body weight has increased from < 40 kg 
to t 40 kg from the study Baseline visit.  The site will enter the subjects' body weight into 
the IVRS and the dose will be adjusted, if applicable. 
5.5.2 
Identity of Investigational Product 
The individual study drug information is presented in Table 3.  Pre-filled syringes will be 
provided for this open-label clinical study. 

 
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Table 3.  
Identity of Investigational Products  
Study Drug 
Formulation 
Manufacturer 
Adalimumab 
40 mg/0.8 mL or 20 mg/0.4 mL  
Adalimumab/Mannitol, Citric acid monohydrate, Sodium citrate, 
Disodium phosphate dihydrate, Sodium dihydrogen phosphate 
dihydrate, Sodium chloride, Polysorbate 80, Water for injections, 
Sodium hydroxide added as necessary to adjust pH 
Abbott 
 
5.5.2.1 
Packaging and Labeling 
The following information will appear on the pre-filled syringe or carton labels: 
● Sponsor identification 
● Protocol number 
● Drug identification 
● Quantity of contents 
● Storage conditions 
● Dosing instructions 
● Kit number 
● Route of Administration 
● Excipients 
● Blank spaces to write the subject's identification number, initials, and date 
dispensed (as required) 
● Finishing lot # 
● Expiry Date (as required) 
 
Two pre-filled syringes will be provided in a dosing kit carton (see Table 4).  Detailed 
instructions and training for the administration of study supplies are provided in 
Appendix Q. 

 
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Table 4.  
Study Drug Packaging and Administration 
Open-label Pre-filled Syringes 
Open-label kit cartons containing two pre-filled 
syringes of adalimumab 40 mg/0.8 mL. 
Open-label kit cartons containing two pre-filled 
syringes of adalimumab 20 mg/0.4 mL. 
 
5.5.2.2 
Storage and Disposition of Study Drug 
Pre-filled syringes are to be stored protected from light at 2° to 8°C/ 36° to 46°F.  
DO NOT FREEZE.  A storage temperature log is to be maintained at the site to document 
proper storage conditions.  The refrigerator temperature must be recorded on every 
business day on a temperature log to record proper function.  Malfunctions must be 
reported to the sponsor immediately.  Study drug should be quarantined and not 
dispensed until Abbott GPRD or Abbott Temperature Excursion Management System 
(ATEMS) deems the medication as acceptable.  All clinical supplies must be stored and 
locked in a secure place until they are dispensed for subject use or are returned to Abbott 
Laboratories. 
Investigational products are for investigational use only, and are to be used only within 
the context of this study. 
5.5.3 
Method of Assigning Subjects to Treatment Groups 
This is an open-label study; all subjects will be receiving adalimumab. 
All subjects will be centrally registered using an IVRS.  The telephone number and 
call − in directions for the IVRS will be provided to each site.  Subjects will keep their 
study subject number from the previous study (M06 − 806). 
Study drug will be administered at the study visits summarized in Table 1 and detailed in 
Section 5.3.1.1. 

 
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5.5.4 
Selection and Timing of Dose for Each Subject 
Subjects who enroll into the study from blinded therapy in Study M06-806 will receive 
open-label therapy at a dose dependent on their body weight.  Subjects who weigh 
t 40 kg will receive 40 mg eow of adalimumab, while subjects who weigh < 40 kg will 
receive 20 mg eow of adalimumab.  Beginning from Week 8, subjects who have a disease 
flare may be switched to ew treatment at the same dose of adalimumab received while on 
eow treatment. 
Subjects who enroll into the study from open-label therapy in Study M06-806 will 
continue to receive the same dose they were receiving (i.e., 40 mg ew or 20 mg ew) at the 
Week 52 visit of the M06-806 study.  
Subjects who develop a flare while receiving ew open-label therapy or have a PCDAI 
score t 15 points when compared to their Baseline (the Week 52 visit of the M06-806 
study) PCDAI score (regardless of study visit), may be discontinued from the study at the 
discretion of the Investigator.  
The Baseline Visit date for this study should be 364 ± 7 days from Baseline Visit date of 
M06-806 study.  All clinic visits for the subject should be scheduled on the same day as 
the Baseline visit for this study.  For home administration of drug, subjects will be 
instructed to inject study drug on the same day of the week as their Baseline visit day.  
Subjects must inject within a +/-3 day window of this day.  If the subject is out of the 
dosing window, the Medical Monitor should be contacted to determine the timing of the 
next dose.  The subject must record all dosing information on the subject dosing diary 
(Appendix P). 
5.5.5 
Blinding 
This is an open-label study. 

 
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5.5.6 
Treatment Compliance 
The Investigator or his/her designated representatives will administer study drug only to 
subjects enrolled in the study.  
In order to document compliance with the treatment regimen, all pre-filled syringes will 
be counted and documented in source documents and on the appropriate drug 
accountability form. 
5.5.7 
Drug Accountability 
The Investigator or designee will verify that study drug supplies are received intact, at the 
appropriate temperature, and in the correct amounts from the drug depot.  This will be 
documented by signing and dating the Proof of Receipt (POR) or similar document.  The 
original POR or similar document will be kept in the site files as a record of what was 
received.  An accurate running inventory of study drug will be kept by the site, and will 
include the kit number, lot number(s), the number of pre-filled syringes dispensed, and 
the date study drug was dispensed for each subject.  An overall accountability of the 
study drug will be performed and verified by the Clinical Research Associate (CRA) 
throughout the study and at the site close-out visit.  All unused pre-filled syringes will be 
inventoried and returned to an identified vendor for disposal as designated by Abbott 
Laboratories.  A copy of the Drug Accountability Form, in accordance with instructions 
provided by the CRA, will also be included in the Returned Goods for disposal shipment.  
A sample Drug Accountability Form is included in Appendix S.  A copy of the Drug 
Accountability Disposal Form, in accordance with instructions provided by the CRA, will 
also be included in the Pharmacy Binder provided to the site. 
All used (expelled) pre-filled syringes will be inventoried by the site and verified by the 
CRA.  The used syringes will be discarded on site, using appropriate biohazard 
precautions.  CRAs and site staff will complete study drug accountability via study drug 
logs, source documents, verification of empty used syringe kit boxes, subject diaries and 
by visually counting the syringes in the sharp's container whenever possible.  Used 
sharp's containers should never be opened.  Each subject will be given their own sharps 

 
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disposal container to store expelled syringes.  Sharps containers should be returned by the 
subject at each visit, for accountability and compliance purposes.  New containers will be 
issued to subjects as necessary.  Once the CRA has verified drug accountability at the 
site, the site staff and CRA will sign off that the expelled pre-filled syringes have been 
destroyed. 
5.6 
Discussion and Justification of Study Design 
5.6.1 
Discussion of Study Design and Choice of Control Groups 
The design of this clinical study was chosen to demonstrate adalimumab as an effective 
therapy for maintaining clinical response in pediatric subjects with CD and to gather 
long-term safety and tolerability data in this subject population. 
5.6.2 
Appropriateness of Measurements 
Standard statistical, clinical, and laboratory procedures will be utilized in this study.  All 
efficacy measurements in this study are standard for assessing disease activity in pediatric 
subjects with Crohn's disease.  All clinical and laboratory procedures in this study are 
standard and generally accepted. 
5.6.3 
Suitability of Subject Population 
Pediatric subjects with CD who have participated in and successfully completed Protocol 
M06-806 through Week 52 and who meet all of the inclusion and none of the exclusion 
criteria are eligible for this study. 
5.6.4 
Selection of Doses in the Study 
The results of the pivotal adalimumab adult CD maintenance trial M02-404, in 
conjunction with results from adalimumab CD Study M02-433, support a maintenance 
dose of adalimumab 40 mg eow.  Data also suggest that patients who lose response to 
adalimumab at 40 mg eow can be dose-escalated to 40 mg weekly with the potential of 
regaining clinical response.  The proposed dosing regimen for Study M06-807 was 
developed using an analogous approach as that studied in the adult CD population. 

 
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Population pharmacokinetic modeling of serum adalimumab concentration data from 
pediatric subjects with JRA was used to identify doses to be evaluated in the current 
study in children with CD.  A model based on the JRA population was chosen because 
the body weight range will closely parallel that in a juvenile CD population.  Escalation 
to weekly dosing will provide average adalimumab concentrations at steady state about 
twice that observed with every other week dosing.  However, these concentrations are 
within the range of systemic exposures that were safely studied in adult subjects with CD. 
6.0 
Adverse Events 
The Investigator will monitor each subject for clinical and laboratory evidence of AEs on 
a routine basis throughout the study.  The Investigator will assess and record any AE in 
detail including the date of onset, description, severity, time course, duration and 
outcome, relationship of the AE to study drug, an event diagnosis, if known, and any 
action(s) taken.  For SAEs not considered "probably related" to study drug, the 
Investigator must provide another cause of event.  For AEs to be considered sporadic, the 
events must be of similar nature and severity.  AEs, whether in response to a query, 
observed by site personnel, or reported spontaneously by the subject will be recorded in 
source documentation and on the appropriate CRF page. 
All AEs will be followed to a satisfactory conclusion. 
6.1 
Definitions 
6.1.1 
Adverse Event 
An AE is defined as any untoward medical occurrence in a patient or clinical 
investigation subject administered a pharmaceutical product and which does not 
necessarily have a causal relationship with this treatment.  An AE can therefore be any 
unfavorable and unintended sign (including an abnormal laboratory finding), symptom, 
or disease temporally associated with the use of a medicinal (investigational) product, 
whether or not the event is considered causally related to the use of the product. 

 
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Such an event can result from use of the drug as stipulated in the protocol or labeling, as 
well as from accidental or intentional overdose, drug abuse, or drug withdrawal.  Any 
worsening of a pre-existing condition or illness is considered an AE.  Laboratory 
abnormalities and changes in vital signs are considered to be AEs only if they result in 
discontinuation from the study, necessitate therapeutic medical intervention, and/or if the 
Investigator considers them to be AEs. 
An elective surgery/procedure scheduled to occur during a study will not be considered 
an AE if the surgery/procedure is being performed for a pre-existing condition and the 
surgery/procedure has been pre-planned prior to study entry.  However, if the pre-existing 
condition deteriorates unexpectedly during the study (e.g., surgery performed earlier than 
planned), then the deterioration of the condition for which the elective surgery/procedure 
is being done will be considered an AE. 
6.1.2 
Serious Adverse Events 
If an AE meets any of the following criteria, it is to be reported to Abbott as an SAE 
within 24 hours of the site being made aware of the SAE.  Additionally, if follow-up 
information is received, it must also be reported to Abbott within 24 hours of being made 
aware of the information. 
Death of Subject 
An event that results in the death of a subject. 
Life-Threatening 
An event that, in the opinion of the Investigator, will have resulted in 
immediate fatality if medical intervention had not been taken.  This does 
not include an event that will have been fatal if it had occurred in a more 
severe form. 
Hospitalization 
An event that results in an admission to the hospital for any length of 
time.  This does not include an emergency room visit or admission to an 
outpatient facility. 
Prolongation of 
Hospitalization 
An event that occurs while the study subject is hospitalized and prolongs 
the subject's hospital stay. 
Congenital Anomaly 
An anomaly detected at or after birth, or any anomaly that results in fetal 
loss. 

 
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Persistent or Significant 
Disability/Incapacity 
An event that results in a condition that substantially interferes with the 
activities of daily living of a study subject.  Disability is not intended to 
include experiences of relatively minor medical significance such as 
headache, nausea, vomiting, diarrhea, influenza, and accidental trauma 
(e.g., sprained ankle). 
Important Medical Event 
Requiring Medical or 
Surgical Intervention to 
Prevent Serious Outcome 
An important medical event that may not be immediately life-threatening 
or result in death or hospitalization, but based on medical judgment may 
jeopardize the subject and may require medical or surgical intervention to 
prevent any of the outcomes listed above (i.e., death of subject, life 
threatening, hospitalization, prolongation of hospitalization, congenital 
anomaly, or persistent or significant disability/incapacity).  Examples of 
such events include allergic bronchospasm requiring intensive treatment 
in an emergency room or at home, blood dyscrasias or convulsions that do 
not result in inpatient hospitalization, or the development of drug 
dependency or drug abuse. 
Spontaneous Abortion 
Miscarriage experienced by study subject. 
Elective Abortion 
Elective abortion performed on study subject. 
 
6.2 
Adverse Event Severity 
The Investigator will use the following definitions to rate the severity of each AE: 
Mild 
The AE is transient and easily tolerated by the subject. 
Moderate 
The AE causes the subject discomfort and interrupts the subject's usual 
activities. 
Severe 
The AE causes considerable interference with the subject's usual activities 
and may be incapacitating or life threatening.   
 
6.3 
Relationship to Study Drug 
The Investigator will use the following definitions to assess the relationship of the AE to 
the use of study drug:   
Probably Related 
An adverse event has a strong temporal relationship to study drug or 
recurs on re-challenge and an other cause of event is unlikely or 
significantly less likely. 
Possibly Related 
An AE has a strong temporal relationship to the study drug and an other 
cause of event is equally or less likely compared to the potential 
relationship to study drug. 

 
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Probably Not Related 
An AE has little or no temporal relationship to the study drug and/or a 
more likely other cause of event exists. 
Not Related 
An AE is due to an underlying or concurrent illness or effect of another 
drug and is not related to the study drug (e.g., has no temporal 
relationship to study drug or has a much more likely other cause of event). 
 
If an Investigator's opinion of possibly, probably not, or not related to study drug for an 
SAE is given, an alternative cause of the event must be provided by the Investigator for 
the SAE. 
6.4 
Adverse Event Collection Period 
All AEs reported from the time of informed consent until 5 half-lives (70 days), 
following discontinuation of study drug administration have elapsed will be collected, 
whether elicited or spontaneously reported by the subject.  In addition, SAEs will be 
collected from the time the subject or parent/legal guardian has signed the study-specific 
informed consent. 
Adverse event information will be collected as shown in Figure 2. 
Figure 2.  
Adverse Event Collection 
SAEs and Non-serious AEs 
Elicited and/or Spontaneously Reported 
_ 
 
_ 
 
_ 
 
_ 
Consent 
Signed 
 
Study Drug 
Start 
 
Study Drug 
Stopped 
 
70 Days After 
Study Drug 
Stopped 
 
6.5 
Adverse Event Reporting 
In the event of an SAE, whether related to study drug or not, the investigator will notify 
one of the following people by faxing the appropriate SAE forms to one of the following 
people within 24 hours of the site being made aware of the SAE. 

 
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For all sites: 
 
 
For questions regarding SAEs, please contact: 
6.5.1 
Collection of Data Regarding Known Manifestations of the 
Disease Under Study 
Flare, of Crohn's disease events per study definition, are not required to be captured as 
AEs, but may be captured per Investigator discretion.  Additionally, CD pre-existing 
conditions will not be captured as AEs unless the condition has worsened or is considered 
clinically significant in the opinion of the Investigator. 
6.6 
Pregnancy 
Abbott Laboratories must be notified within 1 working day of a site's learning if a female 
subject becomes pregnant during the study or within 150 days of receiving the last dose 
of study drug (see Section 6.5 for contact information). 

 
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Females who become pregnant during the study will be discontinued from study drug as 
described in Section 5.4.  Data regarding the outcome of any pregnancy occurring in a 
study subject will be collected.  Upon notification of a pregnancy Abbott will forward a 
form to the site, for the Investigator to complete and send back to Abbott.  A second form 
will also be sent approximately 9 months from the date of notification to collect 
information on the outcome of the pregnancy.  This form will also need to be completed 
and sent back to Abbott. 
To monitor outcomes of pregnant women exposed to adalimumab, a pregnancy registry 
has been established for the United States, Canada and Puerto Rico.  Physicians in the 
United States are encouraged to register subjects by calling 
and/or 
provide this information to the subject. 
Pregnancy in a study subject is not considered an AE.  However, the medical outcome of 
an elective or a spontaneous abortion, stillbirth or congenital anomaly is considered a 
SAE, and must be reported to the sponsor with 24 hours of the site learning of the event. 
7.0 
Protocol Deviations 
The investigator should not implement any deviation from the protocol without prior 
review and agreement by the Sponsor and in accordance with the IEC/IRB and local 
regulations, except when necessary to eliminate an immediate hazard to study subjects.  
When a deviation from the protocol is deemed necessary for an individual subject, the 
investigator must contact the following Abbott representative: 
 
 

 
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For purposes of this protocol, reportable deviations are defined as:   
● Subject entered into the study even though they did not satisfy entry criteria 
● Subject who developed withdrawal criteria during the study and was not 
withdrawn 
● Subject who received wrong treatment or incorrect dose 
● Subject who received excluded concomitant treatment 
 
Such contact must be made as soon as possible to permit a review by Abbott to determine 
the impact of the deviation on the subject and/or the study.  Any significant protocol 
deviations affecting subject eligibility and/or safety must be reviewed and/or approved by 
the IEC/IRB and regulatory authorities, as applicable, prior to implementation. 
8.0 
Statistical Methods and Determination of Sample 
Size 
8.1 
Statistical and Analytical Plans 
8.1.1 
Analyzable Population 
Efficacy analyses will be conducted in the intent-to-treat (ITT) population, which is 
defined as all subjects who received at least one dose of adalimumab in Study M06-807.  
In order to evaluate the impact of major protocol violations / deviations on the results of 
the study, additional analyses may be performed on the per-protocol population, which 
excludes all subjects with major protocol deviations.  The safety population consists of all 
subjects who received at least one dose of adalimumab in Study M06-807. 
8.1.2 
Planned Methods of Statistical Analysis 
All statistical analyses are to be performed descriptively.  Descriptive summary statistics 
will be provided for the demographic and baseline characteristics, efficacy, and safety 
parameters.  Continuous variables will be summarized using the number of observation, 

 
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mean, standard deviation, 1st quartile, median, 3rd quartile, minimum, and maximum; 
whereas discrete variables will be summarized using count and percentages.  
8.1.2.1 
Demographics and Baseline Characteristics 
Summary statistics for the demographic and baseline characteristics will be computed 
based on the Week 52 values (from double-blind study M06-806). 
8.1.2.2 
Primary Efficacy Analysis 
Summary statistics will be provided for each visit, based on observed data.  An additional 
summary will be provided for the last visit, using the last observation carried forward 
(LOCF).  That is, the subject's last non-missing, post-baseline value (i.e., post-Week 52 
M06-806 double-blind value) will be carried forward to the last visit. 
8.1.3 
Other Analyses 
The primary endpoint will be analyzed for the following subgroups in the ITT population. 
● Sex [Male, Female] 
● Age [< 13 years, t 13 years] 
● Ethnicity [White, Non-white] 
● Weight [< 40 kg, t 40 kg] 
● Prior infliximab use [No, Yes] 
● Baseline CRP [< 1.0 mg/dL, t 1.0 mg/dL] 
● Concomitant use of immunosuppressants and/or oral corticosteroids [No, Yes] 
 
8.1.4 
Safety Analyses 
Safety analyses will be based on the safety population.  Treatment-emergent, and 
post − treatment AEs will be summarized.  An overview of treatment-emergent AEs 
including AEs of special interest, such as AEs leading to death and AEs leading to 
premature discontinuation, AEs by (MedDRA® version 10.0 or later) preferred term and 

 
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system organ class, AEs by maximum relationship to study drug, and AEs by maximum 
severity will be summarized.  Treatment-emergent AEs are defined as new events that 
begin either on or after the first dose of the study drug and within 70 days after the last 
dose of the study drug. 
Adverse events with missing or unknown severity will be categorized as severe.  Adverse 
events with missing or unknown relationship to study drug will be categorized as 
probably related. 
Adverse events that are reported more than 70 days after last study injection will be 
excluded from the summaries; however, all reported AEs will be included in the AE data 
listings. 
For laboratory parameters, the normal range of the analyzing laboratory will be used and 
all values outside the normal range will be flagged and listed.  Additionally, descriptive 
statistics for the mean change from baseline to minimum (smallest) value, maximum 
(largest) value and final value during the study will be calculated for the continuous 
clinical laboratory parameters.  
Shift tables will be provided to cross-classify and tabulate subjects' value from baseline to 
final value by the presence of clinically significant laboratory results.  Each subject's 
baseline value and final value will be flagged in reference to the normal range (low, 
normal, high) and also categorized as clinically non-significant (CTC grade < 3) or 
clinically significant (CTC grade t 3).  Further details will be provided in the SAP. 
8.1.4.1 
Pharmacokinetic Analyses 
Adalimumab trough serum concentrations will be summarized by treatment group at each 
time point using descriptive statistics including number of subjects, number of non 
missing observations (nnmiss), mean, median, standard deviation, coefficient of 
variation, minimum, and maximum.  The relationship between adalimumab 
concentrations and efficacy and/or safety variables may be explored.  Additional analysis 
may be performed. 

 
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8.1.5 
Interim Analysis 
There are no planned interim analyses. 
8.2 
Determination of Sample Size 
Subjects who successfully completed Study M06-806 through Week 52 may be eligible 
to participate in this study. It is expected that approximately 70% (130) of subjects from 
the M06-806 study will enroll in this study. 
8.3 
Randomization Methods 
All subjects will be centrally registered using an IVRS.  This is an open-label study; 
therefore, subjects will not be randomized before the study is initiated, the telephone 
number and call in directions for the IVRS will be provided to each site.  Subjects will 
keep their subject number from the previous study (M06-806). 
9.0 
Ethics 
9.1 
Independent Ethics Committee (IEC) or Institutional Review 
Board (IRB) 
Good Clinical Practice (GCP) requires that the clinical protocol, any protocol 
amendments, the Investigator's Brochure, the informed consent and all other forms of 
subject information related to the study (e.g., advertisements used to recruit subjects) and 
any other necessary documents be reviewed by an IEC/IRB.  IEC/IRB approval of the 
protocol, informed consent and subject information and/or advertising, as relevant, will 
be obtained prior to the authorization of drug shipment to a study site. 
Any amendments to the protocol will require IEC/IRB approval prior to implementation 
of any changes made to the study design.  A list of the documents required prior to 
initiation of the study can be found in Appendix C. 
Any SAEs that meet the reporting criteria, as dictated by local regulations, will be 
reported to both responsible Ethics Committees and Regulatory Agencies, as required by 

 
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local regulations.  During the conduct of the study, the Investigator should promptly 
provide written reports (e.g., ICH Expedited Reports, and any additional reports required 
by local regulations) to the IEC/IRB of any changes that affect the conduct of the study 
and/or increase the risk to subjects, unless otherwise submitted by the sponsor.  Written 
documentation of the submission to the IEC/IRB should also be provided to Abbott. 
9.2 
Ethical Conduct of the Study 
The study will be conducted in accordance with the protocol, International Conference on 
Harmonization (ICH) guidelines, applicable regulations and guidelines governing clinical 
trial conduct, and the ethical principles that have their origin in the Declaration of 
Helsinki.  Responsibilities of the clinical Investigator are specified in Appendix D. 
9.3 
Subject Information and Consent 
Prior to any study-related procedures or discontinuation of any medications for this study, 
the Investigator or his/her representative will explain the nature of the study to the subject 
of legal age (in the state of residence) or to the parent or legal guardian (as appropriate) 
of a subject who is not of legal age and answer all questions regarding this study.  
Subjects will be included in all discussions. 
The ICF will be reviewed, signed and dated by the subject of legal age (in the state of 
residence) or by the parent or legal guardian (as appropriate) of a subject who is not of 
legal age, and the person who administered the informed consent.  If a subject who was 
not of legal age at the onset of this study becomes of legal age during the course of the 
study, an informed consent will need to be obtained at that time.  Additionally, in keeping 
with each institution's IRB requirements an Informed Assent will also be obtained from 
the subject, as required.   
A copy of the signed ICF and Assent Form will be given to the subject and the subject's 
parent/legal guardian.  The original signed ICF and Assent Form will be placed in the 
subject's medical record.  An entry must also be made in the subject's dated source 

 
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documents to confirm that informed consent was obtained prior to any study-related 
procedures and that the subject received a signed copy. 
If an updated informed consent is approved after a subject has completed or terminated 
early from the study, but is within the 70-day follow-up window, the subject will not be 
required to return to the site for the purposes of signing the updated ICF.  The subject of 
legal age, parent or legal guardian (as appropriate) should be contacted regarding any 
changes and the documentation of the contact should be present in the subject's source.  
10.0 
Source Documents and Case Report Form 
Completion 
10.1 
Source Documents 
Source documents are defined as original documents, data and records.  This may include 
hospital records, clinical and office charts, laboratory data/information, subjects' diaries 
or evaluation checklists, pharmacy dispensing and other records, recorded data from 
automated instruments, microfiches, photographic negatives, microfilm or magnetic 
media, and/or x-rays.  Data collected during this study must be recorded on the 
appropriate source documents. 
The Investigator(s)/institution(s) will permit study-related monitoring, audits, IEC/IRB 
review, and regulatory inspection(s), providing direct access to source data documents. 
The IMPACT III questionnaire and the WPAI questionnaire will be recorded directly on 
the CRF(s) by the subject, parent or legal guardian (as appropriate) and these CRFs will 
be considered source data. 
10.2 
Case Report Forms 
Case report forms will be supplied by Abbott.  These forms will be used to transmit 
information collected during the study to Abbott and regulatory authorities, as applicable.  
Case report forms must be completed for each subject enrolled in this study.  All case 
report forms must be legible and completed in indelible black ballpoint ink.  Any 

 
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necessary corrections are to be made by drawing a single line through the incorrect entry 
and writing in the revision.  All revisions must be initialed and dated by the Investigator 
or his/her representative.  Data are not to be obliterated by blacking out, using correction 
fluid or by erasing the original entry.  If the reason for the correction is not obvious, a 
brief explanation (e.g., transcription error) should accompany the change.  All 
information written on the case report forms must also be reflected in the subject source 
documents with the exception of the case report forms discussed above in Section 10.1. 
The Principal Investigator will review the case report forms for completeness and 
accuracy and sign and date each set of case report forms where indicated.  The case 
report forms will be reviewed periodically for completeness, legibility and acceptability 
by Abbott personnel (or their representatives).  Abbott (or their representatives) will be 
allowed access to all source documents in order to verify case report form entries. 
Once the original case report form has been removed from the site, all changes must be 
made via the appropriate change form specified by Abbott.  The Principal Investigator 
will review the change form for completeness and accuracy and sign and date the change 
form where indicated. 
11.0 
Data Quality Assurance 
Prior to the initiation of the study, an Investigator's meeting will be held with Abbott 
personnel, the Investigators and their study coordinators, the CRO's project manager and 
the CRAs for the study.  This meeting will include a detailed discussion of the protocol, 
performance of study procedures, CRF and Subject Diary completion, and specimen 
collection methods.  In addition to or instead of the Investigator's meeting, the study 
personnel at each site may be trained on the study procedures by a CRA at a study 
initiation visit and will be given a CRF completion workbook for reference. 
The CRAs will monitor at each site throughout the study.  One hundred percent (100%) 
source document review will be performed against entries on the CRF and a quality 
assurance check will be performed to ensure that the Investigator is complying with the 

 
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protocol and regulations.  In addition, after CRFs are retrieved by the CRA, a review of 
the data will be conducted by a physician and a clinical review team at Abbott 
Laboratories. 
All data hand entered in the database will be verified by a double-key entry procedure at 
Abbott.  Any discrepancies will be reviewed against the hard copy CRF and corrected on-
line. After completion of the entry process, computer logic checks will be run to check 
for such items as inconsistent study dates and outlying laboratory values.  Any necessary 
corrections will be made to the database and documented via addenda, queries, source 
data clarification form or audit trail.  A manual review of selected line listings will also 
be performed at the end of the study. 
Routine hematology, serum chemistry, and serology will be conducted using a central 
laboratory.  ESR analysis will be done at a local lab designated by the site. The data from 
these analyses will be electronically transferred from the central laboratory to the study 
database.  Urinalysis will be completed locally.  If a microscopic urinalysis is necessary, 
this testing will be conducted using the central laboratory.  A final review of all 
laboratory results will be conducted by a physician and clinical review team at 
Abbott Laboratories. 
Sites will provide Abbott (or designate) with laboratory certifications (CAP and CLIA), 
CV of local lab director, and reference ranges for each local lab used.  The full name, 
address, phone number, and fax number for each local lab will also be included. 
12.0 
Use of Information and Publication 
12.1 
Use of Information 
All information concerning adalimumab and Abbott Laboratories' operations, such as 
Abbott Laboratories' patent applications, formulas, manufacturing processes, basic 
scientific data, or formulation information, supplied by Abbott Laboratories and not 
previously published is considered confidential information. 

 
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The information developed during the conduct of this clinical study is also considered 
confidential and will be used by Abbott Laboratories in connection with the development 
of adalimumab.  This information may be disclosed as deemed necessary by 
Abbott Laboratories to other clinical Investigators, other pharmaceutical companies, to 
the FDA,  and to other government agencies.  To allow for the use of the information 
derived from this clinical study and to ensure complete and thorough analysis, the 
Investigator is obligated to provide Abbott Laboratories with complete test results and all 
data developed in this study and to provide direct access to source data/documents for 
study- related monitoring, audits, IEC/IRB review, and regulatory inspection. 
This confidential information shall remain the sole property of Abbott Laboratories, shall 
not be disclosed to others without the written consent of Abbott Laboratories, and shall 
not be used except in the performance of this study. 
The Investigator will maintain a confidential subject identification code list of all subjects 
enrolled in the study (by name and subject number).  This list will be maintained at the 
site and will not be retrieved by Abbott. 
12.2 
Internet Sites 
Information regarding this study may be posted on various internet web sites and will 
maximally include study name, number, general population to be enrolled, entrance 
qualifications, brief description of the study, study objectives, doses, accruing 
Investigators (upon their approval) and number of subjects to be enrolled. 
13.0 
Completion of the Study 
The Investigator will conduct this study in compliance with the protocol, and will 
complete the study within the timeframe specified in the contract between the 
Investigator and Abbott.  Continuation of the study beyond this time must be mutually 
agreed upon in writing by both the Investigator and Abbott.  The Investigator will 
provide a summary of the study's outcome to the IEC/IRB following conclusion of the 
study, and will forward a copy of this summary to Abbott or their designee. 

 
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Abbott may terminate this study prematurely, either in its entirety or at individual sites, 
for reasonable cause provided that written notice is submitted a reasonable time in 
advance of the intended termination.  The Investigator may also terminate the study at 
their site for reasonable cause, after providing written notice to Abbott a reasonable time 
in advance of the intended termination.  Advance notice is not required by either party if 
the study is stopped due to safety concerns.  If Abbott terminates the study for safety 
reasons, it will immediately notify the Investigator by telephone and subsequently 
provide written instructions for study termination. 
Abbott will select the signatory Investigator from the Investigators who participate in the 
study.  Selection criteria for this Investigator will include level of participation as well as 
significant knowledge of the clinical research, investigational drug and study protocol.  
The signatory Investigator for the study will review and sign the final study report in 
accordance with the European Agency for the Evaluation of Medicinal Products (EMEA) 
Guidance on Investigator's Signature for Study Reports. 
The Investigator will retain all essential documents until at least two years after the last 
approval of a marketing application in an ICH region and until there are no pending or 
contemplated marketing applications in an ICH region or at least two years have elapsed 
since the formal discontinuation of clinical development of the investigational product.  It 
is the responsibility of the sponsor to inform the Investigator/institution as to when these 
documents no longer need to be retained. 
The end-of-study is defined as the date of the last subject's last scheduled visit or the 
actual date of follow-up contact, whichever is longer. 
 

 
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14.0 
Investigator's Agreement 
1. I have received and reviewed the Investigator Brochure for Humira. 
2. I have read this protocol and agree that the study is ethical. 
3. I agree to conduct the study as outlined and in accordance with all applicable 
regulations and guidelines. 
4. I agree to maintain the confidentiality of all information received or developed in 
connection with this protocol. 
 
 
 
 
Protocol Title: 
A Multi-center, Open-label Study of the Human Anti-TNF 
Monoclonal Antibody Adalimumab to Evaluate the Efficacy and the 
Long-term Safety and Tolerability of Repeated Administration of 
Adalimumab in Pediatric Subjects with Crohn's Disease Who Have 
Demonstrated a Clinical Response in the M06-806 Study 
Protocol Date: 
26 August 2010 
 
 
 
 
 
 
Signature of Principal Investigator 
 
Date 
 
 
 
Name of Principal Investigator (printed or typed) 
 
 
 
 

 
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15.0 
Reference List 
1. 
Hanauer SB, Sandborn W.  Management of Crohn's disease in adults.  Am J 
Gastroenterol 2001;96:635-43. 
2. 
Loftus Jr. EV.  Clinical epidemiology of inflammatory bowel disease: Incidence, 
prevalence, and environmental influences.  Gastroenterology 2004;126:1504-17. 
3. 
Seidman EG.  Recent advances in the diagnosis and treatment of pediatric 
inflammatory bowel disease.  Curr Gastroenterol Rep 2000;2:248-52. 
4. 
Auvin S, Molinie F, Gower-Rousseau C, Brazier F, Merle V, Grandbastient B, 
et al.  Incidence, clinical presentation and location at diagnosis of pediatric 
inflammatory bowel disease: a prospective population-based study in northern 
France (1988-1999).  J Pediatr Gastroenterol Nutr 2005;41(1):49-55. 
5. 
Kugathasan S, Judd RH, Hoffmann RG, Heikenen J, Telega G, Khan F, et al.  
Epidemiologic and clinical characteristics of children with newly diagnosed 
inflammatory bowel disease in Wisconsin; a statewide population-based study.  
J Pediatr 2003;143(4):525-31. 
6. 
Cosgrove M, Al-Atia RF, Jenkins HR.  The epidemiology of pediatric 
inflammatory bowel disease.  Arch Dis Child 1996;74:460-1. 
7. 
Hassan K, Cowan FJ, Jenkins HR.  The incidence of childhood inflammatory 
bowel disease in Wales.  Eur J Pediatr 2000;159:261-3. 
8. 
Barton JR, Gillon S, Ferguson A.  Incidence of inflammatory bowel disease in 
Scottish children between 1968 and 1983; marginal fall in ulcerative colitis, three-
fold rise in Crohn's Disease.  Gut 1989;30:618-22. 
9. 
Sawczenko A, Sandhu BK, Logan RFA, et al.  Prospective survey of childhood 
inflammatory bowel disease in the British Isles.  Lancet 2001;357:1093-4. 

 
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10. 
Olafsdottir EJ, Fluge G, Haug K.  Chronic inflammatory bowel disease in children 
in western Norway.  J Pediatr Gastroenterol Nutr 1989;8:454-8. 
11. 
Lindberg E, Lindquist B, Holmquist L, Hildebrand H.  Inflammatory bowel 
disease in children and adolescents in Sweden (1984-1995).  J Pediatr 
Gastroenterol Nutr 2000;30:259-64. 
12. 
Hildebrand H, Finkel Y, Grahnquist L, Lindholm J, Ekbom A, Askling J.  
Changing pattern of paediatric inflammatory bowel disease in northern Stockholm 
1990-2001. Gut 2003;52:1432. 
13. 
Heyman MB, Kirshner BS, Gold BD, Ferry G, Baldassano R, Cohen SA, et al.  
Children with early onset inflammatory bowel disease (IBD): analysis of a 
pediatric IBD consortium registry.  J Pediatr 2005;146(1):35-40. 
14. 
Lindberg E, Lindquist B, Holmquist L, Hildebrand H.  Inflammatory bowel 
disease in children and adolescents in Sweden, 1984-1995.  J Pediatr Gastroenterol 
Nutr 2000;30(3):259-64. 
15. 
Sawczenko A, Sandhu BK.  Presenting features of inflammatory bowel disease in 
Great Britain and Ireland.  Arch Dis Child 2003;88:995-1000. 
16. 
Griffiths AM.  Specificities of inflammatory bowel disease in childhood.  Best 
Pract Res Clin Gastroenterol 2004;18(3):509-23. 
17. 
Griffiths AM, Nguyen P, Smith C, MacMillan JH, Sherman PM.  Growth and 
clinical course of children with Crohn's disease.  Gut 1993;34(7):939-43. 
18. 
Kanof ME, Lake AM, Bayless TM.  Decreased height velocity in children and 
adolescents before the diagnosis of Crohn's disease.  Gastroenterology 
1988;95(6):1523-7. 
19. 
Markowitz J, Grancher K, Rosa J, Aiges H, Daum F.  Growth failure in pediatric 
inflammatory bowel disease.  J Pediatr Gastroenterol Nutr 1993;16(4):373-80. 

 
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20. 
Kleinman RE, Baldassano RN, Caplan A, Griffiths AM, Heyman MB, 
Issenman RM, et al.  Nutrition support for pediatric patients with inflammatory 
bowel disease: a clinical report of the North America Society for Pediatric 
Gastroenterology, Hepatology and Nutrition.  J Pediatr Gastroenterol Nutr 
2004;39(1):15-27. 
21. 
Gokhale R, Favus MJ, Karrison T, Sutton MM, Rich B, Kirshner BS.  Bone 
mineral density assessment in children with inflammatory bowel disease.  
Gastroenterology 1998;114:902-11. 
22. 
Boot AM, Bouquet J, Krennings EP, de Muinck Keizer-Schrama SMPF.  Bone 
mineral density and nutritional status in children with chronic inflammatory bowel 
disease.  Gut 1998;42:188-94. 
23. 
Ballinger AB, Savage MO, Sanderson IR.  Delayed puberty associated with 
Inflammatory bowel disease.  Pediatr Res 2003;53:205-10. 
24. 
Harpavat M, Greenspan SL, O'Brien C, Chang C-C, Bowen A, Keljo DJ.  Altered 
bone mass in children at diagnosis of Crohn's disease: a pilot study.  J Pediatr 
Gastroenterol Nutr 2005;40:295-300. 
25. 
Hyams JS, Wyzga N, Kreutzer DL, Justinich CJ, Gronowicz GA.  Alterations in 
bone metabolism in children with inflammatory bowel disease: an in vitro study. 
J Pediatr Gastroenterol Nutr 1997;24(3):289-95. 
26. 
Hanauer S, Lukas M, MacIntosh D, Rutgeerts P, Sandborn W, Pollack P.  A 
randomized, double-blind, placebo-controlled trial of the human anti-TNF-D 
monoclonal antibody adalimumab for the induction of remission in patients with 
moderate to severely active Crohn's disease.  Gastroenterology 2004;127(1):332. 
27. 
Data on file at Abbott Laboratories. 
28. 
Abbott Study DE038, Data on file. 

 
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29. 
Humira® (adalimumab) [package insert].  North Chicago, IL:  
Abbott Laboratories:  June 2006. 
30. 
Present DH, Rutgeerts P, Targan S, Hanauer SB, Mayer L, van Hogezand RA, 
et al.  Infliximab for the treatment of fistulas in patients with Crohn's disease. 
N Eng J Med.  1999;340(18):1398-405. 
31. 
Greulich and Pyle Radiographic Atlas of Skeletal Development of the Hand and 
Wrist:  June 1959. 
32. 
Centers for Disease Control and Prevention.  Targeted tuberculin testing and 
treatment of latent tuberculosis infection.  MMWR 2006 April. 
 

 
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Appendix A.  
List of Abbreviations and Definition of Terms 
Abbreviations 
AAA 
Anti-adalimumab antibody 
AE 
Adverse Event 
ALT 
Alanine Transaminase 
ANA 
Antinuclear antibody 
AST 
Aspartate transaminase 
BMI 
Body Mass Index 
BSAP 
Bone-specific alkaline phosphatase 
BUN 
Blood Urea Nitrogen 
CD 
Crohn's disease 
CDC 
Center for Disease Control 
CNS 
Central Nervous Systems 
CRA 
Clinical Research Associate 
CRF 
Case Report Form 
CRP 
C-Reactive Protein 
CTC 
Common Toxicity Criteria 
DMC 
Data Monitoring Committee 
DNA 
Deoxyribonucleic acid 
dsDNA 
Double Stranded DNA 
eow 
Every other week 
ESR 
Erythrocyte sedimentation rate 
ET 
Early Termination 
EU 
European Union 
ew 
Every week 
FDA 
U.S. Food and Drug Administration 
GCP 
Good Clinical Practice 
HCT 
Hematocrit 
HIV 
Human immunodeficiency virus 
ICH 
International Conference on Harmonization 
IEC 
Independent Ethics Committee 
IgG1 
Immunoglobulin 
ICF 
Informed Consent Form 

 
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IRB 
Institutional Review Board 
ITT 
Intent-to Treat 
IVRS 
Interactive Voice Response System 
JRA 
Juvenile Rheumatoid Arthritis 
LOCF 
Last Observation Carried Forward 
MTX 
Methotrexate 
Ntx  
N − telopeptide 
OL 
Open-Label 
PCDAI 
Pediatric Crohn's Disease Activity Index 
PK 
Pharmacokinetics 
POR 
Proof of Receipt 
RA 
Rheumatoid Arthritis 
SAE 
Serious Adverse Event 
SAP 
Statistical analysis plan 
SC 
Subcutaneous 
SSC 
Sponsor Steering Committee 
TB 
Tuberculosis 
TNF 
Tumor Necrosis Factor 
TPN 
Total Parenteral Nutrition 
US 
United States 
WPAI 
Work Productivity and Activity Impairment Questionnaire 
WPAI-CD 
Work Productivity and Activity Impairment Questionnaire: Crohn's 
Disease 
 

 
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Appendix B.  
List of Protocol Signatories 
Name 
Title 
Functional Area 
Statistics 
Clinical 
Clinical 
Clinical 
 

 
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Appendix C.  
Documents Required Prior to Initiation of the Study 
As sponsor of a clinical study, Abbott has an obligation to ensure that the study will be 
conducted by a qualified investigator with sufficient resources (of time, personnel, and 
physical facilities) to conduct the study and to ensure that the investigator understands 
and agrees to comply with Good Clinical Practices and applicable regulations, policies, 
and procedures.  Prior to the beginning of any clinical study, the investigator will be 
asked to provide the following documentation.  
1. 
A signed and dated Investigator's agreement page for the study. 
2. 
A signed and dated Form FDA 1572 certifying the investigator's agreement to 
comply with the appropriate regulations governing the conduct of the study. 
 
A signed and dated Investigator Information and Agreement Form certifying the 
investigator's agreement to comply with the appropriate (e.g., ICH GCP) 
regulations governing the conduct of the study. These will be required only for 
sites that are recruited under this amendment, or when existing sites update study 
documentation. 
3. 
 Current curriculum vitae for the investigator.  If subinvestigators will participate 
in the study, curriculum vitae for each. 
4. 
Requirements for the Independent Ethics Committee (IEC)/Institutional Review 
Board (IRB). 
● A copy of the signed and dated letter of approval of the IEC/IRB.  The letter 
must specify that both the protocol and informed consent form were approved 
(unless separate documentation that the informed consent was approved is 
provided). 
● A dated list containing the names and affiliations of the members of the 
IEC/IRB, or the institution's General Assurance Number. 

 
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● If the investigator and/or subinvestigator is a member of the IEC/IRB, a letter 
stating that he/she did not participate in the review or approval of the protocol 
or informed consent form. 
5. 
A specimen copy of the IEC/IRB-approved informed consent document to be used 
in the study. 
6. 
A list of reference ranges of values for all laboratory tests specified by the protocol 
for all laboratories utilized. 
7. 
A copy of the laboratory(ies) certification(s) or the authorization number of the 
certification(s), the name of the certifying authority, and the period of certification. 
8. 
Financial Disclosure Certification forms must be completed by each investigator 
and all subinvestigators identified on the Form FDA 1572 or Investigator 
Information and Agreement Form.  A Financial Disclosure, EU Consent, is 
required to be completed for each investigator and/or subinvestigator who is a 
resident of the European Union 
 

 
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Appendix D.  
Responsibilities of the Clinical Investigator 
Clinical research studies sponsored by Abbott are subject to the regulations of the U.S. 
Food and Drug Administration (FDA).  The responsibilities imposed upon Investigators 
by the FDA are summarized in the "Statement of Investigator" (Form FDA 1572), which 
is a form letter addressed to the sponsor (Abbott), summarizing the Investigator's 
qualifications for the study and his/her willingness to follow FDA regulations with 
respect to the study. 
In signing a Form FDA 1572, the Investigator agrees to assume the following 
responsibilities:   
1. 
To conduct the study(ies) in accordance with the relevant, current protocol(s) and 
only make changes in a protocol after notifying Abbott, except when necessary to 
protect the safety, rights, or welfare of subjects. 
2. 
To personally conduct or supervise the described investigation(s). 
3. 
To inform any subjects, or any persons used as controls, that the drugs are being 
used for investigational purposes and to ensure that the requirements relating to 
obtaining informed consent in 21 CFR Part 50 and Independent Ethics Committee 
(IEC)/Institutional Review Board (IRB) review and approval in 21 CFR Part 56 
are met. 
4. 
To report to Abbott adverse experiences that occur in the course of the 
investigation(s) in accordance with 21 CFR 312.64. 
5. 
To read and understand the information in the Investigator's Brochure, including 
the potential risks and side effects of the drug. 
6. 
To ensure that all associates, colleagues, and employees assisting in the conduct of 
the study(ies) are informed about their obligations in meeting the above 
commitments. 

 
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7. 
To maintain adequate and accurate records of the conduct of the study and make 
those records available for inspection by representatives of Abbott, the IEC/IRB 
and/or the appropriate regulatory agency, and to retain all study-related documents 
until notification from Abbott.  The Investigator must notify Abbott when they are 
no longer able to retain the study related documents. 
8. 
To ensure that an IEC/IRB that complies with the requirements of 21 CFR Part 56 
will be responsible for the initial and continuing review and approval of the 
clinical investigation. 
9. 
To promptly report to the IEC/IRB all changes in the research activity and all 
unanticipated problems involving risks to human subjects or others (including 
submission of any Expedited Safety Reports received from Abbott to the 
IEC/IRB), and to make no changes in the research without IEC/IRB approval, 
except where necessary to eliminate apparent immediate hazards to human 
subjects. 
10. 
To comply with all other requirements regarding the obligations of clinical 
Investigators and all other pertinent requirements in 21 CFR Part 312. 
 

 
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Appendix E.  
CDC Treatment of Tuberculosis Infection (Preventive Therapy) 
Centers for Disease Control and Prevention 
Tuberculosis Information 
Treatment of Tuberculosis Infection (Preventive Therapy), Latent Tuberculosis 
Infection (LBTI)32 
 
 

 
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Appendix F.  
Non-Drug Materials Provided to the Study Site(s) 
Study sites will receive the following supplies prior to or during the study: 
Tote Bags 
Cooler 
Sharps Containers 
Ice Packs 
CDAI subject diary 
Dosing Diaries 
Subject Medication Log 
Self Injection Instructions 

 
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Appendix G.  
Pediatric Crohn's Disease Activity Index (PCDAI) 
1. Abdominal pain rating 
 
- None 
 
- Mild - Brief, does not interfere with activities 
 
- Moderate/severe-Daily, longer lasting, affects activities, nocturnal 
 
= 0 p 
= 5 p 
= 10 p 
Score 
2. Stools (per day) 
 
- 0–1 liquid stools, no blood 
 
- Up to 2 semi-formed with small blood, or 2–5 liquid 
 
- Gross bleeding, or t 6 liquid, or nocturnal diarrhea 
 
= 0 p 
= 5 p 
= 10 p 
 
3. Patient Functioning, General Well-Being 
 
- No limitation of activities, well 
 
- Occasional difficulty in maintaining age appropriate activities, below par 
 
- Frequent limitation of activity, very poor 
 
= 0 p 
= 5 p 
= 10 p 
 
LABORATORY 
Score 
4. HCT: Male and female  d 10 years: 
 
 
t 33 
= 0 p 
 
 
28-32 
= 2.5 p 
 
 
< 28 
= 5 p 
 
Male 11–14 years: 
 
 
t35 
= 0 p 
 
 
30-34 
= 2.5 p 
 
 
<30 
= 5 p 
 
 
Female 11–19 years: t 34 
= 0 p 
 
 
29-33 
= 2.5 p 
 
 
< 29 
= 5 p 
 
Male 15–19 years: 
t37 
= 0 p 
 
 
32-36 
= 2.5 p 
 
 
<32 
= 5 p 
 
5. 
ESR (mm/hr) 
< 20 
= 0 p 
 
 
20-50 
= 2.5 p 
 
 
> 50 
= 5 p 
 
6. 
Albumin (g/dL) 
t 3.5 
= 0 p 
 
 
3.1-3.4 
= 5 p 
 
 
d 3.0 
= 10 p 
 

 
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EXAMINATION 
Score 
7. 
Weight 
- Weight gain or voluntary weight stable/loss 
 
 
- Involuntary weight stable, weight loss 1–9% 
 
 
- Weight loss t 10% 
= 0 p 
= 5 p 
= 10 p 
 
8. 
Height 
 
 
 
 
 
 
 
 
Height velocity t -1SD 
 
 
 
Height velocity < -1SD, > -2SD 
 
 
 
Height velocity d -2SD 
 
= 0 p 
= 5 p 
= 10 p 
 
9. 
Abdomen 
- No tenderness, no mass 
 
 
- Tenderness, or mass without tenderness 
 
 
- Tenderness, involuntary guarding, definite mass 
= 0 p 
= 5 p 
= 10 p 
 
10. Perirectal disease 
- None, asymptomatic tags 
 
 
- 1–2 indolent fistula, scant drainage, no tenderness 
 
 
- Active fistula, drainage, tenderness, or abscess 
= 0 p 
= 5 p 
= 10 p 
 
11. Extra-intestinal Manifestations 
 
(Fever t 38.5 for 3 days over past week, definite arthritis, uveitis, E. nodosum, 
P. gangrenosum) 
 
- None 
 
- One 
 
- t Two 
 
 
= 0 p 
= 5 p 
= 10 p 
 
TOTAL SCORE  
Pediatric Crohn's Disease Activity Index (PCDAI) 
 
 

 
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Appendix H.  
PCDAI User's Guide and Guideline for Reference Weight and 
Reference Height 
This guide is intended to help nurse coordinators and physicians complete the PCDAI in 
order to assess disease activity in children with Crohn's disease participating in clinical 
trials. 
History 
All calculations are based upon a one-week (7 day) history recall of symptoms.  The 
history recall should be solicited from the subject and/or caregiver. 
Item 1.  Abdominal pain 
The descriptions in the PCDAI of "mild" and "moderate/severe" should be used to guide 
in scoring the pain. Note that duration, effect on activities, and nocturnal occurrence 
separate moderate/severe from mild.  If pain varies in severity during the week, subject 
should be scored according to the most severe pain. However, mild pain should be 
present on at least two days to score 5 points rather than 0 points. 
Item 2.  Stools 
The intent is to score the stool pattern during the preceding week. 
To facilitate scoring, first categorize the subject as having blood in the stool or not. 
If there is no blood in the stool, score as follows:   
Formed stools or up to 1 loose stool daily = 0 
2-5 liquid or very loose stools on 1 or more days = 5 
6 or more liquid or very loose stools on 1 or more days or any nocturnal diarrhea = 10 

 
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If blood is present in the stool on any day during the past week, score as follows:   
Small amounts of blood in stool (on toilet paper or small spots in stool, etc.) = 5 
Any gross bleeding (large amounts on stool or colors the water in the toilet, etc.) = 10 
Item 3.  Subject functioning, general well-being 
If there is variation during the week, subject should be scored according to the most 
significant limitation of activity, even if it occurs during only one day of the week, as 
long as it is likely due to Crohn's disease and not to an intercurrent illness. 
Item 4.  Hematocrit 
Hematocrit values should be rounded to a whole number prior to completing the 
calculation.   Numbers that fall between the range of 0.1-0.4 must be rounded down.   
Numbers that fall between the range of 0.5-0.9 must be rounded up. 
Physical Examination 
Item 7.  Weight (The intent is to assess the ability to normally maintain or gain weight) 
Reference weight to be used for calculation of weight gain/loss during the study: 
From Baseline to Week 264: use weight from previous visit 
Voluntary weight stable/loss means subject maintaining or losing weight on purpose. 
Involuntary weight stable means subject wants to gain weight but cannot. 
To calculate percentage weight loss use formula:   
Weight from previous visit – Current weight X 100 = % weight loss 
 
Weight from previous visit 

 
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Item 8.  Height 
Reference height for calculation of height velocity 
● From Baseline to Week 24, use height from 6 months prior to Baseline 
● From Week 24 to Week 48, use height from Baseline visit 
● From Week 48 to Week 72, use height from Week 24 
● From Week 72 to Week 96, use height from Week 48 
● From Week 96 to Week 120, use height from Week 72 
● From Week 120 to Week 144, use height from Week 96 
● From Week 144 to Week 168, use height from Week 120 
● From Week 168 to Week 192, use height from Week 144 
● From Week 192 to Week 216, use height from Week 168 
● From Week 216 to Week 240, use height from Week 192 
● From Week 240 to Week 264, use height from Week 216 
 
The intent is to assess the normalcy vs. impairment of the subject's recent linear growth.  
Note that post-pubertal subjects will score 0 points.  For subjects still growing, there are 
two options for scoring.  Method (a) is preferred.  Method (b) to be used if data required 
for (a) are unavailable. 
1. 
Height velocity (cm/year), the most sensitive parameter, should be calculated as 
below: 
Present height –  Appropriate height measurement (from above)  x  12  = Height velocity (cm/year) 
  
        Interval (months) between heights 
Using height velocity chart below, determine centile for height velocity. 

 
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2. 
Scoring for the PCDAI:   
a. Velocity less than "Minus 2 SD" scores 10 points. 
b. Velocity between "Minus 2 SD" and "Minus 1 SD" scores 5 points. 
c. Velocity greater than "Minus 1 SD" scores zero points. 
 
* 
Please note that subjects should score zero points if a subject is a female above 14.5 years of age or a 
male above 17.5 years of age. 
 

 
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Height Velocity Reference Values for Calculating the PCDAI (Males) 
 
Height Velocity in cm per year (Males) 
Age (years) 
Minus 2SD 
Minus 1SD 
Mean 
2.5 
5.7 
7.0 
8.3 
3 
5.4 
6.6 
7.8 
3.5 
5.1 
6.3 
7.4 
4 
4.9 
6.0 
7.1 
4.5 
4.7 
5.8 
6.8 
5 
4.6 
5.6 
6.6 
5.5 
4.5 
5.4 
6.4 
6 
4.3 
5.3 
6.2 
6.5 
4.2 
5.1 
6.0 
7 
4.2 
5.0 
5.9 
7.5 
4.1 
4.9 
5.8 
8 
3.9 
4.8 
5.6 
8.5 
3.8 
4.6 
5.4 
9 
3.8 
4.5 
5.3 
9.5 
3.7 
4.5 
5.2 
10 
3.7 
4.4 
5.1 
10.5 
3.7 
4.4 
5.1 
11 
3.7 
4.4 
5.2 
11.5 
3.8 
4.6 
5.3 
12 
4.0 
4.9 
5.7 
12.5 
4.8 
5.8 
6.7 
13 
6.2 
7.4 
8.6 
13.5 
7.1 
8.3 
9.5 
14 
6.1 
7.2 
8.4 
14.5 
4.1 
5.3 
6.5 
15 
2.4 
3.6 
4.7 
15.5 
1.2 
2.3 
3.3 
16 
0.4 
1.3 
2.2 
16.5 
0.1 
0.7 
1.5 
17 
0.1 
0.4 
0.9 
17.5 
0.1 
0.1 
0.5 
 

 
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Height Velocity Reference Values for Calculating the PCDAI (Females) 
 
Height Velocity in cm per year (Females) 
Age (years) 
Minus 2SD 
Minus 1SD 
Mean 
2.5 
5.9 
7.3 
8.6 
3 
5.5 
6.9 
8.1 
3.5 
5.2 
6.4 
7.6 
4 
4.9 
6.1 
7.2 
4.5 
4.7 
5.8 
6.8 
5 
4.6 
5.6 
6.6 
5.5 
4.5 
5.5 
6.4 
6 
4.4 
5.3 
6.2 
6.5 
4.3 
5.2 
6.1 
7 
4.3 
5.2 
6.0 
7.5 
4.3 
5.1 
5.9 
8 
4.2 
5.0 
5.8 
8.5 
4.2 
4.9 
5.7 
9 
4.2 
5.0 
5.8 
9.5 
4.3 
5.0 
5.8 
10 
4.4 
5.3 
6.2 
10.5 
4.7 
5.7 
6.8 
11 
5.7 
6.6 
7.7 
11.5 
6.1 
7.2 
8.3 
12 
5.2 
6.3 
7.3 
12.5 
3.6 
4.8 
5.9 
13 
2.4 
3.3 
4.3 
13.5 
1.3 
2.2 
2.9 
14 
0.4 
1.1 
1.8 
14.5 
0.0 
0.5 
1.0 
 

 
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Appendix I.  
Crohn's Disease Activity Index (CDAI) 
 
 
 
Factor 
Subtotal 
1. Number of liquid or very soft stools
(Record the frequency per day) 
         __+___+___+___+___+___+___=___ 
Days: 1     2      3      4 
5      6 
  7   Sum 
X 
2 
 
2.  Abdominal pain rating: 
0=none, 1=mild, 2=moderate, 
3=severe 
          __+___+___+___+___+___+___=___ 
Days: 1     2      3      4 
5      6 
  7   Sum 
X 
5 
 
3. General well-being: 
0=generally well, 1=slightly 
underpar, 2=poor, 3=very poor, 
4=terrible 
         __+___+___+___+___+___+___=___ 
Days: 1     2      3      4 
5      6 
  7   Sum 
X 
7 
 
4. Number of 6 listed categories the 
subject now has: 
Check all items that apply: 
□  Arthritis/arthralgia 
□  Iritis/uveitis 
□  Erythema nodosum/  
 pyoderma gangrenosum/ 
 aphthous stomatitis 
□  Fissure, abscess and/or anal 
fistula (draining/non-draining) 
□  Other cutaneous fistula 
(draining/non-draining) fistula 
□  Fever over 100°F (37.8°C) during 
past week 
 
 
 
 
 
 
  
________ 
 
 
 
Record "0" if no categories checked 
X 
20 
 
5.   Taking Lomotil / Imodium / 
Loperamide /opiates for diarrhea  
0=no, 1=yes 
________ X 
30 
 
6.   Abdominal mass 
0=none, 2=questionable, 5=defined 
________ X 
10 
 
7.   Hematocrit: ______ 
Male: 
(47 - hematocrit) = 
Female: (42 - hematocrit) = Subtotal ______ 
If hematocrit > normal, enter "0" 
X 
6 
 
8.   Body weight: __  __  __ . __ (kg) 
Ideal weight for height: 
__  __  __ . __ (kg) 
100 x [1 - (Body wt/Ideal wt)] =  
Percent below ideal weight: ______ 
If body wt > ideal wt, enter "0" 
X 
1 
 
 
 
 
Total 
 
* 
Ideal weight is obtained from CDC growth charts.  The subtotal of box 8 should be rounded to a whole number.  
Numbers that fall between the range of .1-.4 must be rounded down.   Numbers that fall between the range of .5-.9 
must be rounded up.  To ensure consistency across all sites and to take into account the varying growth rates of 
subjects in this study, the IBW should be calculated at each visit. 
* 
Hematocrit values should be rounded to a whole number prior to completing the calculation in box 7 of the CDAI.   
Numbers that fall between the range of .1-.4 must be rounded down.   Numbers that fall between the range of .5-.9 
must be rounded up. 

 
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Appendix J.  
Subject CDAI Diary 
Crohn's Disease Activity Index 
Subject Diary Card 
Enter all values legibly using a black 
ballpoint pen. 
Add item requested for each day. 
Day 
Date___ 
Day 
Date___ 
Day 
Date___ 
Day 
Date___ 
Day 
Date___ 
Day 
Date___ 
Day 
Date___ 
Number (total) of liquid or very soft 
stools per day. 
 
 
 
 
 
 
 
Daily abdominal pain rating. 
(0=none, 1=mild, 2=moderate, 3=severe) 
 
 
 
 
 
 
 
Daily rating of general well being. 
(0=well, 1=slightly below par, 2=poor, 
3=very poor, 4=terrible) 
 
 
 
 
 
 
 
Subject Initials:___________ 
Subject's Signature:__________________________ 
 
Investigator or Designee's Signature:______________________ 

 
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Question 1. 
How much has your stomach been hurting you in the past two weeks? 
□ 
□ 
□ 
□ 
□ 
Not at all 
 Hardly hurting 
at all 
Hurting 
somewhat  
Hurting 
quite a bit 
Hurting 
very much 
 
Question 2.  
Taking medicines or tablets bothers you 
□ 
□ 
□ 
□ 
□ 
Not at all 
 Hardly bothers 
at all 
Bothers 
somewhat  
Bothers  
quite a bit 
Bothers 
very much 
 
Question 3. 
How often has your inflammatory bowel disease prevented you from 
eating what you want in the past two weeks? 
□ 
□ 
□ 
□ 
□ 
Never 
 Rarely 
Sometimes 
Often 
Very often 
 
Question 4. 
How often have you been worrying about having a flare-up (increase of 
symptoms) in the last two weeks? 
□ 
□ 
□ 
□ 
□ 
Never 
 Rarely 
Sometimes 
Often 
Very often 
 
Question 5. 
How much does it bother you that you have an illness that does not just go 
away? 
□ 
□ 
□ 
□ 
□ 
Not at all 
 Hardly bothers 
at all 
Bothers 
somewhat  
Bothers quite a 
bit 
Bothers very 
much 
 
Question 6. 
How much energy did you have during the past two weeks? 
□ 
□ 
□ 
□ 
□ 
Very much 
energy 
Quite a bit of 
energy 
Some energy 
 A little energy 
No energy at 
all  

 
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Question 7. 
How do you feel about your weight? 
□ 
□ 
□ 
□ 
□ 
I feel great 
about my 
weight 
I feel good 
about my 
weight 
I don't feel 
good or bad 
about my 
weight 
I feel bad about 
my weight 
I feel awful 
about my 
weight 
 
Question 8. 
How has your inflammatory bowel disease affected your family? 
□ 
□ 
□ 
□ 
□ 
The effect has 
been great 
The effect has 
been good 
It has not 
affected our 
family 
The effect has 
been bad 
The effect has 
been awful 
 
Question 9. 
How often did you have to miss out on certain things (hobbies, play, 
parties) because of your inflammatory bowel disease in the past two weeks? 
□ 
□ 
□ 
□ 
□ 
Never 
Rarely 
Sometimes 
Often 
Very often 
 
Question 10. How often have you been bothered by diarrhea (loose or frequent bowel 
movements) in the past two weeks? 
□ 
□ 
□ 
□ 
□ 
Never 
Rarely 
Sometimes 
Often 
Very often 
 
Question 11. How often do you worry about health problems you might have in the 
future? 
□ 
□ 
□ 
□ 
□ 
Never 
Rarely 
Sometimes 
Often 
Very often 
 

 
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Question 12. How often do you think it is unfair that you have inflammatory bowel 
disease? 
□ 
□ 
□ 
□ 
□ 
Never 
Rarely 
Sometimes 
Often 
Very often 
 
Question 13. During the past two weeks, were you ever angry that you have 
inflammatory bowel disease? 
□ 
□ 
□ 
□ 
□ 
Never 
Rarely 
Sometimes 
Often 
Very often 
 
Question 14. Do you think too many rules or limits are placed on you because of your 
inflammatory bowel disease? 
□ 
□ 
□ 
□ 
□ 
Never 
Rarely 
Sometimes 
Often 
Very often 
 
Question 15. How do you feel about the way you look? 
□ 
□ 
□ 
□ 
□ 
I think I look 
great 
I think I look 
good 
I don't think I 
look good or 
bad 
I think I look 
bad 
I think I look 
awful 
 
Question 16. Are you embarrassed because of your bowel condition? 
□ 
□ 
□ 
□ 
□ 
Not at all 
 Hardly 
embarrassed at 
all 
Embarrassed 
somewhat  
Embarrassed 
quite a bit 
Embarrassed 
very much 
 
Question 17. Did you have fun during the past two weeks? 
□ 
□ 
□ 
□ 
□ 
Very often 
Often 
Sometimes 
Rarely 
Never 

 
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Question 18. Is it harder to make friends because of your inflammatory bowel disease? 
□ 
□ 
□ 
□ 
□ 
Not at all 
harder 
 A little harder 
Quite a bit 
harder 
Much harder 
Very much 
harder 
 
Question 19.  How often do you worry about your stool (bowel movement) containing 
blood? 
□ 
□ 
□ 
□ 
□ 
Never 
Rarely 
Sometimes 
Often 
Very often 
 
Question 20. Are you worried you cannot go out on a date or have a boyfriend or 
girlfriend because of your inflammatory bowel disease? 
□ 
□ 
□ 
□ 
□ 
Not at all 
worried 
 Hardly 
worried at all 
Worried 
somewhat  
Worried quite a 
bit 
Worried very 
much 
 
Question 21. How often did you feel sick to your stomach in the past two weeks? 
□ 
□ 
□ 
□ 
□ 
Never 
Rarely 
Sometimes 
Often 
Very often 
 
Question 22. How do you feel about the tests you have to go through? 
□ 
□ 
□ 
□ 
□ 
I do not mind 
them at all 
I mind them a 
tiny bit 
I mind them a 
little 
I mind them a 
lot 
I hate them 
 
Question 23. Do other children bully you or leave you out of things because of your 
inflammatory bowel disease or its treatment? 
□ 
□ 
□ 
□ 
□ 
Never 
Rarely 
Sometimes 
Often 
Very often 

 
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Question 24. How often do you worry about having an operation? 
□ 
□ 
□ 
□ 
□ 
Never 
Rarely 
Sometimes 
Often 
Very often 
 
Question 25. In the past two weeks how often were you afraid you may have an 
accident or not get to the toilet in time? 
□ 
□ 
□ 
□ 
□ 
Never 
Rarely 
Sometimes 
Often 
Very often 
 
Question 26. Do you try to keep your inflammatory bowel disease a secret from other 
people? 
□ 
□ 
□ 
□ 
□ 
No, I do not try 
at all 
I don't try 
much 
I try a little 
I try hard 
Yes, I try very 
hard 
 
Question 27. Does your inflammatory bowel disease make it difficult to travel or go on 
a holiday? 
□ 
□ 
□ 
□ 
□ 
No, not 
difficult 
A little difficult
Quite difficult 
Very difficult 
Yes, extremely 
difficult 
 
Question 28.  How did you feel during the past two weeks? 
□ 
□ 
□ 
□ 
□ 
Great 
Good 
Not good or 
bad 
Bad  
Awful 
 
Question 29. Are you happy with your life? 
□ 
□ 
□ 
□ 
□ 
Yes, very 
happy 
Happy 
Not happy or 
unhappy 
Unhappy 
Very unhappy 

 
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Question 30. Do you feel there is someone you can talk to about your inflammatory 
bowel disease? 
□ 
□ 
□ 
□ 
□ 
Always  
Often  
Sometimes  
Rarely 
Never 
 
Question 31. How often did you have to pass gas in the past two weeks? 
□ 
□ 
□ 
□ 
□ 
Never 
Rarely 
Sometimes 
Often 
Very often 
 
Question 32. How tired have you felt in the past two weeks? 
□ 
□ 
□ 
□ 
□ 
Not at all tired 
 A little tired 
Quite tired 
Tired  
Very tired 
 
Question 33. How do you feel about your height? 
□ 
□ 
□ 
□ 
□ 
I feel great 
about my 
height 
I feel good 
about my 
height 
I don't feel 
good or bad 
about my 
height 
I feel bad about 
my height 
I feel awful 
about my 
height 
 
Question 34. Does your inflammatory bowel disease get in the way of playing sports the 
way you would like to? 
□ 
□ 
□ 
□ 
□ 
Never 
Rarely 
Sometimes 
Often 
Always 
 
Question 35. In the past two weeks how often were you able to go to school? (If you are 
in the middle of a school break or the summer holidays, answer as if school was on) 
□ 
□ 
□ 
□ 
□ 
Always  
Most days  
Half the days 
A few days 
Never 
 

 
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End of questionnaire 
This completes the questionnaire. Do you have anything else to add which you feel is 
important about having inflammatory bowel disease, or do you have any other 
remarks? Please write them below. 
 
_________________________________________________________ 
_________________________________________________________ 
_________________________________________________________ 

 
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Appendix L.  
Excluded Medications 
Cyclosporine 
Tacrolimus 
Therapeutic enemas and suppositories (not including those done in conjunction with 
routine colonoscopy) 
Live vaccines 
The combination of budesonide and prednisone (or equivalent) 
Infliximab 
Mycophenolate mofetil (MMF or CellCept® ) 
Growth Hormone 
Kineret® (anakinra) 
Tysabri (natalizumab) 
Orencia (abatacept) 
Concurrent biologic therapy 
Any investigational agent 
Any previous anti-TNF medication except infliximab before the M06-806 study 
(including adalimumab). 
 

 
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Appendix M.  
Day 70 Phone Call 
Site Name / Number: ________ 
Subject Number:________ 
Subject Initials:________ 
Please contact all Subjects 70 days following drug discontinuation. 
 
 
 
Date of Call: ____________ 
 
 
□     Lost to Follow-Up (Please check this box if subject was not willing to provide any follow-up 
information or you were unable to speak to the subject following at least one attempt). 
 
 
□      No Events Reported 
 
List any Adverse Events (AE) and/or Serious Adverse Events (SAE) that occurred since the subject was 
last seen in clinic for this study.  Please document all adverse events on a 500 AE CRF to be submitted to 
data management.  (Please report all SAEs to Abbott within 24 hours of being made aware of the event.  
Follow-up information must also be reported within 24 hours of being made aware of the information.). 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
If events are listed above, your monitor will review and retrieve the appropriate CRF pages during 
their next visit.  Please fax this form to Paragon at 
. 
 

 
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Appendix N.  
Unscheduled Outpatient Visits, Emergency Room Visits and 
Hospitalizations 
1. 
Since the last study visit has the subject had any physician/health care visits for 
their Crohn's disease other than the protocol required visits? 
Yes ___ 
No  ___ 
If yes provide the following: 
I. 
Since the last visit, has the subject been seen by a physician for their Crohn's 
Disease? 
YES:_____ 
NO:_____ 
If YES, how many times:_______ 
 
 
II. Since the last visit, has the subject been seen in the Emergency Room for their 
Crohn's Disease? 
YES:_____ 
NO:______ 
If YES, how many times:_____ 
III. Since the last visit, has the subject been admitted to the hospital due to their 
Crohn's Disease? 
YES:_____ 
NO:______ 
If YES, how many times:_____ 
If YES, please indicate the total number of days in the hospital:_____ 
 
 

 
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Appendix O.  
Subject Medication Log 
Instructions:  As a participant in this study, it is also important to keep a record of all mediations you take (new and old) throughout the study.  Please take this 
sheet home with you and write down any medications you take during the study.  It will be VERY important that you bring this sheet back to your doctor's office 
and speak with your doctor about everything you have written down. 
 
Name of Medication 
Date you took
first dose 
Date you took
last dose 
What dose of medicine 
did you take? 
How often did you 
take the medicine? 
Why did you take the 
medicine? 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
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Week 25 - Week 36 
Subject Initials: __________ 
Subject Study #: ___________ 
 
Date 
day/mm/yr 
Day or 
Week # 
Time of Study 
Drug 
Administration 
Dose (mL) 
Administered
Kit #
Initials of Person 
Administering 
Study Medication 
Comments 
18/MAR/04 EXAMPLE 
9:35 am 
0.8 
 
MM 
none 
 
Week 25 
 
 
 
 
 
 
Week 26 
 
 
 
 
 
 
Week 27 
 
 
 
 
 
 
Week 28 
 
 
 
 
 
 
Week 29 
 
 
 
 
 
 
Week 30 
 
 
 
 
 
 
Week 31 
 
 
 
 
 
 
Week 32 
 
 
 
 
 
 
Week 33 
 
 
 
 
 
 
Week 34 
 
 
 
 
 
 
Week 35 
 
 
 
 
 
 
Week 36 
 
 
 
 
 
 

 
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Week 241 - Week 263 
Subject Initials: __________ 
Subject Study #: ___________ 
 
Date 
day/mm/yr 
Day or 
Week # 
Time of Study 
Drug 
Administration 
Dose (mL) 
Administered
Kit #
Initials of Person 
Administering 
Study Medication Comments
18/MAR/04 
EXAMPLE 
9:35 am 
0.8 
 
MM 
none 
 
Week 241 
 
 
 
 
 
 
Week 242 
 
 
 
 
 
 
Week 243 
 
 
 
 
 
 
Week 244 
 
 
 
 
 
 
Week 245 
 
 
 
 
 
 
Week 246 
 
 
 
 
 
 
Week 247 
 
 
 
 
 
 
Week 248 
 
 
 
 
 
 
Week 249 
 
 
 
 
 
 
Week 250 
 
 
 
 
 
 
Week 251 
 
 
 
 
 
 
Week 252 
 
 
 
 
 
 
Week 253 
 
 
 
 
 
 
Week 254 
 
 
 
 
 
 
Week 255 
 
 
 
 
 
 
Week 256 
 
 
 
 
 
 
Week 257 
 
 
 
 
 
 
Week 258 
 
 
 
 
 
 
Week 259 
 
 
 
 
 
 
Week 260 
 
 
 
 
 
 
Week 261 
 
 
 
 
 
 
Week 262 
 
 
 
 
 
 
Week 263* 
 
 
 
 
 
* 
Week 259 dose will only be taken if on every-week dosing schedule. 
 

 
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Appendix Q.  
Self Injection Instructions 
 
 
Subject Instructions 
0.8 mL or 0.4 mL dose 
(Administered as a single dose-prefilled syringe (PFS)) 
 
Protocol M06-807 
 

 
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Tables of Contents 
Dosing Schedule 
General Information & Supplies 
Injection Procedures 
 

 
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Study Drug Dosing Schedule 
Open-Label (PFS) 
Subject Number:_____________________________________ 
You will require subcutaneous (SC) injections throughout the study.  
Injections at scheduled study visits (Baseline, Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 
108, 120, 144, 168, 192, 216 and 240) will be done during your visit, at the doctor's 
office.  On weeks between office visits, study drug will be self-administered at home by 
you or someone trained to give you the injections. 
One pre-filled syringe will contain 0.8 mL of liquid.  The total available dose is 0.8 mL. 
The drug should be administered in one (1) SC injection, on the same day of the week for 
each dose. 
Please return all used and unused syringes to the clinic on your next visit. Used syringes 
should be placed in the special sharps container provided. All unused syringes should be 
returned in the original box. 
If an injection is missed or something occurs where the full dose cannot be injected, 
contact your study center immediately for further instructions. Please record any missed 
doses on your subject diary. 
Remember to complete your dosing diary after each injection and to call the doctor's 
office if you are having problems administering your study drug. 

 
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General Information 
 
 
 
 
 
 
 
PFS 
● Prefilled syringes will be labeled "adalimumab." 
● Store all adalimumab prefilled syringes in your refrigerator NOT in the 
freezer.  Should the syringes accidentally become frozen, call your study 
coordinator. 
● 0.8 mL = 0.8 cc 
● Study drug should be taken at about the same time of day, on the same day of 
the week as directed by your study doctor. 
● USE A NEW SYRINGE EVERY INJECTION DAY. There may be 
medication left in the syringe. DO NOT RE-USE. 
● Save all study drugs. Prefilled syringes (used and unused) must be returned 
to the study center at each visit. Used syringes will be disposed of in a sharps 
container provided to you. 
● Whenever possible, have someone with you for at least 15 to 30 minutes after 
your injection. 
● Call your doctor IMMEDIATELY if you experience any itching, hives, 
shortness of breath, or any symptom that has you concerned. If you are unable 
to reach your doctor or if you experience life-threatening symptoms call 911, 
or proceed to your nearest emergency room. 
 

 
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Injection Procedures 
 
 
 
 
 
 
 
PFS 
1. Clean your workspace, gather your supplies, and wash your hands. 
 
 
2. Identify the area on your abdomen or thigh (or upper arm 
if not self injecting). Make sure the area you choose does 
not have any redness, tenderness, swelling, bruising, or 
psoriasis. The area must also be at least 2 cm 
(approximately 1 inch) away from the previous injection 
site. IT IS VERY IMPORTANT TO CHANGE THE 
INJECTION SITE EVERY TIME!!! 
 
 
3. Using a circular motion (starting at the injection site and 
moving outward) clean the selected injection site with 
an alcohol pad. Allow skin to dry.  
4. Remove the needle cap. Do not touch the needle. Expel 
any air bubbles from the syringe by tapping on the 
syringe. If the needle becomes contaminated, discard all 
supplies and obtain a new syringe of study drug.  
5. Once the air is expelled from the syringe, the amount of 
solution in the syringe should be 0.8 mL. 
 
 
6.   Hold the syringe "like a dart" between your thumb and 
first finger close to the syringe/needle connection. 

 
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PFS 
 
7. With your other hand, pinch the skin around the 
injection site, forming a bulge in the skin. 
 
 
 
 
 
 
8. Insert the needle into the skin at a 45-degree angle. 
Release pinched skin. 
 
 
 
 
9. 
GENTLY pull back on the syringe plunger. If blood 
appears, withdraw needle - DO NOT INJECT! Contact 
your study center immediately for further instructions. 
 
10. Inject drug by pushing slowly on syringe plunger with 
thumb. 
 
11. Remove needle while maintaining a 45-degree angle. 
 
12. You may apply a Band-Aid over the injection site and 
apply gentle pressure, if necessary. DO NOT RUB 
SITE. 
 
13. 
DO NOT RECAP NEEDLE. DO NOT SEPARATE THE NEEDLE FROM THE 
 
SYRINGE BEFORE DISPOSING. Discard used syringes into Sharps Container. 
EACH TIME THAT YOU GIVE YOURSELF AN INJECTION OF STUDY DRUG, 
REMEMBER TO RECORD THE INFORMATION ON YOUR SUBJECT DOSING 
DIARY. 
 

 
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Appendix R.  
Standard Weights 
 
 

 
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Appendix S.  
Subject Abbott Laboratories Site Drug Accountability Form 
 

 
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Appendix T.  
Work Productivity and Activity Impairment Questionnaire: 
Crohn's Disease (WPAI-CD) - Caregiver 
The following questions ask about the effect of your child's Crohn's disease on your 
ability to work and perform regular activities.  Please fill in the blanks or circle a 
number, as indicated. 
1.  Are you currently employed (working for pay)?  
_____ NO ___ YES 
  If NO, check "NO" and skip to question 6. 
The next questions are about the past seven days, not including today. 
 
 
2. During the past seven days, how many hours did you miss from work because of 
problems associated with your child's Crohn's disease?  Include hours you missed on 
sick days, times you went in late, left early, etc., because of your child's Crohn's 
disease.  Do not include time you missed for your child to participate in this study. 
 
_____ HOURS 
 
3. During the past seven days, how many hours did you miss from work because of any 
other reason, such as vacation, holidays, time off for your child to participate in this 
study? 
 
_____HOURS 
 
4. During the past seven days, how many hours did you actually work? 
 
_____HOURS  (If "0," skip to question 6.) 
 

 
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5. During the past seven days, how much did your child's Crohn's disease affect your 
productivity while you were working?   
 
Think about days you were limited in the amount or kind of work you could do, days 
you accomplished less than you would like, or days you could not do your work as 
carefully as usual.  If your child's Crohn's disease affected your work only a little, 
choose a low number.  Choose a high number if your child's Crohn's disease affected 
your work a great deal.   
Consider only how much your child's Crohn's disease affected  
your productivity while you were working. 
 
 
 
 
 
 
 
 
 
 
 
My child's Crohn's 
disease had no 
effect on my work 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
My child's Crohn's 
disease completely 
prevented me from 
working 
CIRCLE A NUMBER 
6. During the past seven days, how much did your child's Crohn's Disease affect your 
ability to do your regular daily activities, other than work at a job?   
 
By regular activities, we mean the usual activities you do, such as work around the 
house, shopping, childcare, exercising, studying, etc.  Think about times you were 
limited in the amount or kind of activities you could do and times you accomplished 
less than you would like.  If your child's Crohn's Disease affected your activities only 
a little, choose a low number.  Choose a high number if your child's Crohn's Disease 
affected your activities a great deal.   
 
Consider only how much your child's Crohn's disease affected your ability  
to do your regular daily activities, other than work at a job. 
 
 
 
 
 
 
 
 
 
 
 
My child's 
Crohn's disease 
had no effect on 
my daily 
activities 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
My child's Crohn's 
disease completely 
prevented me from 
doing my daily 
activities 
 
 
                           
CIRCLE A NUMBER 
WPAI:CD-Caregiver (US English) 

 
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Appendix U.  
Protocol Amendment:  List of Changes 
The summary of changes is listed in Section 1.1. 
Specific Protocol Changes: 
Section 1.0  Title Page 
"Emergency Contact:" previously read: 
Has been changed to read: 
Section 5.1  Overall Study Design and Plan:  Description 
First paragraph previously read: 
This study is a multi-center, open-label study of the human anti-TNF monoclonal 
antibody adalimumab.  Approximately 55 sites that have enrolled subjects in the 

 
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M06 − 806 clinical trial will participate in the M06-807 clinical trial.  Approximately 
130 pediatric subjects are expected to enroll in this study.   
Has been changed to read: 
This study is a multi-center, open-label study of the human anti-TNF monoclonal 
antibody adalimumab.  Approximately 31 sites that have enrolled subjects in the 
M06-806 clinical trial will participate in the M06-807 clinical trial.  Approximately 
130 pediatric subjects were expected to enroll in this study; final enrollment was 
100 subjects.   
Section 5.1  Overall Study Design and Plan:  Description 
Third paragraph previously read: 
Subjects may be allowed to enroll in the M06-807 study if they have participated in, and 
successfully completed Protocol M06-806 through Week 52.  At the end of 
Study M06 − 806, a subject must be a responder to enroll in this trial.  A responder is 
defined as a subject who had a PCDAI score that was at least 15 points lower than the 
M06-806 baseline score. 
Has been changed to read: 
Subjects may be allowed to enroll in the M06-807 study if they have participated in, and 
successfully completed Protocol M06-806 through Week 52.  A subject must be a 
responder at any time point during the M06-806 study.  A responder is defined as a 
subject who had a PCDAI score that was at least 15 points lower than the M06-806 
baseline score. 
Section 5.1  Overall Study Design and Plan:  Description 
Eleventh paragraph previously read: 
The duration of the study could last up to 104 weeks.  Subjects who complete, or who 
early terminate from the study will be contacted 70 days after their last dose of study drug 
to obtain information on any ongoing and new AEs.   

 
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Has been changed to read: 
The duration of the study could last up to 264 weeks (approximately 5 years).  Subjects 
who complete, or who early terminate from the study will be contacted 70 days after their 
last dose of study drug to obtain information on any ongoing and new AEs.   
This study will conclude approximately 12 weeks after the following criteria have been 
satisfied: 
● Study drug receives country and local (if applicable) regulatory approval for 
pediatric Crohn's Disease. 
● All applicable local reimbursement procedures are completed. 
 
Sites will be notified once these criteria are met. 
Following country and local (if applicable) regulatory approval and applicable local 
reimbursement approval of the study drug in a country, subjects should return to their 
next scheduled study visit as specified in the protocol.  The termination visit should be 
conducted in place of their regular scheduled study visit.  These subjects should be 
considered as having completed the study. 
 

 
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Table 1.  Study Activities  
Previously read: 
Activity 
Base-
line 
Week
4 
Week
8 
Week
12 
Week
24 
Week
36 
Week
48 
Week 
60 
Week 
72 
Week 
84 
Week 
96 
Week 
104/ 
Early 
Term 
Unscheduled 
visit 
70-Day 
Follow-up 
Phone Call
Inclusion/exclusion criteria 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Previous and concomitant 
medications 
Xa 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Urine pregnancy testb 
Xa 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Vital signsc 
Xa 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Physical exam 
Xa 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
General LABd 
Xa 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Urinalysise 
Xa 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Erythrocyte sedimentation 
rate 
Xa 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
CRP 
Xa 
 
 
 
X 
 
X 
 
X 
 
 
X 
 
 
ANA 
Xa 
 
 
X 
 
 
 
 
 
 
 
X 
 
 
Anti-dsDNAf 
Xa 
 
 
X 
 
 
 
 
 
 
 
X 
 
 
PCDAI 
Xa 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
CDAIg 
Xa 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
IMPACT III Questionnaireh 
Xa 
 
 
X 
X 
 
X 
 
X 
 
 
X 
 
 
 

 
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Table 1.  
Study Activities (Continued) 
Activity 
Base-
line 
Week
4 
Week
8 
Week
12 
Week
24 
Week
36 
Week
48 
Week 
60 
Week 
72 
Week 
84 
Week 
96 
Week 
104/ 
Early 
Term 
Unscheduled 
visit 
70-Day 
Follow-up 
Phone Call
Unscheduled outpatient 
visits, emergency room 
visits and hospitalizations 
questionnaire 
Xa 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
Work Productivity and 
Impairment Questionnaire: 
Crohn's Disease  
(WPAI − CD) 
Xa 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
X-ray for bone age 
Xa 
 
 
 
 
 
X 
 
 
 
 
X 
 
 
Serum bone markers 
Xa 
 
 
 
X 
 
X 
 
X 
 
 
X 
 
 
Adverse eventsi 
Xa 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Dispense study drug 
Xa 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Xj 
 
a. 
At the Baseline Visit, the following procedures will be completed as part of Week 52 of the M06-806 study. 
b. 
Performed on all females of child-bearing potential - Urine pregnancy test at all study visits. 
c. 
Vital sign determinations of height, weight, sitting blood pressure, heart rate, respiratory rate, and body temperature will be obtained at each visit. 
d. 
Blood draws should be performed after questionnaire and vital signs determinations and before study drug administration. 
e. 
Microscopic urinalysis will be performed at any visit if dipstick UA is abnormal (protein greater than a trace, blood greater than 5-10 Ery/ul, moderate or large ketone count 
or glucose greater than 50 mg/dL). 
f.  
If an ANA result is positive, anti-dsDNA will be performed automatically. 
g.  For subjects who are age 13 or older at the M06-807 Baseline Visit, a CDAI will be completed at each visit. 
h. 
For subjects who are age 10 or older at the M06-807 Baseline Visit, an IMPACT III Assessment will be completed at Baseline, Weeks 12, 24, 48, 72, and 104/ET. 
i. 
All AEs, including SAEs, will be captured throughout the study from the time that the subject signs the Informed Consent Form. SAEs will be captured throughout the 70 day 
follow-up period (if applicable). 
j. 
If an unscheduled visit is performed to change the frequency of study drug from OL eow to OL ew, study drug may be dispensed. 
 

 
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Has been changed to read: 
Activity 
Baseline 
Week 4 
Week 8 
Week 12 
Week 24 
Week 36 
Week 48 
Week 60 
Week 72 
Week 84 
Week 96 
Week 108
Inclusion/exclusion criteria 
X 
 
 
 
 
 
 
 
 
 
 
 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
 
 
Previous and concomitant 
medications 
Xa 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Urine pregnancy testb 
Xa 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Vital signsc 
Xa 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Physical exam 
Xa 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
General LABd 
Xa 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Urinalysise 
Xa 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Erythrocyte sedimentation 
rate 
Xa 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
CRP 
Xa 
 
 
 
X 
 
X 
 
X 
 
 
X 
ANA 
Xa 
 
 
X 
 
 
 
 
 
 
 
X 
Anti-dsDNAf 
Xa 
 
 
X 
 
 
 
 
 
 
 
X 
PCDAI 
Xa 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
CDAIg 
Xa 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
IMPACT III Questionnaireh 
Xa 
 
 
X 
X 
 
X 
 
X 
 
 
X 
 

 
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Table 1.  
Study Activities (Continued) 
Activity 
Baseline 
Week 4 
Week 8 
Week 12 
Week 24 
Week 36 
Week 48 
Week 60 
Week 72 
Week 84 
Week 96 
Week 108
Unscheduled outpatient 
visits, emergency room 
visits and hospitalizations 
questionnaire 
Xa 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Work Productivity and 
Impairment Questionnaire: 
Crohn's Disease (WPAI − 
CD) 
Xa 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X-ray for bone age 
Xa 
 
 
 
 
 
X 
 
 
 
 
X 
Serum bone markers 
Xa 
 
 
 
X 
 
X 
 
X 
 
 
X 
PK Blood Sample 
 
 
 
 
X 
 
X 
 
X 
 
X 
 
Anti-adalimumab blood 
levels (AAA) 
 
 
 
 
X 
 
X 
 
X 
 
X 
 
Adverse eventsi 
Xa 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Dispense study drug 
Xa 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 

 
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Table 1.  
Study Activities (Continued) 
Activity 
Week 
120 
Week 
132 
Call 
Week 
144 
Week 
156 
Call 
Week 
168 
Week 
180 
Call 
Week 
192 
Week 
204 
Call 
Week 
216 
Week 
228 
Call 
Week 
240 
Week 
252 
Call 
Week 
264/ 
Early 
Term 
Unsched 
Visit 
70-Day 
Follow-up 
Call 
Inclusion/exclusion 
criteria 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Informed consent 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Previous and concomitant 
medications 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Urine pregnancy testb 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
 
Vital signsc 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
 
Physical exam 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
 
General LABd 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
 
Urinalysise 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
 
Erythrocyte 
sedimentation rate 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
 
CRP 
 
 
X 
 
X 
 
X 
 
X 
 
 
 
X 
 
 
ANA 
 
 
X 
 
 
 
X 
 
 
 
 
 
X 
 
 
Anti-dsDNAf 
 
 
X 
 
 
 
X 
 
 
 
 
 
X 
 
 
PCDAI 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
 
CDAIg 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
 
IMPACT III 
Questionnaireh 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
 

 
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Table 1.  
Study Activities (Continued) 
Activity 
Week 
120 
Week 
132 
Call 
Week 
144 
Week 
156 
Call 
Week 
168 
Week 
180 
Call 
Week 
192 
Week 
204 
Call 
Week 
216 
Week 
228 
Call 
Week 
240 
Week 
252 
Call 
Week 
264/ 
Early 
Term 
Unsched 
Visit 
70-Day 
Follow-up 
Call 
Unscheduled outpatient 
visits, emergency room 
visits and 
hospitalizations 
questionnaire 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Work Productivity and 
Impairment 
Questionnaire: Crohn's 
Disease  (WPAI − CD) 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
 
X-ray for bone age 
 
 
X 
 
 
 
X 
 
 
 
 
 
X 
X 
 
Serum bone markers 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
 
PK Blood Samplei 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
 
Anti-adalimumab blood 
levels (AAA)i 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
 
Adverse eventsj 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Dispense study drug 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
 
Xk 
 
 

 
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Table 1.  
Study Activities (Continued) 
a. 
At the Baseline Visit, the following procedures will be completed as part of Week 52 of the M06-806 study. 
b. 
Performed on all females of child-bearing potential - Urine pregnancy test at all study visits. 
c. 
Vital sign determinations of height, weight, sitting blood pressure, heart rate, respiratory rate, and body temperature will be obtained at each visit. 
d. 
Blood draws should be performed after questionnaire and vital signs determinations and before study drug administration. 
e. 
Microscopic urinalysis will be performed at any visit if dipstick UA is abnormal (protein greater than a trace, blood greater than 5-10 Ery/ul, moderate or large ketone count 
or glucose greater than 50 mg/dL). 
f.  
If an ANA result is positive, anti-dsDNA will be performed automatically. 
g.  For subjects who are age 13 or older at the M06-807 Baseline Visit, a CDAI will be completed at each visit. 
h. 
For subjects who are age 10 or older at the M06-807 Baseline Visit, an IMPACT III Assessment will be completed at Baseline, Weeks 12, 24, 48, 72, 108, 144, 168, 192, 216, 
240 and 264/ET. 
i. 
In addition to blood draws every 24 weeks, PK and AAA blood draws to be performed if subject meets flare criteria and dose escalated to ew dosing. 
j. 
All AEs, including SAEs, will be captured throughout the study from the time that the subject signs the Informed Consent Form. SAEs will be captured throughout the 70 day 
follow-up period (if applicable). 
k. 
If an unscheduled visit is performed to change the frequency of study drug from OL eow to OL ew, study drug may be dispensed. 
 
 
 

 
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Section 5.3.1.1  Study Procedures 
First paragraph previously read: 
The M06-806 Week 52 visit will serve as the Baseline visit for the M06-807 study.  The 
study procedures outlined in Table 1 are discussed in detail in this section, with the 
exception of the collection of AE information (discussed in Section 6.0).  All study data 
will be recorded in source documents and on the appropriate CRFs. 
Has been changed to read: 
The M06-806 Week 52 visit will serve as the Baseline visit for the M06-807 study.  The 
study procedures outlined in Table 1 are discussed in detail in this section, with the 
exception of the collection of AE information (discussed in Section 6.0).  All study data 
will be recorded in source documents and on the appropriate CRFs.  The site will call the 
subjects at Weeks 132, 156, 180, 204, 228 and 252 in order to collect any safety 
information from the subject as illustrated in Table 1. 
Section 5.3.1.1  Study Procedures 
Subsection Previous and Concomitant Medications 
First paragraph, first sentence previously read: 
Changes in concomitant medications will be assessed at each study visit from Baseline 
through Week 104/ET visit.   
Has been changed to read: 
Changes in concomitant medications will be assessed at each study visit from Baseline 
through the Week 264/ET visit.   
Section 5.3.1.1  Study Procedures 
Subsection Immunologic Laboratory Assessments 
First paragraph previously read: 
CRP assessments will be performed at Baseline (Week 52 of the M06-806 Study), 
Weeks 24, 48, 72 and 104/ET.  Antinuclear antibody (ANA) will be performed at 
Baseline (Week 52 of the M06-806 Study), Week 12, and Week 104/ET.  If an ANA 

 
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result is positive, anti-double-stranded DNA (anti-dsDNA) will be performed 
automatically. All CRP, ANA, anti-dsDNA will be performed by the central laboratory. 
Has been changed to read: 
CRP, adalimumab levels, anti-adalimumab antibody levels (AAA) and antinuclear 
antibody (ANA) assessments will be performed as indicated in Table 1.  If an ANA result 
is positive, anti-double-stranded DNA (anti-dsDNA) will be performed automatically. All 
CRP, ANA, anti-dsDNA will be performed by the central laboratory. 
Section 5.3.1.1  Study Procedures 
Subsection Markers of Bone Metabolism 
First sentence previously read: 
Serum markers of bone metabolism will be measured at Baseline (Week 52 of the 
M06−806 Study), Weeks 24, 48, 72 and 104/ET.   
Has been changed to read: 
Serum markers of bone metabolism will be measured as indicated in Table 1.   
Section 5.3.1.1  Study Procedures 
Subsection IMPACT III Questionnaire 
First paragraph, first sentence previously read: 
Subjects t 10 years old at the Baseline visit of the M06-807 study will complete an 
IMPACT III questionnaire at Baseline, Weeks 12, 24, 48, 72, and 104/ET as indicated in 
Table 1.   
Has been changed to read: 
Subjects t 10 years old at the Baseline visit of the M06-807 study will complete an 
IMPACT III questionnaire as indicated in Table 1.   

 
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Section 5.3.1.1  Study Procedures 
Subsection Bone Age 
First sentence previously read: 
An x-ray of the wrist for the assessment of bone age will be obtained at Baseline 
(Week 52 of M06-806), Week 48, and Week 104/ET to determine changes in bone 
maturation as indicated in Table 1.   
Has been changed to read: 
An x-ray of the wrist for the assessment of bone age will be obtained as indicated in 
Table 1.   
Section 5.3.1.1  Study Procedures 
Subsection Adverse Events 
First paragraph, first sentence previously read: 
Adverse events will be assessed at every study visit from Baseline through Week 104 / 
Early Termination visit.   
Has been changed to read: 
Adverse events will be assessed at every study visit from Baseline through the 
Week 264/ET visit.   
Section 5.3.1.1  Study Procedures 
Subsection Study Drug Administration 
First paragraph, first sentence previously read: 
At each study visit, the subject or their trained designated friend, family member or 
health care professional will perform study drug injections under the supervision of a 
trained medical personnel to reinforce proper aseptic SC injection technique.   

 
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Has been changed to read: 
At each study visit, the subject or their trained designated friend, family member or 
health care professional will perform study drug injections under the supervision of a 
trained medical professional to reinforce proper aseptic SC injection technique.   
Section 5.3.2  Drug Concentration Measurements 
Previously read: 
No drug concentration measurements will be obtained in this trial. 
Has been changed to read: 
Blood samples for the assay of adalimumab and AAA serum concentrations will be 
collected at Baseline and every 24 weeks thereafter.  In addition, blood samples for 
adalimumab and AAA concentration analysis will also be collected if a subject meets 
flare criteria and dose escalated to ew dosing.  Study visits in which blood samples will 
be collected are listed in Table 1.  At each visit, blood samples will be collect prior to 
study drug administration at each visit. 
The time that each blood sample is collected will be recorded to the nearest minute in the 
source documents and on the appropriate CRF. 
Section 5.3.2.1  Collection of Samples for Analysis 
Add:  new section 
Collection of Samples for Adalimumab Analysis 
Blood samples for adalimumab analysis will be collected by venipuncture into 
appropriately labeled 4-mL evacuated serum collection tubes without gel separator at 
visits indicated in Table 1.  All samples will be obtained immediately prior to dosing at 
visits indicated in Table 1.  Sufficient blood will be collected to provide approximately 
2 mL serum.  Allow the blood to clot for 30 minutes at room temperature before 
centrifugation. 

 
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A maximum of 13 samples are planned to be collected per subject for the analysis of 
adalimumab concentrations. 
Collection of Samples for AAA Analysis 
Blood samples for AAA assay will be collected by venipuncture into appropriately 
labeled 4-mL evacuated serum collection tubes without gel separator at visits indicated in 
Table 1.  All samples will be obtained immediately prior to dosing at visits indicated in 
Table 1.  Sufficient blood will be collected to provide approximately 2 mL serum.  Blood 
will be allowed to clot for 30 minutes at room temperature before centrifugation. 
A maximum of 13 blood samples are planned to be collected per subject for AAA 
analysis. 
Section 5.3.2.2  Handling/Processing of Samples 
Add:  new section 
The blood samples for adalimumab and AAA, assay will be centrifuged within 30 to 
60 minutes of collection to separate the serum.  The serum samples will be transferred 
using plastic pipettes into screw-capped polypropylene vials labeled with the type of 
sample (serum, SRM), the protocol number, subject number, the study week and the 
assay (PK-Adalimumab, AAA).  The serum samples will be frozen within 2 hours after 
collection and will remain frozen in a –20°C or colder until shipped.  Sites that do not 
have access to a −20°C or colder freezer will need to ship the samples the day they are 
collected.  (Detailed instructions provided in the ICON Laboratory Manual). 
Section 5.3.2.3  Disposition of Samples 
Add:  new section 
The PK and AAA samples will be shipped to ICON with all other samples being shipped 
to ICON.  Refer to the ICON Lab Manual for further instruction.  Neither Abbott nor 
ICON will supply dry ice for this study.  Study sites will identify a dry ice source and 
purchase the necessary dry ice. 

 
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Section 5.3.2.4  Measurement Methods 
Add:  new section 
Serum concentrations of adalimumab will be determined using a validated ELISA 
method under the supervision of the Drug Analysis Department at Abbott Laboratories.  
Only serum samples that have adalimumab levels < 2.0 Pg/mL will be selected for AAA 
concentration measurement. 
Serum concentrations of AAA will be determined using a validated ELISA method under 
the supervision of the Drug Analysis Department at Abbott Laboratories. 
Section 5.3.3  Efficacy Variables 
Second paragraph previously read: 
Other measures of disease activity being assessed in this study will be summarized, 
including CDAI scores, IMPACT III scores, WPAI-CD Caregiver, z-score for height 
velocity, bone x-ray, serological markers of bone metabolism, and healthcare resource 
utilization (unscheduled outpatient visits). 
Has been changed to read: 
Other measures of disease activity being assessed in this study will be summarized, 
including CDAI scores, IMPACT III scores, WPAI-CD Caregiver, z-score for height 
velocity, bone x-ray, serological markers of bone metabolism, healthcare resource 
utilization (unscheduled outpatient visits), adalimumab levels and anti-adalimumab levels 
(AAA). 
Section 5.3.4  Safety Variables 
Add:  second paragraph 
Treatment-emergent events will be summarized and reported by treatment group and by 
AAA status (AAA+ versus AAA-). 

 
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Section 5.3.5  Pharmacokinetic Variables 
Add:  new section 
Serum concentrations of adalimumab and AAA will be determined from samples 
collected at the study visits listed in Table 1. 
Section 5.4.1  Discontinuation of Individual Subjects 
Second paragraph, first sentence previously read: 
If the subject prematurely discontinues study drug use, the procedures outlined for the 
Week 104/ET Visit must be completed within 2 weeks of the last dose of study drug, and 
preferably prior to the initiation of another therapy.   
Has been changed to read: 
If the subject prematurely discontinues study drug use, the procedures outlined for the 
Week 264/ET Visit must be completed within 2 weeks of the last dose of study drug, and 
preferably prior to the initiation of another therapy.   
Section 5.4.3  Stopping Rules 
Previously read: 
An independent Data Monitoring Committee (DMC) will meet to discuss unblinded data 
from the study every six (6) months or at a frequency determined by the DMC and render 
their recommendation for either the continuation of the study or an amendment to the 
study.  A Sponsor Steering Committee (SSC), composed of senior executives not directly 
participating in this study, will make final decisions based on DMC recommendations.  In 
addition, an ad-hoc DMC meeting will be convened if either of the following criteria is 
met. 
● The overall proportion of subjects with SAEs, with an investigator-assessed 
causality of at least possibly related or higher, evaluated on a per subject 
basis, exceeds 0.20 (or 20%); or 
● The overall proportion of subjects with serious infectious SAEs, evaluated on 
a per subject basis, exceeds 0.20 (or 20%). 

 
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If either of the above criteria is met, the DMC will meet within 2 weeks to consider 
whether or not to recommend a temporary suspension of enrollment. 
Has been changed to read: 
An independent Data Monitoring Committee (DMC) will meet to discuss data from the 
study approximately every six (6) months or at a frequency determined by the DMC and 
render their recommendation for either the continuation of the study or an amendment to 
the study.  A Sponsor Steering Committee (SSC), composed of senior executives not 
directly participating in this study, will make final decisions based on DMC 
recommendations. 
Section 6.5  Adverse Event Reporting 
Previously read: 
In the event of an SAE, whether related to study drug or not, the investigator will notify 
one of the following people by faxing the appropriate SAE forms to one of the following 
people within 24 hours of the site being made aware of the SAE. 
For all sites: 
 

 
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For questions regarding SAEs, please contact: 
Has been changed to read: 
In the event of an SAE, whether related to study drug or not, the investigator will notify 
one of the following people by faxing the appropriate SAE forms to one of the following 
people within 24 hours of the site being made aware of the SAE. 
For all sites: 
 
 
For questions regarding SAEs, please contact: 
 

 
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Section 6.6  Pregnancy 
Third paragraph previously read: 
To monitor outcomes of pregnant women exposed to adalimumab, a pregnancy registry 
has been established for the United States.  Physicians in the United States are 
encouraged to register subjects by calling 
 and/or provide this 
information to the subject. 
Has been changed to read: 
To monitor outcomes of pregnant women exposed to adalimumab, a pregnancy registry 
has been established for the United States, Canada and Puerto Rico.  Physicians in the 
United States are encouraged to register subjects by calling 
 and/or 
provide this information to the subject. 
Section 7.0  Protocol Deviations 
First paragraph and contact previously read: 
The investigator should not implement any deviation from the protocol without prior 
review and agreement by the Sponsor and in accordance with the IEC/IRB and local 
regulations, except when necessary to eliminate an immediate hazard to study subjects.  
When a deviation from the protocol is deemed necessary for an individual subject, the 
investigator must contact the following Abbott representative: 
 
 

 
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Has been changed to read: 
The investigator should not implement any deviation from the protocol without prior 
review and agreement by the Sponsor and in accordance with the IEC/IRB and local 
regulations, except when necessary to eliminate an immediate hazard to study subjects.  
When a deviation from the protocol is deemed necessary for an individual subject, the 
investigator must contact the following Abbott representative: 
 
 
Section 8.1.4.1  Pharmacokinetic Analyses 
Add:  new section 
Adalimumab trough serum concentrations will be summarized by treatment group at each 
time point using descriptive statistics including number of subjects, number of non 
missing observations (nnmiss), mean, median, standard deviation, coefficient of 
variation, minimum, and maximum.  The relationship between adalimumab 
concentrations and efficacy and/or safety variables may be explored.  Additional analysis 
may be performed. 
Appendix A.  List of Abbreviations and Definition of Terms 
Add: 
AAA 
Anti-adalimumab antibody 
PK 
Pharmacokinetics 

 
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Appendix B.  List of Protocol Signatories 
Add:  new appendix 
Name 
Title 
Functional Area 
Statistics 
Clinical 
Clinical 
Clinical 
 
Appendix G.  PCDAI User's Guide and Guideline for Reference Weight and 
Reference Height 
"Item 7," second line previously read: 
From Baseline to Week 104: use weight from previous visit 
Has been changed to read: 
From Baseline to Week 264: use weight from previous visit 
Appendix G.  PCDAI User's Guide and Guideline for Reference Weight and 
Reference Height 
"Item 8," bullets previously read: 
● From Baseline to Week 24, use height from 6 months prior to Baseline 
● From Week 24 to Week 48, use height from Baseline visit 
● From Week 48 to Week 72, use height from Week 24 
● From Week 72, use height from Week 48 
 
Has been changed to read: 
● From Baseline to Week 24, use height from 6 months prior to Baseline 
● From Week 24 to Week 48, use height from Baseline visit 
● From Week 48 to Week 72, use height from Week 24 
● From Week 72 to Week 96, use height from Week 48 

 
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● From Week 96 to Week 120, use height from Week 72 
● From Week 120 to Week 144, use height from Week 96 
● From Week 144 to Week 168, use height from Week 120 
● From Week 168 to Week 192, use height from Week 144 
● From Week 192 to Week 216, use height from Week 168 
● From Week 216 to Week 240, use height from Week 192 
● From Week 240 to Week 264, use height from Week 216 
 
Appendix H.  Crohn's Disease Activity Index (CDAI) 
Footnote previously read: 
* 
Ideal weight is obtained from CDC growth charts.  The subtotal of box 8 should 
be rounded to a whole number.  Numbers that fall between the range of .1-.4 must 
be rounded down.  Numbers that fall between the range of .5-.9 must be rounded 
up. 
Has been changed to read: 
* 
Ideal weight is obtained from CDC growth charts.  The subtotal of box 8 should 
be rounded to a whole number.  Numbers that fall between the range of .1-.4 must 
be rounded down.   Numbers that fall between the range of .5-.9 must be rounded 
up.  To ensure consistency across all sites and to take into account the varying 
growth rates of subjects in this study, the IBW should be calculated at each visit. 
 

 
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Appendix O.  Subject Dosing Diary 
"Week 97 - Week 104" previously read: 
Week 97 - Week 104 
Subject Initials: __________ 
Subject Study #: ___________ 
 
Date 
day/mm/yr 
Day or 
Week # 
Time of Study 
Drug 
Administration 
Dose (mL) 
Administered
Kit #
Initials of Person 
Administering 
Study Medication Comments
18/MAR/04 
EXAMPLE 
9:35 am 
0.8 
 
MM 
none 
 
Week 97 
 
 
 
 
 
 
Week 98 
 
 
 
 
 
 
Week 99 
 
 
 
 
 
 
Week 100 
 
 
 
 
 
 
Week 101 
 
 
 
 
 
 
Week 102 
 
 
 
 
 
 
Week 103* 
 
 
 
 
 
*The dose at Week 103 will only be taken if you are on weekly dosing. 
 

 
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Week 241 - Week 263 
Subject Initials: __________ 
Subject Study #: ___________ 
 
Date 
day/mm/yr 
Day or 
Week # 
Time of Study 
Drug 
Administration 
Dose (mL) 
Administered
Kit #
Initials of Person 
Administering 
Study Medication Comments
18/MAR/04 
EXAMPLE 
9:35 am 
0.8 
 
MM 
none 
 
Week 241 
 
 
 
 
 
 
Week 242 
 
 
 
 
 
 
Week 243 
 
 
 
 
 
 
Week 244 
 
 
 
 
 
 
Week 245 
 
 
 
 
 
 
Week 246 
 
 
 
 
 
 
Week 247 
 
 
 
 
 
 
Week 248 
 
 
 
 
 
 
Week 249 
 
 
 
 
 
 
Week 250 
 
 
 
 
 
 
Week 251 
 
 
 
 
 
 
Week 252 
 
 
 
 
 
 
Week 253 
 
 
 
 
 
 
Week 254 
 
 
 
 
 
 
Week 255 
 
 
 
 
 
 
Week 256 
 
 
 
 
 
 
Week 257 
 
 
 
 
 
 
Week 258 
 
 
 
 
 
 
Week 259 
 
 
 
 
 
 
Week 260 
 
 
 
 
 
 
Week 261 
 
 
 
 
 
 
Week 262 
 
 
 
 
 
 
Week 263* 
 
 
 
 
 
* 
Week 259 dose will only be taken if on every-week dosing schedule. 
 

 
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Appendix P.  Self Injection Instructions 
Heading Study Drug Dosing Schedule 
Third paragraph, first sentence previously read: 
Injections at scheduled study visits (Baseline, Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84, and 
96) will be done during your visit, at the doctor's office. 
Has been changed to read: 
Injections at scheduled study visits (Baseline, Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84, 96, 
108, 120, 144, 168, 192, 216 and 240) will be done during your visit, at the doctor's 
office. 
Appendix R.  Abbott Laboratories Site Drug Accountability Form 
Appendix title previously read: 
Abbott Laboratories Site Drug Accountability Form 
Has been changed to read: 
Subject Abbott Laboratories Site Drug Accountability Form 

 
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1.0 
Title Page 
CLINICAL TRIAL PROTOCOL M06-807 
A Multi-center, Open-label Study of the Human 
Anti−TNF Monoclonal Antibody Adalimumab to 
Evaluate the Efficacy and the Long-term Safety and 
Tolerability of Repeated Administration of 
Adalimumab in Pediatric Subjects with 
Crohn's Disease Who Have Demonstrated a Clinical 
Response in the M06-806 Study 
Incorporating Administrative Changes 1 and 2  
and Amendment 1 
Abbott Number /  
 Investigational Product: 
 
Adalimumab 
Date:  
10 October 2008 
Development Phase: 
3 
Study Design:  
A multi-center, open-label safety and tolerability pediatric study in the 
United States, Canada and Europe. 
EudraCT Number:  
2007-006494-90 
Investigator: 
Multicenter (Investigator information on file at Abbott Laboratories). 
Sponsor: 
European Union Countries: 
Abbott GmbH & Co.KG  
Knollstrasse 50 
67061 Ludwigshafen, Germany 
Non European Union Countries: 
Abbott Laboratories, US  
100 Abbott Park Road 
Abbott Park, IL 60064 
Emergency Contact: 
This study will be conducted in compliance with the protocol, Good Clinical Practice and all other 
applicable regulatory requirements, including the archiving of essential documents. 
Confidential Information 
No use or disclosure outside Abbott is permitted without prior written authorization from Abbott. 
 

 
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1.1 
Protocol Amendment:  Summary of Changes 
The purpose of this amendment is to: 
● Section 5.2.1 (Inclusion Criteria):  Inclusion Criterion Number 2 updated to 
clarify that a subject must be a responder during the M06-806 study.  Because 
hematocrit scores are needed to determine if a subject is eligible to enter the 
study, there is not enough time to have the labs drawn at Week 52 of M06-
806/Baseline M06-807 and have the results back from the lab prior to the 
subject rolling over.  In addition, Abbott does not want to exclude subjects 
who have responded at another time point within the M06-806 study. 
● Amend the stopping rules in Section 5.4.3 as follows: 
The rate of possibly related SAEs or higher, on a per subject per year basis in 
excess of 0.45, was changed to the proportion of SAEs, possibly related or 
higher, on a per subject basis in excess of 0.20. 
Rationale:  The new stopping boundary of 0.20 is based on the 'Any SAEs' 
proportion of 0.20 reported in the Infliximab Pediatric Crohn's Disease trial. 
The original rate of 0.45/patient-years was chosen based on SAE data from 
adult trials in Rheumatoid Arthritis (RA).  This rate could allow for as many 
as 5 events based on the 11.1 patient-years accrued as at the time of the first 
DMC meeting on 20 Mar 2008, although only 1 SAE of at least possibly drug 
related had actually been reported.  (Reference:  "Induction and Maintenance 
Infliximab Therapy for the Treatment of Moderate-to-Severe Crohn's Disease 
in Children," Hyams et al., Gastroenterology Vol. 132, No. 3, pages 863-873, 
March 2007).  During a teleconference between Abbott and the DMC on 
03 Jun 2008, the DMC reviewed and agreed with the revised stopping rules. 
● The overall rate, in excess of 0.09 infectious SAEs on a per patient per year 
basis was changed to the overall proportion of infectious SAEs in excess of 
0.20 on a per subject basis. 
Rationale:  The new stopping boundary of 0.20 is calculated as 2.5 u (the 
'Serious Infection' proportion of 0.08 reported in the Infliximab Pediatric 
Crohn's Disease trial).  The choice of 2.5 u the Serious Infection rate from the 

 
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infliximab study data was arbitrary, but based on clinical judgment.  The 
serious infection rate reported in the infliximab trial ranged from 5.7% to 
22.2%, and the rate for the combined infliximab group was 8.0%.  Based on 
clinical judgment, the team decided to choose a value in multiples of 8% but 
not exceeding the high extreme of 22.2%.  Thus the value of 20% (which 
resulted from 2.5u 8.0%) was thought to be clinically reasonable for a 
stopping boundary.  The original rate of 0.09/patient-years was chosen based 
on 'Serious Infectious SAE' data from adult Rheumatoid Arthritis (RA) trials. 
This rate is not applicable because it is not suitable for a stopping boundary.  
At the time of the first DMC meeting (20 Mar 2008), when the study was 
experiencing slow enrollment and had only accrued 11.1 patient-years of 
follow-up, this old rate only allowed just 1 infectious SAE (that is, 
1/11.1 = 0.09/patient-years).  This meant that even with 2 infectious SAEs, the 
study would cross the original stopping boundary.  This is obviously not an 
acceptable option in this pediatric Crohn's study where infections are part of 
the underlining nature of the disease.  During a teleconference between 
Abbott and the DMC on 03 Jun 2008, the DMC reviewed and agreed with the 
revised stopping rules. 
● The paragraph in the protocol with the text "If either of these criteria is met, 
no new enrollment will occur until the DMC or the SSC makes their 
recommendations" was changed to "If either of the above criteria is met, the 
DMC will meet within 2 weeks to consider whether or not to recommend a 
temporary suspension of enrollment." 
Rationale:  The original text calling for the study to be "temporarily 
suspended if either of the above criteria is met" was copied from a previous 
adult Crohn's protocol.  The DMC review of the SAEs and safety data 
indicated that there was no need to suspend the study at all, since infections 
are part of the underlining nature of Crohn's disease in children.  The revised 
wording will allow the DMC to first consider a meeting to review the safety 
data in detail and render its recommendation on whether or not to 
temporarily suspend the trial.  During a teleconference between Abbott and 
the DMC on 03 Jun 2008, the DMC reviewed and agreed with the revised text 
in the protocol. 

 
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● Section 12.2 regarding publication has been removed. 
Rationale:  Publication of data from this study is covered in the site contract 
and is not required in the protocol. 
● Administrative Changes: 
o Section 1.0 (Title Page) and 14.0 (Investigator's Agreement):  Updated 
date of protocol. 
○ Section 3.0 (Introduction):  Approvals from other indications have been 
updated to reflect the most current data available. 
○ Section 5.5.1 (Treatment Administered):  A typographical error has been 
corrected to clarify dose of 20 mg/0.4 ml and not 20 mg/0.8 ml. 
○ Section 5.5.4 (Selection and Timing of Dose for Each Subject:  A 
typographical error has been corrected to remove "of the" in sentence, "All 
clinic visits for the subject should be scheduled on the same day of the as 
the Baseline visit for this study." 
○ Section 6.5 (Adverse Event Reporting):  Safety Hotline address and 
contact information have been updated. 
○ Section 15.0 (Reference) updated to add reference for the current 
guidelines for the treatment of latent TB. 
o Appendix C (Documents Required Prior to Initiation of the Study):  
Updated to reflect the current regulatory requirements. 
o Appendix D (Responsibilities of the Clinical Investigator):  Updated to 
reflect the current regulatory requirements. 
○ Appendix E [CDC Treatment of Tuberculosis Infection (Preventive 
Therapy)]:  Updated with the current guidelines for the treatment of latent 
TB 
○ Appendix H (PCDAI User's Guide and Guideline for Reference Weight 
and Reference Height):  Updated to clarify from Week 48 to Week 72 and 
from post Week 72, use height from Week 48.  Original text states 
Week 52, however there is no Week 52 visit, which is why it has been 
changed to Week 48. 

 
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○ Appendix L (Excluded Medications):  Updated to state any previous 
anti-TNF medication except infliximab before the M06-806 study. 
○ Appendix M (Day 70 Phone Call):  Faxing contact information has been 
updated. 
● Minor typographical formatting errors corrected throughout protocol. 
 
See Appendix T for an itemized list made to this protocol under Amendment 1. 

 
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2.0 
Table of Contents 
1.0 
Title Page .................................................................................1 
1.1 
Protocol Amendment:  Summary of Changes...........................................2 
2.0 
Table of Contents....................................................................6 
3.0 
Introduction...........................................................................11 
4.0 
Study Objective .....................................................................17 
5.0 
Investigational Plan ..............................................................17 
5.1 
Overall Study Design and Plan:  Description..........................................17 
5.2 
Selection of Study Population .................................................................20 
5.2.1 
Inclusion Criteria.....................................................................................20 
5.2.2 
Exclusion Criteria....................................................................................21 
5.2.3 
Prior and Concomitant Therapy ..............................................................23 
5.2.3.1 
Prior Therapy...........................................................................................23 
5.2.3.2 
Concomitant Therapy..............................................................................24 
5.2.3.3 
Rescue Therapy .......................................................................................25 
5.2.3.4 
Prohibited Therapy ..................................................................................25 
5.3 
Efficacy, and Safety Assessments/Variables...........................................25 
5.3.1 
Efficacy and Safety Measurements Assessed and Flow Chart................25 
5.3.1.1 
Study Procedures.....................................................................................28 
5.3.2 
Drug Concentration Measurements.........................................................35 
5.3.3 
Efficacy Variables ...................................................................................36 
5.3.4 
Safety Variables.......................................................................................36 
5.4 
Removal of Subjects from Therapy or Assessment ................................36 
5.4.1 
Discontinuation of Individual Subjects ...................................................36 
5.4.2 
Discontinuation of Entire Study..............................................................37 
5.4.3 
Stopping Rules.........................................................................................37 
5.5 
Treatments ...............................................................................................38 

 
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5.5.1 
Treatments Administered ........................................................................38 
5.5.2 
Identity of Investigational Product ..........................................................39 
5.5.2.1 
Packaging and Labeling ..........................................................................39 
5.5.2.2 
Storage and Disposition of Study Drug...................................................40 
5.5.3 
Method of Assigning Subjects to Treatment Groups ..............................41 
5.5.4 
Selection and Timing of Dose for Each Subject .....................................41 
5.5.5 
Blinding...................................................................................................42 
5.5.6 
Treatment Compliance ............................................................................42 
5.5.7 
Drug Accountability................................................................................42 
5.6 
Discussion and Justification of Study Design .........................................43 
5.6.1 
Discussion of Study Design and Choice of Control Groups...................43 
5.6.2 
Appropriateness of Measurements ..........................................................43 
5.6.3 
Suitability of Subject Population.............................................................43 
5.6.4 
Selection of Doses in the Study...............................................................44 
6.0 
Adverse Events......................................................................44 
6.1 
Definitions...............................................................................................45 
6.1.1 
Adverse Event .........................................................................................45 
6.1.2 
Serious Adverse Events...........................................................................45 
6.2 
Adverse Event Severity...........................................................................46 
6.3 
Relationship to Study Drug .....................................................................47 
6.4 
Adverse Event Collection Period ............................................................47 
6.5 
Adverse Event Reporting ........................................................................48 
6.5.1 
Collection of Data Regarding Known Manifestations of the 
Disease Under Study ...............................................................................49 
6.6 
Pregnancy ................................................................................................50 
7.0 
Protocol Deviations...............................................................50 
8.0 
Statistical Methods and Determination of Sample 
Size..........................................................................................51 

 
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8.1 
Statistical and Analytical Plans ...............................................................51 
8.1.1 
Analyzable Population.............................................................................51 
8.1.2 
Planned Methods of Statistical Analysis .................................................52 
8.1.2.1 
Demographics and Baseline Characteristics ...........................................52 
8.1.2.2 
Primary Efficacy Analysis.......................................................................52 
8.1.3 
Other Analyses ........................................................................................52 
8.1.4 
Safety Analyses .......................................................................................53 
8.1.5 
Interim Analysis ......................................................................................54 
8.2 
Determination of Sample Size.................................................................54 
8.3 
Randomization Methods..........................................................................54 
9.0 
Ethics......................................................................................54 
9.1 
Independent Ethics Committee (IEC) or Institutional Review 
Board (IRB).............................................................................................54 
9.2 
Ethical Conduct of the Study...................................................................55 
9.3 
Subject Information and Consent ............................................................55 
10.0 
Source Documents and Case Report Form 
Completion.............................................................................56 
10.1 
Source Documents...................................................................................56 
10.2 
Case Report Forms ..................................................................................56 
11.0 
Data Quality Assurance........................................................57 
12.0 
Use of Information and Publication....................................58 
12.1 
Use of Information ..................................................................................58 
12.2 
Internet Sites............................................................................................59 
13.0 
Completion of the Study.......................................................59 
14.0 
Investigator's Agreement .....................................................61 
15.0 
Reference List........................................................................62 
 

 
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List of Tables 
Table 1.  
Study Activities .......................................................................................26 
Table 2.  
Clinical Laboratory Tests ........................................................................31 
Table 3.  
Identity of Investigational Products.........................................................39 
Table 4.  
Study Drug Packaging and Administration.............................................40 
 
List of Figures 
Figure 1.  
Study Schematic ......................................................................................19 
Figure 2.  
Adverse Event Collection........................................................................48 
 
List of Appendices 
Appendix A.  
List of Abbreviations and Definition of Terms .......................................66 
Appendix B.  
Documents Required Prior to Initiation of the Study..............................68 
Appendix C.  
Responsibilities of the Clinical Investigator............................................70 
Appendix D.  
CDC Treatment of Tuberculosis Infection (Preventive Therapy)...........72 
Appendix E.  
Non-Drug Materials Provided to the Study Site(s) .................................74 
Appendix F.  
Pediatric Crohn's Disease Activity Index (PCDAI) ................................75 
Appendix G.  
PCDAI User's Guide and Guideline for Reference Weight and 
Reference Height.....................................................................................77 
Appendix H.  
Crohn's Disease Activity Index (CDAI)..................................................82 
Appendix I.  
Subject CDAI Diary ................................................................................83 
Appendix J.  
IMPACT III Questionnaire......................................................................84 
Appendix K.  
Excluded Medications .............................................................................92 
Appendix L.  
Day 70 Phone Call...................................................................................93 
Appendix M.  Unscheduled Outpatient Visits, Emergency Room Visits and 
Hospitalizations .......................................................................................94 
Appendix N.  
Subject Medication Log ..........................................................................95 
Appendix O.  
Subject Dosing Diary ..............................................................................96 

 
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Appendix P.  
Self Injection Instructions......................................................................107 
Appendix Q.  
Standard Weights...................................................................................113 
Appendix R.  
Abbott Laboratories Site Drug Accountability Form............................115 
Appendix S.  
Work Productivity and Activity Impairment Questionnaire: 
Crohn's Disease (WPAI-CD) - Caregiver..............................................116 
Appendix T.  
Protocol Amendment:  List of Changes ................................................118 
 

 
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3.0 
Introduction 
Crohn's Disease (CD) is a chronic, debilitating, and currently incurable inflammatory 
disease that can affect the entire digestive system as well as extraintestinal organs.  CD is 
primarily manifested by focal asymmetric, transmural, and occasionally, granulomatous 
inflammation affecting any segment of the gastrointestinal tract1 which can consist of 
mucosal edema, aphthous and linear ulcerations, asymmetrical narrowing and strictures.  
Noncaseating granulomas are virtually diagnostic in the correct clinical setting.  The most 
commonly involved area of the bowel is the small bowel, particularly the distal ileum, 
which is involved in 70% of cases often in combination with colitis, occurring in 50% of 
cases.  Extraintestinal manifestations can also occur, and include symptoms of joint, 
ocular and hepatic inflammation.  Genetic, geographic, ethnic, and environmental risk 
factors have all been described, but the basic etiology of the disease remains unknown. 
The incidence in North America is similar to that in other western nations and is 
estimated from 3.1 to 14.6 cases per 100,000 person years and prevalence ranges from 
26 to 199 cases per 100,000 persons.2  The disease can affect persons of any age but the 
most common age of onset is in the second and third decades with a female 
preponderance.  While predominantly a disease of adults, approximately 10% to 15% of 
CD cases are diagnosed before adulthood.3 
In addition, the incidence of CD in patients less than 18 years of age appears to be 
increasing in both North America and Europe.4,5  Reported incidence rates range from 
1.2 to 4.9 per 100,000 persons in the UK, Europe, and North America6-12 with one study 
reporting an incidence of 4.6 per 100,000 persons in the United States.5  CD has been 
reported at all ages but is rare in early childhood.  In one study of patients with CD, 
17 years of age and younger, 9.1% of the patients were diagnosed before the age of 6.13  
In a second study of patients diagnosed with CD before the age of 15, 7.5% of the 
patients were under the age of 5.14 
Despite obvious physiologic and development differences, the presentation of CD in the 
pediatric population is generally similar to that seen in older patients and is 

 
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heterogeneous with regard to anatomic localization and clinical severity.5,15,16  The 
unique aspect of this disease in children is its impact on nutrition and growth, with 
marked growth retardation being a prominent component of the disease in this age 
group.17-19  The use of accepted methodologies for assessing nutritional status, including 
the anthropometric measures of height, weight, triceps skin fold thickness and mid arm 
circumference as well as linear growth (height velocity and assessment of height velocity 
for chronological age "z-score") have documented the growth impairment that can occur 
in this age group, and also have been used to assess the efficacy of interventions.20  
Profound impairment of bone formation and increased bone resorption are associated 
complications and are related to the effect of glucocorticoids,21,22 delayed puberty,22,23 
decreased mobility,24 as well as to the effects of cytokines on bone formation.25 
Initial symptoms are often subtle, and there is an average delay of almost six months 
between onset of symptoms and diagnosis.  The most common presentation is with 
abdominal pain, diarrhea, loss of appetite and weight loss.  However, isolated weight 
loss, anorexia, perianal disease and extraintestinal manifestations can occur in the 
absence of GI symptoms in a substantial number of patients. 
The general approach to the treatment of CD in children is similar to adults with the goals 
being induction and maintenance of remission, prevention of relapse and hospitalizations, 
improved quality of life, and avoidance of disease and drug related complications.  
Restoration and/or preservation of normal growth and pubertal development are 
additional therapeutic goals.  The medical armamentarium is likewise similar to adults 
and includes induction of remission with corticosteroids, and ongoing maintenance 
therapy of immunomodulators, aminosalicylates and nutritional therapy.  Anti-tumor 
necrosis factor (TNF) therapy with infliximab has been evaluated for the therapy of CD 
in this age group as it has in adults.  The FDA and EMEA have recently approved 
Infliximab for use in children with CD. 
Adalimumab is a recombinant human immunoglobulin (IgG1) monoclonal antibody 
exclusively containing human peptide sequences.  It is produced by recombinant 
deoxyribonucleic acid (DNA) technology in a mammalian cell expression system.  

 
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Adalimumab consists of 1330 amino acids and has a molecular weight of approximately 
148 kilodaltons.  It binds specifically with high affinity to the soluble and transmembrane 
forms of TNFD and inhibits the binding of TNFD with its receptors. 
TNF is a naturally occurring cytokine that is involved in normal inflammatory and 
immune responses.  Elevated levels of TNF play an important role in pathologic 
inflammation.  Adalimumab binds specifically to TNF and neutralizes the biological 
function of TNF by blocking its interaction with the p55 and p75 cell surface TNF 
receptors. 
Adalimumab was first approved for treatment of rheumatoid arthritis (RA) on 
31 Dec 2002 in the United States (US), on 08 Sep 2003 in the European Union (EU) and 
through August 2008 in a total of 76 countries.  Indication extensions to include 
treatment of psoriatic arthritis and early RA were granted in the EU on 01 Aug 2005 and 
in the US on 03 Oct 2005.  A further indication extension to include treatment of 
ankylosing spondylitis was approved in the EU on 01 Jun 2006 and was approved in the 
US on 28 Jul 2006.  Adalimumab was approved for the treatment of Crohn's disease in 
the United States on 27 Feb 2007, in the European Union on 04 Jun 2007 and in Canada 
on 05 July 2007 for the adult population.  In December 2007 and January 2008, 
respectively, adalimumab was approved for the treatment of psoriasis in adult patients in 
the EU, Canada and USA.  Additionally, adalimumab was approved for the treatment of 
juvenile idiopathic arthritis in the USA in February 2008. 
Adalimumab has been shown to be a safe and effective treatment of moderately to 
severely active Crohn's disease.  In the CD development program, adalimumab was 
studied in over 1400 adult subjects in three pivotal studies (two induction studies and a 
maintenance study). 
Study M02-403 was a multicenter, randomized, double-blind, placebo-controlled 
Phase 2/3 study to evaluate the efficacy and safety of adalimumab for the induction of 
remission in subjects with moderate to severe CD.26  A total of 299 subjects were 
randomized to receive one of four proposed induction treatment regimens (three active 

 
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treatment groups or placebo):  adalimumab 160 mg at Baseline (Week 0) followed by 
80 mg at Week 2, adalimumab 80 mg at Baseline followed by 40 mg at Week 2, 
adalimumab 40 mg at Baseline followed by 20 mg at Week 2 or placebo at Baseline and 
Week 2.  Eligible subjects could not have been previously treated with any anti TNF 
agent.  Only the group of subjects treated with adalimumab 160/80 mg had a statistically 
significantly greater remission rate at Week 4 (primary endpoint) compared to placebo 
(35.5% vs. 12.2%; p = 0.001).  In addition, statistically significantly greater proportions 
of subjects in the adalimumab 160/80 mg group than in the placebo group experienced 
clinical response CR-100 (48.7% and 24.3%, respectively) and clinical response CR-70 
(57.9% and 36.8%, respectively) at Week 4. 
Study M04-691, a second induction study, was a multicenter, randomized, double-blind, 
placebo-controlled, Phase 3 study to evaluate the efficacy and safety of adalimumab as 
induction treatment for subjects with moderate to severe CD who either initially 
responded to administration of infliximab but stopped responding or were intolerant.27  
A total of 325 subjects were randomized to receive adalimumab 160/80 mg or placebo.  
Eligible subjects must have previously been treated with infliximab and discontinued use 
due to loss of response to or intolerance to infliximab therapy.  The proportion of subjects 
who achieved clinical remission at Week 4 (primary endpoint) was statistically 
significantly greater in the adalimumab 160/80 mg group compared to the placebo group 
(21.4% vs. 7.2%).  The proportion of subjects achieving clinical response CR-100 and 
CR-70 at Week 4 was statistically significantly greater in the adalimumab 160/80 mg 
group (38.4% and 51.6%, respectively) compared to the placebo group (24.7% and 
33.7%, respectively). 
Study M02-404 was a multicenter, randomized, double-blind, placebo-controlled Phase 3 
study to assess the efficacy and safety of adalimumab for the maintenance of clinical 
remission in subjects with moderate to severe CD.27  A total of 854 subjects (both naïve 
to or previously treated with TNF antagonists [primarily infliximab]) were enrolled and 
received open-label adalimumab 80 mg at Baseline (Week 0) and adalimumab 40 mg at 
Week 2.  At Week 4, subjects were stratified by responder status (subjects who achieved 

 
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clinical response CR-70) and previous anti-TNF use and were randomized in a 1:1:1 ratio 
to one of three blinded treatment groups:  adalimumab 40 mg every week (ew), 
adalimumab 40 mg every other week (eow), or placebo.  Subjects who met clinical 
response CR-70 after Week 8 could be tapered from corticosteroids. 
The proportion of Week 4 responders (N = 499) who achieved clinical remission at 
Weeks 26 and 56 (co-primary endpoint) were statistically significantly greater in the 
adalimumab 40 mg eow (39.5% and 36.0%, respectively) and 40 mg ew (46.5% and 
41.4%, respectively) groups compared to the placebo group (17.1% and 11.8%, 
respectively).  The differences between the adalimumab 40 mg eow and 
adalimumab 40 mg ew groups at both of these time points were not statistically 
significant.  The median time in first clinical remission was greater in the adalimumab 
40 mg eow group (378 days) compared to the placebo group (127 days).  The median 
time in remission could not be estimated in the adalimumab 40 mg ew group because 
more than 50% remained in clinical remission at the end of the study.  Approximately six 
times as many subjects treated with adalimumab maintenance therapy compared to 
placebo were able to discontinue corticosteroids for at least 90 days and achieve 
remission at Week 26 and Week 56.  Efficacy was independent of Baseline C-reactive 
protein (CRP), concomitant therapies, such as corticosteroids or immunosuppressants, or 
prior anti-TNF experience.  The adalimumab safety profile in CD was similar to that seen 
in the other rheumatologic populations previously studied, except for expected 
manifestations of CD. 
Currently, there are two ongoing extension studies of adalimumab therapy in adult 
subjects with CD.  M04-690 trial is a long-term safety and tolerability study of repeated 
administration of adalimumab in adult subjects with CD who had previously participated 
in M02-404 or M04-691.  The other trial is a long-term open-label extension study 
following the initial first-year study period of the M02-433 study. 
The efficacy and safety of adalimumab in children has recently been demonstrated in 
juvenile rheumatoid arthritis (JRA).28  One hundred and seventy-one pediatric patients 
(4 to 17 years of age) were initially enrolled into a 16-week open label segment and 

 
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133 subjects continued in a 32-week double blind segment.  Clinically significant 
improvements were noted in ACR30, ACR50 and ACR70 as well as other indices of 
arthritis activity.  Adverse events (AEs) were similar as those noted in adult RA patients.  
There were no deaths, malignancies, or opportunistic infections, including tuberculosis 
(TB).  Thirteen serious adverse events (SAEs) in 8 subjects were observed in the 16-week 
open label portion of the study.  These included 4 subjects with JRA, one patient with 
two episodes of leukopenia/neutropenia, and one case each of femur fracture, herpes 
simplex, and pneumonia.  Six SAEs were observed in 6 subjects (2 placebo, 
4 adalimumab) during the 32-week double blind portion (closed head injury, 
gastroduodenitis, retinal detachment, appendicitis, abdominal pain and urinary tract 
infection).  Infections, AEs at least possibly related to study drug, and injection site 
reactions were reported by similar proportions of patients in all treatment groups during 
the double-blind therapy (32 weeks). 
Fatalities, serious infections, and sepsis have been reported with the use of TNF 
antagonists.  Many of the serious infections have occurred in subjects on concomitant 
immunosuppressive therapy that, in addition to their underlying immune disorder, could 
predispose them to infections.  TB has also been observed in subjects treated with TNF 
antagonists, including adalimumab.  The event rate for TB in the CD development 
program is consistent with the global adalimumab rate.29 
TNF antagonists, including adalimumab, have been associated with cases of malignancy 
and demyelinating disease.  Serious allergic adverse reactions have been reported in RA 
subjects following subcutaneous (SC) administration of adalimumab; none were reported 
in the CD program. 
A detailed discussion of the pre-clinical toxicology, metabolism, pharmacology, and 
safety experience can be found in the current Investigator's Brochure. 
The goal of this study is to demonstrate the efficacy of adalimumab in the maintenance of 
clinical response and to demonstrate the long-term safety and tolerability of repeated 
administration of adalimumab in pediatric subjects with Crohn's disease.  The subject 

 
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population will consist of subjects who participated in and successfully completed the 
M06-806 study and who meet all the inclusion and none of the exclusion criteria of 
Protocol M06-807.  Qualifying subjects will administer open-label adalimumab by SC 
injection.  Subjects receiving every other weekly therapy who continue to have a disease 
flare or develop another flare may be switched to every week therapy at the investigator's 
discretion.  Subjects receiving weekly therapy who continue to have a disease flare or 
develop another flare may be withdrawn from the study at the Investigator's discretion.  
For a detailed description of the study please see Section 5.0. 
4.0 
Study Objective 
The objective of the study is to evaluate the long-term maintenance of clinical response, 
safety and tolerability of repeated administration of adalimumab in pediatric subjects 
with Crohn's disease who participated in, and successfully completed, Protocol M06-806 
through Week 52 and who meet all the inclusion and none of the exclusion criteria of 
Protocol M06-807.
5.0 
Investigational Plan 
5.1 
Overall Study Design and Plan:  Description 
This study is a multi-center, open-label study of the human anti-TNF monoclonal 
antibody adalimumab.  Approximately 55 sites that have enrolled subjects in the 
M06 − 806 clinical trial will participate in the M06-807 clinical trial.  Approximately 
130 pediatric subjects are expected to enroll in this study.   
The Week 52 visit from the M06-806 study will be the Baseline Visit for those subjects 
entering study M06-807.  The visit window for M06-806 Week 52 visit is 364 ± 7 days 
from the Baseline Visit date of M06-806. 
Subjects may be allowed to enroll in the M06-807 study if they have participated in, and 
successfully completed Protocol M06-806 through Week 52.  At the end of 
Study M06 − 806, a subject must be a responder to enroll in this trial.  A responder is 

 
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defined as a subject who had a PCDAI score that was at least 15 points lower than the 
M06-806 baseline score. 
All subjects will be on open-label maintenance therapy.  Subjects who enroll into the 
study from blinded therapy in Study M06-806 will receive open-label therapy at a dose 
dependent on their body weight.  Subjects who weigh t 40 kg at Baseline will receive 
40 mg eow of adalimumab, while subjects who weigh < 40 kg at Baseline will receive 
20 mg eow of adalimumab.  Beginning at Week 8, subjects who have a disease flare may 
be switched to ew treatment at the same dose of adalimumab received while on eow 
treatment.  A disease flare is defined as an increase in the Pediatric Crohn's Disease 
Activity Index (PCDAI) of t 15 points when compared to the PCDAI score obtained at 
the subject's previous visit. 
Subjects who enroll into the study from open-label therapy in Study M06-806 will 
continue to receive the same dose they were receiving (i.e. 40 mg ew or 20 mg ew) at the 
Week 52 visit of the M06-806 study.  
Subjects who develop a flare while receiving ew open-label therapy or have a PCDAI 
score t 15 points when compared to their Baseline (the Week 52 visit of the M06-806 
study) PCDAI score (regardless of study visit), may be discontinued from the study at the 
discretion of the Investigator.  
Beginning from Week 8, the dose of adalimumab may be increased to 40 mg, at the 
discretion of the Investigator, for subjects whose body weight has increased from < 40 kg 
to t 40 kg from the Baseline (Week 52 of the M06-806 Study) visit.  The site will enter 
the subjects' body weight into the Interactive Voice Response System (IVRS) and the 
dose will be adjusted, if applicable.  
Reductions in concomitant therapy will be allowed for Crohn's treatment related 
toxicities (e.g., leukopenia, anemia, neuropathy) of Grade 3 or higher. 
Subjects may be allowed to decrease prednisone (or equivalent) and budesonide if 
qualifications are met (please see Section 5.2.3.2 for required timing and rate of taper). 

 
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3. 
If female, subjects who are sexually active and are of child-bearing potential 
should be practicing an approved method of birth control throughout the study and 
for 150 days after study drug administration.  Examples of approved methods of 
birth control include the following: 
● Condoms, sponge, foam, jellies, diaphragm or intrauterine device (IUD) 
● Oral, parenteral or intravaginal contraceptives 
● A vasectomized partner 
4. 
Subject of legal age, parent or legal guardian, as required, has voluntarily signed 
and dated an Institutional Review Board (IRB)/Independent Ethics Committee 
(IEC) approved informed consent form, after the nature of the study has been 
explained and the subject of legal age, subject's parent, or legal guardian, as 
required, has had the opportunity to ask questions.  Subjects will be included in all 
discussions, and if required, their signature on an assent form will be obtained. 
5. 
Parent or legal guardian of subject who is not of legal age, as required, must be 
willing to actively supervise storage and administration of study drug and to 
ensure that the time of each dose is accurately recorded in the subject's diary. 
6. 
If a subject of legal age, must be willing to actively store, administer, and 
accurately record study drug administration in the subject diary. 
7. 
Subject is judged to be in acceptable medical condition, as determined by the 
Principal Investigator based upon results of clinical and laboratory evaluations 
done throughout the preceding Crohn's disease study M06-806. 
 
5.2.2 
Exclusion Criteria 
A subject will be excluded from the study if he/she meets any of the following criteria:  
1. 
For any reason, the subject is considered by the Investigator to be an unsuitable 
candidate for continuing therapy in the M06-807 study. 

 
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2. 
Subject has abnormal laboratory or other test results that in the opinion of the 
Investigator will make the subject unsuitable to participate in this study. 
3. 
History of cancer or lymphoproliferative disease other than a successfully and 
completely treated cutaneous squamous cell or basal cell carcinoma or 
carcinoma − in-situ of the cervix. 
4. 
History of listeriosis, histoplasmosis, chronic or active hepatitis B infection, 
human immunodeficiency virus (HIV) infection, any immunodeficiency 
syndrome, central nervous system (CNS) demyelinating disease or active TB 
(receiving treatment or not receiving treatment).  Ongoing severe infections such 
as sepsis and opportunistic infections will be exclusionary. 
5. 
Subject with known, symptomatic obstructive strictures. 
6. 
Subject who is planning surgical bowel resection at any time point while enrolled 
in the study. 
7. 
Subject who has short bowel syndrome as determined by the Investigator. 
8. 
Subject who is currently receiving total parenteral nutrition (TPN). 
9. 
Subject who is unwilling to discontinue growth hormone prior to the first dose of 
open-label study drug at the Baseline visit of M06-807. 
10. 
Female subject who is pregnant or currently breast-feeding. 
11. 
Subject with a history of clinically significant drug or alcohol abuse in the last 
year. 
12. 
Subject with a poorly controlled medical condition such as: uncontrolled diabetes, 
recurrent infections, unstable ischemic heart disease, moderate to severe heart 
failure, recent cerebrovascular accidents or any other condition which, in the 

 
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opinion of the Investigator or the Sponsor, will put the subject at risk by 
participation in the protocol. 
13. 
Subject with any prior exposure to Tysabri (natalizumab). 
14. 
Subject with a known hypersensitivity to the excipients of adalimumab as stated in 
the label. 
15. 
Subject with a previous history of dysplasia of the gastrointestinal tract. 
16. 
Subject is not in compliance with Section 5.2.3. 
 
If there are any questions regarding inclusion and exclusion criteria and/or subject 
eligibility, contact the Abbott Laboratories Medical Monitor identified in Section 7.0. 
5.2.3 
Prior and Concomitant Therapy 
5.2.3.1 
Prior Therapy 
Any medication (including over-the-counter medicines such as aspirin) that the subject is 
receiving during the study must be recorded in source documents and on the appropriate 
case report form (CRF) along with the reason for use, dates of administration and 
dosages. 
Any vaccine administered to the subject during the study should be listed as a 
concomitant medication.  Subjects should continue on the recommended vaccination 
schedule; however, vaccinations with live vaccines are prohibited.   
Any medications captured in the M06-806 CRF(s) which are ongoing will be transcribed 
onto the M06-807 source documents and CRF(s). 
If there are any questions regarding prior or concomitant therapy (ies), contact the Abbott 
Laboratories Medical Monitor identified in Section 7.0 

 
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5.2.3.2 
Concomitant Therapy 
Adjustments of Crohn's related concomitant treatments, including Crohn's related 
antibiotics, are not allowed during the first 8 weeks of the M06-807 study, unless subject 
safety is at risk. 
After Week 8, decreases in the dose or discontinuation of Crohn's related antibiotics or 
Crohn's related concomitant treatments are allowed according to the Investigator's 
medical judgment.  These adjustments may be performed without prior discussion with 
the Abbott Medical Monitor.  In addition, Subjects may be able to initiate or reinitiate 
Crohn's related treatments, except immunosuppressants, following eight (8) weeks of 
exposure to open-label adalimumab.  Immunosuppressants may not be started or restarted 
during the study.
Setons are allowed as concomitant therapy in subjects with perianal fistulas.  Their use 
should be documented on the concomitant medications page of the CRF. 
Growth hormone must be discontinued prior to the first dose of open-label study drug and 
Subjects may not begin using it while participating in this study. 
If a subject began to taper corticosteroids during the M06-806 study, they may continue 
this taper immediately upon enrollment into the M06-807 study.  Beginning at Week 8, 
subjects who are not in flare may begin corticosteroid taper according to the following 
schedule: 
Tapering Schedule 
Dose 
Rate 
Prednisone (or equivalent) 
> 10 mg 
d 10 mg  
5 mg/week 
2.5 mg/week 
Budesonide 
d 9 mg  
3 mg/week 
 
Subjects who are in flare or who flare after they have reduced or completely tapered their 
dose of corticosteroid may have their corticosteroid dose increased or restarted, at the 
discretion of the Investigator.  

 
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5.2.3.3 
Rescue Therapy 
If the Investigator decides, during the study, that a subject requires rescue therapy other 
than that described in this protocol, the subject must be terminated from the study.  If 
possible, questions regarding the use of rescue therapy should be discussed with the 
Medical Monitor prior to use. 
5.2.3.4 
Prohibited Therapy 
Live vaccines must not be given concurrently while on study drug and for 70 days after 
the last dose of study drug. 
Infliximab and growth hormone use are prohibited during the study.  At the Baseline 
visit, any subject using Growth hormone must discontinue its use. 
Tysabri (natalizumab), concurrent biological therapy, cyclosporine, tacrolimus, 
mycophenolate mofetil, Kineret® (anakinra), Orencia (abatacept), therapeutic enemas and 
suppositories (not including those done in conjunction with routine colonoscopies) and 
any investigational agent are prohibited during the study (see Appendix K). 
Concurrent use of budesonide and prednisone (or equivalent) is prohibited. 
Subjects with any prior exposure to Tysabri (natalizumab) will be excluded. 
5.3 
Efficacy, and Safety Assessments/Variables 
5.3.1 
Efficacy and Safety Measurements Assessed and Flow 
Chart
Study procedures will be performed as summarized in the study schematic presented in 
Table 1. 

 
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Table 1.  
Study Activities 
Activity 
Base-
line
Week
4
Week
8
Week
12
Week
24
Week
36
Week
48
Week
60
Week
72
Week
84
Week
96
Week
104/ 
Early 
Term
Unscheduled 
visit 
70-Day 
Follow-up 
Phone Call
Inclusion/exclusion criteria 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Previous and concomitant 
medications 
Xa 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Urine pregnancy testb 
Xa 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Vital signsc 
Xa 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Physical exam 
Xa 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
General LABd 
Xa 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Urinalysise 
Xa 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Erythrocyte sedimentation 
rate 
Xa 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
CRP 
Xa 
 
 
 
X 
 
X 
 
X 
 
 
X 
 
 
ANA 
Xa 
 
 
X 
 
 
 
 
 
 
 
X 
 
 
Anti-dsDNAf 
Xa 
 
 
X 
 
 
 
 
 
 
 
X 
 
 
PCDAI 
Xa 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
CDAIg 
Xa 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
IMPACT III Questionnaireh 
Xa 
 
 
X 
X 
 
X 
 
X 
 
 
X 
 
 
 

 
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Table 1.  
Study Activities (Continued) 
Activity 
Base-
line
Week
4
Week
8
Week
12
Week
24
Week
36
Week
48
Week
60
Week
72
Week
84
Week
96
Week
104/ 
Early 
Term
Unscheduled 
visit 
70-Day 
Follow-up 
Phone Call
Unscheduled outpatient 
visits, emergency room 
visits and hospitalizations 
questionnaire 
Xa 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
Work Productivity and 
Impairment Questionnaire: 
Crohn's Disease  
(WPAI − CD) 
Xa 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
X-ray for bone age 
Xa 
 
 
 
 
 
X 
 
 
 
 
X 
 
 
Serum bone markers 
Xa 
 
 
 
X 
 
X 
 
X 
 
 
X 
 
 
Adverse eventsi 
Xa 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Dispense study drug 
Xa 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Xj 
 
a. 
At the Baseline Visit, the following procedures will be completed as part of Week 52 of the M06-806 study. 
b. Performed on all females of child-bearing potential - Urine pregnancy test at all study visits. 
c. 
Vital sign determinations of height, weight, sitting blood pressure, heart rate, respiratory rate, and body temperature will be obtained at each visit. 
d. Blood draws should be performed after questionnaire and vital signs determinations and before study drug administration. 
e. 
Microscopic urinalysis will be performed at any visit if dipstick UA is abnormal (protein greater than a trace, blood greater than 5-10 Ery/ul, moderate or 
large ketone count or glucose greater than 50 mg/dL). 
f.  If an ANA result is positive, anti-dsDNA will be performed automatically. 
g.  For subjects who are age 13 or older at the M06-807 Baseline Visit, a CDAI will be completed at each visit. 
h. For subjects who are age 10 or older at the M06-807 Baseline Visit, an IMPACT III Assessment will be completed at Baseline, Weeks 12, 24, 48, 72, and 
104/ET. 
i. 
All AEs, including SAEs, will be captured throughout the study from the time that the subject signs the Informed Consent Form. SAEs will be captured 
throughout the 70 day follow-up period (if applicable). 
j. 
If an unscheduled visit is performed to change the frequency of study drug from OL eow to OL ew, study drug may be dispensed. 
 

 
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5.3.1.1 
Study Procedures 
The M06-806 Week 52 visit will serve as the Baseline visit for the M06-807 study.  The 
study procedures outlined in Table 1 are discussed in detail in this section, with the 
exception of the collection of AE information (discussed in Section 6.0).  All study data 
will be recorded in source documents and on the appropriate CRFs.
The visit window for all scheduled visits is ±7 days calculated from the Baseline visit of 
the M06-807 study. 
Inclusion/Exclusion Criteria
A subject will be excluded from this study if he/she does not meet all inclusion criteria or 
meets any of the exclusion criteria of Protocol M06-807. 
Informed Consent
A signed Informed Consent Form (ICF) will be obtained from a subject of legal age (in 
the state of residence) or from the parent or legal guardian (as appropriate)of a subject 
who is not of legal age before any study related procedures are undertaken or before any 
medications are discontinued for the purpose of this study.  Additionally, an informed 
consent will be required from those subjects who were not of legal age at the onset of this 
study but become of legal age during the course of the study. 
In keeping with each institution's IRB requirements, an Informed Assent may also be 
required from pediatric subjects.  Pediatric subjects will be included in all discussions in 
order to obtain their signature on an assent form.  Details about how informed consent 
will be obtained and documented are provided in Section 9.3. 
If an updated informed consent is approved after a subject has completed or terminated 
early from the study, but is within the 70-day follow-up window, the subject will not be 
required to return to the site for the purposes of signing the updated ICF.  The subject of 
legal age, parent or legal guardian (as appropriate) should be contacted regarding any 
changes and the documentation of the contact should be present in the subject's source. 

 
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Previous and Concomitant Medications
Changes in concomitant medications will be assessed at each study visit from Baseline 
through Week 104/ET visit.  Concomitant medications that are taken prior to the first 
dose of study drug administration for this study will be captured in the subject's casebook 
from the previous study (M06-806).  They will not be required to be captured in the 
subject's casebook of the M06-807 study unless they were ongoing at the Week 52 visit 
of the M06-806 study.  Ongoing concomitant medications from the M06-806 study will 
be transcribed into the subject's M06-807 casebook.
Subjects of legal age or the parent or guardian (as appropriate) of subjects who are not of 
legal age will be provided with a medication log (see Appendix N) to record all 
medications the subject takes throughout the study.  This log must be returned for review 
at every study visit. 
Serum/Urine Pregnancy Test
All female subjects who are experiencing menses, are nearing sexual maturation (in the 
opinion of the Investigator), or who are of child-bearing potential, will undergo a urine 
pregnancy test at each visit.  Urine pregnancy tests will be performed locally by 
designated study personnel.  If a urine pregnancy test is positive, a serum pregnancy test 
must be performed by the central laboratory.  If the serum pregnancy test is positive, the 
subject will be removed from the study.   
A lactating or pregnant female will not be eligible for participation in this study. 
Vital Signs
Vital sign determinations of sitting blood pressure, heart rate, respiratory rate, body 
temperature, weight and height will be obtained at each visit.  All measurements will be 
recorded in metric units when applicable.  
Weight measurements will be obtained using the same measuring instrument at each visit 
and measured with subjects wearing only undergarments.  Height measurements will be 

 
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obtained using the same measuring equipment at each visit and performed on subjects 
with their shoes taken off. 
Physical Examination
A physical examination will be performed at each visit.  A count of the number of 
cutaneous fistulas draining upon gentle compression will be performed during each 
physical exam.30  Fistulas will be classified as abdominal or perianal/anal. 
Physical exam abnormalities (including fistulas and fissures) noted by the Investigator 
will be evaluated and documented on the corresponding source documents.  Any new 
abnormalities or worsening of pre-existing conditions should be captured as AEs. 
Clinical Laboratory Tests 
Samples will be obtained for the laboratory tests listed in Table 2 at all study visits.  
Blood draws should be performed after questionnaires (PCDAI, IMPACT III 
Questionnaire, etc.) and vital sign determinations during a study visit, and before study 
drug administration. 
ICON central laboratory will be utilized to process and provide results for the general 
laboratory tests.  All abnormal laboratory test results that are considered clinically 
significant by the Investigator will be followed to a satisfactory resolution. 
ICON will provide instructions regarding the collection, processing and shipping of these 
samples. 

 
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Table 2.  
Clinical Laboratory Tests  
Hematologya 
Clinical Chemistry 
Urinalysisb 
Serum Bone Markers 
Hematocrit 
Hemoglobin 
Red Blood Cell (RBC) 
count 
White Blood Cell 
(WBC) count 
Neutrophils 
Bands 
Lymphocytes 
Monocytes 
Basophils 
Eosinophils 
Platelet count (estimate 
not acceptable) 
Blood Urea Nitrogen 
(BUN) 
Creatinine 
Total bilirubin 
Serum glutamic-pyruvic  
 
transaminase 
(SGPT/ALT) 
Serum glutamic-
oxaloacetic 
 
transaminase 
(SGOT/AST) 
Alkaline phosphatase 
Sodium 
Potassium 
Calcium 
Inorganic phosphorus 
Uric acid 
Cholesterol 
Total protein 
Glucose 
Triglycerides 
Albumin 
Specific gravity 
Ketones 
pH 
Protein 
Blood 
Glucose 
Osteocalcin 
Bone-specific alkaline 
phosphatase (BSAP)  
bone resorption (Ntx) 
a. 
Basic hematology testing performed on instrumentation does not include band reporting.  When 
Hematology results reflex to a Manual Differential, if there is a band result over 5, it is reported. 
b. Microscopic urinalysis will be performed at any visits if dipstick UA is abnormal  (protein greater than 
a trace, blood greater than 5-10 Ery/ul, moderate or large ketone count or glucose greater than 
50 mg/dL). 
 
Immunologic Laboratory Assessments  
CRP assessments will be performed at Baseline (Week 52 of the M06-806 Study), 
Weeks 24, 48, 72 and 104/ET.  Antinuclear antibody (ANA) will be performed at 
Baseline (Week 52 of the M06-806 Study), Week 12, and Week 104/ET.  If an ANA 
result is positive, anti-double-stranded DNA (anti-dsDNA) will be performed 
automatically. All CRP, ANA, anti-dsDNA will be performed by the central laboratory. 

 
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Erythrocyte Sedimentation Rate (ESR) assessments will be performed at all visits as 
indicated in Table 1.  ESR assessments will be performed by the site's local laboratory. 
Markers of Bone Metabolism 
Serum markers of bone metabolism will be measured at Baseline (Week 52 of the 
M06−806 Study), Weeks 24, 48, 72 and 104/ET.  The bone formation markers to be 
measured are osteocalcin, bone-specific alkaline phosphatase (BSAP), and bone 
resorption (Ntx). 
Urinalysis
Urine will be assessed by dipstick at each visit (done locally).  All results, including 
abnormalities, will be captured in source documentation and on the appropriate CRF.  
If, at any visit, the dipstick UA results are abnormal, the central lab will perform a 
microscopic urinalysis.  Abnormal is defined as protein greater than a trace, blood greater 
than 5-10 Ery/ul, moderate or large ketone count or glucose greater than 50 mg/dL. 
Pediatric Crohn's Disease Activity Index (PCDAI)
The PCDAI score will be calculated at each visit.  When completing the PCDAI, the 
HCT, albumin, and ESR values will be utilized from the same study visit.  
An example of the PCDAI is located in Appendix F.  Instructions for completing the 
PCDAI score is located in Appendix G. 
Crohn's Disease Activity Index (CDAI)
At each visit, a CDAI score will be calculated for subjects who are age 13 or older at the 
M06-807 Baseline Visit.  The CDAI score will be calculated utilizing the subject diary 
and the HCT value from the same study visit.  A copy of the CDAI subject diary is 
located in Appendix G. 

 
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When completing question five (5) ("Taking Lomotil/Imodium/Loperamide/opiates for 
diarrhea, 0 = no, 1 = yes") on the CDAI, "no" should be answered if a subject is taking an 
opiate(s) solely for pain. 
For the CDAI questions regarding presence of anal fistulas and other fistulas, all fistulas 
detectable on physical examination (draining and non-draining) should be captured on the 
CDAI CRF page and calculated into the CDAI score. 
The calculation of the CDAI score is in Appendix H. 
IMPACT III Questionnaire
Subjects t 10 years old at the Baseline visit of the M06-807 study will complete an 
IMPACT III questionnaire at Baseline, Weeks 12, 24, 48, 72, and 104/ET as indicated in 
Table 1.  A copy of the questionnaire is located in Appendix J.  
The IMPACT III will be recorded directly onto the CRF.  The completed CRF will be 
considered source documentation for this assessment. 
Outcomes
The Unscheduled Outpatient Visits, Emergency Room Visits and Hospitalization 
Questionnaire and the Work Productivity and Activity Impairment Questionnaire:  
Crohn's Disease (WPAI-CD) will be completed at each visit except the Unscheduled 
Visit (Appendix M, Appendix S). 
The subject's parent or legal guardian will complete the WPAI directly onto the CRF.  
The completed CRF will be considered source documentation for this assessment. 
Bone Age
An x-ray of the wrist for the assessment of bone age will be obtained at Baseline 
(Week 52 of M06-806), Week 48, and Week 104/ET to determine changes in bone 
maturation as indicated in Table 1.  Sites should use the Greulich and Pyle method for 

 
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reading the x − ray.31  The x-ray report requires the signature of the radiologist who read 
the films.  The bone age that is determined by the x-ray should be recorded on the CRF.   
Anthropometric Evaluations
Height and weight obtained at each visit will be used by Abbott Data Management and 
Statistical groups for determination of BMI and "z" score (observed height velocity 
(cm/yr) - mean height velocity for age and sex (cm/yr) / SD of the mean) for height. 
Adverse Events
Adverse events will be assessed at every study visit from Baseline through Week 104 / 
Early Termination visit.  Any AEs, which are ongoing in the M06-806 study, will be 
transcribed onto the M06-807 source documents and CRF(s) 
For those subjects who complete the study or terminate early, a phone call will be made 
70 days after the last dose of study drug to obtain follow-up information on any ongoing 
and any new AEs. See Section 6.0 and Appendix L for additional information. 
Study Drug Administration
At each study visit, the subject or their trained designated friend, family member or 
health care professional will perform study drug injections under the supervision of a 
trained medical personnel to reinforce proper aseptic SC injection technique.  Subjects or 
a trained designated friend, family member or health care professional will perform 
injections of study drug in the subject's home during weeks they are not in for scheduled 
clinic visits.  Subjects may return to the study site for injections in between study visits if 
subject or a trained designated friend, family member or health care professional cannot 
inject the study medication. 
Subjects will maintain a dosing diary for all study drug administered outside study visits, 
i.e., at home.  In the diary, the date, initials of the person administering the study drug, 
time study drug is administered, kit number and the dose administered will be recorded.  
Subjects must return this diary and it will be reviewed and verified for compliance at 

 
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each visit by the research personnel at the study center.  All relevant dosing information 
will be retained by the study coordinator and transcribed onto a drug accountability form 
at each visit.  Additionally, any discernible departure from the protocol regarding study 
drug administration will be recorded on source documents and appropriate drug 
accountability forms.  A sample of the Subject Dosing Diary is presented in Appendix O. 
At all office visits subjects should be observed after study drug administration, until 
judged clinically stable by the study personnel.  If an anaphylactic reaction or other 
serious allergic reaction occurs, administration of study drug should be discontinued 
immediately and appropriate therapy initiated.  When dosing at home, subjects should be 
instructed to contact the site immediately with any signs or symptoms of a reaction. 
The dosing dates, for all doses of study drug, should be calculated from the Baseline visit 
date.  The Baseline visit date for this study is 364 ± 7 days from the Baseline Visit date of 
M06-806.  A +/- 3 day window is allowable for scheduled study dosing dates. 
For subjects that deviate from this dosing window, every effort should be made to bring 
the subject back to the original dosing schedule as soon as possible.  For situations where 
bringing the subject back on the original dosing schedule will cause the dose to be out of 
the +/- 3 day window, please contact the Medical Monitor for additional instructions. 
Randomization and Assignment of Subject Numbers
All subjects will be centrally registered using an IVRS.  This is an open-label study; 
subjects will not be randomized.  The telephone number and call in directions for the 
IVRS will be provided to each site.  Subjects will keep their study subject number from 
the previous double-blind study (M06 − 806). 
5.3.2 
Drug Concentration Measurements 
No drug concentration measurements will be obtained in this trial. 

 
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5.3.3 
Efficacy Variables 
Efficacy will be evaluated based on the proportion of subjects who maintain PCDAI 
clinical response at each visit.  Clinical response is defined as PCDAI decrease 
t 15 points from the M06-806 Baseline score. 
Other measures of disease activity being assessed in this study will be summarized, 
including CDAI scores, IMPACT III scores, WPAI-CD Caregiver, z-score for height 
velocity, bone x-ray, serological markers of bone metabolism, and healthcare resource 
utilization (unscheduled outpatient visits). 
5.3.4 
Safety Variables 
AEs, laboratory data, physical examinations and vital signs are the safety parameters and 
these will be assessed throughout the study. 
5.4 
Removal of Subjects from Therapy or Assessment 
5.4.1 
Discontinuation of Individual Subjects 
Subjects will be withdrawn from the study immediately if any of the following occur:   
● Clinically significant abnormal laboratory results or AEs, which rule out 
continuation of the study drug, as determined by the Investigator and the 
Medical Monitor. 
● The Investigator believes it is in the best interest of the subject. 
● The subject or subject's legal guardian requests withdrawal from the study. 
● Selection criteria violation was noted after the subject started study drug, as 
determined by the Medical Monitor (see Sections 5.2.1 and 5.2.2). 
● Introduction of prohibited medications or prohibited concomitant medication 
dosages as determined by the Medical Monitor. 
● The subject is diagnosed with a malignancy except for localized 
non − melanoma skin cancer.  Discontinuation for carcinoma in-situ is at the 
discretion of the Investigator. 

 
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● The subject is diagnosed with dysplasia of the gastrointestinal tract. 
● A female subject who becomes pregnant. 
 
If the subject prematurely discontinues study drug use, the procedures outlined for the 
Week 104/ET Visit must be completed within 2 weeks of the last dose of study drug, and 
preferably prior to the initiation of another therapy.  These procedures should not 
interfere with the initiation of any new treatments or therapeutic modalities that the 
Investigator feels are necessary to treat the subject's condition.  Following 
discontinuation of the study drug, the subject will be treated in accordance with the 
Investigator's best clinical judgment. 
Subjects who prematurely discontinue from the study will not be replaced.  The date of 
last dose and reason for premature discontinuation will be recorded in the source 
document and on the appropriate CRF. 
5.4.2 
Discontinuation of Entire Study 
Abbott reserves the right to discontinue the study at any time and to remove all study 
materials from the site.  Possible reasons for termination of the study include, but are not 
limited to: 
● Safety concerns based on reported data 
● Unsatisfactory enrollment with respect to quantity or quality 
● Inaccurate or incomplete data collection 
● Falsification of records 
● Failure to adhere to the protocol 
 
5.4.3 
Stopping Rules 
An independent Data Monitoring Committee (DMC) will meet to discuss unblinded data 
from the study every six (6) months or at a frequency determined by the DMC and render 
their recommendation for either the continuation of the study or an amendment to the 

 
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study.  A Sponsor Steering Committee (SSC), composed of senior executives not directly 
participating in this study, will make final decisions based on DMC recommendations.  In 
addition, an ad-hoc DMC meeting will be convened if either of the following criteria is 
met. 
● The overall proportion of subjects with SAEs, with an investigator-assessed 
causality of at least possibly related or higher, evaluated on a per subject 
basis, exceeds 0.20 (or 20%); or 
● The overall proportion of subjects with serious infectious SAEs, evaluated on 
a per subject basis, exceeds 0.20 (or 20%). 
 
If either of the above criteria is met, the DMC will meet within 2 weeks to consider 
whether or not to recommend a temporary suspension of enrollment. 
5.5 
Treatments 
5.5.1 
Treatments Administered 
All study drug will be provided as a SC injection solution in pre-filled syringes 
containing adalimumab 40 mg/0.8 mL or adalimumab 20 mg/0.4 mL. 
Subjects who enroll into the study from blinded therapy in Study M06-806 will receive 
open-label therapy at a dose dependent on their body weight.  Subjects who weigh t 40 
kg will receive 40 mg eow of adalimumab, while subjects who weigh < 40 kg will 
receive 20 mg eow of adalimumab.  Beginning from Week 8, subjects who have a disease 
flare may be switched to ew treatment at the same dose of adalimumab received while on 
eow treatment. 
Subjects who enroll into the study from open-label therapy in Study M06-806 will 
continue to receive the same dose they were receiving (i.e. 40 mg ew or 20 mg ew) at the 
Week 52 visit of the M06-806 study. 

 
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Subjects who develop a flare while receiving ew open-label therapy or have a PCDAI 
score t 15 points when compared to their Baseline (Week 52 of M06-806) PCDAI score 
(regardless of study visit), may be discontinued from the study at the discretion of the 
Investigator. 
Beginning from Week 8, the dose of adalimumab may be increased to 40 mg, at the 
discretion of the Investigator, for subjects whose body weight has increased from < 40 kg 
to t 40 kg from the study Baseline visit.  The site will enter the subjects' body weight into 
the IVRS and the dose will be adjusted, if applicable. 
5.5.2 
Identity of Investigational Product 
The individual study drug information is presented in Table 3.  Pre-filled syringes will be 
provided for this open-label clinical study. 
Table 3.  
Identity of Investigational Products  
Study Drug 
Formulation 
Manufacturer 
Adalimumab 
40 mg/0.8 mL or 20 mg/0.4 mL  
Adalimumab/Mannitol, Citric acid monohydrate, Sodium citrate, 
Disodium phosphate dihydrate, Sodium dihydrogen phosphate 
dihydrate, Sodium chloride, Polysorbate 80, Water for injections, 
Sodium hydroxide added as necessary to adjust pH 
Abbott 
 
5.5.2.1 
Packaging and Labeling 
The following information will appear on the pre-filled syringe or carton labels: 
● Sponsor identification 
● Protocol number 
● Drug identification 
● Quantity of contents 
● Storage conditions 
● Dosing instructions 
● Kit number 

 
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● Route of Administration 
● Excipients 
● Blank spaces to write the subject's identification number, initials, and date 
dispensed (as required) 
● Finishing lot # 
● Expiry Date (as required) 
 
Two pre-filled syringes will be provided in a dosing kit carton (see Table 4).  Detailed 
instructions and training for the administration of study supplies are provided in 
Appendix P. 
Table 4.  
Study Drug Packaging and Administration 
Open-label Pre-filled Syringes 
Open-label kit cartons containing two pre-filled 
syringes of adalimumab 40 mg/0.8 mL. 
Open-label kit cartons containing two pre-filled 
syringes of adalimumab 20 mg/0.4 mL. 
 
5.5.2.2 
Storage and Disposition of Study Drug 
Pre-filled syringes are to be stored protected from light at 2° to 8°C/ 36° to 46°F.  
DO NOT FREEZE.  A storage temperature log is to be maintained at the site to document 
proper storage conditions.  The refrigerator temperature must be recorded on every 
business day on a temperature log to record proper function.  Malfunctions must be 
reported to the sponsor immediately.  Study drug should be quarantined and not 
dispensed until Abbott GPRD or Abbott Temperature Excursion Management System 
(ATEMS) deems the medication as acceptable.  All clinical supplies must be stored and 
locked in a secure place until they are dispensed for subject use or are returned to Abbott 
Laboratories. 
Investigational products are for investigational use only, and are to be used only within 
the context of this study. 

 
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5.5.3 
Method of Assigning Subjects to Treatment Groups 
This is an open-label study; all subjects will be receiving adalimumab. 
All subjects will be centrally registered using an IVRS.  The telephone number and 
call − in directions for the IVRS will be provided to each site.  Subjects will keep their 
study subject number from the previous study (M06 − 806). 
Study drug will be administered at the study visits summarized in Table 1 and detailed in 
Section 5.3.1.1. 
5.5.4 
Selection and Timing of Dose for Each Subject 
Subjects who enroll into the study from blinded therapy in Study M06-806 will receive 
open-label therapy at a dose dependent on their body weight.  Subjects who weigh 
t 40 kg will receive 40 mg eow of adalimumab, while subjects who weigh < 40 kg will 
receive 20 mg eow of adalimumab.  Beginning from Week 8, subjects who have a disease 
flare may be switched to ew treatment at the same dose of adalimumab received while on 
eow treatment. 
Subjects who enroll into the study from open-label therapy in Study M06-806 will 
continue to receive the same dose they were receiving (i.e., 40 mg ew or 20 mg ew) at the 
Week 52 visit of the M06-806 study.  
Subjects who develop a flare while receiving ew open-label therapy or have a PCDAI 
score t 15 points when compared to their Baseline (the Week 52 visit of the M06-806 
study) PCDAI score (regardless of study visit), may be discontinued from the study at the 
discretion of the Investigator.  
The Baseline Visit date for this study should be 364 ± 7 days from Baseline Visit date of 
M06-806 study.  All clinic visits for the subject should be scheduled on the same day as 
the Baseline visit for this study.  For home administration of drug, subjects will be 
instructed to inject study drug on the same day of the week as their Baseline visit day.  
Subjects must inject within a +/-3 day window of this day.  If the subject is out of the 

 
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dosing window, the Medical Monitor should be contacted to determine the timing of the 
next dose.  The subject must record all dosing information on the subject dosing diary 
(Appendix O). 
5.5.5 
Blinding 
This is an open-label study. 
5.5.6 
Treatment Compliance 
The Investigator or his/her designated representatives will administer study drug only to 
subjects enrolled in the study.  
In order to document compliance with the treatment regimen, all pre-filled syringes will 
be counted and documented in source documents and on the appropriate drug 
accountability form. 
5.5.7 
Drug Accountability 
The Investigator or designee will verify that study drug supplies are received intact, at the 
appropriate temperature, and in the correct amounts from the drug depot.  This will be 
documented by signing and dating the Proof of Receipt (POR) or similar document.  The 
original POR or similar document will be kept in the site files as a record of what was 
received.  An accurate running inventory of study drug will be kept by the site, and will 
include the kit number, lot number(s), the number of pre-filled syringes dispensed, and 
the date study drug was dispensed for each subject.  An overall accountability of the 
study drug will be performed and verified by the Clinical Research Associate (CRA) 
throughout the study and at the site close-out visit.  All unused pre-filled syringes will be 
inventoried and returned to an identified vendor for disposal as designated by Abbott 
Laboratories.  A copy of the Drug Accountability Form, in accordance with instructions 
provided by the CRA, will also be included in the Returned Goods for disposal shipment.  
A sample Drug Accountability Form is included in Appendix R.  A copy of the Drug 
Accountability Disposal Form, in accordance with instructions provided by the CRA, will 
also be included in the Pharmacy Binder provided to the site. 

 
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All used (expelled) pre-filled syringes will be inventoried by the site and verified by the 
CRA.  The used syringes will be discarded on site, using appropriate biohazard 
precautions.  CRAs and site staff will complete study drug accountability via study drug 
logs, source documents, verification of empty used syringe kit boxes, subject diaries and 
by visually counting the syringes in the sharp's container whenever possible.  Used 
sharp's containers should never be opened.  Each subject will be given their own sharps 
disposal container to store expelled syringes.  Sharps containers should be returned by the 
subject at each visit, for accountability and compliance purposes.  New containers will be 
issued to subjects as necessary.  Once the CRA has verified drug accountability at the 
site, the site staff and CRA will sign off that the expelled pre-filled syringes have been 
destroyed. 
5.6 
Discussion and Justification of Study Design 
5.6.1 
Discussion of Study Design and Choice of Control Groups 
The design of this clinical study was chosen to demonstrate adalimumab as an effective 
therapy for maintaining clinical response in pediatric subjects with CD and to gather 
long-term safety and tolerability data in this subject population. 
5.6.2 
Appropriateness of Measurements 
Standard statistical, clinical, and laboratory procedures will be utilized in this study.  All 
efficacy measurements in this study are standard for assessing disease activity in pediatric 
subjects with Crohn's disease.  All clinical and laboratory procedures in this study are 
standard and generally accepted. 
5.6.3 
Suitability of Subject Population 
Pediatric subjects with CD who have participated in and successfully completed Protocol 
M06-806 through Week 52 and who meet all of the inclusion and none of the exclusion 
criteria are eligible for this study. 

 
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5.6.4 
Selection of Doses in the Study 
The results of the pivotal adalimumab adult CD maintenance trial M02-404, in 
conjunction with results from adalimumab CD Study M02-433, support a maintenance 
dose of adalimumab 40 mg eow.  Data also suggest that patients who lose response to 
adalimumab at 40 mg eow can be dose-escalated to 40 mg weekly with the potential of 
regaining clinical response.  The proposed dosing regimen for Study M06-807 was 
developed using an analogous approach as that studied in the adult CD population. 
Population pharmacokinetic modeling of serum adalimumab concentration data from 
pediatric subjects with JRA was used to identify doses to be evaluated in the current 
study in children with CD.  A model based on the JRA population was chosen because 
the body weight range will closely parallel that in a juvenile CD population.  Escalation 
to weekly dosing will provide average adalimumab concentrations at steady state about 
twice that observed with every other week dosing.  However, these concentrations are 
within the range of systemic exposures that were safely studied in adult subjects with CD. 
6.0 
Adverse Events 
The Investigator will monitor each subject for clinical and laboratory evidence of AEs on 
a routine basis throughout the study.  The Investigator will assess and record any AE in 
detail including the date of onset, description, severity, time course, duration and 
outcome, relationship of the AE to study drug, an event diagnosis, if known, and any 
action(s) taken.  For SAEs not considered "probably related" to study drug, the 
Investigator must provide another cause of event.  For AEs to be considered sporadic, the 
events must be of similar nature and severity.  AEs, whether in response to a query, 
observed by site personnel, or reported spontaneously by the subject will be recorded in 
source documentation and on the appropriate CRF page. 
All AEs will be followed to a satisfactory conclusion. 

 
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6.1 
Definitions 
6.1.1 
Adverse Event 
An AE is defined as any untoward medical occurrence in a patient or clinical 
investigation subject administered a pharmaceutical product and which does not 
necessarily have a causal relationship with this treatment.  An AE can therefore be any 
unfavorable and unintended sign (including an abnormal laboratory finding), symptom, 
or disease temporally associated with the use of a medicinal (investigational) product, 
whether or not the event is considered causally related to the use of the product. 
Such an event can result from use of the drug as stipulated in the protocol or labeling, as 
well as from accidental or intentional overdose, drug abuse, or drug withdrawal.  Any 
worsening of a pre-existing condition or illness is considered an AE.  Laboratory 
abnormalities and changes in vital signs are considered to be AEs only if they result in 
discontinuation from the study, necessitate therapeutic medical intervention, and/or if the 
Investigator considers them to be AEs. 
An elective surgery/procedure scheduled to occur during a study will not be considered 
an AE if the surgery/procedure is being performed for a pre-existing condition and the 
surgery/procedure has been pre-planned prior to study entry.  However, if the pre-existing 
condition deteriorates unexpectedly during the study (e.g., surgery performed earlier than 
planned), then the deterioration of the condition for which the elective surgery/procedure 
is being done will be considered an AE. 
6.1.2 
Serious Adverse Events 
If an AE meets any of the following criteria, it is to be reported to Abbott as an SAE 
within 24 hours of the site being made aware of the SAE.  Additionally, if follow-up 
information is received, it must also be reported to Abbott within 24 hours of being made 
aware of the information. 

 
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Death of Subject 
An event that results in the death of a subject. 
Life-Threatening 
An event that, in the opinion of the Investigator, will have resulted in 
immediate fatality if medical intervention had not been taken.  This does 
not include an event that will have been fatal if it had occurred in a more 
severe form. 
Hospitalization 
An event that results in an admission to the hospital for any length of 
time.  This does not include an emergency room visit or admission to an 
outpatient facility. 
Prolongation of 
Hospitalization 
An event that occurs while the study subject is hospitalized and prolongs 
the subject's hospital stay. 
Congenital Anomaly 
An anomaly detected at or after birth, or any anomaly that results in fetal 
loss. 
Persistent or Significant 
Disability/Incapacity 
An event that results in a condition that substantially interferes with the 
activities of daily living of a study subject.  Disability is not intended to 
include experiences of relatively minor medical significance such as 
headache, nausea, vomiting, diarrhea, influenza, and accidental trauma 
(e.g., sprained ankle). 
Important Medical Event 
Requiring Medical or 
Surgical Intervention to 
Prevent Serious Outcome 
An important medical event that may not be immediately life-threatening 
or result in death or hospitalization, but based on medical judgment may 
jeopardize the subject and may require medical or surgical intervention to 
prevent any of the outcomes listed above (i.e., death of subject, life 
threatening, hospitalization, prolongation of hospitalization, congenital 
anomaly, or persistent or significant disability/incapacity).  Examples of 
such events include allergic bronchospasm requiring intensive treatment 
in an emergency room or at home, blood dyscrasias or convulsions that do 
not result in inpatient hospitalization, or the development of drug 
dependency or drug abuse. 
Spontaneous Abortion 
Miscarriage experienced by study subject. 
Elective Abortion 
Elective abortion performed on study subject. 
 
6.2 
Adverse Event Severity 
The Investigator will use the following definitions to rate the severity of each AE: 
Mild
The AE is transient and easily tolerated by the subject. 
Moderate 
The AE causes the subject discomfort and interrupts the subject's usual 
activities. 
Severe
The AE causes considerable interference with the subject's usual activities 
and may be incapacitating or life threatening.   
 

 
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6.3 
Relationship to Study Drug 
The Investigator will use the following definitions to assess the relationship of the AE to 
the use of study drug:   
Probably Related 
An adverse event has a strong temporal relationship to study drug or 
recurs on re-challenge and an other cause of event is unlikely or 
significantly less likely. 
Possibly Related 
An AE has a strong temporal relationship to the study drug and an other 
cause of event is equally or less likely compared to the potential 
relationship to study drug. 
Probably Not Related 
An AE has little or no temporal relationship to the study drug and/or a 
more likely other cause of event exists. 
Not Related 
An AE is due to an underlying or concurrent illness or effect of another 
drug and is not related to the study drug (e.g., has no temporal 
relationship to study drug or has a much more likely other cause of event). 
 
If an Investigator's opinion of possibly, probably not, or not related to study drug for an 
SAE is given, an alternative cause of the event must be provided by the Investigator for 
the SAE. 
6.4 
Adverse Event Collection Period 
All AEs reported from the time of informed consent until 5 half-lives (70 days), 
following discontinuation of study drug administration have elapsed will be collected, 
whether elicited or spontaneously reported by the subject.  In addition, SAEs will be 
collected from the time the subject or parent/legal guardian has signed the study-specific 
informed consent. 
Adverse event information will be collected as shown in Figure 2. 

 
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Figure 2.  
Adverse Event Collection 
SAEs and Non-serious AEs 
Elicited and/or Spontaneously Reported 
_ 
 
_ 
 
_ 
 
_ 
Consent 
Signed 
 
Study Drug 
Start 
 
Study Drug 
Stopped 
 
70 Days After 
Study Drug 
Stopped 
 
6.5 
Adverse Event Reporting 
In the event of an SAE, whether related to study drug or not, the Investigator will notify 
Abbott by faxing the appropriate SAE forms to one of the following people within 24 
hours of the site being made aware of the SAE.  Additionally, if follow-up information is 
received, it must also be reported to Abbott within 24 hours of being made aware of the 
information. 
For sites located within North America: 
SAE Support Hotline 
 

 
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For sites located outside North America: 
 
For questions regarding SAEs, please contact:   
 
6.5.1 
Collection of Data Regarding Known Manifestations of the 
Disease Under Study 
Flare, of Crohn's disease events per study definition, are not required to be captured as 
AEs, but may be captured per Investigator discretion.  Additionally, CD pre-existing 
conditions will not be captured as AEs unless the condition has worsened or is considered 
clinically significant in the opinion of the Investigator. 

 
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6.6 
Pregnancy 
Abbott Laboratories must be notified within 1 working day of a site's learning if a female 
subject becomes pregnant during the study or within 150 days of receiving the last dose 
of study drug (see Section 6.5 for contact information). 
Females who become pregnant during the study will be discontinued from study drug as 
described in Section 5.4.  Data regarding the outcome of any pregnancy occurring in a 
study subject will be collected.  Upon notification of a pregnancy Abbott will forward a 
form to the site, for the Investigator to complete and send back to Abbott.  A second form 
will also be sent approximately 9 months from the date of notification to collect 
information on the outcome of the pregnancy.  This form will also need to be completed 
and sent back to Abbott. 
To monitor outcomes of pregnant women exposed to adalimumab, a pregnancy registry 
has been established for the United States.  Physicians in the United States are 
encouraged to register subjects by calling 
and/or provide this 
information to the subject. 
Pregnancy in a study subject is not considered an AE.  However, the medical outcome of 
an elective or a spontaneous abortion, stillbirth or congenital anomaly is considered a 
SAE, and must be reported to the sponsor with 24 hours of the site learning of the event. 
7.0 
Protocol Deviations 
The Investigator should not implement any deviation from the protocol without prior 
review and agreement by the Sponsor and in accordance with the IEC/IRB and local 
regulations, except when necessary to eliminate an immediate hazard to study subjects.  
When a deviation from the protocol is deemed necessary for an individual subject, the 
Investigator must contact the following Abbott representative:    

 
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For purposes of this protocol, reportable deviations are defined as:   
● Subject entered into the study even though they did not satisfy entry criteria 
● Subject who developed withdrawal criteria during the study and was not 
withdrawn 
● Subject who received wrong treatment or incorrect dose 
● Subject who received excluded concomitant treatment 
 
Such contact must be made as soon as possible to permit a review by Abbott to determine 
the impact of the deviation on the subject and/or the study.  Any significant protocol 
deviations affecting subject eligibility and/or safety must be reviewed and/or approved by 
the IEC/IRB and regulatory authorities, as applicable, prior to implementation. 
8.0 
Statistical Methods and Determination of Sample 
Size
8.1 
Statistical and Analytical Plans 
8.1.1 
Analyzable Population 
Efficacy analyses will be conducted in the intent-to-treat (ITT) population, which is 
defined as all subjects who received at least one dose of adalimumab in Study M06-807.  
In order to evaluate the impact of major protocol violations / deviations on the results of 

 
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the study, additional analyses may be performed on the per-protocol population, which 
excludes all subjects with major protocol deviations.  The safety population consists of all 
subjects who received at least one dose of adalimumab in Study M06-807. 
8.1.2 
Planned Methods of Statistical Analysis 
All statistical analyses are to be performed descriptively.  Descriptive summary statistics 
will be provided for the demographic and baseline characteristics, efficacy, and safety 
parameters.  Continuous variables will be summarized using the number of observation, 
mean, standard deviation, 1st quartile, median, 3rd quartile, minimum, and maximum; 
whereas discrete variables will be summarized using count and percentages.  
8.1.2.1 
Demographics and Baseline Characteristics 
Summary statistics for the demographic and baseline characteristics will be computed 
based on the Week 52 values (from double-blind study M06-806). 
8.1.2.2 
Primary Efficacy Analysis 
Summary statistics will be provided for each visit, based on observed data.  An additional 
summary will be provided for the last visit, using the last observation carried forward 
(LOCF).  That is, the subject's last non-missing, post-baseline value (i.e., post-Week 52 
M06-806 double-blind value) will be carried forward to the last visit. 
8.1.3 
Other Analyses 
The primary endpoint will be analyzed for the following subgroups in the ITT population. 
● Sex [Male, Female] 
● Age [< 13 years, t 13 years] 
● Ethnicity [White, Non-white] 
● Weight [< 40 kg, t 40 kg] 
● Prior infliximab use [No, Yes] 

 
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● Baseline CRP [< 1.0 mg/dL, t 1.0 mg/dL] 
● Concomitant use of immunosuppressants and/or oral corticosteroids [No, Yes] 
 
8.1.4 
Safety Analyses 
Safety analyses will be based on the safety population.  Treatment-emergent, and 
post − treatment AEs will be summarized.  An overview of treatment-emergent AEs 
including AEs of special interest, such as AEs leading to death and AEs leading to 
premature discontinuation, AEs by (MedDRA® version 10.0 or later) preferred term and 
system organ class, AEs by maximum relationship to study drug, and AEs by maximum 
severity will be summarized.  Treatment-emergent AEs are defined as new events that 
begin either on or after the first dose of the study drug and within 70 days after the last 
dose of the study drug. 
Adverse events with missing or unknown severity will be categorized as severe.  Adverse 
events with missing or unknown relationship to study drug will be categorized as 
probably related. 
Adverse events that are reported more than 70 days after last study injection will be 
excluded from the summaries; however, all reported AEs will be included in the AE data 
listings. 
For laboratory parameters, the normal range of the analyzing laboratory will be used and 
all values outside the normal range will be flagged and listed.  Additionally, descriptive 
statistics for the mean change from baseline to minimum (smallest) value, maximum 
(largest) value and final value during the study will be calculated for the continuous 
clinical laboratory parameters.  
Shift tables will be provided to cross-classify and tabulate subjects' value from baseline to 
final value by the presence of clinically significant laboratory results.  Each subject's 
baseline value and final value will be flagged in reference to the normal range (low, 

 
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normal, high) and also categorized as clinically non-significant (CTC grade < 3) or 
clinically significant (CTC grade t 3).  Further details will be provided in the SAP. 
8.1.5 
Interim Analysis 
There are no planned interim analyses. 
8.2 
Determination of Sample Size 
Subjects who successfully completed Study M06-806 through Week 52 may be eligible 
to participate in this study. It is expected that approximately 70% (130) of subjects from 
the M06-806 study will enroll in this study. 
8.3 
Randomization Methods 
All subjects will be centrally registered using an IVRS.  This is an open-label study; 
therefore, subjects will not be randomized before the study is initiated, the telephone 
number and call in directions for the IVRS will be provided to each site.  Subjects will 
keep their subject number from the previous study (M06-806). 
9.0 
Ethics 
9.1 
Independent Ethics Committee (IEC) or Institutional Review 
Board (IRB) 
Good Clinical Practice (GCP) requires that the clinical protocol, any protocol 
amendments, the Investigator's Brochure, the informed consent and all other forms of 
subject information related to the study (e.g., advertisements used to recruit subjects) and 
any other necessary documents be reviewed by an IEC/IRB.  IEC/IRB approval of the 
protocol, informed consent and subject information and/or advertising, as relevant, will 
be obtained prior to the authorization of drug shipment to a study site. 
Any amendments to the protocol will require IEC/IRB approval prior to implementation 
of any changes made to the study design.  A list of the documents required prior to 
initiation of the study can be found in Appendix B. 

 
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Any SAEs that meet the reporting criteria, as dictated by local regulations, will be 
reported to both responsible Ethics Committees and Regulatory Agencies, as required by 
local regulations.  During the conduct of the study, the Investigator should promptly 
provide written reports (e.g., ICH Expedited Reports, and any additional reports required 
by local regulations) to the IEC/IRB of any changes that affect the conduct of the study 
and/or increase the risk to subjects, unless otherwise submitted by the sponsor.  Written 
documentation of the submission to the IEC/IRB should also be provided to Abbott. 
9.2 
Ethical Conduct of the Study 
The study will be conducted in accordance with the protocol, International Conference on 
Harmonization (ICH) guidelines, applicable regulations and guidelines governing clinical 
trial conduct, and the ethical principles that have their origin in the Declaration of 
Helsinki.  Responsibilities of the clinical Investigator are specified in Appendix C. 
9.3 
Subject Information and Consent 
Prior to any study-related procedures or discontinuation of any medications for this study, 
the Investigator or his/her representative will explain the nature of the study to the subject 
of legal age (in the state of residence) or to the parent or legal guardian (as appropriate) 
of a subject who is not of legal age and answer all questions regarding this study.  
Subjects will be included in all discussions. 
The ICF will be reviewed, signed and dated by the subject of legal age (in the state of 
residence) or by the parent or legal guardian (as appropriate) of a subject who is not of 
legal age, and the person who administered the informed consent.  If a subject who was 
not of legal age at the onset of this study becomes of legal age during the course of the 
study, an informed consent will need to be obtained at that time.  Additionally, in keeping 
with each institution's IRB requirements an Informed Assent will also be obtained from 
the subject, as required.   
A copy of the signed ICF and Assent Form will be given to the subject and the subject's 
parent/legal guardian.  The original signed ICF and Assent Form will be placed in the 

 
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subject's medical record.  An entry must also be made in the subject's dated source 
documents to confirm that informed consent was obtained prior to any study-related 
procedures and that the subject received a signed copy. 
If an updated informed consent is approved after a subject has completed or terminated 
early from the study, but is within the 70-day follow-up window, the subject will not be 
required to return to the site for the purposes of signing the updated ICF.  The subject of 
legal age, parent or legal guardian (as appropriate) should be contacted regarding any 
changes and the documentation of the contact should be present in the subject's source.  
10.0 
Source Documents and Case Report Form 
Completion
10.1 
Source Documents 
Source documents are defined as original documents, data and records.  This may include 
hospital records, clinical and office charts, laboratory data/information, subjects' diaries 
or evaluation checklists, pharmacy dispensing and other records, recorded data from 
automated instruments, microfiches, photographic negatives, microfilm or magnetic 
media, and/or x-rays.  Data collected during this study must be recorded on the 
appropriate source documents. 
The Investigator(s)/institution(s) will permit study-related monitoring, audits, IEC/IRB 
review, and regulatory inspection(s), providing direct access to source data documents. 
The IMPACT III questionnaire and the WPAI questionnaire will be recorded directly on 
the CRF(s) by the subject, parent or legal guardian (as appropriate) and these CRFs will 
be considered source data. 
10.2 
Case Report Forms 
Case report forms will be supplied by Abbott.  These forms will be used to transmit 
information collected during the study to Abbott and regulatory authorities, as applicable.  
Case report forms must be completed for each subject enrolled in this study.  All case 

 
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report forms must be legible and completed in indelible black ballpoint ink.  Any 
necessary corrections are to be made by drawing a single line through the incorrect entry 
and writing in the revision.  All revisions must be initialed and dated by the Investigator 
or his/her representative.  Data are not to be obliterated by blacking out, using correction 
fluid or by erasing the original entry.  If the reason for the correction is not obvious, a 
brief explanation (e.g., transcription error) should accompany the change.  All 
information written on the case report forms must also be reflected in the subject source 
documents with the exception of the case report forms discussed above in Section 10.1. 
The Principal Investigator will review the case report forms for completeness and 
accuracy and sign and date each set of case report forms where indicated.  The case 
report forms will be reviewed periodically for completeness, legibility and acceptability 
by Abbott personnel (or their representatives).  Abbott (or their representatives) will be 
allowed access to all source documents in order to verify case report form entries. 
Once the original case report form has been removed from the site, all changes must be 
made via the appropriate change form specified by Abbott.  The Principal Investigator 
will review the change form for completeness and accuracy and sign and date the change 
form where indicated. 
11.0 
Data Quality Assurance 
Prior to the initiation of the study, an Investigator's meeting will be held with Abbott 
personnel, the Investigators and their study coordinators, the CRO's project manager and 
the CRAs for the study.  This meeting will include a detailed discussion of the protocol, 
performance of study procedures, CRF and Subject Diary completion, and specimen 
collection methods.  In addition to or instead of the Investigator's meeting, the study 
personnel at each site may be trained on the study procedures by a CRA at a study 
initiation visit and will be given a CRF completion workbook for reference. 
The CRAs will monitor at each site throughout the study.  One hundred percent (100%) 
source document review will be performed against entries on the CRF and a quality 

 
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assurance check will be performed to ensure that the Investigator is complying with the 
protocol and regulations.  In addition, after CRFs are retrieved by the CRA, a review of 
the data will be conducted by a physician and a clinical review team at Abbott 
Laboratories. 
All data hand entered in the database will be verified by a double-key entry procedure at 
Abbott.  Any discrepancies will be reviewed against the hard copy CRF and corrected on-
line. After completion of the entry process, computer logic checks will be run to check 
for such items as inconsistent study dates and outlying laboratory values.  Any necessary 
corrections will be made to the database and documented via addenda, queries, source 
data clarification form or audit trail.  A manual review of selected line listings will also 
be performed at the end of the study. 
Routine hematology, serum chemistry, and serology will be conducted using a central 
laboratory.  ESR analysis will be done at a local lab designated by the site. The data from 
these analyses will be electronically transferred from the central laboratory to the study 
database.  Urinalysis will be completed locally.  If a microscopic urinalysis is necessary, 
this testing will be conducted using the central laboratory.  A final review of all 
laboratory results will be conducted by a physician and clinical review team at 
Abbott Laboratories. 
Sites will provide Abbott (or designate) with laboratory certifications (CAP and CLIA), 
CV of local lab director, and reference ranges for each local lab used.  The full name, 
address, phone number, and fax number for each local lab will also be included. 
12.0 
Use of Information and Publication 
12.1 
Use of Information 
All information concerning adalimumab and Abbott Laboratories' operations, such as 
Abbott Laboratories' patent applications, formulas, manufacturing processes, basic 
scientific data, or formulation information, supplied by Abbott Laboratories and not 
previously published is considered confidential information. 

 
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The information developed during the conduct of this clinical study is also considered 
confidential and will be used by Abbott Laboratories in connection with the development 
of adalimumab.  This information may be disclosed as deemed necessary by 
Abbott Laboratories to other clinical Investigators, other pharmaceutical companies, to 
the FDA,  and to other government agencies.  To allow for the use of the information 
derived from this clinical study and to ensure complete and thorough analysis, the 
Investigator is obligated to provide Abbott Laboratories with complete test results and all 
data developed in this study and to provide direct access to source data/documents for 
study- related monitoring, audits, IEC/IRB review, and regulatory inspection. 
This confidential information shall remain the sole property of Abbott Laboratories, shall 
not be disclosed to others without the written consent of Abbott Laboratories, and shall 
not be used except in the performance of this study. 
The Investigator will maintain a confidential subject identification code list of all subjects 
enrolled in the study (by name and subject number).  This list will be maintained at the 
site and will not be retrieved by Abbott. 
12.2 
Internet Sites 
Information regarding this study may be posted on various internet web sites and will 
maximally include study name, number, general population to be enrolled, entrance 
qualifications, brief description of the study, study objectives, doses, accruing 
Investigators (upon their approval) and number of subjects to be enrolled. 
13.0 
Completion of the Study 
The Investigator will conduct this study in compliance with the protocol, and will 
complete the study within the timeframe specified in the contract between the 
Investigator and Abbott.  Continuation of the study beyond this time must be mutually 
agreed upon in writing by both the Investigator and Abbott.  The Investigator will 
provide a summary of the study's outcome to the IEC/IRB following conclusion of the 
study, and will forward a copy of this summary to Abbott or their designee. 

 
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Abbott may terminate this study prematurely, either in its entirety or at individual sites, 
for reasonable cause provided that written notice is submitted a reasonable time in 
advance of the intended termination.  The Investigator may also terminate the study at 
their site for reasonable cause, after providing written notice to Abbott a reasonable time 
in advance of the intended termination.  Advance notice is not required by either party if 
the study is stopped due to safety concerns.  If Abbott terminates the study for safety 
reasons, it will immediately notify the Investigator by telephone and subsequently 
provide written instructions for study termination. 
Abbott will select the signatory Investigator from the Investigators who participate in the 
study.  Selection criteria for this Investigator will include level of participation as well as 
significant knowledge of the clinical research, investigational drug and study protocol.  
The signatory Investigator for the study will review and sign the final study report in 
accordance with the European Agency for the Evaluation of Medicinal Products (EMEA) 
Guidance on Investigator's Signature for Study Reports. 
The Investigator will retain all essential documents until at least two years after the last 
approval of a marketing application in an ICH region and until there are no pending or 
contemplated marketing applications in an ICH region or at least two years have elapsed 
since the formal discontinuation of clinical development of the investigational product.  It 
is the responsibility of the sponsor to inform the Investigator/institution as to when these 
documents no longer need to be retained. 
The end-of-study is defined as the date of the last subject's last scheduled visit or the 
actual date of follow-up contact, whichever is longer. 
 

 
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14.0 
Investigator's Agreement 
1. I have received and reviewed the Investigator Brochure for Humira. 
2. I have read this protocol and agree that the study is ethical. 
3. I agree to conduct the study as outlined and in accordance with all applicable 
regulations and guidelines. 
4. I agree to maintain the confidentiality of all information received or developed in 
connection with this protocol. 
 
 
 
 
Protocol Title: 
A Multi-center, Open-label Study of the Human Anti-TNF 
Monoclonal Antibody Adalimumab to Evaluate the Efficacy and the 
Long-term Safety and Tolerability of Repeated Administration of 
Adalimumab in Pediatric Subjects with Crohn's Disease Who Have 
Demonstrated a Clinical Response in the M06-806 Study 
Protocol Date: 
10 October 2008 
 
 
 
 
 
 
Signature of Principal Investigator 
 
Date 
 
 
 
Name of Principal Investigator (printed or typed) 
 
 
 
 

 
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15.0 
Reference List 
1. 
Hanauer SB, Sandborn W.  Management of Crohn's disease in adults.  Am J 
Gastroenterol 2001;96:635-43. 
2. 
Loftus Jr. EV.  Clinical epidemiology of inflammatory bowel disease: Incidence, 
prevalence, and environmental influences.  Gastroenterology 2004;126:1504-17. 
3. 
Seidman EG.  Recent advances in the diagnosis and treatment of pediatric 
inflammatory bowel disease.  Curr Gastroenterol Rep 2000;2:248-52. 
4. 
Auvin S, Molinie F, Gower-Rousseau C, Brazier F, Merle V, Grandbastient B, 
et al.  Incidence, clinical presentation and location at diagnosis of pediatric 
inflammatory bowel disease: a prospective population-based study in northern 
France (1988-1999).  J Pediatr Gastroenterol Nutr 2005;41(1):49-55. 
5. 
Kugathasan S, Judd RH, Hoffmann RG, Heikenen J, Telega G, Khan F, et al.  
Epidemiologic and clinical characteristics of children with newly diagnosed 
inflammatory bowel disease in Wisconsin; a statewide population-based study.  
J Pediatr 2003;143(4):525-31. 
6. 
Cosgrove M, Al-Atia RF, Jenkins HR.  The epidemiology of pediatric 
inflammatory bowel disease.  Arch Dis Child 1996;74:460-1. 
7. 
Hassan K, Cowan FJ, Jenkins HR.  The incidence of childhood inflammatory 
bowel disease in Wales.  Eur J Pediatr 2000;159:261-3. 
8. 
Barton JR, Gillon S, Ferguson A.  Incidence of inflammatory bowel disease in 
Scottish children between 1968 and 1983; marginal fall in ulcerative colitis, three-
fold rise in Crohn's Disease.  Gut 1989;30:618-22. 
9. 
Sawczenko A, Sandhu BK, Logan RFA, et al.  Prospective survey of childhood 
inflammatory bowel disease in the British Isles.  Lancet 2001;357:1093-4. 

 
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10. 
Olafsdottir EJ, Fluge G, Haug K.  Chronic inflammatory bowel disease in children 
in western Norway.  J Pediatr Gastroenterol Nutr 1989;8:454-8. 
11. 
Lindberg E, Lindquist B, Holmquist L, Hildebrand H.  Inflammatory bowel 
disease in children and adolescents in Sweden (1984-1995).  J Pediatr 
Gastroenterol Nutr 2000;30:259-64. 
12. 
Hildebrand H, Finkel Y, Grahnquist L, Lindholm J, Ekbom A, Askling J.  
Changing pattern of paediatric inflammatory bowel disease in northern Stockholm 
1990-2001. Gut 2003;52:1432. 
13. 
Heyman MB, Kirshner BS, Gold BD, Ferry G, Baldassano R, Cohen SA, et al.  
Children with early onset inflammatory bowel disease (IBD): analysis of a 
pediatric IBD consortium registry.  J Pediatr 2005;146(1):35-40. 
14. 
Lindberg E, Lindquist B, Holmquist L, Hildebrand H.  Inflammatory bowel 
disease in children and adolescents in Sweden, 1984-1995.  J Pediatr Gastroenterol 
Nutr 2000;30(3):259-64. 
15. 
Sawczenko A, Sandhu BK.  Presenting features of inflammatory bowel disease in 
Great Britain and Ireland.  Arch Dis Child 2003;88:995-1000. 
16. 
Griffiths AM.  Specificities of inflammatory bowel disease in childhood.  Best 
Pract Res Clin Gastroenterol 2004;18(3):509-23. 
17. 
Griffiths AM, Nguyen P, Smith C, MacMillan JH, Sherman PM.  Growth and 
clinical course of children with Crohn's disease.  Gut 1993;34(7):939-43. 
18. 
Kanof ME, Lake AM, Bayless TM.  Decreased height velocity in children and 
adolescents before the diagnosis of Crohn's disease.  Gastroenterology 
1988;95(6):1523-7. 
19. 
Markowitz J, Grancher K, Rosa J, Aiges H, Daum F.  Growth failure in pediatric 
inflammatory bowel disease.  J Pediatr Gastroenterol Nutr 1993;16(4):373-80. 

 
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20. 
Kleinman RE, Baldassano RN, Caplan A, Griffiths AM, Heyman MB, 
Issenman RM, et al.  Nutrition support for pediatric patients with inflammatory 
bowel disease: a clinical report of the North America Society for Pediatric 
Gastroenterology, Hepatology and Nutrition.  J Pediatr Gastroenterol Nutr 
2004;39(1):15-27. 
21. 
Gokhale R, Favus MJ, Karrison T, Sutton MM, Rich B, Kirshner BS.  Bone 
mineral density assessment in children with inflammatory bowel disease.  
Gastroenterology 1998;114:902-11. 
22. 
Boot AM, Bouquet J, Krennings EP, de Muinck Keizer-Schrama SMPF.  Bone 
mineral density and nutritional status in children with chronic inflammatory bowel 
disease.  Gut 1998;42:188-94. 
23. 
Ballinger AB, Savage MO, Sanderson IR.  Delayed puberty associated with 
Inflammatory bowel disease.  Pediatr Res 2003;53:205-10. 
24. 
Harpavat M, Greenspan SL, O'Brien C, Chang C-C, Bowen A, Keljo DJ.  Altered 
bone mass in children at diagnosis of Crohn's disease: a pilot study.  J Pediatr 
Gastroenterol Nutr 2005;40:295-300. 
25. 
Hyams JS, Wyzga N, Kreutzer DL, Justinich CJ, Gronowicz GA.  Alterations in 
bone metabolism in children with inflammatory bowel disease: an in vitro study. 
J Pediatr Gastroenterol Nutr 1997;24(3):289-95. 
26. 
Hanauer S, Lukas M, MacIntosh D, Rutgeerts P, Sandborn W, Pollack P.  A 
randomized, double-blind, placebo-controlled trial of the human anti-TNF-D 
monoclonal antibody adalimumab for the induction of remission in patients with 
moderate to severely active Crohn's disease.  Gastroenterology 2004;127(1):332. 
27. 
Data on file at Abbott Laboratories. 
28. 
Abbott Study DE038, Data on file. 

 
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29. 
Humira® (adalimumab) [package insert].  North Chicago, IL:  
Abbott Laboratories:  June 2006. 
30. 
Present DH, Rutgeerts P, Targan S, Hanauer SB, Mayer L, van Hogezand RA, 
et al.  Infliximab for the treatment of fistulas in patients with Crohn's disease. 
N Eng J Med.  1999;340(18):1398-405. 
31. 
Greulich and Pyle Radiographic Atlas of Skeletal Development of the Hand and 
Wrist:  June 1959. 
32. 
Centers for Disease Control and Prevention.  Targeted tuberculin testing and 
treatment of latent tuberculosis infection.  MMWR 2006 April. 
 

 
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Appendix A.  
List of Abbreviations and Definition of Terms 
Abbreviations
AE 
Adverse Event 
ALT 
Alanine Transaminase 
ANA 
Antinuclear antibody 
AST 
Aspartate transaminase 
BMI 
Body Mass Index 
BSAP 
Bone-specific alkaline phosphatase 
BUN 
Blood Urea Nitrogen 
CD 
Crohn's disease 
CDC 
Center for Disease Control 
CNS 
Central Nervous Systems 
CRA 
Clinical Research Associate 
CRF 
Case Report Form 
CRP 
C-Reactive Protein 
CTC 
Common Toxicity Criteria 
DMC 
Data Monitoring Committee 
DNA 
Deoxyribonucleic acid 
dsDNA 
Double Stranded DNA 
eow 
Every other week 
ESR 
Erythrocyte sedimentation rate 
ET 
Early Termination 
EU 
European Union 
ew 
Every week 
FDA 
U.S. Food and Drug Administration 
GCP 
Good Clinical Practice 
HCT 
Hematocrit 
HIV 
Human immunodeficiency virus 
ICH 
International Conference on Harmonization 
IEC 
Independent Ethics Committee 
IgG1 
Immunoglobulin 
ICF 
Informed Consent Form 
IRB 
Institutional Review Board 

 
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ITT 
Intent-to Treat 
IVRS 
Interactive Voice Response System 
JRA 
Juvenile Rheumatoid Arthritis 
LOCF 
Last Observation Carried Forward 
MTX 
Methotrexate 
Ntx  
N − telopeptide 
OL 
Open-Label 
PCDAI 
Pediatric Crohn's Disease Activity Index 
POR 
Proof of Receipt 
RA 
Rheumatoid Arthritis 
SAE 
Serious Adverse Event 
SAP 
Statistical analysis plan 
SC 
Subcutaneous 
SSC 
Sponsor Steering Committee 
TB 
Tuberculosis 
TNF 
Tumor Necrosis Factor 
TPN 
Total Parenteral Nutrition 
US 
United States 
WPAI 
Work Productivity and Activity Impairment Questionnaire 
WPAI-CD 
Work Productivity and Activity Impairment Questionnaire: Crohn's 
Disease 
 

 
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Appendix B.  
Documents Required Prior to Initiation of the Study 
As sponsor of a clinical study, Abbott has an obligation to ensure that the study will be 
conducted by a qualified investigator with sufficient resources (of time, personnel, and 
physical facilities) to conduct the study and to ensure that the investigator understands 
and agrees to comply with Good Clinical Practices and applicable regulations, policies, 
and procedures.  Prior to the beginning of any clinical study, the investigator will be 
asked to provide the following documentation.  
1. 
A signed and dated Investigator's agreement page for the study. 
2. 
A signed and dated Form FDA 1572 certifying the investigator's agreement to 
comply with the appropriate regulations governing the conduct of the study.
A signed and dated Investigator Information and Agreement Form certifying the 
investigator's agreement to comply with the appropriate (e.g., ICH GCP) 
regulations governing the conduct of the study. These will be required only for 
sites that are recruited under this amendment, or when existing sites update study 
documentation. 
3. 
 Current curriculum vitae for the investigator.  If subinvestigators will participate 
in the study, curriculum vitae for each. 
4. 
Requirements for the Independent Ethics Committee (IEC)/Institutional Review 
Board (IRB). 
● A copy of the signed and dated letter of approval of the IEC/IRB.  The letter 
must specify that both the protocol and informed consent form were approved 
(unless separate documentation that the informed consent was approved is 
provided). 
● A dated list containing the names and affiliations of the members of the 
IEC/IRB, or the institution's General Assurance Number. 

 
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● If the investigator and/or subinvestigator is a member of the IEC/IRB, a letter 
stating that he/she did not participate in the review or approval of the protocol 
or informed consent form. 
5. 
A specimen copy of the IEC/IRB-approved informed consent document to be used 
in the study. 
6. 
A list of reference ranges of values for all laboratory tests specified by the protocol 
for all laboratories utilized. 
7. 
A copy of the laboratory(ies) certification(s) or the authorization number of the 
certification(s), the name of the certifying authority, and the period of certification. 
8. 
Financial Disclosure Certification forms must be completed by each investigator 
and all subinvestigators identified on the Form FDA 1572 or Investigator 
Information and Agreement Form.  A Financial Disclosure, EU Consent, is 
required to be completed for each investigator and/or subinvestigator who is a 
resident of the European Union 
 

 
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Appendix C.  
Responsibilities of the Clinical Investigator 
Clinical research studies sponsored by Abbott are subject to the regulations of the U.S. 
Food and Drug Administration (FDA).  The responsibilities imposed upon Investigators 
by the FDA are summarized in the "Statement of Investigator" (Form FDA 1572), which 
is a form letter addressed to the sponsor (Abbott), summarizing the Investigator's 
qualifications for the study and his/her willingness to follow FDA regulations with 
respect to the study. 
In signing a Form FDA 1572, the Investigator agrees to assume the following 
responsibilities:   
1. 
To conduct the study(ies) in accordance with the relevant, current protocol(s) and 
only make changes in a protocol after notifying Abbott, except when necessary to 
protect the safety, rights, or welfare of subjects. 
2. 
To personally conduct or supervise the described investigation(s). 
3. 
To inform any subjects, or any persons used as controls, that the drugs are being 
used for investigational purposes and to ensure that the requirements relating to 
obtaining informed consent in 21 CFR Part 50 and Independent Ethics Committee 
(IEC)/Institutional Review Board (IRB) review and approval in 21 CFR Part 56 
are met. 
4. 
To report to Abbott adverse experiences that occur in the course of the 
investigation(s) in accordance with 21 CFR 312.64. 
5. 
To read and understand the information in the Investigator's Brochure, including 
the potential risks and side effects of the drug. 
6. 
To ensure that all associates, colleagues, and employees assisting in the conduct of 
the study(ies) are informed about their obligations in meeting the above 
commitments. 

 
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7. 
To maintain adequate and accurate records of the conduct of the study and make 
those records available for inspection by representatives of Abbott, the IEC/IRB 
and/or the appropriate regulatory agency, and to retain all study-related documents 
until notification from Abbott.  The Investigator must notify Abbott when they are 
no longer able to retain the study related documents. 
8. 
To ensure that an IEC/IRB that complies with the requirements of 21 CFR Part 56 
will be responsible for the initial and continuing review and approval of the 
clinical investigation. 
9. 
To promptly report to the IEC/IRB all changes in the research activity and all 
unanticipated problems involving risks to human subjects or others (including 
submission of any Expedited Safety Reports received from Abbott to the 
IEC/IRB), and to make no changes in the research without IEC/IRB approval, 
except where necessary to eliminate apparent immediate hazards to human 
subjects. 
10. 
To comply with all other requirements regarding the obligations of clinical 
Investigators and all other pertinent requirements in 21 CFR Part 312. 
 

 
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Appendix D.  
CDC Treatment of Tuberculosis Infection (Preventive Therapy) 
Centers for Disease Control and Prevention 
Tuberculosis Information 
Treatment of Tuberculosis Infection (Preventive Therapy), Latent Tuberculosis 
Infection (LBTI)32
 
 

 
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Appendix E.  
Non-Drug Materials Provided to the Study Site(s) 
Study sites will receive the following supplies prior to or during the study: 
Tote Bags 
Cooler 
Sharps Containers 
Ice Packs 
CDAI subject diary 
Dosing Diaries 
Subject Medication Log 
Self Injection Instructions 

 
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Appendix F.  
Pediatric Crohn's Disease Activity Index (PCDAI) 
1. Abdominal pain rating 
 
- None 
 
- Mild - Brief, does not interfere with activities 
 
- Moderate/severe-Daily, longer lasting, affects activities, nocturnal 
 
= 0 p 
= 5 p 
= 10 p 
Score
2. Stools (per day) 
 
- 0–1 liquid stools, no blood 
 
- Up to 2 semi-formed with small blood, or 2–5 liquid 
 
- Gross bleeding, or t 6 liquid, or nocturnal diarrhea 
 
= 0 p 
= 5 p 
= 10 p 
3. Patient Functioning, General Well-Being 
 
- No limitation of activities, well 
 
- Occasional difficulty in maintaining age appropriate activities, below par 
 
- Frequent limitation of activity, very poor 
 
= 0 p 
= 5 p 
= 10 p 
LABORATORY 
Score 
4. HCT: Male and female  d 10 years: 
 
 
t 33 
= 0 p 
 
 
28-32 
= 2.5 p 
 
 
< 28 
= 5 p 
 
Male 11–14 years: 
 
 
t35 
= 0 p 
 
 
30-34 
= 2.5 p 
 
 
<30 
= 5 p 
 
Female 11–19 years: t 34 
= 0 p 
 
 
29-33 
= 2.5 p 
 
 
< 29 
= 5 p 
 
Male 15–19 years: 
t37 
= 0 p 
 
 
32-36 
= 2.5 p 
 
 
<32 
= 5 p 
5. 
ESR (mm/hr) 
< 20 
= 0 p 
 
 
20-50 
= 2.5 p 
 
 
> 50 
= 5 p 
6. 
Albumin (g/dL) 
t 3.5 
= 0 p 
 
 
3.1-3.4 
= 5 p 
 
 
d 3.0 
= 10 p 

 
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EXAMINATION 
Score 
7. 
Weight 
- Weight gain or voluntary weight stable/loss 
 
 
- Involuntary weight stable, weight loss 1–9% 
 
 
- Weight loss t 10% 
= 0 p 
= 5 p 
= 10 p 
8. 
Height 
 
 
 
 
 
 
 
 
Height velocity t -1SD 
 
 
 
Height velocity < -1SD, > -2SD 
 
 
 
Height velocity d -2SD 
 
= 0 p 
= 5 p 
= 10 p 
9. 
Abdomen 
- No tenderness, no mass 
 
 
- Tenderness, or mass without tenderness 
 
 
- Tenderness, involuntary guarding, definite mass 
= 0 p 
= 5 p 
= 10 p 
10. Perirectal disease 
- None, asymptomatic tags 
 
 
- 1–2 indolent fistula, scant drainage, no tenderness 
 
 
- Active fistula, drainage, tenderness, or abscess 
= 0 p 
= 5 p 
= 10 p 
11. Extra-intestinal Manifestations 
 
(Fever t 38.5 for 3 days over past week, definite arthritis, uveitis, E. nodosum, 
P. gangrenosum) 
 
- None 
 
- One 
 
- t Two 
 
 
= 0 p 
= 5 p 
= 10 p 
TOTAL SCORE  
Pediatric Crohn's Disease Activity Index (PCDAI) 
 
 

 
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Appendix G.  
PCDAI User's Guide and Guideline for Reference Weight and 
Reference Height 
This guide is intended to help nurse coordinators and physicians complete the PCDAI in 
order to assess disease activity in children with Crohn's disease participating in clinical 
trials. 
History
All calculations are based upon a one-week (7 day) history recall of symptoms.  The 
history recall should be solicited from the subject and/or caregiver. 
Item 1.  Abdominal pain 
The descriptions in the PCDAI of "mild" and "moderate/severe" should be used to guide 
in scoring the pain. Note that duration, effect on activities, and nocturnal occurrence 
separate moderate/severe from mild.  If pain varies in severity during the week, subject 
should be scored according to the most severe pain. However, mild pain should be 
present on at least two days to score 5 points rather than 0 points. 
Item 2.  Stools 
The intent is to score the stool pattern during the preceding week. 
To facilitate scoring, first categorize the subject as having blood in the stool or not. 
If there is no blood in the stool, score as follows:   
Formed stools or up to 1 loose stool daily = 0 
2-5 liquid or very loose stools on 1 or more days = 5 
6 or more liquid or very loose stools on 1 or more days or any nocturnal diarrhea = 10 

 
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If blood is present in the stool on any day during the past week, score as follows:   
Small amounts of blood in stool (on toilet paper or small spots in stool, etc.) = 5 
Any gross bleeding (large amounts on stool or colors the water in the toilet, etc.) = 10 
Item 3.  Subject functioning, general well-being 
If there is variation during the week, subject should be scored according to the most 
significant limitation of activity, even if it occurs during only one day of the week, as 
long as it is likely due to Crohn's disease and not to an intercurrent illness. 
Item 4.  Hematocrit 
Hematocrit values should be rounded to a whole number prior to completing the 
calculation.   Numbers that fall between the range of 0.1-0.4 must be rounded down.   
Numbers that fall between the range of 0.5-0.9 must be rounded up. 
Physical Examination
Item 7.  Weight (The intent is to assess the ability to normally maintain or gain weight) 
Reference weight to be used for calculation of weight gain/loss during the study: 
From Baseline to Week 104: use weight from previous visit 
Voluntary weight stable/loss means subject maintaining or losing weight on purpose. 
Involuntary weight stable means subject wants to gain weight but cannot. 
To calculate percentage weight loss use formula:   
Weight from previous visit – Current weight X 100 = % weight loss 
 
Weight from previous visit 

 
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Item 8.  Height 
Reference height for calculation of height velocity 
● From Baseline to Week 24, use height from 6 months prior to Baseline 
● From Week 24 to Week 48, use height from Baseline visit 
● From Week 48 to Week 72, use height from Week 24 
● From Week 72, use height from Week 48 
 
The intent is to assess the normalcy vs. impairment of the subject's recent linear growth.  
Note that post-pubertal subjects will score 0 points.  For subjects still growing, there are 
two options for scoring.  Method (a) is preferred.  Method (b) to be used if data required 
for (a) are unavailable. 
1. 
Height velocity (cm/year), the most sensitive parameter, should be calculated as 
below: 
Present height –  Appropriate height measurement (from above)  x  12  = Height velocity (cm/year) 
  
        Interval (months) between heights 
Using height velocity chart below, determine centile for height velocity. 
2. 
Scoring for the PCDAI:   
a. Velocity less than "Minus 2 SD" scores 10 points. 
b. Velocity between "Minus 2 SD" and "Minus 1 SD" scores 5 points. 
c. Velocity greater than "Minus 1 SD" scores zero points. 
 
* 
Please note that subjects should score zero points if a subject is a female above 14.5 years of age or a 
male above 17.5 years of age. 
 

 
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Height Velocity Reference Values for Calculating the PCDAI (Males) 
 
Height Velocity in cm per year (Males) 
Age (years) 
Minus 2SD 
Minus 1SD 
Mean 
2.5 
5.7 
7.0 
8.3 
3 
5.4 
6.6 
7.8 
3.5 
5.1 
6.3 
7.4 
4 
4.9 
6.0 
7.1 
4.5 
4.7 
5.8 
6.8 
5 
4.6 
5.6 
6.6 
5.5 
4.5 
5.4 
6.4 
6 
4.3 
5.3 
6.2 
6.5 
4.2 
5.1 
6.0 
7 
4.2 
5.0 
5.9 
7.5 
4.1 
4.9 
5.8 
8 
3.9 
4.8 
5.6 
8.5 
3.8 
4.6 
5.4 
9 
3.8 
4.5 
5.3 
9.5 
3.7 
4.5 
5.2 
10 
3.7 
4.4 
5.1 
10.5 
3.7 
4.4 
5.1 
11 
3.7 
4.4 
5.2 
11.5 
3.8 
4.6 
5.3 
12 
4.0 
4.9 
5.7 
12.5 
4.8 
5.8 
6.7 
13 
6.2 
7.4 
8.6 
13.5 
7.1 
8.3 
9.5 
14 
6.1 
7.2 
8.4 
14.5 
4.1 
5.3 
6.5 
15 
2.4 
3.6 
4.7 
15.5 
1.2 
2.3 
3.3 
16 
0.4 
1.3 
2.2 
16.5 
0.1 
0.7 
1.5 
17 
0.1 
0.4 
0.9 
17.5 
0.1 
0.1 
0.5 
 

 
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Height Velocity Reference Values for Calculating the PCDAI (Females) 
 
Height Velocity in cm per year (Females) 
Age (years) 
Minus 2SD 
Minus 1SD 
Mean 
2.5 
5.9 
7.3 
8.6 
3 
5.5 
6.9 
8.1 
3.5 
5.2 
6.4 
7.6 
4 
4.9 
6.1 
7.2 
4.5 
4.7 
5.8 
6.8 
5 
4.6 
5.6 
6.6 
5.5 
4.5 
5.5 
6.4 
6 
4.4 
5.3 
6.2 
6.5 
4.3 
5.2 
6.1 
7 
4.3 
5.2 
6.0 
7.5 
4.3 
5.1 
5.9 
8 
4.2 
5.0 
5.8 
8.5 
4.2 
4.9 
5.7 
9 
4.2 
5.0 
5.8 
9.5 
4.3 
5.0 
5.8 
10 
4.4 
5.3 
6.2 
10.5 
4.7 
5.7 
6.8 
11 
5.7 
6.6 
7.7 
11.5 
6.1 
7.2 
8.3 
12 
5.2 
6.3 
7.3 
12.5 
3.6 
4.8 
5.9 
13 
2.4 
3.3 
4.3 
13.5 
1.3 
2.2 
2.9 
14 
0.4 
1.1 
1.8 
14.5 
0.0 
0.5 
1.0 
 

 
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Appendix H.  
Crohn's Disease Activity Index (CDAI) 
 
 
 
Factor 
Subtotal 
1. Number of liquid or very soft stools
(Record the frequency per day) 
         __+___+___+___+___+___+___=___ 
Days: 1     2      3      4 
5      6 
  7   Sum 
X 
2 
 
2.  Abdominal pain rating: 
0=none, 1=mild, 2=moderate, 
3=severe 
          __+___+___+___+___+___+___=___ 
Days: 1     2      3      4 
5      6 
  7   Sum 
X 
5 
 
3. General well-being: 
0=generally well, 1=slightly 
underpar, 2=poor, 3=very poor, 
4=terrible 
         __+___+___+___+___+___+___=___ 
Days: 1     2      3      4 
5      6 
  7   Sum 
X 
7 
 
4. Number of 6 listed categories the 
subject now has: 
Check all items that apply: 
□  Arthritis/arthralgia 
□  Iritis/uveitis 
□  Erythema nodosum/  
 pyoderma gangrenosum/ 
 aphthous stomatitis 
□  Fissure, abscess and/or anal 
fistula (draining/non-draining) 
□  Other cutaneous fistula 
(draining/non-draining) fistula 
□  Fever over 100°F (37.8°C) during 
past week 
 
 
 
 
 
 
  
________ 
 
 
 
Record "0" if no categories checked 
X 
20 
 
5.   Taking Lomotil / Imodium / 
Loperamide /opiates for diarrhea  
0=no, 1=yes 
________ X 
30 
 
6.   Abdominal mass 
0=none, 2=questionable, 5=defined 
________ X 
10 
 
7.   Hematocrit: ______ 
Male: 
(47 - hematocrit) = 
Female: (42 - hematocrit) = Subtotal ______ 
If hematocrit > normal, enter "0" 
X 
6 
 
8.   Body weight: __  __  __ . __ (kg) 
Ideal weight for height: 
__  __  __ . __ (kg) 
100 x [1 - (Body wt/Ideal wt)] =  
Percent below ideal weight: ______ 
If body wt > ideal wt, enter "0" 
X 
1 
 
 
 
 
Total 
 
* 
Ideal weight is obtained from CDC growth charts.  The subtotal of box 8 should be rounded to a whole number.  
Numbers that fall between the range of .1-.4 must be rounded down.   Numbers that fall between the range of .5-.9 
must be rounded up. 
* 
Hematocrit values should be rounded to a whole number prior to completing the calculation in box 7 of the CDAI.   
Numbers that fall between the range of .1-.4 must be rounded down.   Numbers that fall between the range of .5-.9 
must be rounded up. 

 
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Appendix I.  
Subject CDAI Diary 
Crohn's Disease Activity Index 
Subject Diary Card 
Enter all values legibly using a black 
ballpoint pen. 
Add item requested for each day. 
Day 
Date___ 
Day 
Date___ 
Day 
Date___ 
Day 
Date___ 
Day 
Date___ 
Day 
Date___ 
Day 
Date___ 
Number (total) of liquid or very soft 
stools per day. 
 
 
 
 
 
 
 
Daily abdominal pain rating. 
(0=none, 1=mild, 2=moderate, 3=severe) 
 
 
 
 
 
 
 
Daily rating of general well being. 
(0=well, 1=slightly below par, 2=poor, 
3=very poor, 4=terrible) 
 
 
 
 
 
 
 
Subject Initials:___________ 
Subject's Signature:__________________________ 
 
Investigator or Designee's Signature:______________________ 

 
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Question 1. 
How much has your stomach been hurting you in the past two weeks? 
□ 
□ 
□ 
□ 
□ 
Not at all 
 Hardly hurting 
at all 
Hurting 
somewhat  
Hurting 
quite a bit 
Hurting 
very much 
 
Question 2.  
Taking medicines or tablets bothers you 
□ 
□ 
□ 
□ 
□ 
Not at all 
 Hardly bothers 
at all 
Bothers 
somewhat  
Bothers  
quite a bit 
Bothers 
very much 
 
Question 3. 
How often has your inflammatory bowel disease prevented you from 
eating what you want in the past two weeks? 
□ 
□ 
□ 
□ 
□ 
Never 
 Rarely 
Sometimes 
Often 
Very often 
 
Question 4. 
How often have you been worrying about having a flare-up (increase of 
symptoms) in the last two weeks? 
□ 
□ 
□ 
□ 
□ 
Never 
 Rarely 
Sometimes 
Often 
Very often 
 
Question 5. 
How much does it bother you that you have an illness that does not just go 
away? 
□ 
□ 
□ 
□ 
□ 
Not at all 
 Hardly bothers 
at all 
Bothers 
somewhat  
Bothers quite a 
bit 
Bothers very 
much 
 
Question 6. 
How much energy did you have during the past two weeks? 
□ 
□ 
□ 
□ 
□ 
Very much 
energy 
Quite a bit of 
energy 
Some energy 
 A little energy 
No energy at 
all  

 
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Question 7. 
How do you feel about your weight? 
□ 
□ 
□ 
□ 
□ 
I feel great 
about my 
weight 
I feel good 
about my 
weight 
I don't feel 
good or bad 
about my 
weight 
I feel bad about 
my weight 
I feel awful 
about my 
weight 
 
Question 8. 
How has your inflammatory bowel disease affected your family? 
□ 
□ 
□ 
□ 
□ 
The effect has 
been great 
The effect has 
been good 
It has not 
affected our 
family 
The effect has 
been bad 
The effect has 
been awful 
 
Question 9. 
How often did you have to miss out on certain things (hobbies, play, 
parties) because of your inflammatory bowel disease in the past two weeks? 
□ 
□ 
□ 
□ 
□ 
Never 
Rarely 
Sometimes 
Often 
Very often 
 
Question 10. How often have you been bothered by diarrhea (loose or frequent bowel 
movements) in the past two weeks? 
□ 
□ 
□ 
□ 
□ 
Never 
Rarely 
Sometimes 
Often 
Very often 
 
Question 11. How often do you worry about health problems you might have in the 
future? 
□ 
□ 
□ 
□ 
□ 
Never 
Rarely 
Sometimes 
Often 
Very often 
 

 
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Question 12. How often do you think it is unfair that you have inflammatory bowel 
disease? 
□ 
□ 
□ 
□ 
□ 
Never 
Rarely 
Sometimes 
Often 
Very often 
 
Question 13. During the past two weeks, were you ever angry that you have 
inflammatory bowel disease? 
□ 
□ 
□ 
□ 
□ 
Never 
Rarely 
Sometimes 
Often 
Very often 
 
Question 14. Do you think too many rules or limits are placed on you because of your 
inflammatory bowel disease? 
□ 
□ 
□ 
□ 
□ 
Never 
Rarely 
Sometimes 
Often 
Very often 
 
Question 15. How do you feel about the way you look? 
□ 
□ 
□ 
□ 
□ 
I think I look 
great 
I think I look 
good 
I don't think I 
look good or 
bad 
I think I look 
bad 
I think I look 
awful 
 
Question 16. Are you embarrassed because of your bowel condition? 
□ 
□ 
□ 
□ 
□ 
Not at all 
 Hardly 
embarrassed at 
all 
Embarrassed 
somewhat  
Embarrassed 
quite a bit 
Embarrassed 
very much 
 
Question 17. Did you have fun during the past two weeks? 
□ 
□ 
□ 
□ 
□ 
Very often 
Often 
Sometimes 
Rarely 
Never 

 
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Question 18. Is it harder to make friends because of your inflammatory bowel disease? 
□ 
□ 
□ 
□ 
□ 
Not at all 
harder 
 A little harder 
Quite a bit 
harder 
Much harder 
Very much 
harder 
 
Question 19.  How often do you worry about your stool (bowel movement) containing 
blood? 
□ 
□ 
□ 
□ 
□ 
Never 
Rarely 
Sometimes 
Often 
Very often 
 
Question 20. Are you worried you cannot go out on a date or have a boyfriend or 
girlfriend because of your inflammatory bowel disease? 
□ 
□ 
□ 
□ 
□ 
Not at all 
worried 
 Hardly 
worried at all 
Worried 
somewhat  
Worried quite a 
bit 
Worried very 
much 
 
Question 21. How often did you feel sick to your stomach in the past two weeks? 
□ 
□ 
□ 
□ 
□ 
Never 
Rarely 
Sometimes 
Often 
Very often 
 
Question 22. How do you feel about the tests you have to go through? 
□ 
□ 
□ 
□ 
□ 
I do not mind 
them at all 
I mind them a 
tiny bit 
I mind them a 
little 
I mind them a 
lot 
I hate them 
 
Question 23. Do other children bully you or leave you out of things because of your 
inflammatory bowel disease or its treatment? 
□ 
□ 
□ 
□ 
□ 
Never 
Rarely 
Sometimes 
Often 
Very often 

 
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Question 24. How often do you worry about having an operation? 
□ 
□ 
□ 
□ 
□ 
Never 
Rarely 
Sometimes 
Often 
Very often 
 
Question 25. In the past two weeks how often were you afraid you may have an 
accident or not get to the toilet in time? 
□ 
□ 
□ 
□ 
□ 
Never 
Rarely 
Sometimes 
Often 
Very often 
 
Question 26. Do you try to keep your inflammatory bowel disease a secret from other 
people? 
□ 
□ 
□ 
□ 
□ 
No, I do not try 
at all 
I don't try 
much 
I try a little 
I try hard 
Yes, I try very 
hard 
 
Question 27. Does your inflammatory bowel disease make it difficult to travel or go on 
a holiday? 
□ 
□ 
□ 
□ 
□ 
No, not 
difficult 
A little difficult
Quite difficult 
Very difficult 
Yes, extremely 
difficult 
 
Question 28.  How did you feel during the past two weeks? 
□ 
□ 
□ 
□ 
□ 
Great 
Good 
Not good or 
bad 
Bad  
Awful 
 
Question 29. Are you happy with your life? 
□ 
□ 
□ 
□ 
□ 
Yes, very 
happy 
Happy 
Not happy or 
unhappy 
Unhappy 
Very unhappy 

 
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Question 30. Do you feel there is someone you can talk to about your inflammatory 
bowel disease? 
□ 
□ 
□ 
□ 
□ 
Always  
Often  
Sometimes  
Rarely 
Never 
 
Question 31. How often did you have to pass gas in the past two weeks? 
□ 
□ 
□ 
□ 
□ 
Never 
Rarely 
Sometimes 
Often 
Very often 
 
Question 32. How tired have you felt in the past two weeks? 
□ 
□ 
□ 
□ 
□ 
Not at all tired 
 A little tired 
Quite tired 
Tired  
Very tired 
 
Question 33. How do you feel about your height? 
□ 
□ 
□ 
□ 
□ 
I feel great 
about my 
height 
I feel good 
about my 
height 
I don't feel 
good or bad 
about my 
height 
I feel bad about 
my height 
I feel awful 
about my 
height 
 
Question 34. Does your inflammatory bowel disease get in the way of playing sports the 
way you would like to? 
□ 
□ 
□ 
□ 
□ 
Never 
Rarely 
Sometimes 
Often 
Always 
 
Question 35. In the past two weeks how often were you able to go to school? (If you are 
in the middle of a school break or the summer holidays, answer as if school was on) 
□ 
□ 
□ 
□ 
□ 
Always  
Most days  
Half the days 
A few days 
Never 
 

 
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End of questionnaire 
This completes the questionnaire. Do you have anything else to add which you feel is 
important about having inflammatory bowel disease, or do you have any other 
remarks? Please write them below. 
 
_________________________________________________________ 
_________________________________________________________ 
_________________________________________________________ 

 
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Appendix K.  
Excluded Medications 
Cyclosporine 
Tacrolimus 
Therapeutic enemas and suppositories (not including those done in conjunction with 
routine colonoscopy) 
Live vaccines 
The combination of budesonide and prednisone (or equivalent) 
Infliximab 
Mycophenolate mofetil (MMF or CellCept® ) 
Growth Hormone 
Kineret® (anakinra) 
Tysabri (natalizumab) 
Orencia (abatacept) 
Concurrent biologic therapy 
Any investigational agent 
Any previous anti-TNF medication except infliximab before the M06-806 study 
(including adalimumab). 
 

 
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Appendix L.  
Day 70 Phone Call 
Site Name / Number: ________ 
Subject Number:________ 
Subject Initials:________ 
Please contact all Subjects 70 days following drug discontinuation. 
 
 
 
Date of Call: ____________ 
 
 
□     Lost to Follow-Up (Please check this box if subject was not willing to provide any follow-up 
information or you were unable to speak to the subject following at least one attempt). 
 
 
□      No Events Reported 
 
List any Adverse Events (AE) and/or Serious Adverse Events (SAE) that occurred since the subject was 
last seen in clinic for this study.  Please document all adverse events on a 500 AE CRF to be submitted to 
data management.  (Please report all SAEs to Abbott within 24 hours of being made aware of the event.  
Follow-up information must also be reported within 24 hours of being made aware of the information.). 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
If events are listed above, your monitor will review and retrieve the appropriate CRF pages during 
their next visit.  Please fax this form to Paragon at 
 

 
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Appendix M.  
Unscheduled Outpatient Visits, Emergency Room Visits and 
Hospitalizations 
1. 
Since the last study visit has the subject had any physician/health care visits for 
their Crohn's disease other than the protocol required visits? 
Yes ___ 
No  ___ 
If yes provide the following: 
I. 
Since the last visit, has the subject been seen by a physician for their Crohn's 
Disease? 
YES:_____ 
NO:_____ 
If YES, how many times:_______ 
 
 
II. Since the last visit, has the subject been seen in the Emergency Room for their 
Crohn's Disease? 
YES:_____ 
NO:______ 
If YES, how many times:_____ 
III. Since the last visit, has the subject been admitted to the hospital due to their 
Crohn's Disease? 
YES:_____ 
NO:______ 
If YES, how many times:_____ 
If YES, please indicate the total number of days in the hospital:_____ 
 
 

 
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Appendix N.  
Subject Medication Log 
Instructions:  As a participant in this study, it is also important to keep a record of all mediations you take (new and old) throughout the study.  Please take this 
sheet home with you and write down any medications you take during the study.  It will be VERY important that you bring this sheet back to your doctor's office 
and speak with your doctor about everything you have written down. 
 
Name of Medication 
Date you took
first dose 
Date you took
last dose 
What dose of medicine 
did you take? 
How often did you 
take the medicine? 
Why did you take the 
medicine?
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
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Week 25 - Week 36 
Subject Initials: __________ 
Subject Study #: ___________ 
 
Date 
day/mm/yr 
Day or 
Week # 
Time of Study 
Drug 
Administration 
Dose (mL) 
Administered
Kit #
Initials of Person 
Administering
Study Medication 
Comments 
18/MAR/04 EXAMPLE 
9:35 am 
0.8 
 
MM 
none 
 
Week 25 
 
 
 
 
 
 
Week 26 
 
 
 
 
 
 
Week 27 
 
 
 
 
 
 
Week 28 
 
 
 
 
 
 
Week 29 
 
 
 
 
 
 
Week 30 
 
 
 
 
 
 
Week 31 
 
 
 
 
 
 
Week 32 
 
 
 
 
 
 
Week 33 
 
 
 
 
 
 
Week 34 
 
 
 
 
 
 
Week 35 
 
 
 
 
 
 
Week 36 
 
 
 
 
 
 

 
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Week 97 - Week 104 
Subject Initials: __________ 
Subject Study #: ___________ 
 
Date 
day/mm/yr 
Day or 
Week # 
Time of Study 
Drug 
Administration 
Dose (mL) 
Administered
Kit #
Initials of Person 
Administering
Study Medication Comments
18/MAR/04 
EXAMPLE 
9:35 am 
0.8 
 
MM 
none 
 
Week 97 
 
 
 
 
 
 
Week 98 
 
 
 
 
 
 
Week 99 
 
 
 
 
 
 
Week 100 
 
 
 
 
 
 
Week 101 
 
 
 
 
 
 
Week 102 
 
 
 
 
 
 
Week 103* 
 
 
 
 
 
*The dose at Week 103 will only be taken if you are on weekly dosing. 
 

 
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Appendix P.  
Self Injection Instructions 
 
 
Subject Instructions 
0.8 mL or 0.4 mL dose 
(Administered as a single dose-prefilled syringe (PFS)) 
 
Protocol M06-807 
 

 
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Tables of Contents 
Dosing Schedule 
General Information & Supplies 
Injection Procedures
 

 
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109 
Study Drug Dosing Schedule 
Open-Label (PFS) 
Subject Number:_____________________________________ 
You will require subcutaneous (SC) injections throughout the study.  
Injections at scheduled study visits (Baseline, Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84, and 
96) will be done during your visit, at the doctor's office. On weeks between office visits, 
study drug will be self-administered at home by you or someone trained to give you the 
injections. 
One pre-filled syringe will contain 0.8 mL of liquid.  The total available dose is 0.8 mL. 
The drug should be administered in one (1) SC injection, on the same day of the week for 
each dose. 
Please return all used and unused syringes to the clinic on your next visit. Used syringes 
should be placed in the special sharps container provided. All unused syringes should be 
returned in the original box. 
If an injection is missed or something occurs where the full dose cannot be injected, 
contact your study center immediately for further instructions. Please record any missed 
doses on your subject diary. 
Remember to complete your dosing diary after each injection and to call the doctor's 
office if you are having problems administering your study drug. 

 
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General Information 
 
 
 
 
 
 
 
PFS
● Prefilled syringes will be labeled "adalimumab." 
● Store all adalimumab prefilled syringes in your refrigerator NOT in the 
freezer.  Should the syringes accidentally become frozen, call your study 
coordinator. 
● 0.8 mL = 0.8 cc 
● Study drug should be taken at about the same time of day, on the same day of 
the week as directed by your study doctor. 
● USE A NEW SYRINGE EVERY INJECTION DAY. There may be 
medication left in the syringe. DO NOT RE-USE. 
● Save all study drugs. Prefilled syringes (used and unused) must be returned 
to the study center at each visit. Used syringes will be disposed of in a sharps 
container provided to you. 
● Whenever possible, have someone with you for at least 15 to 30 minutes after 
your injection. 
● Call your doctor IMMEDIATELY if you experience any itching, hives, 
shortness of breath, or any symptom that has you concerned. If you are unable 
to reach your doctor or if you experience life-threatening symptoms call 911, 
or proceed to your nearest emergency room. 
 

 
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Injection Procedures 
 
 
 
 
 
 
 
PFS
1. Clean your workspace, gather your supplies, and wash your hands. 
 
 
2. Identify the area on your abdomen or thigh (or upper arm 
if not self injecting). Make sure the area you choose does 
not have any redness, tenderness, swelling, bruising, or 
psoriasis. The area must also be at least 2 cm 
(approximately 1 inch) away from the previous injection 
site. IT IS VERY IMPORTANT TO CHANGE THE 
INJECTION SITE EVERY TIME!!! 
 
 
3. Using a circular motion (starting at the injection site and 
moving outward) clean the selected injection site with 
an alcohol pad. Allow skin to dry.  
4. Remove the needle cap. Do not touch the needle. Expel 
any air bubbles from the syringe by tapping on the 
syringe. If the needle becomes contaminated, discard all 
supplies and obtain a new syringe of study drug.  
5. Once the air is expelled from the syringe, the amount of 
solution in the syringe should be 0.8 mL. 
 
 
6.   Hold the syringe "like a dart" between your thumb and 
first finger close to the syringe/needle connection. 

 
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PFS
 
7. With your other hand, pinch the skin around the 
injection site, forming a bulge in the skin. 
 
 
 
 
 
 
8. Insert the needle into the skin at a 45-degree angle. 
Release pinched skin. 
 
 
 
 
9. 
GENTLY pull back on the syringe plunger. If blood 
appears, withdraw needle - DO NOT INJECT! Contact 
your study center immediately for further instructions. 
 
10. Inject drug by pushing slowly on syringe plunger with 
thumb. 
 
11. Remove needle while maintaining a 45-degree angle. 
 
12. You may apply a Band-Aid over the injection site and 
apply gentle pressure, if necessary. DO NOT RUB 
SITE. 
 
13. 
DO NOT RECAP NEEDLE. DO NOT SEPARATE THE NEEDLE FROM THE 
 
SYRINGE BEFORE DISPOSING. Discard used syringes into Sharps Container. 
EACH TIME THAT YOU GIVE YOURSELF AN INJECTION OF STUDY DRUG, 
REMEMBER TO RECORD THE INFORMATION ON YOUR SUBJECT DOSING 
DIARY. 
 

 
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Appendix Q.  
Standard Weights 
 
 

 
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Appendix R.  
Abbott Laboratories Site Drug Accountability Form 
 

 
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Appendix S.  
Work Productivity and Activity Impairment Questionnaire: 
Crohn's Disease (WPAI-CD) - Caregiver 
The following questions ask about the effect of your child's Crohn's disease on your 
ability to work and perform regular activities.  Please fill in the blanks or circle a 
number, as indicated. 
1.  Are you currently employed (working for pay)?  
_____ NO ___ YES 
  If NO, check "NO" and skip to question 6. 
The next questions are about the past seven days, not including today. 
 
 
2. During the past seven days, how many hours did you miss from work because of 
problems associated with your child's Crohn's disease?  Include hours you missed on 
sick days, times you went in late, left early, etc., because of your child's Crohn's 
disease.  Do not include time you missed for your child to participate in this study. 
 
_____ HOURS 
 
3. During the past seven days, how many hours did you miss from work because of any 
other reason, such as vacation, holidays, time off for your child to participate in this 
study? 
 
_____HOURS 
 
4. During the past seven days, how many hours did you actually work? 
 
_____HOURS  (If "0," skip to question 6.) 
 

 
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5. During the past seven days, how much did your child's Crohn's disease affect your 
productivity while you were working?   
 
Think about days you were limited in the amount or kind of work you could do, days 
you accomplished less than you would like, or days you could not do your work as 
carefully as usual.  If your child's Crohn's disease affected your work only a little, 
choose a low number.  Choose a high number if your child's Crohn's disease affected 
your work a great deal.   
Consider only how much your child's Crohn's disease affected  
your productivity while you were working. 
 
 
 
 
 
 
 
 
 
 
 
My child's Crohn's 
disease had no 
effect on my work 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
My child's Crohn's 
disease completely 
prevented me from 
working 
CIRCLE A NUMBER 
6. During the past seven days, how much did your child's Crohn's Disease affect your 
ability to do your regular daily activities, other than work at a job?   
 
By regular activities, we mean the usual activities you do, such as work around the 
house, shopping, childcare, exercising, studying, etc.  Think about times you were 
limited in the amount or kind of activities you could do and times you accomplished 
less than you would like.  If your child's Crohn's Disease affected your activities only 
a little, choose a low number.  Choose a high number if your child's Crohn's Disease 
affected your activities a great deal.   
 
Consider only how much your child's Crohn's disease affected your ability  
to do your regular daily activities, other than work at a job. 
 
 
 
 
 
 
 
 
 
 
 
My child's 
Crohn's disease 
had no effect on 
my daily 
activities 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
My child's Crohn's 
disease completely 
prevented me from 
doing my daily 
activities 
 
 
                           
CIRCLE A NUMBER 
WPAI:CD-Caregiver (US English) 

 
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Appendix T.  
Protocol Amendment:  List of Changes 
The summary of changes is listed in Section 1.1. 
Specific Protocol Changes: 
Section 3.0  Introduction 
Tenth paragraph, first sentence previously read: 
Adalimumab was first approved for treatment of rheumatoid arthritis (RA) on 
31 Dec 2002 in the United States (US), on 08 Sep 2003 in the European Union (EU) and 
through July 2007 in a total of 69 countries. 
Has been changed to read: 
Adalimumab was first approved for treatment of rheumatoid arthritis (RA) on 
31 Dec 2002 in the United States (US), on 08 Sep 2003 in the European Union (EU) and 
through August 2008 in a total of 76 countries. 
Section 3.0  Introduction 
Add:  fifth and sixth sentences to tenth paragraph 
In December 2007 and January 2008, respectively, adalimumab was approved for the 
treatment of psoriasis in adult patients in the EU, Canada and USA.  Additionally, 
adalimumab was approved for the treatment of juvenile idiopathic arthritis in the USA in 
February 2008. 
Section 3.0  Introduction 
Eleventh paragraph, second sentence previously read: 
In the CD development program, adalimumab was studied in over 1400 subjects in three 
pivotal studies (two induction studies and a maintenance study). 
Has been changed to read: 
In the CD development program, adalimumab was studied in over 1400 adult subjects in 
three pivotal studies (two induction studies and a maintenance study). 

 
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Section 5.2.1  Inclusion Criteria 
Criterion number 2 previously read: 
Subject must be a responder at Week 52 of Study M06-806. 
Has been changed to read: 
Subject must be a responder at any time point during the M06-806 study. 
Section 5.4.3  Stopping Rules 
Following first paragraph, first and second bullets previously read: 
● The overall rate of SAEs, with an Investigator assessed causality of at least 
possibly related or higher, evaluated on a per subject year basis, 
exceeds 0.45 (0.15 SAEs/subject every four months), or 
● The overall rate of serious infectious SAEs evaluated on a per subject year 
basis, exceeds 0.09 (.03 SAEs/subject every four months). 
 
Has been changed to read: 
● The overall proportion of subjects with SAEs, with an investigator-assessed 
causality of at least possibly related or higher, evaluated on a per subject 
basis, exceeds 0.20 (or 20%); or 
● The overall proportion of subjects with serious infectious SAEs, evaluated on 
a per subject basis, exceeds 0.20 (or 20%). 
 
Section 5.4.3  Stopping Rules 
Second paragraph previously read: 
If either of these criteria is met, no new enrollment will occur until the DMC or the SSC 
makes their recommendation. 
Has been changed to read: 
If either of the above criteria is met, the DMC will meet within 2 weeks to consider 
whether or not to recommend a temporary suspension of enrollment. 

 
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Section 5.5.4  Selection and Timing of Dose for Each Subject 
Fourth paragraph, second sentence previously read: 
All clinic visits for the subject should be scheduled on the same day of the Baseline visit 
for this study. 
Has been changed to read: 
All clinic visits for the subject should be scheduled on the same day as the Baseline visit 
for this study. 
Section 6.5  Adverse Event Reporting 
Second paragraph and address previously read: 
For sites located within North America: 
SAE Support Hotline 
 

 
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Has been changed to read: 
For sites located within North America:   
SAE Support Hotline 
 
Section 12.2  Publication 
Delete:  entire section 
All information concerning adalimumab and Abbott Laboratories' operations, such as 
patent application, formulas, manufacturing processes, basic scientific data or 
formulation information supplied by Abbott Laboratories which have not been previously 
published are considered confidential by Abbott Laboratories and shall remain the sole 
property of Abbott Laboratories.  The Investigator agrees to use this information only to 
perform this study and will not use it for other purposes including publications and 
presentations without Abbott Laboratories' written consent. 
It is understood by the Investigator that the information developed in the clinical trial will 
be used by Abbott Laboratories in connection with the development of adalimumab and, 
therefore, may be disclosed as required to other clinical Investigators, other 
pharmaceutical companies, to the U.S. FDA and to other regulatory agencies.  It is 
understood that there is an obligation to provide Abbott Laboratories with complete test 
results and all data resulting from this study and to provide direct access to source 
data/documents for study related monitoring, audits, IEC/IRB review, and regulatory 
inspection. 

 
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Section 15.0  Reference List 
Add:  new reference number 32 
32. Centers for Disease Control and Prevention.  Targeted tuberculin testing and 
treatment of latent tuberculosis infection.  MMWR 2006 April. 
Appendix B.  Documents Required Prior to Initiation of the Study 
Previously read: 
As sponsor of a clinical trial, Abbott has an obligation to ensure that the study will be 
conducted by a qualified Investigator with sufficient resources (of time, personnel, and 
physical facilities) to conduct the study and to ensure that the Investigator understands 
and agrees to comply with applicable regulations, policies, and procedures.  Prior to the 
beginning of any clinical trial, the Investigator will be asked to provide the following 
documentation. 
1. 
A signed and dated Investigator's agreement page for the study. 
2. 
A signed and dated Form FDA 1572 certifying the Investigator's agreement to 
comply with the appropriate regulations governing the conduct of the study. 
3. 
A current curriculum vita of the Investigator.  If subinvestigators will participate in 
the study, curriculum vita for each. 
4. 
Requirements for the Independent Ethics Committee (IEC)/Institutional Review 
Board (IRB). 
● A copy of the signed and dated letter of approval of the IEC/IRB.  The letter 
must specify that both the protocol and informed consent form were approved 
(unless separate documentation that the informed consent was approved is 
provided). 
● A dated list containing the names and affiliations of the members of the 
IEC/IRB, or the institution's General Assurance Number. 

 
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● If the Investigator and/or subinvestigator is a member of the IEC/IRB, a letter 
stating that he/she did not participate in the review or approval of the protocol 
or informed consent form. 
5. 
A specimen copy of the IEC/IRB-approved informed consent document to be used 
in the study. 
6. 
A list of reference ranges of values for all laboratory tests specified by the protocol 
for all laboratories utilized. 
7. 
A copy of the laboratory(ies) certification(s) or the authorization number of the 
certification(s), the name of the certifying authority, and the period of certification. 
8. 
Financial Disclosure forms must be completed by each Investigator and all 
Subinvestigators identified on the Form FDA 1572.  A Financial Disclosure, 
EU consent, is required to be completed for each Investigator and/or 
Subinvestigator who is a resident of the European Union. 
 
Has been changed to read: 
As sponsor of a clinical study, Abbott has an obligation to ensure that the study will be 
conducted by a qualified investigator with sufficient resources (of time, personnel, and 
physical facilities) to conduct the study and to ensure that the investigator understands 
and agrees to comply with Good Clinical Practices and applicable regulations, policies, 
and procedures.  Prior to the beginning of any clinical study, the investigator will be 
asked to provide the following documentation.  
1. 
A signed and dated Investigator's agreement page for the study. 
2. 
A signed and dated Form FDA 1572 certifying the investigator's agreement to 
comply with the appropriate regulations governing the conduct of the study.
A signed and dated Investigator Information and Agreement Form certifying the 

 
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investigator's agreement to comply with the appropriate (e.g., ICH GCP) 
regulations governing the conduct of the study. These will be required only for 
sites that are recruited under this amendment, or when existing sites update study 
documentation. 
3. 
 Current curriculum vitae for the investigator.  If subinvestigators will participate 
in the study, curriculum vitae for each. 
4. 
Requirements for the Independent Ethics Committee (IEC)/Institutional Review 
Board (IRB). 
● A copy of the signed and dated letter of approval of the IEC/IRB.  The letter 
must specify that both the protocol and informed consent form were approved 
(unless separate documentation that the informed consent was approved is 
provided). 
● A dated list containing the names and affiliations of the members of the 
IEC/IRB, or the institution's General Assurance Number. 
● If the investigator and/or subinvestigator is a member of the IEC/IRB, a letter 
stating that he/she did not participate in the review or approval of the protocol 
or informed consent form. 
5. 
A specimen copy of the IEC/IRB-approved informed consent document to be used 
in the study. 
6. 
A list of reference ranges of values for all laboratory tests specified by the protocol 
for all laboratories utilized. 
7. 
A copy of the laboratory(ies) certification(s) or the authorization number of the 
certification(s), the name of the certifying authority, and the period of certification. 
8. 
Financial Disclosure Certification forms must be completed by each investigator 
and all subinvestigators identified on the Form FDA 1572 or Investigator 
Information and Agreement Form.  A Financial Disclosure, EU Consent, is 

 
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required to be completed for each investigator and/or subinvestigator who is a 
resident of the European Union 
 
Appendix C.  Responsibilities of the Clinical Investigator 
Previously read: 
Clinical research studies sponsored by Abbott are subject to the regulations of the U.S. 
Food and Drug Administration (FDA).  The responsibilities imposed upon Investigators 
by the FDA are summarized in the "Statement of Investigator" (Form FDA 1572), which 
is a form letter addressed to the sponsor (Abbott), summarizing the Investigator's 
qualifications for the study and his/her willingness to follow FDA regulations with 
respect to the study. 
In signing a Form FDA 1572, the Investigator agrees to assume the following 
responsibilities:   
1. 
To conduct the study(ies) in accordance with the relevant, current protocol(s) and 
only make changes in a protocol after notifying Abbott, except when necessary to 
protect the safety, rights, or welfare of subjects. 
2. 
To personally conduct or supervise the described investigation(s). 
3. 
To inform any subjects, or any persons used as controls, that the drugs are being 
used for investigational purposes and to ensure that the requirements relating to 
obtaining informed consent in 21 CFR Part 50 and Independent Ethics Committee 
(IEC)/Institutional Review Board (IRB) review and approval in 21 CFR Part 56 
are met. 
4. 
To report to Abbott adverse experiences that occur in the course of the 
investigation(s) in accordance with 21 CFR 312.64. 
5. 
To read and understand the information in the Investigator's Brochure, including 
the potential risks and side effects of the drug. 

 
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6. 
To ensure that all associates, colleagues, and employees assisting in the conduct of 
the study(ies) are informed about their obligations in meeting the above 
commitments. 
7. 
To maintain adequate and accurate records of the conduct of the study and make 
those records available for inspection by representatives of Abbott, the IEC/IRB 
and/or the appropriate regulatory agency, and to retain all study-related documents 
until notification from Abbott.  The Investigator must notify Abbott when they are 
no longer able to retain the study related documents. 
8. 
To ensure that an IEC/IRB that complies with the requirements of 21 CFR Part 56 
will be responsible for the initial and continuing review and approval of the 
clinical investigation. 
9. 
To promptly report to the IEC/IRB all changes in the research activity and all 
unanticipated problems involving risks to human subjects or others (including 
submission of any Expedited Safety Reports received from Abbott to the 
IEC/IRB), and to make no changes in the research without IEC/IRB approval, 
except where necessary to eliminate apparent immediate hazards to human 
subjects. 
10. 
To comply with all other requirements regarding the obligations of clinical 
Investigators and all other pertinent requirements in 21 CFR Part 312. 
 

 
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Has been changed to read: 
Clinical research studies sponsored by Abbott are subject to the regulations of the U.S. 
Food and Drug Administration (FDA).  The responsibilities imposed upon Investigators 
by the FDA are summarized in the "Statement of Investigator" (Form FDA 1572), which 
is a form letter addressed to the sponsor (Abbott), summarizing the Investigator's 
qualifications for the study and his/her willingness to follow FDA regulations with 
respect to the study. 
In signing a Form FDA 1572, the Investigator agrees to assume the following 
responsibilities:   
1. 
To conduct the study(ies) in accordance with the relevant, current protocol(s) and 
only make changes in a protocol after notifying Abbott, except when necessary to 
protect the safety, rights, or welfare of subjects. 
2. 
To personally conduct or supervise the described investigation(s). 
3. 
To inform any subjects, or any persons used as controls, that the drugs are being 
used for investigational purposes and to ensure that the requirements relating to 
obtaining informed consent in 21 CFR Part 50 and Independent Ethics Committee 
(IEC)/Institutional Review Board (IRB) review and approval in 21 CFR Part 56 
are met. 
4. 
To report to Abbott adverse experiences that occur in the course of the 
investigation(s) in accordance with 21 CFR 312.64. 
5. 
To read and understand the information in the Investigator's Brochure, including 
the potential risks and side effects of the drug. 
6. 
To ensure that all associates, colleagues, and employees assisting in the conduct of 
the study(ies) are informed about their obligations in meeting the above 
commitments. 

 
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7. 
To maintain adequate and accurate records of the conduct of the study and make 
those records available for inspection by representatives of Abbott, the IEC/IRB 
and/or the appropriate regulatory agency, and to retain all study-related documents 
until notification from Abbott.  The Investigator must notify Abbott when they are 
no longer able to retain the study related documents. 
8. 
To ensure that an IEC/IRB that complies with the requirements of 21 CFR Part 56 
will be responsible for the initial and continuing review and approval of the 
clinical investigation. 
9. 
To promptly report to the IEC/IRB all changes in the research activity and all 
unanticipated problems involving risks to human subjects or others (including 
submission of any Expedited Safety Reports received from Abbott to the 
IEC/IRB), and to make no changes in the research without IEC/IRB approval, 
except where necessary to eliminate apparent immediate hazards to human 
subjects. 
10. 
To comply with all other requirements regarding the obligations of clinical 
Investigators and all other pertinent requirements in 21 CFR Part 312. 
 
Appendix D.  CDC Treatment of Tuberculosis Infection (Preventive Therapy) 
Previously read: 
When taken as prescribed, isoniazid therapy is highly effective in preventing latent 
tuberculosis (TB) infection from progressing to TB disease. 
Who should receive preventive therapy? 
The following persons should be given high priority for preventive therapy if they have 
positive skin test results, regardless of their age:   
1. 
Persons with 5 mm induration on their PPD who will receive a TNF inhibitor, 

 
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2. 
Persons known to have or suspected of having HIV infection (5 mm or greater of 
induration), 
3. 
Persons who have been in close contact with someone who has infectious TB 
disease (5 mm or greater), 
4. 
Persons whose skin test results converted from negative to positive within the past 
2 years (10 mm or greater), 
5. 
Persons with abnormal chest radiographs who have never been treated for TB or 
who have been inadequately treated for TB (5 mm or greater), 
6. 
Persons who have injected drugs and who are HIV seronegative (10 mm or 
greater), and 
7. 
Persons with organ transplants and other immunosuppressed subjects (5mm or 
greater), 
8. 
Persons who have medical conditions that increase the risk for TB (10 mm or 
greater). These conditions include diabetes mellitus, gastrectomy, some 
hematologic and reticuloendothelial diseases, and end-stage renal disease, silicosis, 
and body weight that is 10% or more below ideal. 
 
In addition, in the absence of any of the above risk factors, persons in the following 
groups should be evaluated for preventive therapy if their reaction to the tuberculin skin 
test is 10 mm or greater:   
1. 
Foreign-born persons from countries where TB is common; 
2. 
Medically underserved, low-income populations; and 
3. 
Residents of long-term care facilities. 
 

 
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In addition, staff of facilities in which a person with infectious TB disease would pose a 
risk to large numbers of susceptible persons (e.g., health care facilities, correctional 
facilities, and nursing homes) should be evaluated for preventive therapy if they have a 
positive skin test result. 
Persons who have a positive reaction to the tuberculin skin test should not be given 
preventive therapy until the possibility of TB disease has been ruled out. In addition, 
persons who are being considered for preventive therapy should be evaluated for medical 
contraindications, such as:   
1. 
Previous isoniazid-associated hepatic injury, 
2. 
History of severe adverse reactions to isoniazid, and; 
3. 
Acute or active liver disease. 
 
Also, special precautions should be taken for some persons who are receiving preventive 
therapy. 
Precautions are indicated for:   
1. 
Persons who are older than 35, 
2. 
Persons who abuse alcohol, 
3. 
Pregnant women, 
4. 
Persons with chronic liver disease, 
5. 
Persons with peripheral neuropathy, and 
6. 
Persons who in the past have stopped using isoniazid because of adverse effects. 
 

 
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Regimens for Preventive Therapy
The usual preventive therapy regimen is 9 months of daily isoniazid, in a dosage of 
5 milligrams per kilogram of body weight. The maximum daily dose is 300 milligrams. 
HIV-infected persons should receive 9 months of preventive therapy.  An alternative 
regimen for adults is 4 months of rifampin. 
For persons with a strain of M. tuberculosis that is resistant to isoniazid but susceptible to 
rifampin, CDC recommends the use of rifampin alone for 4 months for preventive 
therapy. 
Adverse Reactions
The major toxic effect of isoniazid is hepatitis. The risk for hepatitis increases with 
alcohol consumption. Isoniazid may also cause peripheral neuropathy. Persons at risk for 
neuropathy—for example, persons who abuse alcohol and persons with diabetes—should 
be given pyridoxine, or vitamin B-6, in conjunction with isoniazid therapy. 
Subjects should be educated about the signs and symptoms of toxicity to isoniazid, and 
they should be monitored monthly by appropriately trained personnel. No more than a 
1 month supply of medicine should be dispensed at any visit. If signs or symptoms of 
toxicity appear, isoniazid should be stopped immediately, and the subject reevaluated. 
Subjects should not be given isoniazid preventive therapy if they cannot be monitored 
monthly. 

 
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Has been changed to read:
Centers for Disease Control and Prevention 
Tuberculosis Information 
Treatment of Tuberculosis Infection (Preventive Therapy), Latent Tuberculosis 
Infection (LBTI)32
 
 

 
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Appendix G.  PCDAI User's Guide and Guideline for Reference Weight and 
Reference Height 
Subsection Physical Examination, "Item 8.  Height" 
Second, third and fourth bullets previously read: 
● From Week 24 to Week 52, use height from Baseline visit 
● From Week 52 to Week 72, use height from Week 24 
● From post Week 72, use height from Week 52 
 
Has been changed to read: 
● From Week 24 to Week 48, use height from Baseline visit 
● From Week 48 to Week 72, use height from Week 24 
● From Week 72, use height from Week 48 
 
Appendix K.  Excluded Medication 
Last medication on the list of Appendix K previously read: 
Any previous anti-TNF medication except infliximab before the study (including 
adalimumab). 
Has been changed to read: 
Any previous anti-TNF medication except infliximab before the M06-806 study 
(including adalimumab). 
Appendix L.  Day 70 Phone Call
Fax information at the end of Appendix L previously read: 
If events are listed above, your monitor will review and retrieve the appropriate CRF 
pages during their next visit.  Please fax this form to Paragon at 
. 

 
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1.0 
Title Page 
CLINICAL TRIAL PROTOCOL M06-807 
A Multi-center, Open-label Study of the Human 
Anti−TNF Monoclonal Antibody Adalimumab to 
Evaluate the Efficacy and the Long-term Safety and 
Tolerability of Repeated Administration of 
Adalimumab in Pediatric Subjects with 
Crohn's Disease Who Have Demonstrated a Clinical 
Response in the M06-806 Study 
Abbott Number /  
 Investigational Product: 
 
Adalimumab 
Date:  
11 January 2008 
Development Phase: 
3 
Study Design:  
A multi-center, open-label safety and tolerability pediatric study in the 
United States, Canada and Europe 
EudraCT Number:  
2007-006494-90 
 
Investigator:   
Multicenter (Investigator information on file at Abbott Laboratories). 
Sponsor:  
European Union Countries: 
Abbott GmbH & Co.KG  
Knollstrasse 50 
67061 Ludwigshafen, Germany 
Non European Union Countries: 
Abbott Laboratories, US  
100 Abbott Park Road 
Abbott Park, IL 60064 
Emergency Contact:  
 
This study will be conducted in compliance with the protocol, Good Clinical Practice and all other 
applicable regulatory requirements, including the archiving of essential documents. 
 
Confidential Information 
No use or disclosure outside Abbott is permitted without prior written authorization from Abbott. 
 

 
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2.0 
Table of Contents 
1.0 
Title Page .................................................................................1 
2.0 
Table of Contents....................................................................2 
3.0 
Introduction.............................................................................7 
4.0 
Study Objective .....................................................................13 
5.0 
Investigational Plan ..............................................................13 
5.1 
Overall Study Design and Plan:  Description..........................................13 
5.2 
Selection of Study Population .................................................................16 
5.2.1 
Inclusion Criteria.....................................................................................16 
5.2.2 
Exclusion Criteria....................................................................................17 
5.2.3 
Prior and Concomitant Therapy ..............................................................19 
5.2.3.1 
Prior Therapy...........................................................................................19 
5.2.3.2 
Concomitant Therapy..............................................................................20 
5.2.3.3 
Rescue Therapy .......................................................................................21 
5.2.3.4 
Prohibited Therapy ..................................................................................21 
5.3 
Efficacy, and Safety Assessments/Variables...........................................21 
5.3.1 
Efficacy and Safety Measurements Assessed and Flow Chart................21 
5.3.1.1 
Study Procedures.....................................................................................24 
5.3.2 
Drug Concentration Measurements.........................................................31 
5.3.3 
Efficacy Variables ...................................................................................31 
5.3.4 
Safety Variables.......................................................................................32 
5.4 
Removal of Subjects from Therapy or Assessment ................................32 
5.4.1 
Discontinuation of Individual Subjects ...................................................32 
5.4.2 
Discontinuation of Entire Study..............................................................33 
5.4.3 
Stopping Rules.........................................................................................33 
5.5 
Treatments ...............................................................................................34 
5.5.1 
Treatments Administered ........................................................................34 

 
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5.5.2 
Identity of Investigational Product ..........................................................35 
5.5.2.1 
Packaging and Labeling ..........................................................................35 
5.5.2.2 
Storage and Disposition of Study Drug...................................................36 
5.5.3 
Method of Assigning Subjects to Treatment Groups ..............................36 
5.5.4 
Selection and Timing of Dose for Each Subject .....................................37 
5.5.5 
Blinding...................................................................................................37 
5.5.6 
Treatment Compliance ............................................................................38 
5.5.7 
Drug Accountability................................................................................38 
5.6 
Discussion and Justification of Study Design .........................................39 
5.6.1 
Discussion of Study Design and Choice of Control Groups...................39 
5.6.2 
Appropriateness of Measurements ..........................................................39 
5.6.3 
Suitability of Subject Population.............................................................39 
5.6.4 
Selection of Doses in the Study...............................................................39 
6.0 
Adverse Events......................................................................40 
6.1 
Definitions...............................................................................................40 
6.1.1 
Adverse Event .........................................................................................40 
6.1.2 
Serious Adverse Events...........................................................................41 
6.2 
Adverse Event Severity...........................................................................42 
6.3 
Relationship to Study Drug .....................................................................42 
6.4 
Adverse Event Collection Period ............................................................43 
6.5 
Adverse Event Reporting ........................................................................43 
6.5.1 
Collection of Data Regarding Known Manifestations of the 
Disease Under Study ...............................................................................45 
6.6 
Pregnancy ................................................................................................45 
7.0 
Protocol Deviations...............................................................46 
8.0 
Statistical Methods and Determination of Sample 
Size..........................................................................................47 
8.1 
Statistical and Analytical Plans ...............................................................47 

 
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8.1.1 
Analyzable Population.............................................................................47 
8.1.2 
Planned Methods of Statistical Analysis .................................................47 
8.1.2.1 
Demographics and Baseline Characteristics ...........................................47 
8.1.2.2 
Primary Efficacy Analysis.......................................................................48 
8.1.3 
Other Analyses ........................................................................................48 
8.1.4 
Safety Analyses .......................................................................................48 
8.1.5 
Interim Analysis ......................................................................................49 
8.2 
Determination of Sample Size.................................................................49 
8.3 
Randomization Methods..........................................................................49 
9.0 
Ethics......................................................................................50 
9.1 
Independent Ethics Committee (IEC) or Institutional Review 
Board (IRB).............................................................................................50 
9.2 
Ethical Conduct of the Study...................................................................50 
9.3 
Subject Information and Consent ............................................................51 
10.0 
Source Documents and Case Report Form 
Completion.............................................................................52 
10.1 
Source Documents...................................................................................52 
10.2 
Case Report Forms ..................................................................................52 
11.0 
Data Quality Assurance........................................................53 
12.0 
Use of Information and Publication....................................54 
12.1 
Use of Information ..................................................................................54 
12.2 
Publication...............................................................................................55 
12.3 
Internet Sites............................................................................................56 
13.0 
Completion of the Study.......................................................56 
14.0 
Investigator's Agreement .....................................................58 
15.0 
Reference List........................................................................59 
 

 
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List of Tables 
Table 1. 
Study Activities .......................................................................................22 
Table 2. 
Clinical Laboratory Tests ........................................................................27 
Table 3. 
Identity of Investigational Products.........................................................35 
Table 4. 
Study Drug Packaging and Administration.............................................36 
 
List of Figures 
Figure 1. 
Study Schematic ......................................................................................15 
Figure 2. 
Adverse Event Collection........................................................................43 
 
List of Appendices 
Appendix A. 
List of Abbreviations and Definition of Terms .......................................63 
Appendix B. 
Documents Required Prior to Initiation of the Study..............................65 
Appendix C. 
Responsibilities of the Clinical Investigator............................................67 
Appendix D. 
CDC Treatment of Tuberculosis Infection (Preventive Therapy)...........69 
Appendix E. 
Non-Drug Materials Provided to the Study Site(s) .................................73 
Appendix F. 
Pediatric Crohn's Disease Activity Index (PCDAI) ................................74 
Appendix G. 
PCDAI User's Guide and Guideline for Reference Weight and 
Reference Height.....................................................................................76 
Appendix H. 
Crohn's Disease Activity Index (CDAI)..................................................81 
Appendix I. 
Subject CDAI Diary ................................................................................82 
Appendix J. 
IMPACT III Questionnaire......................................................................83 
Appendix K. 
Excluded Medications .............................................................................91 
Appendix L. 
Day 70 Phone Call...................................................................................92 
Appendix M. 
Unscheduled Outpatient Visits, Emergency Room Visits and 
Hospitalizations .......................................................................................93 
Appendix N. 
Subject Medication Log ..........................................................................94 
Appendix O. 
Subject Dosing diary ...............................................................................95 

 
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Appendix P. 
Self Injection Instructions......................................................................106 
Appendix Q. 
Standard Weights...................................................................................112 
Appendix R. 
Abbott Laboratories Site Drug Accountability Form............................114 
Appendix S. 
Work Productivity and Activity Impairment Questionnaire: 
Crohn's Disease (WPAI-CD) - Caregiver..............................................115 
 

 
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3.0 
Introduction 
Crohn's Disease (CD) is a chronic, debilitating, and currently incurable inflammatory 
disease that can affect the entire digestive system as well as extraintestinal organs.  CD is 
primarily manifested by focal asymmetric, transmural, and occasionally, granulomatous 
inflammation affecting any segment of the gastrointestinal tract1 which can consist of 
mucosal edema, aphthous and linear ulcerations, asymmetrical narrowing and strictures.  
Noncaseating granulomas are virtually diagnostic in the correct clinical setting.  The most 
commonly involved area of the bowel is the small bowel, particularly the distal ileum, 
which is involved in 70% of cases often in combination with colitis, occurring in 50% of 
cases.  Extraintestinal manifestations can also occur, and include symptoms of joint, 
ocular and hepatic inflammation.  Genetic, geographic, ethnic, and environmental risk 
factors have all been described, but the basic etiology of the disease remains unknown. 
The incidence in North America is similar to that in other western nations and is 
estimated from 3.1 to 14.6 cases per 100,000 person years and prevalence ranges from 
26 to 199 cases per 100,000 persons.2  The disease can affect persons of any age but the 
most common age of onset is in the second and third decades with a female 
preponderance.  While predominantly a disease of adults, approximately 10% to 15% of 
CD cases are diagnosed before adulthood.3 
In addition, the incidence of CD in patients less than 18 years of age appears to be 
increasing in both North America and Europe.4,5  Reported incidence rates range from 
1.2 to 4.9 per 100,000 persons in the UK, Europe, and North America6-12 with one study 
reporting an incidence of 4.6 per 100,000 persons in the United States.5  CD has been 
reported at all ages but is rare in early childhood.  In one study of patients with CD, 
17 years of age and younger, 9.1% of the patients were diagnosed before the age of 6.13  
In a second study of patients diagnosed with CD before the age of 15, 7.5% of the 
patients were under the age of 5.14 
Despite obvious physiologic and development differences, the presentation of CD in the 
pediatric population is generally similar to that seen in older patients and is 

 
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heterogeneous with regard to anatomic localization and clinical severity.5,15,16  The 
unique aspect of this disease in children is its impact on nutrition and growth, with 
marked growth retardation being a prominent component of the disease in this age 
group.17-19  The use of accepted methodologies for assessing nutritional status, including 
the anthropometric measures of height, weight, triceps skin fold thickness and mid arm 
circumference as well as linear growth (height velocity and assessment of height velocity 
for chronological age "z-score") have documented the growth impairment that can occur 
in this age group, and also have been used to assess the efficacy of interventions.20  
Profound impairment of bone formation and increased bone resorption are associated 
complications and are related to the effect of glucocorticoids,21,22 delayed puberty,22,23 
decreased mobility,24 as well as to the effects of cytokines on bone formation.25 
Initial symptoms are often subtle, and there is an average delay of almost six months 
between onset of symptoms and diagnosis.  The most common presentation is with 
abdominal pain, diarrhea, loss of appetite and weight loss.  However, isolated weight 
loss, anorexia, perianal disease and extraintestinal manifestations can occur in the 
absence of GI symptoms in a substantial number of patients. 
The general approach to the treatment of CD in children is similar to adults with the goals 
being induction and maintenance of remission, prevention of relapse and hospitalizations, 
improved quality of life, and avoidance of disease and drug related complications.  
Restoration and/or preservation of normal growth and pubertal development are 
additional therapeutic goals.  The medical armamentarium is likewise similar to adults 
and includes induction of remission with corticosteroids, and ongoing maintenance 
therapy of immunomodulators, aminosalicylates and nutritional therapy.  Anti-tumor 
necrosis factor (TNF) therapy with infliximab has been evaluated for the therapy of CD 
in this age group as it has in adults.  The FDA and EMEA have recently approved 
Infliximab for use in children with CD. 
Adalimumab is a recombinant human immunoglobulin (IgG1) monoclonal antibody 
exclusively containing human peptide sequences.  It is produced by recombinant 
deoxyribonucleic acid (DNA) technology in a mammalian cell expression system.  

 
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Adalimumab consists of 1330 amino acids and has a molecular weight of approximately 
148 kilodaltons.  It binds specifically with high affinity to the soluble and transmembrane 
forms of TNFD and inhibits the binding of TNFD with its receptors. 
TNF is a naturally occurring cytokine that is involved in normal inflammatory and 
immune responses. Elevated levels of TNF play an important role in pathologic 
inflammation. Adalimumab binds specifically to TNF and neutralizes the biological 
function of TNF by blocking its interaction with the p55 and p75 cell surface TNF 
receptors. 
Adalimumab was first approved for treatment of rheumatoid arthritis (RA) on 
31 Dec 2002 in the United States (US), on 08 Sep 2003 in the European Union (EU) and 
through July 2007 in a total of 69 countries.  Indication extensions to include treatment of 
psoriatic arthritis and early RA were granted in the EU on 01 Aug 2005 and in the US on 
03 Oct 2005.  A further indication extension to include treatment of ankylosing 
spondylitis was approved in the EU on 01 Jun 2006 and was approved in the US on 
28 Jul 2006.  Adalimumab was approved for the treatment of Crohn's disease in the 
United States on 27 Feb 2007, in the European Union on 04 Jun 2007 and in Canada on 
05 July 2007 for the adult population.  
Adalimumab has been shown to be a safe and effective treatment of moderately to 
severely active Crohn's disease.  In the CD development program, adalimumab was 
studied in over 1400 subjects in three pivotal studies (two induction studies and a 
maintenance study). 
Study M02-403 was a multicenter, randomized, double-blind, placebo-controlled 
Phase 2/3 study to evaluate the efficacy and safety of adalimumab for the induction of 
remission in subjects with moderate to severe CD.26  A total of 299 subjects were 
randomized to receive one of four proposed induction treatment regimens (three active 
treatment groups or placebo):  adalimumab 160 mg at Baseline (Week 0) followed by 
80 mg at Week 2, adalimumab 80 mg at Baseline followed by 40 mg at Week 2, 
adalimumab 40 mg at Baseline followed by 20 mg at Week 2 or placebo at Baseline and 

 
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Week 2.  Eligible subjects could not have been previously treated with any anti TNF 
agent.  Only the group of subjects treated with adalimumab 160/80 mg had a statistically 
significantly greater remission rate at Week 4 (primary endpoint) compared to placebo 
(35.5% vs. 12.2%; p = 0.001).  In addition, statistically significantly greater proportions 
of subjects in the adalimumab 160/80 mg group than in the placebo group experienced 
clinical response CR-100 (48.7% and 24.3%, respectively) and clinical response CR-70 
(57.9% and 36.8%, respectively) at Week 4. 
Study M04-691, a second induction study, was a multicenter, randomized, double-blind, 
placebo-controlled, Phase 3 study to evaluate the efficacy and safety of adalimumab as 
induction treatment for subjects with moderate to severe CD who either initially 
responded to administration of infliximab but stopped responding or were intolerant.27  A 
total of 325 subjects were randomized to receive adalimumab 160/80 mg or placebo.  
Eligible subjects must have previously been treated with infliximab and discontinued use 
due to loss of response to or intolerance to infliximab therapy.  The proportion of subjects 
who achieved clinical remission at Week 4 (primary endpoint) was statistically 
significantly greater in the adalimumab 160/80 mg group compared to the placebo group 
(21.4% vs. 7.2%).  The proportion of subjects achieving clinical response CR-100 and 
CR-70 at Week 4 was statistically significantly greater in the adalimumab 160/80 mg 
group (38.4% and 51.6%, respectively) compared to the placebo group (24.7% and 
33.7%, respectively). 
Study M02-404 was a multicenter, randomized, double-blind, placebo-controlled Phase 3 
study to assess the efficacy and safety of adalimumab for the maintenance of clinical 
remission in subjects with moderate to severe CD.27  A total of 854 subjects (both naïve 
to or previously treated with TNF antagonists [primarily infliximab]) were enrolled and 
received open-label adalimumab 80 mg at Baseline (Week 0) and adalimumab 40 mg at 
Week 2.  At Week 4, subjects were stratified by responder status (subjects who achieved 
clinical response CR-70) and previous anti-TNF use and were randomized in a 1:1:1 ratio 
to one of three blinded treatment groups:  adalimumab 40 mg every week (ew), 

 
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adalimumab 40 mg every other week (eow), or placebo.  Subjects who met clinical 
response CR-70 after Week 8 could be tapered from corticosteroids. 
The proportion of Week 4 responders (N = 499) who achieved clinical remission at 
Weeks 26 and 56 (co-primary endpoint) were statistically significantly greater in the 
adalimumab 40 mg eow (39.5% and 36.0%, respectively) and 40 mg ew (46.5% and 
41.4%, respectively) groups compared to the placebo group (17.1% and 11.8%, 
respectively).  The differences between the adalimumab 40 mg eow and adalimumab 
40 mg ew groups at both of these time points were not statistically significant.  The 
median time in first clinical remission was greater in the adalimumab 40 mg eow group 
(378 days) compared to the placebo group (127 days).  The median time in remission 
could not be estimated in the adalimumab 40 mg ew group because more than 50% 
remained in clinical remission at the end of the study.  Approximately six times as many 
subjects treated with adalimumab maintenance therapy compared to placebo were able to 
discontinue corticosteroids for at least 90 days and achieve remission at Week 26 and 
Week 56.  Efficacy was independent of Baseline C-reactive protein (CRP), concomitant 
therapies, such as corticosteroids or immunosuppressants, or prior anti-TNF experience.  
The adalimumab safety profile in CD was similar to that seen in the other rheumatologic 
populations previously studied, except for expected manifestations of CD. 
Currently, there are two ongoing extension studies of adalimumab therapy in adult 
subjects with CD.  M04-690 trial is a long-term safety and tolerability study of repeated 
administration of adalimumab in adult subjects with CD who had previously participated 
in M02-404 or M04-691.  The other trial is a long-term open-label extension study 
following the initial first-year study period of the M02-433 study. 
The efficacy and safety of adalimumab in children has recently been demonstrated in 
juvenile rheumatoid arthritis (JRA).28  One hundred and seventy-one pediatric patients 
(4 to 17 years of age) were initially enrolled into a 16-week open label segment and 
133 subjects continued in a 32-week double blind segment.  Clinically significant 
improvements were noted in ACR30, ACR50 and ACR70 as well as other indices of 
arthritis activity.  Adverse events (AEs) were similar as those noted in adult RA patients.  

 
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There were no deaths, malignancies, or opportunistic infections, including tuberculosis 
(TB).  Thirteen serious adverse events (SAEs) in 8 subjects were observed in the 16-week 
open label portion of the study.  These included 4 subjects with JRA, one patient with 
two episodes of leukopenia/neutropenia, and one case each of femur fracture, herpes 
simplex, and pneumonia.  Six SAEs were observed in 6 subjects (2 placebo, 
4 adalimumab) during the 32-week double blind portion (closed head injury, 
gastroduodenitis, retinal detachment, appendicitis, abdominal pain and urinary tract 
infection).  Infections, AEs at least possibly related to study drug, and injection site 
reactions were reported by similar proportions of patients in all treatment groups during 
the double-blind therapy (32 weeks). 
Fatalities, serious infections, and sepsis have been reported with the use of TNF 
antagonists.  Many of the serious infections have occurred in subjects on concomitant 
immunosuppressive therapy that, in addition to their underlying immune disorder, could 
predispose them to infections.  TB has also been observed in subjects treated with TNF 
antagonists, including adalimumab.  The event rate for TB in the CD development 
program is consistent with the global adalimumab rate.29 
TNF antagonists, including adalimumab, have been associated with cases of malignancy 
and demyelinating disease.  Serious allergic adverse reactions have been reported in RA 
subjects following subcutaneous (SC) administration of adalimumab; none were reported 
in the CD program. 
A detailed discussion of the pre-clinical toxicology, metabolism, pharmacology, and 
safety experience can be found in the current Investigator's Brochure. 
The goal of this study is to demonstrate the efficacy of adalimumab in the maintenance of 
clinical response and to demonstrate the long-term safety and tolerability of repeated 
administration of adalimumab in pediatric subjects with Crohn's disease.  The subject 
population will consist of subjects who participated in and successfully completed the 
M06-806 study and who meet all the inclusion and none of the exclusion criteria of 
Protocol M06-807.  Qualifying subjects will administer open-label adalimumab by SC 

 
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injection.  Subjects receiving every other weekly therapy who continue to have a disease 
flare or develop another flare may be switched to every week therapy at the investigator's 
discretion.  Subjects receiving weekly therapy who continue to have a disease flare or 
develop another flare may be withdrawn from the study at the Investigator's discretion.  
For a detailed description of the study please see Section 5.0. 
4.0 
Study Objective 
The objective of the study is to evaluate the long-term maintenance of clinical response, 
safety and tolerability of repeated administration of adalimumab in pediatric subjects 
with Crohn's disease who participated in, and successfully completed, Protocol M06-806 
through Week 52 and who meet all the inclusion and none of the exclusion criteria of 
Protocol M06-807.
5.0 
Investigational Plan 
5.1 
Overall Study Design and Plan:  Description 
This study is a multi-center, open-label study of the human anti-TNF monoclonal 
antibody adalimumab.  Approximately 55 sites that have enrolled subjects in the 
M06 − 806 clinical trial will participate in the M06-807 clinical trial. Approximately 
130 pediatric subjects are expected to enroll in this study.   
The Week 52 visit from the M06-806 study will be the Baseline Visit for those subjects 
entering study M06-807.  The visit window for M06-806 Week 52 visit is 364 ± 7 days 
from the Baseline Visit date of M06-806. 
Subjects may be allowed to enroll in the M06-807 study if they have participated in, and 
successfully completed Protocol M06-806 through Week 52.  At the end of 
Study M06 − 806, a subject must be a responder to enroll in this trial.  A responder is 
defined as a subject who had a PCDAI score that was at least 15 points lower than the 
M06-806 baseline score. 

 
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All subjects will be on open-label maintenance therapy.  Subjects who enroll into the 
study from blinded therapy in Study M06-806 will receive open-label therapy at a dose 
dependent on their body weight. Subjects who weigh t 40 kg at Baseline will receive 
40 mg eow of adalimumab, while subjects who weigh < 40 kg at Baseline will receive 
20 mg eow of adalimumab. Beginning at Week 8, subjects who have a disease flare may 
be switched to ew treatment at the same dose of adalimumab received while on eow 
treatment. A disease flare is defined as an increase in the Pediatric Crohn's Disease 
Activity Index (PCDAI) of t 15 points when compared to the PCDAI score obtained at 
the subject's previous visit. 
Subjects who enroll into the study from open-label therapy in Study M06-806 will 
continue to receive the same dose they were receiving (i.e. 40 mg ew or 20 mg ew) at the 
Week 52 visit of the M06-806 study.  
Subjects who develop a flare while receiving ew open-label therapy or have a PCDAI 
score t 15 points when compared to their Baseline (the Week 52 visit of the M06-806 
study) PCDAI score (regardless of study visit), may be discontinued from the study at the 
discretion of the Investigator.  
Beginning from Week 8, the dose of adalimumab may be increased to 40 mg, at the 
discretion of the Investigator, for subjects whose body weight has increased from < 40 kg 
to t 40 kg from the Baseline (Week 52 of the M06-806 Study) visit. The site will enter 
the subjects' body weight into the Interactive Voice Response System (IVRS) and the 
dose will be adjusted, if applicable.  
Reductions in concomitant therapy will be allowed for Crohn's treatment related 
toxicities (e.g., leukopenia, anemia, neuropathy) of Grade 3 or higher. 
Subjects may be allowed to decrease prednisone (or equivalent) and budesonide if 
qualifications are met (please see Section 5.2.3.2 for required timing and rate of taper). 
Subjects may be allowed to adjust their Crohn's specific concomitant medications as 
specified in Section 5.2.3.2. 

 
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3. 
If female, subjects who are sexually active and are of child-bearing potential 
should be practicing an approved method of birth control throughout the study and 
for 150 days after study drug administration. Examples of approved methods of 
birth control include the following: 
● Condoms, sponge, foam, jellies, diaphragm or intrauterine device (IUD) 
● Oral, parenteral or intravaginal contraceptives 
● A vasectomized partner 
4. 
Subject of legal age, parent or legal guardian, as required, has voluntarily signed 
and dated an Institutional Review Board (IRB)/Independent Ethics Committee 
(IEC) approved informed consent form, after the nature of the study has been 
explained and the subject of legal age, subject's parent, or legal guardian, as 
required, has had the opportunity to ask questions.  Subjects will be included in all 
discussions, and if required, their signature on an assent form will be obtained. 
5. 
Parent or legal guardian of subject who is not of legal age, as required, must be 
willing to actively supervise storage and administration of study drug and to 
ensure that the time of each dose is accurately recorded in the subject's diary. 
6. 
If a subject of legal age, must be willing to actively store, administer, and 
accurately record study drug administration in the subject diary. 
7. 
Subject is judged to be in acceptable medical condition, as determined by the 
Principal Investigator based upon results of clinical and laboratory evaluations 
done throughout the preceding Crohn's disease study M06-806. 
 
5.2.2 
Exclusion Criteria 
A subject will be excluded from the study if he/she meets any of the following criteria:  
1. 
For any reason, the subject is considered by the Investigator to be an unsuitable 
candidate for continuing therapy in the M06-807 study. 

 
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2. 
Subject has abnormal laboratory or other test results that in the opinion of the 
Investigator will make the subject unsuitable to participate in this study. 
3. 
History of cancer or lymphoproliferative disease other than a successfully and 
completely treated cutaneous squamous cell or basal cell carcinoma or 
carcinoma − in-situ of the cervix. 
4. 
History of listeriosis, histoplasmosis, chronic or active hepatitis B infection, 
human immunodeficiency virus (HIV) infection, any immunodeficiency 
syndrome, central nervous system (CNS) demyelinating disease or active TB 
(receiving treatment or not receiving treatment). Ongoing severe infections such as 
sepsis and opportunistic infections will be exclusionary. 
5. 
Subject with known, symptomatic obstructive strictures. 
6. 
Subject who is planning surgical bowel resection at any time point while enrolled 
in the study. 
7. 
Subject who has short bowel syndrome as determined by the Investigator. 
8. 
Subject who is currently receiving total parenteral nutrition (TPN). 
9. 
Subject who is unwilling to discontinue growth hormone prior to the first dose of 
open-label study drug at the Baseline visit of M06-807. 
10. 
Female subject who is pregnant or currently breast-feeding. 
11. 
Subject with a history of clinically significant drug or alcohol abuse in the last 
year. 
12. 
Subject with a poorly controlled medical condition such as: uncontrolled diabetes, 
recurrent infections, unstable ischemic heart disease, moderate to severe heart 
failure, recent cerebrovascular accidents or any other condition which, in the 

 
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opinion of the Investigator or the Sponsor, will put the subject at risk by 
participation in the protocol. 
13. 
Subject with any prior exposure to Tysabri (natalizumab). 
14. 
Subject with a known hypersensitivity to the excipients of adalimumab as stated in 
the label. 
15. 
Subject with a previous history of dysplasia of the gastrointestinal tract. 
16. 
Subject is not in compliance with Section 5.2.3. 
 
If there are any questions regarding inclusion and exclusion criteria and/or subject 
eligibility, contact the Abbott Laboratories Medical Monitor identified in Section 7.0. 
5.2.3 
Prior and Concomitant Therapy 
5.2.3.1 
Prior Therapy 
Any medication (including over-the-counter medicines such as aspirin) that the subject is 
receiving during the study must be recorded in source documents and on the appropriate 
case report form (CRF) along with the reason for use, dates of administration and 
dosages. 
Any vaccine administered to the subject during the study should be listed as a 
concomitant medication.  Subjects should continue on the recommended vaccination 
schedule; however, vaccinations with live vaccines are prohibited.   
Any medications captured in the M06-806 CRF(s) which are ongoing will be transcribed 
onto the M06-807 source documents and CRF(s). 
If there are any questions regarding prior or concomitant therapy (ies), contact the Abbott 
Laboratories Medical Monitor identified in Section 7.0 

 
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5.2.3.2 
Concomitant Therapy 
Adjustments of Crohn's related concomitant treatments, including Crohn's related 
antibiotics, are not allowed during the first 8 weeks of the M06-807 study, unless subject 
safety is at risk. 
After Week 8, decreases in the dose or discontinuation of Crohn's related antibiotics or 
Crohn's related concomitant treatments are allowed according to the Investigator's 
medical judgment.  These adjustments may be performed without prior discussion with 
the Abbott Medical Monitor.  In addition, Subjects may be able to initiate or reinitiate 
Crohn's related treatments, except immunosuppressants, following eight (8) weeks of 
exposure to open-label adalimumab.  Immunosuppressants may not be started or restarted 
during the study.
Setons are allowed as concomitant therapy in subjects with perianal fistulas.  Their use 
should be documented on the concomitant medications page of the CRF. 
Growth hormone must be discontinued prior to the first dose of open-label study drug and 
Subjects may not begin using it while participating in this study. 
If a subject began to taper corticosteroids during the M06-806 study, they may continue 
this taper immediately upon enrollment into the M06-807 study.  Beginning at Week 8, 
subjects who are not in flare may begin corticosteroid taper according to the following 
schedule: 
Tapering Schedule 
Dose 
Rate 
Prednisone (or equivalent) 
> 10 mg 
d 10 mg  
5 mg/week 
2.5 mg/week 
Budesonide 
d 9 mg  
3 mg/week 
 
Subjects who are in flare or who flare after they have reduced or completely tapered their 
dose of corticosteroid may have their corticosteroid dose increased or restarted, at the 
discretion of the Investigator.  

 
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5.2.3.3 
Rescue Therapy 
If the Investigator decides, during the study, that a subject requires rescue therapy other 
than that described in this protocol, the subject must be terminated from the study.  If 
possible, questions regarding the use of rescue therapy should be discussed with the 
Medical Monitor prior to use. 
5.2.3.4 
Prohibited Therapy 
Live vaccines must not be given concurrently while on study drug and for 70 days after 
the last dose of study drug. 
Infliximab and growth hormone use are prohibited during the study.  At the Baseline 
visit, any subject using Growth hormone must discontinue its use. 
Tysabri (natalizumab), concurrent biological therapy, cyclosporine, tacrolimus, 
mycophenolate mofetil, Kineret® (anakinra), Orencia (abatacept), therapeutic enemas and 
suppositories (not including those done in conjunction with routine colonoscopies) and 
any investigational agent are prohibited during the study (see Appendix K). 
Concurrent use of budesonide and prednisone (or equivalent) is prohibited. 
Subjects with any prior exposure to Tysabri (natalizumab) will be excluded. 
5.3 
Efficacy, and Safety Assessments/Variables 
5.3.1 
Efficacy and Safety Measurements Assessed and Flow 
Chart
Study procedures will be performed as summarized in the study schematic presented in 
Table 1. 

 
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Table 1. 
Study Activities 
Activity 
Base-
line
Week
4
Week
8
Week
12
Week
24
Week
36
Week
48
Week
60
Week
72
Week
84
Week
96
Week
104/ 
Early 
Term
Unscheduled 
visit 
70-Day 
Follow-up 
Phone Call
Inclusion/exclusion criteria 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Previous and concomitant 
medications 
Xa 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Urine pregnancy testb 
Xa 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Vital signsc 
Xa 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Physical exam 
Xa 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
General LABd 
Xa 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Urinalysise 
Xa 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Erythrocyte sedimentation 
rate 
Xa 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
CRP 
Xa 
 
 
 
X 
 
X 
 
X 
 
 
X 
 
 
ANA 
Xa 
 
 
X 
 
 
 
 
 
 
 
X 
 
 
Anti-dsDNAf 
Xa 
 
 
X 
 
 
 
 
 
 
 
X 
 
 
PCDAI 
Xa 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
CDAIg 
Xa 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
IMPACT III Questionnaireh 
Xa 
 
 
X 
X 
 
X 
 
X 
 
 
X 
 
 
Unscheduled outpatient 
visits, emergency room 
visits and hospitalizations 
questionnaire 
Xa 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 

 
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Activity 
Base-
line
Week
4
Week
8
Week
12
Week
24
Week
36
Week
48
Week
60
Week
72
Week
84
Week
96
Week
104/ 
Early 
Term
Unscheduled 
visit 
70-Day 
Follow-up 
Phone Call
Work Productivity and 
Impairment Questionnaire: 
Crohn's Disease  
(WPAI − CD) 
Xa 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
X-ray for bone age 
Xa 
 
 
 
 
 
X 
 
 
 
 
X 
 
 
Serum bone markers 
Xa 
 
 
 
X 
 
X 
 
X 
 
 
X 
 
 
Adverse eventsi 
Xa 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Dispense study drug 
Xa 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Xj 
 
a. 
At the Baseline Visit, the following procedures will be completed as part of Week 52 of the M06-806 study. 
b. Performed on all females of child-bearing potential - Urine pregnancy test at all study visits. 
c. 
Vital sign determinations of height, weight, sitting blood pressure, heart rate, respiratory rate, and body temperature will be obtained at each visit. 
d. Blood draws should be performed after questionnaire and vital signs determinations and before study drug administration. 
e. 
Microscopic urinalysis will be performed at any visit if dipstick UA is abnormal (protein greater than a trace, blood greater than 5-10 Ery/ul, moderate or 
large ketone count or glucose greater than 50 mg/dL). 
f.  If an ANA result is positive, anti-dsDNA will be performed automatically. 
g.  For subjects who are age 13 or older at the M06-807 Baseline Visit, a CDAI will be completed at each visit. 
h. For subjects who are age 10 or older at the M06-807 Baseline Visit, an IMPACT III Assessment will be completed at Baseline, Weeks 12, 24, 48, 72, and 
104/ET. 
i. 
All AEs, including SAEs, will be captured throughout the study from the time that the subject signs the Informed Consent Form. SAEs will be captured 
throughout the 70 day follow-up period (if applicable). 
j. 
If an unscheduled visit is performed to change the frequency of study drug from OL eow to OL ew, study drug may be dispensed. 
 

 
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5.3.1.1 
Study Procedures 
The M06-806 Week 52 visit will serve as the Baseline visit for the M06-807 study.  The 
study procedures outlined in Table 1 are discussed in detail in this section, with the 
exception of the collection of AE information (discussed in Section 6.0).  All study data 
will be recorded in source documents and on the appropriate CRFs.  
The visit window for all scheduled visits is ±7 days calculated from the Baseline visit of 
the M06-807 study. 
Inclusion/Exclusion Criteria
A subject will be excluded from this study if he/she does not meet all inclusion criteria or 
meets any of the exclusion criteria of Protocol M06-807. 
Informed Consent
A signed Informed Consent Form (ICF) will be obtained from a subject of legal age (in 
the state of residence) or from the parent or legal guardian (as appropriate)of a subject 
who is not of legal age before any study related procedures are undertaken or before any 
medications are discontinued for the purpose of this study. Additionally, an informed 
consent will be required from those subjects who were not of legal age at the onset of this 
study but become of legal age during the course of the study. 
In keeping with each institution's IRB requirements, an Informed Assent may also be 
required from pediatric subjects. Pediatric subjects will be included in all discussions in 
order to obtain their signature on an assent form. Details about how informed consent 
will be obtained and documented are provided in Section 9.3. 
If an updated informed consent is approved after a subject has completed or terminated 
early from the study, but is within the 70-day follow-up window, the subject will not be 
required to return to the site for the purposes of signing the updated ICF.  The subject of 
legal age, parent or legal guardian (as appropriate) should be contacted regarding any 
changes and the documentation of the contact should be present in the subject's source. 

 
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Previous and Concomitant Medications
Changes in concomitant medications will be assessed at each study visit from Baseline 
through Week 104/ET visit.  Concomitant medications that are taken prior to the first 
dose of study drug administration for this study will be captured in the subject's casebook 
from the previous study (M06-806).  They will not be required to be captured in the 
subject's casebook of the M06-807 study unless they were ongoing at the Week 52 visit 
of the M06-806 study. Ongoing concomitant medications from the M06-806 study will 
be transcribed into the subject's M06-807 casebook.
Subjects of legal age or the parent or guardian (as appropriate) of subjects who are not of 
legal age will be provided with a medication log (see Appendix N) to record all 
medications the subject takes throughout the study.  This log must be returned for review 
at every study visit. 
Serum/Urine Pregnancy Test
All female subjects who are experiencing menses, are nearing sexual maturation (in the 
opinion of the Investigator), or who are of child-bearing potential, will undergo a urine 
pregnancy test at each visit.  Urine pregnancy tests will be performed locally by 
designated study personnel.  If a urine pregnancy test is positive, a serum pregnancy test 
must be performed by the central laboratory.  If the serum pregnancy test is positive, the 
subject will be removed from the study.   
A lactating or pregnant female will not be eligible for participation in this study. 
Vital Signs
Vital sign determinations of sitting blood pressure, heart rate, respiratory rate, body 
temperature, weight and height will be obtained at each visit.  All measurements will be 
recorded in metric units when applicable.  
Weight measurements will be obtained using the same measuring instrument at each visit 
and measured with subjects wearing only undergarments. Height measurements will be 

 
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obtained using the same measuring equipment at each visit and performed on subjects 
with their shoes taken off. 
Physical Examination
A physical examination will be performed at each visit.  A count of the number of 
cutaneous fistulas draining upon gentle compression will be performed during each 
physical exam.30  Fistulas will be classified as abdominal or perianal/anal. 
Physical exam abnormalities (including fistulas and fissures) noted by the Investigator 
will be evaluated and documented on the corresponding source documents.  Any new 
abnormalities or worsening of pre-existing conditions should be captured as AEs. 
Clinical Laboratory Tests 
Samples will be obtained for the laboratory tests listed in Table 2 at all study visits. 
Blood draws should be performed after questionnaires (PCDAI, IMPACT III 
Questionnaire, etc.) and vital sign determinations during a study visit, and before study 
drug administration. 
ICON central laboratory will be utilized to process and provide results for the general 
laboratory tests. All abnormal laboratory test results that are considered clinically 
significant by the Investigator will be followed to a satisfactory resolution. 
ICON will provide instructions regarding the collection, processing and shipping of these 
samples. 

 
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Table 2. 
Clinical Laboratory Tests  
Hematologya 
Clinical Chemistry 
Urinalysisb 
Serum Bone Markers 
Hematocrit 
Hemoglobin 
Red Blood Cell (RBC) 
count 
White Blood Cell 
(WBC) count 
Neutrophils 
Bands 
Lymphocytes 
Monocytes 
Basophils 
Eosinophils 
Platelet count (estimate 
not acceptable) 
Blood Urea Nitrogen 
(BUN) 
Creatinine 
Total bilirubin 
Serum glutamic-pyruvic  
 
transaminase 
(SGPT/ALT) 
Serum glutamic-
oxaloacetic 
 
transaminase 
(SGOT/AST) 
Alkaline phosphatase 
Sodium 
Potassium 
Calcium 
Inorganic phosphorus 
Uric acid 
Cholesterol 
Total protein 
Glucose 
Triglycerides 
Albumin 
Specific gravity 
Ketones 
pH 
Protein 
Blood 
Glucose 
Osteocalcin 
Bone-specific alkaline 
phosphatase (BSAP)  
bone resorption (Ntx) 
a. 
Basic hematology testing performed on instrumentation does not include band reporting.  When 
Hematology results reflex to a Manual Differential, if there is a band result over 5, it is reported. 
b. Microscopic urinalysis will be performed at any visits if dipstick UA is abnormal  (protein greater than 
a trace, blood greater than 5-10 Ery/ul, moderate or large ketone count or glucose greater than 
50 mg/dL). 
 
Immunologic Laboratory Assessments  
CRP assessments will be performed at Baseline (Week 52 of the M06-806 Study), 
Weeks 24, 48, 72 and 104/ET. Antinuclear antibody (ANA) will be performed at 
Baseline (Week 52 of the M06-806 Study), Week 12, and Week 104/ET. If an ANA 
result is positive, anti-double-stranded DNA (anti-dsDNA) will be performed 
automatically. All CRP, ANA, anti-dsDNA will be performed by the central laboratory. 
Erythrocyte Sedimentation Rate (ESR) assessments will be performed at all visits as 
indicated in Table 1. ESR assessments will be performed by the site's local laboratory. 

 
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Markers of Bone Metabolism 
Serum markers of bone metabolism will be measured at Baseline (Week 52 of the 
M06−806 Study), Weeks 24, 48, 72 and 104/ET.  The bone formation markers to be 
measured are osteocalcin, bone-specific alkaline phosphatase (BSAP), and bone 
resorption (Ntx). 
Urinalysis
Urine will be assessed by dipstick at each visit (done locally).  All results, including 
abnormalities, will be captured in source documentation and on the appropriate CRF. If, 
at any visit, the dipstick UA results are abnormal, the central lab will perform a 
microscopic urinalysis. Abnormal is defined as protein greater than a trace, blood greater 
than 5-10 Ery/ul, moderate or large ketone count or glucose greater than 50 mg/dL. 
Pediatric Crohn's Disease Activity Index (PCDAI)
The PCDAI score will be calculated at each visit.  When completing the PCDAI, the 
HCT, albumin, and ESR values will be utilized from the same study visit.  
An example of the PCDAI is located in Appendix F.  Instructions for completing the 
PCDAI score is located in Appendix G. 
Crohn's Disease Activity Index (CDAI)
At each visit, a CDAI score will be calculated for subjects who are age 13 or older at the 
M06-807 Baseline Visit. The CDAI score will be calculated utilizing the subject diary 
and the HCT value from the same study visit. A copy of the CDAI subject diary is 
located in Appendix G. 
When completing question five (5) ("Taking Lomotil/Imodium/Loperamide/opiates for 
diarrhea, 0 = no, 1 = yes") on the CDAI, "no" should be answered if a subject is taking an 
opiate(s) solely for pain. 

 
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For the CDAI questions regarding presence of anal fistulas and other fistulas, all fistulas 
detectable on physical examination (draining and non-draining) should be captured on the 
CDAI CRF page and calculated into the CDAI score. 
The calculation of the CDAI score is in Appendix H. 
IMPACT III Questionnaire
Subjects t 10 years old at the Baseline visit of the M06-807 study will complete an 
IMPACT III questionnaire at Baseline, Weeks 12, 24, 48, 72, and 104/ET as indicated in 
Table 1.  A copy of the questionnaire is located in Appendix J.  
The IMPACT III will be recorded directly onto the CRF.  The completed CRF will be 
considered source documentation for this assessment. 
Outcomes
The Unscheduled Outpatient Visits, Emergency Room Visits and Hospitalization 
Questionnaire and the Work Productivity and Activity Impairment Questionnaire:  
Crohn's Disease (WPAI-CD) will be completed at each visit except the Unscheduled 
Visit (Appendix M, Appendix S). 
The subject's parent or legal guardian will complete the WPAI directly onto the CRF.  
The completed CRF will be considered source documentation for this assessment. 
Bone Age
An x-ray of the wrist for the assessment of bone age will be obtained at Baseline 
(Week 52 of M06-806), Week 48, and Week 104/ET to determine changes in bone 
maturation as indicated in Table 1.  Sites should use the Greulich and Pyle method for 
reading the x − ray.31  The x-ray report requires the signature of the radiologist who read 
the films.  The bone age that is determined by the x-ray should be recorded on the CRF.   

 
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Anthropometric Evaluations
Height and weight obtained at each visit will be used by Abbott Data Management and 
Statistical groups for determination of BMI and "z" score (observed height velocity 
(cm/yr) - mean height velocity for age and sex (cm/yr) / SD of the mean) for height. 
Adverse Events
Adverse events will be assessed at every study visit from Baseline through Week 104 / 
Early Termination visit. Any AEs, which are ongoing in the M06-806 study, will be 
transcribed onto the M06-807 source documents and CRF(s) 
For those subjects who complete the study or terminate early, a phone call will be made 
70 days after the last dose of study drug to obtain follow-up information on any ongoing 
and any new AEs. See Section 6.0 and Appendix L for additional information. 
Study Drug Administration
At each study visit, the subject or their trained designated friend, family member or 
health care professional will perform study drug injections under the supervision of a 
trained medical personnel to reinforce proper aseptic SC injection technique.  Subjects or 
a trained designated friend, family member or health care professional will perform 
injections of study drug in the subject's home during weeks they are not in for scheduled 
clinic visits. Subjects may return to the study site for injections in between study visits if 
subject or a trained designated friend, family member or health care professional cannot 
inject the study medication. 
Subjects will maintain a dosing diary for all study drug administered outside study visits, 
i.e., at home.  In the diary, the date, initials of the person administering the study drug, 
time study drug is administered, kit number and the dose administered will be recorded. 
Subjects must return this diary and it will be reviewed and verified for compliance at 
each visit by the research personnel at the study center.  All relevant dosing information 
will be retained by the study coordinator and transcribed onto a drug accountability form 
at each visit. Additionally, any discernible departure from the protocol regarding study 

 
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drug administration will be recorded on source documents and appropriate drug 
accountability forms. A sample of the Subject Dosing Diary is presented in Appendix O. 
At all office visits subjects should be observed after study drug administration, until 
judged clinically stable by the study personnel.  If an anaphylactic reaction or other 
serious allergic reaction occurs, administration of study drug should be discontinued 
immediately and appropriate therapy initiated.  When dosing at home, subjects should be 
instructed to contact the site immediately with any signs or symptoms of a reaction. 
The dosing dates, for all doses of study drug, should be calculated from the Baseline visit 
date.  The Baseline visit date for this study is 364 ± 7 days from the Baseline Visit date of 
M06-806.  A +/- 3 day window is allowable for scheduled study dosing dates.   
For subjects that deviate from this dosing window, every effort should be made to bring 
the subject back to the original dosing schedule as soon as possible.  For situations where 
bringing the subject back on the original dosing schedule will cause the dose to be out of 
the +/- 3 day window, please contact the Medical Monitor for additional instructions. 
Randomization and Assignment of Subject Numbers
All subjects will be centrally registered using an IVRS.  This is an open-label study; 
subjects will not be randomized.  The telephone number and call in directions for the 
IVRS will be provided to each site.  Subjects will keep their study subject number from 
the previous double-blind study (M06 − 806). 
5.3.2 
Drug Concentration Measurements 
No drug concentration measurements will be obtained in this trial. 
5.3.3 
Efficacy Variables 
Efficacy will be evaluated based on the proportion of subjects who maintain PCDAI 
clinical response at each visit. Clinical response is defined as PCDAI decrease 
t 15 points from the M06-806 Baseline score. 

 
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Other measures of disease activity being assessed in this study will be summarized, 
including CDAI scores, IMPACT III scores, WPAI-CD Caregiver, z-score for height 
velocity, bone x-ray, serological markers of bone metabolism, and healthcare resource 
utilization (unscheduled outpatient visits). 
5.3.4 
Safety Variables 
AEs, laboratory data, physical examinations and vital signs are the safety parameters and 
these will be assessed throughout the study. 
5.4 
Removal of Subjects from Therapy or Assessment 
5.4.1 
Discontinuation of Individual Subjects 
Subjects will be withdrawn from the study immediately if any of the following occur:   
● Clinically significant abnormal laboratory results or AEs, which rule out 
continuation of the study drug, as determined by the Investigator and the 
Medical Monitor. 
● The Investigator believes it is in the best interest of the subject. 
● The subject or subject's legal guardian requests withdrawal from the study. 
● Selection criteria violation was noted after the subject started study drug, as 
determined by the Medical Monitor (see Sections 5.2.1 and 5.2.2). 
● Introduction of prohibited medications or prohibited concomitant medication 
dosages as determined by the Medical Monitor. 
● The subject is diagnosed with a malignancy except for localized 
non − melanoma skin cancer.  Discontinuation for carcinoma in-situ is at the 
discretion of the Investigator. 
● The subject is diagnosed with dysplasia of the gastrointestinal tract. 
● A female subject who becomes pregnant. 
 
If the subject prematurely discontinues study drug use, the procedures outlined for the 
Week 104/ET Visit must be completed within 2 weeks of the last dose of study drug, and 

 
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preferably prior to the initiation of another therapy.  These procedures should not 
interfere with the initiation of any new treatments or therapeutic modalities that the 
Investigator feels are necessary to treat the subject's condition.  Following 
discontinuation of the study drug, the subject will be treated in accordance with the 
Investigator's best clinical judgment. 
Subjects who prematurely discontinue from the study will not be replaced.  The date of 
last dose and reason for premature discontinuation will be recorded in the source 
document and on the appropriate CRF. 
5.4.2 
Discontinuation of Entire Study 
Abbott reserves the right to discontinue the study at any time and to remove all study 
materials from the site.  Possible reasons for termination of the study include, but are not 
limited to:   
● Safety concerns based on reported data 
● Unsatisfactory enrollment with respect to quantity or quality 
● Inaccurate or incomplete data collection 
● Falsification of records 
● Failure to adhere to the protocol 
 
5.4.3 
Stopping Rules 
An independent Data Monitoring Committee (DMC) will meet to discuss unblinded data 
from the study every six (6) months or at a frequency determined by the DMC and render 
their recommendation for either the continuation of the study or an amendment to the 
study. A Sponsor Steering Committee (SSC), composed of senior executives not directly 
participating in this study, will make final decisions based on DMC recommendations. In 
addition, an ad-hoc DMC meeting will be convened if either of the following criteria is 
met. 

 
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● The overall rate of SAEs, with an Investigator assessed causality of at least 
possibly related or higher, evaluated on a per subject-year basis, exceeds 
0.45 (0.15 SAEs/subject every four months), or 
● The overall rate of serious infectious SAEs evaluated on a per subject-year 
basis, exceeds 0.09 (.03 SAEs/subject every four months). 
 
If either of these criteria is met, no new enrollment will occur until the DMC or the SSC 
makes their recommendations. 
5.5 
Treatments 
5.5.1 
Treatments Administered 
All study drug will be provided as a SC injection solution in pre-filled syringes 
containing adalimumab 40 mg/0.8 mL or adalimumab 20 mg/0.8 mL. 
Subjects who enroll into the study from blinded therapy in Study M06-806 will receive 
open-label therapy at a dose dependent on their body weight. Subjects who weigh t 40 kg 
will receive 40 mg eow of adalimumab, while subjects who weigh < 40 kg will receive 
20 mg eow of adalimumab. Beginning from Week 8, subjects who have a disease flare 
may be switched to ew treatment at the same dose of adalimumab received while on eow 
treatment. 
Subjects who enroll into the study from open-label therapy in Study M06-806 will 
continue to receive the same dose they were receiving (i.e. 40 mg ew or 20 mg ew) at the 
Week 52 visit of the M06-806 study. 
Subjects who develop a flare while receiving ew open-label therapy or have a PCDAI 
score t 15 points when compared to their Baseline (Week 52 of M06-806) PCDAI score 
(regardless of study visit), may be discontinued from the study at the discretion of the 
Investigator. 
Beginning from Week 8, the dose of adalimumab may be increased to 40 mg, at the 
discretion of the Investigator, for subjects whose body weight has increased from < 40 kg 

 
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to t 40 kg from the study Baseline visit. The site will enter the subjects' body weight into 
the IVRS and the dose will be adjusted, if applicable. 
5.5.2 
Identity of Investigational Product 
The individual study drug information is presented in Table 3.  Pre-filled syringes will be 
provided for this open-label clinical study. 
Table 3. 
Identity of Investigational Products  
Study Drug 
Formulation 
Manufacturer 
Adalimumab 
40 mg/0.8 mL or 20 mg/0.4 mL  
Adalimumab/Mannitol, Citric acid monohydrate, Sodium citrate, 
Disodium phosphate dihydrate, Sodium dihydrogen phosphate 
dihydrate, Sodium chloride, Polysorbate 80, Water for injections, 
Sodium hydroxide added as necessary to adjust pH 
Abbott 
 
5.5.2.1 
Packaging and Labeling 
The following information will appear on the pre-filled syringe or carton labels: 
● Sponsor identification 
● Protocol number 
● Drug identification 
● Quantity of contents 
● Storage conditions 
● Dosing instructions 
● Kit number 
● Route of Administration 
● Excipients 
● Blank spaces to write the subject's identification number, initials, and date 
dispensed (as required) 
● Finishing lot # 
● Expiry Date (as required) 

 
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Two pre-filled syringes will be provided in a dosing kit carton (see Table 4).  Detailed 
instructions and training for the administration of study supplies are provided in 
Appendix P. 
Table 4. 
Study Drug Packaging and Administration 
Open-label Pre-filled Syringes 
Open-label kit cartons containing two pre-filled 
syringes of adalimumab 40 mg/0.8 mL. 
Open-label kit cartons containing two pre-filled 
syringes of adalimumab 20 mg/0.4 mL. 
 
5.5.2.2 
Storage and Disposition of Study Drug 
Pre-filled syringes are to be stored protected from light at 2° to 8°C/ 36° to 46°F.  
DO NOT FREEZE.  A storage temperature log is to be maintained at the site to document 
proper storage conditions. The refrigerator temperature must be recorded on every 
business day on a temperature log to record proper function. Malfunctions must be 
reported to the sponsor immediately. Study drug should be quarantined and not dispensed 
until Abbott GPRD or Abbott Temperature Excursion Management System (ATEMS) 
deems the medication as acceptable.  All clinical supplies must be stored and locked in a 
secure place until they are dispensed for subject use or are returned to Abbott 
Laboratories. 
Investigational products are for investigational use only, and are to be used only within 
the context of this study. 
5.5.3 
Method of Assigning Subjects to Treatment Groups 
This is an open-label study; all subjects will be receiving adalimumab. 
All subjects will be centrally registered using an IVRS.  The telephone number and 
call − in directions for the IVRS will be provided to each site.  Subjects will keep their 
study subject number from the previous study (M06 − 806). 

 
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Study drug will be administered at the study visits summarized in Table 1 and detailed in 
Section 5.3.1.1. 
5.5.4 
Selection and Timing of Dose for Each Subject 
Subjects who enroll into the study from blinded therapy in Study M06-806 will receive 
open-label therapy at a dose dependent on their body weight. Subjects who weigh t 40 kg 
will receive 40 mg eow of adalimumab, while subjects who weigh < 40 kg will receive 
20 mg eow of adalimumab.  Beginning from Week 8, subjects who have a disease flare 
may be switched to ew treatment at the same dose of adalimumab received while on eow 
treatment. 
Subjects who enroll into the study from open-label therapy in Study M06-806 will 
continue to receive the same dose they were receiving (i.e. 40 mg ew or 20 mg ew) at the 
Week 52 visit of the M06-806 study.  
Subjects who develop a flare while receiving ew open-label therapy or have a PCDAI 
score t 15 points when compared to their Baseline (the Week 52 visit of the M06-806 
study) PCDAI score (regardless of study visit), may be discontinued from the study at the 
discretion of the Investigator.  
The Baseline Visit date for this study should be 364 ± 7 days from Baseline Visit date of 
M06-806 study. All clinic visits for the subject should be scheduled on the same day of 
the as the Baseline visit for this study. For home administration of drug, subjects will be 
instructed to inject study drug on the same day of the week as their Baseline visit day.  
Subjects must inject within a +/-3 day window of this day. If the subject is out of the 
dosing window, the Medical Monitor should be contacted to determine the timing of the 
next dose.  The subject must record all dosing information on the subject dosing diary 
(Appendix O). 
5.5.5 
Blinding 
This is an open-label study. 

 
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5.5.6 
Treatment Compliance 
The Investigator or his/her designated representatives will administer study drug only to 
subjects enrolled in the study.  
In order to document compliance with the treatment regimen, all pre-filled syringes will 
be counted and documented in source documents and on the appropriate drug 
accountability form. 
5.5.7 
Drug Accountability 
The Investigator or designee will verify that study drug supplies are received intact, at the 
appropriate temperature, and in the correct amounts from the drug depot.  This will be 
documented by signing and dating the Proof of Receipt (POR) or similar document.  The 
original POR or similar document will be kept in the site files as a record of what was 
received.  An accurate running inventory of study drug will be kept by the site, and will 
include the kit number, lot number(s), the number of pre-filled syringes dispensed, and 
the date study drug was dispensed for each subject.  An overall accountability of the 
study drug will be performed and verified by the Clinical Research Associate (CRA) 
throughout the study and at the site close-out visit.  All unused pre-filled syringes will be 
inventoried and returned to an identified vendor for disposal as designated by Abbott 
Laboratories.  A copy of the Drug Accountability Form, in accordance with instructions 
provided by the CRA, will also be included in the Returned Goods for disposal shipment.  
A sample Drug Accountability Form is included in Appendix R.  A copy of the Drug 
Accountability Disposal Form, in accordance with instructions provided by the CRA, will 
also be included in the Pharmacy Binder provided to the site. 
All used (expelled) pre-filled syringes will be inventoried by the site and verified by the 
CRA.  The used syringes will be discarded on site, using appropriate biohazard 
precautions. CRAs and site staff will complete study drug accountability via study drug 
logs, source documents, verification of empty used syringe kit boxes, subject diaries and 
by visually counting the syringes in the sharp's container whenever possible.  Used 
sharp's containers should never be opened.  Each subject will be given their own sharps 

 
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disposal container to store expelled syringes. Sharps containers should be returned by the 
subject at each visit, for accountability and compliance purposes.  New containers will be 
issued to subjects as necessary.  Once the CRA has verified drug accountability at the 
site, the site staff and CRA will sign off that the expelled pre-filled syringes have been 
destroyed. 
5.6 
Discussion and Justification of Study Design 
5.6.1 
Discussion of Study Design and Choice of Control Groups 
The design of this clinical study was chosen to demonstrate adalimumab as an effective 
therapy for maintaining clinical response in pediatric subjects with CD and to gather 
long-term safety and tolerability data in this subject population. 
5.6.2 
Appropriateness of Measurements 
Standard statistical, clinical, and laboratory procedures will be utilized in this study. All 
efficacy measurements in this study are standard for assessing disease activity in pediatric 
subjects with Crohn's disease.  All clinical and laboratory procedures in this study are 
standard and generally accepted. 
5.6.3 
Suitability of Subject Population 
Pediatric subjects with CD who have participated in and successfully completed Protocol 
M06-806 through Week 52 and who meet all of the inclusion and none of the exclusion 
criteria are eligible for this study. 
5.6.4 
Selection of Doses in the Study 
The results of the pivotal adalimumab adult CD maintenance trial M02-404, in 
conjunction with results from adalimumab CD Study M02-433, support a maintenance 
dose of adalimumab 40 mg eow. Data also suggest that patients who lose response to 
adalimumab at 40 mg eow can be dose-escalated to 40 mg weekly with the potential of 
regaining clinical response. The proposed dosing regimen for Study M06-807 was 
developed using an analogous approach as that studied in the adult CD population. 

 
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Population pharmacokinetic modeling of serum adalimumab concentration data from 
pediatric subjects with JRA was used to identify doses to be evaluated in the current 
study in children with CD. A model based on the JRA population was chosen because the 
body weight range will closely parallel that in a juvenile CD population. Escalation to 
weekly dosing will provide average adalimumab concentrations at steady state about 
twice that observed with every other week dosing.  However, these concentrations are 
within the range of systemic exposures that were safely studied in adult subjects with CD. 
6.0 
Adverse Events 
The Investigator will monitor each subject for clinical and laboratory evidence of AEs on 
a routine basis throughout the study.  The Investigator will assess and record any AE in 
detail including the date of onset, description, severity, time course, duration and 
outcome, relationship of the AE to study drug, an event diagnosis, if known, and any 
action(s) taken.  For SAEs not considered "probably related" to study drug, the 
Investigator must provide another cause of event.  For AEs to be considered sporadic, the 
events must be of similar nature and severity.  AEs, whether in response to a query, 
observed by site personnel, or reported spontaneously by the subject will be recorded in 
source documentation and on the appropriate CRF page. 
All AEs will be followed to a satisfactory conclusion. 
6.1 
Definitions 
6.1.1 
Adverse Event 
An AE is defined as any untoward medical occurrence in a patient or clinical 
investigation subject administered a pharmaceutical product and which does not 
necessarily have a causal relationship with this treatment.  An AE can therefore be any 
unfavorable and unintended sign (including an abnormal laboratory finding), symptom, 
or disease temporally associated with the use of a medicinal (investigational) product, 
whether or not the event is considered causally related to the use of the product. 

 
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Such an event can result from use of the drug as stipulated in the protocol or labeling, as 
well as from accidental or intentional overdose, drug abuse, or drug withdrawal.  Any 
worsening of a pre-existing condition or illness is considered an AE.  Laboratory 
abnormalities and changes in vital signs are considered to be AEs only if they result in 
discontinuation from the study, necessitate therapeutic medical intervention, and/or if the 
Investigator considers them to be AEs. 
An elective surgery/procedure scheduled to occur during a study will not be considered 
an AE if the surgery/procedure is being performed for a pre-existing condition and the 
surgery/procedure has been pre-planned prior to study entry.  However, if the pre-existing 
condition deteriorates unexpectedly during the study (e.g., surgery performed earlier than 
planned), then the deterioration of the condition for which the elective surgery/procedure 
is being done will be considered an AE. 
6.1.2 
Serious Adverse Events 
If an AE meets any of the following criteria, it is to be reported to Abbott as an SAE 
within 24 hours of the site being made aware of the SAE.  Additionally, if follow-up 
information is received, it must also be reported to Abbott within 24 hours of being made 
aware of the information. 
Death of Subject 
An event that results in the death of a subject. 
Life-Threatening 
An event that, in the opinion of the Investigator, will have resulted in 
immediate fatality if medical intervention had not been taken.  This does 
not include an event that will have been fatal if it had occurred in a more 
severe form. 
Hospitalization 
An event that results in an admission to the hospital for any length of 
time.  This does not include an emergency room visit or admission to an 
outpatient facility. 
Prolongation of 
Hospitalization 
An event that occurs while the study subject is hospitalized and prolongs 
the subject's hospital stay. 
Congenital Anomaly 
An anomaly detected at or after birth, or any anomaly that results in fetal 
loss. 

 
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Persistent or Significant 
Disability/Incapacity 
An event that results in a condition that substantially interferes with the 
activities of daily living of a study subject.  Disability is not intended to 
include experiences of relatively minor medical significance such as 
headache, nausea, vomiting, diarrhea, influenza, and accidental trauma 
(e.g., sprained ankle). 
Important Medical Event 
Requiring Medical or 
Surgical Intervention to 
Prevent Serious Outcome 
An important medical event that may not be immediately life-threatening 
or result in death or hospitalization, but based on medical judgment may 
jeopardize the subject and may require medical or surgical intervention to 
prevent any of the outcomes listed above (i.e., death of subject, life 
threatening, hospitalization, prolongation of hospitalization, congenital 
anomaly, or persistent or significant disability/incapacity).  Examples of 
such events include allergic bronchospasm requiring intensive treatment 
in an emergency room or at home, blood dyscrasias or convulsions that do 
not result in inpatient hospitalization, or the development of drug 
dependency or drug abuse. 
Spontaneous Abortion 
Miscarriage experienced by study subject. 
Elective Abortion 
Elective abortion performed on study subject. 
 
6.2 
Adverse Event Severity 
The Investigator will use the following definitions to rate the severity of each AE: 
Mild
The AE is transient and easily tolerated by the subject. 
Moderate 
The AE causes the subject discomfort and interrupts the subject's usual 
activities. 
Severe
The AE causes considerable interference with the subject's usual activities 
and may be incapacitating or life threatening.   
 
6.3 
Relationship to Study Drug 
The Investigator will use the following definitions to assess the relationship of the AE to 
the use of study drug:   
Probably Related 
An adverse event has a strong temporal relationship to study drug or 
recurs on re-challenge and an other cause of event is unlikely or 
significantly less likely. 
Possibly Related 
An AE has a strong temporal relationship to the study drug and an other 
cause of event is equally or less likely compared to the potential 
relationship to study drug. 

 
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Probably Not Related 
An AE has little or no temporal relationship to the study drug and/or a 
more likely other cause of event exists. 
Not Related 
An AE is due to an underlying or concurrent illness or effect of another 
drug and is not related to the study drug (e.g., has no temporal 
relationship to study drug or has a much more likely other cause of event). 
 
If an Investigator's opinion of possibly, probably not, or not related to study drug for an 
SAE is given, an alternative cause of the event must be provided by the Investigator for 
the SAE. 
6.4 
Adverse Event Collection Period 
All AEs reported from the time of informed consent until 5 half-lives (70 days), 
following discontinuation of study drug administration have elapsed will be collected, 
whether elicited or spontaneously reported by the subject.  In addition, SAEs will be 
collected from the time the subject or parent/legal guardian has signed the study-specific 
informed consent. 
Adverse event information will be collected as shown in Figure 2. 
Figure 2. 
Adverse Event Collection 
SAEs and Non-serious AEs 
Elicited and/or Spontaneously Reported 
_ 
 
_ 
 
_ 
 
_ 
Consent 
Signed 
 
Study Drug 
Start 
 
Study Drug 
Stopped 
 
70 Days After 
Study Drug 
Stopped 
 
6.5 
Adverse Event Reporting 
In the event of an SAE, whether related to study drug or not, the Investigator will notify 
Abbott by faxing the appropriate SAE forms to one of the following people within 24 
hours of the site being made aware of the SAE.  Additionally, if follow-up information is 
received, it must also be reported to Abbott within 24 hours of being made aware of the 
information. 

 
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For sites located within North America:   
SAE Support Hotline 
 
For sites located outside North America:   
 

 
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For questions regarding SAEs, please contact:   
6.5.1 
Collection of Data Regarding Known Manifestations of the 
Disease Under Study 
Flare, of Crohn's disease events per study definition, are not required to be captured as 
AEs, but may be captured per Investigator discretion.  Additionally, CD pre-existing 
conditions will not be captured as AEs unless the condition has worsened or is considered 
clinically significant in the opinion of the Investigator. 
6.6 
Pregnancy 
Abbott Laboratories must be notified within 1 working day of a site's learning if a female 
subject becomes pregnant during the study or within 150 days of receiving the last dose 
of study drug (see Section 6.5 for contact information). 
Females who become pregnant during the study will be discontinued from study drug as 
described in Section 5.4.  Data regarding the outcome of any pregnancy occurring in a 
study subject will be collected.  Upon notification of a pregnancy Abbott will forward a 
form to the site, for the Investigator to complete and send back to Abbott.  A second form 
will also be sent approximately 9 months from the date of notification to collect 
information on the outcome of the pregnancy.  This form will also need to be completed 
and sent back to Abbott. 

 
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To monitor outcomes of pregnant women exposed to adalimumab, a pregnancy registry 
has been established for the United States.  Physicians in the United States are 
encouraged to register subjects by calling
 and/or provide this 
information to the subject. 
Pregnancy in a study subject is not considered an AE.  However, the medical outcome of 
an elective or a spontaneous abortion, stillbirth or congenital anomaly is considered a 
SAE, and must be reported to the sponsor with 24 hours of the site learning of the event. 
7.0 
Protocol Deviations 
The Investigator should not implement any deviation from the protocol without prior 
review and agreement by the Sponsor and in accordance with the IEC/IRB and local 
regulations, except when necessary to eliminate an immediate hazard to study subjects.  
When a deviation from the protocol is deemed necessary for an individual subject, the 
Investigator must contact the following Abbott representative:    
 
For purposes of this protocol, reportable deviations are defined as:   
● Subject entered into the study even though they did not satisfy entry criteria 
● Subject who developed withdrawal criteria during the study and was not 
withdrawn 

 
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● Subject who received wrong treatment or incorrect dose 
● Subject who received excluded concomitant treatment 
 
Such contact must be made as soon as possible to permit a review by Abbott to determine 
the impact of the deviation on the subject and/or the study.  Any significant protocol 
deviations affecting subject eligibility and/or safety must be reviewed and/or approved by 
the IEC/IRB and regulatory authorities, as applicable, prior to implementation. 
8.0 
Statistical Methods and Determination of Sample 
Size
8.1 
Statistical and Analytical Plans 
8.1.1 
Analyzable Population 
Efficacy analyses will be conducted in the intent-to-treat (ITT) population, which is 
defined as all subjects who received at least one dose of adalimumab in Study M06-807.  
In order to evaluate the impact of major protocol violations / deviations on the results of 
the study, additional analyses may be performed on the per-protocol population, which 
excludes all subjects with major protocol deviations. The safety population consists of all 
subjects who received at least one dose of adalimumab in Study M06-807. 
8.1.2 
Planned Methods of Statistical Analysis 
All statistical analyses are to be performed descriptively.  Descriptive summary statistics 
will be provided for the demographic and baseline characteristics, efficacy, and safety 
parameters. Continuous variables will be summarized using the number of observation, 
mean, standard deviation, 1st quartile, median, 3rd quartile, minimum, and maximum; 
whereas discrete variables will be summarized using count and percentages.  
8.1.2.1 
Demographics and Baseline Characteristics 
Summary statistics for the demographic and baseline characteristics will be computed 
based on the Week 52 values (from double-blind study M06-806). 

 
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8.1.2.2 
Primary Efficacy Analysis 
Summary statistics will be provided for each visit, based on observed data.  An additional 
summary will be provided for the last visit, using the last observation carried forward 
(LOCF).  That is, the subject's last non-missing, post-baseline value (i.e., post-Week 52 
M06-806 double-blind value) will be carried forward to the last visit. 
8.1.3 
Other Analyses 
The primary endpoint will be analyzed for the following subgroups in the ITT population. 
● Sex [Male, Female] 
● Age [< 13 years, t 13 years] 
● Ethnicity [White, Non-white] 
● Weight [< 40 kg, t 40 kg] 
● Prior infliximab use [No, Yes] 
● Baseline CRP [< 1.0 mg/dL, t 1.0 mg/dL] 
● Concomitant use of immunosuppressants and/or oral corticosteroids [No, Yes] 
 
8.1.4 
Safety Analyses 
Safety analyses will be based on the safety population.  Treatment-emergent, and 
post − treatment AEs will be summarized. An overview of treatment-emergent AEs 
including AEs of special interest, such as AEs leading to death and AEs leading to 
premature discontinuation, AEs by (MedDRA® version 10.0 or later) preferred term and 
system organ class, AEs by maximum relationship to study drug, and AEs by maximum 
severity will be summarized. Treatment-emergent AEs are defined as new events that 
begin either on or after the first dose of the study drug and within 70 days after the last 
dose of the study drug. 

 
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Adverse events with missing or unknown severity will be categorized as severe.  Adverse 
events with missing or unknown relationship to study drug will be categorized as 
probably related. 
Adverse events that are reported more than 70 days after last study injection will be 
excluded from the summaries; however, all reported AEs will be included in the AE data 
listings. 
For laboratory parameters, the normal range of the analyzing laboratory will be used and 
all values outside the normal range will be flagged and listed.  Additionally, descriptive 
statistics for the mean change from baseline to minimum (smallest) value, maximum 
(largest) value and final value during the study will be calculated for the continuous 
clinical laboratory parameters.  
Shift tables will be provided to cross-classify and tabulate subjects' value from baseline to 
final value by the presence of clinically significant laboratory results. Each subject's 
baseline value and final value will be flagged in reference to the normal range (low, 
normal, high) and also categorized as clinically non-significant (CTC grade < 3) or 
clinically significant (CTC grade t 3).  Further details will be provided in the SAP. 
8.1.5 
Interim Analysis 
There are no planned interim analyses. 
8.2 
Determination of Sample Size 
Subjects who successfully completed Study M06-806 through Week 52 may be eligible 
to participate in this study. It is expected that approximately 70% (130) of subjects from 
the M06-806 study will enroll in this study. 
8.3 
Randomization Methods 
All subjects will be centrally registered using an IVRS.  This is an open-label study; 
therefore, subjects will not be randomized before the study is initiated, the telephone 

 
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number and call in directions for the IVRS will be provided to each site.  Subjects will 
keep their subject number from the previous study (M06-806). 
9.0 
Ethics 
9.1 
Independent Ethics Committee (IEC) or Institutional Review 
Board (IRB) 
Good Clinical Practice (GCP) requires that the clinical protocol, any protocol 
amendments, the Investigator's Brochure, the informed consent and all other forms of 
subject information related to the study (e.g., advertisements used to recruit subjects) and 
any other necessary documents be reviewed by an IEC/IRB.  IEC/IRB approval of the 
protocol, informed consent and subject information and/or advertising, as relevant, will 
be obtained prior to the authorization of drug shipment to a study site. 
Any amendments to the protocol will require IEC/IRB approval prior to implementation 
of any changes made to the study design.  A list of the documents required prior to 
initiation of the study can be found in Appendix B. 
Any SAEs that meet the reporting criteria, as dictated by local regulations, will be 
reported to both responsible Ethics Committees and Regulatory Agencies, as required by 
local regulations.  During the conduct of the study, the Investigator should promptly 
provide written reports (e.g., ICH Expedited Reports, and any additional reports required 
by local regulations) to the IEC/IRB of any changes that affect the conduct of the study 
and/or increase the risk to subjects, unless otherwise submitted by the sponsor.  Written 
documentation of the submission to the IEC/IRB should also be provided to Abbott. 
9.2 
Ethical Conduct of the Study 
The study will be conducted in accordance with the protocol, International Conference on 
Harmonization (ICH) guidelines, applicable regulations and guidelines governing clinical 
trial conduct, and the ethical principles that have their origin in the Declaration of 
Helsinki.  Responsibilities of the clinical Investigator are specified in Appendix C. 

 
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9.3 
Subject Information and Consent 
Prior to any study-related procedures or discontinuation of any medications for this study, 
the Investigator or his/her representative will explain the nature of the study to the subject 
of legal age (in the state of residence) or to the parent or legal guardian (as appropriate)of 
a subject who is not of legal age and answer all questions regarding this study.  Subjects 
will be included in all discussions. 
The ICF will be reviewed, signed and dated by the subject of legal age (in the state of 
residence) or by the parent or legal guardian (as appropriate) of a subject who is not of 
legal age, and the person who administered the informed consent. If a subject who was 
not of legal age at the onset of this study becomes of legal age during the course of the 
study, an informed consent will need to be obtained at that time.  Additionally, in keeping 
with each institution's IRB requirements an Informed Assent will also be obtained from 
the subject, as required.   
A copy of the signed ICF and Assent Form will be given to the subject and the subject's 
parent/legal guardian.  The original signed ICF and Assent Form will be placed in the 
subject's medical record.  An entry must also be made in the subject's dated source 
documents to confirm that informed consent was obtained prior to any study-related 
procedures and that the subject received a signed copy. 
If an updated informed consent is approved after a subject has completed or terminated 
early from the study, but is within the 70-day follow-up window, the subject will not be 
required to return to the site for the purposes of signing the updated ICF.  The subject of 
legal age, parent or legal guardian (as appropriate) should be contacted regarding any 
changes and the documentation of the contact should be present in the subject's source.  

 
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10.0 
Source Documents and Case Report Form 
Completion
10.1 
Source Documents 
Source documents are defined as original documents, data and records.  This may include 
hospital records, clinical and office charts, laboratory data/information, subjects' diaries 
or evaluation checklists, pharmacy dispensing and other records, recorded data from 
automated instruments, microfiches, photographic negatives, microfilm or magnetic 
media, and/or x-rays.  Data collected during this study must be recorded on the 
appropriate source documents. 
The Investigator(s)/institution(s) will permit study-related monitoring, audits, IEC/IRB 
review, and regulatory inspection(s), providing direct access to source data documents. 
The IMPACT III questionnaire and the WPAI questionnaire will be recorded directly on 
the CRF(s) by the subject, parent or legal guardian (as appropriate) and these CRFs will 
be considered source data. 
10.2 
Case Report Forms 
Case report forms will be supplied by Abbott.  These forms will be used to transmit 
information collected during the study to Abbott and regulatory authorities, as applicable.  
Case report forms must be completed for each subject enrolled in this study.  All case 
report forms must be legible and completed in indelible black ballpoint ink.  Any 
necessary corrections are to be made by drawing a single line through the incorrect entry 
and writing in the revision.  All revisions must be initialed and dated by the Investigator 
or his/her representative.  Data are not to be obliterated by blacking out, using correction 
fluid or by erasing the original entry.  If the reason for the correction is not obvious, a 
brief explanation (e.g., transcription error) should accompany the change.  All 
information written on the case report forms must also be reflected in the subject source 
documents with the exception of the case report forms discussed above in Section 10.1. 

 
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The Principal Investigator will review the case report forms for completeness and 
accuracy and sign and date each set of case report forms where indicated.  The case 
report forms will be reviewed periodically for completeness, legibility and acceptability 
by Abbott personnel (or their representatives).  Abbott (or their representatives) will be 
allowed access to all source documents in order to verify case report form entries. 
Once the original case report form has been removed from the site, all changes must be 
made via the appropriate change form specified by Abbott.  The Principal Investigator 
will review the change form for completeness and accuracy and sign and date the change 
form where indicated. 
11.0 
Data Quality Assurance 
Prior to the initiation of the study, an Investigator's meeting will be held with Abbott 
personnel, the Investigators and their study coordinators, the CRO's project manager and 
the CRAs for the study. This meeting will include a detailed discussion of the protocol, 
performance of study procedures, CRF and Subject Diary completion, and specimen 
collection methods.  In addition to or instead of the Investigator's meeting, the study 
personnel at each site may be trained on the study procedures by a CRA at a study 
initiation visit and will be given a CRF completion workbook for reference. 
The CRAs will monitor at each site throughout the study.  One hundred percent (100%) 
source document review will be performed against entries on the CRF and a quality 
assurance check will be performed to ensure that the Investigator is complying with the 
protocol and regulations.  In addition, after CRFs are retrieved by the CRA, a review of 
the data will be conducted by a physician and a clinical review team at Abbott 
Laboratories. 
All data hand entered in the database will be verified by a double-key entry procedure at 
Abbott.  Any discrepancies will be reviewed against the hard copy CRF and corrected on-
line. After completion of the entry process, computer logic checks will be run to check 
for such items as inconsistent study dates and outlying laboratory values.  Any necessary 

 
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corrections will be made to the database and documented via addenda, queries, source 
data clarification form or audit trail.  A manual review of selected line listings will also 
be performed at the end of the study. 
Routine hematology, serum chemistry, and serology will be conducted using a central 
laboratory.  ESR analysis will be done at a local lab designated by the site. The data from 
these analyses will be electronically transferred from the central laboratory to the study 
database.  Urinalysis will be completed locally.  If a microscopic urinalysis is necessary, 
this testing will be conducted using the central laboratory.  A final review of all 
laboratory results will be conducted by a physician and clinical review team at 
Abbott Laboratories. 
Sites will provide Abbott (or designate) with laboratory certifications (CAP and CLIA), 
CV of local lab director, and reference ranges for each local lab used.  The full name, 
address, phone number, and fax number for each local lab will also be included. 
12.0 
Use of Information and Publication 
12.1 
Use of Information 
All information concerning adalimumab and Abbott Laboratories' operations, such as 
Abbott Laboratories' patent applications, formulas, manufacturing processes, basic 
scientific data, or formulation information, supplied by Abbott Laboratories and not 
previously published is considered confidential information. 
The information developed during the conduct of this clinical study is also considered 
confidential and will be used by Abbott Laboratories in connection with the development 
of adalimumab.  This information may be disclosed as deemed necessary by 
Abbott Laboratories to other clinical Investigators, other pharmaceutical companies, to 
the FDA,  and to other government agencies.  To allow for the use of the information 
derived from this clinical study and to ensure complete and thorough analysis, the 
Investigator is obligated to provide Abbott Laboratories with complete test results and all 

 
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data developed in this study and to provide direct access to source data/documents for 
study- related monitoring, audits, IEC/IRB review, and regulatory inspection. 
This confidential information shall remain the sole property of Abbott Laboratories, shall 
not be disclosed to others without the written consent of Abbott Laboratories, and shall 
not be used except in the performance of this study. 
The Investigator will maintain a confidential subject identification code list of all subjects 
enrolled in the study (by name and subject number).  This list will be maintained at the 
site and will not be retrieved by Abbott. 
12.2 
Publication 
All information concerning adalimumab and Abbott Laboratories' operations, such as 
patent application, formulas, manufacturing processes, basic scientific data or 
formulation information supplied by Abbott Laboratories which have not been previously 
published are considered confidential by Abbott Laboratories and shall remain the sole 
property of Abbott Laboratories.  The Investigator agrees to use this information only to 
perform this study and will not use it for other purposes including publications and 
presentations without Abbott Laboratories' written consent. 
It is understood by the Investigator that the information developed in the clinical trial will 
be used by Abbott Laboratories in connection with the development of adalimumab and, 
therefore, may be disclosed as required to other clinical Investigators, other 
pharmaceutical companies, to the U.S. FDA and to other regulatory agencies.  It is 
understood that there is an obligation to provide Abbott Laboratories with complete test 
results and all data resulting from this study and to provide direct access to source 
data/documents for study related monitoring, audits, IEC/IRB review, and regulatory 
inspection. 

 
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12.3 
Internet Sites 
Information regarding this study may be posted on various internet web sites and will 
maximally include study name, number, general population to be enrolled, entrance 
qualifications, brief description of the study, study objectives, doses, accruing 
Investigators (upon their approval) and number of subjects to be enrolled. 
13.0 
Completion of the Study 
The Investigator will conduct this study in compliance with the protocol, and will 
complete the study within the timeframe specified in the contract between the 
Investigator and Abbott.  Continuation of the study beyond this time must be mutually 
agreed upon in writing by both the Investigator and Abbott.  The Investigator will 
provide a summary of the study's outcome to the IEC/IRB following conclusion of the 
study, and will forward a copy of this summary to Abbott or their designee. 
Abbott may terminate this study prematurely, either in its entirety or at individual sites, 
for reasonable cause provided that written notice is submitted a reasonable time in 
advance of the intended termination.  The Investigator may also terminate the study at 
their site for reasonable cause, after providing written notice to Abbott a reasonable time 
in advance of the intended termination.  Advance notice is not required by either party if 
the study is stopped due to safety concerns.  If Abbott terminates the study for safety 
reasons, it will immediately notify the Investigator by telephone and subsequently 
provide written instructions for study termination. 
Abbott will select the signatory Investigator from the Investigators who participate in the 
study.  Selection criteria for this Investigator will include level of participation as well as 
significant knowledge of the clinical research, investigational drug and study protocol.  
The signatory Investigator for the study will review and sign the final study report in 
accordance with the European Agency for the Evaluation of Medicinal Products (EMEA) 
Guidance on Investigator's Signature for Study Reports. 

 
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The Investigator will retain all essential documents until at least two years after the last 
approval of a marketing application in an ICH region and until there are no pending or 
contemplated marketing applications in an ICH region or at least two years have elapsed 
since the formal discontinuation of clinical development of the investigational product.  It 
is the responsibility of the sponsor to inform the Investigator/institution as to when these 
documents no longer need to be retained. 
The end-of-study is defined as the date of the last subject's last scheduled visit or the 
actual date of follow-up contact, whichever is longer. 

 
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14.0 
Investigator's Agreement 
1. I have received and reviewed the Investigator Brochure for Humira. 
2. I have read this protocol and agree that the study is ethical. 
3. I agree to conduct the study as outlined and in accordance with all applicable 
regulations and guidelines. 
4. I agree to maintain the confidentiality of all information received or developed in 
connection with this protocol. 
 
 
 
 
Protocol Title: 
A Multi-center, Open-label Study of the Human Anti-TNF 
Monoclonal Antibody Adalimumab to Evaluate the Efficacy and the 
Long-term Safety and Tolerability of Repeated Administration of 
Adalimumab in Pediatric Subjects with Crohn's Disease Who Have 
Demonstrated a Clinical Response in the M06-806 Study 
Protocol Date: 
11 January 2008 
 
 
 
 
 
 
Signature of Principal Investigator 
 
Date 
 
 
 
Name of Principal Investigator (printed or typed) 
 
 
 
 

 
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15.0 
Reference List 
1. 
Hanauer SB, Sandborn W. Management of Crohn's disease in adults. Am J 
Gastroenterol 2001;96:635-43. 
2. 
Loftus Jr. EV.  Clinical epidemiology of inflammatory bowel disease: Incidence, 
prevalence, and environmental influences.  Gastroenterology 2004;126:1504-17. 
3. 
Seidman EG. Recent advances in the diagnosis and treatment of pediatric 
inflammatory bowel disease. Curr Gastroenterol Rep 2000;2:248-52. 
4. 
Auvin S, Molinie F, Gower-Rousseau C, Brazier F, Merle V, Grandbastient B, 
et al.  Incidence, clinical presentation and location at diagnosis of pediatric 
inflammatory bowel disease: a prospective population-based study in northern 
France (1988-1999). J Pediatr Gastroenterol Nutr 2005;41(1):49-55. 
5. 
Kugathasan S, Judd RH, Hoffmann RG, Heikenen J, Telega G, Khan F, et al.  
Epidemiologic and clinical characteristics of children with newly diagnosed 
inflammatory bowel disease in Wisconsin; a statewide population-based study. 
J Pediatr 2003;143(4):525-31. 
6. 
Cosgrove M, Al-Atia RF, Jenkins HR.  The epidemiology of pediatric 
inflammatory bowel disease. Arch Dis Child 1996;74:460-1. 
7. 
Hassan K, Cowan FJ, Jenkins HR. The incidence of childhood inflammatory 
bowel disease in Wales. Eur J Pediatr 2000;159:261-3. 
8. 
Barton JR, Gillon S, Ferguson A. Incidence of inflammatory bowel disease in 
Scottish children between 1968 and 1983; marginal fall in ulcerative colitis, three-
fold rise in Crohn's Disease. Gut 1989;30:618-22. 
9. 
Sawczenko A, Sandhu BK, Logan RFA, et al. Prospective survey of childhood 
inflammatory bowel disease in the British Isles. Lancet 2001;357:1093-4. 

 
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10. 
Olafsdottir EJ, Fluge G, Haug K. Chronic inflammatory bowel disease in children 
in western Norway. J Pediatr Gastroenterol Nutr 1989;8:454-8. 
11. 
Lindberg E, Lindquist B, Holmquist L, Hildebrand H.  Inflammatory bowel 
disease in children and adolescents in Sweden (1984-1995). J Pediatr 
Gastroenterol Nutr 2000;30:259-64. 
12. 
Hildebrand H, Finkel Y, Grahnquist L, Lindholm J, Ekbom A, Askling J. 
Changing pattern of paediatric inflammatory bowel disease in northern Stockholm 
1990-2001. Gut 2003;52:1432. 
13. 
Heyman MB, Kirshner BS, Gold BD, Ferry G, Baldassano R, Cohen SA, et al.  
Children with early onset inflammatory bowel disease (IBD): analysis of a 
pediatric IBD consortium registry. J Pediatr 2005;146(1):35-40. 
14. 
Lindberg E, Lindquist B, Holmquist L, Hildebrand H. Inflammatory bowel disease 
in children and adolescents in Sweden, 1984-1995. J Pediatr Gastroenterol Nutr 
2000;30(3):259-64. 
15. 
Sawczenko A, Sandhu BK. Presenting features of inflammatory bowel disease in 
Great Britain and Ireland. Arch Dis Child 2003;88:995-1000. 
16. 
Griffiths AM. Specificities of inflammatory bowel disease in childhood. Best Pract 
Res Clin Gastroenterol 2004;18(3):509-23. 
17. 
Griffiths AM, Nguyen P, Smith C, MacMillan JH, Sherman PM. Growth and 
clinical course of children with Crohn's disease. Gut 1993;34(7):939-43. 
18. 
Kanof ME, Lake AM, Bayless TM. Decreased height velocity in children and 
adolescents before the diagnosis of Crohn's disease. Gastroenterology 
1988;95(6):1523-7. 
19. 
Markowitz J, Grancher K, Rosa J, Aiges H, Daum F. Growth failure in pediatric 
inflammatory bowel disease. J Pediatr Gastroenterol Nutr 1993;16(4):373-80. 

 
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20. 
Kleinman RE, Baldassano RN, Caplan A, Griffiths AM, Heyman MB, 
Issenman RM, et al.  Nutrition support for pediatric patients with inflammatory 
bowel disease: a clinical report of the North America Society for Pediatric 
Gastroenterology, Hepatology and Nutrition. J Pediatr Gastroenterol Nutr 
2004;39(1):15-27. 
21. 
Gokhale R, Favus MJ, Karrison T, Sutton MM, Rich B, Kirshner BS. Bone 
mineral density assessment in children with inflammatory bowel disease. 
Gastroenterology 1998;114:902-11. 
22. 
Boot AM, Bouquet J, Krennings EP, de Muinck Keizer-Schrama SMPF. Bone 
mineral density and nutritional status in children with chronic inflammatory bowel 
disease. Gut 1998;42:188-94. 
23. 
Ballinger AB, Savage MO, Sanderson IR. Delayed puberty associated with 
Inflammatory bowel disease. Pediatr Res 2003;53:205-10. 
24. 
Harpavat M, Greenspan SL, O'Brien C, Chang C-C, Bowen A, Keljo DJ. Altered 
bone mass in children at diagnosis of Crohn's disease: a pilot study.  J Pediatr 
Gastroenterol Nutr 2005;40:295-300. 
25. 
Hyams JS, Wyzga N, Kreutzer DL, Justinich CJ, Gronowicz GA. Alterations in 
bone metabolism in children with inflammatory bowel disease: an in vitro study. 
J Pediatr Gastroenterol Nutr 1997;24(3):289-95. 
26. 
Hanauer S, Lukas M, MacIntosh D, Rutgeerts P, Sandborn W, Pollack P. A 
randomized, double-blind, placebo-controlled trial of the human anti-TNF-D 
monoclonal antibody adalimumab for the induction of remission in patients with 
moderate to severely active Crohn's disease. Gastroenterology 2004;127(1):332. 
27. 
Data on file at Abbott Laboratories. 
28. 
Abbott Study DE038, Data on file. 

 
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29. 
Humira® (adalimumab) [package insert].  North Chicago, IL: Abbott Laboratories:  
June 2006. 
30. 
Present DH, Rutgeerts P, Targan S, Hanauer SB, Mayer L, van Hogezand RA, 
et al. Infliximab for the treatment of fistulas in patients with Crohn's disease. 
N Eng J Med 1999;340(18):1398-405. 
31. 
Greulich and Pyle Radiographic Atlas of Skeletal Development of the Hand and 
Wrist:  June 1959. 
 
 

 
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Appendix A. 
List of Abbreviations and Definition of Terms 
Abbreviations
AE 
Adverse Event 
ALT 
Alanine Transaminase 
ANA 
Antinuclear antibody 
AST 
Aspartate transaminase 
BMI 
Body Mass Index 
BSAP 
Bone-specific alkaline phosphatase 
BUN 
Blood Urea Nitrogen 
CD 
Crohn's disease 
CDC 
Center for Disease Control 
CNS 
Central Nervous Systems 
CRA 
Clinical Research Associate 
CRF 
Case Report Form 
CRP 
C-Reactive Protein 
CTC 
Common Toxicity Criteria 
DMC 
Data Monitoring Committee 
DNA 
Deoxyribonucleic acid 
dsDNA 
Double Stranded DNA 
eow 
Every other week 
ESR 
Erythrocyte sedimentation rate 
ET 
Early Termination 
EU 
European Union 
ew 
Every week 
FDA 
U.S. Food and Drug Administration 
GCP 
Good Clinical Practice 
HCT 
Hematocrit 
HIV 
Human immunodeficiency virus 
ICH 
International Conference on Harmonization 
IEC 
Independent Ethics Committee 
IgG1 
Immunoglobulin 
ICF 
Informed Consent Form 
IRB 
Institutional Review Board 

 
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ITT 
Intent-to Treat 
IVRS 
Interactive Voice Response System 
JRA 
Juvenile Rheumatoid Arthritis 
LOCF 
Last Observation Carried Forward 
MTX 
Methotrexate 
Ntx  
N − telopeptide 
OL 
Open-Label 
PCDAI 
Pediatric Crohn's Disease Activity Index 
POR 
Proof of Receipt 
RA 
Rheumatoid Arthritis 
SAE 
Serious Adverse Event 
SAP 
Statistical analysis plan 
SC 
Subcutaneous 
SSC 
Sponsor Steering Committee 
TB 
Tuberculosis 
TNF 
Tumor Necrosis Factor 
TPN 
Total Parenteral Nutrition 
US 
United States 
WPAI 
Work Productivity and Activity Impairment Questionnaire 
WPAI-CD 
Work Productivity and Activity Impairment Questionnaire: Crohn's 
Disease 
 

 
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Appendix B. 
Documents Required Prior to Initiation of the Study 
As sponsor of a clinical trial, Abbott has an obligation to ensure that the study will be 
conducted by a qualified Investigator with sufficient resources (of time, personnel, and 
physical facilities) to conduct the study and to ensure that the Investigator understands 
and agrees to comply with applicable regulations, policies, and procedures.  Prior to the 
beginning of any clinical trial, the Investigator will be asked to provide the following 
documentation. 
1. 
A signed and dated Investigator's agreement page for the study. 
2. 
A signed and dated Form FDA 1572 certifying the Investigator's agreement to 
comply with the appropriate regulations governing the conduct of the study. 
3. 
A current curriculum vita of the Investigator.  If subinvestigators will participate in 
the study, curriculum vita for each. 
4. 
Requirements for the Independent Ethics Committee (IEC)/Institutional Review 
Board (IRB). 
● A copy of the signed and dated letter of approval of the IEC/IRB.  The letter 
must specify that both the protocol and informed consent form were approved 
(unless separate documentation that the informed consent was approved is 
provided). 
● A dated list containing the names and affiliations of the members of the 
IEC/IRB, or the institution's General Assurance Number. 
● If the Investigator and/or subinvestigator is a member of the IEC/IRB, a letter 
stating that he/she did not participate in the review or approval of the protocol 
or informed consent form. 
5. 
A specimen copy of the IEC/IRB-approved informed consent document to be used 
in the study. 

 
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6. 
A list of reference ranges of values for all laboratory tests specified by the protocol 
for all laboratories utilized. 
7. 
A copy of the laboratory(ies) certification(s) or the authorization number of the 
certification(s), the name of the certifying authority, and the period of certification. 
8. 
Financial Disclosure forms must be completed by each Investigator and all 
Subinvestigators identified on the Form FDA 1572.  A Financial Disclosure, 
EU consent, is required to be completed for each Investigator and/or 
Subinvestigator who is a resident of the European Union. 
 

 
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Appendix C. 
Responsibilities of the Clinical Investigator 
Clinical research studies sponsored by Abbott are subject to the regulations of the U.S. 
Food and Drug Administration (FDA).  The responsibilities imposed upon Investigators 
by the FDA are summarized in the "Statement of Investigator" (Form FDA 1572), which 
is a form letter addressed to the sponsor (Abbott), summarizing the Investigator's 
qualifications for the study and his/her willingness to follow FDA regulations with 
respect to the study. 
In signing a Form FDA 1572, the Investigator agrees to assume the following 
responsibilities:   
1. 
To conduct the study(ies) in accordance with the relevant, current protocol(s) and 
only make changes in a protocol after notifying Abbott, except when necessary to 
protect the safety, rights, or welfare of subjects. 
2. 
To personally conduct or supervise the described investigation(s). 
3. 
To inform any subjects, or any persons used as controls, that the drugs are being 
used for investigational purposes and to ensure that the requirements relating to 
obtaining informed consent in 21 CFR Part 50 and Independent Ethics Committee 
(IEC)/Institutional Review Board (IRB) review and approval in 21 CFR Part 56 
are met. 
4. 
To report to Abbott adverse experiences that occur in the course of the 
investigation(s) in accordance with 21 CFR 312.64. 
5. 
To read and understand the information in the Investigator's Brochure, including 
the potential risks and side effects of the drug. 
6. 
To ensure that all associates, colleagues, and employees assisting in the conduct of 
the study(ies) are informed about their obligations in meeting the above 
commitments. 

 
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7. 
To maintain adequate and accurate records of the conduct of the study and make 
those records available for inspection by representatives of Abbott, the IEC/IRB 
and/or the appropriate regulatory agency, and to retain all study-related documents 
until notification from Abbott.  The Investigator must notify Abbott when they are 
no longer able to retain the study related documents. 
8. 
To ensure that an IEC/IRB that complies with the requirements of 21 CFR Part 56 
will be responsible for the initial and continuing review and approval of the 
clinical investigation. 
9. 
To promptly report to the IEC/IRB all changes in the research activity and all 
unanticipated problems involving risks to human subjects or others (including 
submission of any Expedited Safety Reports received from Abbott to the 
IEC/IRB), and to make no changes in the research without IEC/IRB approval, 
except where necessary to eliminate apparent immediate hazards to human 
subjects. 
10. 
To comply with all other requirements regarding the obligations of clinical 
Investigators and all other pertinent requirements in 21 CFR Part 312. 
 

 
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Appendix D. 
CDC Treatment of Tuberculosis Infection (Preventive Therapy) 
When taken as prescribed, isoniazid therapy is highly effective in preventing latent 
tuberculosis (TB) infection from progressing to TB disease. 
Who should receive preventive therapy? 
The following persons should be given high priority for preventive therapy if they have 
positive skin test results, regardless of their age:   
1. 
Persons with 5 mm induration on their PPD who will receive a TNF inhibitor, 
2. 
Persons known to have or suspected of having HIV infection (5 mm or greater of 
induration), 
3. 
Persons who have been in close contact with someone who has infectious TB 
disease (5 mm or greater), 
4. 
Persons whose skin test results converted from negative to positive within the past 
2 years (10 mm or greater), 
5. 
Persons with abnormal chest radiographs who have never been treated for TB or 
who have been inadequately treated for TB (5 mm or greater), 
6. 
Persons who have injected drugs and who are HIV seronegative (10 mm or 
greater), and 
7. 
Persons with organ transplants and other immunosuppressed subjects (5mm or 
greater), 
8. 
Persons who have medical conditions that increase the risk for TB (10 mm or 
greater). These conditions include diabetes mellitus, gastrectomy, some 
hematologic and reticuloendothelial diseases, and end-stage renal disease, silicosis, 
and body weight that is 10% or more below ideal. 
 

 
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In addition, in the absence of any of the above risk factors, persons in the following 
groups should be evaluated for preventive therapy if their reaction to the tuberculin skin 
test is 10 mm or greater:   
1. 
Foreign-born persons from countries where TB is common; 
2. 
Medically underserved, low-income populations; and 
3. 
Residents of long-term care facilities. 
 
In addition, staff of facilities in which a person with infectious TB disease would pose a 
risk to large numbers of susceptible persons (e.g., health care facilities, correctional 
facilities, and nursing homes) should be evaluated for preventive therapy if they have a 
positive skin test result. 
Persons who have a positive reaction to the tuberculin skin test should not be given 
preventive therapy until the possibility of TB disease has been ruled out. In addition, 
persons who are being considered for preventive therapy should be evaluated for medical 
contraindications, such as:   
1. 
Previous isoniazid-associated hepatic injury, 
2. 
History of severe adverse reactions to isoniazid, and; 
3. 
Acute or active liver disease. 
 
Also, special precautions should be taken for some persons who are receiving preventive 
therapy. 

 
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Precautions are indicated for:   
1. 
Persons who are older than 35, 
2. 
Persons who abuse alcohol, 
3. 
Pregnant women, 
4. 
Persons with chronic liver disease, 
5. 
Persons with peripheral neuropathy, and 
6. 
Persons who in the past have stopped using isoniazid because of adverse effects. 
 
Regimens for Preventive Therapy
The usual preventive therapy regimen is 9 months of daily isoniazid, in a dosage of 
5 milligrams per kilogram of body weight. The maximum daily dose is 300 milligrams. 
HIV-infected persons should receive 9 months of preventive therapy.  An alternative 
regimen for adults is 4 months of rifampin. 
For persons with a strain of M. tuberculosis that is resistant to isoniazid but susceptible to 
rifampin, CDC recommends the use of rifampin alone for 4 months for preventive 
therapy. 
Adverse Reactions
The major toxic effect of isoniazid is hepatitis. The risk for hepatitis increases with 
alcohol consumption. Isoniazid may also cause peripheral neuropathy. Persons at risk for 
neuropathy—for example, persons who abuse alcohol and persons with diabetes—should 
be given pyridoxine, or vitamin B-6, in conjunction with isoniazid therapy. 
Subjects should be educated about the signs and symptoms of toxicity to isoniazid, and 
they should be monitored monthly by appropriately trained personnel. No more than a 

 
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1 month supply of medicine should be dispensed at any visit. If signs or symptoms of 
toxicity appear, isoniazid should be stopped immediately, and the subject reevaluated. 
Subjects should not be given isoniazid preventive therapy if they cannot be monitored 
monthly. 

 
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Appendix E. 
Non-Drug Materials Provided to the Study Site(s) 
Study sites will receive the following supplies prior to or during the study:   
Tote Bags 
Cooler 
Sharps Containers 
Ice Packs 
CDAI subject diary 
Dosing Diaries 
Subject Medication Log 
Self Injection Instructions 

 
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Appendix F. 
Pediatric Crohn's Disease Activity Index (PCDAI) 
1. Abdominal pain rating 
 
- None 
 
- Mild - Brief, does not interfere with activities 
 
- Moderate/severe-Daily, longer lasting, affects activities, nocturnal 
 
= 0 p 
= 5 p 
= 10 p 
Score
2. Stools (per day) 
 
- 0–1 liquid stools, no blood 
 
- Up to 2 semi-formed with small blood, or 2–5 liquid 
 
- Gross bleeding, or t 6 liquid, or nocturnal diarrhea 
 
= 0 p 
= 5 p 
= 10 p 
3. Patient Functioning, General Well-Being 
 
- No limitation of activities, well 
 
- Occasional difficulty in maintaining age appropriate activities, below par 
 
- Frequent limitation of activity, very poor 
 
= 0 p 
= 5 p 
= 10 p 
LABORATORY 
Score 
4. HCT: Male and female  <10 years: 
 
 
t33 
= 0 p 
 
 
28-32 
= 2.5 p 
 
 
<28 
= 5 p 
 
Male 11–14 years: 
 
 
t35 
= 0 p 
 
 
30-34 
= 2.5 p 
 
 
<30 
= 5 p 
 
Female 11–19 years: t34 
= 0 p 
 
 
29-33 
= 2.5 p 
 
 
<29 
= 5 p 
 
Male 15–19 years: 
t37 
= 0 p 
 
 
32-36 
= 2.5 p 
 
 
<32 
= 5 p 
5. 
ESR (mm/hr) 
<20 
= 0 p 
 
 
20-50 
= 2.5 p 
 
 
>50 
= 5 p 
6. 
Albumin (g/dL) 
t3.5 
= 0 p 
 
 
3.1-3.4 
= 5 p 
 
 
d3.0 
= 10 p 

 
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EXAMINATION 
Score 
7. 
Weight 
- Weight gain or voluntary weight stable/loss 
 
 
- Involuntary weight stable, weight loss 1–9% 
 
 
- Weight loss t10% 
= 0 p 
= 5 p 
= 10 p 
8. 
Height 
 
 
 
 
 
 
 
 
Height velocity t -1SD 
 
 
 
Height velocity < -1SD, > -2SD 
 
 
 
Height velocity d -2SD 
 
= 0 p 
= 5 p 
= 10 p 
9. 
Abdomen 
- No tenderness, no mass 
 
 
- Tenderness, or mass without tenderness 
 
 
- Tenderness, involuntary guarding, definite mass 
= 0 p 
= 5 p 
= 10 p 
10. Perirectal disease 
- None, asymptomatic tags 
 
 
- 1–2 indolent fistula, scant drainage, no tenderness 
 
 
- Active fistula, drainage, tenderness, or abscess 
= 0 p 
= 5 p 
= 10 p 
11. Extra-intestinal Manifestations 
 
(Fever t38.5 for 3 days over past week, definite arthritis, uveitis, E. nodosum, 
P. gangrenosum) 
 
- None 
 
- One 
 
- tTwo 
 
 
= 0 p 
= 5 p 
= 10 p 
TOTAL SCORE  
Pediatric Crohn's Disease Activity Index (PCDAI) 
 
 

 
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Appendix G. 
PCDAI User's Guide and Guideline for Reference Weight and 
Reference Height 
This guide is intended to help nurse coordinators and physicians complete the PCDAI in 
order to assess disease activity in children with Crohn's disease participating in clinical 
trials. 
History
All calculations are based upon a one-week (7 day) history recall of symptoms.  The 
history recall should be solicited from the subject and/or caregiver. 
Item 1.  Abdominal pain 
The descriptions in the PCDAI of "mild" and "moderate/severe" should be used to guide 
in scoring the pain. Note that duration, effect on activities, and nocturnal occurrence 
separate moderate/severe from mild.  If pain varies in severity during the week, subject 
should be scored according to the most severe pain. However, mild pain should be 
present on at least two days to score 5 points rather than 0 points. 
Item 2.  Stools 
The intent is to score the stool pattern during the preceding week. 
To facilitate scoring, first categorize the subject as having blood in the stool or not. 
If there is no blood in the stool, score as follows:   
Formed stools or up to 1 loose stool daily = 0 
2-5 liquid or very loose stools on 1 or more days = 5 
6 or more liquid or very loose stools on 1 or more days or any nocturnal diarrhea = 10 

 
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If blood is present in the stool on any day during the past week, score as follows:   
Small amounts of blood in stool (on toilet paper or small spots in stool, etc.) = 5 
Any gross bleeding (large amounts on stool or colors the water in the toilet, etc.) = 10 
Item 3.  Subject functioning, general well-being 
If there is variation during the week, subject should be scored according to the most 
significant limitation of activity, even if it occurs during only one day of the week, as 
long as it is likely due to Crohn's disease and not to an intercurrent illness. 
Item 4.  Hematocrit 
Hematocrit values should be rounded to a whole number prior to completing the 
calculation.   Numbers that fall between the range of 0.1-0.4 must be rounded down.   
Numbers that fall between the range of 0.5-0.9 must be rounded up. 
Physical Examination
Item 7.  Weight (The intent is to assess the ability to normally maintain or gain weight) 
Reference weight to be used for calculation of weight gain/loss during the study: 
From Baseline to Week 104: use weight from previous visit 
Voluntary weight stable/loss means subject maintaining or losing weight on purpose. 
Involuntary weight stable means subject wants to gain weight but cannot. 
To calculate percentage weight loss use formula:   
Weight from previous visit – Current weight X 100 = % weight loss 
 
Weight from previous visit 

 
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Item 8.  Height 
Reference height for calculation of height velocity 
● From Baseline to Week 24, use height from 6 months prior to Baseline 
● From Week 24 to Week 52, use height from Baseline visit 
● From Week 52 to Week 72, use height from Week 24 
● From post Week 72, use height from Week 52  
 
The intent is to assess the normalcy vs. impairment of the subject's recent linear growth.  
Note that post-pubertal subjects will score 0 points.  For subjects still growing, there are 
two options for scoring.  Method (a) is preferred.  Method (b) to be used if data required 
for (a) are unavailable. 
1. 
Height velocity (cm/year), the most sensitive parameter, should be calculated as 
below: 
Present height –  Appropriate height measurement (from above)  x  12  = Height velocity (cm/year) 
  
        Interval (months) between heights 
Using height velocity chart below, determine centile for height velocity. 
2. 
Scoring for the PCDAI:   
a. Velocity less than "Minus 2 SD" scores 10 points. 
b. Velocity between "Minus 2 SD" and "Minus 1 SD" scores 5 points. 
c. Velocity greater than "Minus 1 SD" scores zero points. 
 
* 
Please note that subjects should score zero points if a subject is a female above 14.5 years of age or a 
male above 17.5 years of age. 
 

 
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Height Velocity Reference Values for Calculating the PCDAI (Males) 
 
Height Velocity in cm per year (Males) 
Age (years) 
Minus 2SD 
Minus 1SD 
Mean 
2.5 
5.7 
7.0 
8.3 
3 
5.4 
6.6 
7.8 
3.5 
5.1 
6.3 
7.4 
4 
4.9 
6.0 
7.1 
4.5 
4.7 
5.8 
6.8 
5 
4.6 
5.6 
6.6 
5.5 
4.5 
5.4 
6.4 
6 
4.3 
5.3 
6.2 
6.5 
4.2 
5.1 
6.0 
7 
4.2 
5.0 
5.9 
7.5 
4.1 
4.9 
5.8 
8 
3.9 
4.8 
5.6 
8.5 
3.8 
4.6 
5.4 
9 
3.8 
4.5 
5.3 
9.5 
3.7 
4.5 
5.2 
10 
3.7 
4.4 
5.1 
10.5 
3.7 
4.4 
5.1 
11 
3.7 
4.4 
5.2 
11.5 
3.8 
4.6 
5.3 
12 
4.0 
4.9 
5.7 
12.5 
4.8 
5.8 
6.7 
13 
6.2 
7.4 
8.6 
13.5 
7.1 
8.3 
9.5 
14 
6.1 
7.2 
8.4 
14.5 
4.1 
5.3 
6.5 
15 
2.4 
3.6 
4.7 
15.5 
1.2 
2.3 
3.3 
16 
0.4 
1.3 
2.2 
16.5 
0.1 
0.7 
1.5 
17 
0.1 
0.4 
0.9 
17.5 
0.1 
0.1 
0.5 
 

 
Adalimumab 
M06-807 Protocol  
EudraCT # 2007-006494-90 
 
 
80 
Height Velocity Reference Values for Calculating the PCDAI (Females) 
 
Height Velocity in cm per year (Females) 
Age (years) 
Minus 2SD 
Minus 1SD 
Mean 
2.5 
5.9 
7.3 
8.6 
3 
5.5 
6.9 
8.1 
3.5 
5.2 
6.4 
7.6 
4 
4.9 
6.1 
7.2 
4.5 
4.7 
5.8 
6.8 
5 
4.6 
5.6 
6.6 
5.5 
4.5 
5.5 
6.4 
6 
4.4 
5.3 
6.2 
6.5 
4.3 
5.2 
6.1 
7 
4.3 
5.2 
6.0 
7.5 
4.3 
5.1 
5.9 
8 
4.2 
5.0 
5.8 
8.5 
4.2 
4.9 
5.7 
9 
4.2 
5.0 
5.8 
9.5 
4.3 
5.0 
5.8 
10 
4.4 
5.3 
6.2 
10.5 
4.7 
5.7 
6.8 
11 
5.7 
6.6 
7.7 
11.5 
6.1 
7.2 
8.3 
12 
5.2 
6.3 
7.3 
12.5 
3.6 
4.8 
5.9 
13 
2.4 
3.3 
4.3 
13.5 
1.3 
2.2 
2.9 
14 
0.4 
1.1 
1.8 
14.5 
0.0 
0.5 
1.0 
 

 
Adalimumab 
M06-807 Protocol  
EudraCT # 2007-006494-90 
 
 
81 
Appendix H. 
Crohn's Disease Activity Index (CDAI) 
 
 
 
Factor 
Subtotal 
1. Number of liquid or very soft stools
(Record the frequency per day) 
         __+___+___+___+___+___+___=___ 
Days: 1     2      3      4 
5      6 
  7   Sum 
X 
2 
 
2.  Abdominal pain rating: 
0=none, 1=mild, 2=moderate, 
3=severe 
          __+___+___+___+___+___+___=___ 
Days: 1     2      3      4 
5      6 
  7   Sum 
X 
5 
 
3. General well-being: 
0=generally well, 1=slightly 
underpar, 2=poor, 3=very poor, 
4=terrible 
         __+___+___+___+___+___+___=___ 
Days: 1     2      3      4 
5      6 
  7   Sum 
X 
7 
 
4. Number of 6 listed categories the 
subject now has: 
Check all items that apply: 
□  Arthritis/arthralgia 
□  Iritis/uveitis 
□  Erythema nodosum/  
 pyoderma gangrenosum/ 
 aphthous stomatitis 
□  Fissure, abscess and/or anal 
fistula (draining/non-draining) 
□  Other cutaneous fistula 
(draining/non-draining) fistula 
□  Fever over 100°F (37.8°C) during 
past week 
 
 
 
 
 
 
  
________ 
 
 
 
Record "0" if no categories checked 
X 
20 
 
5.   Taking Lomotil / Imodium / 
Loperamide /opiates for diarrhea  
0=no, 1=yes 
________ X 
30 
 
6.   Abdominal mass 
0=none, 2=questionable, 5=defined 
________ X 
10 
 
7.   Hematocrit: ______ 
Male: 
(47 - hematocrit) = 
Female: (42 - hematocrit) = Subtotal ______ 
If hematocrit > normal, enter "0" 
X 
6 
 
8.   Body weight: __  __  __ . __ (kg) 
Ideal weight for height: 
__  __  __ . __ (kg) 
100 x [1 - (Body wt/Ideal wt)] =  
Percent below ideal weight: ______ 
If body wt > ideal wt, enter "0" 
X 
1 
 
 
 
 
Total 
 
* 
Ideal weight is obtained from CDC growth charts.  The subtotal of box 8 should be rounded to a whole number.  
Numbers that fall between the range of .1-.4 must be rounded down.   Numbers that fall between the range of .5-.9 
must be rounded up. 
* 
Hematocrit values should be rounded to a whole number prior to completing the calculation in box 7 of the CDAI.   
Numbers that fall between the range of .1-.4 must be rounded down.   Numbers that fall between the range of .5-.9 
must be rounded up. 

 
Adalimumab 
M06-807 Protocol  
EudraCT # 2007-006494-90 
 
 
82 
Appendix I. 
Subject CDAI Diary 
Crohn's Disease Activity Index 
Subject Diary Card 
Enter all values legibly using a black 
ballpoint pen. 
Add item requested for each day. 
Day 
Date___ 
Day 
Date___ 
Day 
Date___ 
Day 
Date___ 
Day 
Date___ 
Day 
Date___ 
Day 
Date___ 
Number (total) of liquid or very soft 
stools per day. 
 
 
 
 
 
 
 
Daily abdominal pain rating. 
(0=none, 1=mild, 2=moderate, 3=severe) 
 
 
 
 
 
 
 
Daily rating of general well being. 
(0=well, 1=slightly below par, 2=poor, 
3=very poor, 4=terrible) 
 
 
 
 
 
 
 
Subject Initials:___________ 
Subject's Signature:__________________________ 
 
Investigator or Designee's Signature:______________________ 

 
Adalimumab 
M06-807 Protocol  
EudraCT # 2007-006494-90 
 
 
84 
Question 1. 
How much has your stomach been hurting you in the past two weeks? 
□ 
□ 
□ 
□ 
□ 
Not at all 
 Hardly hurting 
at all 
Hurting 
somewhat  
Hurting 
quite a bit 
Hurting 
very much 
 
Question 2.
Taking medicines or tablets bothers you 
□ 
□ 
□ 
□ 
□ 
Not at all 
 Hardly bothers 
at all 
Bothers 
somewhat  
Bothers  
quite a bit 
Bothers 
very much 
 
Question 3. 
How often has your inflammatory bowel disease prevented you from 
eating what you want in the past two weeks? 
□ 
□ 
□ 
□ 
□ 
Never 
 Rarely 
Sometimes 
Often 
Very often 
 
Question 4. 
How often have you been worrying about having a flare-up (increase of 
symptoms) in the last two weeks? 
□ 
□ 
□ 
□ 
□ 
Never 
 Rarely 
Sometimes 
Often 
Very often 
 
Question 5.
How much does it bother you that you have an illness that does not just go 
away? 
□ 
□ 
□ 
□ 
□ 
Not at all 
 Hardly bothers 
at all 
Bothers 
somewhat  
Bothers quite a 
bit 
Bothers very 
much 
 
Question 6.
How much energy did you have during the past two weeks? 
□ 
□ 
□ 
□ 
□ 
Very much 
energy 
Quite a bit of 
energy 
Some energy 
 A little energy 
No energy at 
all  

 
Adalimumab 
M06-807 Protocol  
EudraCT # 2007-006494-90 
 
 
85 
Question 7. 
How do you feel about your weight? 
□ 
□ 
□ 
□ 
□ 
I feel great 
about my 
weight 
I feel good 
about my 
weight 
I don't feel 
good or bad 
about my 
weight 
I feel bad about 
my weight 
I feel awful 
about my 
weight 
 
Question 8. 
How has your inflammatory bowel disease affected your family? 
□ 
□ 
□ 
□ 
□ 
The effect has 
been great 
The effect has 
been good 
It has not 
affected our 
family 
The effect has 
been bad 
The effect has 
been awful 
 
Question 9. 
How often did you have to miss out on certain things (hobbies, play, 
parties) because of your inflammatory bowel disease in the past two weeks? 
□ 
□ 
□ 
□ 
□ 
Never 
Rarely 
Sometimes 
Often 
Very often 
 
Question 10.
How often have you been bothered by diarrhea (loose or frequent bowel 
movements) in the past two weeks? 
□ 
□ 
□ 
□ 
□ 
Never 
Rarely 
Sometimes 
Often 
Very often 
 
Question 11. How often do you worry about health problems you might have in the 
future? 
□ 
□ 
□ 
□ 
□ 
Never 
Rarely 
Sometimes 
Often 
Very often 
 

 
Adalimumab 
M06-807 Protocol  
EudraCT # 2007-006494-90 
 
 
86 
Question 12. How often do you think it is unfair that you have inflammatory bowel 
disease? 
□ 
□ 
□ 
□ 
□ 
Never 
Rarely 
Sometimes 
Often 
Very often 
 
Question 13.
During the past two weeks, were you ever angry that you have 
inflammatory bowel disease? 
□ 
□ 
□ 
□ 
□ 
Never 
Rarely 
Sometimes 
Often 
Very often 
 
Question 14. Do you think too many rules or limits are placed on you because of your 
inflammatory bowel disease? 
□ 
□ 
□ 
□ 
□ 
Never 
Rarely 
Sometimes 
Often 
Very often 
 
Question 15. How do you feel about the way you look? 
□ 
□ 
□ 
□ 
□ 
I think I look 
great 
I think I look 
good 
I don't think I 
look good or 
bad 
I think I look 
bad 
I think I look 
awful 
 
Question 16. Are you embarrassed because of your bowel condition? 
□ 
□ 
□ 
□ 
□ 
Not at all 
 Hardly 
embarrassed at 
all 
Embarrassed 
somewhat  
Embarrassed 
quite a bit 
Embarrassed 
very much 
 
Question 17. Did you have fun during the past two weeks? 
□ 
□ 
□ 
□ 
□ 
Very often 
Often 
Sometimes 
Rarely 
Never 

 
Adalimumab 
M06-807 Protocol  
EudraCT # 2007-006494-90 
 
 
87 
Question 18. Is it harder to make friends because of your inflammatory bowel disease? 
□ 
□ 
□ 
□ 
□ 
Not at all 
harder 
 A little harder 
Quite a bit 
harder 
Much harder 
Very much 
harder 
 
Question 19.  How often do you worry about your stool (bowel movement) containing 
blood? 
□ 
□ 
□ 
□ 
□ 
Never 
Rarely 
Sometimes 
Often 
Very often 
 
Question 20. Are you worried you cannot go out on a date or have a boyfriend or 
girlfriend because of your inflammatory bowel disease? 
□ 
□ 
□ 
□ 
□ 
Not at all 
worried 
 Hardly 
worried at all 
Worried 
somewhat  
Worried quite a 
bit 
Worried very 
much 
 
Question 21. How often did you feel sick to your stomach in the past two weeks? 
□ 
□ 
□ 
□ 
□ 
Never 
Rarely 
Sometimes 
Often 
Very often 
 
Question 22. How do you feel about the tests you have to go through? 
□ 
□ 
□ 
□ 
□ 
I do not mind 
them at all 
I mind them a 
tiny bit 
I mind them a 
little 
I mind them a 
lot 
I hate them 
Question 23. Do other children bully you or leave you out of things because of your 
inflammatory bowel disease or its treatment? 
□ 
□ 
□ 
□ 
□ 
Never 
Rarely 
Sometimes 
Often 
Very often 

 
Adalimumab 
M06-807 Protocol  
EudraCT # 2007-006494-90 
 
 
88 
Question 24. How often do you worry about having an operation? 
□ 
□ 
□ 
□ 
□ 
Never 
Rarely 
Sometimes 
Often 
Very often 
 
Question 25. In the past two weeks how often were you afraid you may have an 
accident or not get to the toilet in time? 
□ 
□ 
□ 
□ 
□ 
Never 
Rarely 
Sometimes 
Often 
Very often 
 
Question 26. Do you try to keep your inflammatory bowel disease a secret from other 
people? 
□ 
□ 
□ 
□ 
□ 
No, I do not try 
at all 
I don't try 
much 
I try a little 
I try hard 
Yes, I try very 
hard 
 
Question 27. Does your inflammatory bowel disease make it difficult to travel or go on 
a holiday? 
□ 
□ 
□ 
□ 
□ 
No, not 
difficult 
A little difficult
Quite difficult 
Very difficult 
Yes, extremely 
difficult 
 
Question 28.  How did you feel during the past two weeks? 
□ 
□ 
□ 
□ 
□ 
Great 
Good 
Not good or 
bad 
Bad  
Awful 
 
Question 29. Are you happy with your life? 
□ 
□ 
□ 
□ 
□ 
Yes, very 
happy 
Happy 
Not happy or 
unhappy 
Unhappy 
Very unhappy 

 
Adalimumab 
M06-807 Protocol  
EudraCT # 2007-006494-90 
 
 
89 
Question 30. Do you feel there is someone you can talk to about your inflammatory 
bowel disease? 
□ 
□ 
□ 
□ 
□ 
Always  
Often  
Sometimes  
Rarely 
Never 
 
Question 31. How often did you have to pass gas in the past two weeks? 
□ 
□ 
□ 
□ 
□ 
Never 
Rarely 
Sometimes 
Often 
Very often 
 
Question 32. How tired have you felt in the past two weeks? 
□ 
□ 
□ 
□ 
□ 
Not at all tired 
 A little tired 
Quite tired 
Tired  
Very tired 
 
Question 33. How do you feel about your height? 
□ 
□ 
□ 
□ 
□ 
I feel great 
about my 
height 
I feel good 
about my 
height 
I don't feel 
good or bad 
about my 
height 
I feel bad about 
my height 
I feel awful 
about my 
height 
 
Question 34. Does your inflammatory bowel disease get in the way of playing sports the 
way you would like to? 
□ 
□ 
□ 
□ 
□ 
Never 
Rarely 
Sometimes 
Often 
Always 
 
Question 35. In the past two weeks how often were you able to go to school? (If you are 
in the middle of a school break or the summer holidays, answer as if school was on) 
□ 
□ 
□ 
□ 
□ 
Always  
Most days  
Half the days 
A few days 
Never 
 

 
Adalimumab 
M06-807 Protocol  
EudraCT # 2007-006494-90 
 
 
90 
End of questionnaire 
This completes the questionnaire. Do you have anything else to add which you feel is 
important about having inflammatory bowel disease, or do you have any other 
remarks? Please write them below. 
 
_________________________________________________________ 
_________________________________________________________ 
_________________________________________________________ 

 
Adalimumab 
M06-807 Protocol  
EudraCT # 2007-006494-90 
 
 
91 
Appendix K. 
Excluded Medications 
Cyclosporine 
Tacrolimus 
Therapeutic enemas and suppositories (not including those done in conjunction with 
routine colonoscopy) 
Live vaccines 
The combination of budesonide and prednisone (or equivalent) 
Infliximab 
Mycophenolate mofetil (MMF or CellCept®) 
Growth Hormone 
Kineret® (anakinra) 
Tysabri (natalizumab) 
Orencia (abatacept) 
Concurrent biologic therapy 
Any investigational agent 
Any previous anti-TNF medication except infliximab before the study (including 
adalimumab). 
 

 
Adalimumab 
M06-807 Protocol  
EudraCT # 2007-006494-90 
 
 
92 
Appendix L. 
Day 70 Phone Call 
Site Name / Number: ________ 
Subject Number:________ 
Subject Initials:________ 
Please contact all Subjects 70 days following drug discontinuation. 
 
 
 
Date of Call: ____________ 
 
 
□     Lost to Follow-Up (Please check this box if subject was not willing to provide any follow-up 
information or you were unable to speak to the subject following at least one attempt). 
 
 
□      No Events Reported 
 
List any Adverse Events (AE) and/or Serious Adverse Events (SAE) that occurred since the subject was 
last seen in clinic for this study.  Please document all adverse events on a 500 AE CRF to be submitted to 
data management.  (Please report all SAEs to Abbott within 24 hours of being made aware of the event.  
Follow-up information must also be reported within 24 hours of being made aware of the information.). 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
If events are listed above, your monitor will review and retrieve the appropriate CRF pages during 
their next visit.  Please fax this form to Abbott at 
 

 
Adalimumab 
M06-807 Protocol  
EudraCT # 2007-006494-90 
 
 
93 
Appendix M. 
Unscheduled Outpatient Visits, Emergency Room Visits and 
Hospitalizations 
1. 
Since the last study visit has the subject had any physician/health care visits for 
their Crohn's disease other than the protocol required visits? 
Yes ___ 
No  ___ 
If yes provide the following: 
I. 
Since the last visit, has the subject been seen by a physician for their Crohn's 
Disease? 
YES:_____ 
NO:_____ 
If YES, how many times:_______ 
 
 
II. Since the last visit, has the subject been seen in the Emergency Room for their 
Crohn's Disease? 
YES:_____ 
NO:______ 
If YES, how many times:_____ 
III. Since the last visit, has the subject been admitted to the hospital due to their 
Crohn's Disease? 
YES:_____ 
NO:______ 
If YES, how many times:_____ 
If YES, please indicate the total number of days in the hospital:_____ 
 
 

 
Adalimumab 
M06-807 Protocol  
EudraCT # 2007-006494-90 
 
 
94 
Appendix N. 
Subject Medication Log 
Instructions:  As a participant in this study, it is also important to keep a record of all mediations you take (new and old) throughout the study.  Please take this 
sheet home with you and write down any medications you take during the study.  It will be VERY important that you bring this sheet back to your doctor's office 
and speak with your doctor about everything you have written down. 
 
Name of Medication 
Date you took
first dose 
Date you took
last dose 
What dose of medicine 
did you take? 
How often did you 
take the medicine? 
Why did you take the 
medicine?
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
Adalimumab 
M06-807 Protocol  
EudraCT # 2007-006494-90 
 
 
99 
Week 25 - Week 36 
Subject Initials: __________ 
Subject Study #: ___________ 
 
Date 
day/mm/yr 
Day or 
Week # 
Time of Study 
Drug 
Administration 
Dose (mL) 
Administered
Kit #
Initials of Person 
Administering
Study Medication 
Comments 
18/MAR/04 EXAMPLE 
9:35 am 
0.8 
 
MM 
none 
 
Week 25 
 
 
 
 
 
 
Week 26 
 
 
 
 
 
 
Week 27 
 
 
 
 
 
 
Week 28 
 
 
 
 
 
 
Week 29 
 
 
 
 
 
 
Week 30 
 
 
 
 
 
 
Week 31 
 
 
 
 
 
 
Week 32 
 
 
 
 
 
 
Week 33 
 
 
 
 
 
 
Week 34 
 
 
 
 
 
 
Week 35 
 
 
 
 
 
 
Week 36 
 
 
 
 
 
 

 
Adalimumab 
M06-807 Protocol  
EudraCT # 2007-006494-90 
 
 
105 
Week 97 - Week 104 
Subject Initials: __________ 
Subject Study #: ___________ 
 
Date 
day/mm/yr 
Day or 
Week # 
Time of Study 
Drug 
Administration 
Dose (mL) 
Administered
Kit #
Initials of Person 
Administering
Study Medication Comments
18/MAR/04 
EXAMPLE 
9:35 am 
0.8 
 
MM 
none 
 
Week 97 
 
 
 
 
 
 
Week 98 
 
 
 
 
 
 
Week 99 
 
 
 
 
 
 
Week 100 
 
 
 
 
 
 
Week 101 
 
 
 
 
 
 
Week 102 
 
 
 
 
 
 
Week 103* 
 
 
 
 
 
*The dose at Week 103 will only be taken if you are on weekly dosing. 
 

 
Adalimumab 
M06-807 Protocol  
EudraCT # 2007-006494-90 
 
 
106 
Appendix P. 
Self Injection Instructions 
 
 
Subject Instructions 
0.8 mL or 0.4 mL dose 
(Administered as a single dose-prefilled syringe (PFS)) 
 
Protocol M06-807 
 

 
Adalimumab 
M06-807 Protocol  
EudraCT # 2007-006494-90 
 
 
107 
Tables of Contents 
Dosing Schedule 
General Information & Supplies 
Injection Procedures
 

 
Adalimumab 
M06-807 Protocol  
EudraCT # 2007-006494-90 
 
 
108 
Study Drug Dosing Schedule 
Open-Label (PFS) 
Subject Number:_____________________________________ 
You will require subcutaneous (SC) injections throughout the study.  
Injections at scheduled study visits (Baseline, Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84, and 
96) will be done during your visit, at the doctor's office. On weeks between office visits, 
study drug will be self-administered at home by you or someone trained to give you the 
injections. 
One pre-filled syringe will contain 0.8 mL of liquid.  The total available dose is 0.8 mL. 
The drug should be administered in one (1) SC injection, on the same day of the week for 
each dose. 
Please return all used and unused syringes to the clinic on your next visit. Used syringes 
should be placed in the special sharps container provided. All unused syringes should be 
returned in the original box. 
If an injection is missed or something occurs where the full dose cannot be injected, 
contact your study center immediately for further instructions. Please record any missed 
doses on your subject diary. 
Remember to complete your dosing diary after each injection and to call the doctor's 
office if you are having problems administering your study drug. 

 
Adalimumab 
M06-807 Protocol  
EudraCT # 2007-006494-90 
 
 
109 
General Information 
 
 
 
 
 
 
 
PFS
● Prefilled syringes will be labeled "adalimumab." 
● Store all adalimumab prefilled syringes in your refrigerator NOT in the 
freezer.  Should the syringes accidentally become frozen, call your study 
coordinator. 
● 0.8 mL = 0.8 cc 
● Study drug should be taken at about the same time of day, on the same day of 
the week as directed by your study doctor. 
● USE A NEW SYRINGE EVERY INJECTION DAY. There may be 
medication left in the syringe. DO NOT RE-USE. 
● Save all study drugs. Prefilled syringes (used and unused) must be returned 
to the study center at each visit. Used syringes will be disposed of in a sharps 
container provided to you. 
● Whenever possible, have someone with you for at least 15 to 30 minutes after 
your injection. 
● Call your doctor IMMEDIATELY if you experience any itching, hives, 
shortness of breath, or any symptom that has you concerned. If you are unable 
to reach your doctor or if you experience life-threatening symptoms call 911, 
or proceed to your nearest emergency room. 
 

 
Adalimumab 
M06-807 Protocol  
EudraCT # 2007-006494-90 
 
 
110 
Injection Procedures 
 
 
 
 
 
 
 
PFS
1. Clean your workspace, gather your supplies, and wash your hands. 
 
 
2. Identify the area on your abdomen or thigh (or upper arm 
if not self injecting). Make sure the area you choose does 
not have any redness, tenderness, swelling, bruising, or 
psoriasis. The area must also be at least 2 cm 
(approximately 1 inch) away from the previous injection 
site. IT IS VERY IMPORTANT TO CHANGE THE 
INJECTION SITE EVERY TIME!!! 
 
 
3. Using a circular motion (starting at the injection site and 
moving outward) clean the selected injection site with 
an alcohol pad. Allow skin to dry.  
4. Remove the needle cap. Do not touch the needle. Expel 
any air bubbles from the syringe by tapping on the 
syringe. If the needle becomes contaminated, discard all 
supplies and obtain a new syringe of study drug.  
5. Once the air is expelled from the syringe, the amount of 
solution in the syringe should be 0.8 mL. 
 
 
6.   Hold the syringe "like a dart" between your thumb and 
first finger close to the syringe/needle connection. 

 
Adalimumab 
M06-807 Protocol  
EudraCT # 2007-006494-90 
 
 
111 
 
 
 
 
 
 
 
 
PFS
 
7. With your other hand, pinch the skin around the 
injection site, forming a bulge in the skin. 
 
 
 
 
 
 
8. Insert the needle into the skin at a 45-degree angle. 
Release pinched skin. 
 
 
 
 
9. 
GENTLY pull back on the syringe plunger. If blood 
appears, withdraw needle - DO NOT INJECT! Contact 
your study center immediately for further instructions. 
 
10. Inject drug by pushing slowly on syringe plunger with 
thumb. 
 
11. Remove needle while maintaining a 45-degree angle. 
 
12. You may apply a Band-Aid over the injection site and 
apply gentle pressure, if necessary. DO NOT RUB 
SITE. 
 
13. 
DO NOT RECAP NEEDLE. DO NOT SEPARATE THE NEEDLE FROM THE 
 
SYRINGE BEFORE DISPOSING. Discard used syringes into Sharps Container. 
EACH TIME THAT YOU GIVE YOURSELF AN INJECTION OF STUDY DRUG, 
REMEMBER TO RECORD THE INFORMATION ON YOUR SUBJECT DOSING 
DIARY. 
 

 
Adalimumab 
M06-807 Protocol  
EudraCT # 2007-006494-90 
 
 
112 
Appendix Q. 
Standard Weights 
 
 

 
Adalimumab 
M06-807 Protocol  
EudraCT # 2007-006494-90 
 
 
113 
 
 

 
Adalimumab 
M06-807 Protocol  
EudraCT # 2007-006494-90 
 
 
114 
Appendix R. 
Abbott Laboratories Site Drug Accountability Form 
 

 
Adalimumab 
M06-807 Protocol  
EudraCT # 2007-006494-90 
 
 
115 
Appendix S. 
Work Productivity and Activity Impairment Questionnaire: 
Crohn's Disease (WPAI-CD) - Caregiver 
The following questions ask about the effect of your child's Crohn's disease on your 
ability to work and perform regular activities.  Please fill in the blanks or circle a 
number, as indicated. 
1.  Are you currently employed (working for pay)?  
_____ NO ___ YES 
  If NO, check "NO" and skip to question 6. 
The next questions are about the past seven days, not including today. 
 
 
2. During the past seven days, how many hours did you miss from work because of 
problems associated with your child's Crohn's disease?  Include hours you missed on 
sick days, times you went in late, left early, etc., because of your child's Crohn's 
disease.  Do not include time you missed for your child to participate in this study. 
_____ HOURS 
 
3. During the past seven days, how many hours did you miss from work because of any 
other reason, such as vacation, holidays, time off for your child to participate in this 
study? 
 
_____HOURS 
 
4. During the past seven days, how many hours did you actually work? 
 
_____HOURS  (If "0," skip to question 6.) 

 
Adalimumab 
M06-807 Protocol  
EudraCT # 2007-006494-90 
 
 
116 
5. During the past seven days, how much did your child's Crohn's disease affect your 
productivity while you were working?   
Think about days you were limited in the amount or kind of work you could do, days 
you accomplished less than you would like, or days you could not do your work as 
carefully as usual.  If your child's Crohn's disease affected your work only a little, 
choose a low number.  Choose a high number if your child's Crohn's disease affected 
your work a great deal.
Consider only how much your child's Crohn's disease affected  
your productivity while you were working. 
 
 
 
 
 
 
 
 
 
 
 
My child's Crohn's 
disease had no 
effect on my work 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
My child's Crohn's 
disease completely 
prevented me from 
working 
CIRCLE A NUMBER 
6. During the past seven days, how much did your child's Crohn's Disease affect your 
ability to do your regular daily activities, other than work at a job?   
 
By regular activities, we mean the usual activities you do, such as work around the 
house, shopping, childcare, exercising, studying, etc.  Think about times you were 
limited in the amount or kind of activities you could do and times you accomplished 
less than you would like.  If your child's Crohn's Disease affected your activities only 
a little, choose a low number.  Choose a high number if your child's Crohn's Disease 
affected your activities a great deal.
Consider only how much your child's Crohn's disease affected your ability  
to do your regular daily activities, other than work at a job. 
 
 
 
 
 
 
 
 
 
 
 
My child's 
Crohn's disease 
had no effect on 
my daily 
activities 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
My child's Crohn's 
disease completely 
prevented me from 
doing my daily 
activities 
 
 
CIRCLE A NUMBER 
WPAI:CD-Caregiver (US English)