A Multicenter, Randomized, Double-Blind Study of the Human Anti-TNF Monoclonal Antibody Adalimumab in Pediatric Subjects With Moderate to Severe Ulcerative Colitis
Phase: PHASE3
Conditions: Ulcerative Colitis
Sponsor: AbbVie

NCT02065557

Adalimumab
M11-290 Protocol Amendment 5
EudraCT 2013-003032-77
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1.1
Protocol Amendment:  Summary of Changes
Previous Protocol Versions
Protocol 
Date
Original
27June 2013
Amendment 1
06 September 2013
Administrative Change 1
20 November 2013
Amendment 2
02 April 2014
Administrative Change 2
16 May 2014
Administrative Change 3
22 May 2015
Amendment 3
28 August 2015
Amendment 4
02 November 2017
The purpose of this amendment is to:
●
Modify statistical analyses and ranking of study endpoints.
Rationale:  To update external placebo rates as derived from meta-analyses. 
To specify confirmatory testing of combined adalimumab dose groups as well 
as individual adalimumab dose groups versus external placebo with 
multiplicity adjustment for co-primary and ranked secondary endpoints 
(number reduced to four based on availability of external placebo data) .  
Other secondary analyses will be exploratory.
●
Reflect final sample size of 93 subjects (and up to approximately 9 subjects in 
the Japan sub-study).
Rationale:  To ensure the needed sample size for planned testing of combined 
adalimumab dose groups as well as individual adalimumab dose groups 
versus external placebo.  
●
Adapted the number of samples collected for adalimumab, AAA, Infliximab, 
HACA assays based on final sample size.
●
Incorporate minor typographical and grammatical changes and provide 
clarifications throughout the protocol.

Adalimumab
M11-290 Protocol Amendment 5
EudraCT 2013-003032-77
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An itemized list of all changes made to this protocol amendment can be found in 
Appendix O.

Adalimumab
M11-290 Protocol Amendment 5
EudraCT 2013-003032-77
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1.2
Synopsis
AbbVie Inc.
Protocol Number:  M11-290
Name of Study Drug:  Adalimumab
Phase of Development:  3
Name of Active Ingredient:  Adalimumab
Date of Protocol Synopsis:  20 November 2018
Protocol Title:
A Multicenter, Randomized, Double-Blind Study of the Human Anti-TNF Monoclonal Antibody 
Adalimumab in Pediatric Subjects with Moderate to Severe Ulcerative Colitis
Objective:
The objective of the study is to demonstrate the efficacy and safety, and to assess the pharmacokinetics of 
adalimumab administered subcutaneously (SC) in pediatric subjects with moderate to severe ulcerative 
colitis (UC).
Investigators:  Multicenter
Study Sites:  Approximately 50 sites worldwide for the main study and approximately 10 sites for the 
Japan sub-study.
Study Population:
Subjects with moderate-to-severe UC from the ages of 4 to 17 prior to Baseline dosing.
Number of Subjects to be Enrolled:  93 subjects for the main study and up to approximately 9 subjects 
for the Japan sub-study
Methodology:
This is a Phase 3, multicenter, randomized, double-blind trial designed to evaluate the efficacy and safety 
of adalimumab in pediatric subjects with moderate to severe ulcerative colitis, who have failed therapy 
with corticosteroids and/or immunosuppressants.

Adalimumab
M11-290 Protocol Amendment 5
EudraCT 2013-003032-77
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Methodology (Continued):
93 pediatric subjects for the main study (and up to approximately 9 subjects for the Japan sub-study) with 
moderate-to-severe UC (Mayo Score of 6 to 12 points with an endoscopy subscore of 2 to 3, confirmed 
by central reader) will be enrolled at approximately 50 sites worldwide (and approximately 10 sites for 
the Japan sub-study).  The study will allow enrollment of up to 25% of anti-TNF experienced subjects.  
Prior to Amendment 4, subjects who met all of the inclusion criteria and none of the exclusion criteria 
were to be enrolled and randomized 3:2 at Baseline to one of two double-blinded adalimumab induction 
doses (high dose or standard dose).  The randomization was to be stratified by baseline disease severity 
(per Mayo Score), prior exposure to anti-TNF, and corticosteroid use at Baseline.  During the randomized 
double-blind induction period, subjects assigned to high induction dose group received adalimumab 2.4 
mg/kg (maximum dose of 160 mg) at Baseline and at Week 1.  At Week 2, subjects received adalimumab 
1.2 mg/kg (maximum dose of 80 mg), followed by a dose of 0.6 mg/kg (maximum dose of 40 mg) at 
Week 4 and Week 6.  Subjects randomized to the standard induction dose group received adalimumab 2.4 
mg/kg (maximum dose of 160 mg) at Baseline and matching placebo at Week 1, adalimumab 1.2 mg/kg 
(maximum dose of 80 mg) at Week 2, followed by a dose of 0.6 mg/kg (maximum dose of 40 mg) at 
Week 4 and Week 6.  After Amendment 4, subjects who meet all of the inclusion criteria and none of the 
exclusion criteria will be enrolled into the study and receive open-label adalimumab high induction dose.  
During the open-label induction period, subjects will receive adalimumab 2.4 mg/kg (maximum dose of 
160 mg) at Baseline and at Week 1.  At Week 2, subjects will receive adalimumab 1.2 mg/kg (maximum 
dose of 80 mg), followed by a dose of 0.6 mg/kg (maximum dose of 40 mg) at Week 4 and Week 6.  
Ongoing subjects randomized prior to Amendment 4 will continue their blinded treatment during the 
induction period until Week 8.  
Prior to Amendment 4, at Week 8, subjects demonstrating a clinical response per Partial Mayo Score 
(PMS) (defined as a decrease in PMS ≥ 2 points and ≥ 30% from Baseline) were randomized and 
stratified by Week 8 remission status per PMS (defined as a PMS ≤ 2 and no individual subscore > 1) and 
Induction dose in a 2:2:1 ratio to one of two adalimumab maintenance treatment groups (Standard dose 
[0.6 mg/kg (maximum dose of 40 mg) every other week] or High dose [0.6 mg/kg (maximum dose of 
40 mg) every week]) or to placebo, respectively.
After Amendment 4, at Week 8, subjects demonstrating a clinical response per PMS (defined as a 
decrease in PMS ≥ 2 points and ≥ 30% from Baseline) will be randomized and stratified by Week 8 
remission status per PMS (defined as a PMS ≤ 2 and no individual subscore > 1) in a 1:1 ratio to one of 
two adalimumab maintenance treatment groups (Standard dose [0.6 mg/kg (maximum dose of 40 mg) 
every other week] or High dose [0.6 mg/kg (maximum dose of 40 mg) every week]).
Subjects will receive blinded treatment every week (ew) beginning at Week 8 and will remain on 
double-blinded therapy through Week 52.
!
Subjects who are randomized to standard dose will receive a maintenance dose of 0.6 mg/kg 
(maximum dose of 40 mg) every other week (eow) and will receive the matching placebo at the 
alternate week.
!
Subjects who are randomized to high dose will receive a maintenance dose of 0.6 mg/kg 
(maximum dose of 40 mg) ew.
!
Subjects who were randomized to placebo prior to Amendment 4 receive matching placebo ew.  

Adalimumab
M11-290 Protocol Amendment 5
EudraCT 2013-003032-77
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Methodology (Continued):
Ongoing subjects randomized prior to Amendment 4 will continue their blinded treatment during the 
maintenance period until Week 52 and re-randomization to treatment for disease flare will be done 
according to Amendment 3 stipulations in these subjects.
At Week 8, subjects who have not achieved a clinical response per PMS will be discontinued.  A safety 
evaluation call will be made 70 days after the last dose of study drug is administered to obtain follow-up 
information on any ongoing or new adverse events.
The duration of the study could be up to 66 weeks, which includes a Screening Period of up to 28 days, 
8-week induction period and a 44-week double-blind maintenance period and a 70-day follow-up.  Upon 
completion of the study, subjects will have the option to enroll into an open-label extension study where 
they will receive open-label adalimumab.
Treatment of Subjects with Disease Flare During the Study:
Criteria for Disease Flare are as follows:
!
Subjects with a Week 8 PMS of 0 to 2 who present with a PMS at least 3 points greater than 
their Week 8 score.
!
Subjects with a Week 8 PMS of 3 to 4 who present with a PMS at least 2 points greater than 
their Week 8 score.
!
Subjects with a Week 8 PMS of 5 to 6 who present with a PMS at least 1 point greater than their 
Week 8 score.
Subjects will be expected to remain on blinded therapy throughout the 44-week maintenance period.  
However, subjects with a disease flare, may be re-randomized to receive the following blinded-treatment 
at or after Week 12:
!
Subjects who are randomized to Standard maintenance dose (0.6 mg/kg [maximum dose of 
40 mg] eow) will be re-randomized to receive either adalimumab re-induction dose (2.4 mg/kg 
[maximum of 160 mg]) or adalimumab (0.6 mg/kg [maximum of 40 mg]) at the visit.  
Afterwards, all subjects will resume receiving the standard dose (0.6 mg/kg [maximum of 
40 mg] eow) within the original dosing schedule.
!
Subjects who are randomized to High maintenance dose (0.6 mg/kg [maximum dose of 40 mg] 
ew) will be re-randomized to receive either adalimumab re-induction dose (2.4 mg/kg 
[maximum of 160 mg]) or adalimumab (0.6 mg/kg [maximum of 40 mg]) at the visit.  The 
following week, all subjects will resume receiving the high dose (0.6 mg/kg [maximum of 
40 mg] ew).
!
Subjects who were randomized to placebo prior to Amendment 4 will be re-randomized to 
receive either adalimumab re-induction dose (2.4 mg/kg [maximum of 160 mg] or to receive 
adalimumab (0.6 mg/kg [maximum of 40 mg]) at the visit.  Afterwards, all subjects will receive 
the standard dose (0.6 mg/kg [maximum of 40 mg] eow) within the original dosing schedule.
If a subject continues to meet the definition of disease flare (2nd time) following at least a 4-week course 
of blinded therapy since the subject has been re-randomized for disease flare, they may be switched to 
open-label adalimumab every week at the dose 0.6 mg/kg [maximum of 40 mg].  If a subject was 
re-randomized at Week 12 (to receive either re-induction dose (2.4 mg/kg [maximum of 160 mg]) or to 
receive adalimumab (0.6 mg/kg [maximum of 40 mg]), then the earliest that subject could be evaluated to 
determine if the subject meets the criteria for disease flare for switch to OL (0.6 mg/kg [maximum of 
40 mg]) weekly dosing is at Week 16.

Adalimumab
M11-290 Protocol Amendment 5
EudraCT 2013-003032-77
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Methodology (Continued):
Treatment of Subjects with Disease Flare During the Study (Continued):
If a subject continues to meet the definition of disease flare (3rd time) following a 4-week course of 
open-label adalimumab every week at the dose 0.6 mg/kg [maximum of 40 mg], they may be switched to 
receive adalimumab open-label 40 mg ew (maximum dose, not weight-based).
Subjects with persistent disease flare while on adalimumab 40 mg ew (max dose) may be withdrawn 
from the study at the investigator's discretion.
During open-label rescue therapy, subjects who are responders and have been in remission for at least 
8 consecutive weeks (PMS ≤ 2 with no individual subscore > 1) may have their dosage decreased from 
ew to eow.  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.  The investigator should receive prior approval 
from the medical monitor before taking any action with regard to dose re-escalation.
For subjects who meet the criteria for dose change, blood samples (adalimumab, AAA and hs-CRP) will 
be collected just prior to receiving any dose change (blinded therapy, escape to open-label adalimumab, 
dose de-escalation and dose re-escalation).
Subjects are allowed to be treated with stable doses of UC-related concomitant medications during the 
study, with the following exceptions and requirements:
!
At or after Week 4, subjects taking corticosteroid therapy at Baseline may have their 
corticosteroid therapy tapered based on the investigator's discretion.  A proposed tapering 
schedule is specified in Section 5.3.1.1.
!
From Week 4 to Week 12, if the subject should experience an increase in symptoms after 
corticosteroid was tapered, the subject may have their corticosteroid dose increased back up to 
the corticosteroid dose at Baseline.  This increase must be discussed with and approved by the 
Medical Monitor prior to any changes in these treatments.
!
Subjects who experience disease flare at or after Week 12 are allowed to change their dose or 
initiate treatment with corticosteroids, immunosuppressant or 5-ASA; these increases must be 
discussed with and approved by the Medical Monitor prior to any changes in these treatments.
!
Immunosuppressant doses may be decreased or terminated in the event of moderate-to-severe 
treatment-related toxicities.
!
Immunosuppressant therapy may be discontinued at or after Week 12 at the investigator's 
discretion.
At each study visit, in addition to routine physical examination including evaluation of extra intestinal 
manifestations and calculation of the PMS and PUCAI, the following will be collected:
!
Anthropometric evaluations at Baseline, Week 26 and Week 52/Premature Discontinuation for 
determination of body mass index (BMI), and "z" scores for height and weight.
!
IMPACT III Quality of Life questionnaire at Baseline, Week 8, Week 26 and 
Week 52/Premature Discontinuation Visit will be completed for subjects 9 years or older at the 
Baseline study visit.
!
Bone age determination by x-ray of the wrist at Screening and at Week 52/Premature 
Discontinuation Visit in subjects who have not completed linear growth.
!
Serum for measurement of adalimumab concentrations just prior to dosing at Baseline, Week 2, 
Week 4, Week 8, Week 12, Week 26 Week 34 and Week 52/Premature Discontinuation Visit 
and at Unscheduled Visit requiring dose change.

Adalimumab
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Methodology (Continued):
Treatment of Subjects with Disease Flare During the Study (Continued):
!
Serum for measurement of Anti-Adalimumab Antibodies (AAA) just prior to dosing at 
Baseline, Week 4, Week 8, Week 26 and Week 52/Premature Discontinuation Visit and at 
Unscheduled Visit requiring dose change.
!
Tanner stage at Baseline, Week 26 and Week 52/Premature Discontinuation Visit.
!
Endoscopy subscore at Screening and Week 52/Premature Discontinuation Visit.
Diagnosis and Main Criteria for Inclusion/Exclusion:
Main Inclusion:
1.
Subjects from the ages of 4 to 17 prior to baseline dosing.
2.
Subjects with a diagnosis of UC for at least 12 weeks prior to screening confirmed by endoscopy 
with biopsy.
A colonoscopy will be performed during the screening period unless the subject underwent a 
colonoscopy within 12 months prior to Screening and appropriate documentation is available (to 
confirm the diagnosis without evidence of dysplasia, colon cancer or infection).  In this case the 
screening endoscopy may be either a colonoscopy or a flexible sigmoidoscopy.
If the subject underwent an endoscopy within 56 days of Baseline, and a video recording of the 
endoscopy is available, the video recording may be used and no additional endoscopy will be 
performed during the Screening period provided that the conditions noted in Section 5.3.1.1 are met 
and all technical requirements are fulfilled.
Note:
!
If no appropriate documentation for confirmation of the diagnosis is available as per the 
investigator's judgment a diagnostic biopsy must also be performed.  
!
Biopsies to rule out dysplasia, colon cancer and infection may be taken at the investigator's 
discretion.
3.
Active ulcerative colitis with a Mayo Score of 6 – 12 points and endoscopy subscore of 2 – 3 
(confirmed by central reader) despite concurrent treatment with at least one of the following (oral 
corticosteroids or immunosuppressants or both as defined below):
!
Oral prednisone of ≥ 2 mg/day or equivalent, but not exceeding 40 mg/day, or oral budesonide 
≥3 mg/day, but not exceeding 9 mg/day, with a stable dose for at least 7 days prior to Baseline; 
and/or
!
At least a consecutive 28-day course of azathioprine or 6-MP or methotrexate (MTX) prior to 
Baseline, with a stable dose prior to Baseline of azathioprine ≥ 1.5 mg/kg/day or 6-MP 
≥1 mg/kg/day (rounded to the nearest available tablet or half tablet formulation) or a 
documented 6-TGN level of 230 – 450 pmol/8 × 108 RBC on the current dosing regimen or 
MTX ≥ 15 mg/m2 body surface area/week, or a dose that is the highest tolerated by the subject 
(e.g., due to leukopenia, elevated liver enzymes, nausea) during that time.
Note:  If subjects are on both oral corticosteroid and immunosuppressants BOTH of the drugs 
need to meet the above criteria; and/or
!
Concurrent therapy with corticosteroids or immunosuppressants (azathioprine, 6-MP or 
MTX) is not required for subjects who were previously treated during the past 1 year and 
have confirmed documentation of failure to respond, or were previously treated during the 
past 5 years and have confirmed documentation indicating lack of tolerability.

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EudraCT 2013-003032-77
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Diagnosis and Main Criteria for Inclusion/Exclusion (Continued):
Main Inclusion (Continued):
4.
Parent or guardian has voluntarily signed and dated an informed consent form, approved by an 
Institutional Review Board (IRB)/Independent Ethics Committee (IEC), after the nature of the study 
has been explained and the subject's parent or legal guardian has had the opportunity to ask 
questions.  The informed consent must be signed before any study-specific procedures are performed 
or before any concomitant medication is discontinued for the purpose of this study.  Pediatric 
subjects will be included in all discussions in order to obtain verbal and/or written assent.
5.
Subjects must be able and willing to self-administer SC injections or have a qualified person 
available to administer SC injections.
6.
Subject has a negative TB Screening Assessment.
If a subject has a positive (≥5 mm induration) PPD test and/or IGRA test at Screening, a CXR 
(PA and lateral view) must be performed for evaluation of active TB disease.  If the subject has 
evidence of a latent TB infection, the subject must initiate and complete a minimum of 2 weeks (or 
per local guidelines, whichever is longer) of an ongoing course of TB prophylaxis or have 
documented completion of a full course of TB prophylaxis, prior to Baseline.
7.
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 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, foams, jellies, diaphragm or intrauterine device (IUD);
!
Hormonal contraceptives for 90 days prior to study drug administration;
!
A vasectomized partner.
8.
Subject is judged to be in good health as determined by the Principal Investigator based upon the 
results of medical history, laboratory profile, physical examination, chest x-ray (CXR), and a 12-lead 
electrocardiogram (ECG) performed during Screening.
Main Exclusion:
1.
Subject with Crohn's disease (CD) or indeterminate colitis (IC).
2.
Current diagnosis of fulminant colitis and/or toxic megacolon.
3.
Subjects with disease limited to the rectum (ulcerative proctitis) during the screening endoscopy.
4.
Therapeutic enema or suppository within 14 days prior to the Screening endoscopy and during the 
remainder of the Screening Period.
5.
History of colectomy or subtotal colectomy (with ostomy) or is planning bowel surgery.
6.
Received cyclosporine, tacrolimus, or mycophenolate mofetil, within 30 days prior to Baseline.
7.
Female subjects who are breast-feeding or considering becoming pregnant during the study.
8.
Positive pregnancy test at Screening or Baseline.
9.
History of clinically significant drug or alcohol abuse in the last 12 months.

Adalimumab
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Diagnosis and Main Criteria for Inclusion/Exclusion (Continued):
Main Exclusion (Continued):
10. Subjects on azathioprine or 6-mercaptopurine (6-MP) or MTX and subjects:
!
Have not been on stable doses of these medications for at least 28 days prior to Baseline; or 
!
Have discontinued these medications within 28 days of Baseline.
11. Subjects on oral aminosalicylates who:
!
Have not been on stable doses of these medications for at least 14 days prior to Baseline; or
!
Have discontinued use of aminosalicylates within 14 days of Baseline.
12. Subjects on growth hormone who have not been on a stable dose for at least 4 weeks prior to 
Baseline.
13. Subjects on oral corticosteroids who:
!
Have not been on stable doses of these drugs for at least 7 days prior to Baseline; or
!
Discontinued use of oral corticosteroid within 14 days of Baseline; or
!
Have been taking both budesonide and prednisone (or equivalent) simultaneously.
14. Received intravenous corticosteroids within 5 days prior to Screening or during the Screening 
Period.
15. Subject who has previously used infliximab or any anti-TNF agent within 56 days of Baseline.
16. Subject who has previously used infliximab or any anti-TNF agent and has not clinically responded 
at any time ("primary non-responder") unless subject experienced a treatment limiting reaction.
17. Previous treatment with adalimumab or previous participation in an adalimumab clinical study.
18. Positive Clostridium difficile (C. difficile) stool assay during the Screening Period.
19. Currently receiving total parenteral nutrition (TPN).
20. History of demyelinating disease (including myelitis) or neurologic symptoms suggestive of 
demyelinating disease.
21. History of invasive infection (e.g., listeriosis and histoplasmosis), human immunodeficiency 
syndrome (HIV).
22. 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.
23. Subjects with any active viral infection that based on the investigator's clinical assessment makes the 
subject an unsuitable candidate for the study.
24. Subject with a positive result for the Hepatitis B surface antigen (HBs Ag) or any HBV DNA PCR 
result that meets or exceeds detection sensitivity will be excluded.
25. Chronic recurring infections or active TB.
26. Subject has been treated with any investigational drug of chemical or biologic nature or any 
investigational procedure (including previous fecal transplantation) within 30 days or 5 half-lives 
(whichever is longer) of the drug prior to the Baseline Visit.
27. Infection(s) requiring treatment with intravenous (IV) anti-infectives within 30 days prior to the 
Baseline Visit or oral anti-infectives within 14 days prior to the Baseline Visit.
28. Prior exposure to biologics that have a potential or known association with PML (i.e., natalizumab 
(Tysabri®) or efalizumab (Raptiva®) or rituximab (Rituxan®).

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Diagnosis and Main Criteria for Inclusion/Exclusion (Continued):
Main Exclusion (Continued):
29. Known hypersensitivity to adalimumab or its excipients.
30. Evidence of dysplasia or 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.
If the Screening endoscopy shows evidence of dysplasia or malignancy, subject may not be enrolled in 
the study.
31. Screening laboratory and other analyses show any of the following abnormal results:
!
ECG – with clinically significant abnormalities;
!
Aspartate transaminases (AST) or alanine transaminase (ALT) > 1.75 × the upper limit of the 
reference range;
!
Total bilirubin ≥ 3 mg/dL;
!
Serum creatinine > 1.6 mg/dL;
!
Clinically significant abnormal screening laboratory results as evaluated by the Investigator.
32. Subject is considered by the Investigator, for any reason, to be an unsuitable candidate for the study.
Investigational Product:
Adalimumab
Induction Dose:
Body weight adjusted induction dose regimen
Prior to Amendment 4 subjects were randomized to receive one of 
2 double-blind adalimumab induction doses.
Standard Induction Dose:  2.4 mg/kg (maximum dose of 160 mg) at 
Week 0 and matching placebo at Week 1.  Subjects received 
1.2 mg/kg (maximum dose of 80 mg) at Week 2.  At Weeks 4 and 6, 
subjects received a dosing regimen of 0.6 mg/kg (maximum dose of 
40 mg).
High Induction Dose:  2.4 mg/kg (maximum dose of 160 mg) at 
Week 0 and Week 1.  Subjects received 1.2 mg/kg (maximum dose of 
80 mg) at Week 2.  At Weeks 4 and 6, subjects received a dosing 
regimen of 0.6 mg/kg (maximum dose of 40 mg).
After Amendment 4 subjects will receive the open-label adalimumab 
high induction dose.
High Induction Dose:  2.4 mg/kg (maximum dose of 160 mg) at 
Week 0 and Week 1.  Subjects will receive 1.2 mg/kg (maximum 
dose of 80 mg) at Week 2.  At Weeks 4 and 6, subjects will receive a 
dosing regimen of 0.6 mg/kg (maximum dose of 40 mg).

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Double-Blind Maintenance 
Doses (in Week 8 PMS 
Responders only):
Body weight adjusted maintenance dose regimen
Blinded adalimumab Standard dosing regimen:  0.6 mg/kg 
(maximum dose of 40 mg) eow with matching placebo at the 
alternate week
Blinded adalimumab High dosing regimen:  0.6 mg/kg (maximum 
dose of 40 mg) ew
Subjects who were randomized to placebo (prior to Amendment 4) 
receive placebo ew.  
At or after Week 12 subjects who demonstrate a disease flare may be 
re-randomized to receive the following blinded-treatment.
!
Subjects, who are randomized to standard maintenance 
dose, will be re-randomized to receive either adalimumab 
re-induction dose (2.4 mg/kg [maximum of 160 mg]) or to 
adalimumab (0.6 mg/kg [maximum of 40 mg]) at the visit.  
Afterwards, all subjects will resume to receiving the 
standard dose adalimumab (0.6 mg/kg [maximum of 40 mg] 
eow) within the original dosing schedule.
!
Subjects who are randomized to high maintenance dose, will 
be re-randomized to receive either adalimumab re-induction 
dose (2.4 mg/kg [maximum of 160 mg]) or to receive 
adalimumab (0.6 mg/kg [maximum of 40 mg]) at the visit.  
The following week, all subjects will resume to receiving 
the high dose (0.6 mg/kg [maximum of 40 mg] ew).
!
Subjects who were randomized to placebo prior to 
Amendment 4 will be re-randomized to receive either 
adalimumab re-induction dose (2.4 mg/kg [maximum of 
160 mg] or to receive adalimumab (0.6 mg/kg [maximum of 
40 mg]) at the visit.  Afterwards, all subjects will receive the 
standard dose (0.6 mg/kg [maximum of 40 mg] eow) within 
the original dosing schedule.
Open-Label Maintenance 
Doses:
High dose body weight adjusted.
0.6 mg/kg (maximum dose of 40 mg) ew
If a subject continues to meet the definition of disease flare following 
a 4-week course of open-label adalimumab ew at the dose 0.6 mg/kg 
[maximum of 40 mg], they may be switched to receive adalimumab 
40 mg ew (maximum dose, not weight-based).
Mode of Administration:
Subcutaneous injection (SC)
Reference Therapy:
NA (after Amendment 4); Placebo (prior to Amendment 4)
Dose:
NA
Mode of Administration:
NA (after Amendment 4); Subcutaneous injection (SC) (prior to 
Amendment 4)

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Duration of Treatment:  52 weeks
!
The subjects will visit the site at Screening, Baseline, Weeks 1, 2, 4, 8, 12, 18, 26, 34, 42, and 
52/Premature Discontinuation and Unscheduled Visits.
!
Subjects who qualify will be given the opportunity to enroll into an open-label study of the 
Long-term Safety and Tolerability of Repeated Administration of Adalimumab.
A 70-Day Follow-Up phone call will be completed for all subjects who either terminate early from the 
study or do not rollover into the extension study.
Criteria for Evaluation:
Efficacy analysis will be based on the Intent-To-Treat-Efficacy (ITT-E) population for the induction 
period and modified ITT (mITT) population for the maintenance period.  The ITT-E population is a 
subpopulation of the ITT population, which consists of all subjects who received at least one SC injection 
of the study medication during the induction period.  Subjects who receive open-label high induction 
dose, because they enrolled after Protocol Amendment 4 was released, will be excluded from the ITT-E 
population.  The mITT population consists of all Week 8 PMS Responders among the ITT population 
who were randomized at Week 8 and received at least one SC injection of the study medication during 
maintenance period.  
The safety analysis set will include all subjects who received at least one SC injection of the study 
medication.
Efficacy:
This study will utilize the Mayo Score, PMS and Mayo subscores to measure efficacy.  The PUCAI will 
also be utilized as applicable.  Please refer to 'Statistical Methods' for details on the sequentially rejective 
multiple test procedure  of the dose groups used in this study versus external placebo for co-primary and 
ranked secondary endpoints.
Efficacy Endpoints
The co-primary efficacy endpoints are:
1.
The proportion of subjects who achieve clinical remission at Week 8 as measured by PMS (defined 
as a PMS ≤ 2 and no individual subscore > 1);
2.
The proportion of subjects who responded at Week 8 per PMS and achieve clinical remission at 
Week 52 as measured by Mayo Score (defined as a Mayo Score ≤ 2 and no individual subscore > 1).
Ranked secondary efficacy endpoints are:
1.
Proportion of subjects in Mayo clinical response at Week 52 in Week 8 responders per PMS;
2.
Proportion of subjects who achieve mucosal healing at Week 52 as measured by Mayo endoscopy 
subscore (defined as ≤ 1) in Week 8 responders per PMS;
3.
Proportion of subjects who achieve Mayo clinical remission at Week 52 in Week 8 remitters per 
PMS;
4.
Proportion of subjects receiving corticosteroid at Baseline who discontinue corticosteroid prior to 
Week 52 and are in Mayo clinical remission at Week 52 in Week 8 responders per PMS.

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Criteria for Evaluation (Continued):
Efficacy (Continued):
Additional exploratory secondary analyses:
!
Proportion of subjects in PMS clinical remission at Week 52 in Week 8 responders per PMS;
!
Proportion of subjects in PUCAI remission (defined as < 10) at Week 8;
!
Proportion of subjects in PUCAI response (defined as a decrease in PUCAI ≥ 20 points from 
Baseline) at Week 8;
!
Proportion of subjects in PUCAI remission (defined as < 10) at Week 52 in Week 8 responders 
per PMS;
!
Proportion of subjects in PUCAI response (defined as a decrease in PUCAI ≥ 20 points from 
Baseline) at Week 52 in Week 8 responders per PMS;
!
Proportion of subjects receiving corticosteroid at Baseline who discontinue corticosteroid prior 
to Week 52 and are in PUCAI remission at Week 52 in Week 8 responders per PMS;
!
Change from Baseline in total IMPACT III Quality of Life scores over time for subjects at least 
9 years old at Baseline;
!
Change from Baseline in WPAI scores over time;
!
Change from Baseline in "z" scores for height (observed height velocity [cm/yr] – mean height 
velocity for age and sex [cm/yr]/SD of the mean) at Week 26 and Week 52;
!
Change from Baseline in BMI at Week 26 and Week 52;
!
Change from Baseline in "z" scores for weight-for-age at Week 26 and Week 52;
!
Proportion of subjects at appropriate Tanner stage at Week 26 and Week 52 compared to 
Baseline;
!
Proportion of subjects in PMS response over time;
!
Proportion of subjects in PMS remission over time;
!
Proportion of subjects in PUCAI response over time;
!
Proportion of subjects in PUCAI remission over time;
!
Change from Baseline in number of daily stool over time;
!
Change from Baseline in albumin and total protein at different time points;
!
Change from Baseline in hemoglobin, hematocrit, red blood cell count at different time points;
!
Change from Baseline in hs-CRP levels at different time points;
!
Proportion of subjects with extraintestinal manifestations (EIM) at Week 26 and Week 52 
compared to Baseline;
!
Proportion of subjects with Mayo endoscopy subscore of 0 or 1 (without friability) at Week 52;
!
Proportion of subjects being hospitalized during the study;
!
Proportion of subjects undergoing colectomy during the study;
!
Proportion of subjects receiving corticosteroid at Baseline who discontinue corticosteroid prior 
to Week 52 and completed Week 52;
!
Correlation between PMS and PUCAI at different time points;

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Criteria for Evaluation (Continued):
Efficacy (Continued):
!
Proportion of subjects in a 9 point Mayo (without SFS) clinical remission (defined as ≤ 2 and no 
individual subscore > 1) at Week 52 in Week 8 responders per PMS;
!
Proportion of subjects in a 9 point Mayo (without PGA) clinical remission (defined as ≤ 2 and 
no individual subscore > 1) at Week 52 in Week 8 responders per PMS;
!
Proportion of subjects in a 9 point Mayo (without RBS) clinical remission (defined as ≤ 2 and 
no individual subscore > 1) at Week 52 in Week 8 responders per PMS;
!
Proportion of subjects in a 6 point Mayo (without SFS and endoscopy subscore) clinical 
remission (defined as ≤ 1) at Week 8;
!
Proportion of subjects in a 6 point Mayo (without PGA and endoscopy subscore) clinical 
remission (defined as ≤ 1) at Week 8;
!
Proportion of subjects in a 6 point Mayo (without RBS and endoscopy subscore) clinical 
remission (defined as ≤ 1) at Week 8;
!
Change from Baseline in Mayo Score at Week 52;
!
Change from Baseline in PMS over time;
!
Change from Baseline in PUCAI over time;
!
Change from Baseline in endoscopy subscore at Week 52;
!
Change from Baseline in SFS over time;
!
Change from Baseline in RBS over time;
!
Change from Baseline in PGA over time.
Pharmacokinetic:
Blood samples will be collected for the measurement of serum adalimumab concentrations just prior to 
dosing at Baseline, Weeks 2, 4, 8, 12, 26, 34 and 52/Premature Discontinuation Visits, and at 
Unscheduled Visits requiring dose change.  Blood samples will be collected for the measurement of 
serum anti-adalimumab antibody (AAA) just prior to dosing at Baseline, Weeks 4, 8, 26 and 
52/Premature Discontinuation Visits and at Unscheduled Visits requiring dose change.  Blood samples 
will be collected for the measurement of serum Infliximab and HACA at Baseline (prior to dosing).
Safety:
Adverse events, laboratory data, and vital signs will be assessed at all visits throughout the study.
Statistical Methods:
Efficacy:
The efficacy analysis will be performed in the ITT-E set for the induction period and in the mITT set for 
the maintenance period.  NRI method will be used to impute missing values for binary efficacy 
endpoints.  Subjects who do not complete the induction period or who receive rescue therapy during the 
maintenance period will be considered as failures from that time point forward.  Both LOCF and 
observed case analyses will be performed for continuous efficacy endpoints.
The confirmatory efficacy analyses for the co-primary endpoints and ranked secondary endpoints are 
based on the following external placebo assumptions.  

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Statistical Methods (Continued):
External Placebo Assumptions for Co-Primary and Ranked Secondary Efficacy Endpoints
Endpoint
External Placebo Rate 
(95% CI Upper Limit from Meta-
Analysis)
Week 8 PMS Remission 
19.83%
Week 52 FMS Remission in Week 8 Responders per PMS
18.37%
Week 52 FMS Response in Week 8 Responders per PMS
26.10%
Week 52 Mucosal Healing in Week 8 Responders per PMS
22.03%
Week 52 FMS Remission in Week 8 Remitters per PMS
14.79%
Week 52 FMS Remission in Week 8 Responders per PMS with 
CS at Baseline and Discontinued CS prior to Week 52
24.08%
FMS = Full Mayo Score; PMS = Partial Mayo Score; CS = Corticosteroids
  
Co-primary and ranked secondary endpoints will be summarized by treatment group with 95% 
confidence intervals (CI) and adalimumab dose groups will be tested against external placebo in a 
sequentially rejective multiple test procedure in order to ensure that the multiple significance level of 5% 
is controlled, using one sample two-sided Chi-square tests.  The below graph describes the structure of 
the multiple test procedure that starts with testing the co-primary endpoints for the combined high and 
standard adalimumab dose groups versus external placebo and then individual dose groups versus 
external placebo separately: 

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Statistical Methods (Continued):
Multiple Test Procedure for the Co-Primary and Ranked Secondary Endpoints
Assuming ε = 0.0005; C = testing the endpoint for the combined high and standard adalimumab dose groups against 
external placebo; HD = testing the endpoint for the high adalimumab dose against external placebo; SD = testing the 
endpoint for the standard adalimumab dose against external placebo; P1 = co-primary induction endpoint; P2 = co-
primary maintenance endpoint; Si = ranked secondary endpoint i (i=1,…,4)

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Statistical Methods (Continued):
Additional exploratory secondary endpoints that are of the categorical type will be summarized by 
treatment group with 95% CIs.  Additional exploratory secondary endpoints that are of the continuous 
type will be analyzed as changes from baseline, and reported by treatment group including 95% CIs.  
The following subset of endpoints will be tested for the high adalimumab dose against the standard 
adalimumab dose in an exploratory manner:
!
Proportion of subjects in PMS clinical remission at Week 8;
!
Proportion of subjects who achieve mucosal healing at Week 52 as measured by Mayo 
endoscopy subscore (defined as ≤ 1) in Week 8 responders per PMS;
!
Proportion of subjects in PUCAI remission (defined as < 10) at Week 52 in Week 8 responders 
per PMS;
!
Proportion of subjects in Mayo clinical response at Week 52 in Week 8 responders per PMS;
!
Proportion of subjects in Mayo clinical remission at Week 52 in Week 8 responders per PMS;
!
Proportion of subjects in PUCAI response (defined as a decrease in PUCAI ≥ 20 points from 
Baseline) at Week 52 in Week 8 responders per PMS;
!
Proportion of subjects receiving corticosteroid at Baseline who discontinue corticosteroid  prior 
to Week 52 and are in Mayo clinical remission at Week 52 in Week 8 responders per PMS;
!
Proportion of subjects receiving corticosteroid at Baseline who discontinue corticosteroid prior 
to Week 52 and are in PUCAI remission at Week 52 in Week 8 responders per PMS;
!
Proportion of subjects in PMS clinical remission at Week 52 in Week 8 responders per PMS;
!
Proportion of subjects in PUCAI remission at Week 8;
!
Proportion of subjects in PUCAI response at Week 8.
Pharmacokinetic:
Adalimumab trough serum concentrations will be summarized by treatment group at each time point 
using descriptive statistics.  In addition, pharmacokinetic model based analyses will be performed with 
the focus on apparent clearance (CL/F) and apparent volume of distribution (V/F) of adalimumab.
Immunogenicity:
AAA will be evaluated for each subject and each regimen, and rates of AAA positive will be calculated.  
As appropriate, the effect of AAA on adalimumab pharmacokinetics, efficacy variable(s), and 
treatment-emergent adverse events may be evaluated.  HACA will be evaluated for each subject and each 
regimen, and rates of HACA positive will be calculated.
Safety:
Treatment-emergent Adverse Events (AEs) and serious adverse events (SAEs) 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.  Changes in laboratory and vital sign data will be summarized using descriptive 
statistics.  Shift tables will be provided.

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Statistical Methods (Continued):
Sample Size:
The co-primary endpoints will be tested first for the combined high and standard adalimumab dose 
groups versus external placebo and then for the individual dose groups versus external placebo 
separately, controlling the multiple significance level of 5%.  For each individual test the nominal power 
is calculated. 
Assuming a 48% remission rate per PMS at Week 8 for the combined standard and high adalimumab 
induction dose groups and a remission rate per PMS of 19.83% for external placebo, a total of 77 subjects 
(high:standard = 46:31) in ITT-E population provides at least 99% power for a one sample two-sided 
Chi-square test using a significance level of 5%. 
Assuming a 36% remission rate per Mayo Score at Week 52 for the combined standard and high 
maintenance dose groups and a remission rate per Mayo Score of 18.37% for external placebo, a total of 
57 subjects in the combined adalimumab maintenance dose groups in mITT population (e.g., 
high:standard = 28:29) provide 88% power for a one sample two-sided Chi-square test using a 
significance level of 5%. 
Assuming that the high adalimumab dose regimen is associated with higher efficacy than the standard 
adalimumab dose regimen, assuming a 52% remission rate per PMS at Week 8 for the high adalimumab 
induction dose group and a remission rate per PMS of 19.83% for external placebo, 46 subjects in the 
high adalimumab induction dose group of ITT-E population provide at least 99% power for a one sample 
two-sided Chi-square test using a significance level of 4.95%. 
Assuming a 41% remission rate per Mayo Score at Week 52 for the high adalimumab maintenance dose 
group and a remission rate per Mayo Score of 18.37% for external placebo, a total of 28 subjects in the 
high adalimumab maintenance dose group of mITT population provide at least 80% power for a 
one sample two-sided Chi-square test using a significance level of 4.95%.
Based on the assumption of a 75% response rate at Week 8, 93 subjects will have to be included in the 
study (including ~12 internal placebo subjects in the maintenance part of the study who were included 
prior to Amendment 4) to ensure 57 subjects in the combined adalimumab maintenance dose groups.  

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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
Centers for Disease Control and Prevention
CLIA
Clinical Laboratory Improvement Amendments
CNS
Central nervous system
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
EC
Ethics Committee
ECG
Electrocardiogram
EDTA
Edetic acid (ethylenediaminetetraacetic acid)
EIM
Extraintestinal manifestation
eow
every other week
ew
every week
EP
European Pharmacopoeia
ESR
Erythrocyte sedimentation rate

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FC
Fecal calprotectin
FDA
Food and Drug Administration
FMS
Full Mayo Score
GCP
Good Clinical Practice
HACA
Human antichimeric antibody
HAQ
Health Assessment Questionnaire
HAV-IgM
Hepatitis A virus immunoglobulin M
HbsAg
Hepatitis B surface antigen
HCV Ab
Hepatitis C virus antibody
HIV
Human immunodeficiency virus
hs-CRP
High Sensitivity C-Reactive protein
IBD
Inflammatory bowel disease
IBDQ
Inflammatory Bowel Disease Questionnaire
ICH
International Conference on Harmonization
IDMC
Independent Data Monitoring Committee
IEC
Independent Ethics Committee
IgG
Immunoglobulin G
IL
Interleukin
IND
Investigational New Drug
IRB
Institutional Review Board
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
OL
Open-label
PA
Posteroanterior
PBO
Placebo
PD
Premature Discontinuation
PG
Pharmacogenetic
PIP
Pediatric Investigational Plan

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PK
Pharmacokinetics
PMS
Partial Mayo Score
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
sc
Subcutaneous
TB
Tuberculosis
Th1
Type 1 T helper
TNF
Tumor necrosis factor
TPN
Total parenteral nutrition
UC
Ulcerative Colitis
USP
United States Pharmacopoeia
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................................................................................................. 4
1.3
List of Abbreviations and Definition of Terms...................................... 20
2.0
Table of Contents ................................................................ 23
3.0
Introduction......................................................................... 28
3.1
Adalimumab Overview......................................................................... 28
3.2
Ulcerative Colitis and Current Treatments Overview............................ 28
3.3
Safety Information................................................................................ 31
3.3.1
Differences Statement .......................................................................... 31
3.4
Benefits and Risks................................................................................ 32
4.0
Study Objective ................................................................... 32
5.0
Investigational Plan.............................................................32
5.1
Overall Study Design and Plan:  Description ........................................ 32
5.2
Selection of Study Population............................................................... 44
5.2.1
Inclusion Criteria.................................................................................. 44
5.2.2
Exclusion Criteria................................................................................. 46
5.2.3
Prior and Concomitant Therapy............................................................ 50
5.2.3.1
Prior Therapy ....................................................................................... 50
5.2.3.2
Concomitant Therapy........................................................................... 51
5.2.3.3
Prohibited Therapy............................................................................... 53
5.3
Efficacy, Pharmacokinetic and Safety Assessments/Variables .............. 55
5.3.1
Efficacy and Safety Measurements Assessed and Flow Chart ............... 55
5.3.1.1
Study Procedures.................................................................................. 62
5.3.1.2
Blood Samples for Pharmacogenetic Analysis (Optional) ..................... 83
5.3.1.3
Blood Samples for Serologic Markers and Cytokine Analysis 
(Optional)............................................................................................. 83
5.3.1.4
Blood Samples for mRNA Analysis (Optional) .................................... 84
5.3.2
Drug Concentration Measurements....................................................... 84
5.3.2.1
Collection of Samples for Analysis....................................................... 84
5.3.2.2
Handling/Processing of Samples........................................................... 86

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5.3.2.3
Disposition of Samples......................................................................... 86
5.3.2.4
Measurement Methods ......................................................................... 87
5.3.3
Efficacy Variables................................................................................ 88
5.3.3.1
Primary Variables................................................................................. 89
5.3.3.2
Secondary Variables............................................................................. 89
5.3.4
Safety Variables ................................................................................... 92
5.3.5
Pharmacokinetic Variables ................................................................... 92
5.3.6
Pharmacogenetic, mRNA and Serologic Variables ............................... 92
5.3.6.1
Pharmacogenetic Variable .................................................................... 92
5.3.6.2
Cytokines, Serologic Markers and mRNA Variables ............................ 93
5.4
Removal of Subjects from Therapy or Assessment ............................... 93
5.4.1
Discontinuation of Individual Subjects ................................................. 93
5.4.2
Discontinuation of Entire Study............................................................ 94
5.5
Treatments ........................................................................................... 95
5.5.1
Treatments Administered...................................................................... 95
5.5.2
Identity of Investigational Products ...................................................... 97
5.5.2.1
Packaging and Labeling........................................................................ 98
5.5.2.2
Storage and Disposition of Study Drugs ............................................... 98
5.5.3
Method of Assigning Subjects to Treatment Groups............................. 99
5.5.4
Selection and Timing of Dose for Each Subject.................................... 99
5.5.5
Blinding ..............................................................................................100
5.5.5.1
Blinding of Investigational Product .....................................................100
5.5.5.2
Blinding of Data for Independent Data Monitoring Committee 
(IDMC) ...............................................................................................100
5.5.6
Treatment Compliance ........................................................................101
5.5.7
Drug Accountability............................................................................101
5.6
Discussion and Justification of Study Design.......................................102
5.6.1
Discussion of Study Design and Choice of Control Groups .................102
5.6.2
Appropriateness of Measurements.......................................................102
5.6.3
Suitability of Subject Population .........................................................103
5.6.4
Selection of Doses in the Study ...........................................................104
6.0
Complaints......................................................................... 105
6.1
Medical Complaints ............................................................................105

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6.1.1
Definitions ..........................................................................................106
6.1.1.1
Adverse Event.....................................................................................106
6.1.1.2
Serious Adverse Events.......................................................................106
6.1.2
Adverse Event Severity .......................................................................108
6.1.3
Relationship to Study Drug..................................................................108
6.1.4
Adverse Event Collection Period.........................................................109
6.1.5
Adverse Event Reporting.....................................................................109
6.1.6
Pregnancy............................................................................................111
6.1.7
Toxicity Management..........................................................................112
6.2
Product Complaint...............................................................................112
6.2.1
Definition............................................................................................112
6.2.2
Reporting ............................................................................................113
7.0
Protocol Deviations ........................................................... 113
8.0
Statistical Methods and Determination of Sample 
Size ..................................................................................... 114
8.1
Statistical and Analytical Plans............................................................114
8.1.1
Analyzable Population.........................................................................115
8.1.2
Planned Methods of Statistical Analysis ..............................................115
8.1.3
Demographics and Baseline Characteristics.........................................116
8.1.4
Statistical Analyses of Efficacy ...........................................................116
8.1.4.1
Co-Primary and Ranked Secondary Efficacy Variables .......................116
8.1.4.2
Additional Exploratory Secondary Efficacy Variables .........................118
8.1.4.3
Derivation of External Placebo Control Rates......................................119
8.1.5
Statistical Analyses of Safety...............................................................121
8.1.6
Interim Analysis..................................................................................121
8.1.7
Pharmacokinetic Analyses...................................................................121
8.2
Determination of Sample Size .............................................................122
8.3
Randomization Methods......................................................................123
9.0
Ethics.................................................................................. 124
9.1
Independent Ethics Committee (IEC) or Institutional Review 
Board (IRB) ........................................................................................124
9.2
Ethical Conduct of the Study...............................................................125
9.3
Subject Information and Consent.........................................................125

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10.0
Source Documents and Case Report Form 
Completion ........................................................................ 126
10.1
Source Documents...............................................................................126
10.2
Case Report Forms..............................................................................126
10.3
Electronic Patient Reported Outcomes (ePRO)....................................128
10.4
Data Collection Process.......................................................................129
11.0
Data Quality Assurance .................................................... 129
12.0
Use of Information ............................................................ 129
13.0
Completion of the Study ................................................... 130
14.0
Investigator's Agreement.................................................. 132
15.0
Reference List.................................................................... 133
List of Tables
Table 1.
Study Activities.................................................................................... 56
Table 2.
Clinical Laboratory Tests ..................................................................... 72
Table 3.
Definitions ........................................................................................... 75
Table 4.
Identity of Investigational Products ...................................................... 98
Table 5.
External Placebo Assumptions for Co-Primary and Ranked 
Secondary Efficacy Endpoints.............................................................120
List of Figures
Figure 1.
Study Design Schematic Prior to Amendment 4 ................................... 40
Figure 2.
Study Design Schematic After Amendment 4....................................... 41
Figure 3.
Study Design Schematic for Dose Escalation Prior to 
Amendment 4....................................................................................... 42
Figure 4.
Study Design Schematic for Dose Escalation After Amendment 4........ 43
Figure 5.
Adverse Event Collection....................................................................109
List of Appendices
Appendix A.
Responsibilities of the Clinical Investigator.........................................136
Appendix B.
List of Protocol Signatories .................................................................138

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Appendix C.
Pediatric Ulcerative Colitis Activity Index (PUCAI)............................139
Appendix D.
Mayo Scoring System..........................................................................140
Appendix E.
Loss of Response and Intolerance to Anti-TNF Agent .........................144
Appendix F.
Work Productivity and Activity Impairment Questionnaire: 
Ulcerative Colitis V2.0 (WPAI:  UC) – Caregiver ...............................145
Appendix G.
Study Drug Packaging and Administration ..........................................148
Appendix H.
Body Weight Adjusted Volumes of Study Drug for 
Administration of Induction and Maintenance Doses...........................158
Appendix I.
Body Weight Adjusted Volumes of Study Drug for 
Administration of Dose After Re-Randomization for Disease 
Flare....................................................................................................164
Appendix J.
Body Weight Adjusted Volumes of Study Drug for 
Administration of OL Adalimumab 0.6 mg/kg Dosing (weight 
based)..................................................................................................167
Appendix K.
70-Day Follow-Up Call – Sample........................................................168
Appendix L.
Injection Instructions – Sample Vial....................................................169
Appendix M.
Non-Drug Materials Provided to the Study Sites..................................176
Appendix N.
The Measurements and Volume(s) of Blood Samples to Be Drawn .....177
Appendix O.
Protocol Amendment:  List of Changes ...............................................179

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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 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 Ireland6).  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 99).  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 anemia 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 double-blind clinical trials (Study M06-826 and Study M06-827) and a 
completed 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.  
AbbVie is participating in an FDA-requested, TNF inhibitor class-wide exploration of the 
rare appearance of malignancy in subjects who are 30 years old or younger at the time of 
diagnosis.  The risk of malignancy in this age group has not been established and is 
difficult to study due to its rarity.  AbbVie appreciates your attention to the additional 
reporting requirements needed in this unlikely event, outlined in Section 6.1.5 under 
Adverse Event Reporting.
3.3.1
Differences Statement
Pediatric subjects with moderate-to-severe UC between the ages of 4 and 17 who have 
failed conventional therapy with corticosteroids or immunosuppressants will be 
considered for participation in the study.  To date, the efficacy, safety and the 
pharmacokinetics of adalimumab in pediatric subjects with moderate-to-severe ulcerative 
colitis (UC) have not been evaluated in a double-blind, controlled trial.

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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.  
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).
4.0
Study Objective
The objective of the study is to demonstrate the efficacy and safety, and to assess the 
pharmacokinetics of adalimumab administered subcutaneously (SC) in pediatric subjects 
with moderate-to-severe ulcerative colitis (UC).
5.0
Investigational Plan
5.1
Overall Study Design and Plan:  Description
The study is designed to enroll 93 subjects (not including the Japanese sub-study) to meet 
scientific and regulatory objectives without enrolling an undue number of subjects in 
alignment with ethical considerations.  Therefore, if the target number of subjects has 
been enrolled, there is a possibility that additional subjects in screening will not be 
enrolled.
This is a Phase 3, multicenter, randomized, double-blind study designed to evaluate the 
efficacy and safety of the human anti-TNF monoclonal antibody adalimumab in pediatric 
subjects with moderate to severe ulcerative colitis (UC).
The present study is to confirm the efficacy and safety of adalimumab in pediatric 
subjects with ulcerative colitis, in accordance with pediatric legislation in EU and US.  
The study protocol was reviewed and incorporated comments by the PDCO of the EMA 
and the FDA.

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93 pediatric subjects with moderate-to-severe ulcerative colitis (Mayo Score of 6 to 
12 points with endoscopy subscore of 2 to 3, confirmed by central reader) will be enrolled 
at approximately 50 sites worldwide (Section 5.3.1.1).
There also will be up to approximately 9 Japanese subjects in a Japan sub-study to be 
enrolled at approximately 10 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.
The study will allow enrollment of up to 25% of anti-TNF experienced subjects. 
Prior to Amendment 4, subjects who met all of the inclusion criteria and none of the 
exclusion criteria were enrolled into the study and randomized 3:2 at Baseline to one of 
two double-blinded adalimumab induction doses (high induction dose or standard 
induction dose).  The randomization was stratified by Baseline disease severity (Mayo 
Score [≤ 9, > 9]), prior exposure to infliximab and corticosteroid use at Baseline.
During the randomized double-blind induction period, subjects assigned to high dose 
group received adalimumab 2.4 mg/kg (maximum dose of 160 mg) at Baseline and at 
Week 1.  At Week 2, subjects received adalimumab 1.2 mg/kg (maximum dose of 80 mg), 
followed by a dose of 0.6 mg/kg (maximum dose of 40 mg) at Week 4 and Week 6.  
Subjects randomized to standard dose group received adalimumab 2.4 mg/kg (maximum 
dose of 160 mg) at Baseline and matching placebo at Week 1, adalimumab 1.2 mg/kg 
(maximum dose of 80 mg) at Week 2, followed by a dose of 0.6 mg/kg (maximum dose 
of 40 mg) at Week 4 and Week 6.
Ongoing subjects randomized prior to Amendment 4 will continue their blinded treatment 
during the induction period until Week 8.
At Week 8, subjects demonstrating a clinical response per Partial Mayo Score (PMS) 
(defined as a decrease in PMS ≥ 2 points and ≥ 30% from Baseline) were randomized in a 
2:2:1 ratio to one of two adalimumab maintenance treatment groups (standard dose 
[0.6 mg/kg (maximum dose of 40 mg) every other week] or high dose [0.6 mg/kg 

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(maximum dose of 40 mg) every week]) or to placebo, respectively.  The randomization 
was stratified by Week 8 remission status per PMS (defined as a PMS ≤ 2 and no 
individual subscore > 1) and induction dose.
Ongoing subjects randomized prior to Amendment 4 will continue their blinded treatment 
during the maintenance period until Week 52 and re-randomization to treatment for 
disease flare will be done according to Amendment 3 stipulations in these subjects.
After Amendment 4, subjects who meet all of the inclusion criteria and none of the 
exclusion criteria will be enrolled into the study and receive open-label (OL) adalimumab 
high induction dose.  During the OL induction period, subjects will receive adalimumab 
2.4 mg/kg (maximum dose of 160 mg) at Baseline and at Week 1.  At Week 2, subjects 
will receive adalimumab 1.2 mg/kg (maximum dose of 80 mg), followed by a dose of 
0.6 mg/kg (maximum dose of 40 mg) at Week 4 and Week 6.
At Week 8, subjects demonstrating a clinical response per PMS (defined as a decrease in 
PMS ≥ 2 and ≥ 30% from Baseline) will be randomized and stratified by Week 8 
remission status per PMS (defined as a PMS ≤ 2 and no individual subscore > 1) in a 
1:1 ratio to one of two adalimumab maintenance treatment groups (standard dose 
[0.6 mg/kg (maximum dose of 40 mg) every other week] or high dose [0.6 mg/kg 
(maximum dose of 40 mg) every week]).
Subjects will receive blinded treatment every week (ew) beginning at Week 8 and will 
remain on double-blinded therapy through Week 52.
●
Subjects who are randomized to standard dose will receive a maintenance dose 
of 0.6 mg/kg (maximum dose of 40 mg) every other week (eow) and will 
receive the matching placebo at the alternate week.
●
Subjects who are randomized to high dose will receive a maintenance dose of 
0.6 mg/kg (maximum dose of 40 mg) ew.
●
Subjects who were randomized to placebo prior to Amendment 4 receive 
matching placebo ew.

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At Week 8, subjects who have not achieved a clinical response per PMS will be 
discontinued from the study.  A safety evaluation call will be made 70 days after the last 
dose of study drug is administered to obtain follow-up information on any ongoing or new 
adverse events.
The duration of the study could be up to 66 weeks, which includes a Screening Period of 
up to 28 days, an 8-week induction period and a 44-week double-blind 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.
The Screening period may be extended as necessary after consultation with the AbbVie 
Medical Monitor for subjects who require initiation of prophylactic anti-TB therapy, or in 
case of external, not subject-related circumstances (e.g., due to delay of availability of 
screening test results).
Upon completion of the study, subjects will have the option to enroll into an open-label 
extension study where they will continue to receive open-label adalimumab.
Efficacy and safety measurements will be performed throughout the study (Section 5.3.1).  
Clinical evaluation will be at Baseline, Weeks 1, 2, 4, 8, 12, 18, 26, 34, 42, and 
52/Premature Discontinuation and unscheduled Visits.  Subjects will undergo 
colonoscopy or flexible sigmoidoscopy during the Screening period and at 
Weeks 52/Premature Discontinuation Visit to assess disease activity.  If the subject 
underwent an endoscopy within 56 days of Baseline and a video recording of the 
endoscopy is available, the video recording may be used to assess disease activity and no 
additional endoscopy will be performed during the Screening period provided that the 
conditions noted in Section 5.3.1.1 are met, and all technical requirements are fulfilled.
Blood samples for the measurement of adalimumab concentrations will be collected at 
Baseline, Weeks 2, 4, 8, 12, 26, 34 and 52/Premature Discontinuation Visits and at 
Unscheduled Visits requiring dose change.  Blood samples for measurement of 

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anti-adalimumab antibodies (AAAs) will be collected at Baseline, Weeks 4, 8, 26 and 
52/Premature Discontinuation Visits and at Unscheduled Visits requiring dose change.
Blood samples for measurement of human anti-chimeric antibody (HACA) to infliximab 
as well as infliximab drug levels will also be collected at Week 0.
Subjects are allowed to be treated with stable doses of UC-related concomitant 
medications during the study, with the following exceptions and requirements:
●
At or after Week 4, subjects taking corticosteroid therapy at Baseline may have 
their corticosteroid therapy tapered based on the investigator's discretion.  A 
proposed tapering schedule is specified in Section 5.3.1.1.
●
From Week 4 to Week 12, if the subject should experience an increase in 
symptoms after corticosteroid was tapered, the subject may have their 
corticosteroid dose increased back up to the corticosteroid dose at Baseline.  
This increase must be discussed with and approved by the Medical Monitor 
prior to any changes in these treatments.
●
Subjects who experience disease flare at or after Week 12 are allowed to 
change their dose or initiate treatment with corticosteroids, 
immunosuppressants or 5-ASA; these increases must be discussed with and 
approved by the Medical Monitor prior to any changes in these treatments.
●
Immunosuppressant doses may be decreased or terminated in the event of 
moderate-to-severe treatment-related toxicities (e.g., leukopenia or elevated 
liver enzyme) considered moderate to severe in the opinion of the investigator.
●
Immunosuppressant therapy may be discontinued at or after Week 12 at the 
investigator's discretion.
Treatment of Subjects with a Disease Flare During the Study
Criteria for Disease Flare are as follows:
●
Subjects with a Week 8 PMS of 0 to 2 who present with a PMS at least 
3 points greater than their Week 8 score.

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●
Subjects with a Week 8 PMS of 3 to 4 who present with a PMS at least 
2 points greater than their Week 8 score.
●
Subjects with a Week 8 PMS of 5 to 6 who present with a PMS at least 1 point 
greater than their Week 8 score.
Subjects will be expected to remain on blinded therapy throughout the 44-week 
maintenance period.  However, subjects with a disease flare may be re-randomized to 
receive the following blinded-treatment at or after Week 12, Figure 4.
●
Subjects who are randomized to standard maintenance dose (0.6 mg/kg eow 
[maximum of 40 mg eow]) will be re-randomized to receive either 
adalimumab re-induction dose (2.4 mg/kg [maximum of 160 mg]) or 
adalimumab (0.6 mg/kg [maximum of 40 mg]) at the visit.  Afterwards, all 
subjects will resume receiving the standard dose (0.6 mg/kg [maximum of 
40 mg] eow) within the original dosing schedule.
●
Subjects who are randomized to high maintenance dose (0.6 mg/kg ew 
[maximum of 40 mg ew]) will be re-randomized to receive either adalimumab 
re-induction dose (2.4 mg/kg [maximum of 160 mg]) or adalimumab
(0.6 mg/kg [maximum of 40 mg]) at the visit.  The following week, all 
subjects will resume receiving the high dose (0.6 mg/kg [maximum of 40 mg] 
ew).
●
Subjects who were randomized to placebo prior to Amendment 4 will be re-
randomized to receive either adalimumab re-induction dose (2.4 mg/kg 
[maximum of 160 mg]) or to receive adalimumab (0.6 mg/kg [maximum of 
40 mg]) at the visit.  Afterwards, all subjects will receive the standard dose 
(0.6 mg/kg [maximum of 40 mg] eow) within the original dosing schedule.
If a subject continues to meet the definition of disease flare (2nd time) following at least a 
4-week course of blinded therapy since the subject has been re-randomized for the disease 
flare, they may be switched to open-label adalimumab every week at the dose 0.6 mg/kg 
[maximum of 40 mg].  (If a subject was re-randomized at Week 12 (to receive either 
re-induction dose (2.4 mg/kg [maximum of 160 mg]) or to receive adalimumab (0.6 mg/kg 
[maximum of 40 mg]), then the earliest that subject could be evaluated to determine if 

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they meet the criteria for disease flare for switch to OL (0.6 mg/kg [maximum of 40 mg]) 
weekly dosing is at Week 16.  
If a subject continues to meet the definition of disease flare (3rd time) following a 4-week 
course of open-label adalimumab every week at the dose 0.6 mg/kg [maximum of 40 mg], 
they may be switched to receive adalimumab open-label 40 mg ew (maximum dose, not 
weight based).
Subjects with persistent disease flare while on adalimumab 40 mg ew (max dose) may be 
withdrawn from the study at the investigator's discretion.
During open-label rescue therapy, subjects who are responders and have been in remission 
for at least 8 consecutive weeks (PMS ≤ 2 with no individual subscore > 1) may have 
their dosage decreased from ew to eow. 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.  The investigator 
should receive prior approval from the Medical Monitor before taking any action with 
regard to dose re-escalation.
For subjects who meet the criteria for dose change, blood samples (for the determination 
of adalimumab and AAA concentrations, hs-CRP) will be collected just prior to receiving 
any dose change (blinded therapy, escape to open-label adalimumab, dose de-escalation 
and dose re-escalation).
No study drug will be administered or injected at the final visit.
Subjects may discontinue adalimumab treatment at any time during study participation.  
Subjects who 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.

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Re-screening
Subjects who initially screen fail for the study may be permitted to re-screen following 
re-consent.  All screening procedures with the possible exceptions noted below will be 
repeated.  The subject must meet all inclusion and none of the exclusion criteria as far as 
they are assessable at the time of re-screening in order to qualify for the study.  There is 
no minimum period of time a subject must wait to re-screen for the study.  If the subject 
had a complete initial screening evaluation including the assessment of a PPD test, (or 
equivalent), or Interferon-Gamma Release Assay (IGRA; QuantiFERON-TB Gold 
In-Tube test or T-SPOT TB test), chest x-ray (if applicable), x-ray of the wrist and ECG, 
these tests will not be required to be repeated for re-screening provided the conditions 
noted in Section 5.3.1.1 are met and no more than 3 months (90 days) have passed.  An 
endoscopy will not be required to be repeated for re-screening provided that the prior 
endoscopy confirmed subject's eligibility, the conditions noted in Section 5.3.1.1 are met 
and no more than 56 days have passed from Baseline.
For subjects in re-screening, lab assessments will not need to be repeated if the time 
between Screening and Re-screening is less than 28 days.
However, lab assessments will need to be repeated at Baseline if the time between lab 
assessments during previous Screening and Baseline is greater than 28 days.
Additionally, a PG sample will not be required to be repeated for re-screening provided 
that a PG sample has already been collected during previous Screening and is still 
available for analysis.  As appropriate, sites are encouraged to contact the AbbVie 
Medical Monitor to confirm if subjects should or should not be re-screened.

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Figure 2.
Study Design Schematic After Amendment 4

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Figure 3.
Study Design Schematic for Dose Escalation Prior to Amendment 4

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Figure 4.
Study Design Schematic for Dose Escalation After Amendment 4

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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.
Subjects from the ages of 4 and 17 prior to baseline dosing.
2.
Subjects with a diagnosis of UC for at least 12 weeks prior to screening confirmed 
by endoscopy with biopsy.
A colonoscopy will be performed during the screening period unless the subject 
underwent a colonoscopy within 12 months prior to Screening and appropriate 
documentation is available (to confirm the diagnosis without evidence of dysplasia, 
colon cancer or infection).  In this case the screening endoscopy may be either a 
colonoscopy or a flexible sigmoidoscopy.
If the subject underwent an endoscopy within 56 days of Baseline and a video 
recording of the endoscopy is available, the video recording may be used and no 
additional endoscopy will be performed during the Screening period provided that 
the conditions noted in Section 5.3.1.1 are met, and all technical requirements are 
fulfilled.
Note:
●
If no appropriate documentation for confirmation of the diagnosis is available 
as per the investigator's judgment a diagnostic biopsy must also be performed.
●
Biopsies to rule out dysplasia, colon cancer and infection may be taken at the 
investigator's discretion.
3.
Active ulcerative colitis with a Mayo Score of 6 to 12 points and endoscopy 
subscore of 2 to 3 (confirmed by central reader) despite concurrent treatment with 
at least one of the following (oral corticosteroids or immunosuppressants or both as 
defined below):

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●
Oral prednisone of ≥ 2 mg/day or equivalent, but not exceeding 40 mg/day, or 
oral budesonide ≥ 3 mg/day, but not exceeding 9 mg/day, with a stable dose 
for at least 7 days prior to Baseline;
and/or
●
At least a consecutive 28 day course of azathioprine or 6-MP or methotrexate 
(MTX) prior to Baseline, with a stable dose prior to Baseline of azathioprine 
≥1.5 mg/kg/day or 6-MP ≥ 1 mg/kg/day (rounded to the nearest available 
tablet or half tablet formulation) or a documented 6-TGN level of 
230 – 450 pmol/8 × 108 RBC on the current dosing regimen or MTX 
≥15 mg/m2 body surface area/week, or a dose that is the highest tolerated by 
the subject (e.g., due to leukopenia, elevated liver enzymes, nausea) during 
that time.
Note:  If subjects are on both oral corticosteroid and immunosuppressants 
BOTH of the drugs need to meet the above criteria.
and/or
●
Concurrent therapy with corticosteroids or immunosuppressants (azathioprine, 
6-MP or MTX) is not required for subjects who were previously treated during 
the past 1 year and have confirmed documentation of failure to respond, or 
were previously treated during the past 5 years and have confirmed 
documentation indicating lack of tolerability.
4.
Parent or guardian has voluntarily signed and dated an informed consent form, 
approved by an Institutional Review Board (IRB)/Independent Ethics Committee 
(IEC), after the nature of the study has been explained and the subject's parent or 
legal guardian has had the opportunity to ask questions.  The informed consent 
must be signed before any study-specific procedures are performed or before any 
concomitant medication is discontinued for the purpose of this study.  Pediatric 
subjects will be included in all discussions in order to obtain verbal and/or written 
assent.

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5.
Subjects must be able and willing to self-administer SC injections or have a 
qualified person available to administer SC injections.
6.
Subject has a negative TB Screening Assessment.
If a subject has a positive (≥5 mm induration) PPD test and/or IGRA test at 
Screening, a CXR (PA and lateral view) must be performed for evaluation of active 
TB disease.  If the subject has evidence of a latent TB infection, the subject must 
initiate and complete a minimum of 2 weeks (or per local guidelines, whichever is 
longer) of an ongoing course of TB prophylaxis or have documented completion of 
a full course of TB prophylaxis, prior to Baseline (Section 5.3.1).
7.
If female, subject who is either not of childbearing potential, defined as 
premenstrual, 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 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, foams, jellies, diaphragm or intrauterine device (IUD);
●
Hormonal contraceptives for 90 days prior to study drug administration;
●
A vasectomized partner.
8.
Subject is judged to be in good health as determined by the Principal Investigator 
based upon the results of medical history, laboratory profile, physical examination, 
chest x-ray (CXR), and a 12-lead electrocardiogram (ECG) performed during 
Screening.
5.2.2
Exclusion Criteria
A subject will be excluded from the study if he/she meets any of the following criteria:
1.
Subject with Crohn's disease (CD) or indeterminate colitis (IC).
2.
Current diagnosis of fulminant colitis and/or toxic megacolon.

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3.
Subjects with disease limited to the rectum (ulcerative proctitis) during the 
screening endoscopy.
4.
Therapeutic enema or suppository within 14 days prior to the Screening endoscopy 
and during the remainder of the Screening Period.
5.
History of colectomy or subtotal colectomy (with ostomy) or is planning bowel 
surgery.
6.
Received cyclosporine, tacrolimus, or mycophenolate mofetil, within 30 days prior 
to Baseline.
7.
Female subjects who are breast-feeding or considering becoming pregnant during 
the study.
8.
Positive pregnancy test at Screening or Baseline.
9.
History of clinically significant drug or alcohol abuse in the last 12 months.
10.
Subjects on azathioprine or 6-mercaptopurine (6-MP) or MTX and subjects:
●
Have not been on stable doses of these medications for at least 28 days prior to 
Baseline; or
●
Have discontinued these medications within 28 days of Baseline.
11.
Subjects on oral aminosalicylates who:
●
Have not been on stable doses of these medications for at least 14 days prior to 
Baseline; or
●
Have discontinued use of aminosalicylates within 14 days of Baseline.
12.
Subjects on growth hormone who have not been on a stable dose for at least 
4 weeks prior to Baseline.
13.
Subjects on oral corticosteroids who:
●
Have not been on stable doses of these drugs for at least 7 days prior to 
Baseline; or
●
Discontinued use of oral corticosteroid within 14 days of Baseline; or

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●
Have been taking both budesonide and prednisone (or equivalent) 
simultaneously.
14.
Received intravenous corticosteroids within 5 days prior to Screening or during the 
Screening Period.
15.
Subject who has previously used infliximab or any anti-TNF agent within 56 days 
of Baseline.
16.
Subject who has previously used infliximab or any anti-TNF agent and has not 
clinically responded at any time ("primary non-responder") unless subject 
experienced a treatment limiting reaction.
17.
Previous treatment with adalimumab or previous participation in an adalimumab 
clinical study.
18.
Positive Clostridium difficile (C. difficile) stool assay during the Screening Period.
19.
Currently receiving total parenteral nutrition (TPN).
20.
History of demyelinating disease (including myelitis) or neurologic symptoms 
suggestive of demyelinating disease.
21.
History of invasive infection (e.g., listeriosis and histoplasmosis), human 
immunodeficiency syndrome (HIV).
22.
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.
23.
Subjects with any active viral infection that, based on the investigator's clinical 
assessment, makes the subject an unsuitable candidate for the study.
24.
Subjects with a positive result for Hepatitis B surface antigen (HBs Ag) or any 
HBV DNA PCR result that meets or exceeds detection sensitivity will be excluded.
25.
Chronic recurring infections or active TB.

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26.
Subject has been treated with any investigational drug of chemical or biologic 
nature or any investigational procedure (including previous fecal transplantation) 
within 30 days or 5 half-lives (whichever is longer) of the drug prior to the Baseline 
Visit.
27.
Infection(s) requiring treatment with intravenous (IV) anti-infectives within 
30 days prior to the Baseline Visit or oral anti-infectives within 14 days prior to the 
Baseline Visit.
28.
Prior exposure to biologics that have a potential or known association with PML 
(i.e., natalizumab [Tysabri®] or efalizumab [Raptiva®] or rituximab [Rituxan®]).
29.
Known hypersensitivity to adalimumab or its excipients.
30.
Evidence of dysplasia or 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.
If the Screening endoscopy shows evidence of dysplasia or malignancy, subject 
may not be enrolled in the study.
31.
Screening laboratory and other analyses show any of the following abnormal 
results:
●
ECG – with clinically significant abnormalities;
●
Aspartate transaminases (AST) or alanine transaminase (ALT) > 1.75 × the 
upper limit of the reference range;
●
Total bilirubin ≥ 3 mg/dL;
●
Serum creatinine > 1.6 mg/dL;
●
Clinically significant abnormal screening laboratory results as evaluated by the 
investigator.
32.
Subject is considered by the investigator, for any reason, to be an 
unsuitable candidate for the study.

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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 has received within 30 days prior to 
Baseline, is receiving at the time of enrollment, or 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.
Any antibiotic that the subject has received within 60 days prior to Baseline, is receiving 
at the time of enrollment, or 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.
Ulcerative colitis specific medications (including corticosteroids, aminosalicylates and 
immunosuppressant agents) that the subject has received within 90 days of Baseline 
should be recorded on the appropriate page of the electronic case report form (eCRF) and 
should include the dates of administration and dosages.
Subjects who were previously treated with corticosteroids or immunosuppressants 
(azathioprine, 6-MP or MTX) during the past 1 year and have confirmed documentation 
of failure to respond, or were previously treated during the past 5 years and have 
confirmed documentation indicating lack of tolerability will have the last dosage and 
dates of administration and reasons for discontinuation recorded in appropriate eCRF.
In addition, subjects who failed to respond or were intolerant to treatment with 
corticosteroids or immunosuppressants within the past 1 year will have the highest 
previous administered dose recorded in appropriate eCRF.

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Prior azathioprine, 6-MP and MTX use (since birth) will be asked.  If subjects have/had 
ever been treated with azathioprine and/or 6-MP and/or MTX, the duration of therapy, 
maximum dose, reason for use and reason(s) for termination of treatment will be recorded 
in appropriated eCRF.
For subjects previously treated with biologics (e.g., etanercept and/or infliximab ), the 
biologic therapy history will be recorded, this included the duration of therapy, maximum 
dose, reason for use and reason(s) for termination of treatment with these products should 
be documented.
The AbbVie study-designated physician identified in Section 6.1.5 should be contacted if 
there are any questions regarding concomitant or prior therapy.
In addition for subjects age ≤ 30 with a reported malignancy adverse event, prior exposure 
to, or current use of, antineoplastics, or other drugs which have a risk of malignancy as 
stated in their label and other relevant dosing information to estimate total exposure will 
be collected in the source documents and appropriate eCRF pages.  At the time of the 
reported malignancy adverse event, sites will be asked if any of the prior and concomitant 
medications contributed to the event.  Any medications used prior to the study will be 
captured on the appropriate 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
Subjects may continue their doses of azathioprine, 6-MP or MTX provided they are on 
these medications for at least 28 days prior to Baseline and that doses have been stable for 
at least 28 days prior to Baseline.  Doses of these concomitant medications (azathioprine, 
6-MP or MTX) must remain stable for the first 12 weeks of participation, except in the 
event of treatment-related toxicities (e.g., leukopenia or elevated liver enzymes) 
considered moderate to severe in the opinion of the investigator.  Immunosuppressant 

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dose (azathioprine and 6-MP or MTX) can be discontinued starting at Week 12 per 
investigator's discretion.  Subjects who experience disease flare at or after Week 12 are 
allowed to change their dose or initiate treatment with corticosteroids, 
immunosuppressants or 5-ASA; these increases must be discussed with and approved by 
the Medical Monitor prior to any changes in these treatments.
Subjects may continue doses of aminosalicylates provided they are on these medications 
for at least 14 days prior to Baseline and that doses have been stable for at least 14 days 
prior to Baseline.  Oral antibiotics are permitted prior to Baseline and subjects may 
continue these medications provided that they were prescribed for ulcerative colitis but 
not for treatment of an infection.  Corticosteroids are permitted if the subject has been on 
stable doses prior to Baseline as outlined in inclusion criterion 3 in Section 5.2.1.  
Subjects are not allowed to change the corticosteroid dose during the first 4 weeks of the 
study.  At or after Week 4, subjects who are taking corticosteroid therapy at Baseline may 
have their corticosteroid therapy tapered off based on the investigator's discretion.
A proposed schedule to taper corticosteroid dose starts with a weekly decrease by 
5 mg/day prednisone (or equivalent) for doses > 10 mg/day of prednisone (or equivalent) 
until a 10 mg/day (or equivalent) dose is reached, then a weekly decrease by 2.5 mg/day 
(or equivalent) until discontinuation.
A proposed schedule to taper budesonide dose starts with a weekly decrease by 3 mg/day 
until discontinuation.
From Week 4 to Week 12, if the subject should experience an increase in symptoms after 
corticosteroid was tapered, the subject may have their corticosteroid dose increased back 
up to the corticosteroid dose at Baseline. This increase must be discussed with and 
approved by the Medical Monitor before.
At or after Week 12, if the subject should experience disease flare, the subject may have 
their corticosteroid dose initiated, reinitiated or increased (as mentioned above).  These 

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initiations, reinitiations or increases must be discussed with and approved by the Medical 
Monitor prior to any changes in these treatments.
Subjects may not be on both budesonide and prednisone (or equivalent) simultaneously.
Subjects who enter the study on probiotics may continue this therapy provided the dose 
remains unchanged.
Subsequent changes in all concomitant medications will be assessed at each study visit 
from Baseline (Week 0) through Week 52/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.
All non-UC medications (prescription and over-the-counter) used during the 30 days prior 
to Baseline will be recorded and must include all doses and date ranges of administration.  
Vaccines administered to the subject within 30 days prior to Baseline will be listed as a 
concomitant medication.  Any antibiotic used during the 60 days prior to Baseline will be 
recorded and must include all doses and date ranges of administration.
The AbbVie study Primary Therapeutic MD identified in Section 6.1.5 should be 
contacted if there are any questions regarding concomitant or prior therapy(ies).
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®);

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○
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 cyclosporine, tacrolimus, or mycophenolate mofetil is prohibited 
within 30 days prior to Baseline and during the study.
●
Rectal therapy with any therapeutic enemas or suppositories is prohibited 
within 14 days prior to Screening endoscopy, during the remainder of the 
Screening Period and during the study.  Rectal medication for bowel 
preparation prior to endoscopy is permitted.
●
Intravenous corticosteroid use is prohibited within 5 days prior to Screening, 
during the Screening Period and during the study.
●
Any investigational drug of chemical or biologic nature or any investigational 
procedure (including previous fecal transplantation) are prohibited within 
30 days or 5 half-lives (whichever is longer) of the drug prior to the Baseline 
and during the study.
The AbbVie Primary Therapeutic MD identified in Section 6.1.5 should be contacted if 
there are any questions regarding prohibited therapy.

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5.3
Efficacy, Pharmacokinetic 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.

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Table 1.
Study Activities
Activity
Scr
Baseline 
(Wk 0)a
Wk
1
Wk
2
Wk
4
Wk
8
Wk
12
Wk
18
Wk
26
Wk
34
Wk
42
Wk 52/
Premature 
Discontinuation
Unscheduled
Visit
70 Day 
Follow-up 
Phone 
Callw
Informed Consent
X
Inclusion/Exclusion
X
X
Medical/Surgical History
X
X
Tobacco and Alcohol Use
X
Previous and Concomitant 
Medication
X
X
X
X
X
X
X
X
X
X
X
X
X
Vital Signsb
X
X
X
X
X
X
X
X
X
X
X
X
X
Endoscopyc,d
Xc
Xd
Physical Examinatione
X
X
X
X
X
X
X
X
X
X
X
X
X
TB Screeningf
X
Xh
Chest X-rayg
Xg
Xh
ECGi
X
Chemistry and 
Hematologyj
X
Xk
X
X
X
X
X
X
X
X
X
X
Urinalysisl
X
Xk
X
X
X
X
X
X
X
X
X
X
Pregnancy Testsm
Xm
Xn
Xn
Xn
Xn
Xn
Xn
Xn
Xn
Xn
Xn
Xm
C. difficile toxin
X

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Table 1.
Study Activities (Continued)
Activity
Scr
Baseline 
(Wk 0)a
Wk
1
Wk
2
Wk
4
Wk
8
Wk
12
Wk
18
Wk
26
Wk
34
Wk
42
Wk 52/
Premature 
Discontinuation
Unscheduled
Visit
70 Day 
Follow-up 
Phone 
Callw
ANA/dsDNAo
X
HBV Screening
Xz
Infliximab and HACA 
Concentration
X
Adalimumab 
Concentrationp,q
X
X
X
X
X
X
X
X
Xq
AAA Concentrationp,q
X
X
X
X
X
Xq
hs-CRPq
X
X
X
X
X
X
X
X
X
X
Xq
PUCAI
X
X
X
X
X
X
X
X
X
X
X
X
Partial Mayo Score
X
X
X
X
X
X
X
X
X
X
X
X
Mayo Score
X
X
IMPACT III 
Questionnairer
X
X
X
X
Work Productivity and 
Impairment Questionnaire 
(WPAI):  UC – Caregivers
X
X
X
X
X
X
X
X
X
X
X
Tanner Stagey
X
X
X
X-ray for Bone Age
Xae
X
Anthropometric 
Evaluations
X
X
X
PG (optional)x
X

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Table 1.
Study Activities (Continued)
Activity
Scr
Baseline 
(Wk 0)a
Wk
1
Wk
2
Wk
4
Wk
8
Wk
12
Wk
18
Wk
26
Wk
34
Wk
42
Wk 52/
Premature 
Discontinuation
Unscheduled
Visit
70 Day 
Follow-up 
Phone 
Callw
Serologic Markers/mRNA 
(optional)aa
X
X
X
X
mRNA (optional)ad
X
X
X
X
Corticosteroid Tapert
X
X
X
X
X
X
X
X
Monitor Adverse Eventsu
X
X
X
X
X
X
X
X
X
X
X
X
X
Subject Diary Dispensing/ 
Reviewingac
Xab
X
X
X
X
X
X
X
X
X
X
X
X
Study Drug Dispensing/ 
Administrationv
X
X
X
X
X
X
X
X
X
X
Xv
Scr = Screening
a.
The Baseline visit date will serve as the reference for all subsequent visits.  A ± 3-day window is permitted around scheduled study visits.  Medical/surgical history at 
Baseline is an update since Screening.
b.
Vital sign determinations of weight, sitting blood pressure, pulse rate, respiratory rate, body temperature will be obtained at each visit.
c.
A colonoscopy will be performed during screening unless the subject underwent a colonoscopy within 12 months prior to Screening and appropriate documentation for both 
colonoscopy are available (to confirm the diagnosis and no evidence of dysplasia, colon cancer or infection).  In this case the screening endoscopy may be either a 
colonoscopy or a flexible sigmoidoscopy.  If the subject underwent an endoscopy within 56 days of Baseline and the video recording of endoscopy is available the video 
recording may be used and no additional endoscopy will be performed during the Screening period provided that the conditions noted in Section 5.3.1.1 are met, and all 
technical requirements are fulfilled.  If no appropriate documentation for confirmation of the diagnosis is available as per the investigator's judgment a diagnostic biopsy must 
be performed.  Biopsies to rule out dysplasia, colon cancer and infection may be taken at the investigator's discretion.

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Table 1.
Study Activities (Continued)
d.
At Week 52, a colonoscopy or flexible sigmoidoscopy will be performed.  In patients who prematurely discontinue, a colonoscopy or flexible sigmoidoscopy will only be 
performed if premature discontinuation occurs after Week 26.
e.
Physical examinations performed at Screening, Baseline, Week 26, and Week 52/Premature Discontinuation Visits are full physical examinations and those performed at all 
other visits are symptom based.
f.
Subjects with negative PPD test and/or Interferon-Gamma Release Assay (IGRA; QuantiFERON-TB Gold In-Tube test or T-SPOT TB test) within 90 days of Screening 
would not require a repeat test, if all protocol required documentation is available, provided nothing has changed in the subject's medical history to warrant a repeat test.  
PPD skin test is to be read 48 to 72 hours after placement.
g.
All subjects with a positive PPD test or positive Interferon-Gamma Release Assay (IGRA; QuantiFERON-TB Gold In-Tube test or T-SPOT TB test) will undergo a standard 
CXR (posterior-anterior [PA] and lateral views) at the Screening Visit to rule out the presence of TB or other clinically relevant findings.  The CXR will not be required if the 
subject had a previous normal chest x-ray within 90 days of Screening, provided all protocol required documentation is available at the site.
h.
For subjects with a negative TB test at Screening, TB test will be required at Week 52.  If the annual TB screen is positive, a CXR may be required for evaluation of active 
TB.  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, 
Screening, or testing performed at any time point during the study).  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 Week 52.
i.
Subjects with normal ECG within 90 days of Screening would not require a repeat ECG, if documentation is available.
j.
Blood draws should be performed after completion of all clinical assessments and questionnaires.
k.
Lab assessments will only need to be repeated at Baseline if the time between Screening lab assessments and Baseline is greater than 28 days, or any new concomitant 
medication with potential impact on laboratory parameters was started during the Screening Period.  For subjects in re-screening lab assessments will not need to be repeated 
if the time between Screening and Re-screening is less than or equal to 28 days.  However, lab assessments will need to be repeated at Baseline if the time between lab 
assessments during previous Screening and Baseline is greater than 28 days.
l.
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.
m.
All females of childbearing potential will have a serum pregnancy test at Screening, and Week 52/Premature Discontinuation Visit.
n.
At the Baseline 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.
Monthly pregnancy tests will be performed throughout the study if required by country regulatory authorities.

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Table 1.
Study Activities (Continued)
o.
Anti-dsDNA performed if ANA result is positive.
p.
Blood samples for the measurement of adalimumab and AAA concentrations will be collected prior to dosing at the said weeks of sampling.
q.
Blood samples (for measurement of serum adalimumab and AAA concentrations and hs-CRP) will be collected for subject just prior to any dose change (blinded therapy, 
escape to open-label, dose escalation, dose de-escalation and re-escalation).
r.
IMPACT III Quality of Life questionnaire at Baseline, Weeks 8, 26 and 52/Premature Discontinuation Visit will be completed for subjects 9 or older at the baseline study 
visit.
s.
WPAI will be completed by subject's parent or legal guardian at every visit except the Unscheduled Visit.  The questionnaire will not be completed if the subject's parent or 
legal guardian is not taking care of the subject anymore.
t.
Subjects may begin corticosteroid taper at Week 4, based on the investigator's discretion.
u.
Collection of SAEs begins the day the subject signs the informed consent.
v.
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.
w.
Site personnel will contact all subjects approximately 70 days following study drug discontinuation to determine the occurrence of AEs or SAEs.
x.
Verify subject has signed consent for optional pharmacogenetic sample.  If the sample is not collected at Baseline, it may be collected at any time during the study.  If the 
sample was collected at Screening visit, no PG sample should be collected at Baseline.
A PG sample will not be required to be repeated for re-screening provided that a PG sample has already been collected during previous Screening and is still available for 
analysis.
y.
Tanner Stage will be assessed at Screening (or at Baseline as appropriate), Week 26 and 52/Premature Discontinuation Visit if premature discontinuation occurs after 
Week 26.
z.
Subjects will be tested for the presence of Hepatitis B Virus (HBV) at Screening.  A positive result for the Hepatitis B surface antigen (HBs Ag) will be exclusionary.  
Samples that are negative for HBs Ag will be tested for HBs Ab and HBc Ab Total.  Subjects who are HBs Ag (–), HBs Ab (–), and HBc Ab Total (+) require PCR qualitative 
testing for HBV DNA.  Any HBV DNA PCR result that meets or exceeds detection sensitivity will be exclusionary.  Subjects with a negative HBs Ag test and tests showing 
the results below, do not require HBV DNA PCR qualitative testing.
!
HBc Ab Total (–) and HBs Ab (–)
!
HBc Ab Total (–) and HBs Ab (+)
!
HBc Ab Total (+) and HBs Ab (+)

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Table 1.
Study Activities (Continued)
aa.
If subject has signed consent for optional serologic markers, blood samples will be collected at Baseline, Week 8, 26 and 52/Premature Discontinuation Visit.
ab. Subjects will be dispensed a subject diary at Screening and will be trained on how to complete the diary by site staff during the Screening visit.  
ac.
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 52//Premature Discontinuation Visit.
ad. If subject has signed consent for optional mRNA, blood samples will be collected at Baseline, Week 8, 26 and 52/Premature Discontinuation Visit.
ae.
An x-ray of the wrist at Screening will not be required if the subject had an x-ray within 90 days of Screening, provided all protocol required documentation is available.  An 
x-ray of the wrist will not be required at a Premature Discontinuation visit.  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.

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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 drug concentration measurements and antibody measurements (discussed in 
Section 5.3.2), and the collection of adverse event (AE) information (discussed in 
Section 6.1.4).  All study data will be recorded in source documents and on the 
appropriate eCRFs.
Inclusion/Exclusion Criteria
Subjects will be evaluated to ensure they meet all inclusion criteria and none of the 
exclusion criteria at both the Screening and Baseline Visits.
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.
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.

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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.
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 
during the Screening Period.  The date of the most recent endoscopy requiring bowel 
preparation prior to Screening will be asked.  An updated medical history will be obtained 
at the Baseline Visit to ensure that the subject still qualifies.
Prior azathioprine, 6-MP or MTX use (since birth) will be asked.  If subjects have/had 
ever treated with azathioprine and/or 6-MP and/or MTX, the duration of therapy, 
maximum dose, reason for use and reason(s) for termination of treatment with 
azathioprine and/or 6-MP and/or MTX will be recorded in appropriated eCRF.
A detailed medical history with respect to TB exposure needs to be documented.  This 
information needs to include BCG vaccination, cohabitation with individuals who have 
had TB, and/or who reside or work in TB endemic locations.
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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TB Screening
A PPD skin test (alternatively, also known as tuberculin skin test) must be placed or a 
Interferon-Gamma Release Assay (IGRA; QuantiFERON-TB Gold In-Tube test or 
T-SPOT TB test) must be performed during the Screening Period for all subjects 
including those with a prior history of Bacille Calmette-Guérin (BCG) administration.
If a subject had a negative PPD test or IGRA test within 90 days prior to Screening, and 
all protocol required documentation is available, the test does not need to be repeated, 
provided nothing has changed in the subject's medical history to warrant a repeat test.  
These cases 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 (or according to manufacturer's guide) after placement 
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 induration must be recorded in mm not as positive or negative.  The absence 
of induration should be recorded, as "0 mm," not "negative."  (If required by 
specific countries a two-step test may be performed per local guidelines.  The 
result of the second test should be recorded.  An induration of 5 mm or greater 
will be considered as PPD positive.)
Subjects who have had an ulcerating reaction to PPD skin test in the past should 
not be re-exposed and should not be tested at Screening but will be considered 
PPD positive. 
If there are sites where the accepted testing materials are not available, an 
alternative tuberculin skin test may be substituted, but the method must be 
submitted and approved by AbbVie prior to use with study subjects.  

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In the assessment of the CXR a radiologist must note the presence or absence of 
(1) calcified granulomas, (2) pleural scarring/thickening, (3) signs of active TB.  The 
Principal Investigator will indicate the clinical significance of any findings and will sign 
and date the report.  If the CXR demonstrates changes suggestive of previous TB 
(e.g., calcified nodule, fibrotic scar, apical or basilar pleural thickening) or other findings 
that are clinically significant, the Principal Investigator must contact the AbbVie Medical 
Monitor before enrolling the subject.
If the PPD or the IGRA test is positive or the subject has a CXR indicative of latent TB, 
the subject will be required to initiate and have taken at least 2 weeks (or per local 
guidelines, whichever is longer) of an ongoing course of Centers for Disease Control and 
Prevention (CDC) recommended prophylaxis or prophylaxis per local guidelines prior to 
starting study therapy.  The Screening period may be extended as necessary for subjects 
who require initiation of prophylactic anti-TB therapy.  
Subjects with a prior history of latent TB that have a documented completion of the CDC 
recommended or local guideline recommended prophylaxis may be permitted to enroll.  If 
the subject has a prior history of latent TB but has not completed or received prophylaxis, 
prophylaxis must be initiated for at least 2 weeks (or per local guidelines, whichever is 
longer) before enrolling into the study and must be continued until completion as per 
CDC recommendation.
If the subject has a prior history of active TB they must have documentation of 
completion of CDC recommended or local guideline recommended treatment and 
documentation of resolution of the infection.
In the event both a PPD test and IGRA test are performed, the result of the IGRA test will 
supersede the result of the PPD test.  If the IGRA test is indeterminate, the site should 
repeat the test with another blood sample or perform a PPD test.  If the second IGRA test 
is also indeterminate, the subject is considered to be positive and should initiate TB 
prophylaxis.

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Newly initiated prophylactic treatment should be captured on the concomitant 
medications page in the eCRF and in the source documents.  Prior therapy should be 
captured in medical history.
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 Tuberculosis exposure.  This information needs to include BCG 
vaccination, cohabitation with individuals who have had TB, and/or who 
reside or work in TB endemic locations.  The information obtained by the 
pulmonologist must be documented in the subject's source note, dated and 
signed by the pulmonologist.
●
A pulmonologist must review the results of the PPD skin test or the IGRA test 
and the chest x-ray and has to give his/her opinion about the eligibility of each 
subject to be enrolled to the study.  This opinion must be documented in 
writing in the subject's source documents.
●
All subjects with a positive PPD or IGRA test need to be approved for entry 
into the trial by both the Czech pulmonologist and the AbbVie medical 
monitor and all such subjects need to receive prophylaxis for latent 
Tuberculosis.  Under no circumstances can a subject with a positive PPD or 
IGRA test result and no prior history of treatment for active or latent 
Tuberculosis be allowed into this trial.
Annual TB Testing
For subjects with a negative TB test at Screening, either an annual PPD or IGRA test will 
be required for any subject participating in the trial at Week 52 (Table 1).  If the annual 
TB screen is positive (PPD is positive or the IGRA test is positive), a CXR may be 
required for evaluation of active TB.  For any subject with a positive annual TB screen, 
the site should contact the AbbVie Medical Monitor for further discussion.  Subjects 
found to have latent TB, will be required to start a course of CDC recommended 
prophylaxis or prophylaxis per local guidelines as soon as possible.  Subjects found to 

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have active TB must discontinue study drug and receive CDC recommended or local 
guideline recommended treatment.  Any positive TB screen after the subject has started 
the study, should be reported as an AE.
An annual TB screen with PPD or IGRA testing will not be required for subjects who 
have been treated for latent or active TB or have had a positive TB test (PPD or IGRA) at 
any time (prior to the study, Screening, annual evaluation, or testing performed at any 
time point during the study).  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 52 (Table 1).  For any subject with clinical signs/symptoms of active 
TB or newly identified TB risk factors, a CXR may be required for evaluation of active 
TB, and it is recommended to contact the Medical Monitor for further guidance.  Subjects 
with a confirmed active TB should be discontinued from the study and receive standard of 
care.
Chest X-ray (CXR)
All subjects with a positive PPD test or positive Interferon-Gamma Release Assay (IGRA; 
QuantiFERON-TB Gold In-Tube test or T-SPOT TB test) will undergo a standard CXR 
(posterior-anterior [PA] and lateral views) at the Screening Visit to rule out the presence 
of TB or other clinically relevant findings.  In the event both a PPD test and IGRA test are 
performed, a CXR will only be required if the IGRA test is positive.  The CXR will not be 
required if the subject had a previous normal chest x-ray within 90 days of Screening, 
provided all protocol required documentation is available at the site.
Subjects can have a repeat CXR at any time during the study as warranted based on the 
opinion of the Investigator.
Electrocardiogram (ECG)
A resting 12-lead ECG will be performed at Screening in Table 1.  A qualified physician 
will interpret, sign, and date each ECG.

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The global interpretation using the following categories:
●
Normal ECG
●
Abnormal ECG – not clinically significant
●
Abnormal ECG – clinically significant
Any clinically significant findings will be documented in the source documents and later 
transcribed on to the appropriate eCRF.  Each signed original ECG will be monitored by 
the responsible CRA and kept with subject's source documents onsite.
For subjects with a normal ECG taken within 90 days of Screening, a repeat ECG at 
Screening will not be required, provided all protocol required documentation is available.  
If there are other findings that are clinically significant, the Principal Investigator must 
contact the Medical Monitor before enrolling the subject.
Subjects can have a repeat ECG at any time during the study as warranted based on the 
opinion of the Investigator.
Physical Examination
A full physical examination will be performed at Screening, Baseline, Week 26 and 
Week 52/Premature Discontinuation Visits.  Symptom-based physical examinations will 
be performed at all other visits.
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.
Hepatitis B Testing
All subjects will be tested for the presence of the Hepatitis B Virus (HBV) at Screening.  
A positive result for the Hepatitis B surface antigen (HBs Ag) will be exclusionary.  
Samples that are negative for HBs Ag will be tested for surface antibodies (HBs Ab) and 

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core antibodies (HBc Ab Total).  Subjects who are HBs Ag (–), HBs Ab (–), and HBc Ab 
Total (+) require PCR qualitative testing for HBV DNA.  Any HBV DNA PCR result that 
meets or exceeds detection sensitivity will be exclusionary. 
Subjects with a negative HBs Ag test and tests showing the results below do not require 
HBV DNA PCR qualitative testing. 
●
HBc Ab Total (–) and HBs Ab (–)
●
HBc Ab Total (–) and HBs Ab (+)
●
HBc Ab Total (+) and HBs Ab (+)
Pregnancy Tests
A serum pregnancy test will be performed at the Screening and Week 52/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.  
At the Baseline Visit and all 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.
Clinical Laboratory Tests
Blood samples will be obtained for the laboratory tests listed in Table 2 at the Screening, 
Baseline, Weeks 2, 4, 8, 12, 18, 26, 34, 42 and 52/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.
Lab assessments will only need to be repeated at Baseline if the time between Screening 
lab assessments and Baseline is greater than 28 days. 

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For subjects in re-screening lab assessments will not need to be repeated if the time 
between Screening and Re-screening is less than or equal to 28 days.  However, lab 
assessments will need to be repeated at Baseline if the time between lab assessments 
during previous Screening and Baseline is greater than 28 days.
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.
C. difficile
During the Screening Period, a stool sample will be collected and sent to the central 
laboratory for testing.  The sample will be assessed for the presence of C. difficile toxin.
The AbbVie Medical Monitor should be contacted to determine if subjects who had a 
positive C. difficile test at Screening and were treated appropriately, are eligible for 
re-screening.
The sample must be shipped to the central laboratory using dry ice.  Additional 
information is available in the Investigator Manual provided by the central laboratory.
ANA/anti dsDNA
Blood samples for antinuclear antibody (ANA) will be obtained at Screening.  
Anti-double-stranded DNA (anti dsDNA) assessments will be performed if ANA is 
positive.
In the event that subject develops Lupus-like symptoms, ANA and anti dsDNA samples 
will be obtained.

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hs-CRP
Blood samples for high-sensitivity C-Reactive Protein (hs-CRP) will be obtained at the 
Baseline, Weeks 2, 4, 8, 12, 18, 26, 34, 42 and 52/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 hs-CRP sample will be collected prior to dose change (blinded therapy, escape to 
receive open-label drug, dose escalation, dose de-escalation and dose re-escalation).
Urinalysis
Urine samples will be obtained and sent to the central lab for the tests listed in Table 2 at 
the Screening, Baseline, Weeks 2, 4, 8, 12, 18, 26, 34, 42 and 52/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.

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Table 2.
Clinical Laboratory Tests
Hematology
Clinical Chemistry
Urinalysisa
Hematocrit
Hemoglobin
Red Blood Cell (RBC) count
White Blood Cell (WBC)
count
Neutrophils
Bands
Lymphocytes
Monocytes
Basophils
Eosinophils
Platelet count (estimate not
acceptable)
Blood Urea Nitrogen (BUN)
Creatinine
Total bilirubin
Serum glutamic-pyruvic 
transaminase
(SGPT/ALT)
Serum glutamic-oxaloacetic
transaminase
(SGOT/AST)
Alkaline phosphatase
Sodium
Potassium
Calcium
Inorganic phosphorus
Uric acid
Cholesterol
Total protein
Glucose
Triglycerides
Albumin
Specific gravity
Ketones
pH
Protein
Blood
Glucose
Others
High-sensitivity C-reactive 
protein (hs-CRP)
Antinuclear antibody (ANA)
Anti-double-stranded DNA 
(anti-dsDNA) – if ANA positive
β-HCG
HBV
C. difficile toxin
Additional Blood Samples Collected
Pharmacokinetic 
Pharmacogenetic (optional)
Serologic biomarkers and cytokines (optional)
mRNA (optional)
a.
Microscopic urinalysis will be analyzed when dipstick results are abnormal.
Bone Age
An x-ray of the wrist for the assessment of bone age will be obtained at Screening and at 
Week 52/Premature Discontinuation visit to determine changes in bone maturation.  Sites 
should use the Greulich and Pyle method for reading the x-ray.20  The x-ray report 
requires the signature of the radiologist who read the films or of the investigator.  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 with the Premature Discontinuation visit at or 
before Week 26.  An x-ray of the wrist for the assessment of bone age at Screening will 

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not be required if the subject had an x-ray within 90 days of Screening, provided all 
protocol required documentation is available at the site.  
Anthropometric Evaluations
Height and weight obtained at Baseline, Week 26 and Week 52/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 6 months prior to Screening and maximal weight attained within 
preceding 6 months will be recorded.
Tanner Stage
Tanner Stage will be assessed at Screening (or at Baseline as appropriate), Week 26 and 
Week 52/Premature Discontinuation Visit if premature discontinuation occurs after 
Week 26.  Tanner Staging should be captured on the appropriate eCRF page.
Pediatric Ulcerative Colitis Activity Index (PUCAI)
A PUCAI score will also be calculated at all study visits beginning at Baseline.
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 

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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
The following definitions will be used:

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Table 3.
Definitions
Term
Definition
Mayo Score
Composite score of UC disease activity based on the subscores of stool 
frequency (0 – 3), rectal bleeding (0 – 3), physician's global assessment (0 – 3) 
and endoscopic subscore (0 – 3).  This score ranges from 0 – 12 points with 
higher scores representing more severe disease.
Partial Mayo Score
Composite score of UC disease activity based on the subscores of stool 
frequency, rectal bleeding, and physician's global assessment and DOES NOT 
include the endoscopic subscore.  This score ranges from 0 – 9 points.
9 point Mayo Score 
(without SFS)
Composite score of UC disease activity based on the subscores of rectal 
bleeding (0 – 3), physician's global assessment (0 – 3) and endoscopic subscore 
(0 – 3).  This score ranges from 0 – 9 points with higher scores representing 
more severe disease.
9 point Mayo Score 
(without PGA)
Composite score of UC disease activity based on the subscores of stool 
frequency (0 – 3), rectal bleeding (0 – 3), and endoscopic subscore (0 – 3).  
This score ranges from 0 – 9 points with higher scores representing more severe 
disease.
9 point Mayo Score 
(without RBS)
Composite score of UC disease activity based on the subscores of stool 
frequency (0 – 3), physician's global assessment (0 – 3) and endoscopic 
subscore (0 – 3).  This score ranges from 0 – 9 points with higher scores 
representing more severe disease.
6 point Mayo Score 
(without SFS and 
endoscopy subscore)
Composite score of UC disease activity based on the subscores of rectal 
bleeding (0 – 3) and physician's global assessment (0 – 3).  This score ranges 
from 0 – 6 points with higher scores representing more severe disease.
6 point Mayo Score 
(without PGA and 
endoscopy subscore)
Composite score of UC disease activity based on the subscores of stool 
frequency (0 – 3) and rectal bleeding (0 – 3).  This score ranges from 
0 – 6 points with higher scores representing more severe disease.
6 point Mayo Score 
(without RBS and 
endoscopy subscore)
Composite score of UC disease activity based on the subscores of stool 
frequency (0 – 3) and physician's global assessment (0 – 3).  This score ranges 
from 0 – 6 points with higher scores representing more severe disease.
All subjects will be provided with a Subject Diary at the Screening 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 
subscores of abdominal discomfort and functional assessment to determine the physician's 
global assessment subscore.

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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 0 and Week 52).  The 
endoscopy score used in the calculation of the Mayo Score at Week 0 (Baseline) will be 
from the Screening endoscopy.  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, Week 8 PMS will be rounded up or down to 
the nearest full number.  For example, if a patient had a PMS of 5.4 at Week 8 and came 
in for a disease flare assessment, then the Week 8 PMS would be rounded down to 5.0 for 
this purpose.  If a patient had a PMS of 5.5 at Week 8 and came in for a disease flare 
assessment, then the Week 8 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.
In addition, all endoscopies will undergo a central review process.
IMPACT III Questionnaire23
Subjects ≥ 9 years old at Baseline will complete an IMPACT III questionnaire at Baseline, 
Week 8, Week 26 and Week 52/Premature Discontinuation Visit.

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WPAI Questionnaire
Work Productivity and Activity Impairment Questionnaire (WPAI) will be completed at 
every visit except the Unscheduled Visit (Appendix F).
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.
Corticosteroid Therapy
At or after Week 4, subjects taking corticosteroid therapy at Baseline may have their 
corticosteroid therapy tapered based on the investigator's discretion.  Following is the 
proposed tapering schedule:
Daily Dose
Rate of Tapering Daily Dose
Prednisone (or equivalent)
> 10 mg
≤ 10 mg
5 mg/week
2.5 mg/week
Budesonide
≤ 9 mg
3 mg/week
From Week 4 to Week 12, if the subject should experience an increase in symptoms after 
corticosteroid was tapered, the subject may have their corticosteroid dose increased back 
up to the corticosteroid dose at Baseline.  This increase must be discussed with and 
approved by the Medical Monitor prior to any changes in these treatments.
At or after Week 12, if the subjects should experience disease flare, the subjects may have 
their corticosteroid dose initiated, reinitiated or increased above the corticosteroid dose at 
Baseline. These initiations, reinitiations or increases must be discussed with and 
approved by the Medical Monitor prior to any changes in these treatments.
Immunosuppressant Therapy
At and after Week 12, subjects who are on immunosuppressant (azathioprine, 6-MP or 
MTX) and have experienced a significant improvement in their clinical response are 
permitted to discontinue their dose according to the investigator's discretion.

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At or after Week 12, if the subject should experience a loss of clinical response the subject 
may have their immunosuppressant dose increased, initiated or reinitiated with 
immunosuppressants.  These increases, initiations or re-initiations must be discussed with 
and approved by the Medical Monitor prior to any changes in these treatments.
Subject Diary/Dosing Log
Subjects will be dispensed an electronic diary at Screening and will be trained on how to 
complete the diary by site staff during the Screening visit.  All subjects should complete 
their subject diary on a daily basis throughout the entire study.  The diary will be reviewed 
by site personnel with the subject at each visit and collected at the Week 52/Premature 
Discontinuation Visit.
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 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 of study drug to be administered 
each week until the next site visit.
Guidelines for Body Weight Adjusted Volumes of Study Drug for Administration of
Induction and Maintenance doses are listed under Appendix H:
●
Appendix H, Part 1 provides the guidelines for body weight adjusted volume 
for administration of Induction Dose at BL and Week 1.
●
Appendix H, Part 2 provides the guidelines for body weight adjusted volume 
for administration of Induction dose at Week 2. 
●
Appendix H, Part 3 provides the guidelines for body weight adjusted volume 
for administration of study drug at Weeks 4 and 6.  
●
Appendix H, Part 4 provides the guidelines for body weight adjusted volume 
for administration of study drug starting at Week 8 to Week 51. 

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Please note, the tables contained in Parts 2, 3, and 4 are also broken down by the weight 
of the subject, and will provide guidance for whether 1 or 2 vials shall be administered.
Guidelines for Body Weight Adjusted Volumes of Study Drug for Administration of Dose 
After Re-Randomization for Disease Flare and of OL Adalimumab are listed in 
Appendix I and Appendix J, respectively.
●
Appendix I provides the guidelines for body weight adjusted volume for 
administration of dose after re-randomization for disease flare (First disease 
flare).
●
Appendix J provides the guidelines for body weight adjusted volume for 
administration of OL drug (Second disease flare).
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 onsite by either site medical staff, the 
subjects or designee (friend, family member or healthcare professional) during all the 
visits from Baseline through Week 4.  Subject or a designated family member or friend 
will be given instructions on subcutaneous injection administration during these 
first four site visits.
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 

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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 
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 who 
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 IVRS/IWRS.  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 of study drug to be administered. 
Subjects will be instructed to return all used and unused syringes, Sharps containers and 
empty boxes at each visit for accountability.
Endoscopy
An endoscopy will be performed on the following occasions:
●
During Screening
●
Week 52/Premature Discontinuation

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A colonoscopy will be performed during the Screening period unless the subject 
underwent a colonoscopy within 12 months prior to Screening and appropriate endoscopy 
documentation is available (to confirm the diagnosis and extent of disease and no 
evidence of dysplasia, colon cancer or infection as per review by the investigator).  In this 
case the screening endoscopy may be either colonoscopy or a flexible sigmoidoscopy.
If the subject underwent an endoscopy within 56 days of Baseline and a video recording 
of endoscopy is available, the video recording may be used and no additional endoscopy 
will be performed during the Screening period provided that the conditions noted in 
Section 5.3.1.1 are met, and all technical requirements are fulfilled.
Note:
●
If no appropriate documentation for confirmation of the diagnosis is available 
as per the investigator's judgment a diagnostic biopsy must also be performed.  
●
Biopsies to rule out dysplasia, colon cancer and infection may be taken at the 
investigator's discretion.
The endoscopy during the Screening period (or video recording of endoscopy within 
56 days of Baseline) will be used to provide the endoscopy subscore for calculating the 
Mayo Score at Baseline.  If, in the assessment of the endoscopist, the Screening 
endoscopy does not indicate an endoscopy subscore of 2 or 3 per eligibility requirements, 
the subject should be screen-failed and the video should not be sent for central review.  
Additionally, if the investigator determines that the subject is not eligible because an 
inclusion criterion is not fulfilled or an exclusion criterion is met for any other reason the 
video should not be sent for central review.
At Week 52/Premature Discontinuation Visit, subjects will undergo either colonoscopy or 
flexible sigmoidoscopy for evaluation of mucosal healing.  The evaluation will be done by 
usage of the endoscopy subscore scale of the Mayo Score.  Endoscopies will include an 
assessment of friability.

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If subjects prematurely discontinue from the study before or at Week 26, the endoscopy at 
the Premature Discontinuation Visit will not be required.
All endoscopies will be recorded and will be reviewed by a central reviewer who is 
blinded to the therapy.  The central reviewer will assess the endoscopy subscore.  The 
endoscopy subscore result from the central reviewer will be used to evaluate the eligibility 
of a subject for the study, as well as to evaluate mucosal healing at Week 52.  
Discrepancies between the central reviewer and the site endoscopist regarding a subject's 
score and eligibility will be finally judged through adjudication by a second central 
reviewer.  The adjudicator will not provide an assessment but will select the assessment 
with whom he/she agrees.  The adjudicator's assessment will be considered final.
The endoscopy subscore will be reviewed by the endoscopist at the site for each 
endoscopy and the site endoscopist will document the endoscopy subscore and friability 
status in subject's source.  The site's endoscopy subscore will be noted in the database but 
the central reviewer's endoscopy subscore will be used for the efficacy analyses.
The same endoscopist should perform all endoscopies for an individual subject 
throughout the study.  In addition, where possible, the investigator or subinvestigator 
should be the endoscopist for the study.
For re-screening, an endoscopy will not be required to be repeated provided that the prior 
endoscopy confirmed subject's eligibility, the conditions noted above are met and the date 
of the prior endoscopy is within 56 days from Baseline.
Biopsy During Endoscopy
During the Screening Period and at the Week 52/Premature Discontinuation Visit, biopsy 
samples may be taken at the investigator's discretion and evaluated by a qualified local 
pathologist and the results reviewed by the investigator to confirm the diagnosis and no 
evidence of dysplasia/malignancy or infection.  If no appropriate documentation for 
confirmation of the diagnosis is available from previous biopsy reports as per the 
investigator's judgment a diagnostic biopsy must be performed.  The signed pathology 

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report will be monitored by the responsible CRA and kept with the subject's source 
documents onsite.  Subjects would not be enrolled if colon dysplasia or colon cancer is 
discovered at Screening endoscopy.  If a diagnosis of colon dysplasia or colon cancer or 
an infection is discovered during any subsequent endoscopic evaluation during the course 
of the study, the findings should be recorded as an adverse event and the subject should be 
discontinued from the study.
5.3.1.2
Blood Samples for Pharmacogenetic Analysis (Optional)
One 2 mL whole blood sample for DNA isolation will be collected at the Baseline Visit 
from each subject who consents for pharmacogenetic analysis.  If the sample is not drawn 
at the Baseline visit, it may be drawn at any other visit during the study.  The procedure 
for obtaining and documenting informed consent is discussed in Section 9.3.  Specific 
instructions for preparation and storage of DNA samples will be provided by the central 
laboratory, the Sponsor, or its designee.
A PG sample will not be required to be repeated for re-screening provided that a PG 
sample has already been collected during previous Screening and is still available for 
analysis.
AbbVie will store the DNA samples in a secure storage space with adequate measures to 
protect confidentiality.  The samples will be retained for no longer than 20 years after 
completion of the study (where allowed by local regulations) for possible future research.
The site or the subject will not receive the results of the genetic analysis.
5.3.1.3
Blood Samples for Serologic Markers and Cytokine Analysis 
(Optional)
One 4 mL of blood sample for serologic markers and cytokines analysis will be collected 
at the time points indicated in Table 1, from each subject who consents for serologic 
analysis.  The procedure for obtaining and documenting informed consent is discussed in 
Section 9.3.  Specific instructions for preparation and storage of samples for serologic 

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markers and cytokines will be provided by the central laboratory, the Sponsor, or its 
designee.
Sample will be stored in a secure storage space with adequate measures to protect 
confidentiality.  The samples will be retained for up to 20 years (where allowed by local 
regulations) after completion of the study research.
The site or the subject will not receive the results of the serologic markers and cytokine 
analysis.
5.3.1.4
Blood Samples for mRNA Analysis (Optional)
One 2.5 mL of blood sample for mRNA analysis will be collected at the time points 
indicated in Table 1, from each subject who consents for optional analyses.  The 
procedure for obtaining and documenting informed consent is discussed in Section 9.3.  
Please refer to the laboratory manual for instructions.
The samples will be stored in a secure storage space with adequate measures to protect 
confidentiality.  The samples will be retained for up to 20 years (where allowed by local 
regulations) after completion of the study research.
The site or the subject will not receive the results of mRNA analysis.
5.3.2
Drug Concentration Measurements
5.3.2.1
Collection of Samples for Analysis
Blood samples for adalimumab, AAA, infliximab, and HACA assays will be obtained at 
the time points as indicated in Table 1.
The time that each blood sample is collected will be recorded to the nearest minute in the 
source document and on the appropriate eCRF.
The samples will be retained for no longer than 20 years after completion of the study 
(where allowed by local guidelines).

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Collection of Samples for Adalimumab and AAA Assays
Blood samples for adalimumab and AAA assays will be collected into appropriately 
labeled serum collection tubes (one tube for adalimumab and one tube for AAA) without 
gel separator.  For adalimumab assay, all samples will be obtained immediately prior to 
dosing at Weeks 0 (Baseline), 2, 4, 8, 12, 26, 34 and 52/Premature Discontinuation Visits 
and at Unscheduled Visits requiring dose change.  For AAA assay, all samples will be 
obtained immediately prior to dosing at Weeks 0 (Baseline), 4, 8, 26 and 52/Premature 
Discontinuation Visits.  Sufficient blood will be collected to provide approximately 1 mL 
serum for adalimumab assay and 1 mL serum for AAA assay.
Beginning at Week 12, for subjects who meet the criteria for disease flare, blood samples 
for the measurement of serum adalimumab and AAA concentrations will be collected just 
prior to receiving study drug at the visit requiring dose change (blinded therapy, 
open-label and dose-escalation).
If a subject undergoes dose de-escalation (from ew to eow dosing), blood samples will be 
collected for the determination of serum adalimumab and AAA concentrations, just prior 
to dose de-escalation.  If these same subjects dose re-escalate (from eow to ew dosing) 
following disease flare, blood samples will be collected for the determination of serum 
adalimumab and AAA concentrations just prior to the dose re-escalation.
A minimum of 13 samples are planned to be collected per subject for adalimumab 
(8 samples) and AAA (5 samples) assays.  The number of samples planned is 
744 (8 samples × 93 subjects) for the adalimumab assay and 
465 (5 samples × 93 subjects) for the AAA assay for the entire study.
For subjects who have a disease flare following Week 12 and require dose change 
(blinded therapy, escape to open-label drug, and further require dose escalation), up to 
6 additional samples are planned to be collected per subject for adalimumab (3-samples) 
and AAA (3-samples) assays.

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For subjects who enter the dose de-escalation and dose re-escalation phase, up to 
4 additional samples are planned to be collected per subject for adalimumab (2-samples) 
and AAA (2-samples) assays.
In total, the maximum number of samples that a subject could have collected over the 
duration of the study would be 23 blood samples:  13 samples for the determination of 
adalimumab concentrations, and 10 samples for the determination of AAA concentrations.
Collection of Samples for Infliximab and HACA Assays
Blood samples for infliximab and HACA assay will be collected at Week 0 (Baseline) 
into appropriately labeled serum collection tubes (one tube for infliximab and one tube for 
HACA) without gel separator at Baseline.  The sample will be obtained immediately prior 
to dosing.  Sufficient blood will be collected to provide approximately 1 mL serum for 
infliximab assay and 1 mL serum for HACA assay.
The total number of samples planned will not exceed 186 (2 samples × 93 subjects) for 
the entire study.
5.3.2.2
Handling/Processing of Samples
The blood samples for adalimumab, AAA, infliximab and HACA assays will be 
centrifuged to separate the serum.  Each serum sample will be transferred into 
appropriately labeled vials.  Serum samples will be frozen within 2 hours after collection 
and will remain frozen at –20°C or colder until shipped.  Sites that do not have access to a 
–20°C or colder freezer will need to ship the samples the day they are collected.
Detailed instructions for the handling and processing of samples will be provided from the 
central laboratory.
5.3.2.3
Disposition of Samples
Study sites will identify a supplier and purchase the necessary dry ice.  The frozen serum 
samples will be packed in dry ice (pellet form) sufficient to last during transport.  Samples 

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will be shipped pursuant to instructions from the AbbVie Monitor.  An inventory of the 
samples included will accompany the package.  Arrangements will be made with the 
central laboratory for the transfer of samples.
5.3.2.4
Measurement Methods
Serum concentrations of adalimumab will be determined using a validated ligand binding 
assay (LBA) method under the supervision of the Drug Analysis Department at AbbVie.
Serum concentrations of AAA will be determined using a validated LBA method under 
the supervision of the Drug Analysis Department at AbbVie.
Serum concentrations of infliximab and HACA will be determined using validated assay 
methods under the supervision of the Drug Analysis Department at AbbVie.

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5.3.3
Efficacy Variables
The following definitions are used to describe the primary and secondary variables:
Term
Definition
Clinical response per Partial Mayo Score
defined as a decrease in PMS ≥ 2 points and ≥ 30% from 
Baseline
Clinical remission per Partial Mayo Score
defined as a PMS ≤ 2 and no individual subscore > 1
Mucosal healing
Endoscopy subscore of 0 or 1
PUCAI remission
defined as < 10
PUCAI response
defined as a decrease in PUCAI ≥ 20 points from 
Baseline
Clinical remission per Mayo Score
defined as a Mayo Score ≤ 2 and no individual subscore 
> 1
Clinical response per Mayo Score
defined as a decrease in Mayo Score ≥ 3 points and 
≥30% from Baseline
Clinical remission per 9 point Mayo Score 
(without SFS)
defined as a 9 point Mayo Score (without SFS) ≤ 2 and 
no individual subscore > 1
Clinical remission per 6 point Mayo Score 
(without SFS and endoscopy subscore)
defined as a 6 point Mayo Score (without SFS and 
endoscopy subscore) ≤ 1 
Clinical remission per 9 point Mayo Score 
(without PGA)
defined as a 9 point Mayo Score (without PGA) ≤ 2 and 
no individual subscore > 1
Clinical remission per 6 point Mayo Score 
(without PGA and endoscopy subscore)
defined as a 6 point Mayo Score (without PGA and 
endoscopy subscore) ≤ 1
Clinical remission per 9 point Mayo Score 
(without RBS)
defined as a 9 point Mayo Score ≤ 2 (without RBS) and 
no individual subscore > 1
Clinical remission per 6 point Mayo Score 
(without RBS and endoscopy subscore)
defined as a 6 point Mayo Score (without RBS and 
endoscopy subscore) ≤ 1 
Please refer to Section 8.1.4 for details on the sequentially rejective multiple test 
procedure of the dose groups used in this study versus external placebo for co-primary 
and ranked secondary endpoints.

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5.3.3.1
Primary Variables
The co-primary efficacy endpoints are:
1.
The proportion of subjects who achieve clinical remission at Week 8 as measured 
by PMS (defined as a PMS ≤ 2 and no individual subscore > 1);
2.
The proportion of subjects who responded at Week 8 per PMS and achieve clinical 
remission at Week 52 as measured by Mayo score (defined as a Mayo Score ≤ 2 
and no individual subscore > 1).
5.3.3.2
Secondary Variables
Ranked secondary efficacy variables are:
1.
Proportion of subjects in Mayo clinical response at Week 52 in Week 8 responders 
per PMS;
2.
Proportion of subjects who achieve mucosal healing at Week 52 as measured by 
Mayo endoscopy subscore (defined as ≤ 1) in Week 8 responders per PMS;
3.
Proportion of subjects who achieve Mayo clinical remission at Week 52 in Week 8 
remitters per PMS;
4.
Proportion of subjects receiving corticosteroid at Baseline who have discontinued 
corticosteroid prior to Week 52 and are in Mayo clinical remission at Week 52 in 
Week 8 responders per PMS.
Additional exploratory secondary analyses will be performed for:
●
Proportion of subjects in PMS clinical remission at Week 52 in Week 8 
responders per PMS;
●
Proportion of subjects in PUCAI remission (defined as < 10) at Week 8;
●
Proportion of subjects in PUCAI response (defined as a decrease in PUCAI 
≥20 points from Baseline) at Week 8;

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●
Proportion of subjects in PUCAI remission (defined as < 10) at Week 52 in 
Week 8 responders per PMS;
●
Proportion of subjects in PUCAI response (defined as a decrease in PUCAI 
≥20 points from Baseline) at Week 52 in Week 8 responders per PMS;
●
Proportion of subjects receiving corticosteroid at Baseline who discontinue 
corticosteroid prior to Week 52 and are in PUCAI remission at Week 52 in 
Week 8 responders per PMS;
●
Change from Baseline in total IMPACT III Quality of Life scores over time 
for subjects at least 9 years old at Baseline;
●
Change from Baseline in WPAI scores over time;
●
Change from Baseline in "z" scores for height (observed height velocity 
[cm/yr] – mean height velocity for age and sex [cm/yr]/SD of the mean) at 
Week 26 and Week 52;
●
Change from Baseline in BMI at Week 26 and Week 52;
●
Change from Baseline in "z" scores for weight-for-age at Week 26 and 
Week 52;
●
Proportion of subjects at appropriate Tanner stage at Week 26 and Week 52 
compared to Baseline;
●
Proportion of subjects in PMS response over time;
●
Proportion of subjects in PMS remission over time;
●
Proportion of subjects in PUCAI response over time;
●
Proportion of subjects in PUCAI remission over time;
●
Change from Baseline in number of daily stool over time;
●
Change from Baseline in albumin and total protein at different time points;
●
Change from Baseline in hemoglobin, hematocrit, red blood cell count at 
different time points;
●
Change from Baseline in hs-CRP levels at different time points;
●
Proportion of subjects with EIM at Week 26 and Week 52 compared to 
Baseline;
●
Proportion of subjects with Mayo endoscopy subscore of 0 or 1 (without 
friability) at Week 52;

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●
Proportion of subjects being hospitalized during the study;
●
Proportion of subjects undergoing colectomy during the study;
●
Proportion of subjects receiving corticosteroid at Baseline who have 
discontinued corticosteroid prior to Week 52 and completed Week 52;
●
Correlation between PMS and PUCAI at different time points;
●
Proportion of subjects in a 9 point Mayo (without SFS) clinical remission 
(defined as ≤ 2 and no individual subscore > 1) at Week 52 in Week 8 
responders per PMS;
●
Proportion of subjects in a 9 point Mayo (without PGA) clinical remission 
(defined as ≤ 2 and no individual subscore > 1) at Week 52 in Week 8 
responders per PMS;
●
Proportion of subjects in a 9 point Mayo (without RBS) clinical remission 
(defined as ≤ 2 and no individual subscore > 1) at Week 52 in Week 8 
responders per PMS;
●
Proportion of subjects in a 6 point Mayo (without SFS and endoscopy 
subscore) clinical remission (defined as ≤ 1) at Week 8;
●
Proportion of subjects in a 6 point Mayo (without PGA and endoscopy 
subscore) clinical remission (defined as ≤ 1) at Week 8;
●
Proportion of subjects in a 6 point Mayo (without RBS and endoscopy 
subscore) clinical remission (defined as ≤ 1) at Week 8;
●
Change from Baseline in Mayo score at Week 52;
●
Change from Baseline in PMS over time;
●
Change from Baseline in PUCAI over time;
●
Change from Baseline in endoscopy subscore at Week 52;
●
Change from Baseline in SFS over time;
●
Change from Baseline in RBS over time;
●
Change from Baseline in PGA over time.

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5.3.4
Safety Variables
Vital signs, laboratory profiles, physical examinations, and adverse events will be 
assessed throughout the study.
5.3.5
Pharmacokinetic Variables
Pharmacokinetic
Adalimumab trough serum concentrations will be summarized by dose at each time point 
using descriptive statistics.  In addition, pharmacokinetic model based analyses will be 
performed with the focus on apparent clearance (CL/F) and apparent volume of 
distribution (V/F) of adalimumab.
Immunogenicity
AAA will be evaluated for each subject and each dose, and rates of AAA positive will be 
calculated.  As appropriate, the effect of AAA on adalimumab pharmacokinetics, efficacy 
variable(s), and treatment-emergent adverse events may be evaluated.  HACA will be 
evaluated for each subject and each dose, and rates of HACA positive will be calculated.
5.3.6
Pharmacogenetic, mRNA and Serologic Variables
5.3.6.1
Pharmacogenetic Variable
Samples may be sequenced and data analyzed for genetic factors contributing to the 
disease or to the subject's response to adalimumab, in terms of pharmacokinetics, efficacy, 
tolerability and safety.  Such genetic factors may include genes for drug metabolizing 
enzymes, drug transport proteins, genes within the target pathway, or other genes that may 
be related to the disease or to drug response.  Some genes that are currently 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 
pharmacogenetic analyses may not be reported with the study summary.

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5.3.6.2
Cytokines, Serologic Markers and mRNA Variables
Samples may be analyzed for serologic antibodies, cytokines and mRNA profiles that may 
help predict disease behavior and help determine disease phenotypes or response to or 
tolerability of treatment.  Some antibodies, immune markers or transcripts 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.
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 7.0).
●
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.

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●
Subject has known dysplasia of the gastrointestinal tract or a malignancy, 
except for localized non-melanoma skin cancer.  Discontinuation for 
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.
●
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.
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 approximately 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 who 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 

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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.
5.5
Treatments
5.5.1
Treatments Administered
Prior to Amendment 4, at Baseline, subjects were randomized 3:2 to one of 
two double-blind adalimumab induction doses (high:standard).
During the randomized double-blind induction period, subjects assigned to high dose 
group received adalimumab 2.4 mg/kg (maximum dose of 160 mg) at Baseline and at 
Week 1.  At Week 2, subjects received adalimumab 1.2 mg/kg (maximum dose of 80 mg), 
followed by a dose of 0.6 mg/kg (maximum dose of 40 mg) at Weeks 4 and 6.  Subjects 
randomized to standard dose group received adalimumab 2.4 mg/kg (maximum dose of 
160 mg) at Baseline and matching placebo at Week 1, subjects received adalimumab 
1.2 mg/kg (maximum dose of 80 mg) at Week 2, followed by a dose of 0.6 mg/kg 
(maximum dose of 40 mg) at Weeks 4 and 6.
Ongoing subjects randomized prior to Amendment 4 will continue their blinded treatment 
during the induction period until Week 8.
At Week 8, subjects demonstrating a clinical response per Partial Mayo Score were 
randomized 2:2:1 to one of two adalimumab maintenance treatment groups (standard dose 
[0.6 mg/kg (maximum dose of 40 mg) every other week and matching placebo at the 
alternate week] or high dose [0.6 mg/kg (maximum dose of 40 mg) every week]) or to 
placebo, respectively.

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Ongoing subjects randomized prior to Amendment 4 will continue their blinded treatment 
during the maintenance period until Week 52 and re-randomization to treatment for 
disease flare will be done according to Amendment 3 stipulations in these subjects.
After Amendment 4, subjects will receive the open-label adalimumab high induction dose.  
At Week 8, subjects demonstrating a clinical response per Partial Mayo Score will be 
randomized 1:1 to one of two adalimumab maintenance treatment groups (standard dose 
[0.6 mg/kg (maximum dose of 40 mg) every other week and matching placebo at the 
alternate week] or high dose [0.6 mg/kg (maximum dose of 40 mg) every week]).
Subjects will receive blinded treatment every week (ew) beginning at Week 8 and will 
remain on double-blinded therapy through Week 52.
Treatment of Subjects with Disease Flare During the Study
At or after Week 12:
●
Subjects who are randomized to standard maintenance dose (0.6 mg/kg 
[maximum of 40 mg] eow) will be re-randomized to receive either 
adalimumab re-induction dose (2.4 mg/kg [maximum of 160 mg]) or 
adalimumab (0.6 mg/kg [maximum of 40 mg]) at the visit.  Afterwards, all 
subjects will resume receiving the standard dose (0.6 mg/kg [maximum of 
40 mg] eow) within the original dosing schedule.
●
Subjects who are randomized to high maintenance dose (0.6 mg/kg [maximum 
of 40 mg] ew) will be re-randomized to receive either adalimumab 
re-induction dose (2.4 mg/kg [maximum of 160 mg]) or adalimumab 
(0.6 mg/kg [maximum of 40 mg]) at the visit.  The following week, all 
subjects will resume the high dose (0.6 mg/kg [maximum of 40 mg] ew).
●
Subjects who were randomized to placebo prior to Amendment 4 will be re-
randomized to receive either adalimumab re-induction dose (2.4 mg/kg 
[maximum of 160 mg] or to receive adalimumab (0.6 mg/kg [maximum of 
40 mg]) at the visit.  Afterwards, all subjects will receive the standard dose 
(0.6 mg/kg [maximum of 40 mg] eow) within the original dosing schedule.

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If a subject continues to meet the definition of disease flare (2nd time) following at least a 
4-week course of blinded therapy since the subject was re-randomized for disease flare, 
they may be switched to open-label adalimumab every week at the dose 0.6 mg/kg 
[maximum of 40 mg].
Note:  If a subject was re-randomized at Week 12 (to receive either re-induction dose 
[2.4 mg/kg {maximum of 160 mg}] or to receive adalimumab [0.6 mg/kg {maximum of 
40 mg}]), then the earliest that subject could be evaluated to determine if they meet the 
criteria for disease flare for switch to OL weekly dosing is at Week 16.
If a subject continues to meet the definition of disease flare (3rd time) following a 4-week 
course of open-label adalimumab every week at the dose 0.6 mg/kg [maximum of 40 mg], 
they may be switched to receive adalimumab open-label 40 mg ew (maximum dose, not 
weight based).
Subjects with persistent disease flare while on adalimumab 40 mg ew (max dose) may be 
withdrawn from the study at the investigator's discretion.
During open-label rescue therapy, subjects who are responders and have been in remission 
for at least 8 consecutive weeks (PMS ≤ 2 with no individual subscore > 1) may have 
their dosage decreased from ew to eow.  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.  The investigator 
should receive prior approval from the Medical Monitor before taking any action with 
regard to dose re-escalation.
5.5.2
Identity of Investigational Products
The individual study drug information is presented in Table 4.

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Table 4.
Identity of Investigational Products
Study Drug
Formulation
Manufacturer
Adalimumab
40 mg/0.8 mL
Adalimumab/Mannitol, Citric acid monohydrate, Sodium citrate, 
Disodium phosphate dihydrate, Sodium dihydrogen phosphate 
dihydrate, Sodium chloride, Polysorbate 80, Water for injections, 
Sodium hydroxide added as necessary to adjust pH
AbbVie
Placebo
0.8 mL
0.8 mL solution for injection Mannitol, Citric acid monohydrate, 
Sodium citrate, Disodium phosphate dihydrate, Sodium dihydrogen 
phosphate dihydrate, Sodium chloride, Polysorbate 80, Water for 
injections, Sodium Hydroxide added as necessary to adjust pH
AbbVie
5.5.2.1
Packaging and Labeling
All Treatment Types
Investigational product will be packaged separately in 0.8 mL vial containing either 
adalimumab 40 mg/0.8 mL or matching placebo for adalimumab.  Each dosing kit carton 
will have a unique kit ID and contains two labeled vials.  Each vial 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 instructions and training for the administration of study supplies are provided in 
Appendix L.
5.5.2.2
Storage and Disposition of Study Drugs
Adalimumab/placebo vials 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 

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AbbVie Temperature Excursion Management System (ATEMS) deems the medication as 
acceptable.
All clinical supplies must be stored and locked in a secure place until they are dispensed 
for subject use or are returned to AbbVie 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
All subjects will be assigned a unique identification number by the Interactive Voice 
Response System (IVRS)/Interactive Web Response System (IWRS) as they are screened 
for the study.  Subjects who meet the selection criteria in Section 5.2.1 and Section 5.2.2
will proceed to enter the study.  The randomization at Week 8 for subjects who 
demonstrated a clinical response per PMS will be stratified by Week 8 remission status by 
PMS.  This treatment group assignment will be maintained by the IVRS and not provided 
to the site, as the subject will be referred to by the subject number assigned at screening.  
The sites will be provided with appropriate kit number(s) for drug-dispensing purpose for 
each subject by the IVRS.  Before the study is initiated, the telephone number and call-in 
directions for the IVRS 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.

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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.
5.5.5
Blinding
5.5.5.1
Blinding of Investigational Product
All AbbVie personnel with direct oversight of the conduct and management of the trial 
(with the exception of AbbVie Drug Supply Management Team) the Investigator, study 
site personnel and the subject will remain blinded to each subject's treatment throughout 
the blinded period of the study.  The IVRS/IWRS will provide access to blinded subject 
treatment information in the case of medical emergency.
In the event of a medical emergency in which the Investigator believes that knowledge of 
study drug treatment is required, every effort must be made to contact the AbbVie 
Medical Monitor (see Section 7.0 prior to breaking the blind).  The date and reason that 
the blind was broken must be conveyed to AbbVie and recorded on the appropriate eCRF.
5.5.5.2
Blinding of Data for Independent Data Monitoring 
Committee (IDMC)
AbbVie will establish a DMC to review the safety and key efficacy data generated during 
the study and to provide recommendations to AbbVie about continuing or modifying the 
study.  The DMC will review unblinded safety data and efficacy during the study.  The 
DMC charter will establish the frequency of meetings and suggest relevant data for 
review.  Full details of DMC responsibilities and members and credentials will be 
included in the DMC Charter for Study M11-290.

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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 (ePRO device) 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, 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 information should be documented on the source documents as per "best recollection" 
and when possible, re-verified when the subject diary/dosing log (ePRO device) 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, 
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.

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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 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 and Sharps containers should be returned by the subject at each 
visit for accountability and compliance purposes and new containers issued as necessary.  
Empty boxes, used and unused vials 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, 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 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.
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 failed 
conventional treatment.  Prior to Amendment 4, at Baseline, subjects were stratified and 
randomized via the IVRS according to their Baseline disease severity, corticosteroid use 
at Baseline, and their prior exposure to anti-TNF to receive either one of the two induction 

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dose of adalimumab.  For subjects who met the criteria for response per PMS at Week 8, 
the randomization was stratified by Week 8 remission status per PMS and Induction dose.  
After Amendment 4, subjects will receive open-label adalimumab high induction dose.  
At Week 8, subjects demonstrating a clinical response per PMS will be randomized 1:1 to 
one of two adalimumab maintenance treatment groups stratified by Week 8 remission 
status per PMS.
Since use of steroids and immunosuppressants are associated with significant adverse 
effects, subjects taking corticosteroid therapy at Baseline may have their corticosteroid 
therapy tapered based on the investigator's discretion starting at Week 4 and may have 
their immunosuppressants discontinued starting at Week 12.
Prior to Amendment 4, internal placebo was chosen as the control group during 
maintenance period per regulatory requirement.  After Amendment 4, per agreement with 
the regulatory agencies, randomization to the internal placebo group will be ceased, and 
external placebo will be used as comparator for efficacy endpoints instead.
Standard statistical, clinical, and laboratory procedures will be utilized in this study.  The 
clinical efficacy measurements in this study (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 meet all inclusion criteria 
and none of the exclusion criteria are eligible for this study.  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.

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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.
The goal of the simulations was to select a standard dosing regimen that is predicted to 
achieve similar exposures in pediatric UC subjects compared to those exposures observed 
in adult UC subjects treated with a 160 mg dose at Week 0, 80 mg at Week 2, and 40 mg 
at Weeks 4 and 6.  The high dose regimen was then selected to achieve and evaluate a 
higher exposure.  Prior to Amendment 4, the proposed standard dosing regimen was an 
induction dosing regimen of 2.4 mg/kg (maximum dose of 160 mg) at Week 0 and 
1.2 mg/kg (maximum dose of 80 mg) at Week 2, followed by a maintenance dose of 
0.6 mg/kg (maximum dose of 40 mg) eow starting at Week 4.  The proposed high dosing 
regimen was an induction regimen of 2.4 mg/kg (maximum dose of 160 mg) at Weeks 0 
and 1, 1.2 mg/kg (maximum dose of 80 mg) at Week 2, and 0.6 mg/kg (maximum dose of 
40 mg) at Week 4.
At Week 8, subjects demonstrating a clinical response per Partial Mayo Score were 
randomized 2:2:1 to one of two adalimumab maintenance treatment groups (standard dose 
[0.6 mg/kg (maximum dose of 40 mg) every other week and matching placebo at the 
alternate week] or high dose [0.6 mg/kg (maximum dose of 40 mg) every week]) or to 
placebo, respectively.

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After Amendment 4, subjects will receive open-label adalimumab high induction dose.  
At Week 8, subjects demonstrating a clinical response per PMS will be randomized 1:1 to 
the two above mentioned adalimumab maintenance treatment groups.
6.0
Complaints
A Complaint is any written, electronic, or oral communication that alleges deficiencies 
related to the physical characteristics, identity, quality, purity, potency, durability, 
reliability, safety, effectiveness, or performance of a product/device after it is released for 
distribution.
The investigational product in this trial contains: 
●
Biologic compound(s)
Complaints associated with any component of this investigational product must be 
reported to the Sponsor (Section 6.2.2).  For medical complaints, please refer to 
Section 6.1.  For product complaints, please refer to Section 6.2.
6.1
Medical Complaints
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 
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.

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6.1.1
Definitions
6.1.1.1
Adverse Event
An adverse event (AE) is defined as any untoward medical occurrence in a subject 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 (refer to Section 6.1.7 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 
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.
6.1.1.2
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.

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Death of Subject
An event that results in the death of a subject.
Life-Threatening
An event that, in the opinion of the investigator, 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).
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.

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6.1.2
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.
6.1.3
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:
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.

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6.1.4
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 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.
Adverse event information will be collected as shown in Figure 5.
Figure 5.
Adverse Event Collection
SAEs
SAEs and Nonserious AEs
Elicited and/or Spontaneously Reported
∀
∀
∀
∀
Consent 
Signed
Study 
Drug 
Start
Study 
Drug 
Stopped
70 Days After 
Study Drug 
Stopped
6.1.5
Adverse Event Reporting
In the event of a serious adverse event, and additionally, any nonserious event of 
malignancy in subjects 30 years of age and younger, whether related to study drug or not, 
the physician will notify the AbbVie Clinical Pharmacovigilance within 24 hours of the 
physician becoming aware of the event by entering the serious adverse event or 

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nonserious event of malignancy in subjects 30 years of age and younger data into the 
electronic data capture (EDC) system.  Serious adverse events and nonserious events of 
malignancy in subjects 30 years of age and younger, that occur prior to the site having 
access to the Rave system should be documented on the SAE Non-CRF forms and sent to 
Clinical Pharmacovigilance within 24 hours of being made aware of the adverse event by 
fax or email.
FAX to:  
For safety concerns, contact the Immunology Safety Team at:
Immunology Safety Team
AbbVie
1 North Waukegan Road
North Chicago, IL  60064
Telephone Contact Information:
Safety Hotline:
Email:

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Information regarding a pregnancy occurrence in a study subject and the outcome of the 
pregnancy will be collected.
Pregnancy in a study subject is not considered an AE.  However, the medical outcome of 
an elective or spontaneous abortion, stillbirth or congenital anomaly is considered a SAE 
and must be reported to AbbVie within 24 hours of the site becoming aware of the event.
6.1.7
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 6.0 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.
6.2
Product Complaint 
6.2.1
Definition
A Product Complaint is any Complaint (see Section 6.0 for the definition) related to the 
biologic or drug component of the product or to the medical device component(s).
For a product this may include, but is not limited to, damaged/broken product or 
packaging, product appearance whose color/markings do not match the labeling, labeling 

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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 by the device to the 
events outlined directly above should be captured.
6.2.2
Reporting
Product Complaints concerning the investigational product and/or device must be reported 
to the Sponsor within 24 hours of the study site's knowledge of the event via the Product 
Complaint form.  Product Complaints occurring during the study will be followed-up to a 
satisfactory conclusion.  All follow-up information is to be reported to the Sponsor (or an 
authorized representative) and documented in source as required by the Sponsor.  Product 
Complaints associated with adverse events will be reported in the study summary.  All 
other complaints will be monitored on an ongoing basis.
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.
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), and the following AbbVie 
Representative:

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8.1.1
Analyzable Population
The following populations will be used for analyses in this study:
Intent-To-Treat (ITT):  The ITT population includes all subjects who received at least 
one dose of the study medication during induction period.  ITT subjects will be analyzed 
as randomized/enrolled.  
ITT-E:  The ITT-E population will be a subpopulation of the ITT population, where 
subjects who have received open-label high induction dose will be excluded.  ITT-E is the 
primary population for the induction period efficacy analyses.
Modified ITT (mITT):  Consists of all Week 8 PMS Responders who were randomized at 
Week 8 and received at least one dose of the study medication during maintenance period.  
mITT is the primary population for the maintenance period efficacy analyses.
Re-Randomized population:  Consists of all subjects with a disease flare who were 
re-randomized at or after Week 12 and received at least one dose of the study medication 
after the re-randomization.
Safety:  Includes all subjects who received at least one dose of the study drug.  The safety 
set will be analyzed as treated, according to treatment the subject actually received.  The 
safety set will be used only for safety analysis.
8.1.2
Planned Methods of Statistical Analysis
Descriptive statistics will include the number of observations, mean, standard deviation, 
minimum, first quartile, median, third quartile, and maximum for continuous variables; 
and counts and percentages for discrete variables.  For confirmatory tests the multiple 
significance level of 0.05 will be controlled.  The analysis will be performed using SAS®
(SAS Institute Inc., Cary, NC, USA).

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8.1.3
Demographics and Baseline Characteristics
Demographics and Baseline characteristics of the study subjects will be summarized for 
each treatment group using descriptive statistics.  P values will be provided to assess the 
comparability of the treatment groups assigned by randomization.  Continuous variables 
will be analyzed using analysis of variance (ANOVA) with treatment group as factor, and 
discrete variables will be analyzed using Chi-square test or Fisher's exact test.
8.1.4
Statistical Analyses of Efficacy
The efficacy analysis will be performed in the ITT-E population for the Week 8 efficacy 
endpoints and in the mITT population for the Week 52 efficacy endpoints.  Non-
responder imputation (NRI) will be used to impute missing values for binary efficacy 
endpoints.  Subjects who do not complete the induction period or who receive rescue 
therapy during the maintenance period will be considered as failures from that time point 
forward.  Both LOCF and observed case analyses will be performed for continuous 
efficacy endpoints.
8.1.4.1
Co-Primary and Ranked Secondary Efficacy Variables
Co-primary and ranked secondary endpoints will be summarized by treatment group with 
95% confidence intervals (CI) and adalimumab dose groups will be tested against external 
placebo in a sequentially rejective multiple test procedure in order to ensure that the 
multiple significance level of 5% is controlled, using one sample two-sided Chi-square 
tests.  The below graph describes the structure of the multiple test procedure that starts 
with testing the co-primary endpoints for the combined high and standard adalimumab 
dose groups versus external placebo and then individual dose groups versus external 
placebo separately:

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Multiple Test Procedure for the Co-Primary and Ranked Secondary Endpoints
Assuming ε = 0.0005; C = testing the endpoint for the combined high and standard adalimumab dose groups against 
external placebo; HD = testing the endpoint for the high adalimumab dose against external placebo; SD = testing the 
endpoint for the standard adalimumab dose against external placebo; P1 = co-primary induction endpoint; P2 = co-
primary maintenance endpoint; Si = ranked secondary endpoint i (i = 1,…,4)

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Section 8.1.4.3 contains details on assumed external placebo rates.
8.1.4.2
Additional Exploratory Secondary Efficacy Variables
Exploratory secondary endpoints that are of the binary type will be analyzed as 
proportions by treatment group including 95% CIs.  Exploratory secondary endpoints that 
are of the continuous type will be analyzed as changes from baseline, and reported by 
treatment group including 95% CIs.  Non-responder imputation (NRI) will be used to 
impute missing values for binary efficacy endpoints.  Both LOCF and observed case 
analyses will be performed for continuous efficacy endpoints. 
The following subset of endpoints will be tested for the high adalimumab dose against the 
standard adalimumab dose in an exploratory manner:
●
Proportion of subjects in PMS clinical remission at Week 8;
●
Proportion of subjects who achieve mucosal healing at Week 52 as measured 
by Mayo endoscopy subscore (defined as ≤ 1) in Week 8 responders per PMS;
●
Proportion of subjects in PUCAI remission (defined as < 10) at Week 52 in 
Week 8 responders per PMS;
●
Proportion of subjects in Mayo clinical response at Week 52 in Week 8 
responders per PMS;
●
Proportion of subjects in Mayo clinical remission at Week 52 in Week 8 
responders per PMS;
●
Proportion of subjects in PUCAI response (defined as a decrease in PUCAI 
≥20 points from Baseline) at Week 52 in Week 8 responders per PMS;
●
Proportion of subjects receiving corticosteroid at Baseline who discontinue 
corticosteroid  prior to Week 52 and are in Mayo clinical remission at Week 52 
in Week 8 responders per PMS;
●
Proportion of subjects receiving corticosteroid at Baseline who discontinue 
corticosteroid prior to Week 52 and are in PUCAI remission at Week 52 in 
Week 8 responders per PMS;
●
Proportion of subjects in PMS clinical remission at Week 52 in Week 8 
responders per PMS;

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●
Proportion of subjects in PUCAI remission at Week 8;
●
Proportion of subjects in PUCAI response at Week 8.
8.1.4.3
Derivation of External Placebo Control Rates
In order to derive robust external placebo assumptions for the co-primary and ranked 
secondary endpoints, a thorough literature search of placebo-controlled clinical studies in 
subjects with moderate to severe UC who had failed conventional therapy was performed.  
Studies M06-826 and M06-827 were the only available data sources with PMS data at 
Week 8.  Studies GEMINI 1 and OCTAVE Sustain were the only studies with a similar 
subject population (i.e., failure or intolerance to prior corticosteroids or IMMs), study 
design (i.e., randomized withdrawal), and endpoint definitions for derivation of external 
placebo rates for the Week 52 endpoints in Study M11-290. 
For all co-primary and ranked secondary endpoints where available, separate estimates for 
anti-TNF naïve placebo patients and anti-TNF experienced placebo patients were derived 
as described by endpoint below.  The estimates for anti-TNF naïve placebo patients and 
anti-TNF experienced placebo patients were then combined as a weighted mean according 
to the assumed proportion of anti-TNF naïve and experienced subjects as per the 
Study M11-290 protocol, i.e., 0.75 × rate in anti-TNF naïve + 0.25 × rate in anti-TNF 
experienced subjects.  To be conservative, the upper limit of the 95% CI for the weighted 
mean was used as the external placebo assumption.
For PMS remission at Week 8:  A remission rate of anti-TNF naïve placebo patients was 
estimated using logistic regression with anti-TNF naïve placebo patients from 
Studies M06-826 and M06-827 and study as a fixed effect, in order to weight the studies 
according to their sample sizes.  Anti-TNF experienced placebo patients were only 
available in Study M06-827, so the remission rate from this study only was used as 
remission rate for anti-TNF experienced placebo patients.
For Mayo Score remission and mucosal healing at Week 52 in Week 8 responders per 
PMS, as well as for Mayo Score remission at Week 52 in Week 8 remitters per PMS:  

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Separate remission rates of anti-TNF naïve and anti-TNF experienced placebo patients 
were estimated using separate logistic regression models with anti-TNF naïve placebo 
patients and anti-TNF experienced placebo patients, respectively, from GEMINI 1 and 
OCTAVE Sustain and study as a fixed effect, in order to weight the studies according to 
their sample sizes.
For Mayo Score response Week 52 in Week 8 responders per PMS: Results were not 
available by anti-TNF naïve versus anti-TNF experienced placebo patients, so the overall 
response rates in placebo subjects from GEMINI 1 and OCTAVE Sustain were combined 
via logistic regression with study as a fixed effect, in order to weight the studies according 
to their sample sizes.
For steroid-free remission per Mayo Score at Week 52 in Week 8 responders per PMS 
with corticosteroids at Baseline:  Only data from GEMINI 1 was available.  Rates of anti-
TNF naïve and anti-TNF experienced placebo patients from GEMINI 1 were combined to 
a weighted mean (0.75 × rate in anti-TNF naïve + 0.25 × rate in anti TNF experienced 
subjects) and the upper bound of the 95% CI for the weighted mean was used.
Table 5.
External Placebo Assumptions for Co-Primary and Ranked 
Secondary Efficacy Endpoints
Endpoint
External Placebo Rate 
(95% CI Upper Limit from Meta-Analysis)
Week 8 PMS Remission 
19.83%
Week 52 FMS Remission in Week 8 Responders per PMS
18.37%
Week 52 FMS Response in Week 8 Responders per PMS
26.10%
Week 52 Mucosal Healing in Week 8 Responders per PMS
22.03%
Week 52 FMS Remission in Week 8 Remitters per PMS
14.79%
Week 52 FMS Remission in Week 8 Responders per PMS with CS 
at Baseline and Discontinuation of CS prior to Week 52
24.08%
FMS = Full Mayo Score; PMS = Partial Mayo Score; CS = Corticosteroids

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8.1.5
Statistical Analyses of Safety
Adverse events (AEs), laboratory data and vital signs are the primary safety parameters in 
this study.  All safety comparisons will be performed within the safety analysis set.  
Treatment-emergent AEs are defined as new events that begin either on or after the 
first dose of the study medication and within 70 days after the last dose of the study 
medication.
Treatment-emergent adverse events (AEs) will be summarized by treatment group using 
descriptive statistics.  AEs, including serious AEs, AEs of special interest such as AEs 
leading to death and AEs leading to premature discontinuation (see details in the SAP), 
will be tabulated by system organ class and preferred term whereby the most current 
implemented MedDRA dictionary will be used.  Also, summaries by severity and 
relationship to study drug will be done.  
Other safety variables like laboratory data will be described by descriptive statistics as 
mentioned before.  In addition, shift tables and listings will be provided for abnormal 
values, whereby the normal range of the analyzing laboratory will be used.
Details of this and all other analyses will be provided in the SAP.
8.1.6
Interim Analysis
No interim analyses are planned.
8.1.7
Pharmacokinetic Analyses
Pharmacokinetic:
Adalimumab trough serum concentrations will be summarized by dose at each time point 
using descriptive statistics.  In addition, pharmacokinetic model based analyses will be 
performed with the focus on apparent clearance (CL/F) and apparent volume of 
distribution (V/F) of adalimumab.

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Immunogenicity:
AAA will be evaluated for each subject and each dose, and rates of AAA positive will be 
calculated.  As appropriate, the effect of AAA on adalimumab pharmacokinetics, efficacy 
variable(s), and treatment-emergent adverse events may be evaluated.  HACA will be 
evaluated for each subject and each dose, and rates of HACA positive will be calculated.
Exposure/Response:
The relationship between adalimumab concentrations and clinical response will be 
determined as appropriate.
8.2
Determination of Sample Size
The co-primary endpoints will be tested first for the combined high and standard 
adalimumab dose groups versus external placebo and then individual dose groups versus 
external placebo separately, controlling the multiple significance level of 5%.  For each 
individual test the nominal power is calculated. 
Assuming a 48% remission rate per PMS at Week 8 for the combined standard and high 
adalimumab induction dose groups and a remission rate per PMS of 19.83% for external 
placebo, a total of 77 subjects (high:standard = 46:31) in ITT-E population provides at 
least 99% power for a one sample two-sided Chi-square test using a significance level of 
5%. 
Assuming a 36% remission rate per Mayo Score at Week 52 for the combined standard 
and high maintenance dose groups and a remission rate per Mayo Score of 18.37% for 
external placebo, a total of 57 subjects in the combined adalimumab maintenance dose 
groups in mITT population (e.g., high:standard = 28:29) provide 88% power for a one 
sample two-sided Chi-square test using a significance level of 5%. 
Assuming that the high adalimumab dose regimen is associated with higher efficacy than 
the standard adalimumab dose regimen and assuming a 52% remission rate per PMS at 
Week 8 for the high adalimumab induction dose group and a remission rate per PMS of 

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19.83% for external placebo, 46 subjects in the high adalimumab induction dose group of 
ITT-E population provide at least 99% power for a one sample two-sided Chi-square test 
using a significance level of 4.95%. 
Assuming a 41% remission rate per Mayo Score at Week 52 for the high adalimumab 
maintenance dose groups and a remission rate per Mayo Score of 18.37% for external 
placebo, a total of 28 subjects in the high adalimumab maintenance dose group of the 
mITT population provide at least 80% power for a one sample two-sided Chi-square test 
using a significance level of 4.95%.
Based on the assumption of a 75% response rate at Week 8, 93 subjects will have to be 
included in the study (including ~12 internal placebo subjects in the maintenance part of 
the study who were included prior to Amendment 4) to ensure 57 subjects in the 
combined adalimumab maintenance dose groups.
8.3
Randomization Methods
Prior to Amendment 4, at baseline, subjects were randomized 3:2 to one of the double-
blinded adalimumab induction doses (high dose or standard dose).  The randomization 
was to be stratified by baseline disease severity (per Mayo score), prior exposure to anti-
TNF, and corticosteroid use at Baseline.
At Week 8, subjects demonstrating a clinical response per Partial Mayo Score (defined as 
a decrease in PMS ≥ 2 points and ≥ 30% from Baseline) were randomized in a 2:2:1 ratio 
to one of two adalimumab maintenance treatment groups (standard dose or high dose) or 
to placebo, respectively.  The randomization was stratified according to Week 8 remission 
status per PMS and induction dose.  
After Amendment 4, at Baseline, subjects will receive open-label adalimumab high 
induction dose.  
At Week 8, subjects demonstrating a clinical response per Partial Mayo Score (defined as 
a decrease in PMS ≥ 2 points and ≥ 30% from Baseline) will be randomized in a 1:1 ratio 

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to one of two adalimumab maintenance treatment groups (standard dose or high dose).  
The randomization will be stratified according to Week 8 remission status per PMS.  
At or after Week 12, subjects with a disease flare may be re-randomized to receive the 
blinded-treatments as shown in Figure 4.
The randomization schedule will be prepared by the Statistics Department of AbbVie.
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.
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 screening 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.
A copy of the informed consent form and the assent 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.
Genetic and non-genetic biomarker analysis will only be performed if the subject's 
parent/legal guardian has voluntarily signed and dated a separate genetic and 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 genetic and non-genetic biomarker informed consent must 
be signed before the genetic and non-genetic biomarker testing is performed.  If the 

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subject's parent/legal guardian does not consent to the genetic and non-genetic biomarker 
testing, it will not impact the subject's participation in the study.
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:
●
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.
10.2
Case Report Forms
Case report forms (CRF) must be completed for each subject screened/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 

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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.  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.
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 

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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 
(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 

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subject will record the required pieces of information on a daily basis.  In addition, study 
drug administration data (such as kit number, vial number and amount 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.
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 

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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.
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.
Any pharmacogenetic research that may be done using DNA samples from this study will 
be experimental in nature and the results will not be suitable for clinical decision making 
or subject management.  Hence, neither the investigator, the subject, nor the subject's 
physician (if different from the investigator) will be informed of individual subject results, 
should analyses be performed, nor will anyone not directly involved in this research.  
Correspondingly, researchers will have no access to subject identifiers.  Individual results 
will not be reported to anyone not directly involved in this research other than for 
regulatory purposes.  Aggregate pharmacogenetic information from this study may be 
used in scientific publications or presented at medical conventions.  Pharmacogenetic 
information will be published or presented only in a way that does not identify any 
individual subject.
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 

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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 Multicenter, Randomized, Double-Blind Study of the Human 
Anti-TNF Monoclonal Antibody Adalimumab in Pediatric Subjects 
with Moderate to Severe Ulcerative Colitis
Protocol Date:
20 November 2018
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.  
Journal of Crohn's and Colitis.  2011;5 Suppl. 1:S87, P181.

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20.
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.
21.
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.
22.
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.
23.
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.
24.
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.

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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 et al., and from Lewis et al.21,22
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.

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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.
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 

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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.
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 

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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).
The endoscopy will be recorded on a video tape and will undergo a central review process 
for endoscopy subscore assessment.

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Appendix E.
Loss of Response and Intolerance to Anti-TNF Agent
To enroll in this study, subjects who have previously been exposed to an anti-TNF agent, 
including infliximab, must meet one of the two conditions defined below.
Loss of Response
The investigator judges the subject to have responded to the anti-TNF agent in the past 
and demonstrated a loss of response after a full and adequate course of anti-TNF therapy 
based on the investigator's assessment.
Intolerance to Anti-TNF Agent
A subject is defined as intolerant when, in the opinion of the investigator, therapy was 
discontinued as a result of a significant acute or delayed reaction to the medication.

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Appendix F.
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 seven 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 seven 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?

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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 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 seven 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 G.
Study Drug Packaging and Administration
Prior to Amendment 4
During the Double-Blind Induction Period
Week
Standard Induction Dose
High Induction Dose
0 (Baseline)
Blinded study drug
adalimumab 2.4 mg/kg
Maximum dose of 160 mg
Maximum amount to administer is 3.2 mL
Blinded study drug
adalimumab 2.4 mg/kg
Maximum dose of 160 mg
Maximum amount to administer is 3.2 mL
1
Matching PBO
Maximum amount to administer is 3.2 mL
Blinded study drug
adalimumab 2.4 mg/kg
Maximum dose of 160 mg
Maximum amount to administer is 3.2 mL
2
Blinded study drug
adalimumab 1.2 mg/kg
Maximum dose of 80 mg
Maximum amount to administer is 1.6 mL
Blinded study drug
adalimumab 1.2 mg/kg
Maximum dose of 80 mg
Maximum amount to administer is 1.6 mL
4
Blinded study drug
adalimumab 0.6 mg/kg
Maximum dose of 40 mg
Maximum amount to administer is 0.8 mL
Blinded study drug
adalimumab 0.6 mg/kg 
Maximum dose of 40 mg
Maximum amount to administer is 0.8 mL
6
Blinded study drug
adalimumab 0.6 mg/kg
Maximum dose of 40 mg
Maximum amount to administer is 0.8 mL
Blinded study drug
adalimumab 0.6 mg/kg
Maximum dose of 40 mg
Maximum amount to administer is 0.8 mL

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During the Maintenance Period
Week
PBO
Standard Maintenance Dose
High Maintenance Dose
8 – 50
i.e., Wks 8, 10, 12, 14, 
16, 18 to Wk 50)
Matching PBO
Maximum amount to administer is 0.8 mL
Blinded Study Drug
adalimumab 0.6 mg/kg
Maximum dose of 40 mg
Maximum amount to administer is 0.8 mL
Blinded Study Drug
adalimumab  0.6 mg/kg
Maximum dose of 40 mg
Maximum amount to administer is 0.8 mL
9 – 51
i.e., Wks 9, 11, 13, 15, 
17, 19… to Wk 51
Matching PBO
Maximum amount to administer is 0.8 mL
Matching PBO
Maximum amount to administer is 0.8 mL
Blinded Study Drug
adalimumab 0.6 mg/kg
Maximum dose of 40 mg
Maximum amount to administer is 0.8 mL 

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Disease Flare During Maintenance Period
Week
PBO
Standard Maintenance Dose
High Maintenance Dose
Disease Flare
Re-Induction Dose 
of 2.4 mg/kg (max 
160 mg)
Dose 0.6 mg/kg 
(max 40 mg)
Re-Induction Dose 
of 2.4 mg/kg (max 
160 mg)
Dose 0.6 mg/kg 
(max 40 mg)
Re-Induction Dose 
of 2.4 mg/kg (max 
160 mg)
Dose 0.6 mg/kg 
(max 40 mg)
Re-Induction Dose
(1st time)
At or after Week 12
Blinded study drug
adalimumab 
2.4 mg/kg
Maximum dose of 
160 mg
Maximum amount to 
administer is 3.2 mL
Blinded study 
drug
adalimumab 
0.6 mg/kg
Maximum dose of 
40 mg
Plus
Matching Placebo
Maximum amount 
to administer is 
3.2 mL 
Blinded study drug
adalimumab 
2.4 mg/kg
Maximum dose of 
160 mg
Maximum amount to 
administer is 3.2 mL
Blinded study 
drug
adalimumab 
0.6 mg/kg
Maximum dose of 
40 mg
Plus
Matching Placebo
Maximum amount 
to administer is 
3.2 mL 
Blinded study drug
adalimumab 
2.4 mg/kg
Maximum dose of 
160 mg
Maximum amount to 
administer is 3.2 mL
Blinded study 
drug
adalimumab 
0.6 mg/kg
Maximum dose 
of 40 mg
Plus
Matching Placebo
Maximum amount 
to administer is 
3.2 mL

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Disease Flare During Maintenance Period (Continued)
Week
PBO
Standard Maintenance Dose
High Maintenance Dose
Disease Flare
Re-Induction Dose 
of 2.4 mg/kg (max 
160 mg)
Dose 0.6 mg/kg 
(max 40 mg)
Re-Induction Dose 
of 2.4 mg/kg (max 
160 mg)
Dose 0.6 mg/kg 
(max 40 mg)
Re-Induction Dose 
of 2.4 mg/kg (max 
160 mg)
Dose 0.6 mg/kg 
(max 40 mg)
One week after 
Re-Induction dose 
If subject receives Re-Induction dose at 
site on Even week (i.e., Wk 22, 24, 
26, …), then subject must start with 
vial 2 at home at the week after 
Re-Induction dose.
Matching PBO
Maximum amount to administer is 0.8 mL
The following weeks, subject will use 
vial 1, then vial 2, continue like this until 
next site visit.
If subject receives Re-Induction dose at 
site on Even week (i.e., Wk 22, 24, 
26, …), then subject must start with 
vial 2 at home at the week after 
Re-Induction dose.
Matching PBO
Maximum amount to administer is 0.8 mL
The following weeks, subject will use 
vial 1, then vial 2, continue like this until 
next site visit.
If subject receives Re-Induction dose at 
site on Even week (i.e., Wk 22, 24, 
26, …), then subject must start with 
vial 2 at home at the week after 
Re-Induction dose.
Blinded study drug
adalimumab 0.6 mg/kg
Maximum dose of 40 mg
Maximum amount to administer is 0.8 mL
The following weeks, subject will use 
vial 1, then vial 2, continue like this until 
next site visit.

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Disease Flare During Maintenance Period (Continued)
Week
PBO
Standard Maintenance Dose
High Maintenance Dose
Disease Flare
Re-Induction Dose 
of 2.4 mg/kg (max 
160 mg)
Dose 0.6 mg/kg 
(max 40 mg)
Re-Induction Dose 
of 2.4 mg/kg (max 
160 mg)
Dose 0.6 mg/kg 
(max 40 mg)
Re-Induction Dose 
of 2.4 mg/kg (max 
160 mg)
Dose 0.6 mg/kg 
(max 40 mg)
One week after 
Re-Induction dose 
(continued)
If subject receives Re-Induction dose at 
site on Odd week (i.e., Wk 21, 23, 
25, …), then subject must start with 
vial 1 at home at the week after 
Re-Induction dose.
Blinded study drug
adalimumab 0.6 mg/kg
Maximum dose of 40 mg
Maximum amount to administer is 0.8 mL
The following weeks, subject will use 
vial 2, then vial 1, continue like this until 
next site visit.
If subject receives Re-Induction dose at 
site on Odd week (i.e., Wk 21, 23, 
25, …), then subject must start with 
vial 1 at home at the week after 
Re-Induction dose.
Blinded study drug
adalimumab 0.6 mg/kg
Maximum dose of 40 mg
Maximum amount to administer is 0.8 mL
The following weeks, subject will use 
vial 2, then vial 1, continue like this until 
next site visit.
If subject receives Re-Induction dose at 
site on Odd week (i.e., Wk 21, 23, 
25, …), then subject must start with 
vial 1 at home at the week after 
Re-Induction dose.
Blinded study drug
adalimumab 0.6 mg/kg
Maximum dose of 40 mg
Maximum amount to administer is 0.8 mL
The following weeks, subject will use 
vial 2, then vial 1, continue like this until 
next site visit.

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Disease Flare During Maintenance Period (Continued)
Escape to Open-Label Drug (Weight Based)
Disease Flare 
2nd Time (at least 
after 4 weeks of 
re-induction dose)
adalimumab 0.6 mg/kg
Maximum dose of 40 mg
Maximum amount to administer is 0.8 mL
Administered every week
Dose Escalation (MAX DOSE – NOT Weight Based)
Disease Flare 
3rd Time (after at 
least 4 weeks on 
open-label standard 
dose)
Adalimumab 40 mg/0.8 mL
Adalimumab 40 mg
Amount to administer is 0.8 mL
Administered every week
Dose De-Escalation and Dose Re-Escalation During Maintenance Period
Dose De-Escalation
Open-label study drug
adalimumab 40 mg/0.8 mL
Administered every other week
Dose Re-Escalation
Open-label study drug
adalimumab 40 mg/0.8 mL
Administered every week

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After Amendment 4
During the Open-Label Induction Period
Week
High Induction Dose
0 (Baseline)
Open-label study drug
adalimumab 2.4 mg/kg
Maximum dose of 160 mg
Maximum amount to administer is 3.2 mL
1
Open-label study drug
adalimumab 2.4 mg/kg
Maximum dose of 160 mg
Maximum amount to administer is 3.2 mL
2
Open-label study drug
adalimumab 1.2 mg/kg
Maximum dose of 80 mg
Maximum amount to administer is 1.6 mL
4
Open-label study drug
adalimumab 0.6 mg/kg 
Maximum dose of 40 mg
Maximum amount to administer is 0.8 mL
6
Open-label study drug
adalimumab 0.6 mg/kg
Maximum dose of 40 mg
Maximum amount to administer is 0.8 mL
During the Maintenance Period
Week
Standard Maintenance Dose
High Maintenance Dose
8 – 50
i.e., Wks 8, 10, 12, 14, 
16, 18 to Wk 50)
Blinded Study Drug
adalimumab 0.6 mg/kg
Maximum dose of 40 mg
Maximum amount to administer is 
0.8 mL
Blinded Study Drug
adalimumab  0.6 mg/kg
Maximum dose of 40 mg
Maximum amount to administer is 0.8 mL
9 – 51
i.e., Wks 9, 11, 13, 15, 
17, 19… to Wk 51
Matching PBO
Maximum amount to administer is 
0.8 mL
Blinded Study Drug
adalimumab 0.6 mg/kg
Maximum dose of 40 mg
Maximum amount to administer is 0.8 mL 

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Disease Flare During Maintenance Period
Week
Standard Maintenance Dose
High Maintenance Dose
Disease Flare
Re-Induction Dose 
of 2.4 mg/kg 
(max 160 mg)
Dose 0.6 mg/kg 
(max 40 mg)
Re-Induction 
Dose of 
2.4 mg/kg
(max 160 mg)
Dose 0.6 mg/kg 
(max 40 mg)
Re-Induction 
Dose
(1st time)
At or after 
Week 12
Blinded study 
drug adalimumab 
2.4 mg/kg
Maximum dose of 
160 mg
Maximum amount 
to administer is 
3.2 mL
Blinded study 
drug adalimumab 
0.6 mg/kg
Maximum dose of 
40 mg
Plus
Matching Placebo
Maximum amount 
to administer is 
3.2 mL 
Blinded study 
drug adalimumab 
2.4 mg/kg
Maximum dose of 
160 mg
Maximum amount 
to administer is 
3.2 mL
Blinded study 
drug adalimumab 
0.6 mg/kg
Maximum dose of 
40 mg
Plus
Matching Placebo
Maximum amount 
to administer is 
3.2 mL
One week after 
Re-Induction 
dose
If subject receives Re-Induction dose at 
site on Even week (i.e., Wk 22, 24, 
26, …), then subject must start with 
vial 2 at home at the week after 
Re-Induction dose.
Matching PBO
Maximum amount to administer is 0.8 mL
The following weeks, subject will use 
vial 1, then vial 2, continue like this 
until next site visit.
If subject receives Re-Induction dose 
at site on Even week (i.e., Wk 22, 24, 
26, …), then subject must start with 
vial 2 at home at the week after 
Re-Induction dose.
Blinded study drug
adalimumab 0.6 mg/kg
Maximum dose of 40 mg
Maximum amount to administer is 
0.8 mL
The following weeks, subject will use 
vial 1, then vial 2, continue like this 
until next site visit.

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Disease Flare During Maintenance Period (Continued)
Week
Standard Maintenance Dose
High Maintenance Dose
Disease Flare
Re-Induction Dose 
of 2.4 mg/kg 
(max 160 mg)
Dose 0.6 mg/kg 
(max 40 mg)
Re-Induction 
Dose of 
2.4 mg/kg
(max 160 mg)
Dose 0.6 mg/kg 
(max 40 mg)
One week after 
Re-Induction 
dose (continued)
If subject receives Re-Induction dose at 
site on Odd week (i.e., Wk 21, 23, 
25, …), then subject must start with 
vial 1 at home at the week after 
Re-Induction dose.
Blinded study drug
adalimumab 0.6 mg/kg
Maximum dose of 40 mg
Maximum amount to administer is 0.8 mL
The following weeks, subject will use 
vial 2, then vial 1, continue like this 
until next site visit.
If subject receives Re-Induction dose 
at site on Odd week (i.e., Wk 21, 23, 
25, …), then subject must start with 
vial 1 at home at the week after 
Re-Induction dose.
Blinded study drug
adalimumab 0.6 mg/kg
Maximum dose of 40 mg
Maximum amount to administer is 
0.8 mL
The following weeks, subject will use 
vial 2, then vial 1, continue like this 
until next site visit.
Escape to Open-Label Drug (Weight Based)
Disease Flare 
2nd Time (at 
least after 
4 weeks of 
re-induction 
dose)
adalimumab 0.6 mg/kg
Maximum dose of 40 mg
Maximum amount to administer is 0.8 mL
Administered every week
Dose Escalation (MAX DOSE – NOT Weight Based)
Disease Flare 
3rd Time (after 
at least 4 weeks 
on open-label 
standard dose)
Adalimumab 40 mg/0.8 mL
Adalimumab 40 mg
Amount to administer is 0.8 mL
Administered every week

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Dose De-Escalation and Dose Re-Escalation During Maintenance Period
Dose De-Escalation
Open-label study drug
adalimumab 40 mg/0.8 mL
Administered every other week
Dose Re-Escalation
Open-label study drug
adalimumab 40 mg/0.8 mL
Administered every week

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Appendix H.
Body Weight Adjusted Volumes of Study Drug for Administration of Induction and Maintenance Doses
Part 1.  Body Weight Adjusted Volumes of Study Drug for Administration of Induction Dose at BL and Week 1
Weight 
(Kg)
Administered
(# of vial 
used)
Kit 1 
Vial 1
Kit 1 
Vial 2
Kit 2 
Vial 1
Kit 2 
Vial 2
Weight 
(Kg)
Administered
(# of vial 
used)
Kit 1 
Vial 1
Kit 1 
Vial 2
Kit 2 
Vial 1
Kit 2 
Vial 2
Weight 
(Kg)
Administered
(# of vial 
used)
Kit 1 
Vial 1
Kit 1 
Vial 2
Kit 2 
Vial 1
Kit 2 
Vial 2
14
1 x
0.67
NA
NA
NA
36
4 x
0.43
0.43
0.43
0.43
58
4 x
0.70
0.70
0.70
0.70
15
1 x
0.72
NA
NA
NA
37
4 x
0.44
0.44
0.44
0.44
59
4 x
0.71
0.71
0.71
0.71
16
1 x
0.77
NA
NA
NA
38
4 x
0.46
0.46
0.46
0.46
60
4 x
0.72
0.72
0.72
0.72
17
2 x
0.41
0.41
NA
NA
39
4 x
0.47
0.47
0.47
0.47
61
4 x
0.73
0.73
0.73
0.73
18
2 x
0.43
0.43
NA
NA
40
4 x
0.48
0.48
0.48
0.48
62
4 x
0.74
0.74
0.74
0.74
19
2 x
0.46
0.46
NA
NA
41
4 x
0.49
0.49
0.49
0.49
63
4 x
0.76
0.76
0.76
0.76
20
2 x
0.48
0.48
NA
NA
42
4 x
0.50
0.50
0.50
0.50
64
4 x
0.77
0.77
0.77
0.77
21
2 x
0.50
0.50
NA
NA
43
4 x
0.52
0.52
0.52
0.52
65
4 x
0.78
0.78
0.78
0.78
22
2 x
0.53
0.53
NA
NA
44
4 x
0.53
0.53
0.53
0.53
66
4 x
0.79
0.79
0.79
0.79
23
2 x
0.55
0.55
NA
NA
45
4 x
0.54
0.54
0.54
0.54
67
4 x
0.80
0.80
0.80
0.80
24
2 x
0.58
0.58
NA
NA
46
4 x
0.55
0.55
0.55
0.55
68
4 x
0.80
0.80
0.80
0.80
25
2 x
0.60
0.60
NA
NA
47
4 x
0.56
0.56
0.56
0.56
69
4 x
0.80
0.80
0.80
0.80
26
2 x
0.62
0.62
NA
NA
48
4 x
0.58
0.58
0.58
0.58
70
4 x
0.80
0.80
0.80
0.80
27
2 x
0.65
0.65
NA
NA
49
4 x
0.59
0.59
0.59
0.59
71
4 x
0.80
0.80
0.80
0.80
28
2 x
0.67
0.67
NA
NA
50
4 x
0.60
0.60
0.60
0.60
72
4 x
0.80
0.80
0.80
0.80
29
2 x
0.70
0.70
NA
NA
51
4 x
0.61
0.61
0.61
0.61
73
4 x
0.80
0.80
0.80
0.80
30
2 x
0.72
0.72
NA
NA
52
4 x
0.62
0.62
0.62
0.62
74
4 x
0.80
0.80
0.80
0.80
31
2 x
0.74
0.74
NA
NA
53
4 x
0.64
0.64
0.64
0.64
75
4 x
0.80
0.80
0.80
0.80

Adalimumab
M11-290 Protocol Amendment 5
EudraCT 2013-003032-77
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Weight 
(Kg)
Administered
(# of vial 
used)
Kit 1 
Vial 1
Kit 1 
Vial 2
Kit 2 
Vial 1
Kit 2 
Vial 2
Weight 
(Kg)
Administered
(# of vial 
used)
Kit 1 
Vial 1
Kit 1 
Vial 2
Kit 2 
Vial 1
Kit 2 
Vial 2
Weight 
(Kg)
Administered
(# of vial 
used)
Kit 1 
Vial 1
Kit 1 
Vial 2
Kit 2 
Vial 1
Kit 2 
Vial 2
32
2 x
0.77
0.77
NA
NA
54
4 x
0.65
0.65
0.65
0.65
76
4 x
0.80
0.80
0.80
0.80
33
2 x
0.79
0.79
NA
NA
55
4 x
0.66
0.66
0.66
0.66
77
4 x
0.80
0.80
0.80
0.80
34
4 x
0.41
0.41
0.41
0.41
56
4 x
0.67
0.67
0.67
0.67
78
4 x
0.80
0.80
0.80
0.80
35
4 x
0.42
0.42
0.42
0.42
57
4 x
0.68
0.68
0.68
0.68
79
4 x
0.80
0.80
0.80
0.80
80
4 x
0.80
0.80
0.80
0.80
Part 2.  Body Weight Adjusted Volumes of Study Drug for Administration of Induction Dose at Week 2
Weight 
(Kg)
Administered 
(# of vial used)
Kit 1 
Vial 1
Kit 1 
Vial 2
Weight 
(Kg)
Administered 
(# of vial used)
Kit 1 
Vial 1
Kit 1 
Vial 2
Weight 
(Kg)
Administered 
(# of vial used)
Kit 1 Vial 1
Kit 1 Vial 2
14
1 x
0.34
NA
37
2 x
0.44
0.44
60
2 x
0.72
0.72
15
1 x
0.36
NA
38
2 x
0.46
0.46
61
2 x
0.73
0.73
16
1 x
0.38
NA
39
2 x
0.47
0.47
62
2 x
0.74
0.74
17
1 x
0.41
NA
40
2 x
0.48
0.48
63
2 x
0.76
0.76
18
1 x
0.43
NA
41
2 x
0.49
0.49
64
2 x
0.77
0.77
19
1 x
0.46
NA
42
2 x
0.50
0.50
65
2 x
0.78
0.78
20
1 x
0.48
NA
43
2 x
0.52
0.52
66
2 x
0.79
0.79
21
1 x
0.50
NA
44
2 x
0.53
0.53
67
2 x
0.80
0.80
22
1 x
0.53
NA
45
2 x
0.54
0.54
68
2 x
0.80
0.80
23
1 x
0.55
NA
46
2 x
0.55
0.55
69
2 x
0.80
0.80
24
1 x
0.58
NA
47
2 x
0.56
0.56
70
2 x
0.80
0.80
25
1 x
0.60
NA
48
2 x
0.58
0.58
71
2 x
0.80
0.80

Adalimumab
M11-290 Protocol Amendment 5
EudraCT 2013-003032-77
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Weight 
(Kg)
Administered 
(# of vial used)
Kit 1 
Vial 1
Kit 1 
Vial 2
Weight 
(Kg)
Administered 
(# of vial used)
Kit 1 
Vial 1
Kit 1 
Vial 2
Weight 
(Kg)
Administered 
(# of vial used)
Kit 1 Vial 1
Kit 1 Vial 2
26
1 x
0.62
NA
49
2 x
0.59
0.59
72
2 x
0.80
0.80
27
1 x
0.65
NA
50
2 x
0.60
0.60
73
2 x
0.80
0.80
28
1 x
0.67
NA
51
2 x
0.61
0.61
74
2 x
0.80
0.80
29
1 x
0.70
NA
52
2 x
0.62
0.62
75
2 x
0.80
0.80
30
1 x
0.72
NA
53
2 x
0.64
0.64
76
2 x
0.80
0.80
31
1 x
0.74
NA
54
2 x
0.65
0.65
77
2 x
0.80
0.80
32
1 x
0.77
NA
55
2 x
0.66
0.66
78
2 x
0.80
0.80
33
1 x
0.79
NA
56
2 x
0.67
0.67
79
2 x
0.80
0.80
34
2 x
0.41
0.41
57
2 x
0.68
0.68
80
2 x
0.80
0.80
35
2 x
0.42
0.42
58
2 x
0.70
0.70
36
2 x
0.43
0.43
59
2 x
0.71
0.71
Part 3.  Body Weight Adjusted Volumes of Study Drug for Administration of Induction Dose at Week 4 and 6
Weight 
(Kg)
Administered
(# of vial 
used)
Week 4
Kit 1 Vial 1
Volume 
(ml)
Week 6 
Kit 1 
Vial 2
Volume
(ml)
Weight 
(Kg)
Administered
(# of vial 
used)
Week 4
Kit 1 
Vial 1 
Volume
(ml)
Week 6 
Kit 1 
Vial 2 
Volume
(ml)
Weight 
(Kg)
Administered
(# of vial 
used)
Week 4
Kit 1 
Vial 1 
Volume
(ml)
Week 6
Kit 1 
Vial 2 
Volume
(ml)
14
1 x
0.17
0.17
36
1 x
0.43
0.43
58
1 x
0.70
0.70
15
1 x
0.18
0.18
37
1 x
0.44
0.44
59
1 x
0.71
0.71
16
1 x
0.19
0.19
38
1 x
0.46
0.46
60
1 x
0.72
0.72
17
1 x
0.20
0.20
39
1 x
0.47
0.47
61
1 x
0.73
0.73

Adalimumab
M11-290 Protocol Amendment 5
EudraCT 2013-003032-77
161
Weight 
(Kg)
Administered
(# of vial 
used)
Week 4
Kit 1 Vial 1
Volume 
(ml)
Week 6 
Kit 1 
Vial 2
Volume
(ml)
Weight 
(Kg)
Administered
(# of vial 
used)
Week 4
Kit 1 
Vial 1 
Volume
(ml)
Week 6 
Kit 1 
Vial 2 
Volume
(ml)
Weight 
(Kg)
Administered
(# of vial 
used)
Week 4
Kit 1 
Vial 1 
Volume
(ml)
Week 6
Kit 1 
Vial 2 
Volume
(ml)
18
1 x
0.22
0.22
40
1 x
0.48
0.48
62
1 x
0.74
0.74
19
1 x
0.23
0.23
41
1 x
0.49
0.49
63
1 x
0.76
0.76
20
1 x
0.24
0.24
42
1 x
0.50
0.50
64
1 x
0.77
0.77
21
1 x
0.25
0.25
43
1 x
0.52
0.52
65
1 x
0.78
0.78
22
1 x
0.26
0.26
44
1 x
0.53
0.53
66
1 x
0.79
0.79
23
1 x
0.28
0.28
45
1 x
0.54
0.54
67
1 x
0.80
0.80
24
1 x
0.29
0.29
46
1 x
0.55
0.55
68
1 x
0.80
0.80
25
1 x
0.30
0.30
47
1 x
0.56
0.56
69
1 x
0.80
0.80
26
1 x
0.31
0.31
48
1 x
0.58
0.58
70
1 x
0.80
0.80
27
1 x
0.32
0.32
49
1 x
0.59
0.59
71
1 x
0.80
0.80
28
1 x
0.34
0.34
50
1 x
0.60
0.60
72
1 x
0.80
0.80
29
1 x
0.35
0.35
51
1 x
0.61
0.61
73
1 x
0.80
0.80
30
1 x
0.36
0.36
52
1 x
0.62
0.62
74
1 x
0.80
0.80
31
1 x
0.37
0.37
53
1 x
0.64
0.64
75
1 x
0.80
0.80
32
1 x
0.38
0.38
54
1 x
0.65
0.65
76
1 x
0.80
0.80
33
1 x
0.40
0.40
55
1 x
0.66
0.66
77
1 x
0.80
0.80
34
1 x
0.41
0.41
56
1 x
0.67
0.67
78
1 x
0.80
0.80
35
1 x
0.42
0.42
57
1 x
0.68
0.68
79
1 x
0.80
0.80
80
1 x
0.80
0.80

Adalimumab
M11-290 Protocol Amendment 5
EudraCT 2013-003032-77
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Part 4.  Body Weight Adjusted Volumes of Study Drug for Administration of Maintenance Dose Starting at Week 8 to 
Week 51
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 x
0.17
36
1 x
0.43
58
1 x
0.70
15
1 x
0.18
37
1 x
0.44
59
1 x
0.71
16
1 x
0.19
38
1 x
0.46
60
1 x
0.72
17
1 x
0.20
39
1 x
0.47
61
1 x
0.73
18
1 x
0.22
40
1 x
0.48
62
1 x
0.74
19
1 x
0.23
41
1 x
0.49
63
1 x
0.76
20
1 x
0.24
42
1 x
0.50
64
1 x
0.77
21
1 x
0.25
43
1 x
0.52
65
1 x
0.78
22
1 x
0.26
44
1 x
0.53
66
1 x
0.79
23
1 x
0.28
45
1 x
0.54
67
1 x
0.80
24
1 x
0.29
46
1 x
0.55
68
1 x
0.80
25
1 x
0.30
47
1 x
0.56
69
1 x
0.80
26
1 x
0.31
48
1 x
0.58
70
1 x
0.80
27
1 x
0.32
49
1 x
0.59
71
1 x
0.80
28
1 x
0.34
50
1 x
0.60
72
1 x
0.80
29
1 x
0.35
51
1 x
0.61
73
1 x
0.80
30
1 x
0.36
52
1 x
0.62
74
1 x
0.80
31
1 x
0.37
53
1 x
0.64
75
1 x
0.80

Adalimumab
M11-290 Protocol Amendment 5
EudraCT 2013-003032-77
163
Weight 
(Kg)
Administered
(# of vial used)
Volume 
(ml)
Weight 
(Kg)
Administered
(# of vial used)
Volume 
(ml)
Weight 
(Kg)
Administered
(# of vial used)
Volume 
(ml)
32
1 x
0.38
54
1 x
0.65
76
1 x
0.80
33
1 x
0.40
55
1 x
0.66
77
1 x
0.80
34
1 x
0.41
56
1 x
0.67
78
1 x
0.80
35
1 x
0.42
57
1 x
0.68
79
1 x
0.80
80
1 x
0.80

Adalimumab
M11-290 Protocol Amendment 5
EudraCT 2013-003032-77
164
Appendix I.
Body Weight Adjusted Volumes of Study Drug for Administration 
of Dose After Re-Randomization for Disease Flare
Weight (Kg)
Administered
(# of vial used)
Kit 1 Vial 1
Volume (ml)
Kit 1 Vial 2
Volume (ml)
Kit 2 Vial 1
Volume (ml)
Kit 2 Vial 2
Volume (ml)
14
4 x
0.17
0.17
0.17
0.17
15
4 x
0.18
0.18
0.18
0.18
16
4 x
0.19
0.19
0.19
0.19
17
4 x
0.20
0.20
0.20
0.20
18
4 x
0.22
0.22
0.22
0.22
19
4 x
0.23
0.23
0.23
0.23
20
4 x
0.24
0.24
0.24
0.24
21
4 x
0.25
0.25
0.25
0.25
22
4 x
0.26
0.26
0.26
0.26
23
4 x
0.28
0.28
0.28
0.28
24
4 x
0.29
0.29
0.29
0.29
25
4 x
0.30
0.30
0.30
0.30
26
4 x
0.31
0.31
0.31
0.31
27
4 x
0.32
0.32
0.32
0.32
28
4 x
0.34
0.34
0.34
0.34
29
4 x
0.35
0.35
0.35
0.35
30
4 x
0.36
0.36
0.36
0.36
31
4 x
0.37
0.37
0.37
0.37
32
4 x
0.38
0.38
0.38
0.38
33
4 x
0.40
0.40
0.40
0.40
34
4 x
0.41
0.41
0.41
0.41
35
4 x
0.42
0.42
0.42
0.42
36
4 x
0.43
0.43
0.43
0.43
37
4 x
0.44
0.44
0.44
0.44
38
4 x
0.46
0.46
0.46
0.46
39
4 x
0.47
0.47
0.47
0.47
40
4 x
0.48
0.48
0.48
0.48
41
4 x
0.49
0.49
0.49
0.49
42
4 x
0.50
0.50
0.50
0.50

Adalimumab
M11-290 Protocol Amendment 5
EudraCT 2013-003032-77
165
Weight (Kg)
Administered
(# of vial used)
Kit 1 Vial 1
Volume (ml)
Kit 1 Vial 2
Volume (ml)
Kit 2 Vial 1
Volume (ml)
Kit 2 Vial 2
Volume (ml)
43
4 x
0.52
0.52
0.52
0.52
44
4 x
0.53
0.53
0.53
0.53
45
4 x
0.54
0.54
0.54
0.54
46
4 x
0.55
0.55
0.55
0.55
47
4 x
0.56
0.56
0.56
0.56
48
4 x
0.58
0.58
0.58
0.58
49
4 x
0.59
0.59
0.59
0.59
50
4 x
0.60
0.60
0.60
0.60
51
4 x
0.61
0.61
0.61
0.61
52
4 x
0.62
0.62
0.62
0.62
53
4 x
0.64
0.64
0.64
0.64
54
4 x
0.65
0.65
0.65
0.65
55
4 x
0.66
0.66
0.66
0.66
56
4 x
0.67
0.67
0.67
0.67
57
4 x
0.68
0.68
0.68
0.68
58
4 x
0.70
0.70
0.70
0.70
59
4 x
0.71
0.71
0.71
0.71
60
4 x
0.72
0.72
0.72
0.72
61
4 x
0.73
0.73
0.73
0.73
62
4 x
0.74
0.74
0.74
0.74
63
4 x
0.76
0.76
0.76
0.76
64
4 x
0.77
0.77
0.77
0.77
65
4 x
0.78
0.78
0.78
0.78
66
4 x
0.79
0.79
0.79
0.79
67
4 x
0.80
0.80
0.80
0.80
68
4 x
0.80
0.80
0.80
0.80
69
4 x
0.80
0.80
0.80
0.80
70
4 x
0.80
0.80
0.80
0.80
71
4 x
0.80
0.80
0.80
0.80
72
4 x
0.80
0.80
0.80
0.80
73
4 x
0.80
0.80
0.80
0.80
74
4 x
0.80
0.80
0.80
0.80

Adalimumab
M11-290 Protocol Amendment 5
EudraCT 2013-003032-77
166
Weight (Kg)
Administered
(# of vial used)
Kit 1 Vial 1
Volume (ml)
Kit 1 Vial 2
Volume (ml)
Kit 2 Vial 1
Volume (ml)
Kit 2 Vial 2
Volume (ml)
75
4 x
0.80
0.80
0.80
0.80
76
4 x
0.80
0.80
0.80
0.80
77
4 x
0.80
0.80
0.80
0.80
78
4 x
0.80
0.80
0.80
0.80
79
4 x
0.80
0.80
0.80
0.80
80
4 x
0.80
0.80
0.80
0.80

Adalimumab
M11-290 Protocol Amendment 5
EudraCT 2013-003032-77
167
Appendix J.
Body Weight Adjusted Volumes of Study Drug for Administration 
of OL 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 x
0.17
36
1 x
0.43
58
1 x
0.70
15
1 x
0.18
37
1 x
0.44
59
1 x
0.71
16
1 x
0.19
38
1 x
0.46
60
1 x
0.72
17
1 x
0.20
39
1 x
0.47
61
1 x
0.73
18
1 x
0.22
40
1 x
0.48
62
1 x
0.74
19
1 x
0.23
41
1 x
0.49
63
1 x
0.76
20
1 x
0.24
42
1 x
0.50
64
1 x
0.77
21
1 x
0.25
43
1 x
0.52
65
1 x
0.78
22
1 x
0.26
44
1 x
0.53
66
1 x
0.79
23
1 x
0.28
45
1 x
0.54
67
1 x
0.80
24
1 x
0.29
46
1 x
0.55
68
1 x
0.80
25
1 x
0.30
47
1 x
0.56
69
1 x
0.80
26
1 x
0.31
48
1 x
0.58
70
1 x
0.80
27
1 x
0.32
49
1 x
0.59
71
1 x
0.80
28
1 x
0.34
50
1 x
0.60
72
1 x
0.80
29
1 x
0.35
51
1 x
0.61
73
1 x
0.80
30
1 x
0.36
52
1 x
0.62
74
1 x
0.80
31
1 x
0.37
53
1 x
0.64
75
1 x
0.80
32
1 x
0.38
54
1 x
0.65
76
1 x
0.80
33
1 x
0.40
55
1 x
0.66
77
1 x
0.80
34
1 x
0.41
56
1 x
0.67
78
1 x
0.80
35
1 x
0.42
57
1 x
0.68
79
1 x
0.80
80
1 x
0.80

Adalimumab
M11-290 Protocol Amendment 5
EudraCT 2013-003032-77
168
Appendix K.
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.)
If events are listed above, your monitor will review and retrieve the appropriate eCRF 
pages during their next visit.

Adalimumab
M11-290 Protocol Amendment 5
EudraCT 2013-003032-77
169
Appendix L.
Injection Instructions – Sample Vial
Subject Instructions
0.8 mL dose
Protocol M11-290
Tables of Contents
Dosing Schedule
General Information and Supplies
Injection Procedures

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Study Drug Dosing Schedule
Subject Number:_____________________________________
You will require subcutaneous (SC) injections throughout the study.
The injection for the visits at Baseline, Weeks 1, 2, 4, 8, 12, 18, 26, 34, 42 and 52 will be 
done during your visit at the doctor's office.  After Week 4, on weeks between office visits 
(i.e., Weeks 6, 9, 10, 11, 13, etc.) study drug will be self-administered at home by you or 
someone trained to give you the injections.
The study drug should be administered on the same day of the week for each dose.
Starting at Week 8, study drug will be administered once a week by you or someone 
trained to give you the injections.
The vials in the kits will be numbered 1 and 2.  You MUST use the vials in order.
At each visit, site personnel will measure your weight and inform you the volume of study 
drug that you will be taken (milliliter [ml] or cc).  You must use the suggested volume up 
until your site personnel provide you with the new volume of study drug to be taken.
Please return all used and unused vials, the Sharps container and empty boxes to the clinic 
on your next visit.  Used syringes should be placed in the special Sharps container 
provided.  All unused vials should be returned in the original box.
If an injection is missed or something occurs where the suggested dose cannot be injected, 
contact your study center immediately for further instructions.  Please record any missed 
doses on your subject diary/dosing log.
Remember to complete your dosing log after each injection and to call the doctor's office 
if you are having problems administering your study medication.

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General Information
●
Vials will be labeled "Adalimumab" versus Placebo.
●
Store all adalimumab vials in your refrigerator NOT in the freezer.  Should the 
medication accidentally become frozen, call your study doctor's office.
●
Study medication should be taken at about the same time of day, on the same 
day of the week as directed by your study doctor.
●
USE A NEW VIAL AND NEW SYRINGE EVERY INJECTION DAY.  
There may be medication left in the vial.  DO NOT RE-USE.
●
Save all study medications.  All vials (used and unused) and empty boxes 
must be returned to the study center at each visit.  Used syringes will be 
disposed of in a Sharps container provided to you.
●
Whenever possible, have someone with you for at least 15 to 30 minutes after 
your injection.
●
Call your doctor IMMEDIATELY if you experience any itching, hives, 
shortness of breath, or any symptom that has you concerned.  If you are unable 
to reach your doctor or if you experience life-threatening symptoms, call
______________________ or proceed to your nearest emergency room.
Injection Procedures (Vials)
1.
Setting up for an injection
●
Find a clean flat surface.
●
Do not use if the seals on the carton are broken or missing.  Contact your study 
doctor's office if the seals are broken.
●
Take one kit with the vial(s) of adalimumab from the refrigerator.  Do not use 
a vial that has been frozen or if it has been left in direct sunlight.
●
Return any unused vial(s) to the refrigerator.
You will need the following items for each dose:
●
study medication

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sterile capped syringe(s)
●
alcohol prep(s)
●
cotton ball or gauze pad(s)
If you do not have all of the items you need to give yourself an injection, call your study 
physician.  Use only the items provided in the box your adalimumab comes in.
●
Make sure the liquid in the vial is clear and colorless.  Do not use if the liquid 
is cloudy or discolored or has flakes or particles in it.
●
Have a special Sharps (puncture proof) container nearby for disposing of used 
needles and syringes.
For your protection, it is important that you follow these instructions.
2.
Choosing and preparing an injection site
●
Wash your hands well.
●
Choose a site on the front of your thighs or your stomach area (abdomen).  If 
you choose your abdomen, you should avoid the area 2 inches around your 
belly button (navel).

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●
Choose a different site each time you give yourself an injection.  Each new 
injection should be given at least 1 inch from a site you used before.  Never 
inject into areas where the skin is tender, bruised, red or hard or where you 
have scars or stretch marks.
●
If you have psoriasis, you should try not to inject directly into any raised, 
thick, red or scaly skin patches or lesions.
●
You may find it helpful to keep notes on the location of your injection sites.
●
Wipe the site where adalimumab is to be injected with an alcohol prep (swab), 
using a circular motion.  Do not touch this area again until you are ready to 
inject.
3.
How to prepare your adalimumab dose for injection with a vial
●
Remove the plastic cap from the vial.
●
Wipe the gray stopper with an alcohol swab and discard alcohol swab.
●
Place the vial upright on a hard, flat surface.
●
Remove the needle cover from the syringe.  (The needle is sterile, so be very 
careful not to touch the needle or allow it to touch any surface.)
●
With the vial sitting on a hard, flat surface, insert needle straight down through 
the center of the gray stopper.  If the needle is correctly lined up, you should 
feel slight resistance and then a "pop" as the needle penetrates the center of the 
stopper.  (Be careful not to insert the needle at an angle as this may cause the 
needle to bend.  If the needle is not correctly aligned, you will feel constant 
resistance as it penetrates the stopper and will not feel a "pop.")
●
Push the plunger in, forcing air into the vial.

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●
With the needle still in place, turn the vial upside down.  Keeping the vial at 
eye level, slowly pull the plunger back to draw the liquid into the syringe.  
This will cause the bubbles to rise to the top of the syringe.  (As the liquid level 
in the vial drops, you may have to withdraw the needle partially to keep the tip 
of the needle in the liquid.)
●
Adjust the volume in the syringe to the quantity advised by your physician.
●
With the needle still in the vial, check the syringe for air bubbles.  To remove 
any air bubbles, start by gently tapping the syringe.
●
Slowly press the plunger to push any bubbles out of the syringe and into the 
vial.  (If you accidentally push any liquid back into the vial, draw the liquid 
back into the syringe and check again for air bubbles.  It's okay for a small 
amount of liquid to remain in the vial.)
●
Withdraw the needle from the vial, being careful not to touch it to any surface.
●
Take the syringe in one hand.
●
Hold the syringe upright with the needle facing down.
●
Turn the syringe so the needle is facing up and slowly push the plunger in to 
push the air in the syringe out through the needle.  If a small drop of liquid 
comes out of the needle that is okay.
●
Do not shake the syringe.
4.
Injecting Adalimumab
●
With your other hand, gently squeeze an area of the cleaned area of skin and 
hold it firmly.
●
You will inject into this raised area of skin.  Hold the syringe like a pencil at 
about a 45° angle (see picture) to the skin.

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●
With a quick, short, "dart-like" motion, push the needle into the skin.
●
After the needle is in, let go of the skin.  Pull back slightly on the plunger.  If 
blood appears in the syringe it means that you have entered a blood vessel.  Do 
not inject adalimumab.  Pull the needle out of the skin and repeat the steps to 
choose and clean a new injection site.  Do not use the same syringe.  Dispose 
of it in your special Sharps container.  If no blood appears, slowly push the 
plunger all the way in until all of the adalimumab is injected.
●
When the syringe is empty, remove the needle from the skin keeping it at the 
same angle it was when it was pushed into the skin.
●
After injection, immediately apply a single finger stroke to the 
Activation-AssistTM lever arm to activate the shielding mechanism.
●
Press a cotton ball or gauze pad over the injection site and hold it for 
10 seconds.  Do not rub the injection site.  You may have slight bleeding.  This 
is normal.
●
Dispose of the syringe right away into your Sharps container.

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Appendix M.
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 N.
The 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
Screen
Chemistry, hCG#
2.5
12.5
Hepatitis Serology
2.5
ANA/dsDNA
2.5
Hematology
2.0
QuantiFERON TB Gold**
3.0
Baseline
Chemistry, hCG*, hsCRP
2.5
21.0
Hematology
2.0
Infliximab and HACA
4.0
Adalimumab
2.0
AAA
2.0
Serologic Markers and Cytokines***
4.0
mRNA***
2.5
PG***
2.0
Week 1
hCG*
2.5
2.5
Week 2
Chemistry, hCG*, hsCRP
2.5
6.5
Hematology
2.0
Adalimumab
2.0
Week 4
Chemistry, hCG*, hsCRP
2.5
8.5
Hematology
2.0
Adalimumab
2.0
AAA
2.0
Week 8
Chemistry, hCG*, hsCRP
2.5
15.0
Hematology
2.0
Adalimumab
2.0
AAA
2.0
Serologic Markers and Cytokines***
4.0
mRNA***
2.5

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Visit
Measurement
Volume 
(mL)
Total Blood 
Volume (mL)/ 
Visit
Week 12
Chemistry, hCG*, hsCRP
2.5
6.5
Hematology
2.0
Adalimumab
2.0
Week 18
Chemistry, hCG*, hsCRP
2.5
4.5
Hematology
2.0
Week 26
Chemistry, hCG*, hsCRP
2.5
15.0
Hematology
2.0
Adalimumab
2.0
AAA
2.0
Serologic Markers and Cytokines***
4.0
mRNA***
2.5
Week 34
Chemistry, hCG*, hsCRP
2.5
6.5
Hematology
2.0
Adalimumab
2.0
Week 42
Chemistry, hCG*, hsCRP
2.5
4.5
Hematology
2.0
Week 
52/Premature 
Discontinuation
Chemistry, hCG,# hsCRP
2.5
18.0
Hematology
2.0
Adalimumab
2.0
AAA
2.0
Serologic Markers and Cytokines***
4.0
mRNA***
2.5
QuantiFERON TB Gold^
3.0
Total
121
#
Only performed in female of childbearing potential.
*
Only performed in female of childbearing potential that has positive urine pregnancy test.
**
Subjects will not have the QuantiFERON test performed, if a PPD test is used or in case of a negative test within 
90 days prior to Screening, provided nothing has changed in the subject's medical history.
*** Samples will only be collected for subjects who signed the separate informed consent.
^
For subjects with a negative TB test at Screening, TB test will be required at Week 52.  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, at Screening, or testing performed at any time point during the study).

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Appendix O.
Protocol Amendment:  List of Changes
The summary of changes is listed in Section 1.1.
Specific Protocol Changes
Section 1.2  Synopsis
Previously read:
AbbVie Inc.
Protocol Number:  M11-290
Name of Study Drug:  Adalimumab
Phase of Development:  3
Name of Active Ingredient:  Adalimumab
Date of Protocol Synopsis:  02 November 2017
Protocol Title:
A Multicenter, Randomized, Double-Blind Study of the Human Anti-TNF Monoclonal Antibody 
Adalimumab in Pediatric Subjects with Moderate to Severe Ulcerative Colitis
Objective:
The objective of the study is to demonstrate the efficacy and safety, and to assess the pharmacokinetics of 
adalimumab administered subcutaneously (SC) in pediatric subjects with moderate to severe ulcerative 
colitis (UC).
Investigators:  Multicenter
Study Sites:  Approximately 50 sites worldwide for the main study and approximately 10 sites for the 
Japan sub-study.
Study Population:
Subjects with moderate-to-severe UC from the ages of 4 to 17 prior to Baseline dosing.
Number of Subjects to be Enrolled:  Approximately 85 subjects for the main study and up to 
approximately 20 subjects for the Japan sub-study
Methodology:
This is a Phase 3, multicenter, randomized, double-blind trial designed to evaluate the efficacy and safety 
of adalimumab in pediatric subjects with moderate to severe ulcerative colitis, who have failed therapy 
with corticosteroids and/or immunosuppressants.

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Methodology (Continued):
Approximately 85 pediatric subjects for the main study (and up to approximately 20 subjects for the 
Japan sub-study) with moderate-to-severe UC (Mayo Score of 6 to 12 points with an endoscopy subscore 
of 2 to 3, confirmed by central reader) will be enrolled at approximately 50 sites worldwide (and 
approximately 10 sites for the Japan sub-study).  The study will allow enrollment of up to 25% of anti-
TNF experienced subjects.  Prior to Amendment 4, subjects who met all of the inclusion criteria and none 
of the exclusion criteria were to be enrolled and randomized 3:2 at Baseline to one of two double-blinded 
adalimumab induction doses (high dose or standard dose).  The randomization was to be stratified by 
baseline disease severity (per Mayo score), prior exposure to anti-TNF, and corticosteroid use at 
Baseline.  During the randomized double-blind induction period, subjects assigned to high induction dose 
group received adalimumab 2.4 mg/kg (maximum dose of 160 mg) at Baseline and at Week 1.  At 
Week 2, subjects received adalimumab 1.2 mg/kg (maximum dose of 80 mg), followed by a dose of 
0.6 mg/kg (maximum dose of 40 mg) at Week 4 and Week 6.  Subjects randomized to the standard 
induction dose group received adalimumab 2.4 mg/kg (maximum dose of 160 mg) at Baseline and 
matching placebo at Week 1, adalimumab 1.2 mg/kg (maximum dose of 80 mg) at Week 2, followed by a 
dose of 0.6 mg/kg (maximum dose of 40 mg) at Week 4 and Week 6.  After Amendment 4, subjects who 
meet all of the inclusion criteria and none of the exclusion criteria will be enrolled into the study and 
receive open-label adalimumab high induction dose.  During the open-label induction period, subjects 
will receive adalimumab 2.4 mg/kg (maximum dose of 160 mg) at Baseline and at Week 1.  At Week 2, 
subjects will receive adalimumab 1.2 mg/kg (maximum dose of 80 mg), followed by a dose of 0.6 mg/kg 
(maximum dose of 40 mg) at Week 4 and Week 6.  
Ongoing subjects randomized prior to Amendment 4 will continue their blinded treatment during the 
induction period until Week 8.  
Prior to Amendment 4, at Week 8, subjects demonstrating a clinical response per Partial Mayo Score 
(PMS) (defined as a decrease in PMS ≥ 2 points and ≥ 30% from Baseline) were randomized and 
stratified by Week 8 remission status per PMS (defined as a PMS ≤ 2 and no individual subscore > 1) and 
Induction dose in a 2:2:1 ratio to one of two adalimumab maintenance treatment groups (Standard dose 
[0.6 mg/kg (maximum dose of 40 mg) every other week] or High dose [0.6 mg/kg (maximum dose of 
40 mg) every week]) or to placebo, respectively.
After Amendment 4, at Week 8, subjects demonstrating a clinical response per Partial Mayo Score (PMS) 
(defined as a decrease in PMS ≥ 2 points and ≥ 30% from Baseline) will be randomized and stratified by 
Week 8 remission status per PMS (defined as a PMS ≤ 2 and no individual subscore > 1) in a 1:1 ratio to 
one of two adalimumab maintenance treatment groups (Standard dose [0.6 mg/kg (maximum dose of 
40 mg) every other week] or High dose [0.6 mg/kg (maximum dose of 40 mg) every week]).
Subjects will receive blinded treatment every week (ew) beginning at Week 8 and will remain on 
double-blinded therapy through Week 52.
!
Subjects who are randomized to standard dose will receive a maintenance dose of 0.6 mg/kg 
(maximum dose of 40 mg) every other week (eow) and will receive the matching placebo at the 
alternate week.
!
Subjects who are randomized to high dose will receive a maintenance dose of 0.6 mg/kg 
(maximum dose of 40 mg) ew.
!
Subjects who were randomized to placebo prior to Amendment 4 receive matching placebo ew.  

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Methodology (Continued):
Ongoing subjects randomized prior to Amendment 4 will continue their blinded treatment during the 
maintenance period until Week 52 and re-randomization to treatment for disease flare will be done 
according to Amendment 3 stipulations in these subjects.
At Week 8, subjects who have not achieved a clinical response per PMS will be discontinued.  A safety 
evaluation call will be made 70 days after the last dose of study drug is administered to obtain follow-up 
information on any ongoing or new adverse events.
The duration of the study could be up to 66 weeks, which includes a Screening Period of up to 28 days, 
8-week induction period and a 44-week double-blind maintenance period and a 70-day follow-up.  Upon 
completion of the study, subjects will have the option to enroll into an open-label extension study where 
they will receive open-label adalimumab.
Treatment of Subjects with Disease Flare During the Study:
Criteria for Disease Flare are as follows:
!
Subjects with a Week 8 PMS of 0 to 2 who present with a PMS at least 3 points greater than 
their Week 8 score.
!
Subjects with a Week 8 PMS of 3 to 4 who present with a PMS at least 2 points greater than 
their Week 8 score.
!
Subjects with a Week 8 PMS of 5 to 6 who present with a PMS at least 1 point greater than their 
Week 8 score.
Subjects will be expected to remain on blinded therapy throughout the 44-week maintenance period.  
However, subjects with a disease flare, may be re-randomized to receive the following blinded-treatment 
at or after Week 12:
!
Subjects who are randomized to Standard maintenance dose (0.6 mg/kg [maximum dose of 
40 mg] eow) will be re-randomized to receive either adalimumab re-induction dose (2.4 mg/kg 
[maximum of 160 mg]) or adalimumab (0.6 mg/kg [maximum of 40 mg]) at the visit.  
Afterwards, all subjects will resume receiving the standard dose (0.6 mg/kg [maximum of 
40 mg] eow) within the original dosing schedule.
!
Subjects who are randomized to High maintenance dose (0.6 mg/kg [maximum dose of 40 mg] 
ew) will be re-randomized to receive either adalimumab re-induction dose (2.4 mg/kg 
[maximum of 160 mg]) or adalimumab (0.6 mg/kg [maximum of 40 mg]) at the visit.  The 
following week, all subjects will resume receiving the high dose (0.6 mg/kg [maximum of 
40 mg] ew).
!
Subjects who were randomized to placebo prior to Amendment 4 will be re-randomized to 
receive either adalimumab re-induction dose (2.4 mg/kg [maximum of 160 mg] or to receive 
adalimumab (0.6 mg/kg [maximum of 40 mg]) at the visit.  Afterwards, all subjects will receive 
the standard dose (0.6 mg/kg [maximum of 40 mg] eow) within the original dosing schedule.
If a subject continues to meet the definition of disease flare (2nd time) following at least a 4-week course 
of blinded therapy since the subject has been re-randomized for disease flare, they may be switched to 
open-label adalimumab every week at the dose 0.6 mg/kg [maximum of 40 mg].  If a subject was 
re-randomized at Week 12 (to receive either re-induction dose (2.4 mg/kg [maximum of 160 mg]) or to 
receive adalimumab (0.6 mg/kg [maximum of 40 mg]), then the earliest that subject could be evaluated to 
determine if the subject meets the criteria for disease flare for switch to OL (0.6 mg/kg [maximum of 
40 mg]) weekly dosing is at Week 16.

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Methodology (Continued):
Treatment of Subjects with Disease Flare During the Study (Continued):
If a subject continues to meet the definition of disease flare (3rd time) following a 4-week course of 
open-label adalimumab every week at the dose 0.6 mg/kg [maximum of 40 mg], they may be switched to 
receive adalimumab open-label 40 mg ew (maximum dose, not weight-based).
Subjects with persistent disease flare while on adalimumab 40 mg ew (max dose) may be withdrawn 
from the study at the investigator's discretion.
During open-label rescue therapy, subjects who are responders and have been in remission for at least 
8 consecutive weeks (PMS ≤ 2 with no individual subscore > 1) may have their dosage decreased from 
ew to eow.  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.  The investigator should receive prior approval 
from the medical monitor before taking any action with regard to dose re-escalation.
For subjects who meet the criteria for dose change, blood samples (adalimumab, AAA and hs-CRP) will 
be collected just prior to receiving any dose change (blinded therapy, escape to open-label adalimumab, 
dose de-escalation and dose re-escalation).
Subjects are allowed to be treated with stable doses of UC-related concomitant medications during the 
study, with the following exceptions and requirements:
!
At or after Week 4, subjects taking corticosteroid therapy at Baseline may have their 
corticosteroid therapy tapered based on the investigator's discretion.  A proposed tapering 
schedule is specified in Section 5.3.1.1.
!
From Week 4 to Week 12, if the subject should experience an increase in symptoms after 
corticosteroid was tapered, the subject may have their corticosteroid dose increased back up to 
the corticosteroid dose at Baseline.  This increase must be discussed with and approved by the 
Medical Monitor prior to any changes in these treatments.
!
Subjects who experience disease flare at or after Week 12 are allowed to change their dose or 
initiate treatment with corticosteroids, immunosuppressant or 5-ASA; these increases must be 
discussed with and approved by the Medical Monitor prior to any changes in these treatments.
!
Immunosuppressant doses may be decreased or terminated in the event of moderate-to-severe 
treatment-related toxicities.
!
Immunosuppressant therapy may be discontinued at or after Week 12 at the investigator's 
discretion.
At each study visit, in addition to routine physical examination including evaluation of extra intestinal 
manifestations and calculation of the PMS and PUCAI, the following will be collected:
!
Anthropometric evaluations at Baseline, Week 26 and Week 52/Premature Discontinuation for 
determination of body mass index (BMI), and "z" scores for height and weight.
!
IMPACT III Quality of Life questionnaire at Baseline, Week 8, Week 26 and 
Week 52/Premature Discontinuation Visit will be completed for subjects 9 years or older at the 
Baseline study visit.
!
Bone age determination by x-ray of the wrist at Screening and at Week 52/Premature 
Discontinuation Visit in subjects who have not completed linear growth.
!
Serum for measurement of adalimumab concentrations just prior to dosing at Baseline, Week 2, 
Week 4, Week 8, Week 12, Week 26 Week 34 and Week 52/Premature Discontinuation Visit 
and at Unscheduled Visit requiring dose change.

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Methodology (Continued):
Treatment of Subjects with Disease Flare During the Study (Continued):
!
Serum for measurement of Anti-Adalimumab Antibodies (AAA) just prior to dosing at 
Baseline, Week 4, Week 8, Week 26 and Week 52/Premature Discontinuation Visit and at 
Unscheduled Visit requiring dose change.
!
Tanner stage at Baseline, Week 26 and Week 52/Premature Discontinuation Visit.
!
Endoscopy subscore at Screening and Week 52/Premature Discontinuation Visit.
Diagnosis and Main Criteria for Inclusion/Exclusion:
Main Inclusion:
1.
Subjects from the ages of 4 to 17 prior to baseline dosing.
2.
Subjects with a diagnosis of UC for at least 12 weeks prior to screening confirmed by endoscopy 
with biopsy.
A colonoscopy will be performed during the screening period unless the subject underwent a 
colonoscopy within 12 months prior to Screening and appropriate documentation is available (to 
confirm the diagnosis without evidence of dysplasia, colon cancer or infection).  In this case the 
screening endoscopy may be either a colonoscopy or a flexible sigmoidoscopy.
If the subject underwent an endoscopy within 56 days of Baseline, and a video recording of the 
endoscopy is available, the video recording may be used and no additional endoscopy will be 
performed during the Screening period provided that the conditions noted in Section 5.3.1.1 are met 
and all technical requirements are fulfilled.
Note:
!
If no appropriate documentation for confirmation of the diagnosis is available as per the
investigator's judgment a diagnostic biopsy must also be performed.  
!
Biopsies to rule out dysplasia, colon cancer and infection may be taken at the investigator's 
discretion.
3.
Active ulcerative colitis with a Mayo Score of 6 – 12 points and endoscopy subscore of 2 – 3 
(confirmed by central reader) despite concurrent treatment with at least one of the following (oral 
corticosteroids or immunosuppressants or both as defined below):
!
Oral prednisone of ≥ 2 mg/day or equivalent, but not exceeding 40 mg/day, or oral budesonide 
≥3 mg/day, but not exceeding 9 mg/day, with a stable dose for at least 7 days prior to Baseline; 
and/or
!
At least a consecutive 28-day course of azathioprine or 6-MP or methotrexate (MTX) prior to 
Baseline, with a stable dose prior to Baseline of azathioprine ≥ 1.5 mg/kg/day or 6-MP 
≥1 mg/kg/day (rounded to the nearest available tablet or half tablet formulation) or a 
documented 6-TGN level of 230 – 450 pmol/8 × 108 RBC on the current dosing regimen or 
MTX ≥ 15 mg/m2 body surface area/week, or a dose that is the highest tolerated by the subject 
(e.g., due to leukopenia, elevated liver enzymes, nausea) during that time.
Note:  If subjects are on both oral corticosteroid and immunosuppressants BOTH of the drugs 
need to meet the above criteria; and/or
!
Concurrent therapy with corticosteroids or immunosuppressants (azathioprine, 6-MP or 
MTX) is not required for subjects who were previously treated during the past 1 year and 
have confirmed documentation of failure to respond, or were previously treated during the 
past 5 years and have confirmed documentation indicating lack of tolerability.

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Diagnosis and Main Criteria for Inclusion/Exclusion (Continued):
Main Inclusion (Continued):
4.
Parent or guardian has voluntarily signed and dated an informed consent form, approved by an 
Institutional Review Board (IRB)/Independent Ethics Committee (IEC), after the nature of the study 
has been explained and the subject's parent or legal guardian has had the opportunity to ask 
questions.  The informed consent must be signed before any study-specific procedures are performed 
or before any concomitant medication is discontinued for the purpose of this study.  Pediatric 
subjects will be included in all discussions in order to obtain verbal and/or written assent.
5.
Subjects must be able and willing to self-administer SC injections or have a qualified person 
available to administer SC injections.
6.
Subject has a negative TB Screening Assessment.
If a subject has a positive (≥5 mm induration) PPD test and/or IGRA test at Screening, a CXR 
(PA and lateral view) must be performed for evaluation of active TB disease.  If the subject has 
evidence of a latent TB infection, the subject must initiate and complete a minimum of 2 weeks (or 
per local guidelines, whichever is longer) of an ongoing course of TB prophylaxis or have 
documented completion of a full course of TB prophylaxis, prior to Baseline.
7.
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 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, foams, jellies, diaphragm or intrauterine device (IUD);
!
Hormonal contraceptives for 90 days prior to study drug administration;
!
A vasectomized partner.
8.
Subject is judged to be in good health as determined by the Principal Investigator based upon the 
results of medical history, laboratory profile, physical examination, chest x-ray (CXR), and a 12-lead 
electrocardiogram (ECG) performed during Screening.
Main Exclusion:
1.
Subject with Crohn's disease (CD) or indeterminate colitis (IC).
2.
Current diagnosis of fulminant colitis and/or toxic megacolon.
3.
Subjects with disease limited to the rectum (ulcerative proctitis) during the screening endoscopy.
4.
Therapeutic enema or suppository within 14 days prior to the Screening endoscopy and during the 
remainder of the Screening Period.
5.
History of colectomy or subtotal colectomy (with ostomy) or is planning bowel surgery.
6.
Received cyclosporine, tacrolimus, or mycophenolate mofetil, within 30 days prior to Baseline.
7.
Female subjects who are breast-feeding or considering becoming pregnant during the study.
8.
Positive pregnancy test at Screening or Baseline.
9.
History of clinically significant drug or alcohol abuse in the last 12 months.

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Diagnosis and Main Criteria for Inclusion/Exclusion (Continued):
Main Exclusion (Continued):
10. Subjects on azathioprine or 6-mercaptopurine (6-MP) or MTX and subjects:
!
Have not been on stable doses of these medications for at least 28 days prior to Baseline; or 
!
Have discontinued these medications within 28 days of Baseline.
11. Subjects on oral aminosalicylates who:
!
Have not been on stable doses of these medications for at least 14 days prior to Baseline; or
!
Have discontinued use of aminosalicylates within 14 days of Baseline.
12. Subjects on growth hormone who have not been on a stable dose for at least 4 weeks prior to 
Baseline.
13. Subjects on oral corticosteroids who:
!
Have not been on stable doses of these drugs for at least 7 days prior to Baseline; or
!
Discontinued use of oral corticosteroid within 14 days of Baseline; or
!
Have been taking both budesonide and prednisone (or equivalent) simultaneously.
14. Received intravenous corticosteroids within 5 days prior to Screening or during the Screening 
Period.
15. Subject who has previously used infliximab or any anti-TNF agent within 56 days of Baseline.
16. Subject who has previously used infliximab or any anti-TNF agent and has not clinically responded 
at any time ("primary non-responder") unless subject experienced a treatment limiting reaction.
17. Previous treatment with adalimumab or previous participation in an adalimumab clinical study.
18. Positive Clostridium difficile (C. difficile) stool assay during the Screening Period.
19. Currently receiving total parenteral nutrition (TPN).
20. History of demyelinating disease (including myelitis) or neurologic symptoms suggestive of 
demyelinating disease.
21. History of invasive infection (e.g., listeriosis and histoplasmosis), human immunodeficiency 
syndrome (HIV).
22. 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.
23. Subjects with any active viral infection that based on the investigator's clinical assessment makes the 
subject an unsuitable candidate for the study.
24. Subject with a positive result for the Hepatitis B surface antigen (HBs Ag) or any HBV DNA PCR 
result that meets or exceeds detection sensitivity will be excluded.
25. Chronic recurring infections or active TB.
26. Subject has been treated with any investigational drug of chemical or biologic nature or any 
investigational procedure (including previous fecal transplantation) within 30 days or 5 half-lives 
(whichever is longer) of the drug prior to the Baseline Visit.
27. Infection(s) requiring treatment with intravenous (IV) anti-infectives within 30 days prior to the 
Baseline Visit or oral anti-infectives within 14 days prior to the Baseline Visit.
28. Prior exposure to biologics that have a potential or known association with PML (i.e., natalizumab 
(Tysabri®) or efalizumab (Raptiva®) or rituximab (Rituxan®).

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Diagnosis and Main Criteria for Inclusion/Exclusion (Continued):
Main Exclusion (Continued):
29. Known hypersensitivity to adalimumab or its excipients.
30. Evidence of dysplasia or 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.
If the Screening endoscopy shows evidence of dysplasia or malignancy, subject may not be enrolled in 
the study.
31. Screening laboratory and other analyses show any of the following abnormal results:
!
ECG – with clinically significant abnormalities;
!
Aspartate transaminases (AST) or alanine transaminase (ALT) > 1.75 × the upper limit of the 
reference range;
!
Total bilirubin ≥ 3 mg/dL;
!
Serum creatinine > 1.6 mg/dL;
!
Clinically significant abnormal screening laboratory results as evaluated by the Investigator.
32. Subject is considered by the Investigator, for any reason, to be an unsuitable candidate for the study.
Investigational Product:
Adalimumab
Induction Dose:
Body weight adjusted induction dose regimen
Prior to Amendment 4 subjects were randomized to receive one of 
2 double-blind adalimumab induction doses.
Standard Induction Dose:  2.4 mg/kg (maximum dose of 160 mg) at 
Week 0 and matching placebo at Week 1.  Subjects received 
1.2 mg/kg (maximum dose of 80 mg) at Week 2. At Weeks 4 and 6, 
subjects received a dosing regimen of 0.6 mg/kg (maximum dose of 
40 mg).
High Induction Dose:  2.4 mg/kg (maximum dose of 160 mg) at 
Week 0 and Week 1.  Subjects received 1.2 mg/kg (maximum dose of 
80 mg) at Week 2.  At Weeks 4 and 6, subjects received a dosing 
regimen of 0.6 mg/kg (maximum dose of 40 mg).
After Amendment 4 subjects will receive the open-label adalimumab 
high induction dose.
High Induction Dose:  2.4 mg/kg (maximum dose of 160 mg) at 
Week 0 and Week 1.  Subjects will receive 1.2 mg/kg (maximum 
dose of 80 mg) at Week 2.  At Weeks 4 and 6, subjects will receive a 
dosing regimen of 0.6 mg/kg (maximum dose of 40 mg).

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Double-Blind Maintenance 
Doses (in Week 8 PMS 
Responders only):
Body weight adjusted maintenance dose regimen
Blinded adalimumab Standard dosing regimen:  0.6 mg/kg 
(maximum dose of 40 mg) eow with matching placebo at the 
alternate week
Blinded adalimumab High dosing regimen:  0.6 mg/kg (maximum 
dose of 40 mg) ew
Subjects who were randomized to placebo (prior to Amendment 4) 
receive placebo ew.  
At or after Week 12 subjects who demonstrate a disease flare may be 
re-randomized to receive the following blinded-treatment.
!
Subjects, who are randomized to standard maintenance 
dose, will be re-randomized to receive either adalimumab 
re-induction dose (2.4 mg/kg [maximum of 160 mg]) or to 
adalimumab (0.6 mg/kg [maximum of 40 mg]) at the visit.  
Afterwards, all subjects will resume to receiving the 
standard dose adalimumab (0.6 mg/kg [maximum of 40 mg] 
eow) within the original dosing schedule.
!
Subjects who are randomized to high maintenance dose, will 
be re-randomized to receive either adalimumab re-induction 
dose (2.4 mg/kg [maximum of 160 mg]) or to receive 
adalimumab (0.6 mg/kg [maximum of 40 mg]) at the visit.  
The following week, all subjects will resume to receiving 
the high dose (0.6 mg/kg [maximum of 40 mg] ew).
!
Subjects who were randomized to placebo prior to 
Amendment 4 will be re-randomized to receive either 
adalimumab re-induction dose (2.4 mg/kg [maximum of 
160 mg] or to receive adalimumab (0.6 mg/kg [maximum of 
40 mg]) at the visit.  Afterwards, all subjects will receive the 
standard dose (0.6 mg/kg [maximum of 40 mg] eow) within 
the original dosing schedule.
Open-Label Maintenance 
Doses:
High dose body weight adjusted.
0.6 mg/kg (maximum dose of 40 mg) ew
If a subject continues to meet the definition of disease flare following 
a 4-week course of open-label adalimumab ew at the dose 0.6 mg/kg 
[maximum of 40 mg], they may be switched to receive adalimumab 
40 mg ew (maximum dose, not weight-based).
Mode of Administration:
Subcutaneous injection (SC)
Reference Therapy:
NA (after Amendment 4); Placebo (prior to Amendment 4)
Dose:
NA
Mode of Administration:
NA (after Amendment 4); Subcutaneous injection (SC) (prior to 
Amendment 4)

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Duration of Treatment:  52 weeks
!
The subjects will visit the site at Screening, Baseline, Weeks 1, 2, 4, 8, 12, 18, 26, 34, 42, and 
52/Premature Discontinuation and Unscheduled Visits.
!
Subjects who qualify will be given the opportunity to enroll into an open-label study of the 
Long-term Safety and Tolerability of Repeated Administration of Adalimumab.
A 70-Day Follow-Up phone call will be completed for all subjects who either terminate early from the 
study or do not rollover into the extension study.
Criteria for Evaluation:
Efficacy analysis will be based on the Intent-To-Treat (ITT) population for the induction period and 
modified ITT (mITT) population for the maintenance period.  The ITT population consists of all 
randomized subjects who received at least one SC injection of the study medication.  Subjects who 
receive open-label high induction dose will be excluded from the ITT population.  The mITT population 
consists of all Week 8 PMS Responders who were randomized at Week 8 and received at least one SC 
injection of the study medication during maintenance period.  
The safety analysis set will include all subjects who received at least one SC injection of the study 
medication.
Efficacy:
This study will utilize the Mayo Score, PMS and Mayo subscores to measure efficacy.  The PUCAI will 
also be utilized as applicable.
Primary Efficacy Endpoints
The co-primary efficacy endpoints are:
1.
The proportion of subjects who achieve clinical remission at Week 8 as measured by PMS (defined 
as a PMS ≤ 2 and no individual subscore > 1) in the high induction dose group as compared to 
external placebo.
2.
The proportion of subjects who responded at Week 8 per PMS and achieve clinical remission at 
Week 52 as measured by Mayo score (defined as a Mayo Score ≤ 2 and no individual subscore > 1) 
in the high maintenance dose group as compared to external placebo.
External placebo rates will be identified from an ongoing meta-analysis of relevant publically available 
clinical trials.
Ranked secondary efficacy endpoints are:
1.
Proportion of subjects who achieve mucosal healing at Week 52 as measured by Mayo endoscopy 
subscore (defined as ≤ 1) in Week 8 responders per PMS (high maintenance dose versus external 
placebo);
2.
Proportion of subjects who achieve Mayo clinical remission at Week 52 in Week 8 remitters per 
PMS (high maintenance dose versus external placebo) (*);
3.
Proportion of subjects in PUCAI remission (defined as < 10) at Week 52 in Week 8 responders per 
PMS (high maintenance dose versus external placebo) (*);
4.
Proportion of subjects in Mayo clinical response at Week 52 in Week 8 responders per PMS 
(high maintenance dose versus external placebo);
5.
Proportion of subjects in PUCAI response (defined as a decrease in PUCAI ≥ 20 points from 
Baseline) at Week 52 in Week 8 responders per PMS (high maintenance dose versus external 
placebo) (*);

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Criteria for Evaluation (Continued):
Efficacy (Continued):
6.
Proportion of subjects receiving corticosteroid at Baseline who discontinue corticosteroid prior to 
Week 52 and are in Mayo clinical remission at Week 52 in Week 8 responders per PMS (high 
maintenance dose versus external placebo) (*);
7.
Proportion of subjects receiving corticosteroid at Baseline who discontinue corticosteroid prior to 
Week 52 and are in PUCAI remission at Week 52 in Week 8 responders per PMS (high maintenance 
dose versus external placebo) (*);
8.
Proportion of subjects in Partial Mayo clinical remission at Week 52 in Week 8 responders per PMS 
(high maintenance dose versus external placebo);
9.
Proportion of subjects in Partial Mayo clinical remission at Week 8 (standard induction dose versus 
external placebo);
10. Proportion of subjects in Mayo clinical remission at Week 52 in Week 8 responders per PMS 
(standard maintenance dose versus external placebo);
11. Proportion of subjects who achieve mucosal healing at Week 52 as measured by Mayo endoscopy 
subscore in Week 8 responders per PMS (standard maintenance dose versus external placebo);
12. Proportion of subjects who achieve Mayo clinical remission at Week 52 in Week 8 remitters per 
PMS (standard maintenance dose versus external placebo) (*);
13. Proportion of subjects in PUCAI remission at Week 52 in Week 8 responders per PMS 
(standard maintenance dose versus external placebo) (*);
14. Proportion of subjects in Mayo clinical response at Week 52 in Week 8 responders per PMS 
(standard maintenance dose versus external placebo);
15. Proportion of subjects in PUCAI response at Week 52 in Week 8 responders per PMS 
(standard maintenance dose versus external placebo) (*);
16. Proportion of subjects receiving corticosteroid at Baseline who discontinue corticosteroid prior to 
Week 52 and are in Mayo clinical remission at Week 52 in Week 8 responders per PMS (standard 
maintenance dose versus external placebo) (*);
17. Proportion of subjects receiving corticosteroid at Baseline who discontinue corticosteroid prior to 
Week 52 and are in PUCAI remission at Week 52 in Week 8 responders per PMS 
(standard maintenance dose versus external placebo) (*);
18. Proportion of subjects in Partial Mayo clinical remission at Week 52 in Week 8 responders per PMS 
(standard maintenance dose versus external placebo).
(*) If external placebo data are not available, results will only be summarized by maintenance dose 
group and 95% confidence intervals (CI) will be provided.
Additional secondary endpoints are the following:
!
Proportion of subjects in Partial Mayo clinical remission at Week 8 (high induction dose versus 
standard induction dose);
!
Proportion of subjects who achieve mucosal healing at Week 52 as measured by Mayo 
endoscopy subscore (defined as ≤ 1) (high maintenance dose versus standard maintenance 
dose);
!
Proportion of subjects in PUCAI remission (defined as < 10) at Week 52 (high maintenance 
dose versus standard maintenance dose);
!
Proportion of subjects in Mayo clinical response at Week 52 (high maintenance dose versus 
standard maintenance dose);

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Criteria for Evaluation (Continued):
Efficacy (Continued):
!
Proportion of subjects in Mayo clinical remission at Week 52 (high maintenance dose versus 
standard maintenance dose);
!
Proportion of subjects in PUCAI response (defined as a decrease in PUCAI ≥ 20 points from 
Baseline) at Week 52 (high maintenance dose versus standard maintenance dose);
!
Proportion of subjects receiving corticosteroid at Baseline who discontinue corticosteroid  prior 
to Week 52 and are in Mayo clinical remission at Week 52 (high maintenance dose versus 
standard maintenance dose);
!
Proportion of subjects receiving corticosteroid at Baseline who discontinue corticosteroid prior 
to Week 52 and are in PUCAI remission at Week 52 (high maintenance dose versus standard 
maintenance dose);
!
Proportion of subjects in Partial Mayo clinical remission at Week 52 (high maintenance dose 
versus standard maintenance dose);
!
Proportion of subjects in PUCAI remission at Week 8 (high induction dose versus standard 
induction dose);
!
Proportion of subjects in PUCAI response at Week 8 (high induction dose versus standard 
induction dose);
!
Change from Baseline in total IMPACT III Quality of Life scores over time for subjects at least 
9 years old at Baseline;
!
Change from Baseline in WPAI scores over time;
!
Change from Baseline in "z" scores for height (observed height velocity [cm/yr] – mean height 
velocity for age and sex [cm/yr]/SD of the mean) at Week 26 and Week 52;
!
Change from Baseline in BMI at Week 26 and Week 52;
!
Change from Baseline in "z" scores for weight-for-age at Week 26 and Week 52;
!
Proportion of subjects at appropriate Tanner stage at Week 26 and Week 52 compared to 
Baseline;
!
Proportion of subjects in Partial Mayo response over time;
!
Proportion of subjects in Partial Mayo remission over time;
!
Proportion of subjects in PUCAI response over time;
!
Proportion of subjects in PUCAI remission over time;
!
Change from Baseline in number of daily stool over time;
!
Change from Baseline in albumin and total protein at different time points;
!
Change from Baseline in hemoglobin, hematocrit, red blood cell count at different time points;
!
Change from Baseline in hs-CRP levels at different time points;
!
Proportion of subjects with extraintestinal manifestations (EM) at Week 26 and Week 52 
compared to Baseline;
!
Proportion of subjects with Mayo endoscopy subscore of 0 or 1 (without friability) at Week 52;
!
Proportion of subjects being hospitalized during the study;
!
Proportion of subjects undergoing colectomy during the study;
!
Proportion of subjects receiving corticosteroid at Baseline who discontinue corticosteroid prior 
to Week 52 and completed Week 52;
!
Correlation between PMS and PUCAI at different time points;

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Criteria for Evaluation (Continued):
Efficacy (Continued):
!
Proportion of subjects in a 9 point Mayo (without SFS) clinical remission (defined as ≤ 2 and no 
individual subscore > 1) at Week 52 in Week 8 responders per PMS (high maintenance dose 
versus external placebo) (*);
!
Proportion of subjects in a 9 point Mayo (without PGA) clinical remission (defined as ≤ 2 and 
no individual subscore > 1) at Week 52 in Week 8 responders per PMS (high maintenance dose 
versus external placebo) (*);
!
Proportion of subjects in a 9 point Mayo (without RBS) clinical remission (defined as ≤ 2 and 
no individual subscore > 1) at Week 52 in Week 8 responders per PMS (high maintenance dose 
versus external placebo) (*);
!
Proportion of subjects in a 6 point Mayo (without SFS and endoscopy subscore) clinical 
remission (defined as ≤ 1) at Week 8 (high induction dose versus external placebo) (*);
!
Proportion of subjects in a 6 point Mayo (without PGA and endoscopy subscore) clinical 
remission (defined as ≤ 1) at Week 8 (high induction dose versus external placebo) (*);
!
Proportion of subjects in a 6 point Mayo (without RBS and endoscopy subscore) clinical 
remission (defined as ≤ 1) at Week 8 (high induction dose versus external placebo) (*);
!
Change from Baseline in Mayo score at Week 52;
!
Change from Baseline in PMS over time;
!
Change from Baseline in PUCAI over time;
!
Change from Baseline in endoscopy subscore at Week 52;
!
Change from Baseline in SFS over time;
!
Change from Baseline in RBS over time;
!
Change from Baseline in PGA over time.
(*)  If external placebo data are not available, results will only be summarized in the high maintenance or 
high induction dose group, respectively, and 95% CI will be provided.
Pharmacokinetic:
Blood samples will be collected for the measurement of serum adalimumab concentrations just prior to 
dosing at Baseline, Weeks 2, 4, 8, 12, 26, 34 and 52/Premature Discontinuation Visits, and at 
Unscheduled Visits requiring dose change.  Blood samples will be collected for the measurement of 
serum anti-adalimumab antibody (AAA) just prior to dosing at Baseline, Weeks 4, 8, 26 and 
52/Premature Discontinuation Visits and at Unscheduled Visits requiring dose change.  Blood samples 
will be collected for the measurement of serum Infliximab and HACA at Baseline (prior to dosing).
Safety:
Adverse events, laboratory data, and vital signs will be assessed at all visits throughout the study.

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Statistical Methods:
Efficacy:
The efficacy analysis will be performed in the ITT set for the induction period and in the mITT set for the 
maintenance period. NRI method will be used to impute missing values for binary efficacy endpoints.  
Subjects who do not complete the induction period or who receive rescue therapy during the maintenance 
period will be considered as failures from that time point forward.  Both LOCF and observed case 
analyses will be performed for continuous efficacy endpoints.
The primary efficacy analysis for the co-primary endpoint at Week 8 is based on external placebo 
comparison identified from an ongoing meta-analysis of relevant publically available clinical trials.  In 
order to demonstrate efficacy of adalimumab at Week 8 in the pediatric population, the lower limit of the 
95% CI for the remission rate per PMS in the high induction dose group is required to be higher than the 
upper limit of the 95% CI of the remission rate of external placebo (assumptions based on the adult UC 
Studies M06-826 and M06-827 are shown in the following table for illustrative purposes only).
The primary efficacy analysis for the co-primary endpoint at Week 52 is based on the comparison of the 
high maintenance dose group versus external placebo using the same efficacy criterion described above. 
Placebo Data from Adult UC Studies
Endpoint
Placebo Subjects by Prior Anti-TNF Status
Experienced n/N 
(%)
Naïve n/N
(%)
Weighted Average for 25% 
Experienced +75% Naïve
%
95% CI Upper Limit
Week 8 Partial Mayo Score 
Remission (Pooled 
Studies M06-826 and M06-827 
IAS-E seta)
15/101 
(14.9%)
61/367 
(16.6%)
16.18%
19.52%
Week 52 Mayo
3/101
18/145
10.05%
13.81%
Score Remission
(Study M06-827 ITT set)
(3.0%)
(12.4%)
a.
IAS-E data set consisted of all randomized subjects with confirmed UC who received at least 1 dose of blinded 
study drug in either Study M06-826 or Study M06-827.
  
Secondary endpoints that are of the binary type will be analyzed using 95% confidence intervals.  
Comparisons to external placebo will be done as described above.  Secondary endpoints that are of the 
continuous type will be analyzed as changes from baseline, and reported for the two treatment groups 
including 95% confidence intervals.  
Pharmacokinetic:
Adalimumab trough serum concentrations will be summarized by treatment group at each time point 
using descriptive statistics.  In addition, pharmacokinetic model based analyses will be performed with 
the focus on apparent clearance (CL/F) and apparent volume of distribution (V/F) of adalimumab.

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Statistical Methods (Continued):
Immunogenicity:
AAA will be evaluated for each subject and each regimen, and rates of AAA positive will be calculated.  
As appropriate, the effect of AAA on adalimumab pharmacokinetics, efficacy variable(s), and 
treatment-emergent adverse events may be evaluated.  HACA will be evaluated for each subject and each 
regimen, and rates of HACA positive will be calculated.
Safety:
Treatment-emergent Adverse Events (AEs) and serious adverse events (SAEs) 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.  Changes in laboratory and vital sign data will be summarized using descriptive 
statistics.  Shift tables will be provided.
Sample Size:
The Week 8 co-primary endpoint is to compare the lower limit of the 95% CI of the remission rate per 
PMS in the adalimumab high induction dose group in this study to the upper limit of the 95% CI of the 
corresponding external placebo rate to be identified from a meta-analysis of relevant publically available 
clinical trials.  For illustrative purposes only, the following calculations use results from adult UC studies 
(Studies M06-826 and M06-827) as an estimate for the external placebo rates.  Assuming a 48.33% 
remission rate per PMS at Week 8 for the high induction dose group and given an upper limit of the 95% 
CI for the remission rate per PMS of the external placebo of 19.52%, a sample size of 65 subjects 
(high:standard = 39:26) provides at least 97% power for a one sample two-sided Chi-square test using a 
significance level of 5% for the Week 8 co-primary endpoint.
The Week 52 co-primary endpoint is to compare the lower limit of the 95% CI of the remission rate per 
Mayo score in the adalimumab high maintenance dose group in this study to the upper limit of the 95% 
CI of the external placebo rate.  Assuming a 36.63% remission rate per Mayo score at Week 52 for the 
high maintenance dose group and given an upper limit of the 95% CI for the remission rate per Mayo 
score of the external placebo of 13.81%, a sample size of 54 subjects (high:standard = 27:27) in the 
maintenance period of the study provides at least 85% power for a one sample two-sided Chi-square test 
using a significance level of 5% for the Week 52 co-primary endpoint.
Based on the assumption of a 75% response rate at Week 8, a total of 85 subjects are needed in the study 
(including internal placebo subjects enrolled prior to Amendment 4).

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Statistical Methods (Continued):
Sample Size (Continued):
Sample Size Based on Week 8 and Week 52 Co-Primary Endpoints
Endpoints
External 
Placebo 
upper 95% 
CI
Assumption 
for High 
ADA Group
Power
N in High 
ADA 
Group
Randomization Ratio
Total 
Induction 
Phase Sample 
Size
Week 8
PMS 
Remission 
Rate
19.52%a
48.33%
97%
39
Induction
High:Standard 
3:2 = 39:26
85b,c
Endpoints
External 
Placebo
Upper 
95% CI
Assumption 
for High 
ADA Group
Power
N in High 
ADA 
Group
Randomization Ratio
Total 
Maintenance 
Phase Sample 
Size
Week 52 
FMS 
Remission 
Rate
13.81%a
36.63%
85%
27
Maintenance 
High:Standard
1:1 = 27:27
63b,d
PMS = partial Mayo score; FMS = full Mayo score
a.
The upper limit of 95% CI for placebo derived from adult UC Studies M06-826 and M06-827 for illustrative 
purposes only in the absence of results from the ongoing meta-analysis.
b.
Sample size calculation is based on a one group Chi-square test.
c.
85 subjects are needed assuming 75% PMS response rate at Week 8. 
d.
Including subjects enrolled into the internal placebo arm (prior to Amendment 4).
  

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Has been changed to read:
AbbVie Inc.
Protocol Number:  M11-290
Name of Study Drug:  Adalimumab
Phase of Development:  3
Name of Active Ingredient:  Adalimumab
Date of Protocol Synopsis:  20 November 2018
Protocol Title:
A Multicenter, Randomized, Double-Blind Study of the Human Anti-TNF Monoclonal Antibody 
Adalimumab in Pediatric Subjects with Moderate to Severe Ulcerative Colitis
Objective:
The objective of the study is to demonstrate the efficacy and safety, and to assess the pharmacokinetics of
adalimumab administered subcutaneously (SC) in pediatric subjects with moderate to severe ulcerative 
colitis (UC).
Investigators:  Multicenter
Study Sites:  Approximately 50 sites worldwide for the main study and approximately 10 sites for the 
Japan sub-study.
Study Population:
Subjects with moderate-to-severe UC from the ages of 4 to 17 prior to Baseline dosing.
Number of Subjects to be Enrolled:  93 subjects for the main study and up to approximately 9 subjects 
for the Japan sub-study
Methodology:
This is a Phase 3, multicenter, randomized, double-blind trial designed to evaluate the efficacy and safety 
of adalimumab in pediatric subjects with moderate to severe ulcerative colitis, who have failed therapy 
with corticosteroids and/or immunosuppressants.

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Methodology (Continued):
93 pediatric subjects for the main study (and up to approximately 9 subjects for the Japan sub-study) with 
moderate-to-severe UC (Mayo Score of 6 to 12 points with an endoscopy subscore of 2 to 3, confirmed 
by central reader) will be enrolled at approximately 50 sites worldwide (and approximately 10 sites for 
the Japan sub-study).  The study will allow enrollment of up to 25% of anti-TNF experienced subjects.  
Prior to Amendment 4, subjects who met all of the inclusion criteria and none of the exclusion criteria 
were to be enrolled and randomized 3:2 at Baseline to one of two double-blinded adalimumab induction 
doses (high dose or standard dose).  The randomization was to be stratified by baseline disease severity 
(per Mayo Score), prior exposure to anti-TNF, and corticosteroid use at Baseline.  During the randomized 
double-blind induction period, subjects assigned to high induction dose group received adalimumab 2.4 
mg/kg (maximum dose of 160 mg) at Baseline and at Week 1.  At Week 2, subjects received adalimumab 
1.2 mg/kg (maximum dose of 80 mg), followed by a dose of 0.6 mg/kg (maximum dose of 40 mg) at 
Week 4 and Week 6.  Subjects randomized to the standard induction dose group received adalimumab 2.4 
mg/kg (maximum dose of 160 mg) at Baseline and matching placebo at Week 1, adalimumab 1.2 mg/kg 
(maximum dose of 80 mg) at Week 2, followed by a dose of 0.6 mg/kg (maximum dose of 40 mg) at 
Week 4 and Week 6.  After Amendment 4, subjects who meet all of the inclusion criteria and none of the 
exclusion criteria will be enrolled into the study and receive open-label adalimumab high induction dose.  
During the open-label induction period, subjects will receive adalimumab 2.4 mg/kg (maximum dose of 
160 mg) at Baseline and at Week 1.  At Week 2, subjects will receive adalimumab 1.2 mg/kg (maximum 
dose of 80 mg), followed by a dose of 0.6 mg/kg (maximum dose of 40 mg) at Week 4 and Week 6.  
Ongoing subjects randomized prior to Amendment 4 will continue their blinded treatment during the 
induction period until Week 8.  
Prior to Amendment 4, at Week 8, subjects demonstrating a clinical response per Partial Mayo Score 
(PMS) (defined as a decrease in PMS ≥ 2 points and ≥ 30% from Baseline) were randomized and 
stratified by Week 8 remission status per PMS (defined as a PMS ≤ 2 and no individual subscore > 1) and 
Induction dose in a 2:2:1 ratio to one of two adalimumab maintenance treatment groups (Standard dose 
[0.6 mg/kg (maximum dose of 40 mg) every other week] or High dose [0.6 mg/kg (maximum dose of 
40 mg) every week]) or to placebo, respectively.
After Amendment 4, at Week 8, subjects demonstrating a clinical response per PMS (defined as a 
decrease in PMS ≥ 2 points and ≥ 30% from Baseline) will be randomized and stratified by Week 8 
remission status per PMS (defined as a PMS ≤ 2 and no individual subscore > 1) in a 1:1 ratio to one of 
two adalimumab maintenance treatment groups (Standard dose [0.6 mg/kg (maximum dose of 40 mg) 
every other week] or High dose [0.6 mg/kg (maximum dose of 40 mg) every week]).
Subjects will receive blinded treatment every week (ew) beginning at Week 8 and will remain on 
double-blinded therapy through Week 52.
!
Subjects who are randomized to standard dose will receive a maintenance dose of 0.6 mg/kg 
(maximum dose of 40 mg) every other week (eow) and will receive the matching placebo at the 
alternate week.
!
Subjects who are randomized to high dose will receive a maintenance dose of 0.6 mg/kg 
(maximum dose of 40 mg) ew.
!
Subjects who were randomized to placebo prior to Amendment 4 receive matching placebo ew.  

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Methodology (Continued):
Ongoing subjects randomized prior to Amendment 4 will continue their blinded treatment during the 
maintenance period until Week 52 and re-randomization to treatment for disease flare will be done 
according to Amendment 3 stipulations in these subjects.
At Week 8, subjects who have not achieved a clinical response per PMS will be discontinued.  A safety 
evaluation call will be made 70 days after the last dose of study drug is administered to obtain follow-up 
information on any ongoing or new adverse events.
The duration of the study could be up to 66 weeks, which includes a Screening Period of up to 28 days, 
8-week induction period and a 44-week double-blind maintenance period and a 70-day follow-up.  Upon 
completion of the study, subjects will have the option to enroll into an open-label extension study where 
they will receive open-label adalimumab.
Treatment of Subjects with Disease Flare During the Study:
Criteria for Disease Flare are as follows:
!
Subjects with a Week 8 PMS of 0 to 2 who present with a PMS at least 3 points greater than 
their Week 8 score.
!
Subjects with a Week 8 PMS of 3 to 4 who present with a PMS at least 2 points greater than 
their Week 8 score.
!
Subjects with a Week 8 PMS of 5 to 6 who present with a PMS at least 1 point greater than their 
Week 8 score.
Subjects will be expected to remain on blinded therapy throughout the 44-week maintenance period.  
However, subjects with a disease flare, may be re-randomized to receive the following blinded-treatment 
at or after Week 12:
!
Subjects who are randomized to Standard maintenance dose (0.6 mg/kg [maximum dose of 
40 mg] eow) will be re-randomized to receive either adalimumab re-induction dose (2.4 mg/kg 
[maximum of 160 mg]) or adalimumab (0.6 mg/kg [maximum of 40 mg]) at the visit.  
Afterwards, all subjects will resume receiving the standard dose (0.6 mg/kg [maximum of 
40 mg] eow) within the original dosing schedule.
!
Subjects who are randomized to High maintenance dose (0.6 mg/kg [maximum dose of 40 mg] 
ew) will be re-randomized to receive either adalimumab re-induction dose (2.4 mg/kg 
[maximum of 160 mg]) or adalimumab (0.6 mg/kg [maximum of 40 mg]) at the visit.  The 
following week, all subjects will resume receiving the high dose (0.6 mg/kg [maximum of 
40 mg] ew).
!
Subjects who were randomized to placebo prior to Amendment 4 will be re-randomized to 
receive either adalimumab re-induction dose (2.4 mg/kg [maximum of 160 mg] or to receive 
adalimumab (0.6 mg/kg [maximum of 40 mg]) at the visit.  Afterwards, all subjects will receive 
the standard dose (0.6 mg/kg [maximum of 40 mg] eow) within the original dosing schedule.
If a subject continues to meet the definition of disease flare (2nd time) following at least a 4-week course 
of blinded therapy since the subject has been re-randomized for disease flare, they may be switched to 
open-label adalimumab every week at the dose 0.6 mg/kg [maximum of 40 mg].  If a subject was 
re-randomized at Week 12 (to receive either re-induction dose (2.4 mg/kg [maximum of 160 mg]) or to 
receive adalimumab (0.6 mg/kg [maximum of 40 mg]), then the earliest that subject could be evaluated to 
determine if the subject meets the criteria for disease flare for switch to OL (0.6 mg/kg [maximum of 
40 mg]) weekly dosing is at Week 16.

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Methodology (Continued):
Treatment of Subjects with Disease Flare During the Study (Continued):
If a subject continues to meet the definition of disease flare (3rd time) following a 4-week course of 
open-label adalimumab every week at the dose 0.6 mg/kg [maximum of 40 mg], they may be switched to 
receive adalimumab open-label 40 mg ew (maximum dose, not weight-based).
Subjects with persistent disease flare while on adalimumab 40 mg ew (max dose) may be withdrawn 
from the study at the investigator's discretion.
During open-label rescue therapy, subjects who are responders and have been in remission for at least 
8 consecutive weeks (PMS ≤ 2 with no individual subscore > 1) may have their dosage decreased from 
ew to eow.  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.  The investigator should receive prior approval 
from the medical monitor before taking any action with regard to dose re-escalation.
For subjects who meet the criteria for dose change, blood samples (adalimumab, AAA and hs-CRP) will 
be collected just prior to receiving any dose change (blinded therapy, escape to open-label adalimumab, 
dose de-escalation and dose re-escalation).
Subjects are allowed to be treated with stable doses of UC-related concomitant medications during the 
study, with the following exceptions and requirements:
!
At or after Week 4, subjects taking corticosteroid therapy at Baseline may have their 
corticosteroid therapy tapered based on the investigator's discretion.  A proposed tapering 
schedule is specified in Section 5.3.1.1.
!
From Week 4 to Week 12, if the subject should experience an increase in symptoms after 
corticosteroid was tapered, the subject may have their corticosteroid dose increased back up to 
the corticosteroid dose at Baseline.  This increase must be discussed with and approved by the 
Medical Monitor prior to any changes in these treatments.
!
Subjects who experience disease flare at or after Week 12 are allowed to change their dose or 
initiate treatment with corticosteroids, immunosuppressant or 5-ASA; these increases must be 
discussed with and approved by the Medical Monitor prior to any changes in these treatments.
!
Immunosuppressant doses may be decreased or terminated in the event of moderate-to-severe 
treatment-related toxicities.
!
Immunosuppressant therapy may be discontinued at or after Week 12 at the investigator's 
discretion.
At each study visit, in addition to routine physical examination including evaluation of extra intestinal 
manifestations and calculation of the PMS and PUCAI, the following will be collected:
!
Anthropometric evaluations at Baseline, Week 26 and Week 52/Premature Discontinuation for 
determination of body mass index (BMI), and "z" scores for height and weight.
!
IMPACT III Quality of Life questionnaire at Baseline, Week 8, Week 26 and 
Week 52/Premature Discontinuation Visit will be completed for subjects 9 years or older at the 
Baseline study visit.
!
Bone age determination by x-ray of the wrist at Screening and at Week 52/Premature 
Discontinuation Visit in subjects who have not completed linear growth.
!
Serum for measurement of adalimumab concentrations just prior to dosing at Baseline, Week 2, 
Week 4, Week 8, Week 12, Week 26 Week 34 and Week 52/Premature Discontinuation Visit 
and at Unscheduled Visit requiring dose change.

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Methodology (Continued):
Treatment of Subjects with Disease Flare During the Study (Continued):
!
Serum for measurement of Anti-Adalimumab Antibodies (AAA) just prior to dosing at 
Baseline, Week 4, Week 8, Week 26 and Week 52/Premature Discontinuation Visit and at 
Unscheduled Visit requiring dose change.
!
Tanner stage at Baseline, Week 26 and Week 52/Premature Discontinuation Visit.
!
Endoscopy subscore at Screening and Week 52/Premature Discontinuation Visit.
Diagnosis and Main Criteria for Inclusion/Exclusion:
Main Inclusion:
1.
Subjects from the ages of 4 to 17 prior to baseline dosing.
2.
Subjects with a diagnosis of UC for at least 12 weeks prior to screening confirmed by endoscopy 
with biopsy.
A colonoscopy will be performed during the screening period unless the subject underwent a 
colonoscopy within 12 months prior to Screening and appropriate documentation is available (to 
confirm the diagnosis without evidence of dysplasia, colon cancer or infection).  In this case the 
screening endoscopy may be either a colonoscopy or a flexible sigmoidoscopy.
If the subject underwent an endoscopy within 56 days of Baseline, and a video recording of the 
endoscopy is available, the video recording may be used and no additional endoscopy will be 
performed during the Screening period provided that the conditions noted in Section 5.3.1.1 are met 
and all technical requirements are fulfilled.
Note:
!
If no appropriate documentation for confirmation of the diagnosis is available as per the 
investigator's judgment a diagnostic biopsy must also be performed.  
!
Biopsies to rule out dysplasia, colon cancer and infection may be taken at the investigator's 
discretion.
3.
Active ulcerative colitis with a Mayo Score of 6 – 12 points and endoscopy subscore of 2 – 3 
(confirmed by central reader) despite concurrent treatment with at least one of the following (oral 
corticosteroids or immunosuppressants or both as defined below):
!
Oral prednisone of ≥ 2 mg/day or equivalent, but not exceeding 40 mg/day, or oral budesonide 
≥3 mg/day, but not exceeding 9 mg/day, with a stable dose for at least 7 days prior to Baseline; 
and/or
!
At least a consecutive 28-day course of azathioprine or 6-MP or methotrexate (MTX) prior to 
Baseline, with a stable dose prior to Baseline of azathioprine ≥ 1.5 mg/kg/day or 6-MP 
≥1 mg/kg/day (rounded to the nearest available tablet or half tablet formulation) or a 
documented 6-TGN level of 230 – 450 pmol/8 × 108 RBC on the current dosing regimen or 
MTX ≥ 15 mg/m2 body surface area/week, or a dose that is the highest tolerated by the subject 
(e.g., due to leukopenia, elevated liver enzymes, nausea) during that time.
Note:  If subjects are on both oral corticosteroid and immunosuppressants BOTH of the drugs 
need to meet the above criteria; and/or
!
Concurrent therapy with corticosteroids or immunosuppressants (azathioprine, 6-MP or 
MTX) is not required for subjects who were previously treated during the past 1 year and 
have confirmed documentation of failure to respond, or were previously treated during the 
past 5 years and have confirmed documentation indicating lack of tolerability.

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Diagnosis and Main Criteria for Inclusion/Exclusion (Continued):
Main Inclusion (Continued):
4.
Parent or guardian has voluntarily signed and dated an informed consent form, approved by an 
Institutional Review Board (IRB)/Independent Ethics Committee (IEC), after the nature of the study 
has been explained and the subject's parent or legal guardian has had the opportunity to ask 
questions.  The informed consent must be signed before any study-specific procedures are performed 
or before any concomitant medication is discontinued for the purpose of this study.  Pediatric 
subjects will be included in all discussions in order to obtain verbal and/or written assent.
5.
Subjects must be able and willing to self-administer SC injections or have a qualified person 
available to administer SC injections.
6.
Subject has a negative TB Screening Assessment.
If a subject has a positive (≥5 mm induration) PPD test and/or IGRA test at Screening, a CXR 
(PA and lateral view) must be performed for evaluation of active TB disease.  If the subject has 
evidence of a latent TB infection, the subject must initiate and complete a minimum of 2 weeks (or 
per local guidelines, whichever is longer) of an ongoing course of TB prophylaxis or have 
documented completion of a full course of TB prophylaxis, prior to Baseline.
7.
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 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, foams, jellies, diaphragm or intrauterine device (IUD);
!
Hormonal contraceptives for 90 days prior to study drug administration;
!
A vasectomized partner.
8.
Subject is judged to be in good health as determined by the Principal Investigator based upon the 
results of medical history, laboratory profile, physical examination, chest x-ray (CXR), and a 12-lead 
electrocardiogram (ECG) performed during Screening.
Main Exclusion:
1.
Subject with Crohn's disease (CD) or indeterminate colitis (IC).
2.
Current diagnosis of fulminant colitis and/or toxic megacolon.
3.
Subjects with disease limited to the rectum (ulcerative proctitis) during the screening endoscopy.
4.
Therapeutic enema or suppository within 14 days prior to the Screening endoscopy and during the 
remainder of the Screening Period.
5.
History of colectomy or subtotal colectomy (with ostomy) or is planning bowel surgery.
6.
Received cyclosporine, tacrolimus, or mycophenolate mofetil, within 30 days prior to Baseline.
7.
Female subjects who are breast-feeding or considering becoming pregnant during the study.
8.
Positive pregnancy test at Screening or Baseline.
9.
History of clinically significant drug or alcohol abuse in the last 12 months.

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Diagnosis and Main Criteria for Inclusion/Exclusion (Continued):
Main Exclusion (Continued):
10. Subjects on azathioprine or 6-mercaptopurine (6-MP) or MTX and subjects:
!
Have not been on stable doses of these medications for at least 28 days prior to Baseline; or 
!
Have discontinued these medications within 28 days of Baseline.
11. Subjects on oral aminosalicylates who:
!
Have not been on stable doses of these medications for at least 14 days prior to Baseline; or
!
Have discontinued use of aminosalicylates within 14 days of Baseline.
12. Subjects on growth hormone who have not been on a stable dose for at least 4 weeks prior to 
Baseline.
13. Subjects on oral corticosteroids who:
!
Have not been on stable doses of these drugs for at least 7 days prior to Baseline; or
!
Discontinued use of oral corticosteroid within 14 days of Baseline; or
!
Have been taking both budesonide and prednisone (or equivalent) simultaneously.
14. Received intravenous corticosteroids within 5 days prior to Screening or during the Screening 
Period.
15. Subject who has previously used infliximab or any anti-TNF agent within 56 days of Baseline.
16. Subject who has previously used infliximab or any anti-TNF agent and has not clinically responded 
at any time ("primary non-responder") unless subject experienced a treatment limiting reaction.
17. Previous treatment with adalimumab or previous participation in an adalimumab clinical study.
18. Positive Clostridium difficile (C. difficile) stool assay during the Screening Period.
19. Currently receiving total parenteral nutrition (TPN).
20. History of demyelinating disease (including myelitis) or neurologic symptoms suggestive of 
demyelinating disease.
21. History of invasive infection (e.g., listeriosis and histoplasmosis), human immunodeficiency 
syndrome (HIV).
22. 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.
23. Subjects with any active viral infection that based on the investigator's clinical assessment makes the 
subject an unsuitable candidate for the study.
24. Subject with a positive result for the Hepatitis B surface antigen (HBs Ag) or any HBV DNA PCR 
result that meets or exceeds detection sensitivity will be excluded.
25. Chronic recurring infections or active TB.
26. Subject has been treated with any investigational drug of chemical or biologic nature or any 
investigational procedure (including previous fecal transplantation) within 30 days or 5 half-lives 
(whichever is longer) of the drug prior to the Baseline Visit.
27. Infection(s) requiring treatment with intravenous (IV) anti-infectives within 30 days prior to the 
Baseline Visit or oral anti-infectives within 14 days prior to the Baseline Visit.
28. Prior exposure to biologics that have a potential or known association with PML (i.e., natalizumab 
(Tysabri®) or efalizumab (Raptiva®) or rituximab (Rituxan®).

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Diagnosis and Main Criteria for Inclusion/Exclusion (Continued):
Main Exclusion (Continued):
29. Known hypersensitivity to adalimumab or its excipients.
30. Evidence of dysplasia or 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.
If the Screening endoscopy shows evidence of dysplasia or malignancy, subject may not be enrolled in 
the study.
31. Screening laboratory and other analyses show any of the following abnormal results:
!
ECG – with clinically significant abnormalities;
!
Aspartate transaminases (AST) or alanine transaminase (ALT) > 1.75 × the upper limit of the 
reference range;
!
Total bilirubin ≥ 3 mg/dL;
!
Serum creatinine > 1.6 mg/dL;
!
Clinically significant abnormal screening laboratory results as evaluated by the Investigator.
32. Subject is considered by the Investigator, for any reason, to be an unsuitable candidate for the study.
Investigational Product:
Adalimumab
Induction Dose:
Body weight adjusted induction dose regimen
Prior to Amendment 4 subjects were randomized to receive one of 
2 double-blind adalimumab induction doses.
Standard Induction Dose:  2.4 mg/kg (maximum dose of 160 mg) at 
Week 0 and matching placebo at Week 1.  Subjects received 
1.2 mg/kg (maximum dose of 80 mg) at Week 2.  At Weeks 4 and 6, 
subjects received a dosing regimen of 0.6 mg/kg (maximum dose of 
40 mg).
High Induction Dose:  2.4 mg/kg (maximum dose of 160 mg) at 
Week 0 and Week 1.  Subjects received 1.2 mg/kg (maximum dose of 
80 mg) at Week 2.  At Weeks 4 and 6, subjects received a dosing 
regimen of 0.6 mg/kg (maximum dose of 40 mg).
After Amendment 4 subjects will receive the open-label adalimumab 
high induction dose.
High Induction Dose:  2.4 mg/kg (maximum dose of 160 mg) at 
Week 0 and Week 1.  Subjects will receive 1.2 mg/kg (maximum 
dose of 80 mg) at Week 2.  At Weeks 4 and 6, subjects will receive a 
dosing regimen of 0.6 mg/kg (maximum dose of 40 mg).

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Double-Blind Maintenance 
Doses (in Week 8 PMS 
Responders only):
Body weight adjusted maintenance dose regimen
Blinded adalimumab Standard dosing regimen:  0.6 mg/kg 
(maximum dose of 40 mg) eow with matching placebo at the 
alternate week
Blinded adalimumab High dosing regimen:  0.6 mg/kg (maximum 
dose of 40 mg) ew
Subjects who were randomized to placebo (prior to Amendment 4) 
receive placebo ew.  
At or after Week 12 subjects who demonstrate a disease flare may be 
re-randomized to receive the following blinded-treatment.
!
Subjects, who are randomized to standard maintenance 
dose, will be re-randomized to receive either adalimumab 
re-induction dose (2.4 mg/kg [maximum of 160 mg]) or to 
adalimumab (0.6 mg/kg [maximum of 40 mg]) at the visit.  
Afterwards, all subjects will resume to receiving the 
standard dose adalimumab (0.6 mg/kg [maximum of 40 mg] 
eow) within the original dosing schedule.
!
Subjects who are randomized to high maintenance dose, will 
be re-randomized to receive either adalimumab re-induction 
dose (2.4 mg/kg [maximum of 160 mg]) or to receive 
adalimumab (0.6 mg/kg [maximum of 40 mg]) at the visit.  
The following week, all subjects will resume to receiving 
the high dose (0.6 mg/kg [maximum of 40 mg] ew).
!
Subjects who were randomized to placebo prior to 
Amendment 4 will be re-randomized to receive either 
adalimumab re-induction dose (2.4 mg/kg [maximum of 
160 mg] or to receive adalimumab (0.6 mg/kg [maximum of 
40 mg]) at the visit.  Afterwards, all subjects will receive the 
standard dose (0.6 mg/kg [maximum of 40 mg] eow) within 
the original dosing schedule.
Open-Label Maintenance 
Doses:
High dose body weight adjusted.
0.6 mg/kg (maximum dose of 40 mg) ew
If a subject continues to meet the definition of disease flare following 
a 4-week course of open-label adalimumab ew at the dose 0.6 mg/kg 
[maximum of 40 mg], they may be switched to receive adalimumab 
40 mg ew (maximum dose, not weight-based).
Mode of Administration:
Subcutaneous injection (SC)
Reference Therapy:
NA (after Amendment 4); Placebo (prior to Amendment 4)
Dose:
NA
Mode of Administration:
NA (after Amendment 4); Subcutaneous injection (SC) (prior to 
Amendment 4)

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Duration of Treatment:  52 weeks
!
The subjects will visit the site at Screening, Baseline, Weeks 1, 2, 4, 8, 12, 18, 26, 34, 42, and 
52/Premature Discontinuation and Unscheduled Visits.
!
Subjects who qualify will be given the opportunity to enroll into an open-label study of the 
Long-term Safety and Tolerability of Repeated Administration of Adalimumab.
A 70-Day Follow-Up phone call will be completed for all subjects who either terminate early from the 
study or do not rollover into the extension study.
Criteria for Evaluation:
Efficacy analysis will be based on the Intent-To-Treat-Efficacy (ITT-E) population for the induction 
period and modified ITT (mITT) population for the maintenance period.  The ITT-E population is a
subpopulation of the ITT population, which consists of all subjects who received at least one SC injection 
of the study medication during the induction period.  Subjects who receive open-label high induction 
dose, because they enrolled after Protocol Amendment 4 was released, will be excluded from the ITT-E 
population.  The mITT population consists of all Week 8 PMS Responders among the ITT population 
who were randomized at Week 8 and received at least one SC injection of the study medication during 
maintenance period.  
The safety analysis set will include all subjects who received at least one SC injection of the study 
medication.
Efficacy:
This study will utilize the Mayo Score, PMS and Mayo subscores to measure efficacy.  The PUCAI will 
also be utilized as applicable.  Please refer to 'Statistical Methods' for details on the sequentially rejective 
multiple test procedure  of the dose groups used in this study versus external placebo for co-primary and 
ranked secondary endpoints.
Efficacy Endpoints
The co-primary efficacy endpoints are:
1.
The proportion of subjects who achieve clinical remission at Week 8 as measured by PMS (defined 
as a PMS ≤ 2 and no individual subscore > 1);
2.
The proportion of subjects who responded at Week 8 per PMS and achieve clinical remission at 
Week 52 as measured by Mayo Score (defined as a Mayo Score ≤ 2 and no individual subscore > 1).
Ranked secondary efficacy endpoints are:
1.
Proportion of subjects in Mayo clinical response at Week 52 in Week 8 responders per PMS;
2.
Proportion of subjects who achieve mucosal healing at Week 52 as measured by Mayo endoscopy 
subscore (defined as ≤ 1) in Week 8 responders per PMS;
3.
Proportion of subjects who achieve Mayo clinical remission at Week 52 in Week 8 remitters per 
PMS;
4.
Proportion of subjects receiving corticosteroid at Baseline who discontinue corticosteroid prior to 
Week 52 and are in Mayo clinical remission at Week 52 in Week 8 responders per PMS.

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Criteria for Evaluation (Continued):
Efficacy (Continued):
Additional exploratory secondary analyses:
!
Proportion of subjects in PMS clinical remission at Week 52 in Week 8 responders per PMS;
!
Proportion of subjects in PUCAI remission (defined as < 10) at Week 8;
!
Proportion of subjects in PUCAI response (defined as a decrease in PUCAI ≥ 20 points from 
Baseline) at Week 8;
!
Proportion of subjects in PUCAI remission (defined as < 10) at Week 52 in Week 8 responders 
per PMS;
!
Proportion of subjects in PUCAI response (defined as a decrease in PUCAI ≥ 20 points from 
Baseline) at Week 52 in Week 8 responders per PMS;
!
Proportion of subjects receiving corticosteroid at Baseline who discontinue corticosteroid prior 
to Week 52 and are in PUCAI remission at Week 52 in Week 8 responders per PMS;
!
Change from Baseline in total IMPACT III Quality of Life scores over time for subjects at least 
9 years old at Baseline;
!
Change from Baseline in WPAI scores over time;
!
Change from Baseline in "z" scores for height (observed height velocity [cm/yr] – mean height 
velocity for age and sex [cm/yr]/SD of the mean) at Week 26 and Week 52;
!
Change from Baseline in BMI at Week 26 and Week 52;
!
Change from Baseline in "z" scores for weight-for-age at Week 26 and Week 52;
!
Proportion of subjects at appropriate Tanner stage at Week 26 and Week 52 compared to 
Baseline;
!
Proportion of subjects in PMS response over time;
!
Proportion of subjects in PMS remission over time;
!
Proportion of subjects in PUCAI response over time;
!
Proportion of subjects in PUCAI remission over time;
!
Change from Baseline in number of daily stool over time;
!
Change from Baseline in albumin and total protein at different time points;
!
Change from Baseline in hemoglobin, hematocrit, red blood cell count at different time points;
!
Change from Baseline in hs-CRP levels at different time points;
!
Proportion of subjects with extraintestinal manifestations (EIM) at Week 26 and Week 52 
compared to Baseline;
!
Proportion of subjects with Mayo endoscopy subscore of 0 or 1 (without friability) at Week 52;
!
Proportion of subjects being hospitalized during the study;
!
Proportion of subjects undergoing colectomy during the study;
!
Proportion of subjects receiving corticosteroid at Baseline who discontinue corticosteroid prior 
to Week 52 and completed Week 52;
!
Correlation between PMS and PUCAI at different time points;

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Criteria for Evaluation (Continued):
Efficacy (Continued):
!
Proportion of subjects in a 9 point Mayo (without SFS) clinical remission (defined as ≤ 2 and no 
individual subscore > 1) at Week 52 in Week 8 responders per PMS;
!
Proportion of subjects in a 9 point Mayo (without PGA) clinical remission (defined as ≤ 2 and 
no individual subscore > 1) at Week 52 in Week 8 responders per PMS;
!
Proportion of subjects in a 9 point Mayo (without RBS) clinical remission (defined as ≤ 2 and 
no individual subscore > 1) at Week 52 in Week 8 responders per PMS;
!
Proportion of subjects in a 6 point Mayo (without SFS and endoscopy subscore) clinical 
remission (defined as ≤ 1) at Week 8;
!
Proportion of subjects in a 6 point Mayo (without PGA and endoscopy subscore) clinical 
remission (defined as ≤ 1) at Week 8;
!
Proportion of subjects in a 6 point Mayo (without RBS and endoscopy subscore) clinical 
remission (defined as ≤ 1) at Week 8;
!
Change from Baseline in Mayo Score at Week 52;
!
Change from Baseline in PMS over time;
!
Change from Baseline in PUCAI over time;
!
Change from Baseline in endoscopy subscore at Week 52;
!
Change from Baseline in SFS over time;
!
Change from Baseline in RBS over time;
!
Change from Baseline in PGA over time.
Pharmacokinetic:
Blood samples will be collected for the measurement of serum adalimumab concentrations just prior to 
dosing at Baseline, Weeks 2, 4, 8, 12, 26, 34 and 52/Premature Discontinuation Visits, and at 
Unscheduled Visits requiring dose change.  Blood samples will be collected for the measurement of 
serum anti-adalimumab antibody (AAA) just prior to dosing at Baseline, Weeks 4, 8, 26 and 
52/Premature Discontinuation Visits and at Unscheduled Visits requiring dose change.  Blood samples 
will be collected for the measurement of serum Infliximab and HACA at Baseline (prior to dosing).
Safety:
Adverse events, laboratory data, and vital signs will be assessed at all visits throughout the study.
Statistical Methods:
Efficacy:
The efficacy analysis will be performed in the ITT-E set for the induction period and in the mITT set for 
the maintenance period.  NRI method will be used to impute missing values for binary efficacy 
endpoints.  Subjects who do not complete the induction period or who receive rescue therapy during the 
maintenance period will be considered as failures from that time point forward.  Both LOCF and 
observed case analyses will be performed for continuous efficacy endpoints.
The confirmatory efficacy analyses for the co-primary endpoints and ranked secondary endpoints are 
based on the following external placebo assumptions.  

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Statistical Methods (Continued):
External Placebo Assumptions for Co-Primary and Ranked Secondary Efficacy Endpoints
Endpoint
External Placebo Rate 
(95% CI Upper Limit from Meta-
Analysis)
Week 8 PMS Remission 
19.83%
Week 52 FMS Remission in Week 8 Responders per PMS
18.37%
Week 52 FMS Response in Week 8 Responders per PMS
26.10%
Week 52 Mucosal Healing in Week 8 Responders per PMS
22.03%
Week 52 FMS Remission in Week 8 Remitters per PMS
14.79%
Week 52 FMS Remission in Week 8 Responders per PMS with 
CS at Baseline and Discontinued CS prior to Week 52
24.08%
FMS = Full Mayo Score; PMS = Partial Mayo Score; CS = Corticosteroids
  
Co-primary and ranked secondary endpoints will be summarized by treatment group with 95% 
confidence intervals (CI) and adalimumab dose groups will be tested against external placebo in a 
sequentially rejective multiple test procedure in order to ensure that the multiple significance level of 5% 
is controlled, using one sample two-sided Chi-square tests.  The below graph describes the structure of 
the multiple test procedure that starts with testing the co-primary endpoints for the combined high and 
standard adalimumab dose groups versus external placebo and then individual dose groups versus 
external placebo separately: 

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Statistical Methods (Continued):
Multiple Test Procedure for the Co-Primary and Ranked Secondary Endpoints
Assuming ε = 0.0005; C = testing the endpoint for the combined high and standard adalimumab dose groups against 
external placebo; HD = testing the endpoint for the high adalimumab dose against external placebo; SD = testing the 
endpoint for the standard adalimumab dose against external placebo; P1 = co-primary induction endpoint; P2 = co-
primary maintenance endpoint; Si = ranked secondary endpoint i (i=1,…,4)

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Statistical Methods (Continued):
Additional exploratory secondary endpoints that are of the categorical type will be summarized by 
treatment group with 95% CIs.  Additional exploratory secondary endpoints that are of the continuous 
type will be analyzed as changes from baseline, and reported by treatment group including 95% CIs.  
The following subset of endpoints will be tested for the high adalimumab dose against the standard 
adalimumab dose in an exploratory manner:
!
Proportion of subjects in PMS clinical remission at Week 8;
!
Proportion of subjects who achieve mucosal healing at Week 52 as measured by Mayo 
endoscopy subscore (defined as ≤ 1) in Week 8 responders per PMS;
!
Proportion of subjects in PUCAI remission (defined as < 10) at Week 52 in Week 8 responders 
per PMS;
!
Proportion of subjects in Mayo clinical response at Week 52 in Week 8 responders per PMS;
!
Proportion of subjects in Mayo clinical remission at Week 52 in Week 8 responders per PMS;
!
Proportion of subjects in PUCAI response (defined as a decrease in PUCAI ≥ 20 points from 
Baseline) at Week 52 in Week 8 responders per PMS;
!
Proportion of subjects receiving corticosteroid at Baseline who discontinue corticosteroid  prior 
to Week 52 and are in Mayo clinical remission at Week 52 in Week 8 responders per PMS;
!
Proportion of subjects receiving corticosteroid at Baseline who discontinue corticosteroid prior 
to Week 52 and are in PUCAI remission at Week 52 in Week 8 responders per PMS;
!
Proportion of subjects in PMS clinical remission at Week 52 in Week 8 responders per PMS;
!
Proportion of subjects in PUCAI remission at Week 8;
!
Proportion of subjects in PUCAI response at Week 8.
Pharmacokinetic:
Adalimumab trough serum concentrations will be summarized by treatment group at each time point 
using descriptive statistics.  In addition, pharmacokinetic model based analyses will be performed with
the focus on apparent clearance (CL/F) and apparent volume of distribution (V/F) of adalimumab.
Immunogenicity:
AAA will be evaluated for each subject and each regimen, and rates of AAA positive will be calculated.  
As appropriate, the effect of AAA on adalimumab pharmacokinetics, efficacy variable(s), and 
treatment-emergent adverse events may be evaluated.  HACA will be evaluated for each subject and each 
regimen, and rates of HACA positive will be calculated.
Safety:
Treatment-emergent Adverse Events (AEs) and serious adverse events (SAEs) 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.  Changes in laboratory and vital sign data will be summarized using descriptive 
statistics.  Shift tables will be provided.

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Statistical Methods (Continued):
Sample Size:
The co-primary endpoints will be tested first for the combined high and standard adalimumab dose 
groups versus external placebo and then for the individual dose groups versus external placebo 
separately, controlling the multiple significance level of 5%.  For each individual test the nominal power 
is calculated. 
Assuming a 48% remission rate per PMS at Week 8 for the combined standard and high adalimumab 
induction dose groups and a remission rate per PMS of 19.83% for external placebo, a total of 77 subjects 
(high:standard = 46:31) in ITT-E population provides at least 99% power for a one sample two-sided 
Chi-square test using a significance level of 5%. 
Assuming a 36% remission rate per Mayo Score at Week 52 for the combined standard and high 
maintenance dose groups and a remission rate per Mayo Score of 18.37% for external placebo, a total of 
57 subjects in the combined adalimumab maintenance dose groups in mITT population (e.g., 
high:standard = 28:29) provide 88% power for a one sample two-sided Chi-square test using a 
significance level of 5%. 
Assuming that the high adalimumab dose regimen is associated with higher efficacy than the standard 
adalimumab dose regimen, assuming a 52% remission rate per PMS at Week 8 for the high adalimumab 
induction dose group and a remission rate per PMS of 19.83% for external placebo, 46 subjects in the 
high adalimumab induction dose group of ITT-E population provide at least 99% power for a one sample 
two-sided Chi-square test using a significance level of 4.95%. 
Assuming a 41% remission rate per Mayo Score at Week 52 for the high adalimumab maintenance dose 
group and a remission rate per Mayo Score of 18.37% for external placebo, a total of 28 subjects in the 
high adalimumab maintenance dose group of mITT population provide at least 80% power for a 
one sample two-sided Chi-square test using a significance level of 4.95%.
Based on the assumption of a 75% response rate at Week 8, 93 subjects will have to be included in the 
study (including ~12 internal placebo subjects in the maintenance part of the study who were included 
prior to Amendment 4) to ensure 57 subjects in the combined adalimumab maintenance dose groups.  
Section 1.3  List of Abbreviations and Definition of Terms
Subsection Abbreviations
Add: 
EIM
Extraintestinal manifestation
Section 3.2  Ulcerative Colitis and Current Treatments Overview
Last paragraph, first sentence previously read:
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  

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Has been changed to read:
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 double-blind clinical trials (Study M06-826 and Study M06-827) and a 
completed open-label study (Study M10-223).15-18  
Section 5.1  Overall Study Design and Plan:  Description
First paragraph, first sentence previously read:
The study is designed to enroll approximately 85 subjects to meet scientific and regulatory 
objectives without enrolling an undue number of subjects in alignment with ethical 
considerations.  
Has been changed to read:
The study is designed to enroll 93 subjects (not including the Japanese sub-study) to meet 
scientific and regulatory objectives without enrolling an undue number of subjects in 
alignment with ethical considerations.  
Section 5.1  Overall Study Design and Plan:  Description
Fourth paragraph previously read:
Approximately 85 pediatric subjects with moderate-to-severe ulcerative colitis 
(Mayo score of 6 to 12 points with endoscopy subscore of 2 to 3, confirmed by central 
reader) will be enrolled at approximately 50 sites worldwide (Section 5.3.1.1).
Has been changed to read:
93 pediatric subjects with moderate-to-severe ulcerative colitis (Mayo Score of 6 to 
12 points with endoscopy subscore of 2 to 3, confirmed by central reader) will be enrolled 
at approximately 50 sites worldwide (Section 5.3.1.1).

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Section 5.1  Overall Study Design and Plan:  Description
Fifth paragraph, first sentence previously read:
There also will be up to approximately 20 Japanese subjects in a Japan sub-study to be 
enrolled at approximately 10 Japan sites.  
Has been changed to read:
There also will be up to approximately 9 Japanese subjects in a Japan sub-study to be 
enrolled at approximately 10 Japan sites.  
Section 5.3.2.1  Collection of Samples for Analysis
Subsection Collection of Samples for Adalimumab and AAA Assays
Fourth paragraph, last sentence previously read:
The number of samples planned is 680 (8 samples × 85 subjects) for the adalimumab 
assay and 425 (5 samples × 85 subjects) for the AAA assay for the entire study.
Has been changed to read:
The number of samples planned is 744 (8 samples × 93 subjects) for the adalimumab 
assay and 465 (5 samples × 93 subjects) for the AAA assay for the entire study.
Section 5.3.2.1  Collection of Samples for Analysis
Subsection Collection of Samples for Infliximab and HACA Assays
Last paragraph previously read:
The total number of samples planned will not exceed 170 (2 samples × 85 subjects) for 
the entire study.
Has been changed to read:
The total number of samples planned will not exceed 186 (2 samples × 93 subjects) for 
the entire study.

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Section 5.3.3  Efficacy Variables
Add:  new last paragraph
Please refer to Section 8.1.4 for details on the sequentially rejective multiple test 
procedure of the dose groups used in this study versus external placebo for co-primary 
and ranked secondary endpoints.
Section 5.3.3.1  Primary Variable
Section title and text previously read:
5.3.3.1
Primary Variable
The co-primary efficacy endpoints are:
1.
The proportion of subjects who achieve clinical remission at Week 8 as measured 
by PMS (defined as a PMS ≤ 2 and no individual subscore > 1) in the high 
induction dose group as compared to external placebo.
2.
The proportion of subjects who responded at Week 8 per PMS and achieve clinical 
remission at Week 52 as measured by Mayo score (defined as a Mayo Score ≤ 2 
and no individual subscore > 1) in the high maintenance dose group as compared to 
external placebo.
External placebo data will be identified from an ongoing meta-analysis of relevant 
publically available clinical trials (see Section 8.1.4).
Has been changed to read:
5.3.3.1
Primary Variables
The co-primary efficacy endpoints are:
1.
The proportion of subjects who achieve clinical remission at Week 8 as measured 
by PMS (defined as a PMS ≤ 2 and no individual subscore > 1);

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2.
The proportion of subjects who responded at Week 8 per PMS and achieve clinical 
remission at Week 52 as measured by Mayo score (defined as a Mayo Score ≤ 2 
and no individual subscore > 1).
Section 5.3.3.2  Secondary Variables
Previously read:
Ranked secondary efficacy variables are:
1.
Proportion of subjects who achieve mucosal healing at Week 52 as measured by 
Mayo endoscopy subscore (defined as ≤ 1) in Week 8 responders per PMS 
(high maintenance dose versus external placebo);
2.
Proportion of subjects who achieve Mayo clinical remission at Week 52 in Week 8 
remitters per PMS (high maintenance dose versus external placebo) (*);
3.
Proportion of subjects in PUCAI remission (defined as < 10) at Week 52 in Week 8 
responders per PMS (high maintenance dose versus external placebo) (*);
4.
Proportion of subjects in Mayo clinical response at Week 52 in Week 8 responders 
per PMS (high maintenance dose versus external placebo);
5.
Proportion of subjects in PUCAI response (defined as a decrease in PUCAI 
≥20 points from Baseline) at Week 52 in Week 8 responders per PMS (high 
maintenance dose versus external placebo) (*);
6.
Proportion of subjects receiving corticosteroid at Baseline who have discontinued 
corticosteroid prior to Week 52 and are in Mayo clinical remission at Week 52 in 
Week 8 responders per PMS (high maintenance dose versus external placebo) (*);
7.
Proportion of subjects receiving corticosteroid at Baseline who have discontinued 
corticosteroid prior to Week 52 and are in PUCAI remission at Week 52 in Week 8 
responders per PMS (high maintenance dose versus external placebo) (*);
8.
Proportion of subjects in Partial Mayo clinical remission at Week 52 in Week 8 
responders per PMS (high maintenance dose versus external placebo);

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9.
Proportion of subjects in Partial Mayo clinical remission at Week 8 (standard 
induction dose versus external placebo);
10.
Proportion of subjects in Mayo clinical remission at Week 52 in Week 8 responders 
per PMS (standard maintenance dose versus external placebo);
11.
Proportion of subjects who achieve mucosal healing at Week 52 as measured by 
Mayo endoscopy subscore in Week 8 responders per PMS (standard maintenance 
dose versus external placebo);
12.
Proportion of subjects who achieve Mayo clinical remission at Week 52 in Week 8 
remitters per PMS (standard maintenance dose versus external placebo) (*);
13.
Proportion of subjects in PUCAI remission at Week 52 in Week 8 responders per 
PMS (standard maintenance dose versus external placebo) (*);
14.
Proportion of subjects in Mayo clinical response at Week 52 in Week 8 responders 
per PMS (standard maintenance dose versus external placebo);
15.
Proportion of subjects in PUCAI response at Week 52 in Week 8 responders per 
PMS (standard maintenance dose versus external placebo) (*);
16.
Proportion of subjects receiving corticosteroid at Baseline who have discontinued 
corticosteroid prior to Week 52 and are in Mayo clinical remission at Week 52 in 
Week 8 responders per PMS (standard maintenance dose versus external placebo) 
(*);
17.
Proportion of subjects receiving corticosteroid at Baseline who have discontinued 
corticosteroid prior to Week 52 and are in PUCAI remission at Week 52 in Week 8 
responders per PMS (standard maintenance dose versus external placebo) (*);
18.
Proportion of subjects in Partial Mayo clinical remission at Week 52 in Week 8 
responders per PMS (standard maintenance dose versus external placebo);
(*)  If external placebo data are not available, results will only be summarized  by 
maintenance group and 95% CI will be provided.

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Additional secondary variables are:
●
Proportion of subjects in Partial Mayo clinical remission at Week 8 
(high induction dose versus standard induction dose);
●
Proportion of subjects who achieve mucosal healing at Week 52 as measured 
by Mayo endoscopy subscore (defined as ≤ 1) (high maintenance dose versus 
standard maintenance dose);
●
Proportion of subjects in PUCAI remission (defined as < 10) at Week 52 
(high maintenance dose versus standard maintenance dose);
●
Proportion of subjects in Mayo clinical response at Week 52 (high 
maintenance dose versus standard maintenance dose);
●
Proportion of subjects in Mayo clinical remission at Week 52 (high 
maintenance dose versus standard maintenance dose);
●
Proportion of subjects in PUCAI response (defined as a decrease in PUCAI 
≥20 points from Baseline) at Week 52 (high maintenance dose versus standard 
maintenance dose);
●
Proportion of subjects receiving corticosteroid at Baseline who have 
discontinued corticosteroid prior to Week 52 and are in Mayo clinical 
remission at Week 52 (high maintenance dose versus standard maintenance 
dose);
●
Proportion of subjects receiving corticosteroid at Baseline who have 
discontinued corticosteroid prior to Week 52 and are in PUCAI remission at 
Week 52 (high maintenance dose versus standard maintenance dose);
●
Proportion of subjects in Partial Mayo clinical remission at Week 52 
(high maintenance dose versus standard maintenance dose);
●
Proportion of subjects in PUCAI remission at Week 8 (high induction dose 
versus standard induction dose);
●
Proportion of subjects in PUCAI response at Week 8 (high induction dose 
versus standard induction dose);
●
Change from Baseline in total IMPACT III Quality of Life scores over time 
for subjects at least 9 years old at Baseline;
●
Change from Baseline in WPAI scores over time;

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●
Change from Baseline in "z" scores for height (observed height velocity 
[cm/yr] – mean height velocity for age and sex [cm/yr]/SD of the mean) at 
Week 26 and Week 52;
●
Change from Baseline in BMI at Week 26 and Week 52;
●
Change from Baseline in "z" scores for weight-for-age at Week 26 and 
Week 52;
●
Proportion of subjects at appropriate Tanner stage at Week 26 and Week 52 
compared to Baseline;
●
Proportion of subjects in Partial Mayo response over time;
●
Proportion of subjects in Partial Mayo remission over time;
●
Proportion of subjects in PUCAI response over time;
●
Proportion of subjects in PUCAI remission over time;
●
Change from Baseline in number of daily stool over time;
●
Change from Baseline in albumin and total protein at different time points;
●
Change from Baseline in hemoglobin, hematocrit, red blood cell count at 
different time points;
●
Change from Baseline in hs-CRP levels at different time points;
●
Proportion of subjects with extraintestinal manifestations (EM) at Week 26 
and Week 52 compared to Baseline;
●
Proportion of subjects with Mayo endoscopy subscore of 0 or 1 (without 
friability) at Week 52;
●
Proportion of subjects being hospitalized during the study;
●
Proportion of subjects undergoing colectomy during the study;
●
Proportion of subjects receiving corticosteroid at Baseline who have 
discontinued corticosteroid prior to Week 52 and completed Week 52;
●
Correlation between PMS and PUCAI at different time points;
●
Proportion of subjects in a 9 point Mayo (without SFS) clinical remission 
(defined as ≤ 2 and no individual subscore > 1) at Week 52 in Week 8 
responders per PMS (high maintenance dose versus external placebo) (*);

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●
Proportion of subjects in a 9 point Mayo (without PGA) clinical remission 
(defined as ≤ 2 and no individual subscore > 1) at Week 52 in Week 8 
responders per PMS (high maintenance dose versus external placebo) (*);
●
Proportion of subjects in a 9 point Mayo (without RBS) clinical remission 
(defined as ≤ 2 and no individual subscore > 1) at Week 52 in Week 8 
responders per PMS (high maintenance dose versus external placebo) (*);
●
Proportion of subjects in a 6 point Mayo (without SFS and endoscopy 
subscore) clinical remission (defined as ≤ 1) at Week 8 (high induction dose 
versus external placebo) (*);
●
Proportion of subjects in a 6 point Mayo (without PGA and endoscopy 
subscore) clinical remission (defined as ≤ 1) at Week 8 (high induction dose 
versus external placebo) (*);
●
Proportion of subjects in a 6 point Mayo (without RBS and endoscopy 
subscore) clinical remission (defined as ≤ 1) at Week 8 (high induction dose 
versus external placebo) (*);
●
Change from Baseline in Mayo score at Week 52;
●
Change from Baseline in PMS over time;
●
Change from Baseline in PUCAI over time;
●
Change from Baseline in endoscopy subscore at Week 52;
●
Change from Baseline in SFS over time;
●
Change from Baseline in RBS over time;
●
Change from Baseline in PGA over time.
(*)  If external placebo data are not available, results will only be summarized in the high 
maintenance or high induction dose group, respectively, and 95% CI will be provided.
Has been changed to read:
Ranked secondary efficacy variables are:
1.
Proportion of subjects in Mayo clinical response at Week 52 in Week 8 responders 
per PMS;

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2.
Proportion of subjects who achieve mucosal healing at Week 52 as measured by 
Mayo endoscopy subscore (defined as ≤ 1) in Week 8 responders per PMS;
3.
Proportion of subjects who achieve Mayo clinical remission at Week 52 in Week 8 
remitters per PMS;
4.
Proportion of subjects receiving corticosteroid at Baseline who have discontinued 
corticosteroid prior to Week 52 and are in Mayo clinical remission at Week 52 in 
Week 8 responders per PMS.
Additional exploratory secondary analyses will be performed for:
●
Proportion of subjects in PMS clinical remission at Week 52 in Week 8 
responders per PMS;
●
Proportion of subjects in PUCAI remission (defined as < 10) at Week 8;
●
Proportion of subjects in PUCAI response (defined as a decrease in PUCAI 
≥20 points from Baseline) at Week 8;
●
Proportion of subjects in PUCAI remission (defined as < 10) at Week 52 in 
Week 8 responders per PMS;
●
Proportion of subjects in PUCAI response (defined as a decrease in PUCAI 
≥20 points from Baseline) at Week 52 in Week 8 responders per PMS;
●
Proportion of subjects receiving corticosteroid at Baseline who discontinue 
corticosteroid prior to Week 52 and are in PUCAI remission at Week 52 in 
Week 8 responders per PMS;
●
Change from Baseline in total IMPACT III Quality of Life scores over time 
for subjects at least 9 years old at Baseline;
●
Change from Baseline in WPAI scores over time;
●
Change from Baseline in "z" scores for height (observed height velocity 
[cm/yr] – mean height velocity for age and sex [cm/yr]/SD of the mean) at 
Week 26 and Week 52;
●
Change from Baseline in BMI at Week 26 and Week 52;
●
Change from Baseline in "z" scores for weight-for-age at Week 26 and 
Week 52;

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●
Proportion of subjects at appropriate Tanner stage at Week 26 and Week 52 
compared to Baseline;
●
Proportion of subjects in PMS response over time;
●
Proportion of subjects in PMS remission over time;
●
Proportion of subjects in PUCAI response over time;
●
Proportion of subjects in PUCAI remission over time;
●
Change from Baseline in number of daily stool over time;
●
Change from Baseline in albumin and total protein at different time points;
●
Change from Baseline in hemoglobin, hematocrit, red blood cell count at 
different time points;
●
Change from Baseline in hs-CRP levels at different time points;
●
Proportion of subjects with EIM at Week 26 and Week 52 compared to 
Baseline;
●
Proportion of subjects with Mayo endoscopy subscore of 0 or 1 (without 
friability) at Week 52;
●
Proportion of subjects being hospitalized during the study;
●
Proportion of subjects undergoing colectomy during the study;
●
Proportion of subjects receiving corticosteroid at Baseline who have 
discontinued corticosteroid prior to Week 52 and completed Week 52;
●
Correlation between PMS and PUCAI at different time points;
●
Proportion of subjects in a 9 point Mayo (without SFS) clinical remission 
(defined as ≤ 2 and no individual subscore > 1) at Week 52 in Week 8 
responders per PMS;
●
Proportion of subjects in a 9 point Mayo (without PGA) clinical remission 
(defined as ≤ 2 and no individual subscore > 1) at Week 52 in Week 8 
responders per PMS;
●
Proportion of subjects in a 9 point Mayo (without RBS) clinical remission 
(defined as ≤ 2 and no individual subscore > 1) at Week 52 in Week 8 
responders per PMS;
●
Proportion of subjects in a 6 point Mayo (without SFS and endoscopy 
subscore) clinical remission (defined as ≤ 1) at Week 8;

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●
Proportion of subjects in a 6 point Mayo (without PGA and endoscopy 
subscore) clinical remission (defined as ≤ 1) at Week 8;
●
Proportion of subjects in a 6 point Mayo (without RBS and endoscopy 
subscore) clinical remission (defined as ≤ 1) at Week 8;
●
Change from Baseline in Mayo score at Week 52;
●
Change from Baseline in PMS over time;
●
Change from Baseline in PUCAI over time;
●
Change from Baseline in endoscopy subscore at Week 52;
●
Change from Baseline in SFS over time;
●
Change from Baseline in RBS over time;
●
Change from Baseline in PGA over time.
Section 8.1.1  Analyzable Population
Second through fourth paragraph previously read:
Intent-To-Treat (ITT):  Includes all randomized subjects who received at least one dose of 
the induction medication.  ITT subjects will be analyzed as randomized.  Subjects who 
have received open-label high induction dose will be excluded from the ITT population.  
ITT is the primary population for the induction period efficacy analyses.
Modified ITT (mITT):  Consists of all Week 8 PMS Responders who were randomized at 
Week 8 and received at least one SC injection of the study medication during maintenance 
period.  mITT is the primary population for the maintenance period efficacy analyses.
Re-Randomized population:  Consists of all subjects with a disease flare who were 
re-randomized at or after Week 12 and received at least one SC injection of the study 
medication after the re-randomization.

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Has been changed to read:
Intent-To-Treat (ITT):  The ITT population includes all subjects who received at least 
one dose of the study medication during induction period.  ITT subjects will be analyzed 
as randomized/enrolled.  
ITT-E:  The ITT-E population will be a subpopulation of the ITT population, where 
subjects who have received open-label high induction dose will be excluded.  ITT-E is the 
primary population for the induction period efficacy analyses.
Modified ITT (mITT):  Consists of all Week 8 PMS Responders who were randomized at 
Week 8 and received at least one dose of the study medication during maintenance period.  
mITT is the primary population for the maintenance period efficacy analyses.
Re-Randomized population:  Consists of all subjects with a disease flare who were 
re-randomized at or after Week 12 and received at least one dose of the study medication 
after the re-randomization.
Section 8.1.2  Planned Methods of Statistical Analysis
Previously read:
All statistical tests will be two-sided with the significance level 0.05 except where 
indicated otherwise.  Descriptive statistics will be provided.  These include the number of 
observations, mean, standard deviation, minimum, first quartile, median, third quartile, 
and maximum for continuous variables; and counts and percentages for discrete variables.  
The analysis will be performed using SAS® (SAS Institute Inc., Cary, NC, USA).
Has been changed to read:
Descriptive statistics will include the number of observations, mean, standard deviation, 
minimum, first quartile, median, third quartile, and maximum for continuous variables; 
and counts and percentages for discrete variables.  For confirmatory tests the multiple 
significance level of 0.05 will be controlled.  The analysis will be performed using SAS®
(SAS Institute Inc., Cary, NC, USA).

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Section 8.1.4  Statistical Analyses of Efficacy
Previously read:
8.1.4
Statistical Analyses of Efficacy
8.1.4.1
Primary Efficacy Variable
The primary efficacy analysis will be performed in the ITT population for the Week 8 
efficacy endpoints and in the mITT population for the Week 52 efficacy endpoint.  Non-
responder imputation (NRI) will be used to impute missing values for binary efficacy 
endpoints.  Subjects who do not complete the induction period or who receive rescue 
therapy during the maintenance period will be considered as failures from that time point 
forward.  Both LOCF and observed case analyses will be performed for continuous 
efficacy endpoints.
The primary efficacy analysis for the co-primary endpoint at Week 8 is based on external 
placebo comparison identified from an ongoing meta-analysis of relevant publically 
available clinical trials. The lower limit of the 95% CI of the remission rate per PMS in 
the adalimumab high induction dose group in this study will be compared to the upper 
limit of the 95% CI of the corresponding external placebo rate.  In order to demonstrate 
efficacy of adalimumab at Week 8 in the pediatric population, the lower limit of the 95% 
CI for the remission per PMS in the high induction dose group is required to be higher 
than the upper limit of the 95% CI of the remission rate of external placebo (assumptions 
based on adult UC studies Studies M06-826 and M06-827 are shown in for illustrative 
purposes only).
The primary efficacy analysis for the co-primary endpoint at Week 52 is based on the 
comparison of the high maintenance dose group versus external placebo using the 
approach described above.  

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Table 5.
Placebo Data from Adult UC Studies
Placebo Subjects by Prior 
Anti-TNF Status
Weighted Average for 25% 
Experienced +75% Naïve
Experienced 
n/N (%)
Naïve 
n/N (%)
%
95% CI Upper 
Limit
Week 8 Partial Mayo 
Remission (Pooled 
Study M06-826 and 
Study M06-827 IAS-E seta)
15/101 
(14.9%)
61/367 
(16.6%)
16.18%
19.52%
Week 52 Mayo Score 
Remission (Study M06-827 
ITT set)
3/101
(3.0%)
18/145
(12.4%)
10.05%
13.81%
a.
IAS-E data set consisted of all randomized subjects with confirmed UC who received at least 1 dose of blinded 
study drug in either Study M06-826 or Study M06-827.
8.1.4.2
Secondary Efficacy Variables
The secondary endpoints are divided into two groups.  The first group consists of ranked 
secondary efficacy endpoints, which are ranked by hierarchical order and will be tested by 
a step down procedure.  The second group includes all other secondary efficacy endpoints 
and special assessments.
Secondary endpoints that are of the binary type will be analyzed using 95% confidence 
intervals.  Comparisons to external placebo will be done as described in Section 8.1.4.1.  
Comparisons between treatment groups will be done using ANOVA.  The secondary 
endpoints that are of the continuous type will be analyzed as changes from baseline, and 
reported for the two treatment groups including 95% confidence intervals.  Non-responder 
imputation (NRI) will be used to impute missing values for binary efficacy endpoints.  
Both LOCF and observed case analyses will be performed for continuous efficacy 
endpoints.  

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Has been changed to read:
8.1.4
Statistical Analyses of Efficacy
The efficacy analysis will be performed in the ITT-E population for the Week 8 efficacy 
endpoints and in the mITT population for the Week 52 efficacy endpoints.  Non-
responder imputation (NRI) will be used to impute missing values for binary efficacy 
endpoints.  Subjects who do not complete the induction period or who receive rescue 
therapy during the maintenance period will be considered as failures from that time point 
forward.  Both LOCF and observed case analyses will be performed for continuous 
efficacy endpoints.
8.1.4.1
Co-Primary and Ranked Secondary Efficacy Variables
Co-primary and ranked secondary endpoints will be summarized by treatment group with 
95% confidence intervals (CI) and adalimumab dose groups will be tested against external 
placebo in a sequentially rejective multiple test procedure in order to ensure that the 
multiple significance level of 5% is controlled, using one sample two-sided Chi-square 
tests.  The below graph describes the structure of the multiple test procedure that starts 
with testing the co-primary endpoints for the combined high and standard adalimumab 
dose groups versus external placebo and then individual dose groups versus external 
placebo separately:

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Multiple Test Procedure for the Co-Primary and Ranked Secondary Endpoints
Assuming ε = 0.0005; C = testing the endpoint for the combined high and standard adalimumab dose groups against 
external placebo; HD = testing the endpoint for the high adalimumab dose against external placebo; SD = testing the 
endpoint for the standard adalimumab dose against external placebo; P1 = co-primary induction endpoint; P2 = co-
primary maintenance endpoint; Si = ranked secondary endpoint i (i = 1,…,4)

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Section 8.1.4.3 contains details on assumed external placebo rates.
8.1.4.2
Additional Exploratory Secondary Efficacy Variables
Exploratory secondary endpoints that are of the binary type will be analyzed as 
proportions by treatment group including 95% CIs.  Exploratory secondary endpoints that 
are of the continuous type will be analyzed as changes from baseline, and reported by 
treatment group including 95% CIs.  Non-responder imputation (NRI) will be used to 
impute missing values for binary efficacy endpoints.  Both LOCF and observed case 
analyses will be performed for continuous efficacy endpoints. 
The following subset of endpoints will be tested for the high adalimumab dose against the 
standard adalimumab dose in an exploratory manner:
●
Proportion of subjects in PMS clinical remission at Week 8;
●
Proportion of subjects who achieve mucosal healing at Week 52 as measured 
by Mayo endoscopy subscore (defined as ≤ 1) in Week 8 responders per PMS;
●
Proportion of subjects in PUCAI remission (defined as < 10) at Week 52 in 
Week 8 responders per PMS;
●
Proportion of subjects in Mayo clinical response at Week 52 in Week 8 
responders per PMS;
●
Proportion of subjects in Mayo clinical remission at Week 52 in Week 8 
responders per PMS;
●
Proportion of subjects in PUCAI response (defined as a decrease in PUCAI 
≥20 points from Baseline) at Week 52 in Week 8 responders per PMS;
●
Proportion of subjects receiving corticosteroid at Baseline who discontinue 
corticosteroid  prior to Week 52 and are in Mayo clinical remission at Week 52 
in Week 8 responders per PMS;
●
Proportion of subjects receiving corticosteroid at Baseline who discontinue 
corticosteroid prior to Week 52 and are in PUCAI remission at Week 52 in 
Week 8 responders per PMS;
●
Proportion of subjects in PMS clinical remission at Week 52 in Week 8 
responders per PMS;

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●
Proportion of subjects in PUCAI remission at Week 8;
●
Proportion of subjects in PUCAI response at Week 8.
8.1.4.3
Derivation of External Placebo Control Rates
In order to derive robust external placebo assumptions for the co-primary and ranked 
secondary endpoints, a thorough literature search of placebo-controlled clinical studies in 
subjects with moderate to severe UC who had failed conventional therapy was performed.  
Studies M06-826 and M06-827 were the only available data sources with PMS data at 
Week 8.  Studies GEMINI 1 and OCTAVE Sustain were the only studies with a similar 
subject population (i.e., failure or intolerance to prior corticosteroids or IMMs), study 
design (i.e., randomized withdrawal), and endpoint definitions for derivation of external 
placebo rates for the Week 52 endpoints in Study M11-290. 
For all co-primary and ranked secondary endpoints where available, separate estimates for 
anti-TNF naïve placebo patients and anti-TNF experienced placebo patients were derived 
as described by endpoint below.  The estimates for anti-TNF naïve placebo patients and 
anti-TNF experienced placebo patients were then combined as a weighted mean according 
to the assumed proportion of anti-TNF naïve and experienced subjects as per the 
Study M11-290 protocol, i.e., 0.75 × rate in anti-TNF naïve + 0.25 × rate in anti-TNF 
experienced subjects.  To be conservative, the upper limit of the 95% CI for the weighted 
mean was used as the external placebo assumption.
For PMS remission at Week 8:  A remission rate of anti-TNF naïve placebo patients was 
estimated using logistic regression with anti-TNF naïve placebo patients from 
Studies M06-826 and M06-827 and study as a fixed effect, in order to weight the studies 
according to their sample sizes.  Anti-TNF experienced placebo patients were only 
available in Study M06-827, so the remission rate from this study only was used as 
remission rate for anti-TNF experienced placebo patients.
For Mayo Score remission and mucosal healing at Week 52 in Week 8 responders per 
PMS, as well as for Mayo Score remission at Week 52 in Week 8 remitters per PMS:  

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Separate remission rates of anti-TNF naïve and anti-TNF experienced placebo patients 
were estimated using separate logistic regression models with anti-TNF naïve placebo 
patients and anti-TNF experienced placebo patients, respectively, from GEMINI 1 and 
OCTAVE Sustain and study as a fixed effect, in order to weight the studies according to 
their sample sizes.
For Mayo Score response Week 52 in Week 8 responders per PMS: Results were not 
available by anti-TNF naïve versus anti-TNF experienced placebo patients, so the overall 
response rates in placebo subjects from GEMINI 1 and OCTAVE Sustain were combined 
via logistic regression with study as a fixed effect, in order to weight the studies according 
to their sample sizes.
For steroid-free remission per Mayo Score at Week 52 in Week 8 responders per PMS 
with corticosteroids at Baseline:  Only data from GEMINI 1 was available.  Rates of anti-
TNF naïve and anti-TNF experienced placebo patients from GEMINI 1 were combined to 
a weighted mean (0.75 × rate in anti-TNF naïve + 0.25 × rate in anti TNF experienced 
subjects) and the upper bound of the 95% CI for the weighted mean was used.
Table 5.
External Placebo Assumptions for Co-Primary and Ranked 
Secondary Efficacy Endpoints
Endpoint
External Placebo Rate 
(95% CI Upper Limit from Meta-Analysis)
Week 8 PMS Remission 
19.83%
Week 52 FMS Remission in Week 8 Responders per PMS
18.37%
Week 52 FMS Response in Week 8 Responders per PMS
26.10%
Week 52 Mucosal Healing in Week 8 Responders per PMS
22.03%
Week 52 FMS Remission in Week 8 Remitters per PMS
14.79%
Week 52 FMS Remission in Week 8 Responders per PMS with CS 
at Baseline and Discontinuation of CS prior to Week 52
24.08%
FMS = Full Mayo Score; PMS = Partial Mayo Score; CS = Corticosteroids

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Section 8.2  Determination of Sample Size
Previously read:
The sample size was calculated for the co-primary endpoints at Week 8 and Week 52.  
The Week 8 co-primary endpoint is to compare the lower limit of the 95% CI of the 
remission rate per PMS in the adalimumab high induction group in this study to the upper 
limit of the 95% CI of the corresponding external placebo rate to be identified from a 
meta-analysis of relevant publically available clinical trials.  For illustrative purposes 
only, the following calculations use results from adult UC studies (Studies M06-826 and 
M06-827) as an estimate for the external placebo rates. Assuming a 48.33% remission 
rate per PMS at Week 8 for the high induction dose group and given an upper limit of the 
95% CI for the remission rate per PMS of the external placebo of 19.52%, a sample size 
of 65 subjects (high:standard = 39:26) provides at least 97% power for a one sample 
two-sided Chi-square test using a significance level of 5% for the Week 8 co-primary 
endpoint.
The Week 52 co-primary endpoint is to compare the lower limit of the 95% CI of the 
remission rate per Mayo score in the adalimumab high maintenance dose group in this 
study to the upper limit of the 95% CI of the external placebo rate.  Assuming a 36.63% 
remission rate per Mayo score at Week 52 for the high maintenance dose group and given 
an upper limit of the 95% CI for the remission rate per Mayo score of the external placebo 
of 13.81%, a sample size of 54 subjects (high:standard = 27:27) in the maintenance period 
of the study provides at least 85% power for a one sample two-sided Chi-square test using 
a significance level of 5% for the Week 52 co-primary endpoint.
Based on the assumption of a 75% response rate at Week 8, a total of 85 subjects are 
needed in the study (including internal placebo subjects enrolled prior to Amendment 4). 

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Sample Size Based on Week 8 and Week 52 Co-Primary Endpoints
Endpoints
External 
Placebo 
Upper 
95% CI
Assumption 
for High 
ADA Group
Power
N in High 
ADA 
Group
Randomization Ratio
Total 
Induction 
Phase Sample 
Size
Week 8 
PMS 
Remission 
Rate
19.52%a
48.33%
97%
39
Induction
High:Standard
3:2 = 39:26
85b,c
Endpoints
External 
Placebo
Upper 
95% CI
Assumption 
for High 
ADA Group
Power
N in High 
ADA 
Group
Randomization Ratio
Total 
Maintenance 
Phase Sample 
Size
Week 52 
MS 
Remission 
Rate
13.81%a
36.63%
85%
27
Maintenance
High:Standard  
1:1 = 27:27 
63b,d
PMS = partial Mayo score; MS = full Mayo score
a.
The upper limit of 95% CI for placebo derived from adult UC Studies M06-826 and M06-827 for illustrative 
purposes only in the absence of results from the ongoing meta-analysis.
b.
Sample size calculation is based on a one group Chi-square test.
c.
85 subjects are needed assuming 75% PMS response rate at Week 8.
d.
Including subjects enrolled into the internal placebo arm (prior to Amendment 4).
Has been changed to read:
The co-primary endpoints will be tested first for the combined high and standard 
adalimumab dose groups versus external placebo and then individual dose groups versus 
external placebo separately, controlling the multiple significance level of 5%.  For each 
individual test the nominal power is calculated. 
Assuming a 48% remission rate per PMS at Week 8 for the combined standard and high 
adalimumab induction dose groups and a remission rate per PMS of 19.83% for external 
placebo, a total of 77 subjects (high:standard = 46:31) in ITT-E population provides at 
least 99% power for a one sample two-sided Chi-square test using a significance level of 
5%. 
Assuming a 36% remission rate per Mayo Score at Week 52 for the combined standard 
and high maintenance dose groups and a remission rate per Mayo Score of 18.37% for 

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external placebo, a total of 57 subjects in the combined adalimumab maintenance dose 
groups in mITT population (e.g., high:standard = 28:29) provide 88% power for a one 
sample two-sided Chi-square test using a significance level of 5%. 
Assuming that the high adalimumab dose regimen is associated with higher efficacy than 
the standard adalimumab dose regimen and assuming a 52% remission rate per PMS at 
Week 8 for the high adalimumab induction dose group and a remission rate per PMS of 
19.83% for external placebo, 46 subjects in the high adalimumab induction dose group of 
ITT-E population provide at least 99% power for a one sample two-sided Chi-square test 
using a significance level of 4.95%. 
Assuming a 41% remission rate per Mayo Score at Week 52 for the high adalimumab 
maintenance dose groups and a remission rate per Mayo Score of 18.37% for external 
placebo, a total of 28 subjects in the high adalimumab maintenance dose group of the 
mITT population provide at least 80% power for a one sample two-sided Chi-square test 
using a significance level of 4.95%.
Based on the assumption of a 75% response rate at Week 8, 93 subjects will have to be 
included in the study (including ~12 internal placebo subjects in the maintenance part of 
the study who were included prior to Amendment 4) to ensure 57 subjects in the 
combined adalimumab maintenance dose groups.
Appendix B.  List of Protocol Signatories
Previously read:
Name
Title
Functional Area
Statistics
Clinical
Pharmacokinetics 
Clinical
Clinical
Clinical

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Has been changed to read:
Name
Title
Functional Area
Statistics
Clinical
Pharmacokinetics 
Clinical
Clinical
Clinical