A Multi-Center, Open-Label Study of the Human Anti-TNF Monoclonal Antibody Adalimumab to Evaluate Long-Term Safety and Tolerability of Repeated Administration of Adalimumab in Pediatric Subjects With Ulcerative Colitis Who Completed the Study M11-290
Phase: PHASE3
Conditions: Ulcerative Colitis
Sponsor: AbbVie



Adalimumab
M10-870 Protocol Amendment 5
EudraCT 2015-001346-29
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1.1
Protocol Amendment:  Summary of Changes
Previous Protocol Versions
Protocol 
Date
Amendment 0.01 (JP Only)
24 July 2014
Original
07 May 2015
Amendment 1
17 August 2015
Administrative Change 1
11 September 2015
Amendment 2
09 June 2017
Amendment 2.01 (JP Only)
27 June 2017
Amendment 3
30 July 2019
Amendment 3.01 (JP Only)
01 August 2019
Amendment 4
13 January 2021
Amendment 4.01 (JP Only)
24 March 2021
The purpose of this amendment is to add guidance about vaccines against SARS-CoV-2 
and to delete language on reporting of malignancy in subjects who are 30 years old or 
younger:
●
Section 3.3, Section 5.2.3.1, and Section 6.1.7 - removed language about 
collection of malignancy events in subjects who are 30 years old or younger at 
the time of diagnosis.
Rationale:  Text related to the additional reporting requirements for 
malignancy in subjects who are 30 years old or younger (requested by the US 
FDA for the TNF inhibitor class in 2011) has been deleted since the 
postmarketing requirement was considered to be fulfilled by FDA on 
21 May 2021. Of note, any malignancy events will continue to be collected as 
reported by the investigators.
●
Section 5.2.3.2 and Section 6.1.7 – added COVID-19 pandemic-related 
vaccination guidance.
Rationale:  Language on SARS-CoV-2 vaccines and adalimumab dosing as 
well as documentation of SARS-CoV-2 vaccine information was added as per 
regulatory request.
 

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M10-870 Protocol Amendment 5
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1.2
Synopsis
AbbVie Inc.
Protocol Number:  M10-870
Name of Study Drug:  Adalimumab
Phase of Development:  3
Name of Active Ingredient:  Adalimumab
Date of Protocol Synopsis:  04 August 2021
Protocol Title:  A Multi-Center, Open-Label Study of the Human Anti-TNF Monoclonal Antibody 
Adalimumab to Evaluate Long-Term Safety and Tolerability of Repeated Administration of 
Adalimumab in Pediatric Subjects with Ulcerative Colitis Who Completed the Study M11-290
Objective:
The objective of the study is to evaluate the long-term safety, tolerability, and maintenance of clinical 
response, of repeated administration of adalimumab in pediatric subjects with ulcerative colitis who 
participated in, and successfully completed, Protocol M11-290 through Week 52.
Investigators:  Multi-center
Study Sites:  Eleven sites worldwide from the main study and 3 sites from the Japan sub-study.
Study Population:  Subjects with UC who successfully completed Study M11-290.
Number of Subjects to be Enrolled:  Fifty-five subjects from the main study and 4 subjects from the 
Japanese sub-study
Methodology:
This study is a Phase 3, multi-center, open-label study designed to evaluate the long-term maintenance 
of clinical response, safety and tolerability of adalimumab in pediatric subjects with ulcerative colitis.  
Eleven sites worldwide (and 3 sites from Japan) that have enrolled subjects in the Study M11-290 
clinical trial will participate in the Study M10-870 clinical trial.  Fifty-five pediatric subjects from the 
main study and 4 subjects from the Japanese sub-study are expected to enroll in this study.
The Week 52 visit from the Study M11-290 will serve as the Baseline Visit for subjects entering 
Study M10-870.
Subjects will be allowed to enroll in the Study M10-870 if they have successfully completed 
Protocol M11-290 through Week 52 and meet all of the inclusion criteria and none of the exclusion 
criteria for Study M10-870.
All subjects will receive open-label therapy as follows beginning at the Baseline Visit in 
Study M10-870:
Prior to Amendment 4:

Subjects who enrolled into the study from blinded treatment in Study M11-290 were to receive 
open label 0.6 mg/kg (maximum of 40 mg) eow of adalimumab.

Subjects who received open label adalimumab in Study M11-290 were to maintain the same 
dose in Study M10-870.
 

Adalimumab
M10-870 Protocol Amendment 5
EudraCT 2015-001346-29
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Methodology (Continued):
After Amendment 4, ongoing subjects will be switched to receive citrate free adalimumab in PFS of 
20 mg, 40 mg, or 80 mg as follows:

Subjects with a body weight < 25 kg will receive open label 20 mg eow of adalimumab

Subjects with a body weight ≥25 kg - < 40 kg will receive open label 40 mg eow of 
adalimumab

Subjects with a body weight ≥40 kg will receive open label 80 mg eow of adalimumab.
Ongoing subjects will continue to administer the remainder of dispensed vials as per the dose regimen 
prior to Amendment 4 until their first visit with Study Drug Dispensing after Amendment 4 when they 
will transition to the fixed dose regimen. Subjects who demonstrate a disease flare may have their 
dosage adjusted. 
Prior to Amendment 4:

Subjects who were on 0.6 mg/kg (maximum dose of 40 mg) eow of adalimumab could receive 
0.6 mg/kg (maximum of 40 mg) ew of adalimumab

Subjects who were on 0.6 mg/kg ew of adalimumab could receive 40 mg ew of adalimumab 
(max dose)
After Amendment 4:

Subjects who are on 20 mg eow of adalimumab may receive 40 mg eow of adalimumab

Subjects who are on 40 mg eow of adalimumab may receive 80 mg eow of adalimumab
Criteria for Dose Escalation (Increase) of Subjects with Disease Flare:

Subjects with a Baseline Study M10-870 PMS of 0 to 2 who present with a PMS at least 
3 points greater than their Baseline Study M10-870 score.

Subjects with a Baseline Study M10-870 PMS of 3 to 4 who present with a PMS at least 
2 points greater than their Baseline Study M10-870 score.

Subjects with a Baseline Study M10-870 PMS of 5 to 6 who present with a PMS at least 1 point 
greater than their Baseline Study M10-870 score.

Subjects who present with a PMS of at least 2 points greater than their PMS at the previous visit 
and who are not in remission per PMS.
Prior to Amendment 4, subjects with persistently uncontrolled disease while on adalimumab 40 mg ew 
(max dose) were to be discontinued from the study.
After Amendment 4, subjects with persistently uncontrolled disease while on adalimumab 80 mg eow
should be discontinued from the study.
Subjects who have been in remission (PMS ≤ 2 with no individual subscore > 1) for at least 8 weeks and 
for at least 2 consecutive visits may have their dosage de-escalated from ew to eow prior to 
Amendment 4 or to the next lower dose after Amendment 4.  The investigator should receive prior 
approval from the medical monitor before taking any action with regard to dose de-escalation.
Subjects who demonstrate disease flare after dose de-escalation have an opportunity to re escalate their 
dose back to adalimumab ew dosing prior to Amendment 4 or to the next higher dose after 
Amendment 4.  The investigator should receive prior approval from the medical monitor before taking 
any action with regard to dose re-escalation.  One de-escalation within a period of 48 weeks and 
one re-escalation within a period of 48 weeks are permissible.
 

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Methodology (Continued):
UC-related concomitant medication:

Subjects who enroll into the study from blinded treatment in Study M11-290 will be allowed to 
change/initiate/discontinue their steroid dose after 4 weeks in Study M10-870.

Subjects who enroll into the study from blinded treatment in Study M11-290 will be allowed to 
change/initiate/discontinue their azathioprine, 6-MP, MTX, 5-ASA doses after 8 weeks in 
Study M10-870.

Subjects who enroll into the study from open label treatment in Study M11-290 will be allowed 
to change/initiate/discontinue their azathioprine, 6-MP, MTX, 5-ASA at any time point in 
Study M10-870.

Reductions in concomitant corticosteroids, azathioprine, 6-MP, MTX, and 5-ASA will be 
allowed at any time in the event of moderate or severe drug-related toxicities (e.g., leukopenia, 
anemia, neuropathy).
The duration of the study could last up to 298 weeks (approximately 5.5 years).  Subjects who complete, 
or who early terminate from the study will be contacted approximately 70 days after their last dose of 
study drug to obtain information on any ongoing and new adverse events (AEs).  At study visits in 
addition to routine physical examination, laboratory assessments and calculation of the PMS and 
PUCAI, the following will be collected:

Anthropometric evaluations at for determination of body mass index (BMI), and "z" scores for 
height and weight.

IMPACT III Quality of Life questionnaire will be completed for subjects 9 years of age or older

WPAI

Tanner stage 
This study will conclude approximately 12 weeks after one of the following criteria have been satisfied:

Study drug received country and local (if applicable) regulatory approval for pediatric ulcerative 
colitis and application for local reimbursement has been submitted.

The Sponsor determined that continuation of the study does not further promote the scientific 
objective of the study.
Following site notification of upcoming conclusion of the study, 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.
Diagnosis and Main Criteria for Inclusion/Exclusion:  
Main Inclusion:
1.
Subject must have successfully enrolled in and completed Protocol M11-290 through Week 52.
2.
Subject of legal age, and/or 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, and/or Subject's 
parent, or legal guardian, as required, has had the opportunity to ask questions.  The informed 
consent must be signed before any study-specific procedures are performed.  Subjects will be 
included in all discussions, and if required, their signature on an assent form will be obtained.
 

Adalimumab
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Diagnosis and Main Criteria for Inclusion/Exclusion (Continued):
Main Inclusion (Continued):  
3.
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 electronic diary. 
If a subject is of a legal age, subjects must be able and willing to self-administer SC injections or 
have a qualified person available to administer SC injections and to ensure that the time of each dose 
is accurately recorded in the subject's electronic diary.
4.
If female, subject who is either not of childbearing potential, defined as pre-menstrual, or is of 
childbearing potential and is practicing an approved method of birth control throughout the study 
and for 150 days after last dose of the study drug. 
Examples of approved methods of birth control include the following (see local informed consent 
for more detail):

Total abstinence from sexual intercourse;

Condoms, sponge, foam, jellies, diaphragm or intrauterine device (IUD);

Hormonal contraceptives for 90 days prior to study drug administration;

A vasectomized partner.
5.
Subject is judged to be in good medical condition, as determined by the Principal Investigator based 
upon results of clinical and laboratory evaluations done throughout the preceding ulcerative colitis 
Study M11-290.
Main Exclusion:  
1.
Subject is considered by the Investigator, for any reason, to be an unsuitable candidate for 
continuing therapy in the Study M10-870.
2.
Female subjects who are pregnant or currently breastfeeding or considering becoming pregnant 
during the study.
3.
Subject with Crohn's disease (CD) or indeterminate colitis (IC).
4.
History of clinically significant drug or alcohol abuse in the last 12 months.
5.
History of demyelinating disease (including myelitis) or neurologic symptoms suggestive of 
demyelinating disease.
6.
History of chronic or active hepatitis B infection, human immunodeficiency virus (HIV) infection, 
any immunodeficiency syndrome, or active TB (regardless of receiving treatment), or active viral 
infection that, based on the investigator's clinical assessment, makes the subject an unsuitable 
candidate for the study.  
7.
History of moderate to severe congestive heart failure (NYHA class III or IV), recent 
cerebrovascular accident and any other condition which would put the subject at risk by 
participation in the study.
8.
History of malignancy (including lymphoma and leukemia) other than a successfully treated non-
metastatic cutaneous squamous cell or basal cell carcinoma or localized carcinoma in situ of the 
cervix.
9.
Subject who is planning surgical bowel resection at any time point while enrolled in the study.
10. Known hypersensitivity to adalimumab or its excipients.
11. Current diagnosis of fulminant colitis and/or toxic megacolon.
 

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M10-870 Protocol Amendment 5
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Investigational Product:
Adalimumab
Doses:
Prior to Amendment 4:

Open label 0.6 mg/kg (maximum of 40 mg) eow of 
adalimumab.

Open label 0.6 mg/kg (maximum of 40 mg) ew of adalimumab.

Open label adalimumab 40 mg ew.
After Amendment 4

Open label 20 mg, 40 mg or 80 mg eow of adalimumab
Mode of Administration:
Subcutaneous injection (SC)
Reference Therapy:
NA
Dose:
NA
Mode of Administration:
NA
Duration of Treatment:
The study will include an open-label period of approximately 298 weeks.  Prior to Amendment 4, all 
subjects were minimally on open label 0.6 mg/kg (maximum of 40 mg) eow of adalimumab beginning at 
the Baseline visit.  After Amendment 4, all subjects will be on open label 20 mg, 40 mg or 80 mg eow of 
adalimumab.  A 70-Day Follow-Up phone call will be completed for all subjects who either terminate 
early from the study or who complete the study.
Criteria for Evaluation:
Efficacy:
This study will utilize the PMS (and Mayo score if available) and PUCAI to determine efficacy of the 
study drug.
The following efficacy endpoints will be analyzed using summary statistics:

The proportion of subjects who achieve clinical remission as measured by PMS (defined as a 
PMS ≤ 2 and no individual subscore > 1) over time;

The proportion of subjects who achieve clinical response as measured by PMS (defined as a
decrease in PMS ≥ 2 points and ≥ 30% from Baseline) over time;

The proportion of subjects who achieve PUCAI remission (defined as < 10) over time;

The proportion of subjects who achieve PUCAI response (defined as a decrease in PUCAI 
≥20 points from Baseline).
Efficacy will also be evaluated based on other measures of disease activity, including IMPACT III, 
WPAI, z-score for height and weight, bone age, BMI, and laboratory values as applicable.  The 
proportion of subjects who achieve remission/response based on Mayo score and mucosal healing based 
on Mayo endoscopy subscore will be summarized for subjects with available Mayo score.
Pharmacokinetic and Immunogenicity:
As appropriate, population pharmacokinetic analysis and/or any additional analyses may be performed 
on samples for serum adalimumab concentrations and immunogenicity status collected prior to 
Amendment 2.
 

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Criteria for Evaluation (Continued):
Safety:
Safety analyses will be performed on all subjects who receive at least one dose of study drug.  Incidence 
of AEs, changes in vital signs, physical examination results, and clinical laboratory data will be assessed.
Statistical Methods:
All statistical analysis results will be reported using descriptive statistics.  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.
Efficacy:
Summary statistics will be provided for each visit, based on observed data and non-responder imputation 
(NRI) for missing categorical 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 Study M11-290 value) will be carried forward to the last visit.  Details will be 
provided in the Statistical Analysis Plan (SAP).
Safety:
Treatment emergent AEs, serious adverse events (SAEs), and AEs of special interest will be summarized 
by system organ class (SOC) and preferred term (PT) according to the Medical Dictionary for 
Regulatory Activities (MedDRA) AE coding dictionary.  A summary of AEs by severity and 
relationship to study drug will be performed.  Other safety variables such as laboratory and vital sign 
data will be described by descriptive statistics.  In addition, shift tables and listings will be provided.
 

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1.3
List of Abbreviations and Definition of Terms
Abbreviations
5-ASA
5-aminosalicylic acid
6-MP
6-mercaptopurine
AAA
Anti-adalimumab antibody
ADA
Adalimumab
AE
Adverse event
ALT
Alanine transaminase
ANA
Antinuclear antibody
AST
Aspartate transaminase
BCG
Bacillus Calmette-Guérin 
BLA
Biologics License Application
BUN
Blood Urea nitrogen
CD
Crohn's disease
CDC
Center for Disease Control and Prevention
CLIA
Clinical Laboratory Improvement Amendments
CNS
Central nervous system
COVID-19
Coronavirus Disease-2019
CRA
Clinical Research Associate
CRF
Case report form
CRO
Contract Research Organization
CRP
C-Reactive Protein
CTC
Common Toxicity Criteria
CXR
Chest x-ray
DNA
Deoxyribonucleic acid
dsDNA
Double-stranded DNA
DTP
Direct-to-Patient
EC
Ethic committee
ECG
Electrocardiogram
EDTA
Edetic acid (ethylenediaminetetraacetic acid)
Eow
Every other week
Ew
Every week
EP
European Pharmacopoeia
 

Adalimumab
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EudraCT 2015-001346-29
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ESR
Erythrocyte sedimentation rate
FDA
US Food and Drug Administration
GCP
Good Clinical Practice
HAQ
Health Assessment Questionnaire
HCG
Human chorionic gonadotropin
IBDQ
Inflammatory Bowel Disease Questionnaire
ICH
International Conference on Harmonization
IEC
Independent Ethics Committee
IgG
Immunoglobulin G
IL
Interleukin
IND
Investigational New Drug
IEC
Independent Ethics Committee
IRB
Institutional Review Board
IRT
Interactive Response technology
ITT
Intent-to-treat
IVRS
Interactive Voice Response System
LOCF
Last observation carried forward
MedDRA
Medical Dictionary for Regulatory Activities
MMF
Mycophenolate mofetil
MTX
Methotrexate
NDC
National Drug Code
nnmiss
Number of non-missing observations
PA
Posterior Anterior
PBO
Placebo
PFS
Pre-filled syringe
PK
Pharmacokinetics
POR
Proof of Receipt
PPD
Purified protein derivative
PUCAI
Pediatric Ulcerative Colitis Activity Index
QTc
QT interval corrected for heart rate
RA
Rheumatoid arthritis
RBC
Red Blood Cell
RNA
Ribonucleic acid
SAE
Serious Adverse Event
 

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Sc
Subcutaneous
TB
TB Tuberculosis
Th1
Th1 Type 1 T helper
TNF
TNF Tumor necrosis factor
TPN
TPN Total parenteral nutrition
UC
Ulcerative Colitis
USP
United States Pharmacopoeia
WBC
WBC White blood cell
 

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2.0
Table of Contents
1.0
Title Page..................................................................................1
1.1
Protocol Amendment:  Summary of Changes ...........................................2
1.2
Synopsis .....................................................................................................3
1.3
List of Abbreviations and Definition of Terms..........................................9
2.0
Table of Contents...................................................................12
3.0
Introduction ...........................................................................16
3.1
Adalimumab Overview............................................................................16
3.2
Ulcerative Colitis and Current Treatments and Overview.......................16
3.3
Safety Information ...................................................................................19
3.3.1
Differences Statement..............................................................................19
3.4
Benefits and Risks....................................................................................19
4.0
Study Objective......................................................................20
5.0
Investigational Plan...............................................................20
5.1
Overall Study Design and Plan:  Description ..........................................20
5.2
Selection of Study Population..................................................................24
5.2.1
Inclusion Criteria .....................................................................................24
5.2.2
Exclusion Criteria ....................................................................................25
5.2.3
Prior and Concomitant Therapy...............................................................26
5.2.3.1
Prior Therapy ...........................................................................................26
5.2.3.2
Concomitant Therapy...............................................................................27
5.2.3.3
Prohibited Therapy...................................................................................29
5.3
Efficacy, Pharmacokinetic, Pharmacodynamic, Pharmacogenetic 
and Safety Assessments/Variables...........................................................30
5.3.1
Efficacy and Safety Measurements Assessed and Flow Chart ................30
5.3.1.1
Study Procedures .....................................................................................37
5.3.2
Efficacy Variables....................................................................................53
5.3.3
Safety Variables.......................................................................................54
5.3.4
Pharmacokinetic Variables ......................................................................54
5.3.4.1
Cytokines and Serologic Variables..........................................................54
5.4
Removal of Subjects from Therapy or Assessment.................................55
5.4.1
Discontinuation of Individual Subjects....................................................55
 

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5.4.2
Discontinuation of Entire Study...............................................................57
5.5
Treatments................................................................................................58
5.5.1
Treatments Administered.........................................................................58
5.5.2
Identity of Investigational Product...........................................................60
5.5.2.1
Packaging and Labeling...........................................................................61
5.5.2.2
Storage and Disposition of Study Drug ...................................................61
5.5.3
Method of Assigning Subjects to Treatment Groups...............................62
5.5.4
Selection and Timing of Dose for Each Subject......................................62
5.5.5
Blinding....................................................................................................63
5.5.6
Treatment Compliance.............................................................................63
5.5.7
Drug Accountability.................................................................................63
5.6
Discussion and Justification of Study Design..........................................65
5.6.1
Discussion of Study Design and Choice of Control Groups....................65
5.6.2
Appropriateness of Measurements...........................................................65
5.6.3
Suitability of Subject Population .............................................................65
5.6.4
Selection of Doses in the Study ...............................................................65
6.0
Complaints .............................................................................66
6.1
Medical Complaints.................................................................................66
6.1.1
Definitions................................................................................................66
6.1.2
Adverse Event..........................................................................................67
6.1.3
Serious Adverse Events ...........................................................................68
6.1.4
Adverse Event Severity............................................................................69
6.1.5
Relationship to Study Drug......................................................................69
6.1.6
Adverse Event Collection Period.............................................................70
6.1.7
Adverse Event Reporting.........................................................................71
6.1.8
Pregnancy.................................................................................................73
6.2
Product Complaints..................................................................................74
6.2.1
Definitions................................................................................................74
6.3
Toxicity Management ..............................................................................75
7.0
Protocol Deviations................................................................75
8.0
Statistical Methods and Determination of Sample 
Size ..........................................................................................76
8.1
Statistical and Analytical Plans................................................................76
 

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8.1.1
Analyzable Population.............................................................................77
8.1.2
Planned Methods of Statistical Analysis..................................................77
8.1.3
Demographics and Baseline Characteristics............................................77
8.1.4
Efficacy Analysis .....................................................................................77
8.1.5
Statistical Analyses of Safety...................................................................78
8.1.6
Other Analyses.........................................................................................78
8.1.7
Interim Analysis.......................................................................................78
8.2
Determination of Sample Size .................................................................78
8.3
Randomization Methods ..........................................................................79
9.0
Ethics.......................................................................................79
9.1
Independent Ethics Committee (IEC) or Institutional Review 
Board (IRB) .............................................................................................79
9.2
Ethical Conduct of the Study...................................................................80
9.3
Subject Information and Consent.............................................................80
10.0
Source Documents and Case Report Form 
Completion .............................................................................81
10.1
Source Documents ...................................................................................81
10.2
Case Report Forms...................................................................................82
10.3
Electronic Patient Reported Outcomes (ePRO).......................................83
10.4
Data Collection Process ...........................................................................85
11.0
Data Quality Assurance ........................................................85
12.0
Use of Information.................................................................85
13.0
Completion of the Study .......................................................86
14.0
Investigator's Agreement......................................................87
15.0
Reference List ........................................................................88
List of Tables
Table 1.
Study Activities........................................................................................31
Table 2.
Clinical Laboratory Tests.........................................................................45
Table 3.
Identity of Investigational Products.........................................................61
 

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List of Figures
Figure 1.
Adverse Event Collection ........................................................................71
List of Appendices
Appendix A.
Responsibilities of the Clinical Investigator ............................................91
Appendix B.
List of Protocol Signatories......................................................................93
Appendix C.
Pediatric Ulcerative Colitis Activity Index (PUCAI) ..............................94
Appendix D.
Mayo Scoring System ..............................................................................95
Appendix E.
Work Productivity and Activity Impairment Questionnaire:  
Ulcerative Colitis V2.0 (WPAI:  UC) – Caregiver..................................99
Appendix F.
Body Weight Adjusted Volumes of Study Drug for 
Administration of Open Label Adalimumab 0.6 mg/kg Dosing 
(Weight Based) ......................................................................................102
Appendix G.
70-Day Follow-Up Call – Sample .........................................................103
Appendix H.
Non-Drug Materials Provided to the Study Sites ..................................104
Appendix I.
Measurements and Volume(s) of Blood Samples to Be Drawn ............105
 

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3.0
Introduction
3.1
Adalimumab Overview
Adalimumab is a recombinant human immunoglobulin (IgG1) monoclonal antibody 
containing only human peptide sequences.  Adalimumab is produced by recombinant 
DNA technology in a mammalian cell expression system.  It consists of 1330 amino acids 
and has a molecular weight of approximately 148 kilodaltons.  Adalimumab is composed 
of fully human heavy and light chain variable regions, which confer specificity to human 
TNF, and human IgG1 heavy chain and kappa light chain sequences.  Adalimumab binds 
with high affinity and specificity to soluble TNF-α but not to lymphotoxin-α (TNF-β).
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 also modulates biological responses that are induced or regulated 
by TNF.  After treatment with adalimumab, levels of acute phase reactants of 
inflammation (C-reactive protein [CRP] and erythrocyte sedimentation rate [ESR]) and 
serum cytokines rapidly decrease.
Adalimumab was first approved in US and EU for the treatment of RA in 2002 and 2003, 
respectively.  Additional indications have been approved in the US and EU including Ps, 
PsA, AS, CD, JIA and UC.  Additional updates regarding approved indications can be 
found in the current edition of the Humira Investigational Drug Brochure.
3.2
Ulcerative Colitis and Current Treatments and Overview
Ulcerative colitis (UC) is one of the two primary forms of idiopathic inflammatory bowel 
disease (IBD).  It is a chronic, relapsing inflammatory disease of the rectum and/or large 
intestine characterized by inflammation and ulceration of the mucosal and submucosal 
intestinal layers.  The hallmark clinical symptoms include bloody diarrhea associated with 
rectal urgency and tenesmus.  The clinical course is marked by exacerbation and 
 

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remission.  The general clinical features of UC are similar in adults and children; 
however, there are differences in the presentation and progression of the disease.  While 
in adults, the vast majority have limited or left-sided colitis in children proximal extension 
of disease1 and pancolitis involving the entire colon is more common,2 and extra-intestinal 
manifestations seem to be more frequent.  UC onset can occur at any age, but it is 
extremely rare in infants, infrequent in early childhood, and is more commonly diagnosed 
in late adolescence and early adulthood.  Less than 1% of pediatric IBD cases occur 
during the first year of life, most of which are eventually diagnosed as CD and not UC.3  
Studies frequently report no,4,5 or very few cases of UC below age 5 (11 of 211 pediatric 
UC cases in Great Britain and Ireland).6  Reported incidence of UC in Europe before age 
10 is also very low (per 100,000; Northern France 0.3 for ages 5 to 10,7 Scotland 1.4 for 
ages 7 to 11,8 and Northern Stockholm 1.1 for ages 5 to 9).9  In Northern France, crude 
incidence of UC per 100,000 was 0.1, 0.3, 1.1, and 2.5 for age groups 0 to 5, 5 to 10, 10 to 
15, and 15 to 17, respectively.7  A prospective, population-based study in Poland in 
children less than age 18 reported an increase after age 10 in UC incidence (per 
100,000 patient years, 0.1 age 0 to 2; 0.7 age 3 to 5; 0.9 age 6 to 10; 1.9 age 11 to 18).10  
In most pediatric studies, the median age of symptom onset was 12 years.2
The burden of UC on the healthcare system is profound, accounting for nearly 
470,000 physician visits and more than 46,000 hospitalizations per year in the United 
States (US) alone.11
The diagnostic measures to confirm the presence of UC are essentially the same in adults 
and children.  The diagnosis of UC is suspected on clinical grounds and supported by 
diagnostic testing, and elimination of infectious causes, although infection can be present 
in patients with UC.2  Bloody diarrhea accompanied by tenesmus is the leading symptom 
in 84% to 94% of children.1  After exclusion of infections and other causes, UC should be 
suspected in children if bloody diarrhea is chronic (≥ 4 weeks) or recurrent (≥ 2 episodes 
within 6 months), particularly when growth failure and/or pubertal delay, family history 
of UC/IBD, increased inflammatory markers, or anaemia are present.2  It should be noted 
that growth failure is half as common in UC than in CD, perhaps because the interval 
 

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between symptoms and diagnosis is generally shorter.2  The European Society of Pediatric 
Gastroenterology, Hepatology and Nutrition (ESPGHAN) published the Porto Criteria for 
the diagnosis of IBD (UC, CD, and IC) in children in 2005.
Disease of moderate or severe activity may often be associated with anorexia, nausea, 
weight loss, and fever, as well as symptoms associated with anemia and 
hypoalbuminemia.  The most severe intestinal manifestations of UC are toxic megacolon 
and perforation.  Extraintestinal complications include arthritis (sacroiliitis and ankylosing 
spondylitis), dermatological conditions (erythema nodosum, aphthous stomatitis, and 
pyoderma gangrenosum), inflammation of the eye (uveitis), and liver dysfunction 
(primary sclerosing cholangitis).  Patients with UC are at an increased risk for colon 
cancer, and the risk increases with the duration of disease as well as extent of colon 
affected by the disease.12
The pharmacological treatment of UC in childhood is largely the same as in adulthood.  
Conventional pharmaceutical therapies do not completely abate the inflammatory process 
and have significant side effects.  Conventional therapies for the induction of remission 
have included anti-inflammatory agents (5-aminosalicylic acid [5-ASA] derivatives and 
corticosteroids) and the immunomodulatory agent cyclosporine.  5-ASA derivatives as 
well as immunomodulatory agents (azathioprine or 6-mercaptopurine [6-MP]) have been 
used for the maintenance of remission.13  Corticosteroids are not effective for the 
maintenance of remission.  In addition to the induction and maintenance of clinical 
remission, absence of adverse effects on linear growth and maturation is demanded from 
therapy of pediatric UC.  Similar to adults, corticosteroid dependence is frequent, but 
long-term corticosteroids are absolutely contraindicated because they do not maintain 
remission and have a negative effect on linear growth and bone mineralization.2  
Infliximab (a chimeric monoclonal anti-tumor necrosis factor [TNF]-α antibody) was 
approved in Europe for the treatment of pediatric patients with severe UC and in the US 
for the treatment of pediatric patients with moderate to severe UC based on the results of a 
recent study.14
 

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The safety and efficacy of adalimumab for the induction and maintenance of clinical 
remission in adult subjects with moderately to severely active UC has been studied in 
two completed clinical trials (Study M06-826 and Study M06-827) and an ongoing 
open-label study (Study M10-223).15-18  In addition, adalimumab has shown clinically 
relevant improvements in IBDQ scores compared to placebo for up to 52 weeks in these 
subjects.19
3.3
Safety Information
Adalimumab therapy has a well established and well described safety profile in adults 
based on extensive postmarketing experience and continued clinical trial-subject exposure 
since the first approved indication in 2002 for rheumatoid arthritis.  In general, the safety 
profile observed in pediatric studies is consistent with that in the adult population.  A 
detailed discussion of the pre-clinical toxicology, metabolism, pharmacology and safety 
experience with adalimumab can be found in the current Investigator's Brochure.  AbbVie 
is committed to continue to collect safety information including those events that may 
occur in this trial in order to confirm this established safety profile and to identify any 
unknown potential adverse reactions, rare events and those events with a long latency.  
3.3.1
Differences Statement
Pediatric subjects with moderate-to-severe UC between the ages of 4 and 17 who 
participated in, and successfully completed, Protocol M11-290 through Week 52 will be 
considered for participation in the study. 
3.4
Benefits and Risks
Extensive clinical and postmarketing experience exists with adalimumab in a wide range 
of disease states including the IBD indications Crohn's disease and UC.  The safety profile 
of adalimumab in those indications is well established with more than 
50,000 patient-years of adalimumab clinical trial experience.  The clinical studies in adult 
UC have not altered this safety profile and demonstrated a positive benefit/risk balance.  
 

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Conditions which may present a risk specifically for subjects with UC are exclusion 
criteria in this study (e.g., evidence of colonic dysplasia or active infections).
Considering the coronavirus (COVID-19) pandemic, the benefit and risk to subjects 
participating in this study has been re-evaluated. Subjects receiving adalimumab may be 
at an increased risk for COVID-19 infection or experience serious illness if infected. 
Management of these adverse events will be made on a case-by-case basis with 
consideration of benefit/risk. However, based on the population and disease being studied 
and the anticipation that COVID-19 related risks are not expected to differ substantially 
between study subjects and the broader population of subjects receiving treatment for 
ulcerative colitis, no change to the benefit/risk balance for subjects in this study is 
expected. Current published information suggests that the baseline use of biologics is not 
associated with worse Covid-19 outcomes.20
4.0
Study Objective
The objective of the study is to evaluate the long-term safety, tolerability, and 
maintenance of clinical response, of repeated administration of adalimumab in pediatric 
subjects with ulcerative colitis who participated in, and successfully completed, 
Protocol M11-290 through Week 52.
5.0
Investigational Plan
5.1
Overall Study Design and Plan:  Description
The study was designed to enroll approximately 85 subjects from the main study and 
approximately 8 subjects from the Japan sub-study to meet scientific and regulatory 
objectives without enrolling an undue number of subjects in alignment with ethical 
considerations.
Fifty-five pediatric subjects with moderate-to-severe ulcerative colitis who participated in, 
and successfully completed, Protocol M11-290 through Week 52 will be enrolled at 
11 sites worldwide (Section 5.3.1.1).
 

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There also will be 4 Japanese subjects in a Japan sub-study to be enrolled at 3 Japan sites.  
The Japan sub-study will be conducted utilizing the same design as outlined in the main 
study with the exceptions that are outlined in a separate Japan specific protocol.
Subjects who meet all of the inclusion criteria and none of the exclusion criteria will be 
enrolled into the study and will receive open-label study drug.  At the Baseline visit, the 
following procedures will be completed as part of Week 52 of the M11-290 protocol:  
concomitant medication updates, physical exam, vital signs, Chemistry/hematology, 
hs-CRP, urinalysis, pregnancy test, TB testing, Mayo Score, PMS, PUCAI, IMPACT III 
Questionnaire, WPAI UC-Caregiver, Tanner Stage, Anthropometric Evaluations, 
endoscopy and monitoring of adverse events as well as subject diary 
dispensing/reviewing.  Medical History will be updated from the medical history recorded 
during the subject's previous study.
All subjects will receive open-label therapy as follows beginning at the Baseline Visit in 
Study M10-870:
Prior to Amendment 4:
●
Subjects who enrolled into the study from blinded treatment in Study M11-290 
were to receive open label 0.6 mg/kg (maximum of 40 mg) eow of 
adalimumab.
●
Subjects who received open label 0.6 mg/kg (maximum of 40 mg) ew of 
adalimumab in Study M11-290 were to maintain the same dose in 
Study M10-870.
After Amendment 4, ongoing subjects will be switched to receive a fixed-dose regimen, 
by weight cut-off, incorporating citrate free adalimumab in PFS (20 mg, 40 mg, or 80 mg)
as follows:
●
Subjects with a body weight < 25 kg will receive open label 20 mg eow of 
adalimumab
 

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●
Subjects with a body weight ≥25 kg - < 40 kg will receive open label 40 mg 
eow of adalimumab
●
Subjects with a body weight ≥40 kg will received open label 80 mg eow of 
adalimumab.
Ongoing subjects will continue to administer the remainder of dispensed vials as per the 
dose regimen prior to Amendment 4 until their first visit with Study Drug Dispensing 
after Amendment 4 when they will transition to the fixed dose regimen.
The duration of the study could be up to 298 weeks, which includes a 288-week open-
label maintenance period and a 70-day follow-up.  There is a ± 3 day window for all study 
visits.  An effort will be made to bring subjects back to their original scheduled visit 
(calculated from Baseline) if they are out of the visit window.
Efficacy and safety measurements will be performed throughout the study (see Table of 
Activities, Section 5.3.1).  Clinical evaluation will be performed at Baseline, Weeks 4, 8, 
12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 144, 168, 192, 216, 240, 264 and 288/Premature 
Discontinuation and unscheduled Visits.  Subjects may undergo an optional endoscopy 
during Weeks 48, 96, 192, and 288/Premature Discontinuation Visit to assess disease 
activity and for surveillance per the investigator's discretion.
Treatment of Subjects with a Disease Flare
Criteria for Disease Flare are as follows:
●
Subjects with a Baseline Study M10-870 PMS of 0 to 2 who present with a 
PMS at least 3 points greater than their Baseline Study M10-870 score.
●
Subjects with a Baseline Study M10-870 PMS of 3 to 4 who present with a 
PMS at least 2 points greater than their Baseline Study M10-870 score.
●
Subjects with a Baseline Study M10-870 PMS of 5 to 6 who present with a 
PMS at least 1 point greater than their Baseline Study M10-870 score.
●
Subjects who present with a PMS of at least 2 points greater than their PMS at 
the previous visit and who are not in remission per PMS.
 

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Prior to Amendment 4:
●
Subjects with a disease flare who were on 0.6 mg/kg (maximum dose of 
40 mg, weight based) eow of adalimumab could receive 0.6 mg/kg (maximum 
of 40 mg, weight based) ew of adalimumab.
●
Subjects with a disease flare who were on 0.6 mg/kg ew of adalimumab could 
receive 40 mg ew (maximum dose of 40 mg).
Subjects with persistently uncontrolled disease while on adalimumab 40 mg ew (max 
dose) were to be discontinued from the study.
After Amendment 4:
●
Subjects who are on 20 mg eow of adalimumab may receive 40 mg eow of 
adalimumab.
●
Subjects who are on 40 mg eow of adalimumab may receive 80 mg eow of 
adalimumab.
Subjects with persistently uncontrolled disease while on adalimumab 80 mg eow should 
be discontinued from the study.
The Investigator should consider dose escalation in lieu of initiating any rectal therapy 
such as therapeutic enemas or suppositories during the study.  The AbbVie study 
designated physician identified in Section 6.1.7 should be contacted if there are any 
questions regarding rectal therapy.
Dose De-Escalation and Re-Escalation
Subjects who have been in remission (PMS ≤ 2 with no individual subscore > 1) for at 
least 8 weeks and for at least 2 consecutive visits may have their dosage decreased from 
ew to eow prior to Amendment 4 or to the next lower dose after Amendment 4.  The 
investigator should receive prior approval from the medical monitor before taking any 
action with regard to dose de-escalation.
 

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Subjects who demonstrate disease flare after dose de-escalation have the opportunity to 
re-escalate their dose back to adalimumab ew dosing prior to Amendment 4 or to the next 
higher dose after Amendment 4.  The investigator should receive prior approval from the 
medical monitor before taking any action with regard to dose re-escalation. One de-
escalation within a period of 48 weeks and one re-escalation within a period of 48 weeks 
are permissible.
No study drug will be administered or injected at the final visit.
Subjects may discontinue adalimumab treatment at any time during study participation.  
Subjects that end study participation early will have a Termination Visit.  All subjects will 
have a follow-up phone call approximately 70 days after the last administration of study 
drug to obtain information on any new or ongoing AEs.
An Example of 70-Day Follow-Up Call – Form is described in Appendix G.
5.2
Selection of Study Population
5.2.1
Inclusion Criteria
A subject will be eligible for study participation if he/she meets all of the following:
1.
Subject must have successfully enrolled in and completed Protocol M11-290 
through Week 52.
2.
Subject of legal age, and/or 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, and/or Subject's parent, or legal 
guardian, as required, has had the opportunity to ask questions.  The informed 
consent must be signed before any study-specific procedures are performed.  
Subjects will be included in all discussions, and if required, their signature on an 
assent form will be obtained.
 

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3.
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 electronic diary. 
If a subject is of a legal age, subjects must be able and willing to self-administer SC 
injections or have a qualified person available to administer SC injections and to 
ensure that the time of each dose is accurately recorded in the subject's electronic 
diary.
4.
If female, subject who is either not of childbearing potential, defined as 
pre-menstrual, or is of childbearing potential and is practicing an approved method 
of birth control throughout the study and for 150 days after last dose of the study 
drug. 
Examples of approved methods of birth control include the following (see local 
informed consent for more detail):
●
Total abstinence from sexual intercourse;
●
Condoms, sponge, foam, jellies, diaphragm or intrauterine device (IUD);
●
Hormonal contraceptives for 90 days prior to study drug administration;
●
A vasectomized partner.
5.
Subject is judged to be in good medical condition, as determined by the Principal 
Investigator based upon results of clinical and laboratory evaluations done 
throughout the preceding ulcerative colitis Study M11-290.
5.2.2
Exclusion Criteria
1.
Subject is considered by the Investigator, for any reason, to be an unsuitable 
candidate for continuing therapy in the Study M10-870.
2.
Female subjects who are pregnant or currently breastfeeding or considering 
becoming pregnant during the study.
3.
Subject with Crohn's disease (CD) or indeterminate colitis (IC).
 

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4.
History of clinically significant drug or alcohol abuse in the last 12 months.
5.
History of demyelinating disease (including myelitis) or neurologic symptoms 
suggestive of demyelinating disease.
6.
History of chronic or active hepatitis B infection, human immunodeficiency virus 
(HIV) infection, any immunodeficiency syndrome, or active TB (regardless of 
receiving treatment), or active viral infection that, based on the investigator's 
clinical assessment, makes the subject an unsuitable candidate for the study.
7.
History of moderate to severe congestive heart failure (NYHA class III or IV), 
recent cerebrovascular accident and any other condition which would put the 
subject at risk by participation in the study.
8.
History of malignancy (including lymphoma and leukemia) other than a 
successfully treated non-metastatic cutaneous squamous cell or basal cell 
carcinoma or localized carcinoma in situ of the cervix.
9.
Subject who is planning surgical bowel resection at any time point while enrolled 
in the study.
10.
Known hypersensitivity to adalimumab or its excipients.
11.
Current diagnosis of fulminant colitis and/or toxic megacolon.
5.2.3
Prior and Concomitant Therapy
5.2.3.1
Prior Therapy
Any medication or vaccine (including over-the-counter or prescription medicines, 
vitamins and/or herbal supplements) that the subject receives during the study, must be 
recorded in source documents and on the appropriate page of the electronic case report 
form (eCRF), along with the reason for use, dates of administration including start and 
end dates, and dosage information including dose, route and frequency.
 

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The AbbVie study designated physician identified in Section 6.1.7 should be contacted if 
there are any questions regarding concomitant or prior therapy.
Any medications used prior to the study will be captured on the appropriate eCRF.  
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 eCRF pages.
5.2.3.2
Concomitant Therapy
UC-related concomitant medication:
●
Subjects who enroll into the study from blinded treatment in Study M11-290 
will be allowed to change/initiate/discontinue their steroid dose after 4 weeks 
in Study M10-870.
●
Subjects who enroll into the study from blinded treatment in Study M11-290 
will be allowed to change/initiate/discontinue their azathioprine, 6-MP, MTX, 
5-ASA doses after 8 weeks in Study M10-870.
●
Subjects who enroll into the study from open label treatment in 
Study M11-290 will be allowed to change/initiate/discontinue their steroid, 
azathioprine, 6-MP, MTX, 5-ASA doses at any time point in Study M10-870.
●
Reductions in concomitant corticosteroids, azathioprine, 6-MP, MTX, and 
5-ASA will be allowed at any time in the event of moderate or severe 
drug-related toxicities (e.g., leukopenia, anemia, neuropathy).
Subjects may not be on both budesonide and prednisone (or equivalent) simultaneously.
Subsequent changes in all concomitant medications will be assessed at each study visit 
from Baseline (Week 0) through Week 288/Premature Discontinuation Visits.  All 
subjects will be given a Subject Medication Log to help track any change in therapy.  
These changes will be documented in the source documents and captured on the 
appropriate eCRF page.
 

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All non-UC medications (prescription and over-the-counter) used will be recorded and 
must include all doses and date ranges of administration.  Vaccines administered to the 
subject will be listed as a concomitant medication.  Any antibiotic used will be recorded 
and must include all doses and date ranges of administration.
The AbbVie Study Designated Physician identified in Section 6.1.7 should be contacted if 
there are any questions regarding concomitant or prior therapy(ies).
COVID-19 Pandemic -Related Vaccination Guidance
Given the ongoing COVID-19 pandemic, selected non-live vaccines (e.g., mRNA, non-
replicating viral vector, protein subunit, etc.) to prevent SARS-CoV-2 infection may be 
administered during the study as long as components of the vaccine are not 
contraindicated.
The decision to receive a locally available vaccine should be based on local guidance and 
an individual discussion between the treating physician and the subject.
The potential impact of adalimumab on SARS-CoV-2 vaccination is unknown.  
Therefore, adalimumab should be given at least ± 7 days from the SARS-CoV-2 vaccine 
administration.
Note:  The above guidance applies to all SARS-CoV-2 vaccine doses given as part of the 
complete treatment course.
These recommendations may be subject to change based on the evolving knowledge 
around the use of SARS-CoV-2 vaccines and as more data are collected in real-world 
scenarios and clinical trials.
Any SARS-CoV-2 vaccine information must be documented on the COVID-19 vaccine 
electronic case report form (eCRF).  Refer to Section 6.1.7 for instructions on reporting 
any AEs associated with the COVID-19 vaccine.
 

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5.2.3.3
Prohibited Therapy
The following are prohibited medications during the study:
●
Biologic therapy with a potential therapeutic impact on ulcerative colitis 
including but not limited to the following:
○
Anakinra (Kineret®);
○
Abatacept (Orencia®);
○
Natalizumab (Tysabri®);
○
Efalizumab (Raptiva®);
○
Infliximab (Remicade®);
○
Etanercept (Enbrel®);
○
Rituximab (Rituxan®);
○
Tocilizumab (Actemra®);
○
Golimumab (Simponi®);
○
Certolizumab (Cimzia®);
○
Ustekinumab (Stelara®);
○
Belimumab (Benlysta®);
○
Vedolizumab (Entyvio®).
●
The use of Tofacitinib (Xeljanz®) is prohibited during the study.
●
Live vaccines (during the study and for 70 days after the last dose of study 
drug).
●
The use of systemic cyclosporine, tacrolimus, or mycophenolate mofetil is 
prohibited during the study.
●
Intravenous corticosteroid use is prohibited during the study.
●
The use of investigational drugs of chemical or biologic nature are prohibited 
during the study.
The AbbVie study designated physician identified in Section 6.1.7 should be contacted if 
there are any questions regarding prohibited therapy.
 

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5.3
Efficacy, Pharmacokinetic, Pharmacodynamic, 
Pharmacogenetic and Safety Assessments/Variables
5.3.1
Efficacy and Safety Measurements Assessed and Flow 
Chart
Study procedures will be performed as summarized in Table 1.  There is a ± 3-day 
window for all study visits.
Allowed protocol modifications due to states of emergency or pandemic situations are 
detailed in this section.
 

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Table 1.
Study Activities
Activity
Baseline 
(Week 0)a
Week 
4
Week 
8
Week 
12
Week 
24
Week 
36
Week 
48
Week 
60
Week 
72
Week 
84
Week 
96 
Week 
108  
Week 
120 
Week 
132 
Calls
Informed Consent
X
Inclusion/Exclusion
X
Medical/Surgical History
Xd
Tobacco and Alcohol Use
Xd
Previous and Concomitant 
Medication
Xd
X
X
X
X
X
X
X
X
X
X
X
X
X
Vital Signse
Xd
X
X
X
X
X
X
X
X
X
X
X
X
Endoscopy (optional)f
Xd
X
X
Physical Examinationg
Xd
X
X
X
X
X
X
X
X
X
X
X
X
TB testingh
Xd
X
X
Chemistry and Hematologyi
Xd
X
X
X
X
X
X
X
X
X
X
X
Urinalysisj
Xd
X
X
X
X
X
X
Pregnancy Testsk,l
Xd
Xl
Xl
Xl
Xl
Xl
Xk
Xl
Xl
Xl
Xk
Xl
Xl
hs-CRPi 
Xd
X
X
X
X
X
PUCAI
Xd
X
X
X
X
X
X
X
X
X
X
X
X
Partial Mayo Score
Xd
X
X
X
X
X
X
X
X
X
X
X
X
Mayo Scoref
Xd
X
X
IMPACT III Questionnairem
Xd
X
X
X
X
X
Work Productivity and 
Impairment Questionnaire 
(WPAI):  UC – Caregivern
Xd
X
X
X
X
X
 

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Table 1.
Study Activities (Continued)
Activity
Baseline 
(Week 0)a
Week 
4
Week 
8
Week 
12
Week 
24
Week 
36
Week 
48
Week 
60
Week 
72
Week 
84
Week 
96 
Week 
108  
Week 
120 
Week 
132 
Calls
Tanner Stage
Xd
X
X
Anthropometric Evaluations
Xd
X
X
X
X
X-ray for Bone Ageo
Xd
X
X
Monitor Adverse Eventsp
Xd
X
X
X
X
X
X
X
X
X
X
X
X
X
Subject Diary 
Dispensing/Reviewingq
Xd
X
X
X
X
X
X
X
X
X
X
X
X
Study Drug 
Dispensing/Administrationr
X
X
X
X
X
X
X
X
X
X
X
X
X
 

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Table 1.
Study Activities (Continued)
Activity
Week 
144 
Week 
156 
Calls
Week 
168 
Week 
180 
Calls
Week 
192 
Week 
204 
Calls
Week 
216 
Week 
228 
Calls
Week 
240 
Week 
252 
Calls
Week 
264
Week 
276 
Calls
Week 288/ 
Premature 
Discontinuation
Unscheduled 
Visitb
70-Day 
Follow-
Up 
Callc
Informed Consent
Inclusion/Exclusion
Medical/Surgical 
History
Tobacco and 
Alcohol Use
Previous and 
Concomitant 
Medication
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Vital Signse
X
X
X
X
X
X
X
X
Endoscopy 
(optional)f
X
X
Physical 
Examinationg
X
X
X
X
X
X
X
X
TB testingh
X
X
X
X
Chemistry and 
Hematologyi
X
X
X
X
X
X
X
X
Urinalysisj
X
X
X
X
X
X
X
X
Pregnancy Testsk,l
Xk
Xl
Xk
Xl
Xk
Xl
Xk
hs-CRPi
X
X
X
X
X
X
X
X
PUCAI
X
X
X
X
X
X
X
X
 

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Table 1.
Study Activities (Continued)
Activity
Week 
144 
Week 
156 
Calls
Week 
168 
Week 
180 
Calls
Week 
192 
Week 
204 
Calls
Week 
216 
Week 
228 
Calls
Week 
240 
Week 
252 
Calls
Week 
264
Week 
276 
Calls
Week 288/ 
Premature 
Discontinuation
Unscheduled 
Visitb
70-Day 
Follow-
Up 
Callc
Partial Mayo Score
X
X
X
X
X
X
X
X
Mayo Scoref
X
X
IMPACT III 
Questionnairem
X
X
X
X
X
X
X
Work Productivity 
and Impairment 
Questionnaire 
(WPAI): UC –
Caregivern
X
X
X
X
X
X
X
Tanner Stage
X
X
X
X
Anthropometric 
Evaluations
X
X
X
X
X-ray for Bone 
Ageo
X
X
X
X
Monitor Adverse 
Eventsp
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Subject Diary 
Dispensing/ 
Reviewingq
X
X
X
X
X
X
X
X
Study Drug 
Dispensing/ 
Administrationr
X
X
X
X
X
X
X
 

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Table 1.
Study Activities (Continued)
a.
The Baseline visit date will serve as the reference for all subsequent visits.  A ± 3-day window is permitted around scheduled study visits.
b.
Procedures performed as needed.
c.
Site personnel will contact all subjects approximately 70 days following study drug discontinuation to determine the occurrence of AEs or SAEs.
d.
At the Baseline visit, the following procedures for Study M10-870 will be completed as part of Week 52 of the Study M11-290 protocol:  tobacco & alcohol use; concomitant 
medication changes, physical exam, vital signs, Chemistry/hematology, hs-CRP; PUCAI; urinalysis, pregnancy test; TB testing, Partial Mayo Score; Mayo Score, 
IMPACT III Questionnaire, WPAI UC-Caregiver, Tanner Stage, Anthropometric Evaluations, X-ray for Bone age; endoscopy, adverse events and subject diary 
dispensing/reviewing.  Medical History will be updated from the medical history recorded during the subject's previous study.
e.
Vital sign determinations of weight, sitting blood pressure, pulse rate, respiratory rate, body temperature will be obtained at each visit.
f.
The endoscopy is optional at Weeks 48, 96, 192 and 288/Premature Discontinuation.  In this case, endoscopies may be either flexible sigmoidoscopy or colonoscopy.  
Biopsies to rule out malignancy, dysplasia, and infection may be taken at the investigator's discretion.  Mayo score is dependent on availability of endoscopy.
g.
Physical examinations performed at Weeks 48, 96, 144, 192, 240, and 288/Premature Discontinuation Visits are full physical examinations and those performed at all other 
visits are symptom based.
h.
For subjects with a negative TB test, a TB test will be required at Weeks 48, 96, 144, 192, 240 and 288.  If the annual TB screen is positive, a CXR may be required for 
evaluation of active TB.  Annual TB screening will not be required for subjects who have been treated for latent or active TB or have had a positive TB test at any time (prior 
to the study, or testing performed at any time point during Study M11-290).  For such subjects, annual evaluation by a physician for clinical signs/symptoms of active TB 
(including a directed TB history and physical exam including lungs, lymph nodes and skin) or newly identified TB risk factors will be required at Weeks 48, 96, 144, 192, 240 
and 288.
i.
Blood draws should be performed after completion of all clinical assessments and questionnaires.
j.
Dipstick urinalysis will be completed by the sites at all required visits.  A microscopic analysis will be performed by the central laboratory, in the event the dipstick results 
show protein, ketones or blood greater than negative or glucose greater than normal.
k.
All females of childbearing potential will have a serum pregnancy test at Weeks 48, 96, 144, 192, 240 and 288/Premature Discontinuation Visit.
l.
At Week 4 visit and all subsequently scheduled study visits, all females of childbearing potential will have a urine pregnancy test performed locally by designated study 
personnel.  If any urine pregnancy test is positive, a serum pregnancy test will be performed by the central laboratory.  Any subject with a positive urine pregnancy test must 
have a negative serum test performed at the central laboratory prior to enrollment or continuation in the study.
 

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Table 1.
Study Activities (Continued)
m.
IMPACT III Quality of Life questionnaire at Weeks 24, 48, 72, 96, 120, 144, 168, 192, 216, 240, 264 and 288/Premature Discontinuation Visit will be completed for subjects 
9 years of age or older at the baseline study visit.
n.
WPAI will be completed by subject's parent or legal guardian at Weeks 24, 48, 72, 96, 120, 144, 168, 192, 216, 240, 264 and 288/Premature Discontinuation Visit.  The 
questionnaire will not be completed if the subject's parent or legal guardian is not taking care of the subject anymore.
o.
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 can be omitted.  Assessment of bone age is not required 
for subjects at the Premature Discontinuation Visit. 
p.
Collection of SAEs begins the day the subject signs the informed consent.
q.
Subjects will be dispensed a subject diary at Baseline and will be trained on how to complete the diary by site staff during the Baseline visit.  All subjects should complete 
their subject diary on a daily basis throughout the entire study, including if and when hospitalized whenever possible.  The diary will be reviewed by site personnel with the 
subject at each visit and collected at the Week 288/Premature Discontinuation Visit.
r.
Study drug may be dispensed at the Unscheduled Visit if there is a change in the dosing schedule (i.e., subject meets criteria of disease flare) or if damaged drug needs 
replacement.
s.
Phone calls will be made to collect information on concomitant medications and AE/SAE's.
 

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5.3.1.1
Study Procedures
The study procedures outlined in Table 1 are discussed in detail in this section, with the 
exception of the collection of adverse event (AE) information (discussed in Section 6.1.2).  
All study data will be recorded in source documents and on the appropriate eCRFs.
Study visits may be impacted due to states of emergency or pandemic situations.  This 
may include changes such as phone or virtual visits, among others.  Every effort should be 
made to ensure the safety of subjects and site staff, while maintaining the integrity of the 
study.  If visits cannot be conducted onsite due to travel restrictions or other pandemic-
related reasons, follow the updates below on how to proceed.
States of Emergency or Pandemic -Related Acceptable Protocol Modifications
During states of emergency or pandemic situations, if it is not possible for all study 
procedures to be performed as specified due to travel restrictions or other reasons, the 
following modifications are allowed:
Study visits and/or activities may be performed by phone/virtually.  These are indicated 
below;
●
Assess safety (AEs/concomitant medications/contraception, investigation 
product compliance/dosing (including last date and dose of study drug));
●
Investigator assessments (ex. Physician Global Assessment in Partial Mayo 
Score and Mayo Score) can be completed by using the applicable subscores 
and by patient interview.
●
IMPACT III and WPAI questionnaires will be completed over the 
telephone/virtual meeting;
●
Please ensure that the subject completes ePRO diary entries and confirm with 
the subject that diary entries are being completed.
●
The subject must be weighed at home and provide it to the study site so that 
the dose to be administered can be determined.  If there is a deviation in 
weight >10% from the previous body weight, site and parent/subject should 
determine if this is due to calibration of scales between site and home scale.
 

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●
During a virtual visit, the following activities do not need to be performed:  
vital signs (except weight), physical exam, Tanner Stage, height (for 
anthropometric evaluation), and bone age.
●
Lab samples (including pregnancy test for females of childbearing potential) 
may be performed by a local clinic/hospital/laboratory.  All procedures 
performed at local facilities must be performed by appropriately qualified 
personnel.  If lab samples cannot be collected, the study drug cannot be 
dispensed to the subject.  Any local labs should be collected and reported in 
alignment with the protocol requirements and reviewed by the investigator as 
soon as possible.
●
Study Visits and/or activities should be performed as scheduled whenever 
possible.
●
If an activity is missed during a virtual visit, perform the activity at the earliest 
feasible opportunity.
Inclusion/Exclusion Criteria
Subjects will be evaluated to ensure they meet all inclusion criteria and none of the 
exclusion criteria at the Baseline Visit.
Informed Consent
An Independent Ethics Committee (IEC)/Institutional Review Board (IRB) approved, 
study-specific informed consent will be reviewed, signed and dated by the parent or their 
guardian before any study procedures are undertaken, or before any concomitant 
medications are withheld from the subject in order to participate in this study.  Pediatric 
subjects will be included in all discussions.  If a subject becomes of legal age in the state 
of residence during the course of the study, an informed consent will need to be obtained 
at that time.  Additionally, in complying with each institution's IRB requirements, an 
informed assent may also be obtained from the subject.
Details about how informed consent will be obtained and documented are provided in 
Section 9.3.
 

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Before informed consent may be obtained, the investigator or designee will explain the 
nature and purpose of the study and its procedures to the subject.  Ample time and 
opportunity for the subject or the parent or their guardian, or the subject's legally 
acceptable representative to ask any questions about the study will be provided, so that an 
informed consent can be made as to whether or not to participate in the study.  All 
questions about the study will be answered to the satisfaction of the subject.
After the informed consent is signed and dated by the parent or guardian, the person who 
discussed the informed consent will also sign and date the document and provide a copy 
of the informed consent to the subject.  The original informed consent will be placed in 
the subject's medical record with documentation that the informed consent was signed 
prior to the performance of any study procedures and that the subject was given a signed 
and dated copy.
Due to states of emergency or pandemic situations, it is possible that additional protocol 
modifications not outlined in this protocol may become necessary. If this situation arises, 
in addition to the study informed consent, additional verbal consent may be obtained prior 
to these adaptations or substantial changes in study conduct in accordance with local 
regulations.
Medical and Surgical History
A complete medical and surgical history (which includes family history and UC-onset 
date) as well as history of tobacco and alcohol use, will be obtained from each subject 
from Study M11-290.  Medical history will be updated at the Baseline Visit.
Vital Signs
Vital sign determinations of systolic and diastolic blood pressure in sitting position, pulse 
rate, respiratory rate, body weight, and body temperature will be obtained at each visit.  
Blood pressure, pulse rate and respiratory rate should be performed before blood draws 
are performed.  All measurements will be recorded in metric units if possible.
 

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States of Emergency or Pandemic-Related Acceptable Protocol Modifications
Due to states of emergency or pandemic situations, subject visits may be conducted via 
phone or video conference.  In these situations, vital signs (except weight) are not 
required but may be performed by the subject or caregiver as needed.
The vital signs collected at the Week 52 visit of Study M11-290 will be used for the 
Baseline assessment (prior to receiving study drug).
Annual TB testing
For subjects with a negative TB test at the Screening visit of parent Study M11-290, an 
annual PPD or QuantiFERON-TB Gold re-test will be required.
The TB test sample collected at the Week 52 visit of Study M11-290 will be used for the 
Baseline assessment (prior to receiving study drug).  Annual TB screening will not be 
required for subjects who have been treated for latent or active TB or have had a positive 
TB test at any time (prior to the study, or testing performed at any time point during 
Study M11-290).  For such subjects, annual evaluation by a physician for clinical 
signs/symptoms of active TB (including a directed TB history and physical exam 
including lungs, lymph nodes and skin) or newly identified TB risk factors will be 
required at Baseline, Weeks 48, 96, 144, 192, 240 and 288.
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 CXR may be required for evaluation 
of active TB.
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 including those with a prior history of Bacille 
Calmette-Guérin (BCG) administration at the time the subject reaches the scheduled 
visits:  Baseline, Weeks 48, 96, 144, 192, 240 and 288.
 

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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.
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 
 

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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.
Subjects can have a repeat CXR at any time during the study as warranted based on the 
opinion of Investigator.
Physical Examination
A full physical examination will be performed at Baseline, Weeks 48, 96, 144, 192, 240 
and 288/Premature Discontinuation Visits.  Symptom-based physical examinations will be 
performed at all other visits.
The physical exam performed at the Week 52 visit of Study M11-290 will be used for the 
Baseline assessment (prior to receiving study drug).
A physical exam will be performed at the designated study visits in Table 1.
Physical examination findings that are related or part of each subject's medical history 
should be captured on the appropriate eCRF page.
Pregnancy Tests
A serum pregnancy test will be performed at the Baseline, Weeks 48, 96, 144, 192, 240 
and 288/Premature Discontinuation Visits on all female subjects who are experiencing 
menses or are nearing sexual maturation in the opinion of the Investigator or who are of 
childbearing potential. 
The serum pregnancy test collected during the Week 52 of Study M11-290 will be used 
for the Baseline assessment (prior to receiving study drug).
 

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At all other subsequently scheduled study visits, subjects who are experiencing menses or 
are nearing sexual maturation in the opinion of the Investigator or are of childbearing 
potential will have a urine pregnancy test performed locally by designated study 
personnel.  If any urine pregnancy test is positive, a serum pregnancy test will be 
performed by the central laboratory.  A lactating or pregnant female will not be eligible 
for participation or continuation in this study.  Monthly pregnancy tests will be performed 
throughout the study if required by country regulatory authorities.
Clinical Laboratory Tests
Blood samples will be obtained for the laboratory tests listed in Table 2 at the Baseline, 
Weeks 4, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 144, 168, 192, 216, 240, 264, 
288/Premature Discontinuation Visits.  Blood draws should be performed after all clinical 
assessments and questionnaires, vital sign determinations are obtained and before study 
drug administration during a visit.
The Blood sample collected at the Week 52 visit of Study M11-290 will be used for the 
Baseline assessment (prior to receiving study drug).
A certified central laboratory will be utilized to process and provide results for the clinical 
laboratory tests.  All abnormal laboratory tests that are considered clinically significant by 
the investigator will be followed to a satisfactory resolution.
The central laboratory chosen for this study will provide instructions regarding the 
collection, processing and shipping of these samples.
Measurements and Volume(s) of Blood Samples to Be Drawn are described in 
Appendix I.
 

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Other Laboratory Assessments
hs-CRP
Blood samples for high-sensitivity C-Reactive Protein (hs-CRP) will be obtained at the 
Baseline, Weeks 24, 48, 72, 96, 120, 144, 168, 192, 216, 240, 264 and 288/Premature 
Discontinuation Visits.
The Blood sample collected at the Week 52 visit of Study M11-290 will be used for the 
Baseline assessment (prior to receiving study drug).
Blood draws should be performed after all clinical assessments and questionnaires, vital 
sign determinations are obtained and before study drug administration during a visit.
Urinalysis
Urine samples will be obtained and sent to the central lab for the tests listed in Table 2 at 
the Baseline Weeks 4, 24, 48, 72, 96, 120, 144, 168, 192, 216, 240, 264, and 
288/Premature Discontinuation Visits.  Microscopic urinalysis will only be performed by 
the central laboratory if the dipstick UA results are abnormal, where abnormal is defined 
as a ketone, protein, blood or glucose value of greater than a trace.
The urine sample collected at the Week 52 visit of Study M11-290 will be used for the 
Baseline assessment (prior to receiving study drug).
 

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Table 2.
Clinical Laboratory Tests
Hematology
Clinical Chemistry
Urinalysis
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
Albumin
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
Specific gravity
Ketones
pH
Protein
Glucose
Blood
Others
High-sensitivity C-reactive
protein (hs-CRP)
β-HCG
States of Emergency or Pandemic-Related Acceptable Protocol Modifications
If travel restrictions or other changes in local regulations in light of states of emergency or 
pandemic situations prevent the subject from having blood drawn for laboratory testing at 
the study site, if possible, arrange for subjects to have laboratory work done at a local lab, 
hospital, or other facility.  Local lab results should be obtained along with reference 
ranges and kept within the subjects' source documentation.  Local lab results should be 
reviewed by the investigator as soon as possible.
If laboratory samples cannot be obtained, study drug cannot be dispensed to the subject.  
The subject should be scheduled for laboratory draws as soon as feasible prior to the 
scheduled visit.
 

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Bone Age
An x-ray of the wrist for the assessment of bone age will be obtained at Baseline; 
Weeks 48, 96, 144, 192, 240 and 288 visit to determine changes in bone maturation.  Sites 
should use the Greulich and Pyle method for reading the x-ray.21  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 eCRF.  Assessment of bone age will 
not be required for subjects at the Premature Discontinuation visit.
The x-ray collected at the Week 52 visit of Study M11-290 will be used for the Baseline 
assessment (prior to receiving study drug).  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 can be omitted.
Anthropometric Evaluations
Height and weight obtained at Baseline, Weeks 24, 48, 72 and 96, 144, 192, 240 and 
288/Premature Discontinuation 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.
At Baseline, height from the Week 52 visit of Study M11-290 will be used and maximal 
weight attained will be recorded.
Tanner Stage
Tanner Stage will be assessed at Baseline, Weeks 48, 96, 144, 192, 240 and 
288/Premature Discontinuation Visit.  Tanner Staging should be captured on the 
appropriate eCRF page.  The Tanner Stage assessed at the Week 52 visit of 
Study M11-290 will be used for the Baseline assessment (prior to receiving study drug).
 

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Pediatric Ulcerative Colitis Activity Index (PUCAI)
A PUCAI score will also be calculated at all study visits beginning at Baseline.  The 
PUCAI score calculated at the Week 52 visit of Study M11-290 will be used for the 
Baseline assessment (prior to receiving study drug).
An example of the PUCAI is located in Appendix C.
The PUCAI score will be assessed using subject-reported symptoms and activity level.  
The answers should reflect symptoms and activity level during the previous 24 hours.  
The PUCAI scores of the last 2 days prior to each study visit will be averaged and used 
for the PUCAI scores for each study visit.  The total PUCAI score will be rounded up to 
the next 5-point interval as applicable.  In order to account for unavailable or excluded 
diary entries as per the provisions given below diary entries for the PUCAI score of the 
most recent 2 days within 10 days prior to each study visit will be used.
Diary entries of the following days should not be included in the 2 days prior to the visit 
that are evaluated for the PUCAI score:  (1) the day the subject received medication for 
bowel preparation prior to endoscopy, (2) the day the subject underwent an endoscopy, 
and (3) 2 days following the endoscopy.  Earlier diary entries will be used accordingly in 
order to provide the most recent data for 2 days prior to the respective study visit.
The subscore for the number of stools per 24 hours during days which a subject received 
anti-diarrheal medication will be scored as 15.
Mayo Score
All subjects will be provided with a Subject Diary at the Baseline Visit where they will 
record ulcerative colitis related symptoms.  The Partial Mayo Score will be calculated 
from the subject diary at each visit beginning at Baseline.  The average entry from the 
5 days prior to each study visit will be used for each subject-reported subscore.  In 
addition to the physical examination, the investigator should use the subject-reported 
 

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subscores of abdominal discomfort and functional assessment to determine the physician's 
global assessment subscore.
Normal number of bowel movement is the number of stools per day (24 hours) that is 
typical for the subject when having active UC but not experiencing a flare.  Each subject 
serves as his or her own control to establish the degree of abnormality of the stool 
frequency.
The Mayo Score (consisting of the Partial Mayo Score plus the endoscopic subscore) will 
be calculated at weeks where endoscopy is performed (i.e., Week 48, 96, 192 and 288).  
The Partial Mayo Score and the Mayo Score (consisting of the Partial Mayo Score plus 
the endoscopic subscore) assessed at the Week 52 visit of Study M11-290 will be used for 
the Baseline assessment (prior to receiving study drug).  The Mayo Score and the Script 
for collection of Mayo Score are described in Appendix D.
The average stool frequency subscore, rectal bleeding subscore, Partial Mayo score and 
Mayo score for each study visit will be recorded in the eCRF in decimal numbers.
For the purpose of disease flare assessment, Baseline PMS will be rounded up or down to 
the nearest full number.  For example, if a patient had a PMS of 5.4 at Baseline and came 
in for a disease flare assessment, then the Baseline PMS would be rounded down to 5.0 
for this purpose.  If a patient had a PMS of 5.5 at Baseline and came in for a disease flare 
assessment, then the Baseline PMS would be rounded up to 6.0.
Whenever possible, the same physician (investigator or subinvestigator) should determine 
all Mayo Scores and Partial Mayo Scores for an individual subject through the duration of 
the study.
IMPACT III Questionnaire22
Subjects 9 years of age or older at Baseline will complete an IMPACT III questionnaire at 
Baseline, Weeks 24, 48, 72, 96, 120, 144, 168, 192, 216, 240, 264, and 288/Premature 
Discontinuation Visit.
 

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The IMPACT III questionnaire assessed at the Week 52 visit of Study M11-290 will be 
used for the Baseline assessment (prior to receiving study drug).
WPAI Questionnaire
Work Productivity and Activity Impairment Questionnaire (WPAI) will be completed at 
Baseline, Weeks 24, 48, 72, 96, 120, 144, 168, 192, 216, 240, 264, and 288/Premature 
Discontinuation Visit (Appendix E).  The WPAI questionnaire assessed at the Week 52 
visit of Study M11-290 will be used for the Baseline assessment (prior to receiving study 
drug).
The subject's parent or legal guardian will complete the WPAI.  The questionnaire will 
not be completed if the subject's parents or legal guardian do/does not take care of the 
subject anymore.
States of Emergency or Pandemic-Related Acceptable Protocol Modifications
Due to states of emergency or pandemic situations, subject visits may be conducted via 
phone or video conference. PROs eligible for completion by interview at such visits are 
the IMPACT III and WPAI Questionnaires. In this situation, sites will read the PRO 
questions and response options to the subject and record the subject's responses. The 
subject's ability to view the PRO to understand the questions and response options should 
be preserved. Sites may share the questionnaire by videoconference or send the 
questionnaires (email or hard copy) to the subjects to allow them to read/understand the 
questions and responses when the subject is providing responses over the phone. The date 
and time of PRO data collection should be recorded along with who collected the 
information.
Subject Diary/Dosing Log
Subjects will be dispensed an electronic diary at Baseline and will be trained on how to 
complete the diary by site staff during the Baseline visit.  All subjects should complete 
their subject diary on a daily basis throughout the entire study.  The diary will be reviewed 
 

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by site personnel with the subject at each visit and collected at the Week 288/Premature 
Discontinuation Visit.
Non-Drug Materials provided to the Study Sites are described in Appendix H.
Subjects will also be trained on how to complete the dosing log by site staff.  Dosing log 
must be recorded each time a dose is administered.  In the dosing log, the date and time 
study drug administration, the kit number, vial/syringe number and the dose administered 
will be recorded.  At every site visit, the site staff will record subject's body weight and 
will inform the subject or his/her caregivers about the amount/dose of study drug to be 
administered each week until the next site visit.
The dosing records will be reviewed and verified for compliance at each visit by the 
research personnel at the study center and reinforced if necessary.  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 the source documents 
and in the appropriate drug accountability form.
The subject should bring the subject diary/dosing log to every study visit.
Study Drug Dispensing/Administration
Study drug will be administered to all subjects by the subject or their designated family 
member or friend under the supervision of site medical staff to reinforce proper aseptic 
subcutaneous injection technique.  Subjects or a trained designated family member or 
friend or will perform the injections of the study medication in the subject's home during 
the weeks when a clinic visit is not scheduled.
At all office visits, subjects should be observed after study drug administration until 
judged medically appropriate by the study personnel.  If an anaphylactic reaction or other 
serious allergic reaction occurs, administration of study medication should be 
discontinued immediately and appropriate therapy initiated.  When dosing at home 
 

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subjects should be instructed to contact the site immediately with any signs or symptoms 
of a reaction.
Subjects should administer study medication on the same day of the week.  The dosing 
dates for all doses of study drug should be calculated from the Baseline visit date.  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 AbbVie Medical Monitor for additional instructions.
Study drug kits will be assigned by the IRT.  Since the amount of study drug that subject 
gets based on subject's body weight, at every site visit, study personnel will record 
subject's weight and will inform subject the amount/dose of study drug to be administered.
States of Emergency or Pandemic-Related Acceptable Protocol Modifications
Study drug may be shipped from the study site directly to the study subject's home if all 
the following criteria are met:
●
Direct-to-patient (DTP) shipment of study drug is allowed by local regulations 
and the relevant ethics committee
●
Study drug can be administered by the subject (or subject's caregiver) at home
●
Subject agrees to have the study drug shipped directly to their home
○
Shipments may also include other study supplies (e.g., drug dosing diaries, 
paper copies of PROs).  Instructions will be provided by AbbVie as to how 
a study site can initiate a DTP shipment using Marken, a global vendor 
selected by AbbVie to provide this service when necessary.  Shipments of 
study drugs from the study site to a subject's home will be appropriately 
temperature controlled (qualified shipper or temperature monitoring) 
within the labeled storage conditions.  Signature is required upon delivery; 
due to states of emergency or pandemic related social distancing, this may 
 

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be provided by the courier after delivery.  Documentation of the shipment 
is to be retained by the clinical site.
○
AbbVie will not receive subject identifying information related to these 
shipments, as the site will work directly with the courier.
The study site is responsible for meeting IRB/IEC reporting requirements related to DTP 
shipments of study drug, and for obtaining consent to provide delivery information to the 
courier and documenting this consent in source documents.  AbbVie will submit any 
required notifications to the regulatory authority as applicable.
Body Weight Adjusted Volumes of Study Drug for Administration of Open Label 
Adalimumab 0.6 mg/kg Dosing (Weight Based) prior to Amendment 4 are described in
Appendix F.
Subjects will be instructed to return all used and unused vials/syringes, Sharps containers 
and empty boxes at each visit for accountability.
Injections during subsequent study visits will be performed at the site by the subject or 
their designated family member or friend under the supervision of site medical staff to 
reinforce proper aseptic subcutaneous injection technique.  Subjects or a trained 
designated family member or friend or will perform the injections of the study medication 
in the subject's home during the weeks when a clinic visit is not scheduled.
Endoscopy (Optional)
An endoscopy may be performed at the discretion of the investigator on the following 
occasions:
●
Week 48
●
Week 96
●
Week 192
●
Week 288/Premature Discontinuation
 

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In this case, endoscopies may be either flexible sigmoidoscopy or colonoscopy.  
Note:
●
Biopsies to rule out malignancy, dysplasia, colon cancer or infection may be 
taken at the investigator's discretion.
The evaluation of endoscopies will be done by usage of the endoscopy subscore scale of 
the Mayo score and will include an assessment of friability.
5.3.2
Efficacy Variables
This study will utilize the PMS (and Mayo score if available) and PUCAI to determine 
efficacy of the study drug.
The following efficacy endpoints will be analyzed using summary statistics:
●
The proportion of subjects who achieve clinical remission as measured by 
PMS (defined as a PMS ≤ 2 and no individual subscore > 1) over time;
●
The proportion of subjects who achieve clinical response as measured by PMS 
(defined as a decrease in PMS ≥ 2 points and ≥ 30% from Study M11-290 
Baseline) over time;
●
The proportion of subjects who achieve PUCAI remission (defined as < 10) 
over time;
●
The proportion of subjects who achieve PUCAI response (defined as a 
decrease in PUCAI ≥ 20 points from Study M11-290 Baseline).
Efficacy will also be evaluated based on other measures of disease activity, including 
IMPACT III, WPAI, z-score for height and weight, bone age, BMI, and laboratory values 
as applicable.  The proportion of subjects who achieve remission/response based on Mayo 
score and mucosal healing based on Mayo endoscopy subscore will be summarized for 
subjects with available Mayo score.
 

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5.3.3
Safety Variables
Safety analyses will be performed on all subjects who receive at least one dose of study 
drug.  Incidence of adverse events (AEs), changes in vital signs, physical examination 
results, and clinical laboratory data will be assessed.
5.3.4
Pharmacokinetic Variables
Pharmacokinetic and Immunogenicity:
Blood samples for serum adalimumab concentrations and immunogenicity status collected 
prior to Amendment 2 will be maintained for potential analysis of serum adalimumab and 
AAA concentrations.  As appropriate, population pharmacokinetic analysis and/or any 
additional analyses may be performed.
Samples collected prior to Amendment 2 will be stored in a secure storage space with 
adequate measures to protect confidentiality.  The samples may be retained for up to 
5 years (where allowed by local guidelines) after completion of the study research.  
Samples that are not analyzed will be discarded by the end of the 5-year period specified 
above.
5.3.4.1
Cytokines and Serologic Variables
Samples collected prior to Amendment 2 may be analyzed for serologic antibodies and 
cytokines that may help predict disease behavior and help determine disease phenotypes 
or response to or tolerability of treatment.  Some antibodies or immune markers 
insufficiently characterized or unknown may be understood to be important at the time of 
analysis.  The samples may also be used for the development of diagnostic tests.  The 
results of analyses will not be reported with the study summary.
Samples collected prior to Amendment 2 will be stored in a secure storage space with 
adequate measures to protect confidentiality.  The samples may be retained for up to 
5 years (where allowed by local guidelines) after completion of the study research.  
 

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Samples that are not analyzed will be discarded by the end of the 5-year period specified 
above.
5.4
Removal of Subjects from Therapy or Assessment
5.4.1
Discontinuation of Individual Subjects
A subject may withdraw from the study at any time.  The Investigator may discontinue 
any subject's participation for any reason, including an adverse event, safety concerns or 
failure to comply with the protocol.
Subjects will be withdrawn from the study immediately if any one of the following 
occurs:
●
Clinically significant abnormal laboratory result(s) or adverse event(s), as 
determined by the Investigator in consultation with the AbbVie Medical 
Monitor.
●
The Investigator believes it is in the best interest of the subject.
●
The subject requests withdrawal from the study.
●
Inclusion and exclusion criteria violation was noted after the subject started 
study drug, when continuation of the study drug would place the subject at risk 
as determined by the AbbVie Medical Monitor (see Section 5.2 and 
Section 6.1.7).
●
Introduction of prohibited medications or dosages when continuation of the 
study drug would place the subject at risk as determined by the AbbVie 
Medical Monitor.
●
Subject is non-compliant with TB prophylaxis.
●
The subject becomes pregnant while on study medication.
●
Subject is diagnosed with a malignancy, except for localized non-melanoma 
skin cancer.  Discontinuation for dysplasia or carcinoma in-situ of the cervix is 
at the discretion of the Investigator.
●
Subject is diagnosed with lupus-like syndrome, multiple sclerosis or 
demyelinating disease.
 

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●
Subject is significantly non-compliant with study procedures which would put 
the subject at risk for continued participation in the trial, as determined by the 
Investigator, in consultation with the AbbVie Medical Monitor.
States of Emergency or Pandemic-Related Acceptable Protocol Modification
During states of emergency or pandemic situations, it has been necessary to employ 
mitigation strategies to enable the investigator to ensure subject safety and continuity of 
care.  Acceptable mitigation strategies are identified throughout the protocol.
The investigator should contact the sponsor medical contact before discontinuing a subject 
from the study for a state of emergency or pandemic related reason to ensure all 
acceptable mitigation steps have been explored.
Interruption/Discontinuation of Study Drug Due to COVID-19 Infection
During the Study Drug Dosing Period, a subject with confirmed (viral test positive) or 
suspected COVID-19 infection can only be dosed with study drug if the following 
COVID-19 viral clearance criteria are met:
●
Symptomatic subjects:  At least 2 negative viral tests in a row, ≥ 24 hours apart 
after at least 10 days have passed since recovery, defined as resolution of fever 
without use of antipyretics and improvement in respiratory symptoms 
(e.g., cough, shortness of breath)
●
Asymptomatic subjects:  At least 2 negative viral tests in a row, ≥ 24 hours 
apart after at least 10 days have passed since prior positive result (note:  
subjects who develop symptoms will follow guidance above for symptomatic 
subjects)
Delays in study drug dosing due to the above COVID-19 testing guidance for subjects 
must be discussed with the AbbVie medical contact, along with the possibility of 
premature discontinuation from the study drug dosing period.  Frequency or timing of 
COVID-19 testing and intervals between testing for the above viral clearance criteria may 
 

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be adjusted to account for epidemiologic trends, updated information regarding 
infectivity, and local/institutional guidelines.
If, during the course of study drug administration, the subject prematurely discontinues 
study drug use, the procedures outlined for the Termination Visit must be completed 
within 2 weeks of the last dose of study drug, and preferably prior to the initiation of 
another therapy.  However, 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.
A final phone call will be made to the subject at least 70 days after the last dose of study 
drug to determine the status of any ongoing AEs/SAEs or the occurrence of any new 
AEs/SAEs.
All attempts must be made to determine the date of the last dose of study drug and the 
primary reason for premature discontinuation.  The information will be recorded on the 
appropriate eCRF page.
For subjects that are considered lost to follow-up, reasonable attempts must be made to 
obtain information on the final status of the subject.  At a minimum, two phone calls must 
be made and one certified letter must be sent.
5.4.2
Discontinuation of Entire Study
AbbVie may terminate this study prematurely, either in its entirety or at any study site, for 
reasonable cause provided that written notice is submitted in advance of the intended 
termination.  The investigator may also terminate the study at his/her site for reasonable 
cause, after providing written notice to AbbVie 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, AbbVie will immediately 
notify the investigator by telephone and subsequently provide written instructions for 
study termination.
 

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This study may conclude approximately 12 weeks after one of the following criteria have 
been satisfied:
●
Study drug received country and local (if applicable) regulatory approval for 
pediatric ulcerative colitis and application for local reimbursement has been 
submitted.
●
The Sponsor determined that continuation of the study does not further 
promote the scientific objective of the study.
Following site notification of upcoming conclusion of study, 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 are considered 
as having completed the study.
5.5
Treatments
5.5.1
Treatments Administered
Prior to Amendment 4, all subjects received open-label therapy as follows beginning at 
the Baseline Visit in Study M10-870:
●
Subjects who enrolled into the study from blinded treatment in Study M11-290 
were to receive open label 0.6 mg/kg (maximum of 40 mg) eow of 
adalimumab.
●
Subjects who received open label adalimumab in Study M11-290 were to 
maintain the same dose in Study M10-870.
After Amendment 4, ongoing subjects will be switched to receive a fixed dose regimen, 
by weight cutoff, incorporating open-label citrate free adalimumab in PFS (20 mg, 40 mg, 
or 80 mg) as follows:
●
Subjects with a body weight < 25 kg will receive open label 20 mg eow of 
adalimumab
 

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●
Subjects with a body weight ≥ 25 kg - < 40 kg will receive open label 40 mg 
eow of adalimumab
●
Subjects with a body weight ≥ 40 kg will receive open label 80 mg eow of 
adalimumab
Treatment of Subjects with Disease Flare
Prior to Amendment 4:
●
Subjects who were on 0.6 mg/kg (maximum dose of 40 mg, weight based) eow 
of adalimumab could receive 0.6 mg/kg (maximum of 40 mg, weight based) 
ew.
●
Subjects who were on 0.6 mg/kg ew of adalimumab could receive 40 mg ew 
(maximum dose) of adalimumab.
Subjects with persistently uncontrolled disease while on adalimumab 40 mg ew (max 
dose) were to be discontinued from the study.
After Amendment 4:
●
Subjects who are on 20 mg eow of adalimumab may receive 40 mg eow of 
adalimumab.
●
Subjects who are on 40 mg eow of adalimumab may receive 80 mg eow of 
adalimumab.
Subjects with persistently uncontrolled disease while on adalimumab 80 mg eow should 
be discontinued from the study.
Consideration should be given to have the subject return to the study site for unscheduled 
visit in order to collect the required PMS to satisfy the definition of disease flare.
 

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Criteria for Disease Flare are as follows:
●
Subjects with a Baseline Study M10-870 PMS of 0 to 2 who present with a 
PMS at least 3 points greater than their Baseline Study M10-870 score.
●
Subjects with a Baseline Study M10-870 PMS of 3 to 4 who present with a 
PMS at least 2 points greater than their Baseline Study M10-870 score.
●
Subjects with a Baseline Study M10-870 PMS of 5 to 6 who present with a 
PMS at least 1 point greater than their Baseline Study M10-870 score.
●
Subjects who present with a PMS at the current visit of at least 2 points greater 
than their PMS at the previous visit and who are not in remission per PMS.
Subjects who have been in remission (PMS ≤ 2 with no individual subscore > 1) for at 
least 8 weeks and for at least 2 consecutive visits may have their dosage de-escalated from 
ew to eow prior to Amendment 4 or to the next lower dose after Amendment 4.  The 
investigator should receive prior approval from the Medical Monitor before taking any 
action with regard to dose de-escalation.
If subjects demonstrate disease flare after dose de-escalation, subjects also have an 
opportunity to re-escalate their dose back to adalimumab ew dosing prior to Amendment 4 
or to the next higher dose after Amendment 4.  The investigator should receive prior 
approval from the Medical Monitor before taking any action with regard to dose 
re-escalation.  One de-escalation within a period of 48 weeks and one re-escalation within 
a period of 48 weeks are permissible.
5.5.2
Identity of Investigational Product
The individual study drug information is presented in Table 3.
 

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Table 3.
Identity of Investigational Products
Study Drug
Mode of 
Administration
Presentation
Strength
Manufacturer
Adalimumab
Subcutaneous 
injection
Vial or pre-filled 
syringe
Vial:
40 mg/0.8 mL
Pre-filled Syringe: 
20 mg/0.2 mL, 
40 mg/0.4 mL, and 
80 mg/0.8 mL
AbbVie
5.5.2.1
Packaging and Labeling
All Treatment Types
Investigational product will be packaged separately in cartons containing either vials or 
pre-filled syringes.  Each dosing kit carton will have a unique kit ID and contains 
two labeled vials or syringes.  Each vial/syringe and kit will be labeled per local 
regulatory requirements.
All labels must remain affixed to study medication at all times, and should never be 
removed for any reason.
Detailed list of study supplies are provided in Appendix H.
5.5.2.2
Storage and Disposition of Study Drug
Adalimumab vials/syringes are to be stored protected from light at 2°C to 8°C/36°F to 
46°F.  Study medication drug must not be frozen at any time.  A storage temperature log 
is to be maintained to document proper storage conditions.  The refrigerator temperature 
must be recorded every business day on a temperature log to record proper function.  
Malfunctions or any temperature excursion must be reported to the Sponsor immediately.  
Study medication should be quarantined and not dispensed until AbbVie GPRD or 
AbbVie Temperature Excursion Management System (ATEMS) deems the medication as 
acceptable.
 

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All clinical supplies must be stored and locked in a secure place until they are dispensed 
for subject use or are returned to AbbVie or destroyed at the site in accordance with local 
regulations and per instructions from 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
Subjects who meet the selection criteria in Section 5.2.1 and Section 5.2.2 will proceed to 
enter the study.  This is an open-label study, therefore, subjects will not be randomized.  
Subjects will keep their study subject number from the previous Study M11-290.  The
sites will be provided with appropriate kit number(s) for drug-dispensing purpose for each 
subject by the IRT.  Before the study is initiated, the telephone number and call-in 
directions for the IRT will be provided to each site.
5.5.4
Selection and Timing of Dose for Each Subject
Subjects should take study medication as outlined in Section 5.5.1.
If a subject should forget to administer the injection of study medication on their regularly 
scheduled dosing date, they should take the forgotten injection as soon as they remember 
the dose was missed up to the day of their next scheduled dose.  The subject should not 
administer two doses on the same day.
In the event the incorrect dose is taken or a dose is missed, the subject should be 
instructed to contact the site to determine how to proceed with dosing.  The subject must 
record all dosing information on the Subject Diary/Dosing Log.
Doses not administered (e.g., not taken before next dose is scheduled), should be recorded 
as not taken in the source.  The extra dose should be returned to the study site full.  The 
subject should resume their regular dosing schedule based on the first dosing date at 
Baseline.
 

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5.5.5
Blinding
This is an open-label study.
5.5.6
Treatment Compliance
The Investigator or his/her designated representatives will dispense study drug only for 
use by subjects enrolled in the study.  The study drug must not be used for reasons other 
than that described in the protocol.
The subject or their qualified designee will administer all doses of study drug.  
Appropriate site staff will supervise the subject's administration of the study drug at 
required in-office study visits to ensure proper injection technique.  In order to document 
compliance with the treatment regimen, the subject will be given a subject diary/dosing 
log to record all injection dates and times.  Compliance information will be documented 
on the appropriate eCRF.  Subjects will be counseled on missed doses of medication.  If 
the subject does not bring the subject diary/dosing log to the site visit and does not return 
used and unused vials/syringes, IP boxes and sharp containers (when applicable), the site 
should question the subject and obtain as much information as possible as to the dosing of 
the study drug.
The investigator or his/her designated and qualified representatives will 
administer/dispense study drug only to subjects enrolled in the study in accordance with 
the protocol.  The study drug must not be used for reasons other than that described in the 
protocol.
The information should be documented on the source documents as per "best recollection" 
and when possible, re-verified when the subject diary/dosing log is returned before 
completing on the applicable eCRF page.
5.5.7
Drug Accountability
The Investigator or designee will verify that study drug supplies are received intact, at the 
appropriate temperature, (in the US/Puerto Rico adequate temperature is cool to the touch, 
 

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OUS US/Puerto Rico temperature recording devices [templates] are provided in the 
shipments) and in the correct amounts.  This will be accomplished by documenting the 
condition of the shipment, verifying the kit numbers in the package against the Proof of 
Receipt (POR) or similar document included with each drug shipment, and documenting 
this verification by signing and dating the POR or similar document.  The original POR 
Note or similar document will be kept in the site files as a record of what was received.
In addition, an accurate running inventory of study drug will be kept by the site on a Site 
Drug Accountability log including date received, the lot number, kit number(s), date 
dispensed, subject number, and the identification with date of the person dispensing the 
drug.
All empty IP boxes, used and unused vials/syringes will be inventoried by the site.  Each 
subject will be given their own sharps disposal container to store used syringes.  Empty IP 
boxes, used and unused vials/syringes and Sharps containers should be returned by the 
subject at each visit for accountability and compliance purposes and new containers 
issued as necessary.  Empty IP boxes, used and unused vials/syringes and returned Sharps 
containers will be retained (unless prohibited by local law) until the CRA is onsite to 
confirm the returned medication.  CRAs and site staff will complete study medication 
accountability via study medication logs, source documents, subject diary/dosing log from 
ePRO, viewing used and unused vials/syringes, empty IP boxes and by visually inspecting 
the syringes in the Sharps container whenever possible.  Used Sharps containers should 
never be opened.  Once the CRA has verified drug accountability at the site, the site staff 
and CRA will document that the used vials/syringes have been destroyed, using 
appropriate biohazard precautions, when appropriate.  A copy of the destruction 
methodology should be maintained at the site's facility.  Unused medication will be 
returned by the CRA after drug accountability has been completed at the site or destroyed 
at the site in accordance with local regulations and per instructions from AbbVie.
 

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5.6
Discussion and Justification of Study Design
5.6.1
Discussion of Study Design and Choice of Control Groups
5.6.2
Appropriateness of Measurements
The design of this clinical trial was chosen to demonstrate adalimumab as an effective and 
safe therapy in pediatric subjects with moderately to severely active UC who completed 
the Study M11-290.  At Baseline, all subjects will receive open-label therapy.
Standard statistical, clinical, and laboratory procedures will be utilized in this study.  The 
clinical efficacy measurements in this study (Partial Mayo Score and PUCAI) are 
commonly used for assessing disease activity in clinical studies in subjects with UC.  All 
clinical and laboratory procedures in this study are standard or generally accepted.
5.6.3
Suitability of Subject Population
Pediatric subjects with moderately to severely active UC who completed the 
Study M11-290.  The specific subject population chosen was based on unmet medical 
needs of currently available medical therapies as well as previous anti-TNF studies that 
demonstrated effectiveness in UC.
5.6.4
Selection of Doses in the Study
Doses were selected using a population pharmacokinetic model of adalimumab using data 
from pediatric and adult subjects with Crohn's disease (Study M06-806 and 
Study M02-433, respectively) and adult subjects with ulcerative colitis (Study M06-827).  
Because UC disease was not a significant covariate on CL/F and V/F, and literature 
suggests that the demographic characteristics of pediatric subjects with CD and UC are 
similar, simulations were conducted using this PK model and demographic data from the 
pediatric CD study, Study M06-806, including age, weight, albumin concentrations and 
AAA rates.
In consideration of efficacy, safety and population pharmacokinetic results in conjunction 
with exposure-response modeling and simulation both treatments provided evidence of 
 

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efficacy and safety.  Therefore, in order to minimize the systemic exposures to study drug 
to the lowest doses necessary in children with UC the study design provides investigators 
with the option of dose de-escalation by reducing the dose (after Amendment 4) or 
switching from ew to eow (prior to Amendment 4) based on the clinical status of the 
individual patient.
The selected fixed-dose regimen after Amendment 4 is supported by modeling and 
simulation results generated with the final PK model with data from Study M11-290 and 
is aligned with the dosing per recently-approved and anticipated global labeling.  
Modeling and simulation analysis predicted largely overlapping concentration-time 
profiles in pediatric subjects with UC for the selected fixed-dose regimen and the 
respective mg/kg dosing studied in Study M11-290.  In addition, logistic regression 
analysis demonstrated comparable probability of achieving the Week 52 co-primary 
efficacy endpoint for the fixed-dose regimen and the mg/kg eow or ew dosing, 
respectively.
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 after it is released for 
distribution.
Complaints associated with any component of this investigational product must be 
reported to the Sponsor (Section 6.2).  For adverse events, please refer to Sections 6.1.1
and 6.1.7.  For product complaints, please refer to Section 6.2.
6.1
Medical Complaints
6.1.1
Definitions
The investigator will monitor each subject for clinical and laboratory evidence of adverse 
events on a routine basis throughout the study.  The investigator will assess and record 
 

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any adverse event in detail including the date of onset, event diagnosis (if known) or 
sign/symptom, severity, time course (end date, ongoing, intermittent), relationship of the 
adverse event to study drug, and any action(s) taken.  For serious adverse events 
considered as having "no reasonable possibility" of being associated with study drug, the 
investigator will provide an Other cause of the event.  For adverse events to be considered 
intermittent, the events must be of similar nature and severity.  Adverse events, whether in 
response to a query, observed by site personnel, or reported spontaneously by the subject 
will be recorded.
All adverse events will be followed to a satisfactory conclusion.
6.1.2
Adverse Event
An adverse event (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 adverse event 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 adverse event.
Worsening in severity of a reported adverse event should be reported as a new adverse 
event.  Laboratory abnormalities and changes in vital signs are considered to be adverse 
events only if they result in discontinuation from the study, necessitate therapeutic 
medical intervention (see Section 6.7 regarding toxicity management) and/or if the 
investigator considers them to be adverse events.
An elective surgery/procedure scheduled to occur during a study will not be considered an 
adverse event 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 
 

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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 adverse event.
6.1.3
Serious Adverse Events
If an adverse event meets any of the following criteria, it is to be reported to AbbVie as a 
serious adverse event (SAE) within 24 hours of the site being made aware of the serious 
adverse event.
Death of Subject
An event that results in the death of a subject.
Life-Threatening
An event that, in the opinion of the investigator, would have 
resulted in immediate fatality if medical intervention had 
not been taken.  This does not include an event that would 
have been fatal if it had occurred in a more severe form.
Hospitalization or 
Prolongation of 
Hospitalization
An event that results in an admission to the hospital for any 
length of time or prolongs the subject's hospital stay.  This 
does not include an emergency room visit or admission to 
an outpatient facility.
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).
 

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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).  Additionally, any elective or 
spontaneous abortion or stillbirth is considered an important 
medical event.  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.
For serious adverse events with the outcome of death, the date and cause of death will be 
recorded on the appropriate case report form.
6.1.4
Adverse Event Severity
The investigator will use the following definitions to rate the severity of each adverse 
event:
Mild
The adverse event is transient and easily tolerated by the subject.
Moderate
The adverse event causes the subject discomfort and interrupts 
the subject's usual activities.
Severe
The adverse event causes considerable interference with the 
subject's usual activities and may be incapacitating or 
life-threatening.
6.1.5
Relationship to Study Drug
The investigator will use the following definitions to assess the relationship of the adverse 
event to the use of study drug:
 

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Reasonable 
Possibility
An adverse event where there is evidence to suggest a causal 
relationship between the study drug and the adverse event.
No Reasonable 
Possibility
An adverse event where there is no evidence to suggest a causal 
relationship between the study drug and the adverse event.
For causality assessments, events assessed as having a reasonable possibility of being 
related to the study drug will be considered "associated."  Events assessed as having no 
reasonable possibility of being related to study drug will be considered "not associated."  
In addition, when the investigator has not reported a causality or deemed it not assessable, 
AbbVie will consider the event associated.
If an investigator's opinion of no reasonable possibility of being related to study drug is 
given, an Other cause of event must be provided by the investigator for the serious 
adverse event.
6.1.6
Adverse Event Collection Period
All adverse events reported from the time of study drug administration until 70 days 
following discontinuation of study drug administration have elapsed will be collected, 
whether solicited or spontaneously reported by the subject.  In addition, serious adverse 
events and protocol-related nonserious adverse events will be collected from the time the 
subject signed the study-specific informed consent.  Adverse event information will be 
collected and recorded on the appropriate eCRFs.
Subjects will be contacted approximately 70 days following study drug discontinuation 
for an assessment of any new or ongoing AEs.
There may be instances where a 70-day follow-up phone call occurs after the locking of 
the clinical database.  In this situation, any adverse events reported to AbbVie from this 
70-day follow-up phone call will be evaluated for inclusion in the clinical database.  All 
SAEs or adverse events of special interest, as defined by AbbVie, reported during the 
70-day follow-up phone call must be captured in the clinical database.
 

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Adverse event information will be collected as shown in Figure 1.
Figure 1.
Adverse Event Collection
SAEs and 
Protocol-Related 
Nonserious AEs
SAEs and Nonserious AEs
Elicited and/or Spontaneously Reported




Consent 
Signed
Study Drug 
Start
Study Drug 
Stopped
70 Days After 
Study Drug 
Stopped
6.1.7
Adverse Event Reporting
In the event of a serious adverse event, whether related to study drug or not, the 
Investigator will notify Clinical Pharmacovigilance within 24 hours of the site being made 
aware of the serious adverse event by entering the serious adverse event data into the 
RAVE® electronic data capture (EDC) system.  Serious adverse events that occur prior to 
the site having access to the RAVE® system or if RAVE® is not operable should be 
emailed (preferred route) to Clinical Pharmacovigilance within 24 hours of being made 
aware of the adverse event.
Email:  PPDINDPharmacovigilance@abbvie.com 
FAX to:  +1 (847) 938-0660
For safety concerns, contact the Immunology Safety Team at:
Immunology Safety Team
Dept. R48S, Bldg. AP31
AbbVie
1 North Waukegan Road
North Chicago, IL  60064
Telephone Contact Information:
Safety Hotline:
(847) 938-8737
Email:
GPRD_SafetyManagement_Immunology@abbvie.com
 

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COVID-19 infections should be captured as adverse events.  If the event meets the criteria 
for a serious adverse event (SAE), then follow the SAE reporting directions per the 
protocol and above.  The following COVID-19 related supplemental eCRFs should be 
completed:
●
COVID-19 Supplemental Signs/Symptoms
●
COVID-19 Status Form
If a subject has a confirmed or suspected COVID-19 infection and study drug was 
interrupted, the investigator should contact the sponsor emergency medical contact listed 
above before reintroducing study drug.
Reactions known to be associated with the SARS-CoV-2 vaccine should be reported as 
AEs. If the event meets the criteria for an SAE, then follow the SAE reporting directions.  
All AEs associated with the SARS-CoV-2 vaccine will be linked to the vaccine on the 
COVID-19 vaccine eCRF.
6.1.8
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 adverse event.  However, the medical 
outcome of an elective or spontaneous abortion, stillbirth or congenital anomaly is 
considered a serious adverse event and must be reported to AbbVie within 24 hours of the 
site becoming aware of the event.
 

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6.2
Product Complaints
Product Complaints concerning the investigational product 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.
Product Complaints may require return of the product with the alleged complaint 
condition.  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.
6.2.1
Definitions 
A Product Complaint is any Complaint (see Section 6.2 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 or packaging issues.
Any information available to help in the determination of causality to the events outlined 
directly above should be captured.
 

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6.3
Toxicity Management
Subjects who develop a new infection while undergoing treatment with adalimumab 
should be monitored closely.  Administration of study injections should be interrupted if a 
subject develops an infection requiring IV anti-infective treatment or if an infection meets 
the definition of "serious" (refer to Section 6.1.3 for definitions).  Study medication may 
be restarted once the physician determines that the infection has been successfully treated.  
Otherwise prohibited concomitant medications may be given if medically necessary.  
Prior to use, every attempt should be made to contact the AbbVie Study Physician for 
direction on re-introduction of adalimumab therapy after prohibited medication 
administration.
If the subject must undergo elective surgery, the study injections must be interrupted 
2 weeks prior to the surgery.  If the subject must undergo emergency surgery, the study 
injections must be interrupted at the time of the surgery.  The injectable study medication 
can recommence at least 2 weeks after surgery once the physician has examined the 
surgical site and determined that it has healed and there is no sign of infection.
7.0
Protocol Deviations
AbbVie does not allow intentional/prospective deviations from the protocol.  The 
principal investigator is responsible for complying with all protocol requirements, and 
applicable global and local laws regarding protocol deviations.  If a protocol deviation 
occurs (or is identified) after a subject has been enrolled, the principal investigator is 
responsible for notifying Independent Ethics Committee (IEC)/Independent Review 
Board (IRB) regulatory authorities (as applicable) including those that may be due to the
states of emergency or pandemic situations and the following AbbVie Representative:
 

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statistical analysis will be described and fully documented in the Statistical Analysis Plan 
(SAP).  The SAP will be finalized prior to the database lock.
8.1.1
Analyzable Population
The following populations will be used for analyses in this study:
The safety population for analysis of safety and the ITT population for evaluation of 
efficacy endpoints are identical and include all subjects who received at least one dose of 
adalimumab in Study M10-870.
8.1.2
Planned Methods of Statistical Analysis
All statistical analysis results will be reported using descriptive statistics.  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.  For dichotomized efficacy variables, data will be summarized by number 
and percent of subjects with 95% confidence interval.
8.1.3
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 M11-290).
8.1.4
Efficacy Analysis
Summary statistics will be provided for each visit, based on observed data and 
non-responder imputation (NRI) for missing categorical 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 Study M11-290 
value) will be carried forward to the last visit.  Details will be provided in the Statistical 
Analysis Plan (SAP).
 

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8.1.5
Statistical Analyses of Safety
Treatment emergent AEs, serious adverse events (SAEs), and AEs of special interest will 
be summarized by system organ class (SOC) and preferred term (PT) according to the 
Medical Dictionary for Regulatory Activities (MedDRA) AE coding dictionary.  A 
summary of AEs by severity and relationship to study drug will be performed.  Other 
safety variables such as laboratory and vital sign data will be described by descriptive 
statistics.  In addition, shift tables and listings will be provided.
8.1.6
Other Analyses
Details of subgroup analysis and all other analyses will be provided in the SAP.
8.1.7
Interim Analysis
An interim analysis on safety and efficacy will be performed and reported in a full Interim 
Clinical Study Report for inclusion of the Study M10-870 data in the submission of 
applications for regulatory approval of the pediatric UC indication in conjunction with the 
Study M11-290 results.  An interim analysis will be conducted after the last subject 
completed or discontinued from the M11-290 main study. Additional interim analyses 
may be performed, as needed.
8.2
Determination of Sample Size
Subjects who successfully completed Study M11-290 through Week 52 may be eligible to 
participate in this study.  Based on an expected number of 155 subjects being 
re-randomized at Week 8 of the parent study, an expected Study M11-290 completion rate 
of 66% and a roll-over rate of 80% of eligible subjects (based on previous experience with 
the pediatric CD Studies M06-806 and M06-807) it is expected that approximately 
85 subjects from Study M11-290 will enroll into the main study globally and 8 subjects 
from the Japanese sub-study.
 

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8.3
Randomization Methods
All subjects will be centrally registered using an IRT system.  This is an open-label study; 
therefore, subjects will not be randomized.  Before the study is initiated, the IRT log-in 
details will be provided to each site.  Subjects will keep their subject number from the 
previous study (Study M11-290).
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.  The IEC/IRB will review the 
ethical, scientific and medical appropriateness of the study before it is conducted.  
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.  The investigator will be required to submit, 
maintain and archive study essential documents according to ICH GCP.
Any serious adverse events 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.  Written documentation 
of the submission to the IEC/IRB should also be provided to AbbVie.
 

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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 
study conduct and the ethical principles that have their origin in the Declaration of 
Helsinki.  Responsibilities of the clinical investigator are specified in Appendix A.
In the event of a state of emergency or pandemic situations leading to difficulties in 
performing protocol-specified procedures, AbbVie will engage with study site personnel 
in efforts to ensure the safety of subjects, maintain protocol compliance, and minimize 
risks to the integrity of the study while trying to best manage subject continuity of care.  
This may include alternative methods for assessments (e.g., phone contacts or virtual site 
visits), alternative locations for data collection (e.g., use of a local lab instead of a central 
lab), and shipping investigational product and/or supplies direct to subjects to ensure 
continuity of treatment where allowed. In all cases, these alternative measures must be 
allowed by local regulations and permitted by IRB/IEC.  Investigators should notify 
AbbVie if any urgent safety measures are taken to protect the subjects against any 
immediate hazard.
9.3
Subject Information and Consent
The investigator or his/her representative will explain the nature of the study to the subject 
and the subject's parent/legal guardian, and answer all questions regarding this study.  
Pediatric subjects will be included in all discussions in order to obtain verbal or written 
assent.  Prior to any study-related procedures being performed on the subject, the 
informed consent statement will be reviewed and signed and dated by the subject's 
parent/legal guardian, the person who administered the informed consent, and any other 
signatories according to local requirements.  Additionally, in keeping with each 
institution's IRB requirements, an informed assent form may also be obtained by each 
subject prior to any study-related procedures being performed.  If a subject becomes of 
legal age during the course of the study, that subject will need to be re-consented.
 

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Non-genetic biomarker analysis will only be performed if the subject's parent/legal 
guardian has voluntarily signed and dated a separate non-genetic biomarker informed 
consent, approved by an IRB/IEC, after the nature of the testing has been explained and 
the subject and subject's parent/legal guardian has had an opportunity to ask questions.  
The separate non-genetic biomarker informed consent must be signed before the 
non-genetic biomarker testing is performed.  If the subject's parent/legal guardian does not 
consent to the non-genetic biomarker testing, it will not impact the subject's participation 
in the study.
A copy of the informed consent form will be given to the subject and the subject's 
parent/legal guardian and the original 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.
Information regarding incentives for subjects and information regarding provisions for 
treating and/or compensating subjects who are harmed as a consequence of participation 
in the study can be found in the informed consent form.
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 following assessments that will be completed by the subject and/or subject's 
parent/legal guardian or physician will be considered source documentation:
 

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●
IMPACT III
●
WPAI:  UC – Caregiver
The adverse event electronic data capture case report form (eCRF) data segments of:  
alternate etiology, severity, frequency and relationship to study drug, may also be used as 
source and will require an Investigator approval on the eCRF as verification of the 
accuracy of the information.
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.
During the states of emergency or pandemic situations, remote monitoring of data may be 
employed if allowed by the local regulatory authority, IRB/IEC, and the study site.
10.2
Case Report Forms
Case report forms (CRF) must be completed for each subject enrolled in this study.  These 
forms will be used to transmit information collected during the study to AbbVie and 
regulatory authorities, as applicable.  The CRF data for this study are being collected with 
an electronic data capture (EDC) system called Rave® provided by the technology vendor 
Medidata Solutions Incorporated, NY, USA.  The EDC system and the study-specific 
electronic case report forms (eCRFs) will comply with Title 21 CFR Part 11.  The 
documentation related to the validation of the EDC system is available through the 
vendor, Medidata, while the validation of the study-specific eCRFs will be conducted by 
AbbVie and will be maintained in the Trial Master File at AbbVie.
The investigator will document subject data in his/her own subject files.  These subject 
files will serve as source data for the study.  All eCRF data required by this protocol will 
be recorded by investigative site personnel in the EDC system, except for 
subject-completed questionnaires, which will be completed on paper by the subject then 
transcribed into the EDC system.  All data entered into the eCRF will be supported by 
source documentation.
 

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The investigator or an authorized member of the investigator's staff will make any 
necessary corrections to the eCRF.  All change information, including the date and person 
performing the corrections, will be available via the audit trail, which is part of the EDC 
system.  For any correction, a reason for the alteration will be provided.  The eCRFs will 
be reviewed periodically for completeness, legibility, and acceptability by AbbVie 
personnel (or their representatives). AbbVie (or their representatives) will also be allowed 
access to all source documents pertinent to the study in order to verify eCRF entries.  The 
principal investigator will review the eCRFs for completeness and accuracy and provide 
his or her electronic signature and date to eCRFs as evidence thereof.
Medidata will provide access to the EDC system for the duration of the trial through a 
password-protected method of internet access.  Such access will be removed from 
investigator sites at the end of the site's participation in the study.  Data from the EDC 
system will be archived on appropriate data media (CD-ROM, etc.) and provided to the 
investigator at that time as a durable record of the site's eCRF data.  It will be possible for 
the investigator to make paper printouts from that media.
Patient Reported Outcomes (PRO) data is collected directly onto paper CRFs by the 
subjects.  The completion of these forms is verified by the site staff.  The forms are 
entered into the clinical database and then can be viewed within the EDC system by the 
site staff.
All questionnaires must be legible and completed in indelible ballpoint ink.  Any 
necessary corrections are to be made by drawing a single line through the incorrect entry 
and writing in the revision, the date of the correction, the reason for the correction, and the 
initials of the person making the correction.  Data are not to be obliterated by blacking 
out, using correction fluid or by erasing the original entry.
10.3
Electronic Patient Reported Outcomes (ePRO)
Subject reported data must be completed for each subject screened/enrolled in this study.  
Some of these data are being collected with an Electronic Patient Reported Outcome 
 

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(ePRO) tool called Trialmax, provided by the technology vendor CRF Health of Plymouth 
Meeting, PA, USA.  The ePRO system is in compliance with Title 21 CFR Part 11.  The 
documentation related to the system validation of the ePRO tool is available through the 
vendor, CRF Health, while the user acceptance testing of the study-specific ePRO design 
will be conducted and maintained at AbbVie.
The subject will be entering the data into an electronic device, these data will be uploaded 
to a server.  The data on the server will be considered source, and maintained and 
managed by CRF Health.
Internet access to the ePRO data will be provided by CRF Health for the duration of the 
trial.  This access will be available for the duration of the trial to the investigational sites, 
as well as delegated personnel.  Such access will be removed from investigational sites 
following the receipt of the study archive.  Data from the ePRO tool will be archived on 
appropriate data media (CD-ROM, etc.) and provided to the investigational site at that 
time as a durable record of the site's ePRO data.  It will be possible for the investigational 
site to create paper printouts from that media. 
The ePRO data (such as stool frequency, rectal bleeding, abdominal discomfort, and 
general well-being) will be collected electronically via a handheld device into which the 
subject will record the required pieces of information on a daily basis.  In addition, study 
drug administration data (such as kit number, vial/syringe number and amount/dose 
administered) will be collected electronically via a handheld device into which the subject 
will record this required information on a weekly basis.  The electronic device will be 
programmed to allow data entry for throughout the day.  All data entered on the device 
will be immediately stored to the device itself and manually/automatically uploaded to a 
central server administrated by CRF Health.  The investigational site staff will be able to 
access all uploaded subject entered data via a password protected website, up until the 
generation, receipt and confirmation of the study archive.
 

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10.4
Data Collection Process
AbbVie is using an Electronic Patient Reported Outcome (ePRO) tool to capture portions 
of the clinical data defined in this protocol.  The use of ePRO requires certain process 
changes compared to the use of traditional paper PROs.  Trial-Specific Guidelines 
(T-SGs) have been developed to document the changes from the traditional paper PRO 
process.  These T-SGs govern the ePRO processes in this trial.
11.0
Data Quality Assurance
Computer logic and manual checks will be created to identify items such as inconsistent 
study dates.  Any necessary corrections will be made to the eCRF.
12.0
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 
governmental 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 trial-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.
 

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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.
13.0
Completion of the Study
The investigator will conduct the study in compliance with the protocol and complete the 
study within the timeframe specified in the contract between the investigator and AbbVie.  
Continuation of this study beyond this date must be mutually agreed upon in writing by 
both the investigator and AbbVie.  The investigator will provide a final report to the 
IEC/IRB following conclusion of the study, and will forward a copy of this report to 
AbbVie or their representative.
The investigator must retain any records related to the study according to local 
requirements.  If the investigator is not able to retain the records, he/she must notify 
AbbVie to arrange alternative archiving options.
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 Investigator's Signature for Study Reports.
The end-of-study is defined as the date of the last subject's last visit or the actual date of 
follow-up contact, whichever is later.
 

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14.0
Investigator's Agreement
1.
I have received and reviewed the Investigator's Brochure for adalimumab.
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.
5.
I agree that all electronic signatures will be considered the equivalent of a 
handwritten signature and will be legally binding.
Protocol Title: 
A Multi-Center, Open-Label Study of the Human Anti-TNF 
Monoclonal Antibody Adalimumab to Evaluate Long-Term Safety 
and Tolerability of Repeated Administration of Adalimumab in 
Pediatric Subjects with Ulcerative Colitis Who Completed the 
Study M11-290
Protocol Date:
04 August 2021
Signature of Principal Investigator
Date
Name of Principal Investigator (printed or typed)
 

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15.0
Reference List
1.
Griffiths AM.  Specificities of inflammatory bowel disease in childhood.  Best 
Pract Res Clin Gastroenterol.  2004;18(3):509-23.
2.
Biancone L, Michetti P, Travis S, et al; European Crohn's and Colitis Organisation 
(ECCO).  European evidence-based consensus on the management of ulcerative 
colitis:  special situations.  J Crohns Colitis.  2008;2(1):63-92.
3.
Kappelman MD, Grand RJ.  Does inflammatory bowel disease develop in infants?  
Inflamm Bowel Dis.  2008;14 (Suppl 2):S6-8.
4.
Hassan K, Cowan FJ, Jenkins HR.  The incidence of childhood inflammatory 
bowel disease in Wales.  Eur J Pediatr.  2000;159(4):261-3.
5.
Lakatos L, Mester G, Erdelyi Z, et al.  Striking elevation in incidence and 
prevalence of inflammatory bowel disease in a province of western Hungary 
between 1977-2001.  World J Gastroenterol.  2004;10(3):404-9.
6.
Sawczenko A, Sandhu BK.  Presenting features of inflammatory bowel disease in 
Great Britain and Ireland.  Arch Dis Child.  2003;88(11):995-1000.
7.
Auvin S, Molinié F, Gower-Rousseau C, 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.
8.
Armitage E, Drummond HE, Wilson DC, et al.  Increasing incidence of both 
juvenile-onset Crohn's disease and ulcerative colitis in Scotland.  Eur J 
Gastroenterol Hepatol.  2001;13(12):1439-47.
9.
Hildebrand H, Finkel Y, Grahnquist L, et al.  Changing pattern of paediatric 
inflammatory bowel disease in northern Stockholm 1990-2001.  Gut.  
2003;52(10):1432-4.
10.
Karolewska-Bochenek K, Lazowska-Przeorek I, Albrecht P, et al.  Epidemiology 
of inflammatory bowel disease among children in Poland.  A prospective, 
population-based, 2-year study, 2002-2004.  Digestion. 2009;79(2):121-9.
 

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11.
Everhart JE.  The Burden of Digestive Diseases in the United States.  In:  Everhart 
JE, editor.  Inflammatory Bowel Disease.  Washington DC:  US Government 
Printing Office; 2008.  p. 97-106.
12.
Ruter M, Saunders B, Wilkinson K, et al.  Severity of inflammation is a risk factor 
for colorectal neoplasia in ulcerative colitis.  Gastroenterology.  
2004;126(2):451-9.
13.
Kornbluth A, Sachar DB.  Practice Parameters Committee of the American College 
of Gastroenterology.  Ulcerative colitis practice guidelines in adults (update):  
American College of Gastroenterology, Practice Parameters Committee.  Am J 
Gastroenterol.  2004;99(7):1371-85.
14.
Hyams JS, Damaraju L, Blank M, et al.  Induction and maintenance therapy with 
infliximab for children with moderate to severe ulcerative colitis.  Clin 
Gastroenterol Hepatol.  2012;10(4):391-9.e1.
15.
Humira® (adalimumab) [package insert].  North Chicago, IL; AbbVie, 2011.
16.
Reinisch W, Sandborn WJ, Hommes DW, et al.  Adalimumab for induction of 
clinical remission in moderately to severely active ulcerative colitis:  results of a 
randomised controlled trial.  Gut.  2011;60(6):780-7.
17.
Reinisch W, Sandborn WJ, Kumar A, et al.  52-week clinical efficacy with 
adalimumab in patients with moderately to severely active ulcerative colitis who 
failed corticosteroids and/or immunosuppressants.  Gut.  2011;60:A139-40.
18.
Sandborn WJ, Van Assche G, Reinisch W, et al.  Induction and maintenance of 
clinical remission by adalimumab in patients with moderate-to-severe ulcerative 
colitis.  J Crohns Colitis.  2011; (5 Suppl 1):S68.  Abstract P136.
19.
Sandborn WJ, Van Assche G, Thakkar RB, et al.  Adalimumab improves 
health-related quality of life for 52 weeks in patients with ulcerative colitis.  
J Crohn's Colitis.  2011; (5 Suppl 1):S87, P181.
20.
Haberman R, Axelrad J, Chen A, et al.  Covid-19 in Immune-Mediated 
Inflammatory Diseases - Case Series from New York. N Engl J Med. 
2020;383(1):85-8.
 

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21.
Greulich WW, Pyle S, Idell ST.  Radiographic Atlas of Skeletal Development of 
the Hand and Wrist.  Am J Med Scis.  1959;238(3):261-396.
22.
Otley A, Smith C, Nicholas D, et al.  The IMPACT questionnaire:  a valid measure 
of health-related quality of life in pediatric inflammatory bowel disease.  J Pediatr 
Gastroenterol Nutr.  2002;35(4):557-63.
23.
Turner D, Otley AR, Mack D, et al.  Development, validation, and evaluation of a 
pediatric ulcerative colitis activity index:  a prospective multicenter study.  
Gastroenterology.  2007;133(2):423-32.
24.
Schroeder KW, Tremaine WJ, Ilstrup DM.  Coated oral 5-aminosalicylic acid 
therapy for mildly to moderately active ulcerative colitis.  A randomized study.  
N Engl J Med.  1987;317(26):1625-9.
25.
Lewis JD, Chuai S, Nessel L, et al.  Use of the noninvasive components of the 
Mayo Score to assess clinical response in ulcerative colitis.  Inflamm Bowel Dis.  
2008;14(12):1660-6.
 

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Appendix A.
Responsibilities of the Clinical Investigator
Clinical research studies sponsored by AbbVie are subject to the Good Clinical Practices 
(GCP) and local regulations and guidelines governing the study at the site location.  In 
signing the Investigator Agreement in Section 14.0 of this protocol, the investigator is 
agreeing to the following:
1.
Conducting the study in accordance with the relevant, current protocol, making 
changes in a protocol only after notifying AbbVie, except when necessary to 
protect the safety, rights or welfare of subjects.
2.
Personally conducting or supervising the described investigation(s).
3.
Informing all subjects, or persons used as controls, that the drugs are being used for 
investigational purposes and complying with the requirements relating to informed 
consent and ethics committees (e.g., independent ethics committee [IEC] or 
institutional review board [IRB]) review and approval of the protocol and 
amendments.
4.
Reporting adverse experiences that occur in the course of the investigation(s) to 
AbbVie and the site director.
5.
Reading the information in the Investigator's Brochure/safety material provided, 
including the instructions for use and the potential risks and side effects of the 
investigational product(s).
6.
Informing all associates, colleagues, and employees assisting in the conduct of the 
study about their obligations in meeting the above commitments.
7.
Maintaining adequate and accurate records of the conduct of the study, making
those records available for inspection by representatives of AbbVie and/or the 
appropriate regulatory agency, and retaining all study-related documents until 
notification from AbbVie.
8.
Maintaining records demonstrating that an ethics committee reviewed and
approved the initial clinical investigation and all amendments.
 

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9.
Reporting promptly, all changes in the research activity and all unanticipated 
problems involving risks to human subjects or others, to the appropriate individuals 
(e.g., coordinating investigator, institution director) and/or directly to the ethics 
committees and AbbVie.
10.
Following the protocol and not make any changes in the research without ethics 
committee approval, except where necessary to eliminate apparent immediate 
hazards to human subjects.
 

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

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Appendix D.
Mayo Scoring System
The Mayo Score is a composite of the following subscores:  Stool Frequency subscore, 
Rectal Bleeding subscore, Endoscopic appearance subscore, and Physician's Global 
Assessment subscore.
Stool Frequency Subscore
0 = Normal 
1 = 1 – 2 stools/day more than normal
2 = 3 – 4 stools/day more than normal
3 = > 4 stools/day more than normal
Each subject serves as his or her own control to establish normal stool frequency and the degree of 
abnormal stool frequency.
Rectal Bleeding Subscore
0 = None
1 = Visible blood with stool less than half the time
2 =Visible blood with stool half of the time or more
3 = Passing blood alone
A score of 3 for bleeding requires subjects to have at least 50% of bowel motions accompanied by 
visible blood and at least one bowel motion with blood alone.
Endoscopy Subscore:
0 = Normal or inactive disease
1 = Mild disease (erythema, decreased vascular pattern, mild friability)
2 = Moderate disease (marked erythema, absent vascular pattern, friability, erosions)
3 = Severe disease (spontaneous bleeding, ulceration)
Physician's Global Assessment Subscore
0 = Normal
1 = Mild disease
2 = Moderate disease
3 = Severe disease
The physician's global assessment acknowledges the three other subscores, the subject's daily record of 
abdominal discomfort and functional assessment, and other observations such as physical findings, and 
the subject's performance status.
Adapted from Schroeder KW, et al, and Lewis JD, et al.24,25
 

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Script for Collection of Mayo Scores 
The Mayo Score is a composite of the following subscores:  Stool Frequency subscore, 
Rectal Bleeding subscore, Endoscopy subscore, and Physician's Global Assessment 
subscore.
The Partial Mayo Score is a composite of the following subscores:  Stool Frequency 
subscore, Rectal Bleeding subscore, and Physician's Global Assessment subscore.
Stool Frequency Subscore
The stool frequency subscore is calculated by comparing the stool frequency to a normal 
number of bowel movements.  The normal number of bowel movements is the number of 
stools per day (24 hours) that is typical for the subject when having active UC but not 
experiencing a flare and needs to be designated once prior to enrollment.  The normal 
number of bowel movements should represent a full number of at least 1.
Subjects will record the daily number of stools throughout the trial.  Using these numbers, 
the Stool Frequency subscore will be assessed for each study day as follows:
●
A number of bowel movements lower than or equal to the normal number of 
bowel movements should be scored as 0 = Normal.
●
One or 2 bowel movements more than the normal number of bowel 
movements should be scored as 1.
●
Three or 4 bowel movements more than the normal number of bowel 
movements should be scored as 2.
●
Five or more bowel movements more than the normal number of bowel 
movements should be scored as 3.
The Stool Frequency subscores from the 5 days prior to each study visit will be averaged 
and used for the Stool Frequency subscore for each study visit.  In order to account for 
unavailable or excluded diary entries as per the provisions given below diary entries of the 
most recent 5 days within 14 days prior to each study visit will be used.
 

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The Stool Frequency subscore during days which the subject received anti-diarrheal 
medication will be scored as a 3.  Diary entries for stool frequency should not be included 
in the 5 days prior to the visit that are evaluated for the Stool Frequency subscore for the 
following days:  (1) the day the subject received medication for bowel preparation prior to 
endoscopy, (2) the day the subject underwent an endoscopy, and (3) 2 days following the 
endoscopy.  Earlier diary entries will be used accordingly in order to provide the most 
recent data for 5 days prior to the respective study visit.
Rectal Bleeding Subscore
Subjects should record a daily rectal bleeding subscore value as follows:
●
No visible blood with stool during the respective day should be scored as 0.
●
Visible blood with stool less than half the time during the respective day 
should be scored as 1.
●
Visible blood with stool at least half the time during the respective day should 
be scored as 2.
●
A score of 3 for bleeding requires subjects to have at least 50% of bowel 
motions accompanied by visible blood and at least one bowel motion with 
blood alone.
The score entries into subject's diary from the 5 days prior to each study visit will be 
averaged and used for the Rectal Bleeding subscore for each study visit.  In order to 
account for unavailable or excluded diary entries as per the provisions given below diary 
entries of the most recent 5 days within 14 days prior to each study visit will be used.
Diary entries for rectal bleeding should not be included in the 5 days prior to the visit that 
are evaluated for the Rectal Bleeding subscore for the following days:  (1) the day the 
subject received medication for bowel preparation prior to endoscopy, (2) the day the 
subject underwent an endoscopy, and (3) 2 days following the endoscopy.  Earlier diary 
entries will be used accordingly in order to provide the most recent data for 5 days prior to 
the respective study visit.
 

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Physician's Global Assessment Subscore
The physician's global assessment acknowledges the 2 subject-reported subscores, the 
endoscopy subscore as applicable, the subject's daily record of abdominal discomfort and 
functional assessment during the 5 days prior to the visit, and other observations such as 
physical findings, and the subject's performance status in order to assess disease activity 
as follows:
●
0 = Normal
●
1 = Mild disease
●
2 = Moderate disease
●
3 = Severe disease
Endoscopy Subscore
The endoscopist should evaluate each observed segment of the colon (rectum, sigmoid, 
descending colon, transverse colon, ascending colon/cecum) by using the classification as 
follows:
●
0 = Normal or inactive disease
●
1 = Mild disease (erythema, decreased vascular pattern, mild friability)
●
2 = Moderate disease (marked erythema, absent vascular pattern, friability, 
erosions)
●
3 = Severe disease (spontaneous bleeding, ulceration)
The endoscopic subscore for the subject will be the worst score of the observed segments.
The local endoscopist should also separately assess presence or absence of friability 
(yes/no).
 

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Appendix E.
Work Productivity and Activity Impairment Questionnaire:  
Ulcerative Colitis V2.0 (WPAI:  UC) – Caregiver
The following questions ask about the effect of your child's ulcerative colitis 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 7 days, not including today.
2.
During the past 7 days, how many hours did you miss from work because of 
problems associated with your child's ulcerative colitis?  Include hours you missed 
on sick days, times you went in late, left early, etc., because of your child's 
ulcerative colitis.  Do not include time you missed for your child to participate in 
this study.
_____HOURS
3.
During the past 7 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 7 days, how many hours did you actually work?
_____HOURS (If "0," skip to question 6.)
5.
During the past 7 days, how much did your child's ulcerative colitis 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 ulcerative colitis affected your work only 
 

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a little, choose a low number.  Choose a high number if your child's ulcerative 
colitis affected your work a great deal.
Consider only how much your child's ulcerative colitis affected productivity while you 
were working.
My 
child's 
Ulcerative 
colitis had 
no effect 
on my 
work
My child's 
Ulcerative 
colitis 
completely 
prevented 
me from 
working
0
1
2
3
4
5
6
7
8
9
10
CIRCLE A NUMBER
6.
During the past 7 days, how much did your child's ulcerative colitis 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 ulcerative colitis affected your activities 
only a little, choose a low number.  Choose a high number if your child's ulcerative 
colitis affected your activities a great deal.
 

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Consider only how much your child's ulcerative colitis affected your ability to do your 
regular daily activities, other than work at a job.
My 
child's 
Ulcerative 
colitis had 
no effect 
on my 
daily 
activities
My child's 
Ulcerative 
colitis 
completely 
prevented 
me from 
doing my 
daily 
activities
0
1
2
3
4
5
6
7
8
9
10
CIRCLE A NUMBER
WPAI:UC – Caregiver V2.0 (US English)
 

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Appendix F.
Body Weight Adjusted Volumes of Study Drug for Administration 
of Open Label Adalimumab 0.6 mg/kg Dosing (Weight Based)
Weight 
(kg)
Administered 
(# of vial 
used)
Volume 
(mL)
Weight 
(Kg)
Administered 
(# of vial 
used)
Volume 
(mL)
Weight 
(kg)
Administered 
(# of vial 
used)
Volume 
(mL)
14
1×
0.17
36
1 x
0.43
58
1×
0.70
15
1×
0.18
37
1 x
0.44
59
1×
0.71
16
1×
0.19
38
1 x
0.46
60
1×
0.72
17
1×
0.20
39
1 x
0.47
61
1×
0.73
18
1×
0.22
40
1 x
0.48
62
1×
0.74
19
1×
0.23
41
1 x
0.49
63
1×
0.76
20
1×
0.24
42
1 x
0.50
64
1×
0.77
21
1×
0.25
43
1 x
0.52
65
1×
0.78
22
1×
0.26
44
1 x
0.53
66
1×
0.79
23
1×
0.28
45
1 x
0.54
67
1×
0.80
24
1×
0.29
46
1 x
0.55
68
1×
0.80
25
1×
0.30
47
1 x
0.56
69
1×
0.80
26
1×
0.31
48
1 x
0.58
70
1×
0.80
27
1×
0.32
49
1 x
0.59
71
1×
0.80
28
1×
0.34
50
1 x
0.60
72
1×
0.80
29
1×
0.35
51
1 x
0.61
73
1×
0.80
30
1×
0.36
52
1 x
0.62
74
1×
0.80
31
1×
0.37
53
1 x
0.64
75
1×
0.80
32
1×
0.38
54
1 x
0.65
76
1×
0.80
33
1×
0.40
55
1 x
0.66
77
1×
0.80
34
1×
0.41
56
1 x
0.67
78
1×
0.80
35
1×
0.42
57
1 x
0.68
79
1×
0.80
80
1×
0.80
 

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Appendix G.
70-Day Follow-Up Call – Sample
Site Name/Number:  ________
Subject Number:  ________
Please contact subjects who discontinue adalimumab 70 days following study 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 three attempts.)
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.  If needed, provide AE/SAE details on the AE worksheet 
attached.  (Please report all SAEs to AbbVie within 24 hours of being made aware of the event.)
_______________________________________________________
_______________________________________________________
_______________________________________________________
_______________________________________________________
 

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Appendix H.
Non-Drug Materials Provided to the Study Sites
Study sites will receive the following supplies prior to or during the study for distribution 
to subjects:
Tote Bags
Coolers
Gel Packs
Subject Diaries
Sharps Containers
 

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Appendix I.
Measurements and Volume(s) of Blood Samples to Be Drawn
The measurements and volume(s) of blood samples to be drawn at the time point 
indicated in the table below:
Visit
Measurement
Volume 
(mL)
Total Blood 
Volume (mL)/Visit
Baseline samples 
Chemistry, hCG*, hsCRP
2.5
7.5**
Drawn at 
Hematology
2.0
Week 52 Study M11-290
QuantiFERON TB Gold
3.0
Week 4
Chemistry, hCG*
2.5
4.5
Hematology
2.0
Week 8
hCG*
2.5
2.5
Week 12
Chemistry, hCG*
2.5
4.5
Hematology
2.0
Week 24
Chemistry, hCG*, hsCRP
2.5
4.5
Hematology
2.0
Week 36
Chemistry, hCG*,
2.5
4.5
Hematology
2.0
Week 48
Chemistry, hCG*, hsCRP
2.5
Hematology
2.0
7.5
QuantiFERON TB Gold^
3.0
Week 60
Chemistry, hCG*
2.5
4.5
Hematology
2.0
Week 72
Chemistry, hCG*, hsCRP
2.5
4.5
Hematology
2.0
Week 84
Chemistry, hCG*
2.5
4.5
Hematology
2.0
Week 96
Chemistry, hCG*, hsCRP
2.5
Hematology
2.0
7.5
QuantiFERON TB Gold^
3.0
Week 108
Chemistry, hCG*, 
2.5
4.5
Hematology
2.0
 

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Visit
Measurement
Volume 
(mL)
Total Blood 
Volume (mL)/Visit
Week 120
Chemistry, hCG*, hsCRP
2.5
Hematology
2.0
4.5
Week 144
Chemistry, hCG*, hsCRP
2.5
Hematology
2.0
7.5
QuantiFERON TB Gold^
3.0
Week 168
Chemistry, hCG*, hsCRP
2.5
4.5
Hematology
2.0
Week 192
Chemistry, hCG*, hsCRP
2.5
Hematology
2.0
7.5
QuantiFERON TB Gold^
3.0
Week 216
Chemistry, hCG*, hsCRP
2.5
4.5
Hematology
2.0
Week 240
Chemistry, hCG*, hsCRP
2.5
Hematology
2.0
7.5
QuantiFERON TB Gold^
3.0
Week 264
Chemistry, hCG*, hsCRP
2.5
4.5
Hematology
2.0
Week 288/ Premature 
Chemistry, hCG*, hsCRP
2.5
Discontinuation
Hematology
2.0
7.5
QuantiFERON TB Gold^
3.0
Unscheduled Visit
Chemistry, hCG*, hsCRP
2.5
Hematology
2.0
4.5
Total
101.5
*
Only performed in female of childbearing potential that has positive urine pregnancy test.
**
At the Baseline visit, the blood samples for Study M10-870 will be completed as part of Week 52 of the 
Study M11-290 protocol and blood volume is not used to calculate the total blood volume for Study M10-870.
^
Subjects will not have the QuantiFERON test performed if a PPD test is used.  For subjects with a negative TB test, 
a TB test will be required at Week 48, 96, 144, 192, 240 and 288.  An annual TB screen testing will not be required 
for subjects who have been treated for latent or active TB or have had a positive TB test at any time (prior to the 
study, or testing performed at any time point during the Study M11-290).