A Multicenter, Randomized, Double-Blind, Placebo Controlled Study to Evaluate the Efficacy and Safety of Adalimumab for the Induction and Maintenance of Clinical Remission in Chinese Patients With Moderately to Severely Active Crohn's Disease and Elevated High-Sensitivity C-reactive Protein
Phase: PHASE3
Conditions: Crohn's Disease
Sponsor: AbbVie

Adalimumab
M14-233 Protocol
Amendment 1
1
1.0
Title Page
Clinical Study Protocol M14-233
A Multicenter, Randomized, Double-Blind, Placebo 
Controlled Study to Evaluate the Efficacy and Safety 
of Adalimumab for the Induction and Maintenance of 
Clinical Remission in Chinese Patients with 
Moderately to Severely Active Crohn's Disease and 
Elevated High-Sensitivity C-reactive Protein
Incorporating Administrative Change 1 and 
Amendment 1
AbbVie Investigational
  Product:
Adalimumab
Date:
19 October 2015
Development Phase:
3
Study Design:
A randomized, double-blind, placebo controlled, multicenter study of the 
safety and efficacy of adalimumab in Chinese patients with moderately 
to severely active Crohn's disease
Investigators:
Multicenter study.  Investigator's information is on file at AbbVie.
Sponsor:
AbbVie Inc.
This study will be conducted in compliance with the protocol, Good Clinical Practice and all other 
applicable regulatory requirements, including the archiving of essential documents.
Confidential Information
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
/$5

Adalimumab
M14-233 Protocol
Amendment 1
2
1.1
Protocol Amendment:  Summary of Changes
The purpose of this amendment is to:
●
Section 1.0, Title Page, update Global Study Designated Physician.
Rationale:  To provide contact information for the new Global Study 
Designated Physician.
●
Section 3.3, Adalimumab Overview, add additional approved adalimumab 
indications.
Rationale:  To provide additional approved adalimumab indications.
●
Section 5.1, Overall Study Design and Plan:  Description, Re-screening, clarify 
re-screening requirements for anti-HIV-1, HBV, and Anti-Hepatitis C testing.
Rationale:  To clarify re-screening requirements in regards to anti-HIV-1, 
HBV, and Anti-Hepatitis C testing, and to reduce unnecessary testing.
●
Section 5.1, Overall Study Design and Plan:  Description, Re-screening, 
update re-screening window for anti-HIV-1 repeat testing to 50 days.
Rationale:  To align better with the seroconversion window of the 
immunoassay used by the central lab.
●
Section 5.2.1, Inclusion Criteria, add half tablet formulation language for 
azathioprine or 6-MP in Inclusion Criterion 4.
Rationale:  To add that half-tablet formulations should be considered when 
rounding to determine azathioprine or 6-MP dose.
●
Section 5.2.2, Exclusion Criteria, remove efalizumab from Exclusion 
Criterion 12.
Rationale:  To only reference available medications.
●
Section 5.2.2, Exclusion Criteria, clarify Exclusion Criterion 31 to exclude 
subjects with previous history of gastric dysplasia.
Rationale:  To clarify that only gastric dysplasia and not dysplasia of the 
gastrointestinal tract is exclusionary to allow broader enrollment of patients.
●
Section 5.2.3.3, Prohibited Therapy, remove efalizumab from list of prohibited 
medications during study.
Rationale:  To only reference available medications.

Adalimumab
M14-233 Protocol
Amendment 1
3
●
Section 5.3.1, Efficacy and Safety Measurements Assessed and Flow Chart, 
Table 1, Study Activities, table note "n.," clarify re-screening requirements for 
anti-HIV-1, HBV, and Anti-Hepatitis C testing.
Rationale:  To clarify re-screening requirements in regards to anti-HIV-1, 
HBV, and Anti-Hepatitis C testing, and to reduce unnecessary testing.
●
Section 5.3.1, Efficacy and Safety Measurements Assessed and Flow Chart, 
Table 1, Study Activities, table note "n.," update re-screening window for 
anti-HIV-1 repeat testing to 50 days.
Rationale:  To align better with the seroconversion window of the 
immunoassay used by the central lab.
●
Section 5.3.1.1, Study Procedures, Hepatitis and HIV Testing, clarify 
re-screening requirements for anti-HIV-1, HBV, and Anti-Hepatitis C testing.
Rationale:  To clarify re-screening requirements in regards to anti-HIV-1, 
HBV, and Anti-Hepatitis C testing, and to reduce unnecessary testing.
●
Section 5.3.1.1, Study Procedures, Hepatitis and HIV Testing, update 
re-screening window for anti-HIV-1 repeat testing to 50 days.
Rationale:  To align better with the seroconversion window of the 
immunoassay used by the central lab.
●
Section 5.3.1.2, Blood Samples for Pharmacogenetic Analysis, clarify that an 
AbbVie designated laboratory in China will perform testing and long-term 
storage.
Rationale:  To clarify that an AbbVie designated laboratory in China will 
perform testing and long-term storage of pharmacogenetic samples.
●
Section 5.3.1.3, Blood Samples for Biomarkers Analysis, clarify that an
AbbVie designated laboratory in China will perform testing and long-term 
storage.
Rationale:  To clarify that an AbbVie designated laboratory in China will 
perform testing and long-term storage of biomarker samples.
●
Section 5.3.5, Pharmacokinetic Variables, add section.
Rationale:  To specify further the pharmacokinetic variables being studied.

Adalimumab
M14-233 Protocol
Amendment 1
4
●
Section 5.4.1, Discontinuation of Individual Subjects, clarify to withdraw 
subjects if dysplasia occurs.
Rationale:  To clarify that dysplasia and not specifically dysplasia of the 
gastrointestinal tract will require subjects to be withdrawn from the study.
●
Section 5.4.1, Discontinuation of Individual Subjects, add that information 
regarding any ongoing or new AEs/SAEs will be recorded on the appropriate 
eCRF page.
Rationale:  To provide further details on how data for any ongoing or new 
AEs/SAEs gathered during the 70-day follow-up phone call will be captured 
●
Section 6.1.5, Adverse Event Reporting, update Primary Study Designated 
Physician.
Rationale:  To provide contact information for the new Primary Study 
Designated Physician.
●
Section 6.1.5, Adverse Event Reporting, clarify adverse event reporting 
process preferred route and update local pharmacovigilance contact 
information.
Rationale:  To clarify adverse event reporting process preferred route and 
provide new contact information for local pharmacovigilance.
●
Section 7.0, Protocol Deviations, clarify that AbbVie does allow deviations 
when necessary to eliminate an immediate hazard to study subjects.
Rationale:  To ensure study sites can deviate from the protocol when 
necessary if in the best interest of the study subjects.
●
Appendix B, List of Protocol Signatories, update Associate Medical Director, 
remove Program Lead I, and add Study Management Associate III.
Rationale:  To list the new Associate Medical Director signatory and replace 
Program Lead I with Study Management Associate III as signatory.
●
Appendix D, Standard Weights, update references to actual height to adjusted 
height.
Rationale:  To clarify that the height used to determine standard weight for 
CDAI scoring is adjusted to include one inch or 2.5 cm.
●
Appendix E, Sample Injection Instructions for Onsite Administration –
Pre-Filled Syringe, add measurement references in cm.

Adalimumab
M14-233 Protocol
Amendment 1
5
Rationale:  To provide measurements in local units.
●
Appendix F, Sample Injection Instructions for at Home Dosing – Pre-Filled 
Syringe, add measurement references in cm.
Rationale:  To provide measurements in local units.
●
Incorporate administrative changes, correct typographical and grammatical 
errors and make further clarifications throughout the protocol.
An itemized list of all changes made to this protocol amendment can be found in 
Appendix I.

Adalimumab
M14-233 Protocol
Amendment 1
6
1.2
Synopsis
AbbVie Inc.
Protocol Number:  M14-233
Name of Study Drug:  Adalimumab
Phase of Development:  3
Name of Active Ingredient:  Adalimumab
Date of Protocol Synopsis:  19 October 2015
Protocol Title:  A Multicenter, Randomized, Double-Blind, Placebo Controlled Study to Evaluate the 
Efficacy and Safety of Adalimumab for the Induction and Maintenance of Clinical Remission in Chinese 
Patients with Moderately to Severely Active Crohn's Disease and Elevated High-Sensitivity C-reactive 
Protein
Objectives:  The primary objective of this study is to assess the efficacy and safety of adalimumab in 
inducing (at Week 4) and maintaining (at Week 26 in Week 8 responders) clinical remission, defined as 
Crohn's Disease Activity Index (CDAI) < 150, in Chinese subjects with moderately to severely active CD 
and elevated hs-CRP.
Additional Objectives:  To assess the effect of adalimumab treatment on other efficacy outcomes, 
including clinical response, steroid free remission, and improvement in quality of life.
Investigators:  Multicenter in China
Study Sites:  Approximately 12 – 15 sites in China
Study Population:  Chinese males and females 18 to 70 years (inclusive) of age with moderately to 
severely active CD and elevated (≥ 3 mg/L) high-sensitivity C-reactive protein who are naïve to anti-TNF 
therapy.
Number of Subjects to be Enrolled:  Approximately 200 (100 in active group and 100 in placebo 
group).
Methodology:  
This is a Phase 3, randomized, double-blind, placebo controlled, multicenter study of adalimumab in 
anti-TNF naïve Chinese subjects with moderately to severely active CD (220 ≤ Crohn's disease activity 
index [CDAI] ≤ 450) and elevated hs-CRP (≥ 3 mg/L).  The study consists of an 8-week double-blinded 
period followed by an open-label (OL) period of 18 weeks.  Subjects will be randomized in a 1:1 ratio to 
receive adalimumab or placebo at Baseline.  Subjects randomized to adalimumab at Week 0 will receive 
blinded adalimumab 160 mg at Week 0, 80 mg at Week 2, and blinded 40 mg adalimumab and placebo at 
Week 4 and Week 6.  Subjects randomized to placebo at Week 0 will receive blinded placebo at Week 0 
and Week 2, then will receive blinded adalimumab 160 mg at Week 4 and 80 mg at Week 6.  At Week 8, 
all subjects will enroll in an 18-week OL period to receive adalimumab 40 mg every other week (eow).

Adalimumab
M14-233 Protocol
Amendment 1
7
Methodology (Continued):
Adalimumab Treatment Regimen
(Double-Blind Period)
Placebo Treatment Regimen
(Double-Blind Period)
Study Visit
Number 
of Active 
Syringes
Number 
of Placebo 
Syringes
Study Visit
Number 
of Active 
Syringes
Number 
of Placebo 
Syringes
Week 0 – 160 mg ada
4
0
Week 0 – placebo
0
4
Week 2 – 80 mg ada
2
0
Week 2 – placebo
0
2
Week 4 – 40 mg ada
1
3
Week 4 – 160 mg ada
4
0
Week 6 – 40 mg ada
1
1
Week 6 – 80 mg ada
2
0
ada = adalimumab
Note:
At Week 8, study drug will be administered during the OL Period of the study.
The study duration will be up to 39 weeks, and will include a screening period of up to 35 days, an 
8-week double-blind treatment period, an 18-week OL period and a 70-day follow-up period.  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.  The 70-day follow-up phone call will not be 
required for any subject who initiates adalimumab therapy not supplied in the context of the clinical trial 
after the end of study participation.  All subjects will be screened for tuberculosis (TB) during the 
Screening period and throughout the trial.
TB Screening consists of: 
!
QuantiFERON-TB Gold In-Tube test (QTF)
!
CXR (chest CT scan can be used instead of CXR at the Investigator's discretion)
!
Medical history of contact with active TB
If any of the three assessments (QTF, CXR/CT, or medical history) is positive during the Screening 
Period, the subject will be considered to have latent TB infection (LTBI) and will receive TB 
prophylaxis.
For subjects with an indeterminate QTF result during the Screening period, a repeat Screening period test 
should be performed with another blood sample or the subject must initiate TB prophylaxis prior to 
enrolling in the study.  If the repeat testing result during the Screening period is negative the QTF test 
result is considered negative, but if the repeat testing result is indeterminate or positive TB prophylaxis 
should be initiated.
In the assessment of the Screening CXR/chest CT scan, a radiologist must note the presence or absence 
of 1) calcified granulomas, 2) pleural scarring/thickening, and 3) signs of active TB as well as the 
presence of hilar and/or mediastinal lymphadenopathy.  The Principal Investigator must indicate the 
clinical significance of any findings and contact the AbbVie SDP to discuss any clinically significant 
abnormal findings before enrolling the subject.  The Principal Investigator (or designee) will sign and 
date each report.
Subjects who have a diagnosis of LTBI during Screening and do not initiate prophylaxis cannot be 
enrolled.

Adalimumab
M14-233 Protocol
Amendment 1
8
Methodology (Continued):
Subjects who have a diagnosis of LTBI and agree to initiate prophylaxis should be consulted with a TB 
specialist (a physician with TB treatment knowledge and experience) regarding the selection of the 
appropriate TB prophylaxis regimen as per Centers for Disease Control (CDC) recommendations or local 
guidelines.
Initiation of TB prophylaxis in subjects with negative LTBI screening is permitted during the Screening 
period as warranted based on the opinion of the investigator.
Subjects with an LBTI diagnosis or those in whom TB prophylaxis is electively initiated will receive TB 
prophylaxis for at least 21 days (before or on the Day –21 visit) prior to Baseline (Week 0), and are 
required to have a Day –21 and Day –7 visits.  At Day –21, the CDAI and hs-CRP must be obtained and 
must meet the entry criteria in Section 5.2.  For the calculation of the CDAI on Day –21, the hematocrit 
value obtained at the first screening visit will be used.  After initiation of TB prophylaxis, subjects will 
return to the clinical site 7 days (at Day –7) prior to Baseline (Week 0) to have safety labs drawn, 
including hs-CRP.  The hematocrit and hs-CRP values obtained at Day –7 will be used to calculate the 
Baseline (Week 0) CDAI to confirm eligibility for study enrollment.
All subjects will be monitored for signs and symptoms suggestive of active TB at all visits.  Additional 
QTF and chest imaging testing will be performed throughout the study as outlined below:
Chart for TB Assessments at Screening and After Week 0
Screening Period
After Week 0
Monitoring For:
QTF
CXR/CT
Medical 
History
TB 
Prophylaxis 
Required
LTBI
Active TB
+
+
+
Yes
No
Yes^
+
+
-
Yes
No
Yes^
+
-
+
Yes
No 
Yes^
+
-
-
Yes
No
Yes^
-
+
+
Yes
No
Yes^
-
-
+
Yes
No
Yes^
-
+
-
Yes
No
Yes^
-
-
-
No
Yes*
Yes^
*
During follow-up, subjects who are negative for LTBI during screening and are not taking TB prophylaxis will 
have their QTF repeated at Weeks 2, 4, 6, 8, 12, 16, 20, and 26/Premature Discontinuation and the chest 
imaging repeated at Weeks 8, 16, and 26/Premature Discontinuation.  Subjects who are negative for LBTI 
during Screening who initiate TB prophylaxis per the Investigator's discretion do not require repeat QTF testing.
^
All subjects will be monitored for signs and symptoms suggestive of active TB at all visits. CXR (or chest CT, 
at the Investigator's [or designee's] discretion) will be repeated Weeks 8, 16, and 26/Premature Discontinuation.  
If there are signs or symptoms suggestive of active TB, and/or changes in the chest imaging, a diagnostic 
investigation must be done.

Adalimumab
M14-233 Protocol
Amendment 1
9
Methodology (Continued):
All subjects who initiate TB prophylaxis should continue the prophylaxis regimen for the duration of the 
subject's participation in the study, including the 70-day follow-up period.
The randomization will be stratified by Crohn's disease activity (CDAI ≤ 300, > 300) at Baseline 
(Week 0) and systemic corticosteroid use at Baseline.
All subjects will have blood samples drawn for the measurement of adalimumab concentration 
immediately prior to dosing at Baseline (Week 0), and Weeks 4, 8, 12, and 26/Premature Discontinuation 
and anti-adalimumab antibody (AAA) levels just prior to dosing at Baseline (Week 0), Weeks 4, 12 and 
26/Premature Discontinuation.  If a subject meets the criteria for dose escalation, blood samples will also 
be obtained for adalimumab concentration and AAA levels at the time of dose escalation.  Pre-dosing 
serum samples for infliximab concentration and human antichimeric antibodies (HACAs) will be 
collected at Baseline (Week 0).  An optional mRNA sample and an optional pharmacogenetic sample will 
be drawn prior to dosing at Baseline and Week 26/Premature Discontinuation (only if subject 
discontinues at or after Week 8).
At Week 4, all subjects who are on oral steroids will have their steroid dose tapered according to the 
schedule in Section 5.3.1.1.  The steroid taper is mandatory and deviations from the taper (or increases in 
steroid doses) are not permitted.  If the Investigator feels that the steroid taper is not advisable for a 
particular subject at Week 4, the subject must be withdrawn from the study.
If a subject who has tapered their corticosteroid dose is judged by the Investigator to have an inadequate 
response per the PI's judgment, dose escalation (allowed at or after Week 12) should be considered if the 
subject meets the below criteria, otherwise, the subject should be withdrawn from the study.
For the purposes of dose escalation, inadequate response is defined as:
Crohn's disease activity index (CDAI) ≥ 200 and at least one of the following criteria is met:  an increase 
of at least 1 mg/L in level of high-sensitivity C-reactive protein (hs-CRP) from Baseline or a hs-CRP 
≥5 mg/L.  The hs-CRP results used to determine inadequate response should be the most recent available 
results.  Assessment of inadequate response should include consideration by the Investigator to rule out 
symptoms caused by reasons other than Crohn's disease related inflammation.  The most recent hs-CRP 
value should first be assessed in relation to the most recent CDAI from the previous visit.  Then the most 
recent hs-CRP value should be assessed in relation to CDAI calculated at the current visit.  Dose changes 
are to only occur in accordance with the eow dosing schedule.
At or after Week 12, any subject who experiences inadequate response may increase dose to OL 
adalimumab 80 mg eow.  If the subject has received OL 80 mg eow therapy and continues to demonstrate 
inadequate response, he or she should be withdrawn from the study per PI discretion.
Additionally, 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 the designated study visits.  For any subject with clinical signs/symptoms of active TB 
or newly identified TB risk factors, a CXR/chest CT scan (per investigator discretion) may be required 
for evaluation of active TB, and it is recommended to contact the SDP for further guidance.  Subjects 
with confirmed active TB must be discontinued from the study and receive standard of care based on 
consultation with a local TB specialist (a physician with TB treatment knowledge and experience).

Adalimumab
M14-233 Protocol
Amendment 1
10
Methodology (Continued):
During the Screening and Double-Blind Periods, in addition to the TB screening described above, the 
following tests will be performed.  Laboratory tests (hematologic and chemical analysis, including 
hs-CRP) will be performed during Screening and at Weeks 0, 2, 4, and 8/Premature Discontinuation.  
Urinalysis will be performed at Screening and Weeks 0, 4, and 8/Premature Discontinuation.  Serum will 
be collected during the Screening Period for testing for anti-nuclear antibodies (ANA) and reflective 
anti-double-stranded deoxyribonucleic acid (dsDNA) antibodies.
During the OL period, in addition to the TB screening described above, laboratory tests (hematologic and 
chemical analysis, including hs-CRP) will be performed during study visits at Weeks 12, 16, 20, and 
26/Premature Discontinuation, and urinalysis will be performed at Weeks 12, 20, and 26/Premature 
Discontinuation.
AEs will be collected during the study and for 70 days after the last study drug administration.
Crohn's Disease Activity Index (CDAI) will be obtained during the Screening Period and at Weeks 0, 2, 
4, 6, 8, 12, 16, 20, and 26/Premature Discontinuation.  If the subject doses onsite then the CDAI will also 
be completed at Weeks 10, 14, 18, 22, and 24.  The inflammatory bowel disease questionnaire (IDBQ) 
will be administered at Weeks 0, 4, 8, and 26/PD.
Subjects should adhere to the required visit schedule.  Study visits should occur within the ± 3 day visit 
window.  The Baseline visit at Week 0 should occur within 35 days of the Screening visit.
Diagnosis and Main Criteria for Inclusion/Exclusion:  
Main Inclusion:  
1.
Male or female of Chinese descent with full Chinese parentage 18 to 70 years (inclusive) of age at 
Baseline (Week 0).
2.
Confirmed diagnosis of Crohn's disease for at least 3 months prior to Baseline (Week 0).  
Appropriate documentation of biopsy results consistent with the diagnosis of CD, in the assessment 
of the Investigator, must be available.
3.
Subject has hs-CRP ≥ 3 mg/L in all laboratory measurements during the Screening Period.
4.
Crohn's Disease Activity Index (CDAI) ≥ 220 and ≤ 450 at Baseline (Week 0) despite concurrent or 
prior treatment with an adequate course, in the opinion of the investigator, of at least one of the 
following (oral corticosteroids or immunosuppressants or both as defined below):
!
Subjects taking oral corticosteroids, excluding budesonide:
o
Oral corticosteroid dose must be ≤ 20 mg/day (prednisone or equivalent);
!
For subjects with a dose > 10 and ≤ 20 mg/day, dose has been stable for at least 7 days 
prior to Baseline and the duration of the current steroid course has been at least 14 days 
prior to Baseline.
!
For subjects with a dose ≤ 10 mg/day, dose has been stable for at least 10 days prior to 
Baseline (Week 0) and the duration of the current steroid course has been at least 
14 days prior to Baseline (Week 0).
!
Subjects taking oral budesonide:
o
Dose must not exceed 9 mg/day;
!
For subjects with a dose ≥ 6 mg/day, dose has been stable for at least 7 days prior to 
Baseline and the duration of the current steroid course has been at least 14 days prior to 
Baseline.

Adalimumab
M14-233 Protocol
Amendment 1
11
Diagnosis and Main Criteria for Inclusion/Exclusion (Continued):
Main Inclusion (Continued):
!
For subjects with a dose < 6 mg/day, dose has been stable for at least 10 days prior to 
Baseline (Week 0) and the duration of the current steroid course has been at least 
14 days prior to Baseline (Week 0).
and/or,
!
At least a consecutive 42-day course of azathioprine, 6-mercaptopurine (6-MP), or injectable 
methotrexate (MTX) prior to Baseline (Week 0), with a minimum dose of azathioprine 
≥0.75 mg/kg/day or 6-MP ≥ 0.5 mg/kg/day (rounded to the nearest available tablet or half tablet 
formulation) or MTX ≥ 15 mg/week (subcutaneous [SC]/intramuscular [IM]), or a dose that is 
the highest tolerated by the subject (e.g., due to leukopenia, elevated liver enzymes, nausea) 
during that time.
o
Subject must be on a stable dose for at least 28 days prior to Baseline (Week 0).
!
For subjects taking azathioprine, the dose should not exceed 3 mg/kg/day.
!
For subjects taking 6-MP, the dose should not exceed 1 mg/kg/day.
!
For subjects taking IM/SC MTX, dose should not exceed 25 mg per week.
!
Note:  Oral MTX use is allowed during the study (at a stable dose for 28 days prior to 
Baseline), however use of oral MTX is not sufficient for inclusion into the study.
Note:
If a subject is on both an oral corticosteroid and an immunosuppressant listed 
above, BOTH of the drugs need to meet the above criteria.
and/or
!
Concurrent therapy with corticosteroids or the above-mentioned immunosuppressants 
(azathioprine, 6-MP or IM/SC MTX) is not required for subjects not currently taking these 
medications who were previously treated during the past 2 years 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.
5.
Subject has a negative TB Screening Assessment.  If the subject has evidence of a latent TB infection 
during the Screening Assessment, the subject must initiate and complete a minimum of 3 weeks (or 
per local guidelines, whichever is longer) of an ongoing TB prophylaxis prior to Baseline 
(Section 5.3.1).
6.
If female subject, is either not of childbearing potential, defined as postmenopausal for at least 1 year 
or surgically sterile (bilateral tubal ligation, bilateral oophorectomy and/or hysterectomy) 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):
!
Condoms, sponge, foams, jellies, diaphragm or intrauterine device (IUD);
!
Hormonal contraceptives for 90 days prior to study drug administration;
!
A vasectomized partner.
7.
Subject must be able and willing to give written informed consent and to comply with the 
requirements of this study protocol.

Adalimumab
M14-233 Protocol
Amendment 1
12
Diagnosis and Main Criteria for Inclusion/Exclusion (Continued):  
Main Inclusion (Continued):
8.
Subject is judged to be in otherwise good health as determined by the Principal Investigator (or 
designee) based upon the results of medical history, laboratory profile, physical examination, CXR, 
and a 12-lead electrocardiogram (ECG) performed during Screening.
9.
Subject must be able and willing to self-administer subcutaneous (SC) injections or have a qualified 
person available to administer SC injections.
Main Exclusion:  
1.
Subject with a current diagnosis of ulcerative colitis (UC) or indeterminate colitis.
2.
Subject who has discontinued azathioprine or 6-MP or MTX or another immunomodulator within 
14 days of Baseline (Week 0), or, for subjects taking oral MTX or another immunomodulator, has 
not been on a stable dose for at least 28 days prior to Baseline.
3.
Subject who has discontinued use of oral aminosalicylates within 14 days of Baseline (Week 0) or, 
for subjects taking oral aminosalicylates, has not been on a stable dose for at least 28 days prior to 
Baseline.
4.
Subject taking both oral budesonide and oral prednisone (or equivalent) simultaneously, with the 
exception of non-systemic steroids (e.g., inhalers or dermatological preparations), during the 
Screening Period and during the study.
5.
Subject taking intravenous corticosteroids within 14 days prior to Screening, during the Screening 
Period, or who has discontinued oral corticosteroids within 14 days before Baseline (Week 0).
6.
Subject who has had a surgical bowel resection within 6 months of Screening or who is planning a 
resection at any time point in the future.
7.
Subject with symptomatic known obstructive strictures.
8
Subject with an internal or external fistula (with the exception of an anal fistula without abscess).
9.
Subject with an ostomy or ileoanal pouch.
10. Subject with short bowel syndrome.
11. Subject has received therapeutic enema or suppository, other than required for endoscopy, within 
14 days prior to Screening and/or during the Screening period.
12. Subject with prior exposure to medications that have a potential or known association with 
progressive multifocal leukoencephalopathy, including participation in a clinical trial of 
investigational agents targeting white cell trafficking (e.g., natalizumab [Tysabri®] or rituximab 
[Rituxan®]).
13. Subject has been treated with any investigational agent or procedure (including previous fecal 
microbial transplantation) within a minimum of 30 days or 5 half-lives (whichever is longer) of the 
drug prior to the Baseline (Week 0) Visit.
14. Previous participation in an adalimumab clinical study.  Prior exposure to any anti-tumor necrosis 
factor (TNF) agent (including but not limited to branded or biosimilar versions of adalimumab 
[Humira®], infliximab [Remicade®], etanercept [Enbrel®], golimumab [Simponi®] or certolizumab 
pegol [Cimzia®]).  Prior exposure to ustekinumab (Stelara®), tofacitinib (Xeljanz®), tocilizumab 
(Actemra®), anakinra (Kineret®), abatacept (Orencia®) or vedolizumab (Entyvio®).
15. Subject taking Crohn's-related antibiotics who has been on this therapy to treat an active infection or 
who has not been on stable doses of these medications for at least 14 days prior to Baseline.

Adalimumab
M14-233 Protocol
Amendment 1
13
Diagnosis and Main Criteria for Inclusion/Exclusion (Continued):
Main Exclusion (Continued):
16. Subject has received cyclosporine, tacrolimus, or mycophenolate mofetil within 30 days prior to 
Baseline (Week 0).
17. Active infection(s) requiring treatment with intravenous (IV) anti-infectives within 30 days prior to 
the Baseline (Week 0) Visit or oral anti-infectives within 14 days prior to the Baseline Visit.
18. Subject currently receiving total parenteral nutrition (TPN) during Screening and/or at Baseline 
(Week 0) or subject who plans to receive TPN at any time during the course of the study.
19. Subject with positive Clostridium difficile (C. difficile) toxin stool assay during the Screening period.
20. Subject has received any systemic traditional Chinese medicine preparation within 14 days before 
Baseline (Week 0).  
21. Subject has received any thalidomide within 28 days before Baseline (Week 0).
22. Screening laboratory and other analyses show any of the following abnormal results (if a subject 
starts TB prophylaxis, lab results [except ECG] should be confirmed at Day –7):
!
AST, ALT > 1.5 × upper limit of the reference range;
!
WBC count < 3.0 × 109/L;
!
Electrocardiogram (ECG) – with clinically significant abnormalities;
!
Total bilirubin ≥ 3 mg/dL; except for subjects with isolated elevation of indirect bilirubin 
relating to Gilbert syndrome;
!
Serum creatinine > 1.6 mg/dL.
23. Known hypersensitivity to adalimumab or its excipients.
24. History of demyelinating disease (including myelitis) or neurologic symptoms suggestive of 
demyelinating disease.
25. History of invasive infection (e.g., listeriosis and histoplasmosis) or human immunodeficiency virus 
(HIV) or active TB.
26. Subject with any active viral infection that based on the investigator's clinical assessment makes the 
subject an unsuitable candidate for the study.
27. Positive anti-HIV-1 antibody (HIV-1 Ab), unless the screening anti-HIV-1 antibody is subsequently 
found to be negative on confirmatory testing; and/or positive Hepatitis C virus antibody (HCV Ab) 
indicative of a previous or current infection; and/or positive Hepatitis B surface antigen (HBs Ag) or 
detected sensitivity on the Hepatitis B (HBV)-DNA polymerase chain reaction test for Hepatitis B 
core antibody (HBc Ab Total) positive subjects.  If Hepatitis B envelope antigen and antibodies 
(HBe Ag or HBe Ab) are detected, it is per investigator discretion to enroll the subject.
28. Chronic recurring infections or Active TB.
Active TB is considered to be:
!
Subject with CXR (or chest CT scan) findings suggestive of active TB as determined by a 
radiologist;
!
Subject with any clinical symptoms consistent with active TB;
!
With or without micobacteriology/histology examination for Mycobacterium tuberculosis or 
granulomas.

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Diagnosis and Main Criteria for Inclusion/Exclusion (Continued):  
Main Exclusion (Continued):
29. Subjects with any findings indicating a history of TB infection (calcified nodules or granulomas 
and/or fibrotic scar, apical or basilar thickening) by CXR examination (or chest CT scan) at the 
screening evaluation and no documentation of prophylactic treatment.
30. 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.
31. Subject with a previous history of gastric dysplasia.
32. Positive pregnancy test at Screening or Baseline (Week 0).
33. Female subjects who are breastfeeding or considering becoming pregnant during the study.
34. History of clinically significant drug or alcohol abuse, including use of medical marijuana, in the last 
12 months.
35. Clinically significant abnormal screening laboratory results as evaluated by the Investigator.
36. Current evidence of dysplasia or a 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.
37. Subject is considered by the Investigator, for any reason, to be an unsuitable candidate for the study.
Investigational Product:
Adalimumab (40 mg/0.8 mL)
Doses:
8-Week Double-Blind Period:
Adalimumab 160 mg at Week 0, 80 mg at Week 2, 40 mg at Weeks 4 
and 6, or
Matching placebo at Week 0 and at Week 2, 160 mg at Week 4, and 
80 mg at Week 6.
18-Week Open-Label Treatment Period:
Adalimumab 40 mg eow starting at Week 8 through Week 26.
If subject qualifies for dose escalation during the OL Period, the subject 
may escalate to adalimumab 80 mg eow.
Mode of Administration:
Subcutaneous (SC)
Duration of Treatment:  The study will include a Screening Period of up to 35 days, a double-blind 
8-week Treatment Period, and an Open-Label Treatment Period for 18 weeks for all subjects followed by 
a 70-day follow-up period from the last dose of study drug for subjects who complete the study or 
discontinue from the study prematurely.  The 70-day follow-up call will not be required for any subject 
who initiates adalimumab therapy not supplied in the context of the clinical trial after the end of study 
participation.
Criteria for Evaluation:
Efficacy:
Primary Efficacy Endpoint:
Proportion of subjects who achieve clinical remission (CDAI < 150) at Week 4.

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Criteria for Evaluation (Continued):
Efficacy (Continued):
Secondary Endpoints:
The Week 26 Efficacy Endpoint: 
Proportion of subjects who achieve clinical remission at Week 26 (CDAI < 150) in subjects who 
achieved clinical response (decrease in CDAI ≥ 70 points from Baseline) at Week 8.
Key Secondary Endpoints:
!
Proportion of subjects who achieve CDAI < 150 plus a reduction in hs-CRP of at least 50% 
from Baseline at Week 4.
!
Proportion of subjects who achieve CDAI < 150 plus a reduction in hs-CRP of at least 50% 
from Baseline at Week 26 in subjects who achieved decrease in CDAI ≥ 70 points from Baseline 
plus at least 30% reduction in hs-CRP from Baseline at Week 8.
!
Proportion of subjects who discontinue corticosteroid use and achieve clinical remission (CDAI 
< 150) at Week 26 in subjects who were taking steroids at Baseline and who achieved clinical 
response (decrease in CDAI ≥ 70 points from Baseline) at Week 8.
!
Proportion of subjects who discontinue corticosteroid use and achieve CDAI < 150 plus a 
reduction in hs-CRP of at least 50% from Baseline at Week 26 in subjects who were taking 
steroids at Baseline and who achieved decrease in CDAI ≥ 70 points from Baseline plus a 
reduction in hs-CRP of at least 30% from Baseline at Week 8.
!
Proportion of subjects who achieve clinical response (decrease in CDAI ≥ 70 points from 
Baseline) at Week 4.
!
Proportion of subjects who achieve decrease in CDAI ≥ 70 points from Baseline plus a reduction 
in hs-CRP of at least 30% from Baseline at Week 4.
!
Proportion of subjects who achieve CDAI < 150 and hs-CRP < 3 mg/L at Week 4.
!
Proportion of subjects who achieve CDAI < 150, hs-CRP < 3 mg/L at Week 26 in subjects who 
achieved clinical response (decrease in CDAI ≥ 70 points from Baseline) at Week 8.
!
Proportion of subjects who achieve IBDQ remission (IBDQ ≥ 170 points) at Week 4.
!
Proportion of subjects who achieve IBDQ remission at Week 26 in subjects with clinical 
response (decrease in CDAI ≥ 70 points from Baseline) at Week 8.
!
Change from Baseline in fecal calprotectin level at Week 4.
!
Proportion of subjects who achieve CDAI < 150, hs-CRP < 3 mg/L and fecal calprotectin 
< 250 μg/g at Week 4.
!
Proportion of subjects who achieve CDAI < 150, hs-CRP < 3 mg/L and fecal calprotectin 
< 250 μg/g at Week 26 in subjects who achieved clinical response (decrease in CDAI 
≥70 points from Baseline) at Week 8.
Additional Secondary Endpoints:
!
Proportion of subjects with clinical remission (CDAI < 150) over time.
!
Proportion of subjects with CDAI < 150 plus a reduction in hs-CRP of at least 50% from 
Baseline over time.
!
Proportion of subjects with clinical response (decrease in CDAI ≥ 70 points from Baseline over 
time.
!
Proportion of subjects with decrease in CDAI ≥ 70 points from Baseline plus a reduction in 
hs-CRP of at least 30% from Baseline over time.

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Criteria for Evaluation (Continued)
Efficacy (Continued):
Additional Secondary Endpoints (Continued):
!
Change from Baseline in CDAI over time.
!
Change from Baseline in hs-CRP level over time.
!
Change from Baseline in fecal calprotectin level over time.
Additional analyses are outlined in the protocol.
Pharmacokinetic:  
Blood samples will be collected for the measurement of serum adalimumab concentration just prior to 
dosing at Baseline (Week 0), Weeks 4, 8, 12, and Week 26/Premature discontinuation and AAA just prior 
to dosing at Baseline (Week 0), Week 4, Week 12, and Week 26/Premature Discontinuation.  If a subject 
meets the criteria for dose escalation, blood samples will also be obtained for adalimumab concentration 
and AAA levels at the time of dose escalation.  
Blood samples will also be collected for measurement of infliximab serum levels and HACA just prior to 
dosing at Baseline (Week 0).
Safety:  
Safety analyses will be performed on all subjects who receive at least one dose of study drug.  Incidence 
of adverse events, changes in vital signs, physical examination results, and clinical laboratory data will be 
assessed.
Statistical Methods:
Efficacy:  
The primary efficacy variable is the proportion of subjects with moderately to severely active CD who 
have achieved clinical remission, defined as CDAI < 150, at Week 4.  The comparison between treatment 
groups for the primary efficacy variable will be performed using the Cochran-Mantel-Haenszel (CMH) 
test and will be stratified by Crohn's disease severity (CDAI ≤ 300, > 300) at Baseline and corticosteroid 
use at Baseline (Yes/No).  A CMH based two-sided 95% confidence interval for the difference between 
treatment groups will be calculated.  The ITT set includes all subjects who were randomized at baseline.  
Missing CDAI at Week 4 will be imputed using the non-responder imputation (NRI) approach.
For Week 26 efficacy endpoint, the one sample Exact test will be performed and the two-sided 95% CI 
will be provided.  Rates of remission at Week 26 will be evaluated in patients meeting the definition for 
response (reduction in CDAI ≥ 70 points from Baseline) after induction therapy (determined at Week 8) 
and compared against a clinically meaningful remission rate obtained using the data from adult placebo 
from the Western CD Study M02-404 (see Section 8.2 for details).  For key and additional secondary 
efficacy endpoints, continuous variables will be analyzed using Analysis of Covariance (ANCOVA) 
model including factor for treatment group, stratification factors and Baseline values, whereas CMH test 
stratified by stratification factors used for discrete endpoints at Week 4 and one sample Exact test for 
discrete endpoints at Week 26.  NRI for missing data will be used for categorical endpoints.  Both last 
observation carried forward (LOCF) and observed case analyses will be performed for continuous 
endpoint.  The LOCF analysis is considered primary for inferential purposes.

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Statistical Methods (Continued):
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 positivity will be calculated.  
As appropriate, the effect of AAA on adalimumab pharmacokinetics, efficacy variable(s), and treatment 
emergent adverse events may be evaluated.
Safety:  
Adverse events (AEs), laboratory data and vital signs are the primary safety parameters in this study.  All 
safety summary statistics will be provided by treatment groups.  Treatment-emergent AEs are defined as 
events that begin or worsen either on or after the first dose of the study drug and within 70 days after the 
last dose of the study medication.  Treatment-emergent AEs will be summarized separately for the 
double-blind dosing period (Week 0 to Week 8) and the OL period (Week 8 to 70 days after the last dose 
of the study medication).  The number and percent of subjects experiencing AEs will be tabulated by 
body system and Medical Dictionary for Drug Regulatory Activities (MedDRA) preferred term for each 
treatment group.
Changes in laboratory data will be described using statistical characteristics and summarized by treatment 
group.  In addition, shift tables and listings will be provided for abnormal values, whereby the normal 
range of the analyzing laboratory will be used.  Vital signs will be analyzed similarly.

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1.3
List of Abbreviations and Definition of Terms
Abbreviations
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
CD
Crohn's disease
CDAI
Crohn's disease activity index
CDC
Centers for Disease Control and Prevention
CRA
Clinical Research Associate
CRF
Case report form
CRP
C-reactive protein
CT
Computerized tomography
CXR
Chest x-ray
DNA
Deoxyribonucleic acid
dsDNA
Double-stranded DNA
ECG
Electrocardiogram
eCRF
Electronic Case Report Form
EDC
Electronic Data Capture
eow
every other week
FDA
Food and Drug Administration
GCP
Good Clinical Practice
HACA
Human Anti-Chimeric Antibody
HBV
Hepatitis B virus
HBc Ab Total
Hepatitis B core antibody
HBe Ab
Hepatitis B envelope antibody
HBe Ag
Hepatitis B envelope antigen
HBs Ab
Hepatitis B surface antibodies
HBs Ag
Hepatitis B surface antigen

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HIV
Human immunodeficiency virus
hs-CRP
High-sensitivity C-reactive protein
ICH
International Conference on Harmonization
IEC
Independent Ethics Committee
IgG1
Immunoglobulin
IGRA
Interferon-Gamma Release Assay
IM
Intramuscular
IRB
Institutional Review Board
ITT
Intent-to-treat
IVRS
Interactive Voice Response System
IWRS
Interactive Web Response System
JIA
Juvenile Idiopathic Arthritis
LTBI
Latent Tuberculosis Infection
MedDRA
Medical Dictionary for Drug Regulatory Activities
mRNA
Messenger ribonucleic acid 
MTX
Methotrexate
NRI
Non-responder Imputation
OL
Open-Label 
PA
Poster-anterior
PK
Pharmacokinetics
POR
Proof of Receipt
PPD
Purified protein derivative
Ps
Psoriasis
PsA
Psoriatic Arthritis 
RA
Rheumatoid arthritis
RBC
Red blood cell
SAE
Serious adverse event
SC
Subcutaneous
SDP
Study designated physician
TB
Tuberculosis
TNF
Tumor Necrosis Factor
TPN
Total Parenteral Nutrition
UC
Ulcerative Colitis
WBC
White blood cell

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Definition of Terms
Clinical Remission
CDAI < 150
Clinical Response
Decrease in CDAI ≥ 70 points from Baseline 
Inadequate Response (for 
determining eligibility for 
dose escalation)
Crohn's disease activity index (CDAI) ≥ 200 at any one visit and at least 
one of the following criteria is met:  an increase of at least 1 mg/L in 
level of high-sensitivity C-reactive protein (hs-CRP) from Baseline or 
an hs-CRP ≥ 5 mg/L.  The hs-CRP results used to determine inadequate 
response should be the most recent available results.  Assessment of 
inadequate response should include consideration by the Investigator to 
rule out symptoms caused by reasons other than Crohn's disease related 
inflammation.  The most recent hs-CRP value should first be compared
to the most recent CDAI from the previous visit.  Then the most recent 
hs-CRP value should be assessed in relation to CDAI calculated at the 
current visit.  Dose changes are to only occur in accordance with the 
eow dosing schedule.

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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 .....................................................................................................6
1.3
List of Abbreviations and Definition of Terms........................................18
2.0
Table of Contents...................................................................21
3.0
Introduction ...........................................................................25
3.1
Differences Statement..............................................................................26
3.2
Benefits and Risks....................................................................................26
3.3
Adalimumab Overview............................................................................26
3.4
Safety Information ...................................................................................27
4.0
Study Objectives....................................................................28
5.0
Investigational Plan...............................................................28
5.1
Overall Study Design and Plan:  Description ..........................................28
5.2
Selection of Study Population..................................................................32
5.2.1
Inclusion Criteria .....................................................................................32
5.2.2
Exclusion Criteria ....................................................................................35
5.2.3
Prior and Concomitant Therapy...............................................................38
5.2.3.1
Prior Therapy ...........................................................................................39
5.2.3.2
Concomitant Therapy...............................................................................40
5.2.3.3
Prohibited Therapy...................................................................................42
5.3
Efficacy, Pharmacokinetic, Pharmacogenetic and Safety 
Assessments/Variables.............................................................................43
5.3.1
Efficacy and Safety Measurements Assessed and Flow Chart ................43
5.3.1.1
Study Procedures .....................................................................................49
5.3.1.2
Blood Samples for Pharmacogenetic Analysis ........................................65
5.3.1.3
Blood Samples for Biomarkers Analysis .................................................66
5.3.2
Drug Concentration Measurements .........................................................67
5.3.2.1
Collection of Samples for Analysis .........................................................67
5.3.2.2
Handling/Processing of Samples .............................................................68
5.3.2.3
Disposition of Samples ............................................................................69
5.3.2.4
Measurement Methods.............................................................................69

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5.3.3
Efficacy Variables....................................................................................70
5.3.3.1
Primary Variable......................................................................................70
5.3.3.2
Secondary Variables ................................................................................70
5.3.4
Safety Variables .......................................................................................72
5.3.5
Pharmacokinetic Variables ......................................................................72
5.3.6
Pharmacogenetic Variables......................................................................72
5.3.7
mRNA Variables......................................................................................73
5.4
Removal of Subjects from Therapy or Assessment .................................73
5.4.1
Discontinuation of Individual Subjects....................................................73
5.4.2
Discontinuation of Entire Study...............................................................75
5.5
Treatments................................................................................................75
5.5.1
Treatments Administered.........................................................................75
5.5.2
Identity of Investigational Products .........................................................77
5.5.2.1
Packaging and Labeling...........................................................................77
5.5.2.2
Storage and Disposition of Study Drug ...................................................78
5.5.3
Method of Assigning Subjects to Treatment Groups...............................78
5.5.4
Selection and Timing of Dose for Each Subject......................................79
5.5.5
Blinding....................................................................................................79
5.5.5.1
Blinding of Investigational Product.........................................................79
5.5.6
Treatment Compliance.............................................................................80
5.5.7
Drug Accountability.................................................................................80
5.6
Discussion and Justification of Study Design..........................................81
5.6.1
Discussion of Study Design and Choice of Control Groups....................81
5.6.2
Appropriateness of Measurements...........................................................82
5.6.3
Suitability of Subject Population .............................................................82
5.6.4
Selection of Doses in the Study ...............................................................82
6.0
Complaints .............................................................................83
6.1
Medical Complaints.................................................................................83
6.1.1
Definitions................................................................................................84
6.1.1.1
Adverse Event..........................................................................................84
6.1.1.2
Serious Adverse Events ...........................................................................84
6.1.2
Adverse Event Severity............................................................................86
6.1.3
Relationship to Study Drug......................................................................86

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6.1.4
Adverse Event Collection Period.............................................................87
6.1.5
Adverse Event Reporting.........................................................................87
6.1.6
Pregnancy.................................................................................................89
6.1.7
Toxicity Management ..............................................................................89
6.2
Product Complaint ...................................................................................90
6.2.1
Definition .................................................................................................90
6.2.2
Reporting..................................................................................................90
7.0
Protocol Deviations................................................................91
8.0
Statistical Methods and Determination of Sample 
Size ..........................................................................................92
8.1
Statistical and Analysis Plans ..................................................................92
8.1.1
Analyzable Population .............................................................................93
8.1.2
Planned Methods of Statistical Analysis..................................................93
8.1.3
Demographics and Baseline Characteristics............................................93
8.1.4
Statistical Analyses of Efficacy ...............................................................94
8.1.4.1
Primary Efficacy Variable .......................................................................94
8.1.4.2
Additional Efficacy Variables..................................................................94
8.1.5
Statistical Analyses of Safety...................................................................95
8.1.6
Other Statistical Analyses of Efficacy .....................................................96
8.1.7
Pharmacokinetic Analyses .......................................................................96
8.2
Determination of Sample Size .................................................................97
8.3
Randomization Methods ..........................................................................98
9.0
Ethics.......................................................................................98
9.1
Independent Ethics Committee (IEC) or Institutional Review 
Board (IRB) .............................................................................................98
9.2
Ethical Conduct of the Study ...................................................................99
9.3
Subject Information and Consent.............................................................99
10.0
Source Documents, Data Collection and Electronic 
Case Report Forms..............................................................100
10.1
Source Documents .................................................................................100
10.2
Case Report Forms.................................................................................100
11.0
Data Quality Assurance......................................................102
12.0
Use of Information...............................................................102

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13.0
Completion of the Study .....................................................103
14.0
Investigator's Agreement....................................................105
15.0
Reference List ......................................................................106
List of Tables
Table 1.
Study Activities........................................................................................44
Table 2.
Chart for TB Assessments at Screening and After Week 0 .....................55
Table 3.
Clinical Laboratory Tests.........................................................................62
Table 4.
Study Drugs .............................................................................................77
List of Figures
Figure 1.
Study Design............................................................................................31
Figure 2.
Adverse Event Collection ........................................................................87
List of Appendices
Appendix A.
Responsibilities of the Clinical Investigator ..........................................107
Appendix B.
List of Protocol Signatories....................................................................109
Appendix C.
Crohn's Disease Activity Index (CDAI) ................................................110
Appendix D.
Standard Weights ...................................................................................111
Appendix E.
Sample Injection Instructions for Onsite Administration –
Pre-Filled Syringe ..................................................................................114
Appendix F.
Sample Injection Instructions for at Home Dosing – Pre-Filled 
Syringe ...................................................................................................118
Appendix G.
Sample Quality of Life in Inflammatory Bowel Disease 
Questionnaire (IBDQ)............................................................................126
Appendix H.
70-Day Follow-Up Phone Call – Sample ..............................................136
Appendix I.
Protocol Amendment:  List of Changes.................................................137

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3.0
Introduction
Crohn's disease (CD) encompasses a spectrum of clinical and pathological processes 
manifested by focal asymmetric, transmural, and occasionally granulomatous 
inflammation that can affect any segment of the gastrointestinal tract.1  The disease can 
affect persons of any age, and its onset is most common in the second and third decades.  
Females are affected slightly more than males, and the risk for disease is higher in some 
ethnic groups.1,2  In North America, the incidence of CD is estimated to be 3.1 to 
14.6 cases per 100,000 persons.1  Prevalence rates range from 26 to 99 cases per 
100,000 persons.  In Europe, CD has an incidence of 0.7 to 9.8 cases per 100,000 persons 
and a prevalence of 8.3 to 214 cases per 100,000 persons.1
The incidence of CD in Asia is lower than that in the West, ranging from 0.14 to 
1.22 cases per 100,000 persons.3-5  Until recently, CD was not considered a public health 
problem in Asia, perhaps in part to the lack of accurate epidemiological data in Asia.  
However, CD disease location is broadly similar to that reported in Western studies and 
complex disease behavior (defined as stricturing, penetrating, or perianal disease) is 
present in a high proportion of patients, which has implications for the need for medical 
and surgical treatments in this part of the world.6
Guidelines for the management of CD from the Chinese Cooperative Group for the study 
on IBD recommend the use of aminosalicylates or antibiotics for mild disease, and 
steroids or immunomodulators (AZA, 6-mercaptopurine [6-MP], or methotrexate [MTX]) 
for moderate disease.7  Infliximab is recommended for severe or refractory disease.  A 
recent publication reported that short-term infliximab treatment (5 mg/kg at Weeks 0, 2, 
and 6) was effective to induce remission in Chinese patients with CD who had failed 
standard therapies.8  Because infliximab requires administration in an infusion setting, 
which may be inconvenient, and because many patients lose response or become 
intolerant to infliximab over time, additional options are necessary for patients in China 
with CD.

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3.1
Differences Statement
This study is being conducted to evaluate the safety and efficacy of adalimumab in 
Chinese subjects with moderately to severely active CD and elevated high-sensitivity 
C-reactive protein (hs-CRP).  While numerous studies have been conducted on the use of 
adalimumab for treatment of moderately to severely active CD, to date no Phase 3 
adalimumab efficacy and safety CD studies have been conducted in China.
3.2
Benefits and Risks
Extensive clinical and post-marketing experience exists with adalimumab in a wide range 
of disease states including CD and ulcerative colitis (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 CD have not altered 
this safety profile and demonstrated a positive benefit/risk balance.  Conditions which 
may present a risk specifically for patients with CD are exclusion criteria in this study 
(e.g., evidence of colonic dysplasia or active infections).
3.3
Adalimumab Overview
Adalimumab is a recombinant human immunoglobulin (IgG1) monoclonal antibody 
containing only human peptide sequences.  Adalimumab is produced by recombinant 
deoxyribonucleic acid (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 tumor necrosis factor (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).
Tumor necrosis factor (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 

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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 United States (US) and European Union (EU) for the 
treatment of Rheumatoid Arthritis (RA) in 2002 and 2003, respectively.  Additional 
indications have been approved in the US and EU including Psoriasis (Ps), Psoriatic 
Arthritis (PsA), Ankylosing Spondyloarthritis (AS), CD, Ulcerative Colitis (UC), 
polyarticular Juvenile Idiopathic Arthritis (JIA), pediatric CD, pediatric psoriasis as well 
as pediatric Enthesitis Related Arthritis and non-radiographic axial spondyloarthritis in 
the EU, and intestinal Bechet's Disease in Japan.  Additional updates regarding approved 
indications can be found in the current edition of the Humira Investigational Drug 
Brochure.
3.4
Safety Information
Adalimumab therapy has a well-established and well-described safety profile based on 
extensive post-marketing experience and continued clinical trial patient exposure since the 
first approved indication in 2002 for RA.  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 a United 
States Food and Drug Administration (FDA)-requested, TNF inhibitor class wide 
exploration of the rare appearance of malignancy in patients who are 30 years of age 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.

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4.0
Study Objectives
The primary objective of this study is to assess the efficacy and safety of adalimumab in 
inducing (at Week 4) and maintaining (at Week 26 in Week 8 responders) clinical 
remission, defined as Crohn's Disease Activity Index (CDAI) < 150, in Chinese subjects 
with moderately to severely active CD and elevated hs-CRP.
Additional objectives are to assess the effect of adalimumab treatment on other efficacy 
outcomes, including clinical response, steroid free remission, and improvement in quality 
of life.
5.0
Investigational Plan
5.1
Overall Study Design and Plan:  Description
This is a Phase 3, randomized, double-blind, placebo controlled, multicenter study of 
adalimumab in anti-TNF naïve Chinese subjects with moderately to severely active CD 
(220 ≤ Crohn's disease activity index [CDAI] ≤ 450) and elevated hs-CRP (≥ 3 mg/L).  
The study consists of an 8-week double-blinded period followed by an open-label (OL) 
period of 18 weeks.  Subjects will be randomized in a 1:1 ratio to receive adalimumab or 
placebo at Baseline.  Subjects randomized to adalimumab at Week 0 will receive blinded 
adalimumab 160 mg at Week 0, 80 mg at Week 2, and 40 mg at Week 4 and Week 6.  
Subjects randomized to placebo at Week 0 will receive blinded placebo at Week 0 and 
Week 2, then will receive blinded adalimumab 160 mg at Week 4 and 80 mg at Week 6.  
At Week 8, all subjects will enroll in an 18-week OL period to receive adalimumab 40 mg 
every other week (eow).  No drug will be administered at the final study visit.
The study was designed to enroll approximately 200 subjects 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.

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The study duration will be up to 39 weeks, and will include a screening period of up to 
35 days, an 8-week double blind treatment period, an 18-week OL period and a 70-day 
follow-up period.  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.  The 70-day follow-up phone call will not be required for any subject who initiates 
adalimumab therapy not supplied in the context of the clinical trial after the end of study 
participation.  All subjects will be screened for latent tuberculosis infection (LTBI) during 
the Screening period and for LTBI and active TB throughout the trial.
In order to be eligible for randomization, the subject must have met all of the inclusion 
criteria and none of the exclusion criteria of the protocol.
The randomization will be stratified by Crohn's disease activity (CDAI ≤ 300, > 300) at 
Baseline (Week 0) and systemic corticosteroid use at Baseline.
Adalimumab Treatment Regimen
(Double-Blind Period)
Placebo Treatment Regimen
(Double-Blind Period)
Study Visit
Number 
of Active 
Syringes
Number 
of Placebo 
Syringes
Study Visit
Number 
of Active 
Syringes
Number 
of Placebo 
Syringes
Week 0 – 160 mg ada
4
0
Week 0 – placebo
0
4
Week 2 – 80 mg ada
2
0
Week 2 – placebo
0
2
Week 4 – 40 mg ada
1
3
Week 4 – 160 mg ada
4
0
Week 6 – 40 mg ada
1
1
Week 6 – 80 mg ada
2
0
ada = adalimumab
Note:
At Week 8, study drug will be administered during the OL Period of the study.
All subjects will have blood samples drawn for the measurement of adalimumab 
concentration immediately prior to dosing at Baseline (Week 0), and Weeks 4, 8, 12, and 
26/Premature Discontinuation and anti-adalimumab antibody (AAA) levels just prior to 
dosing at Baseline (Week 0), Weeks 4, 12, and 26/Premature Discontinuation.  If a subject 
meets the criteria for dose escalation, blood samples will also be obtained for adalimumab 
concentration and AAA levels at the time of dose escalation.  Pre-dosing serum samples 
for infliximab concentration and human antichimeric antibodies (HACAs) will be 

Adalimumab
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collected at Baseline (Week 0).  An optional mRNA sample and an optional 
pharmacogenetic sample will be drawn prior to dosing at Baseline and 
Week 26/Premature Discontinuation (only if subject discontinues at or after Week 8).
At Week 4, all subjects who are on oral steroids will have their steroid dose tapered 
according to the schedule in Section 5.3.1.1.  The steroid taper is mandatory and 
deviations from the taper (or increases in steroid doses) are not permitted.  If the 
Investigator feels that the steroid taper is not advisable for a particular subject at Week 4, 
the subject must be withdrawn from the study.  If a subject who has tapered their 
corticosteroid dose is judged by the Investigator to have an inadequate response per the 
PI's judgment, dose escalation (allowed at or after Week 12) should be considered if the 
subject meets the below criteria, otherwise, the subject should be withdrawn from the 
study.
For the Purposes of Dose Escalation, Inadequate Response is Defined as:
Crohn's disease activity index (CDAI) ≥ 200 and at least one of the following criteria is 
met:  an increase of at least 1 mg/L in level of high-sensitivity C-reactive protein 
(hs-CRP) from Baseline or an hs-CRP ≥ 5 mg/L.  The hs-CRP results used to determine 
inadequate response should be the most recent available results.  Assessment of 
inadequate response should include consideration by the Investigator to rule out 
symptoms caused by reasons other than Crohn's disease related inflammation.  The most 
recent hs-CRP value should first be compared to the most recent CDAI from the previous 
visit.  Then the most recent hs-CRP value should be assessed in relation to CDAI 
calculated at the current visit.  Dose changes are to only occur in accordance with the eow 
dosing schedule.
At or after Week 12, any subject who experiences inadequate response may increase dose 
to OL adalimumab 80 mg eow.  If the subject has received OL 80 mg eow therapy and 
continues to demonstrate inadequate response, he or she should be withdrawn from the 
study per PI discretion.

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Figure 1.
Study Design
Subjects may discontinue adalimumab treatment at any time during study participation.  
Subjects who end study participation early will have a Premature Discontinuation Visit.  
All subjects who do not initiate adalimumab therapy not supplied in the context of the 
clinical trial after the end of study participation 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.  The 70-day follow-up phone call will not be required for any 
subject who initiates adalimumab therapy not supplied in the context of the clinical trial 
after the end of study participation.
Re-screening
Subjects who initially screen fail for the study are 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 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 QuantiFERON-TB Gold In-Tube test, 

Adalimumab
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CXR (or optional chest CT scan), and electrocardiogram (ECG), these tests will not be 
required to be repeated for re-screening provided the conditions noted in Section 5.2 are 
met.  If the subject had negative anti-HIV-1 test results from the central lab, these tests 
will not be required to be repeated if the results were obtained within 50 days of the 
re-screening visit provided that in the meanwhile nothing has changed in the patient's 
medical history or risk behaviors.  If the subject had negative HBV and Anti-Hepatitis C 
test results from the central lab, these tests will not be required to be repeated if the results 
were obtained within 35 days of the re-screening visit.  As appropriate, sites are 
encouraged to contact the AbbVie SDP to confirm if subjects should or should not be 
re-screened.
5.2
Selection of Study Population
5.2.1
Inclusion Criteria
1.
Male or female of Chinese descent with full Chinese parentage 18 to 70 years 
(inclusive) of age at Baseline (Week 0).
2.
Confirmed diagnosis of Crohn's disease for at least 3 months prior to Baseline 
(Week 0).  Appropriate documentation of biopsy results consistent with the 
diagnosis of CD, in the assessment of the Investigator, must be available.
3.
Subject has hs-CRP ≥ 3 mg/L in all laboratory measurements during the Screening 
Period.
4.
Crohn's Disease Activity Index (CDAI) ≥ 220 and ≤ 450 at Baseline (Week 0) 
despite concurrent or prior treatment with an adequate course, in the opinion of the 
investigator, of at least one of the following (oral corticosteroids or 
immunosuppressants or both as defined below ):
●
Subjects taking oral corticosteroids, excluding budesonide:
○
Oral corticosteroid dose must be ≤ 20 mg/day (prednisone or equivalent);
●
For subjects with a dose > 10 and ≤ 20 mg/day, dose has been stable 
for at least 7 days prior to Baseline and the duration of the current 
steroid course has been at least 14 days prior to Baseline.

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●
For subjects with a dose ≤ 10 mg/day, dose has been stable for at least 
10 days prior to Baseline (Week 0) and the duration of the current 
steroid course has been at least 14 days prior to Baseline (Week 0).
●
Subjects taking oral budesonide:
○
Dose must not exceed 9 mg/day;
●
For subjects with a dose ≥ 6 mg/day, dose has been stable for at least 
7 days prior to Baseline and the duration of the current steroid course 
has been at least 14 days prior to Baseline.
●
For subjects with a dose < 6 mg/day, dose has been stable for at least 
10 days prior to Baseline (Week 0) and the duration of the current 
steroid course has been at least 14 days prior to Baseline (Week 0).
and/or,
●
At least a consecutive 42-day course of azathioprine, 6-mercaptopurine 
(6-MP), or injectable methotrexate (MTX) prior to Baseline (Week 0), with a 
minimum dose of azathioprine ≥ 0.75 mg/kg/day or 6-MP ≥ 0.5 mg/kg/day 
(rounded to the nearest available tablet or half tablet formulation) or MTX 
≥15 mg/week (subcutaneous [SC]/intramuscular [IM]), or a dose that is the 
highest tolerated by the subject (e.g., due to leukopenia, elevated liver 
enzymes, nausea ) during that time.
○
Subject must be on a stable dose for at least 28 days prior to Baseline 
(Week 0).
●
For subjects taking azathioprine, the dose should not exceed 
3 mg/kg/day.
●
For subjects taking 6-MP, the dose should not exceed 1 mg/kg/day.
●
For subjects taking IM/SC MTX, dose should not exceed 25 mg per 
week.
●
Note:  Oral MTX use is allowed during the study (at a stable dose for 
28 days prior to Baseline), however use of oral MTX is not sufficient 
for inclusion into the study.
Note: If a subject is on both an oral corticosteroid and an 
immunosuppressant listed above, BOTH of the drugs need to meet 
the above criteria.

Adalimumab
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and/or
●
Concurrent therapy with corticosteroids or the above-mentioned 
immunosuppressants (azathioprine, 6-MP or IM/SC MTX) is not required for 
subjects not currently taking these medications who were previously treated 
during the past 2 years 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.
5.
Subject has a negative TB Screening Assessment.  If the subject has evidence of a 
latent TB infection during the Screening Assessment, the subject must initiate and 
complete a minimum of 3 weeks (or per local guidelines, whichever is longer) of 
an ongoing TB prophylaxis prior to Baseline (Section 5.3.1).
6.
If female subject, is either not of childbearing potential, defined as postmenopausal 
for at least 1 year or surgically sterile (bilateral tubal ligation, bilateral 
oophorectomy and/or hysterectomy) 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):
●
Condoms, sponge, foams, jellies, diaphragm or intrauterine device (IUD);
●
Hormonal contraceptives for 90 days prior to study drug administration;
●
A vasectomized partner.
7.
Subject must be able and willing to give written informed consent and to comply 
with the requirements of this study protocol.
8.
Subject is judged to be in otherwise good health as determined by the Principal 
Investigator (or designee) based upon the results of medical history, laboratory 
profile, physical examination, CXR, and a 12-lead electrocardiogram (ECG) 
performed during Screening.
9.
Subject must be able and willing to self-administer subcutaneous (SC) injections or 
have a qualified person available to administer SC injections.

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5.2.2
Exclusion Criteria
1.
Subject with a current diagnosis of ulcerative colitis (UC) or indeterminate colitis.
2.
Subject who has discontinued azathioprine or 6-MP or MTX or another 
immunomodulator within 14 days of Baseline (Week 0), or, for subjects taking oral 
MTX or another immunomodulator, has not been on a stable dose for at least 
28 days prior to Baseline.
3.
Subject who has discontinued use of oral aminosalicylates within 14 days of 
Baseline (Week 0) or, for subjects taking oral aminosalicylates, has not been on a 
stable dose for at least 28 days prior to Baseline.
4.
Subject taking both oral budesonide and oral prednisone (or equivalent) 
simultaneously, with the exception of non-systemic steroids (e.g., inhalers or 
dermatological preparations), during the Screening Period and during the study.
5.
Subject taking intravenous corticosteroids within 14 days prior to Screening, during 
the Screening Period and during the study, or who has discontinued oral 
corticosteroids within 14 days before Baseline (Week 0).
6.
Subject who has had a surgical bowel resection within 6 months of Screening or 
who is planning a resection at any time point in the future.
7.
Subject with symptomatic known obstructive strictures.
8.
Subject with an internal or external fistula (with the exception of an anal fistula 
without abscess).
9.
Subject with an ostomy or ileoanal pouch.
10.
Subject with short bowel syndrome.
11.
Subject has received therapeutic enema or suppository, other than required for 
endoscopy, within 14 days prior to Screening and/or during the Screening period.
12.
Subject with prior exposure to medications that have a potential or known 
association with progressive multifocal leukoencephalopathy, including 

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participation in a clinical trial of investigational agents targeting white cell 
trafficking (e.g., natalizumab [Tysabri®] or rituximab [Rituxan®]).
13.
Subject has been treated with any investigational agent or procedure (including 
previous fecal microbial transplantation) within a minimum of 30 days or 
5 half-lives (whichever is longer) of the drug prior to the Baseline (Week 0) Visit.
14.
Previous participation in an adalimumab clinical study.  Prior exposure to any 
anti-tumor necrosis factor (TNF) agent (including but not limited to branded or 
biosimilar versions of adalimumab [Humira®], infliximab [Remicade®], etanercept 
[Enbrel®], golimumab [Simponi®] or certolizumab pegol [Cimzia®]).  Prior 
exposure to ustekinumab (Stelara®), tofacitinib (Xeljanz®), tocilizumab 
(Actemra®), anakinra (Kineret®), abatacept (Orencia®) or vedolizumab (Entyvio®).
15.
Subject taking Crohn's-related antibiotics who has been on this therapy to treat an 
active infection or who has not been on stable doses of these medications for at 
least 14 days prior to Baseline.
16.
Subject has received cyclosporine, tacrolimus, or mycophenolate mofetil within 
30 days prior to Baseline (Week 0).
17.
Active infection(s) requiring treatment with intravenous (IV) anti-infectives within 
30 days prior to the Baseline (Week 0) Visit or oral anti-infectives within 14 days 
prior to the Baseline Visit.
18.
Subject currently receiving total parenteral nutrition (TPN) during Screening and/or 
at Baseline (Week 0) or subject who plans to receive TPN at any time during the 
course of the study.
19.
Subject with positive Clostridium difficile (C. difficile) toxin stool assay during the 
Screening period.
20.
Subject has received any systemic traditional Chinese medicine preparation within 
14 days before Baseline (Week 0).
21.
Subject has received any thalidomide within 28 days before Baseline (Week 0).

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22.
Screening laboratory and other analyses show any of the following abnormal 
results (if a subject starts TB prophylaxis, lab results [except ECG] should be 
confirmed at Day –7):
●
AST, ALT > 1.5 × upper limit of the reference range;
●
WBC count < 3.0 × 109/L;
●
Electrocardiogram (ECG) – with clinically significant abnormalities;
●
Total bilirubin ≥ 3 mg/dL; except for subjects with isolated elevation of 
indirect bilirubin relating to Gilbert syndrome;
●
Serum creatinine > 1.6 mg/dL.
23.
Known hypersensitivity to adalimumab or its excipients.
24.
History of demyelinating disease (including myelitis) or neurologic symptoms 
suggestive of demyelinating disease.
25.
History of invasive infection (e.g., listeriosis and histoplasmosis) or human 
immunodeficiency virus (HIV) or active TB.
26.
Subject with any active viral infection that based on the investigator's clinical 
assessment makes the subject an unsuitable candidate for the study.
27.
Positive anti-HIV-1 antibody (HIV-1 Ab), unless the screening anti-HIV-1 
antibody is subsequently found to be negative on confirmatory testing; and/or 
positive Hepatitis C virus antibody (HCV Ab) indicative of a previous or current 
infection; and/or positive Hepatitis B surface antigen (HBs Ag) or detected 
sensitivity on the Hepatitis B (HBV) DNA polymerase chain reaction test for 
Hepatitis B core antibody (HBc Ab Total) positive subjects.  If Hepatitis B 
envelope antigen and antibodies (HBe Ag or HBe Ab) are detected, it is per 
investigator discretion to enroll the subject.
28.
Chronic recurring infections or Active TB.
Active TB is considered to be:
●
Subject with CXR (or chest CT scan) findings suggestive of active TB as 
determined by a radiologist;

Adalimumab
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●
Subject with any clinical symptoms consistent with active TB;
●
With or without micobacteriology/histology examination for Mycobacterium 
tuberculosis or granulomas.
29.
Subjects with any findings indicating a history of TB infection (calcified nodules or 
granulomas and/or fibrotic scar, apical or basilar thickening) by CXR examination 
(or chest CT scan) at the screening evaluation and no documentation of 
prophylactic treatment.
30.
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.
31.
Subject with a previous history of gastric dysplasia.
32.
Positive pregnancy test at Screening or Baseline (Week 0).
33.
Female subjects who are breastfeeding or considering becoming pregnant during 
the study.
34.
History of clinically significant drug or alcohol abuse, including use of medical 
marijuana, in the last 12 months.
35.
Clinically significant abnormal screening laboratory results as evaluated by the 
Investigator.
36.
Current evidence of dysplasia or a 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.
37.
Subject is considered by the Investigator, for any reason, to be an unsuitable 
candidate for the study.
5.2.3
Prior and Concomitant Therapy
Any medication or vaccine (including over-the-counter or prescription medicines, and/or 
vitamins) that the subject is receiving at the time of screening, or receives during the 

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study, must be recorded along with the reason for use, date(s) of administration including 
start and end dates, and dosage information including dose, route and frequency on the 
appropriate eCRF.
The AbbVie study-designated physician identified in Section 6.1.5 should be contacted if 
there are any questions regarding concomitant or prior therapies.  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.
5.2.3.1
Prior Therapy
Crohn's disease specific medications (including but not limited to CD-related antibiotics, 
corticosteroids, aminosalicylates and immunomodulators) that the subject has received 
within 90 days of Baseline (Week 0) should be recorded on the appropriate page of the 
eCRF and should include the dates of administration and dosages and frequency.
Subjects who are not currently taking a corticosteroid or immunomodulator (specifically, 
azathioprine, 6-MP or SC/IM MTX) require confirmed documentation of failure to 
respond within the past 2 years or lack of tolerability within the past 5 years.
●
For subjects with failure to respond to treatment with corticosteroids or 
immunomodulators (specifically, azathioprine, 6-MP or SC/IM MTX) within 
the past 2 years, the dates (start and end dates) of the most recent course of 
treatment, the maximum daily dosage of the most recent course of treatment, 
and reason(s) for discontinuation are to be recorded in the appropriate eCRF.  

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In addition, the highest known dose taken within the past 2 years will be 
recorded.
●
For subjects who were intolerant to treatment with corticosteroids or 
immunomodulators (specifically, azathioprine, 6-MP or SC/IM MTX) within 
the past 5 years, the dates (start and end dates) of the most recent course of 
treatment, the maximum daily dosage of the most recent course of treatment, 
and reason(s) for discontinuation are to be recorded in the appropriate eCRF.  
In addition, the highest known dose taken within the past 5 years will be 
recorded in appropriate eCRF.
In addition, if subjects have/had ever been treated with azathioprine, 6-MP, or MTX (oral 
or IM/SC), the duration of therapy, maximum dose, reason for use and reason(s) for 
termination of treatment will also be recorded in appropriated eCRF.
5.2.3.2
Concomitant Therapy
Subjects taking immunomodulators at Baseline will continue their dose of azathioprine, 
6-MP, MTX or any other immunomodulators during the study, provided they are on a 
stable dose of the medication for at least 28 days prior to Baseline (Week 0).  Doses of 
these concomitant medications (azathioprine, 6-MP, MTX, or other immunomodulators) 
must remain stable throughout the duration of the study, 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.
Subjects taking aminosalicylates at Baseline will continue aminosalicylates during the 
study, provided they are on stable doses of the medication for at least 28 days prior to 
Baseline (Week 0).  Doses of oral aminiosalicylates must remain stable throughout the 
duration of the study, except in the event of treatment-related toxicities considered 
moderate to severe in the opinion of the investigator.
Subjects taking corticosteroids at Baseline will continue their dose of corticosteroids 
during the study, provided they are on a stable dose prior to Baseline (Week 0) as outlined 
in inclusion criterion 4 in Section 5.2.1.  Subjects will not be permitted to change the 

Adalimumab
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corticosteroid dose during the first 4 weeks of the study, except in the event of 
treatment-related toxicities considered moderate to severe in the opinion of the 
investigator.  At Week 4, all subjects will have their dose tapered according to the 
schedule in Section 5.3.1.1.  The steroid taper is mandatory and deviations from the taper 
(or increases in steroid doses) are not permitted.  If the Investigator feels that the steroid 
taper is not advisable for a particular subject at Week 4, the subject must be withdrawn 
from the study.
●
For steroids other than budesonide, a reduction of 5 mg prednisone (or 
equivalent) per day for doses > 10 mg/day of prednisone (or equivalent) every 
week until a 10 mg/day (or equivalent) dose is reached, then a weekly decrease 
by 2.5 mg (or equivalent) per day until discontinuation.
●
For budesonide, a weekly decrease by 3 mg/day of budesonide until 
discontinuation.
Subjects may not be on both oral budesonide and oral prednisone (or equivalent) 
simultaneously.
Subjects taking CD-related antibiotics at Baseline will continue stable doses of CD-related 
antibiotics during the study, provided they are on a stable dose of the medication for at 
least 14 days prior to Baseline (Week 0).  No changes to the dose at Baseline (Week 0) 
will be allowed except for treatment related toxicities or concerns about development of 
antibiotic resistance.
Subjects who enter the study on probiotics may continue this therapy provided the dose 
remains unchanged.
Setons are authorized as concomitant therapy in subjects with perianal fistulas and should 
be documented in the CRF under concomitant medications.
The AbbVie SDP identified in Section 6.1.5 should be contacted if there are any questions 
regarding concomitant or prior therapy(ies).

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5.2.3.3
Prohibited Therapy
The following are prohibited medications during the study:
●
All biologic therapy with a potential therapeutic impact on the disease being 
studied including but not limited to the following branded or biosimilar 
versions of:
○
Etanercept (Enbrel®);
○
Infliximab (Remicade®);
○
Abatacept (Orencia®);
○
Anakinra (Kineret®);
○
Rituximab (Rituxan®);
○
Natalizumab (Tysabri®);
○
Tocilizumab (Actemra®);
○
Golimumab (Simponi®);
○
Certolizumab pegol (Cimzia®);
○
Ustekinumab (Stelara®);
○
Belimumab (Benlysta®);
○
Vedolizumab (Entyvio®);
●
Live vaccines (during the study and for 70 days after the last dose of study 
drug);
●
Thalidomide.
Rectal therapy with any therapeutic enemas or suppositories, other than required for 
endoscopy, is prohibited within 14 days prior to and during the Screening Period and 
during the study.
Intravenous corticosteroid use is prohibited within 14 days prior to Screening, during the 
Screening Period and during the study.
Use of cyclosporine, tacrolimus, or mycophenolate mofetil is prohibited within 30 days 
prior to Baseline (Week 0) and during the study.

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Tofacitinib (Xeljanz®) is prohibited during the study.
Use of any systemic traditional Chinese medicine preparation within 14 days before 
Baseline (Week 0) and throughout the study.
Investigational agents or procedures (including fecal microbial transplantation) are 
prohibited within 30 days or 5 half-lives (whichever is longer) of the drug prior to the 
Baseline (Week 0) and during the study.
The AbbVie SDP identified in Section 6.1.5 should be contacted if there are any questions 
regarding prohibited therapy.
5.3
Efficacy, Pharmacokinetic, Pharmacogenetic and Safety 
Assessments/Variables
5.3.1
Efficacy and Safety Measurements Assessed and Flow 
Chart
Study procedures will be performed as summarized in Section 5.3.1.1.  All subjects must 
meet the study selection criteria outlined in Section 5.2.1 and Section 5.2.2 in order to be 
randomized in to the study.

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Table 1.
Study Activities
Activity
Screening 
(35 Days)
Day 
–21a Day 
–7a Baseline 
(Wk 0)b Wk 
2
Wk 
4
Wk 
6
Wk 
8
Wk 
10
Wk 
12
Wk 
14
Wk 
16
Wk 
18
Wk 
20
Wk 
22
Wk 
24
Wk 26/
Premature 
Discontinuation
Unscheduled 
Visit
70-Day 
Follow-Up 
Callc
Informed Consent
X
Inclusion/Exclusiond
X
X
X
X
Medical/Surgery 
Historyd
X
X
Alcohol and Tobacco 
Use 
X
Previous and 
Concomitant 
Medicationd
X
X
X
X
X
X
X
X
Xy
X
Xy
X
Xy
X
Xy
Xy
X
X
Vital Signse
X
X
X
X
X
X
Xy
X
Xy
X
Xy
X
Xy
Xy
X
X
Dispense Subject 
CDAI Diaryf
X
Physical Examinationg
X
X
X
X
X
X
X
X
X
Physician TB 
evaluation
X
X
X
X
X
X
X
X
Xy
X
Xy
X
Xy
X
Xy
Xy
X
X
TB Screeningh
X
X
X
X
X
X
X
X
X
Chest x-rayi
X
X
X
X
Initiate TB 
Prophlyaxisj
X
ECGk
X

Adalimumab
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Table 1.
Study Activities (Continued)
Activity
Screening 
(35 Days)
Day 
–21a Day 
–7a Baseline 
(Wk 0)b Wk 
2
Wk 
4
Wk 
6
Wk 
8
Wk 
10
Wk 
12
Wk 
14
Wk 
16
Wk 
18
Wk 
20
Wk 
22
Wk 
24
Wk 26/
Premature 
Discontinuation
Unscheduled 
Visit
70-Day 
Follow-Up 
Callc
Chemistry and 
Hematology
X
X
X
X
X
X
X
X
X
X
X
X
Urinalysisl
X
X
X
X
X
X
X
X
X
Pregnancy Testsm
X
X
X
X
Hepatitis B Screen, 
HCV, and HIVn
X
hs-CRP
X
X
X
X
X
X
X
X
X
X
X
X
C. difficile toxin
X
Antinuclear antibody 
(ANA)/
Anti-double-stranded 
DNA (anti ds-DNA)o
X
Stool Sample (fecal 
calprotectin)
X
X
X
X
Human Antichimeric 
Antibodies (HACA)/ 
Infliximab 
Concentrations
X
Adalimumab 
Concentrationp
X
X
X
X
Xq
Xq
Xq
Xq
Xq
Xq
Xp
AAA Concentrationp
X
X
X
Xq
Xq
Xq
Xq
Xq
Xq
Xp

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Table 1.
Study Activities (Continued)
Activity
Screening 
(35 Days)
Day 
–21a Day 
–7a Baseline 
(Wk 0)b Wk 
2
Wk 
4
Wk 
6
Wk 
8
Wk 
10
Wk 
12
Wk 
14
Wk 
16
Wk 
18
Wk 
20
Wk 
22
Wk 
24
Wk 26/
Premature 
Discontinuation
Unscheduled 
Visit
70-Day 
Follow-Up 
Callc
Optional 
Pharmacogenetic 
Markerr
X
Xs
Optional biomarker 
mRNAr
X
Xs
Crohn's Disease 
Activity Index (CDAI)
X
X
X
X
X
X
Xy
X
Xy
X
Xy
X
Xy
Xy
X
X
Start Corticosteroid 
Tapert
X
Monitor Adverse 
Eventsu
X
X
X
X
X
X
X
X
Xy
X
Xy
X
Xy
X
Xy
Xy
X
X
X
Study Drug 
Dispensing/
Administrationv
X
X
X
X
X
Xw
X
Xw
X
Xw
X
Xw
Xw
Xx
Inflammatory Bowel 
disease Questionnaire 
(IBDQ)
X
X
X
X
a.
Day – 21 and Day –7 visits are required for subjects who initiate TB prophylaxis during the screening period.  If a subject does not initiate TB prophylaxis, these visits are not 
required.
b.
The Baseline (Week 0) visit date will serve as the reference for all subsequent visits.  A ± 3-day window is permitted around scheduled study visits.
c.
Subjects will be contacted 70 days following study drug discontinuation for an assessment of any new or ongoing AEs, except those subjects who initiate adalimumab therapy 
not supplied in the context of the clinical trial after the end of study participation.
d.
Update inclusion/exclusion, prior and concomitant therapy, and medical/surgical history information to assure subject eligibility.
e.
Height will be measured at Screening only.

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Table 1.
Study Activities (Continued)
f.
Diary should be brought back to the site at every visit.
g.
Physical examination performed at Screening, Week 4, Week 8, and Week 26/Premature Discontinuation Visits are full physical examinations and those performed at all 
other visits are symptom-based and TB symptoms are discussed.
h.
Subjects with negative QuantiFERON-TB Gold In-Tube test within 35 days of Screening will not require a repeat test, if documentation is available.  Subjects with a negative 
QuantiFERON-TB Gold In-Tube test during the Screening Period will have repeated QuantiFERON-TB Gold In-Tube test at Weeks 2, 4, 6, 8, 12, 16, 20, and 26/PD, unless 
the Investigator has decided to initiate TB prophylaxis in that subject.  For subjects with an indeterminate result during the Screening period, a repeat Screening period test 
should be performed unless the Investigator decides to initiate TB prophylaxis.  If the repeat testing result during the Screening period is negative the QuantiFERON-TB Gold 
In-Tube test result is considered negative, but if the repeat testing result is indeterminate or positive TB prophylaxis should be initiated at least 3 weeks before Baseline.
Subjects who have a negative QuantiFERON-TB Gold In-Tube test result during Screening and later develop a positive result will be withdrawn from the study.  Subjects 
who have a negative QuantiFERON-TB Gold In-Tube test result during Screening and later develop an indeterminate result will have repeat testing and will be withdrawn 
from the study if the repeat testing confirms indeterminate or positive results.
i.
Chest x-ray includes posterior-anterior (PA) and lateral views.  Subjects with a normal (or one with non-clinically significant findings) CXR within 35 days of Screening 
would not require a repeat CXR, if documentation is available.  All subjects will have repeated CXRs performed to evaluate for TB during the study at Weeks 8, 16, and 
26/Premature Discontinuation.  A chest CT scan may be used instead of the CXR at investigator discretion.  If CXR or chest CTscan was obtained within 4 weeks of 
Premature Discontinuation, a repeat CXR/chest CT scan is not required.  
j.
If during Screening the subject has positive QuantiFERON-TB Gold In-Tube test or signs of latent TB  in the CXR (or chest CT scan), subject will start and continue at least a 
21-day course of TB prophylaxis treatment prior to Baseline (Week 0).  Use of TB prophylaxis in subjects with negative TB screening is permitted if warranted based on the 
opinion of the investigator, but must be started during Screening in this case (i.e., TB prophylaxis should not be initiated after randomization).  Subjects who initiate TB 
prophylaxis should continue the prophylaxis regimen for the duration of the subject's participation in the study (up to the 70 day followcall).  Subjects with signs of active TB 
are excluded from trial participation.
k.
Subjects with a normal (or one with non-clinically significant findings) ECG within 90 days of Screening would not require a repeat ECG, if documentation is available.
l.
Dipstick urinalysis will be completed by the central laboratory 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.

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Table 1.
Study Activities (Continued)
m.
Serum pregnancy test will be performed on all women of childbearing potential at Screening.  Urine pregnancy test will be performed at Baseline (Week 0) Visit, and the
Week 26/Premature Discontinuation Visit for all women of childbearing potential.  The frequency can be increased up to every visitas per local regulations.  If any urine 
pregnancy test is positive, a serum pregnancy test will be performed by the central laboratory.
n.
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.  For 
subjects who are negative for HBs Ag but are positive for core antibodies (HBc Ab Total), HBV DNA PCR will be performed and any result that meets or exceeds detection 
sensitivity will be exclusionary.  Anti-Hepatitis C will be performed at Screening and will be exclusionary.  All subjects will be tested for HIV-1 and documented that the test 
has been performed.  This testing is to be done at a central laboratory.  A subject will not be eligible for study participation if confirmatory testing for anti-HIV-1 antibody is 
positive.  AbbVie will not receive results from the testing and not be made aware of any positive result.  If the subject hadnegative anti-HIV-1 test results from the central lab, 
these tests will not be required to be repeated if the results were obtained within 50 days of the re-screening visit provided that in the meanwhile nothing has changed in the 
patient's medical history or risk behaviors.  If the subject had negative HBV and Anti-Hepatitis C test results from the central lab, these tests will not be required to be 
repeated if the results were obtained within 35 days of the re-screening visit.  
o.
Anti-double-stranded deoxyribonucleic acid (anti-dsDNA) performed if ANA result is positive.
p.
Blood samples for the measurement of adalimumab and anti-adalimumab antibody (AAA) concentrations will be collected prior to dosing.  If the subject Prematurely 
Discontinues, blood samples for the measurement of adalimumab and AAA concentrations will be collected.
q.
Blood samples for the measurement of adalimumab and anti-adalimumab antibody (AAA) concentrations will be collected prior to dosing ONLY if the subject qualifies for 
dose escalation.
r.
Pharmacogenetic and Biomarker mRNA samples are optional.  A separate consent must be signed prior to the sample draw.
s.
Samples are to be obtained if subject discontinues the study at or after Week 8.
t.
Subject will begin mandatory corticosteroid taper at Week 4.  If the Investigator feels that the steroid taper is not advisable for a particular subject at Week 4, he/she must be 
withdrawn from the study.
u.
Collection of Serious Adverse Events (SAEs) and protocol-related nonserious adverse events begins the day the subject signs the informed consent.  Collection of AEs begins 
on Day –7 for subjects who initiate TB prophylaxis.
v.
Administration of drug should be performed after all assessments and examinations scheduled for that day have been completed as much as possible.  Starting at or after 
Week 12 and if the subject qualifies for dose escalation (criteria defined in Section 5.3.1.1 and per investigator discretion), the subject may receive 80 mg of adalimumab eow.  
w.
Dosing may occur onsite by appropriate site staff or the subject or their qualified designee can administer doses when not atthe site.
x.
For damaged or replacement study drug, subject should stay on their dosing schedule established by the Baseline (Week 0) visit.
y.
Procedure should be performed if subject doses onsite, if subject doses at home these procedures are not required.

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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 AE information (discussed in Section 6.1.4).  All 
study data will be recorded in source documents and on the appropriate eCRFs.
Informed Consent
At the Screening visit, the subject will sign and date a study specific, Independent Ethics 
Committee (IEC)/Independent Review Board (IRB) approved, informed consent form 
before any study procedures are performed or any medications are withheld from the 
subject in order to participate in this study.  Details regarding how informed consent will 
be obtained and documented are provided in Section 9.3.
Inclusion/Exclusion Criteria
Subjects will be evaluated to ensure they meet all inclusion criteria and none of the 
exclusion criteria at all Screening Visits and at the Baseline (Week 0) Visit.
Medical and Surgical History
A detailed medical history with respect to TB exposure needs to be documented.  This 
information needs to include Bacille Calmette-Guérin (BCG) vaccination, cohabitation 
with individuals who have had TB, and/or who reside or work in TB endemic locations.
A complete medical and surgical history, history of tobacco and alcohol use, will be 
obtained from each subject during the Screening Period.  An updated medical history will 
be obtained at the Baseline (Week 0) Visit to ensure that the subject still qualifies.
Physical Examination
A physical exam will be performed at the designated study visits in Table 1.  A count of 
the number of cutaneous fistulas draining upon gentle compression must be performed 
during each physical exam.  Fistulas will be classified as abdominal or perianal/anal.  

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Physical examination findings (including fistulas and fissures) that are related or part of 
each subject's medical history should be captured on the appropriate eCRF page.
Vital Signs
Vital sign determinations of systolic and diastolic blood pressure in sitting position, pulse 
rate, respiratory rate, body weight (should be obtained without shoes), and body 
temperature will be obtained at the designated study visits in Table 1.  Blood pressure, 
pulse rate and respiratory rate should be performed before blood draws are performed.  
Height will be measured at the Screening Visit only (with shoes off, and then adding 
1 inch or 2.5 cm for CDAI calculation).  All measurements will be recorded in metric 
units if possible.
12-Lead Electrocardiogram (ECG)
A resting 12-lead ECG will be performed at the designated study visits in Table 1.  A 
qualified physician will interpret the clinical significance of any abnormal finding, sign, 
and date each ECG.  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 clinical research associate (CRA) and kept with 
subject's source documents onsite.
For subjects with a normal (or one with non-clinically significant findings) 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 SDP 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.
Chest X-Ray (CXR)
All subjects 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.  

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The CXR will not be required if the subject had a previous normal (or one with 
non-clinically significant findings) CXR within 35 days of Screening, provided all 
protocol required documentation is available at the site (as outlined below).
Chest computerized tomography (CT) scan may be substituted for CXR if warranted 
based upon the opinion of the investigator.
All subjects will have repeat CXRs performed to evaluate for TB during the study at 
Weeks 8, 16, and 26/Premature Discontinuation.  If CXR or chest CT scan was obtained 
within 4 weeks of Premature Discontinuation, a repeat CXR/chest CT scan is not required.
In the assessment of CXR/chest CT scan, a radiologist must note the presence or absence 
of 1) calcified granulomas, 2) pleural scarring/thickening, and 3) signs of active TB as 
well as the presence of hilar and/or mediastinal lymphadenopathy.  In the assessment of 
the CXR or chest CT scans  at Weeks 8, 16, and 26/PD, a radiologist must compare the 
results to the Screening image and note the presence of the above factors as well as the 
presence of hilar and/or mediastinal lymphadenopathy.  The Principal Investigator (or 
designee) will indicate the clinical significance of any findings and will sign and date the 
report.
TB Screening
All subjects should be screened for latent TB infection (LTBI), including those with a 
prior history of BCG administration.
LTBI screening consists of: 
●
QuantiFERON-TB Gold In-Tube test (QTF), 
●
CXR (or chest CT, at the Investigator's [or designee] discretion),
●
Medical history of contact with active TB.

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During Screening Period:
If any one of the three assessments (QTF, CXR/CT or medical history) is positive, the 
subject will be considered to have LTBI and will receive TB prophylaxis.
For subjects with an indeterminate QTF result during the Screening period, a repeat 
Screening period test should be performed with another blood or the subject must initiate 
TB prophylaxis prior to enrolling in the study.  If the repeat testing result during the 
Screening period is negative the QTF test result is considered negative, but if the repeat 
testing result is indeterminate or positive TB prophylaxis should be initiated.
In the assessment of the Screening period CXR/chest CT scan, a radiologist must note the 
presence or absence of 1) calcified granulomas, 2) pleural scarring/thickening, and 
3) signs of active TB as well as the presence of hilar and/or mediastinal lymphadenopathy.  
The Principal Investigator must indicate the clinical significance of any findings and 
contact the AbbVie SDP to discuss any clinically significant abnormal findings before 
enrolling the subject.  The Principal Investigator (or designee) will sign and date each 
report.
Subjects who have a diagnosis of LTBI during Screening and do not initiate prophylaxis 
cannot be enrolled.
Subjects who have a diagnosis of LTBI and agree to initiate prophylaxis should be 
consulted with a TB specialist (a physician with TB treatment knowledge and experience) 
regarding the selection of the appropriate TB prophylaxis regimen as per Centers for 
Disease Control (CDC) recommendations or local guidelines. 
Initiation of TB prophylaxis in subjects with negative LTBI screening is permitted during 
the Screening period as warranted based on the opinion of the investigator.
Subjects with an LBTI diagnosis or those in whom TB prophylaxis is electively initiated 
will receive TB prophylaxis for at least 21 days (before or on the Day –21 visit) prior to 
Baseline (Week 0), and are required to have a Day –21 and Day –7 visits.  At Day –21, 

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the CDAI and hs-CRP must be obtained and must meet the entry criteria in Section 5.2.  
For the calculation of the CDAI on Day –21, the hematocrit value obtained at the first 
screening visit will be used.  After initiation of TB prophylaxis, subjects will return to the 
clinical site 7 days (at Day –7) prior to Baseline (Week 0) to have safety labs drawn, 
including hs-CRP.  The hematocrit and hs-CRP values obtained at Day –7 will be used to 
calculate the Baseline (Week 0) CDAI to confirm eligibility for study enrollment.  
All subjects who initiate TB prophylaxis should continue the prophylaxis regimen for the 
duration of the subject's participation in the study, including the 70-day follow-up period.  
TB prophylaxis may only be initiated during the Screening period and is not permitted to 
be initiated during the study.  If the Investigator feels initiation of TB prophylaxis is 
warranted after the subject has been randomized, the subject must be withdrawn from the 
study.
Prophylactic treatment for TB should be captured on the concomitant medications page in 
the eCRF and in the source documents.  Prior therapy should be captured in medical 
history.
After Week 0:
All subjects will be monitored for signs and symptoms suggestive of active TB at all 
visits.
Subjects who initiate TB prophylaxis should continue the prophylaxis regimen for the 
duration of the subject's participation in the study and the study follow-up period.  These 
subjects will not require repeat QTF testing but will undergo repeat chest imaging at 
Weeks 8, 16, and 26/Premature Discontinuation.
Subjects who are negative for LTBI during screening and are not taking TB prophylaxis 
will have their QTF repeated at  Weeks 2, 4, 6, 8, 12, 16, 20, and 26/Premature 
Discontinuation and the chest imaging repeated at Weeks 8, 16, and 26/Premature 
Discontinuation.

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In the assessment of the CXR or chest CT scans at Weeks 8, 16, and 26/PD, a radiologist 
must compare the results to the Screening image and note the presence of the following 
factors 1) calcified granulomas, 2) pleural scarring/thickening, and 3) signs of active TB, 
as well as the presence of hilar and/or mediastinal lymphadenopathy.  The Principal 
Investigator must indicate the clinical significance of any findings and contact the AbbVie 
SDP to discuss any clinically significant abnormal findings and determine the next steps.  
The Principal Investigator (or designee) will sign and date each report.
Subjects who have a negative QTF test result during Screening and later develop a 
positive QuantiFERON-TB Gold In-Tube test result will be withdrawn from the study.
Subjects who have a negative QTF test result during Screening and later develop an 
indeterminate result will have repeat testing and will be withdrawn from the study if the 
repeat testing result is indeterminate or positive. 
TB prophylaxis is not permitted to be initiated during the study.
For subjects who develop signs and symptoms suggestive of active TB or with negative 
TB Screening who are withdrawn later from the study due to a positive/indeterminate 
QuantiFERON-TB Gold In-Tube test result or CXR/chest CT findings, a TB specialist (a 
physician with TB treatment knowledge and experience) should be consulted regarding 
appropriate patient management.

Adalimumab
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55
Table 2.
Chart for TB Assessments at Screening and After Week 0
Screening Period
After Week 0
Monitoring For:
QTF
CXR/CT
Medical 
History
TB 
Prophylaxis 
Required
LTBI
Active TB
+
+
+
Yes
No
Yes^
+
+
-
Yes
No
Yes^
+
-
+
Yes
No 
Yes^
+
-
-
Yes
No
Yes^
-
+
+
Yes
No
Yes^
-
-
+
Yes
No
Yes^
-
+
-
Yes
No
Yes^
-
-
-
No
Yes*
Yes^
*
During follow-up, subjects who are negative for LTBI during screening and are not taking TB prophylaxis will 
have their QTF repeated at Weeks 2, 4, 6, 8, 12, 16, 20, and 26/Premature Discontinuation and the chest imaging 
repeated at Weeks 8, 16, and 26/Premature Discontinuation.  Subjects who are negative for LBTI during Screening 
who initiate TB prophylaxis per the Investigator's discretion do not require repeat QTF testing.
^
All subjects will be monitored for signs and symptoms suggestive of active TB at all visits. CXR (or chest CT, at 
the Investigator's [or designee's] discretion) will be repeated Weeks 8, 16, and 26/Premature Discontinuation.  If 
there are signs or symptoms suggestive of active TB, and/or changes in the chest imaging, a diagnostic 
investigation must be done.
Physician TB Evaluation
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 the designated study visits in Table 1.  For any subject 
with clinical signs/symptoms of active TB or newly identified TB risk factors, a 
CXR/chest CT scan (per investigator discretion) may be required for evaluation of active 
TB, and it is recommended to contact the SDP for further guidance.  Subjects with 
confirmed active TB must be discontinued from the study and receive standard of care 
based on consultation with a local TB specialist (a physician with TB treatment 
knowledge and experience).

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Patient Reported Outcomes and Questionnaires
●
IBDQ – Inflammatory Bowel disease Questionnaire (IBDQ) will be completed 
at the time points indicated in (Appendix G).
Crohn's Disease Activity Index (CDAI)
A CDAI will be calculated from a subject diary, physical exam, and appropriate 
laboratory values at the designated study visits in Table 1.
Beginning with the Day –21 Visit (in case subject initiates TB prophylaxis) or Baseline 
(Week 0) evaluation through Week 26 including unscheduled visits, the CDAI will be 
calculated using a hematocrit value from the preceding visit's laboratory work.
CDAI at Visit
HCT Value Utilized
Screening Day –21
Original Screening Visit (Up to Day –35)
Baseline (Week 0)
Original Screening Visit/Screening Day –7
Week 2
Week 0
Week 4
Week 2
Week 6*
Week 4
Week 8*
Week 6
Week 10*
Week 8
Week 12*
Week 8 or unscheduled visit if more recent
Week 14*
Week 12
Week 16*
Week 12 or unscheduled visit if more recent
Week 18*
Week 16
Week 20*
Week 16 or unscheduled visit if more recent
Week 22*
Week 20
Week 24*
Week 20 or unscheduled visit if more recent
Week 26
Week 20 or unscheduled visit if more recent
*
When evaluating any subject on open-label adalimumab 40 mg eow who are being considered for dose escalation 
for inadequate response, the hematocrit value used to determine the CDAI should be obtained at the previous visit 
where blood samples were collected for hematology and chemistry whether it is a scheduled or unscheduled blood 
draw or visit.

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For the CDAI questions regarding presence of anal fistulas and other fistulas, all fistulas 
detectable on physical examination (draining and non-draining) should be captured and 
noted for calculation of the CDAI.
When completing question five (5) ("Taking Lomotil/Imodium/Loperamide/opiates for 
diarrhea, 0 = no, 1 = yes") on the CDAI, "no" should be answered if a subject is taking an 
opiate(s) solely for pain.
For question seven (7), hematocrit results from central laboratory will be used for the 
CDAI calculation.  If the hematocrit value contains more than one decimal point, the 
rounding will be allowed to the tenths decimal (e.g., Hct value 33.44 will be captured as 
33.4, Hct value of 33.45 will be captured as 33.5).  The Hct values either prior to 
completing the calculation or at the subtotal box 7 of the CDAI should not be rounded to a 
whole number.
The height obtained at Screening should be used when selecting the standard weight in 
Appendix D, and this standard weight should be used for calculating every CDAI
throughout subject participation in the study.
Standard height is calculated by using the height obtained at Screening (without shoes) 
plus one inch or 2.5 cm. 
Body weight should be captured without shoes.  If the body weight that obtained at the 
time of assessment is not captured in kilograms (kg), then when converting into kgs, 
rounding should occur using the second digit after the decimal (also known as the 
hundredth place) where if the number is 0 – 4 then keep the first digit after the decimal 
(also known as the tenth place) unchanged.  If the second digit after the decimal is 5 – 9 
then round up the first digit after the decimal (e.g., 90.246 would be captured as 90.2, 
97.687 would be captured as 97.7).
The subtotal of box 8 should not be rounded to a whole number.
The calculation of the CDAI is outlined in Appendix C.

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Corticosteroid Taper
At Week 4, all subjects who are on oral steroids will have their dose tapered according to 
the following schedule:
Dose
Rate
Prednisone (or equivalent)
> 10 mg/day
5 mg/day/week (or equivalent)
≤ 10 mg/day
2.5 mg/day/week (or equivalent)
Budesonide
≤ 9 mg/day
3 mg/day/week
The steroid taper is mandatory and deviations from the taper (or increases in steroid 
doses) are not permitted.  If the Investigator feels that the steroid taper is not advisable for 
a particular subject at Week 4, the subject must be withdrawn from the study.  From If a 
subject who has tapered their corticosteroid dose is judged by the Investigator to have an 
inadequate response per the PI's judgment, dose escalation (allowed at or after Week 12) 
should be considered  if the subject meets the dose escalation criteria (Section 5.3.1.1), 
otherwise, the subject should be withdrawn from the study.
Adverse Event
Adverse events will be assessed at every study visit from Day –7 (if the subject initiates 
TB prophylaxis) or from Baseline (Week 0) through the final study visit (Week 26 or 
Premature Discontinuation visit for those who prematurely discontinue from the 
double-blind or OL periods of the study) and at the 70-day follow-up phone call.
Serious adverse events and protocol-related nonserious adverse events will be collected 
from the time the subject signed the study specific informed consent.
Subjects who complete Week 26 or those who prematurely discontinue the study early, 
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.  The 70-day follow-up 
phone call will not be required for any subject who initiates adalimumab therapy not 
supplied in the context of the clinical trial after the end of study participation.  Refer to 
Section 6.0 for additional information.

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Subject Diary
Subjects will be dispensed a diary 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 Week 26/PD visit.
If the subject chooses to dose at home, their 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 into the eCRF.  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.
Study Drug Dispensing/Administration
Study drug will be administered to all subjects onsite by site medical staff during all the 
visits from Baseline (Week 0) through Week 24.  No study drug will be administered at 
Week 26.  Detailed instructions and training for the administration of adalimumab are 
provided in Appendix E and Appendix F.  Study drug kits are assigned by IRT following 
the subjects randomized treatment schedule.  If the subject chooses to dose outside of the 
clinic at the visit weeks specified in Table 1, adalimumab injections occurring during 
study visits will be performed at the visit by the subject or their designated family 
member, friend or Healthcare Professional under the supervision of trained medical 
personnel to reinforce proper aseptic SC injection technique.  Subjects or a trained 
designated family member, friend or Healthcare Professional will perform the injections 
of adalimumab in the subject's home during the weeks they are not in for scheduled clinic 
visits.
When dosing onsite, each subject will have a Dosing Log or accountability form at 
Baseline (Week 0); this log must be filled out each time a dose is administered.  In the 
dosing log, the date and time study drug is administered, and the dose administered will 
be recorded.  Additionally, any discernible departure from the protocol regarding study 

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drug administration will be recorded on the source documents and on the appropriate drug 
accountability form.
Site medical staff or subjects, if dosing occurs at the subject's home, 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 (Week 0) 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 SDP for additional instructions.
At all office visits, subjects should be observed after study drug administration until 
judged clinically stable by the study personnel.  If an anaphylactic reaction or other 
serious allergic reaction occurs, administration of study drug should be discontinued 
immediately and initiate appropriate therapy.  When dosing at home subjects should be 
instructed to contact the site immediately with any signs or symptoms of a reaction.  If 
subjects are unable to reach their study site or experience life-threatening symptoms, they 
will be instructed to call an emergency number or proceed to the nearest emergency room 
and then inform the site as soon as possible.
Subjects will be instructed to return all used and unused syringes, sharps containers and 
empty boxes at each visit for accountability.
Dose Escalation
At or after Week 12, if any subject experiences inadequate response (defined below), the 
subject may increase dose to open-label adalimumab 80 mg eow.  If the subject has 
received open-label 80 mg eow therapy and continues to demonstrate inadequate 
response, they should be withdrawn from the study.

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For the Purposes of Dose Escalation, Inadequate Response:
Crohn's disease activity index (CDAI) ≥ 200 and at least one of the following criteria 
is met:  an increase of at least 1 mg/L in level of high-sensitivity C-reactive protein 
(hs-CRP) from Baseline or an hs-CRP ≥ 5 mg/L.
The hs-CRP results used to determine inadequate response should be the most recent 
available results.  Assessment of inadequate response should include consideration by 
the Investigator to rule out symptoms caused by reasons other than Crohn's disease 
related inflammation.  The most recent hs-CRP value should first be compared to the 
most recent CDAI from the previous visit.  Then the most recent hs-CRP value 
should be assessed in relation to CDAI calculated at the current visit.  Dose changes 
are to only occur in accordance with the eow dosing schedule.
For example:
Week 12 CDAI was 190 and the hs-CRP obtained at Week 12 visit was 7 mg/L.  The 
subject returns 2 weeks later and the CDAI at Week 14 is 220.  The hs-CRP obtained 
at Week 12 should first be assessed with the Week 12 CDAI to determine if the 
inadequate response criteria have been met; which in this case does not meet criteria 
for dose escalation.  Then the hs-CRP obtained at Week 12 should be assessed with 
Week 14 CDAI, which does meet the criteria for dose escalation; because the latter 
assessment met the criteria, the subject is eligible for dose escalation.
Laboratory Tests
Blood samples will be obtained for the laboratory tests listed in Table 3 at the visits 
described in Table 1.  Blood draws should be performed after all clinical assessments and 
questionnaires (CDAI, IBDQ), vital sign determinations are obtained and before study 
drug administration during a visit, whenever possible.

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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.
Table 3.
Clinical Laboratory Tests
Hematology
Clinical Chemistry
Urinalysis
Other
Pregnancy Test
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
hs-CRP
C. difficile toxin
Fecal calprotectin
Antinuclear antibody 
(ANA)
Anti-double-stranded 
DNA 
(anti-dsDNA) –
if ANA positive
HBs Ag
HBs Ab
HBe Ag
HBe Ab
HBc Ab Total
PCR DNA (if needed)
Pharmacokinetic
HACA
Infliximab
Pharmacogenetic 
(optional) 
mRNA (optional)
HCV
HIV (testing to be 
conducted at 
central lab)
QuantiFERON-TB
Gold In-Tube
Serum HCG
Urine (testing to be 
performed 
locally by 
designated 
study 
personnel)
Hepatitis and HIV Testing
All subjects will be tested for the presence of the HBV at Screening.  A positive result for 
the HBs Ag will be exclusionary.  If HBc Ab test results are positive, polymerase chain 
reaction (PCR) DNA will be performed to exclude the HBV infection, any result that 

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meets or exceeds detection sensitivity will be exclusionary.  If HBe Ag or HBe Ab are 
positive, the subject's eligibility is per investigator's discretion.
Anti-Hepatitis C antibody will be performed at Screening only.  A positive result will be 
exclusionary.
Subjects will be tested for antibodies to HIV-1 at Screening.  This testing is to be done at 
a central laboratory.  A subject will not be eligible for study participation if confirmatory 
testing for anti-HIV-1 antibody is positive.  AbbVie will not receive results from the 
testing and not be made aware of any positive result.  If the subject had negative 
anti-HIV-1 test results from the central lab, these tests will not be required to be repeated 
if the results were obtained within 50 days of the re-screening visit provided that in the 
meanwhile nothing has changed in the patient's medical history or risk behaviors.  
If the subject had negative HBV and Anti-Hepatitis C test results from the central lab, 
these tests will not be required to be repeated if the results were obtained within 35 days 
of the re-screening visit.  
Pregnancy Tests
A serum pregnancy test will be performed at the Screening Visit on all female subjects of 
childbearing potential.  At the Baseline Visit (Week 0) and Week 26/PD subjects 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.
All women of childbearing potential will have a repeat urine pregnancy test at the final 
onsite Study Visit performed locally by designated study personnel.
Urinalysis
Urine samples will be obtained and sent to the central laboratory for the tests listed in 
Table 3 at the visits described in Table 1.  Microscopic urinalysis will only be performed 

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d by the central laboratory if the dipstick urinalysis results are abnormal, where abnormal 
is defined as a ketone, protein, blood value greater than negative or glucose value of 
greater than a normal.
Other Laboratory Assessments
ANA/anti-dsDNA
Blood samples for antinuclear antibody (ANA) will be obtained per Table 1.  
Anti-double-stranded DNA (anti-dsDNA) assessments will be performed if ANA is 
positive.
In the event that subject develops lupus-like symptoms during the study, an additional 
ANA sample will be obtained.
hs-CRP
Blood samples for hs-CRP will be obtained per Table 1.  The site will receive the 
notification from the central laboratory for the Screening Period.  Results obtained during 
the Day –7 Screening visit (for a subject who started TB prophylaxis) will be used for 
entry criteria.
The hs-CRP results from Week 2 through Week 8 will remain blinded to Investigator, 
study site personnel and the subject.  The AbbVie safety team will not be blinded to these 
results.  Since investigators are blinded to hs-CRP, the SDP will notify the investigator of 
an elevated hs-CRP result (> 100 mg/L) and request follow-up.
Blood draws should be performed after all clinical assessments and questionnaires 
(including CDAI), vital sign determinations are obtained and before study drug 
administration during a visit.
Fecal Calprotectin
Fecal calprotectin will be performed for all subjects as indicated in Table 1 and collection 
should be performed before study drug administration during a visit as much as possible.  

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If subjects are unable to provide a sample at the site visit, they will be sent home with a 
stool sample collection supplies and instructions to assist the subjects with the collection 
procedures.
The fecal calprotectin results will remain blinded to Investigator, study site personnel and 
the subject up to and including Week 8.
The central laboratory will be utilized to process and provide results for these laboratory 
tests.
C. Difficile Stool Testing
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 sample must be shipped to the central laboratory using dry ice.  Additional 
information is available in the Investigator Manual provided by the central laboratory.
Subjects who are positive for C. difficile toxin may be treated appropriately and 
re-screened.
Pharmacokinetics
Blood samples for adalimumab and anti-adalimumab (AAA) will be collected starting at 
Baseline (Week 0).  Time points are indicated in Table 1.
Blood samples for Infliximab and Human Anti-Chimeric Antibody (HACA) will be 
collected at Baseline (Week 0).
5.3.1.2
Blood Samples for Pharmacogenetic Analysis
One 4 mL whole blood sample for DNA isolation will be collected at the time points 
indicated in Table 1 from each subject who consents to provide samples for 
pharmacogenetic analysis.  The procedure for obtaining and documenting informed 
consent is discussed in Section 9.3.

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Instructions for the preparation and shipment of pharmacogenetic samples will be 
provided in the lab manual.  Samples will be shipped frozen to the central laboratory in 
China and then to an AbbVie designated laboratory in China for long-term storage.  
Samples should not be allowed to thaw prior to arrival at the designated laboratory.  
Arrangements will be made with the central laboratory for the shipment of PG samples to 
the specified lab for testing in China.
Samples will be stored in a secure storage space with adequate measures to protect 
confidentiality.  The samples will be retained while research on adalimumab (or drugs of 
this class) continues but no longer than 10 years.
5.3.1.3
Blood Samples for Biomarkers Analysis
Collection of Samples for mRNA Assays
One 2.5 mL blood samples for mRNA will be collected at the time points indicated in 
Table 1 from each subject who consents to provide samples for mRNA analysis.  The 
procedure for obtaining and documenting informed consent is discussed in Section 9.3.  
Instructions for the preparation and shipment of biomarker samples will be provided in the 
lab manual.  Samples will be shipped frozen to the central laboratory in China and then to 
an AbbVie designated laboratory in China for long-term storage.  Samples should not be
allowed to thaw prior to arrival at the designated laboratory.  Arrangements will be made 
with the central laboratory for the shipment of mRNA samples to the specified lab for 
testing in China.
Samples will be stored in a secure storage space with adequate measures to protect 
confidentiality.  The samples will be retained while research on adalimumab (or drugs of 
this class) continues but no longer than 10 years.

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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.
Collection of Samples for Adalimumab and AAA Assays
Blood samples for adalimumab and AAA assays will be collected by venipuncture into 
appropriately labeled 4 mL evacuated serum collection tubes (one tube for adalimumab 
and one tube for AAA) without gel separator immediately prior to dosing.  Sufficient 
blood will be collected to provide approximately 2 mL serum for adalimumab assay and 
2 mL serum for AAA assay.  Blood will be allowed to clot for 30 – 60 minutes at room 
temperature before centrifugation.
A maximum of 9 samples are planned to be collected per subject for adalimumab 
(5 samples) and AAA (4 samples) assays if the subject does not dose escalate.  If the 
subject dose escalates, a maximum of 11 samples are planned to be collected per subject 
for adalimumab (6 samples) and AAA (5 samples) assays.  If all subjects dose escalate, 
the total number of samples planned will not exceed 1200 (6 samples × 200 subjects) for 
the adalimumab assay and 1000 (5 samples × 200 subjects) for the AAA assay for the 
entire study.
Collection of Samples for Infliximab and HACA Assays
Blood samples for infliximab and HACA assay will be collected at Week 0 (Baseline) by 
venipuncture into appropriately labeled 4 mL evacuated serum collection tube without gel 
separator at Baseline (Week 0).  The sample will be obtained immediately prior to dosing.  
Blood will be allowed to clot for 30 – 60 minutes at room temperature before 

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centrifugation.  Sufficient blood will be collected to provide approximately two 1 mL 
serum specimens (one tube for infliximab and one tube for HACA).
The total number of samples planned will not exceed 400 (2 samples × 200 subjects) for 
the entire study.
5.3.2.2
Handling/Processing of Samples
The blood samples for adalimumab, AAA, infliximab, and HACA assay will be labeled 
with information such as the following:  the type of sample, the study drug number, 
protocol number, subject number, study week/visit name, and assay type 
(pharmacokinetic [PK]-Adalimumab or AAA; PK-Infliximab or HACA).
Additional detailed instructions for the handling and processing of samples will be 
provided from the central laboratory. 
Handling/Processing of Adalimumab and AAA Assays
The blood samples for adalimumab and AAA assay will be centrifuged at
1100 – 1600 × g for 10 – 15 minutes within 30 – 60 minutes of collection to separate the 
serum.  The serum samples will be transferred using plastic pipettes into screw-capped 
polypropylene vials labeled with information such as the following:  the study drug name, 
protocol number, subject number, study week/visit name, and assay type 
(Pharmacokinetics [PK] Adalimumab or AAA).  The serum samples will be frozen within 
2 hours after collection and will remain frozen in a –20°C or colder freezer 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.
Samples will be shipped frozen from the sites to the designated laboratory in China for 
testing and storage.  Samples should not be allowed to thaw prior to arrival at the 
designated laboratory.  
Additional detailed instructions for the handling and processing of samples will be 
provided from the central laboratory/AbbVie.

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Handling/Processing of Infliximab and HACA Assays
The blood samples for Infliximab and HACA assay will be centrifuged at 1100 – 1600 × g 
for 10 – 15 minutes within 30 – 60 minutes of collection to separate the serum.  The 
serum samples will be transferred using plastic pipettes into screw-capped polypropylene 
vials labeled with information such as the following:  the study drug number, protocol 
number, subject number, study week/visit name, and assay type (Infliximab or HACA).  
The serum samples will be frozen within 2 hours after collection and will remain frozen in 
a –20°C or colder freezer 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.
Samples will be shipped frozen to the designated laboratory in China for testing and 
storage.  Samples should not be allowed to thaw prior to arrival at the designated 
laboratory.
Additional detailed instructions for the handling and processing of samples will be 
provided from the central laboratory/AbbVie.
5.3.2.3
Disposition of Samples
Frozen serum samples will be packed in dry ice (pellet form) sufficient to last 3 days 
during transport.  Samples will be shipped pursuant to instructions from the onsite CRA.  
An inventory of the samples will be included in the package for shipment.  Arrangements 
will be made with the central lab for the transfer of samples.
5.3.2.4
Measurement Methods
Serum concentrations of adalimumab and AAA will be determined using a validated 
ligand binding assay (LBA) method under the supervision of the Bioanalysis Department 
at AbbVie.

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5.3.3
Efficacy Variables
5.3.3.1
Primary Variable
The primary efficacy variable is the proportion of subjects who achieve clinical remission 
(CDAI < 150) at Week 4.
5.3.3.2
Secondary Variables
The Week 26 efficacy endpoint is proportion of subjects who achieve clinical remission at 
Week 26 (CDAI < 150) in subjects who achieved clinical response (decrease in CDAI 
≥70 points from Baseline) at Week 8.
Key secondary efficacy endpoints include:
●
Proportion of subjects who achieve CDAI < 150 plus a reduction in hs-CRP of 
at least 50% from Baseline at Week 4.
●
Proportion of subjects who achieve CDAI < 150 plus a reduction in hs-CRP of 
at least 50% from Baseline at Week 26 in subjects who achieved decrease in 
CDAI ≥ 70 points from Baseline plus at least 30% reduction in hs-CRP from 
Baseline at Week 8.
●
Proportion of subjects who discontinue corticosteroid use and achieve clinical 
remission (CDAI < 150) at Week 26 in subjects who were taking steroids at 
Baseline and who achieved clinical response (decrease in CDAI ≥ 70 points 
from Baseline) at Week 8.
●
Proportion of subjects who discontinue corticosteroid use and achieve CDAI 
< 150 plus a reduction in hs-CRP of at least 50% from Baseline at Week 26 in 
subjects who were taking steroids at Baseline and who achieved decrease in 
CDAI ≥ 70 points from Baseline plus a reduction in hs-CRP of at least 30% 
from Baseline at Week 8.
●
Proportion of subjects who achieve clinical response (decrease in CDAI 
≥70 points from Baseline) at Week 4.
●
Proportion of subjects who achieve decrease in CDAI ≥ 70 points from 
Baseline plus a reduction in hs-CRP of at least 30% from Baseline at Week 4.

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●
Proportion of subjects who achieve CDAI < 150 and hs-CRP < 3 mg/L at 
Week 4.
●
Proportion of subjects who achieve CDAI < 150, hs-CRP < 3 mg/L at 
Week 26 in subjects who achieved clinical response (decrease in CDAI 
≥70 points from Baseline) at Week 8.
●
Proportion of subjects who achieve IBDQ remission (IBDQ ≥ 170 points) at 
Week 4.
●
Proportion of subjects who achieve IBDQ remission at Week 26 in subjects 
with clinical response (decrease in CDAI ≥ 70 points from Baseline) at 
Week 8.
●
Change from Baseline in fecal calprotectin level at Week 4.
●
Proportion of subjects who achieve CDAI <150, hs-CRP < 3 mg/L and fecal 
calprotectin < 250 μg/g at Week 4.
●
Proportion of subjects who achieve CDAI <150, hs-CRP < 3 mg/L and fecal 
calprotectin < 250 μg/g at Week 26 in subjects who achieved clinical response 
(decrease in CDAI ≥ 70 points from Baseline) at Week 8.
Additional secondary endpoints include:
●
Proportion of subjects with clinical remission (CDAI < 150) over time.
●
Proportion of subjects with CDAI < 150 plus a reduction in hs-CRP of at least 
50% from Baseline over time.
●
Proportion of subjects with clinical response (decrease in CDAI ≥ 70 points 
from Baseline) over time.
●
Proportion of subjects with decrease in CDAI ≥ 70 points from Baseline plus a 
reduction in hs-CRP of at least 30% from Baseline over time.
●
Change from Baseline in CDAI over time.
●
Change from Baseline in hs-CRP level over time.
●
Change from Baseline in fecal calprotectin level over time.

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5.3.4
Safety Variables
Safety analyses will be performed on all subjects who receive at least one dose of study 
drug.  Incidence of adverse events, changes in vital signs, physical examination results, 
and clinical laboratory data will be assessed.
5.3.5
Pharmacokinetic Variables
Serum adalimumab concentrations will be determined from samples collected just prior to 
dosing at Baseline (Week 0), Week 4, Week 8, Week 12, and Week 26/Premature 
Discontinuation.  Blood samples for the measurement of serum adalimumab 
concentrations at Week 14, Week 16, Week 18, Week 20, Week 22 and Week 24 will be 
collected prior to dosing only if the subject qualifies for dose escalation.
Serum anti-adalimumab antibody (AAA) will be determined from the samples collected 
just prior to dosing at Baseline (Week 0), Week 4, Week 12 and Week 26/Premature 
Discontinuation. Blood samples for the measurement of serum AAA at Week 14, 
Week 16, Week 18, Week 20, Week 22 and Week 24 will be collected prior to dosing 
only if the subject qualifies for dose escalation.
Blood samples will also be collected for measurement of infliximab serum levels and 
HACA just prior to dosing at Baseline (Week 0).
5.3.6
Pharmacogenetic Variables
DNA samples may be sequenced and data analyzed for genetic factors contributing to the 
disease or the subject's response to adalimumab, or other study treatment, 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 believed to be related to the disease (examples include but are not 
limited to LCN2, CCL20, NOD2) or drug response.  Some genes currently insufficiently 
characterized or unknown may be understood to be important at the time of analysis.  The 
samples may be analyzed as part of a multi-study assessment of genetic factors involved 
in the response to adalimumab, drugs of this class, or the disease.  The samples may also 

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be used for the development of diagnostic tests related to adalimumab, drugs of this class, 
or disease.  The results of pharmacogenetic analyses may not be reported with the study 
summary.
5.3.7
mRNA Variables
Samples from subjects may be analyzed for mRNA expression levels contributing to the 
subject's response to disease or study treatment, in terms of pharmacokinetics, 
pharmacodynamics, efficacy, tolerability and safety.  Messenger RNA levels related to 
disease or response to drug therapy will be measured in peripheral whole blood.  For 
analysis, mRNA expression may be analyzed using a microarray and polymerase chain 
reaction (PCR) technique in peripheral blood samples.  This analysis will measure the 
levels of essentially all mRNAs present in the collected peripheral blood samples.  
Messenger RNA analysis will be limited to studying response to Crohn's disease; no other 
analyses will be performed.  Results of biomarker mRNA are considered exploratory and 
may not be included in 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 SDP.
●
The Investigator believes it is in the best interest of the subject.
●
The subject requests withdrawal from the study.

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●
Inclusion and exclusion criteria violation was noted after the subject started 
study drug, when continuation of the study would place the subject at risk as 
determined by the AbbVie SDP (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 SDP.
●
Subject is non-compliant with TB prophylaxis.
●
Subjects with negative TB Screening before Week 0 who later develop a 
positive/indeterminate QuantiFERON-TB Gold In-Tube test result or 
CXR/chest CT findings.
●
The subject becomes pregnant while on study drug.
●
Subject has dysplasia 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 SDP.
If, during the course of study drug administration, the subject prematurely discontinues 
study drug use, the procedures outlined for the Premature Discontinuation 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.  The information will be recorded on the appropriate eCRF page.  The 70-day 
follow-up phone call will not be required for any subject who initiates adalimumab 
therapy not supplied in the context of the clinical trial after the end of study participation.

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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 
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
Study drug will be provided as a sterile solution for SC injection, contained in pre-filled 
syringes containing adalimumab 40 mg/0.8 mL or matching placebo for adalimumab.  
The investigator or designee will subcutaneously administer study drug to the subject per 
the dosing schedule.
Double-Blind Period (Week 0 – Week 8)
Adalimumab 40 mg/0.8 mL or Placebo for Adalimumab 0.8 mL:
During the randomized double-blind treatment period, subjects will be randomized to one 
of two groups.  Subjects randomized to adalimumab will receive blinded adalimumab 

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160 mg at Week 0, 80 mg at Week 2, and 40 mg at Week 4 and Week 6. Subjects 
randomized to placebo will receive matching placebo at Week 0 and Week 2, adalimumab 
160 mg at Week 4, and adalimumab 80 mg at Week 6.  At Week 8, all subjects will 
commence and 18-week OL period during which they will receive adalimumab 40 mg 
eow.
Open-Label Period (Week 8 – Week 26)
Adalimumab 40 mg/0.8 mL:
Starting at the Week 8 visit all subjects will receive one injection with 40 mg adalimumab 
and then eow until Week 26.  If subject qualifies for dose escalation during the OL Period 
the subject may escalate to adalimumab 80 mg eow.
The duration of the study could be up to 39 weeks which includes a Screening Period of 
up to 35 days, 8 weeks double-blind treatment periods, an 18-week OL period, and a 
follow-up period 70 days from the last dose of study drug to obtain information on any 
new or ongoing AEs.
At or after Week 12, any subject who experiences inadequate response (defined below), 
may increase dose to open-label adalimumab 80 mg eow.  If the subject has received 
open-label 80 mg eow therapy and continues to demonstrate inadequate response, they 
should be withdrawn from the study.
No dose will be given at the final visit (Week 26).
For the Purposes of Dose Escalation, Inadequate Response:
Crohn's disease activity index (CDAI) ≥ 200 and at least one of the following criteria 
is met:  an increase of at least 1 mg/L in level of high-sensitivity C-reactive protein 
(hs-CRP) from Baseline or an hs-CRP ≥ 5 mg/L.
The hs-CRP results used to determine inadequate response should be the most recent 
available results.  Assessment of inadequate response should include consideration by 

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the Investigator to rule out symptoms caused by reasons other than Crohn's disease 
related inflammation.  The most recent hs-CRP value should first be compared to the 
most recent CDAI from the previous visit.  Then the most recent hs-CRP value should 
be assessed in relation to CDAI calculated at the current visit.  Dose changes are to 
only occur in accordance with the eow dosing schedule.
5.5.2
Identity of Investigational Products
The individual study drug information is presented in Table 4.
Table 4.
Study Drugs
Drug
Dosage Form
Device
Formulation
Manufacturer
Adalimumab
Parenteral
Pre-filled 
syringe
40 mg/0.8 mL solution for 
injection 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
Parenteral
Pre-filled 
syringe
0.8 mL solution for injection 
mannitol, Citric Acid 
monohydrate, Sodium citrate, 
Disodium phosphate dehydrate, 
Sodium dihydrogen phosphate 
dehydrate, Sodium chloride, 
Polysorbate 80, water for 
injections, Sodium Hydroxide 
added as necessary to adjust pH
AbbVie
5.5.2.1
Packaging and Labeling
Investigational product will be packaged separately in 0.8 mL syringe containing either 
adalimumab 40 mg/0.8 mL or matching placebo for adalimumab.  Each dosing kit carton 
contains two pre-filled syringes to accommodate study design.  The syringe and/or carton 
labels will minimally contain the information as required per country requirements.

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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 drug supplies are 
provided in Appendix E and Appendix F.
5.5.2.2
Storage and Disposition of Study Drug
Adalimumab pre-filled syringes are to be stored protected from light at 2° to 8°C/36° 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 (daily is recommended) on a temperature log to record proper function.  
Malfunctions or any temperature excursion must be reported to the Sponsor immediately.  
Study medication should be quarantined and not dispensed until AbbVie GPRD or 
AbbVie Temperature Excursion Management System (ATEMS), if applicable, deems the 
medication as acceptable.
All clinical supplies must be stored and locked in a secure place until they are dispensed 
for subject use or are returned to AbbVie.
Investigational products are for investigational use only and are to be used only within the 
context of this study.
5.5.3
Method of Assigning Subjects to Treatment Groups
All subjects will be assigned a unique identification number by the IRT system at the 
screening study visit.  Subjects who meet the entry criteria in Section 5.2.1 and 
Section 5.2.2 will proceed to be enrolled into the study.  Subjects who enter the study will 
be randomized at Baseline (Week 0) in a 1:1 ratio to receive adalimumab or placebo.  The 
randomization will be stratified by Crohn's disease severity (CDAI ≤ 300, > 300) at 
Baseline (Week 0) and corticosteroid use at Baseline.
The sites will be provided with appropriate kit number(s) for drug-dispensing purpose for 
each subject by the IRT.  Before the study is initiated, the access information for the IRT 

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system will be provided to each site.  Study drug will be administered at the study visits 
summarized in Table 1.
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 or miss their regularly scheduled visit for the injection of study 
medication on their regularly scheduled dosing date, they should return to the site to take 
the forgotten or missed 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.
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 remain full at the study site.  The subject 
should resume their regular dosing schedule based on the first dosing date at Baseline 
(Week 0) and the site should obtain new study drug kit assignment from the IRT system.
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 Interactive Response Technology (IRT) 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 SDP 
(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.

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5.5.6
Treatment Compliance
The investigator or his/her designated and qualified representatives will 
administer/dispense study drug only to subjects enrolled in the study in accordance with 
the protocol.  The study drug must not be used for reasons other than that described in the 
protocol.
If the subject doses at home, the subject or their qualified designee will administer all 
doses of assigned 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 diary 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 return the diary, 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 diary 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, and in the correct amounts.  This will be accomplished by 
documenting the condition of the shipment, verifying the kit numbers in the package 
against the Proof of Receipt (POR) or similar document included with each drug 
shipment, and documenting this verification by signing and dating the POR or similar 
document.  The original POR Note or similar document will be kept in the site files as a 
record of what was received.
In addition, an accurate running inventory of study drug will be kept by the site in the IRT 
system including date received, the lot number, box number(s), date dispensed, subject 

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number, drug expiration date, and the identification with date of the person dispensing the 
drug.  All expired drug will be removed from refrigerated storage and placed under 
quarantine until such a time as it can be returned to AbbVie.
All empty Investigational Product (IP) boxes will be inventoried by the site and verified 
by the Monitor.  Monitors and site staff will complete study medication accountability via 
study medication logs and empty IP at each visit.  Once the monitor has verified drug 
accountability at the site, the site staff and monitor will document that the used pre-filled 
syringes have been destroyed, using appropriate biohazard precautions.  Used Sharps 
containers should never be opened.  After verification of drug accountability by the site 
staff and the monitor, used pre-filled syringes will be destroyed by the site.  A copy of the 
destruction methodology should be maintained at the site's facility.  All unused study drug 
must be inventoried, accounted for and returned to Depot for destruction.  The IRT system 
will produce list of study drug being returned; the list should be enclosed with the 
shipment.
5.6
Discussion and Justification of Study Design
5.6.1
Discussion of Study Design and Choice of Control Groups
The study design was chosen to demonstrate the efficacy of adalimumab as induction and 
maintenance therapy for Crohn's disease.  Subjects with active CD who meet all inclusion 
criteria and none of the exclusion criteria are eligible for this study.  The specific subject 
population chosen was based on the unmet medical need for subjects with moderately to 
severely active symptoms plus evidence of active inflammation (as documented by 
hs-CRP).
The first 4 weeks of the double-blinded period will evaluate the efficacy of adalimumab 
(160/80 mg at Week 0/2) to induce clinical remission (CDAI < 150) at Week 4 compared 
to placebo.  Recognizing the severe and debilitating nature of Crohn's disease and the 
associated suffering experienced by subjects, subjects randomized to placebo will receive 
induction with adalimumab 160/80 mg at Weeks 4/6 (subjects randomized to adalimumab 
will receive adalimumab 40 mg at Weeks 4 and 6 with matching placebo to retain 

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blinding).  Beginning at Week 8, all subjects will receive open-label therapy with 
adalimumab 40 mg every other week.  Rates of remission at Week 26 will be evaluated in 
subjects meeting the definition for response (reduction in CDAI ≥ 70 points from 
Baseline) after induction therapy (determined at Week 8) and compared against a 
clinically meaningful remission rate obtained using the data from adult placebo from 
Western CD Study M02-404 (see Section 8.2 for details).
5.6.2
Appropriateness of Measurements
Standard pharmacokinetic, statistical, clinical, and laboratory procedures will be utilized 
in this study.  All efficacy measurements in this study are standard for assessing disease 
activity in subjects with CD.  All clinical and laboratory procedures in this study are 
standard and generally accepted.
5.6.3
Suitability of Subject Population
Subjects with active CD who meet all inclusion criteria and none of the exclusion criteria 
are eligible for this study.  The specific subject population chosen was based on the unmet 
medical need for subjects with moderately to severely active CD in China who also have 
evidence of active inflammation (by hs-CRP).
5.6.4
Selection of Doses in the Study
The dose of adalimumab to be tested in the Chinese patient population is the same dose 
approved globally (US, EU, and Japan package labels) for patients with Crohn's disease 
and was selected based on similar pharmacokinetics in Chinese subjects observed in 
Study M14-232 as in studies conducted in Western subjects.  The 160/80 mg induction 
dose was associated with the greatest efficacy in Study M02-403 and Study M14-232, and 
is the approved dose in the US, Japan, and one of the two approved doses in Europe.  The 
40 mg every other week maintenance dose is the approved dose in the US, EU, and Japan, 
and the 80 mg every other week dose for subjects with inadequate response is the same 
dose approved in Japan for subjects with inadequate response to 40 mg every other week 
maintenance dosing.

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6.0
Complaints
A Complaint is any written, electronic, or oral communication that alleges deficiencies 
related to the physical characteristics, identity, quality, purity, potency, durability, 
reliability, safety, effectiveness, or performance of a product/device after it is released for 
distribution.
The investigational product in this trial contains both: 
●
Biologic compound(s) and
●
Device component(s) (pre-filled syringe).
Complaints associated with any component of this investigational product must be 
reported to the Sponsor (Section 6.2.2).  For adverse events, please refer to Sections 6.1
through 6.1.7.  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 is defined as any untoward medical occurrence in a patient or clinical 
investigation subject administered a pharmaceutical product and which does not 
necessarily have a causal relationship with this treatment.  An adverse event can therefore 
be any unfavorable and unintended sign (including an abnormal laboratory finding), 
symptom, or disease temporally associated with the use of a medicinal (investigational) 
product, whether or not the event is considered causally related to the use of the product.
Such an event can result from use of the drug as stipulated in the protocol or labeling, as 
well as from accidental or intentional overdose, drug abuse, or drug withdrawal.  Any 
worsening of a pre-existing condition or illness is considered an adverse event.  
Worsening in severity of a reported adverse event should be reported as a new adverse 
event.  Laboratory abnormalities and changes in vital signs are considered to be adverse 
events only if they result in discontinuation from the study, necessitate therapeutic 
medical intervention, meet protocol specific criteria (See 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 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 Day –7 for subjects initiating TB prophylaxis 
during the screening period (if applicable) or from the time study drug administration until 
70 days following discontinuation of study drug administration have elapsed will be 
collected, whether solicited or spontaneously reported by the subject.  In addition, serious 
adverse events and protocol-related nonserious adverse events will be collected from the 
time the subject signed the study-specific informed consent.
All subjects who do not initiate adalimumab therapy not supplied in the context of the 
clinical trial after the end of study participation will have a follow-up phone call 70 days 
after the last administration of study drug to obtain information on any new or ongoing 
AEs.
Adverse event information will be collected as shown in Figure 2.
Figure 2.
Adverse Event Collection
SAEs and 
Protocol-Related 
Nonserious AEs
SAEs and Nonserious AEs
Elicited and/or Spontaneously Reported
∀
∀
∀
∀
∀
Consent 
Signed
Day –7*
Study 
Drug Start
Study Drug 
Stopped
70 Days After 
Study Drug 
Stopped
*
If the subject initiates TB prophylaxis during the Screening Period, AEs will be collected starting at the Day –7 
visit.  If the subject does not initiate TB prophylaxis during the Screening Period, AEs will be collected starting at 
Baseline (SAEs and nonserious protocol related AEs are collected starting at the time of consent).
6.1.5
Adverse Event Reporting
In the event of a SAE, and additionally, any nonserious event of malignancy in subjects 
30 years of age or younger, whether associated with study drug or not, the Investigator 
will notify Clinical Pharmacovigilance within 24 hours of the site being made aware of 
the event by entering the SAE or nonserious event of malignancy in subjects 30 years of 
age and younger into the electronic data capture (EDC) system.  Serious adverse events 

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and non-serious events of malignancy in subjects 30 years of age and younger that occur 
prior to the site having access to the RAVE® system or if RAVE is not operable should be 
documented on the SAE Non-CRF forms and emailed (preferred route) or faxed to 
Clinical Pharmacovigilance within 24 hours of being made aware of the serious adverse 
event.
For safety concerns, contact the Immunology Safety Team at:
Immunology Safety Team Hotline

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In case of subject safety concerns or medical emergencies should the Primary Study 
Designated Physician be unavailable, please call the following central back-up number:
6.1.6
Pregnancy
Pregnancy in a study subject must be reported to AbbVie within 1 working day of the site 
becoming aware of the pregnancy.  Subjects who become pregnant during the study must 
be discontinued (Section 5.4.1).  Pregnancies will be collected from the date of the 
first dose through 150 days following the last dose of study drug.
Information regarding a pregnancy occurrence in a study subject and the outcome of the 
pregnancy will be collected.
Pregnancy in a study subject is not considered an adverse event.  However, the medical 
outcome of an elective or spontaneous abortion, stillbirth or congenital anomaly is 
considered a serious adverse event and must be reported to AbbVie within 24 hours of the 
site becoming aware of the event.
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" (see Section 6.1.1 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.

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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 
discrepancies/inadequacies in the labeling/instructions (example:  printing illegible), 
missing components/product, device not working properly, or packaging issues.
For medical devices, a product complaint also includes all deaths of a patient using the 
device, any illness, injury, or adverse event in the proximity of the device, an adverse 
event that could be a result of using the device, any event needing medical or surgical 
intervention including hospitalization while using the device and use errors.
Any information available to help in the determination of causality by the device to the 
events outlined directly above should be captured.
6.2.2
Reporting
Product Complaints concerning the investigational product and/or device must be reported 
to the Sponsor within 24 hours of the study site's knowledge of the event via the Product 
Complaint form.  Product Complaints occurring during the study will be followed-up to a 
satisfactory conclusion.  All follow-up information is to be reported to the Sponsor (or an 
authorized representative) and documented in source as required by the Sponsor.  Product 

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Complaints associated with adverse events will be reported in the study summary.  All 
other complaints will be monitored on an ongoing basis.
Product Complaints may require return of the product with the alleged complaint 
condition (syringe).  In instances where a return is requested, every effort should be made 
by the investigator to return the product within 30 days.  If returns cannot be 
accommodated within 30 days, the site will need to provide justification and an estimated 
date of return.
The description of the complaint is important for AbbVie in order to enable AbbVie to 
investigate and determine if any corrective actions are required.
7.0
Protocol Deviations
AbbVie does not allow intentional/prospective deviations from the protocol unless when 
necessary to eliminate an immediate hazard to study subjects.  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 Clinical Monitors:

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Such contact must be made as soon as possible to permit a review by AbbVie to 
determine the impact of the deviation on the subject and/or the study.
For the purposes of this protocol, reportable deviations are defined as:
●
Subject entered into the study even though she/he did not satisfy entry criteria
●
Subject who developed withdrawal criteria during the study and was not 
withdrawn
●
Subject who received wrong treatment or incorrect dose
●
Subject who received excluded or prohibited concomitant treatment
8.0
Statistical Methods and Determination of Sample 
Size
8.1
Statistical and Analysis Plans
The objectives of the statistical analyses are to evaluate the efficacy and safety of 
adalimumab in inducing and maintaining clinical remission in Chinese subjects with 
moderately to severely active Crohn's disease and elevated hs-CRP.

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Complete, specific details of the statistical analysis will be described and fully 
documented in the Statistical Analysis Plan (SAP).  The SAP will be finalized prior to the 
database lock.
8.1.1
Analyzable Population
The following populations will be used for analyses in this study:
Intent-to-Treat (ITT) set includes all subjects who are randomized.  ITT subjects will be 
analyzed as randomized.  ITT set is the primary population for the efficacy analysis 
during the double-blind and open-label treatment periods.
The safety set consists of all enrolled subjects who received at least one injection of 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
All statistical tests will be two-tailed with the significance level 0.05.  Descriptive 
statistics will be provided.  These include the number of observations, mean, standard 
deviation, minimum, median, 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).
8.1.3
Demographics and Baseline Characteristics
Demographics and Baseline characteristics of the study subjects will be summarized using 
descriptive statistics.  The p-value will be provided to assess the comparability of the 
treatment groups assigned by randomization.  The continuous variables will be analyzed
using the analysis of variance (ANOVA), and discrete variables will be analyzed using the 
chi-square test or Fisher's exact test.

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8.1.4
Statistical Analyses of Efficacy
8.1.4.1
Primary Efficacy Variable
The primary efficacy variable is proportion of subjects who achieve a CDAI < 150 at 
Week 4.
The comparisons between treatment group difference on the primary efficacy variable will 
be performed using the Cochran-Mantel-Haenszel (CMH) test and will be stratified by 
Crohn's disease severity (CDAI ≤ 300, > 300) at Baseline (Week 0) and corticosteroid use 
at Baseline.  A CMH based two-sided 95% confidence interval for the difference between 
the treatment groups will be calculated.  The ITT set will be used for the analysis.  
Missing CDAI or hs-CRP will be imputed using the non-responder imputation (NRI) 
approach.  Subjects who dose escalate will be imputed using NRI for visits after dose 
escalation.  The last observation carried forward (LOCF) method will also be used as the 
sensitivity analyses.
8.1.4.2
Additional Efficacy Variables
The Week 26 efficacy endpoint is proportion of subjects who achieve clinical remission at 
Week 26 (CDAI < 150) in subjects who achieved clinical response (decrease in CDAI 
≥70 points from Baseline) at Week 8.  The one sample Exact test will be performed by 
comparing it to the clinically meaningful constant rate, and the two-sided 95% CI will be 
provided.
For key and additional secondary efficacy endpoints, continuous variables will be 
analyzed using Analysis of Covariance (ANCOVA) model including factor for treatment 
group, stratification factors and Baseline values.  For categorical endpoints with 
comparison between the treatment groups, the difference in proportions of subjects 
between treatment groups will be analyzed using the CMH test adjusted for stratification 
variables.  Additionally, the CHM based two-sided 95% confidence interval for the 
difference in proportions will be provided.  For categorical endpoints with comparison to 
the clinically meaningful constant rate, the one sample Exact test will be performed and 

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the two-sided 95% CI will be provided.  The NRI imputation method will be used for 
subjects with missing data at the time point evaluated.  Subjects who dose escalate will be 
imputed using NRI for visits after dose escalation.  The LOCF method will also be used 
as the sensitivity analyses.
Change from Baseline in continuous endpoints will be analyzed using an ANCOVA 
model including factors of treatment and adjusting for the baseline values and the 
stratification variables.  For analyses of changes from Baseline variables, both LOCF and 
observed case analyses will be performed.  The LOCF analysis is considered primary for 
inferential purposes.
8.1.5
Statistical Analyses of Safety
Laboratory data, adverse events (AEs), and vital signs are the primary safety parameters 
in this study.  All safety analyses will be performed using the Safety set, which includes 
all subjects who enrolled into this study and received at least one dose of study drug.  
Treatment-emergent AEs are defined as events that begin or worsen either on or after the 
first dose of the study drug and within 70 days after the last dose of the study drug.  An 
overview of treatment-emergent AEs, including AEs of special interest such as AEs 
leading to death and AEs leading to premature discontinuation (see details in the SAP), 
AEs by Medical Dictionary for Drug Regulatory Activities (MedDRA version 17.0 or 
later) preferred term and system organ class, AEs by maximum relationship to study drug, 
and AEs by maximum severity will be summarized by number and percentage.  
Treatment-emergent AEs will be summarized separately for the double-blind dosing 
period (Week 0 to Week 8) and the OL period (Week 8 to 70 days after the last dose of 
the study medication).  
Changes in laboratory data will be described using statistical characteristics and compared 
between treatment groups will be performed using a one-way Analysis of Variance 
(ANOVA).  In addition, shift tables and listings will be provided for abnormal values, 
whereby the normal range of the analyzing laboratory will be used.  Vital signs will be 
analyzed similarly.

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8.1.6
Other Statistical Analyses of Efficacy
The subgroups listed below will be used in subgroup analyses of the primary endpoint.  
●
Sex (male, female)
●
Age (≤ median, > median)
●
Baseline fecal calprotectin (≤ median, > median)
●
Baseline fecal calprotectin (≤ 250 μg/g, > 250 μg/g)
●
Baseline corticosteroid use (yes, no)
●
Baseline immunosuppressant use (yes, no)
●
hs-CRP at Baseline (< 10 and ≥ 10 mg/L)
●
hs-CRP at Baseline (< 30 and ≥ 30 mg/L)
●
hs-CRP at Baseline (≤ median, > median)
●
Crohn's disease activity (CDAI ≤ 300, > 300) at Baseline
●
Baseline CDAI (≤ median, > median)
●
Weight (≤ median, > median)
●
Baseline albumin (≤ median, > median)
●
Disease duration (≤3 years, > 3 years)
●
Disease duration (≤ median, > median)
8.1.7
Pharmacokinetic Analyses
Adalimumab trough serum concentrations will be summarized 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.  The relationship between adalimumab concentrations 
and clinical response will be determined as appropriate.
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 AEs may be evaluated.

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8.2
Determination of Sample Size
The Week 4 primary efficacy endpoint is defined as the proportion of subjects achieving 
CDAI < 150.  Based on the adalimumab CD clinical trial results, the remission rate was 
67% in the ADA 160/80 mg treatment group and 40% in the ADA 80/40 mg treatment 
group in China Phase 2 CD Study M14-232 (no placebo group in that study), and 40% in 
the ADA 160/80 mg treatment group and 8% in the placebo group in Western CD Study 
CLASSIC I (Study M02-403) based on subjects with elevated CRP at baseline (hs-CRP 
≥3 mg/L).  Considering that the placebo effect in China Phase 3 study will potentially be 
higher than the Western placebo rate, and the treatment effect in the ADA 160/80 mg 
treatment group will potentially be lower than the China Phase 2 CD study, the 
assumption of remission rates at Week 4 for this study is 24% and 47% for placebo and 
the ADA 160/80 mg treatment groups, respectively, with the expected treatment 
difference of 23%.  A sample size of 100 subjects per arm (total 200 subjects) will provide 
power of 90% to detect the 23% treatment difference in the primary efficacy endpoint 
between the ADA 160/80 mg treatment group and placebo (1:1 randomization ratio), 
using two-sided Fisher's exact test at a 0.05 significance level.
If the overall Week 8 response rate is over 50%, it is expected that approximately 
100 subjects who are Week 8 responders will enter the open-label maintenance period and 
comprise the analysis population for Week 26 endpoints.  Based on the observed Week 26 
remission rate (52% [34/66]) for the ADA 40 mg EOW treatment group in Western CD 
Study M02-404 in anti-TNF naïve subjects with elevated CRP at baseline (hs-CRP 
≥3 mg/L) who responded to adalimumab induction therapy, the sample size of 
100 subjects will allow ≥ 99% power to detect remission rate at Week 26 of 52% against a 
clinically meaningful remission rate of 30% using one-sample Exact test at a two-sided 
0.05 significance level.  The remission rate of 30% was obtained using the upper bound of 
the 95% CI of the adult placebo rate from the Western CD Study M02-404 in the same 
subgroup of patients. 
Prior to the completion of enrollment, assessment of the sample size based on the blinded 
data (overall event rate at Week 4) will be conducted.

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8.3
Randomization Methods
At Baseline (Week 0), subjects will be randomized 1:1 to double-blinded adalimumab or 
placebo.  The randomization will be stratified by Crohn's disease severity (CDAI ≤ 300, 
> 300) at Baseline (Week 0) and corticosteroid use at Baseline.
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) GCP guidelines, applicable regulations and guidelines governing 
clinical study conduct and 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 answer all questions regarding this study.  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, the person who administered the 
informed consent, and any other signatories according to local requirements.  A copy of 
the informed consent form will be given to the subject and the original will be placed in 
the subject's medical record.  An entry must also be made in the subject's dated source 
documents to confirm that informed consent was obtained prior to any study-related 
procedures and that the subject received a signed copy.
Information regarding incentives for subjects and information regarding provisions for 
treating and/or compensating subjects who are harmed as a consequence of participation 
in the study can be found in the informed consent form.
Samples for pharmacogenetic and biomarker analysis will only be collected if the subject 
has voluntarily signed and dated a separate informed consent, approved by an IRB/IEC, 
after the nature of the testing has been explained and the subject has had an opportunity to 
ask questions.  The separate informed consent must be signed before the pharmacogenetic 
and biomarker samples are collected and testing is performed.  If the subject does not 
consent to the pharmacogenetic and biomarker analysis, it will not affect the subject's 
participation in the study.

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10.0
Source Documents, Data Collection and Electronic 
Case Report Forms
10.1
Source Documents
Source documents are defined as original documents, data and records.  This may include 
hospital records, clinical and office charts, laboratory data/information, subjects' diaries or 
evaluation checklists, pharmacy dispensing and other records, recorded data from 
automated instruments, microfiches, photographic negatives, microfilm or magnetic 
media, and/or x-rays.  Data collected during this study must be recorded on the 
appropriate source documents.
The investigator(s)/institution(s) will permit study-related monitoring, audits, IEC/IRB 
review, and regulatory inspection(s), providing direct access to source data documents.
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 
collected with an electronic data capture (EDC) system called Rave® provided by the 
technology vendor Medidata Solutions Incorporated, NY, USA.  The EDC system and the 
study-specific electronic case report forms (eCRFs) will comply with Title 21 CFR 
Part 11.  The documentation related to the validation of the EDC system is available 
through the vendor, Medidata, while the validation of the study-specific eCRFs will be 
conducted by AbbVie and will be maintained in the Trial Master File at AbbVie.
The investigator will document subject data in his/her own subject files.  These subject 
files will serve as source data for the study.  All eCRF data required by this protocol will 
be recorded by investigative site personnel in the EDC system.  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 

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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.
The following assessments will be completed by subjects on paper:
●
IBDQ
Site staff will verify completion of these forms.  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 study subject who is 
making the correction.  Data are not to be obliterated by blacking out, using correction 
fluid or by erasing the original entry.
The questionnaire administrator will review the questionnaire for completeness and 
accuracy.  The subject-completed questionnaires will be transcribed into the EDC system 
by study personnel.  The completed paper questionnaire will be considered source.  
The principal investigator will review the case report forms for completeness and 
accuracy and sign and date the set of case report forms where indicated.  AbbVie 

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personnel (or their representatives) will review the case report forms periodically for 
completeness, legibility, and acceptability.  AbbVie (or their representatives) will be 
allowed access to all source documents in order to verify case report form entries.
11.0
Data Quality Assurance
Computer logic and manual checks will be created to identify items such as inconsistent 
study dates.  Any necessary corrections will be made to the eCRF.
12.0
Use of Information
All information concerning adalimumab and AbbVie operations, such as AbbVie patent 
applications, formulas, manufacturing processes, basic scientific data, or formulation 
information, supplied by AbbVie and not previously published is considered confidential 
information.
The information developed during the conduct of this clinical study is also considered 
confidential and will be used by AbbVie in connection with the development of 
adalimumab.  This information may be disclosed as deemed necessary by AbbVie to other 
clinical investigators, other pharmaceutical companies, to the FDA and to other 
governmental agencies.  To allow for the use of the information derived from this clinical 
study and to ensure complete and thorough analysis, the investigator is obligated to 
provide AbbVie with complete test results and all data developed in this study and to 
provide direct access to source data/documents for trial-related monitoring, audits, 
IEC/IRB review, and regulatory inspection.
This confidential information shall remain the sole property of AbbVie, shall not be 
disclosed to others without the written consent of AbbVie, and shall not be used except in 
the performance of this study.
The investigator will maintain a confidential subject identification code list of all subjects 
enrolled in the study (by name and subject number).  This list will be maintained at the 
site and will not be retrieved by AbbVie.

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Any pharmacogenetic and biomarker research that may be done using DNA/mRNA 
samples from this study will be experimental in nature and the results will not be suitable 
for clinical decision making or patient 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 and biomarker 
information from this study may be used in scientific publications or presented at medical 
conventions.  Pharmacogenetic and biomarker 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 
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.

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The end-of-study is defined as the date of the last subject's last visit.

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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, Placebo Controlled Study 
to Evaluate the Efficacy and Safety of Adalimumab for the Induction 
and Maintenance of Clinical Remission in Chinese Patients with 
Moderately to Severely Active Crohn's Disease and Elevated 
High-Sensitivity C-reactive Protein
Protocol Date: 
19 October 2015
Signature of Principal Investigator
Date
Name of Principal Investigator (printed or typed)

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15.0
Reference List
1.
Hanauer SB, Sandborn W; Practice Parameters Committee of the American 
College of Gastroenterology.  Management of Crohn's disease in adults.  Am J 
Gastroenterol.  2001;96(3):635-43.
2.
Loftus EV Jr.  Clinical epidemiology of inflammatory bowel disease:  incidence, 
prevalence, and environmental influences.  Gastroenterology.  
2004;126(6):1504-17.
3.
Probert CS, Jayanthi V, Rampton DS, et al.  Epidemiology of inflammatory bowel 
disease in different ethnic and religious groups:  limitations of aetiological clues.  
Int J Colorectal Dis.  1996;11(1):25-8.
4.
Ng SC, Tang W, Ching JY, et al; Asia-Pacific Crohn's and Colitis Epidemiologic 
Study (ACCESS) Study Group.  Incidence and phenotype of inflammatory bowel 
disease based on results from the Asia-Pacific Crohn's and colitis epidemiology 
study.  Gastroenterology.  2013;145(1):158-65.
5.
Zhao J, Ng SC, Lei Y, et al.  First prospective, population-based inflammatory 
bowel disease incidence study in mainland of China:  the emergence of "western" 
disease.  Inflamm Bowel Dis.  2013;19(9):1839-45.
6.
Zeng Z, Zhu Z, Yang Y, et al.  Incidence and clinical characteristics of 
inflammatory bowel disease in a developed region of Guandong Province, China:  
a prospective population-based study.  J Gastroenterol Hepatol.  
2013;28(7):1148-53.
7.
Chinese Cooperative Group for the study on IBD, Chinese Society of 
Gastroenterology.  Ouyang Q, Hu PJ, Qian JM, et al.  Consensus on the 
management of inflammatory bowel disease in China in 2007.  J Dig Dis.  
2008;9(1):52-62.
8.
Zheng JJ, Zhi P, Wang YM, et al.  Short-term study of infliximab treatment for 
Crohn's disease in China.  J Dig Dis.  2011;12(2):105-9.

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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
Clinical
Statistics
Pharmacokinetics/Pharmacodynamics
Clinical
Clinical
Clinical

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Appendix C.
Crohn's Disease Activity Index (CDAI)
Factor
Subtotal
1. Number of liquid or very soft stools 
(Record the frequency per day)
__+___+___+___+___+___+___=__ 
Days:  1    2    3    4    5    6    7    Sum
X
2
2. Abdominal pain rating:
0 = none, 1 = mild, 2 = moderate, 
3 = severe
__+___+___+___+___+___+___=__ 
Days:  1    2    3    4    5    6    7    Sum
X
5
3. General well-being:
0 = generally well, 1 = slightly 
underpar, 2 = poor, 3 = very poor, 
4 = terrible
__+___+___+___+___+___+___=__ 
Days:  1    2    3    4    5    6    7    Sum
X
7
4. Number of 6 listed categories the 
subject now has:
Check all items that apply:
□
Arthritis/arthralgia
□
Iritis/uveitis
□
Erythema nodosum/pyoderma 
gangrenosum/aphthous
stomatitis
□
Fissure, abscess and/or anal 
fistula (draining/non-draining)
□
Other cutaneous fistula
(draining/non-draining) Fistula
□
Fever over 100°F (37.8°C) 
during past week
______________________________
______________________________
Record "0" if no categories checked
X
20
5.
Taking Lomotil 
(diphenoxylate/atropine)/Imodium/ 
Loperamide/opiates for diarrhea
0 = no, 1 = yes
________
X
30
6.
Abdominal mass
0 = none, 2 = questionable,
5 = defined
________
X
10
7.
Hematocrit:
Male:  (47 – hematocrit) = 
Female:  (42 – hematocrit) =
Subtotal 
If hematocrit > normal, enter "0"
X
6
8.
Body weight:           (kg)
Standard weight:     (kg)
100 × [1 – (Body wt/Standard wt)] = 
Percent below standard weight:  
_____
If body wt > std. wt, enter "0"
X
1
Total

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Appendix D.
Standard Weights
Standard Height and Weight Tables – Use to Calculate CDAI Score
Adjusted Height*
cm (Inches)
Standard Weight (Men)
kg (Pounds)
Standard Weight (Women) 
kg (Pounds)
121.9 (48.0)
40.8 (89.9)
123.2 (48.5)
41.3 (91.0)
124.5 (49.0)
41.8 (92.1)
125.7 (49.5)
42.3 (93.3)
127.0 (50.0)
42.8 (94.4)
128.3 (50.5)
43.4 (95.6)
129.5 (51.0)
43.9 (96.8)
130.8 (51.5)
44.4 (98.0)
132.1 (52.0)
55.5 (122.4)
45.0 (99.2)
133.4 (52.5)
55.7 (122.7)
45.5 (100.4)
134.6 (53.0)
55.8 (123.1)
46.1 (101.6)
135.9 (53.5)
56.0 (123.5)
46.6 (102.8)
137.2 (54.0)
56.2 (123.9)
47.2 (104.1)
138.4 (54.5)
56.4 (124.4)
47.8 (105.3)
139.7 (55.0)
56.7 (124.9)
48.3 (106.6)
141.0 (55.5)
56.9 (125.5)
48.9 (107.9)
142.2 (56.0)
57.2 (126.1)
49.5 (109.1)
143.5 (56.5)
57.4 (126.7)
50.1 (110.4)
144.8 (57.0)
57.7 (127.3)
50.7 (111.7)
146.1 (57.5)
58.1 (128.0)
51.3 (113.0)
147.3 (58.0)
58.4 (128.7)
52.2 (115.0)
148.6 (58.5)
58.7 (129.5)
52.6 (116.0)
149.9 (59.0)
59.1 (130.3)
53.1 (117.0)
151.1 (59.5)
59.5 (131.1)
53.6 (118.3)
152.4 (60.0)
59.9 (132.0)
54.2 (119.5)
153.7 (60.5)
60.3 (132.9)
54.8 (120.8)
154.9 (61.0)
60.7 (133.8)
55.3 (122.0)
156.2 (61.5)
61.1 (134.8)
56.0 (123.5)
157.5 (62.0)
61.7 (136.0)
56.7 (125.0)

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Standard Height and Weight Tables – Use to Calculate CDAI Score
Adjusted Height*
cm (Inches)
Standard Weight (Men)
kg (Pounds)
Standard Weight (Women) 
kg (Pounds)
158.8 (62.5)
62.1 (137.0)
57.4 (126.5)
160.0 (63.0)
62.6 (138.0)
58.0 (128.0)
161.3 (63.5)
63.0 (139.0)
58.7 (129.5)
162.6 (64.0)
63.5 (140.0)
59.4 (131.0)
163.8 (64.5)
64.1 (141.3)
60.1 (132.5)
165.1 (65.0)
64.6 (142.5)
60.8 (134.0)
166.4 (65.5)
65.2 (143.8)
61.4 (135.5)
167.6 (66.0)
65.8 (145.0)
62.1 (137.0)
168.9 (66.5)
66.4 (146.5)
62.8 (138.5)
170.2 (67.0)
67.1 (148.0)
63.5 (140.0)
171.5 (67.5)
67.8 (149.5)
64.2 (141.5)
172.7 (68.0)
68.5 (151.0)
64.9 (143.0)
174.0 (68.5)
69.2 (152.5)
65.5 (144.5)
175.3 (69.0)
69.8 (154.0)
66.2 (146.0)
176.5 (69.5)
70.5 (155.5)
66.9 (147.5)
177.8 (70.0)
71.2 (157.0)
67.6 (149.0)
179.1 (70.5)
71.9 (158.5)
68.3 (150.5)
180.3 (71.0)
72.6 (160.0)
68.9 (152.0)
181.6 (71.5)
73.4 (161.8)
69.6 (153.5)
182.9 (72.0)
74.1 (163.5)
70.3 (155.0)
184.2 (72.5)
75.0 (165.3)
71.2 (156.9
185.4 (73.0)
75.7 (167.0)
71.9 (158.5)
186.7 (73.5)
76.6 (169.0)
72.6 (160.2)
188.0 (74.0)
77.5 (171.0)
73.4 (161.8)
189.2 (74.5)
78.4 (172.8)
74.1 (163.4)
190.5 (75.0)
79.1 (174.5)
74.9 (165.1)
191.8 (75.5)
80.2 (176.8)
75.6 (166.8)
193.0 (76.0)
81.2 (179.0)
76.4 (168.4)
194.3 (76.5)
82.0 (180.8)
77.2 (170.1)
195.6 (77.0)
82.9 (182.9)
77.9 (171.8)
196.9 (77.5)
83.9 (185.0)
78.7 (173.5)

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Standard Height and Weight Tables – Use to Calculate CDAI Score
Adjusted Height*
cm (Inches)
Standard Weight (Men)
kg (Pounds)
Standard Weight (Women) 
kg (Pounds)
198.1 (78.0)
84.9 (187.2)
79.5 (175.2)
199.4 (78.5)
85.9 (189.4)
80.3 (177.0)
200.7 (79.0)
86.9 (191.6)
81.0 (178.7)
201.9 (79.5)
87.9 (193.9)
81.8 (180.5)
203.2 (80.0)
89.0 (196.2)
82.6 (182.2)
204.5 (80.5)
90.0 (198.6)
*Height in shoes with one inch 
heels
205.7 (81.0)
91.1 (200.9)
*Indoor clothing weighing 
5 pounds for men and 3 pounds 
for women
207.0 (81.5)
92.2 (203.3)
*Centimeters × 0.3937 = inches
208.3 (82.0)
93.3 (205.8)
*Pounds × 0.4535 = kilograms
Notes:
* Values in the Adjusted Height column includes the 1" or 2.5 cm added to the height obtained during 
screening.
If the adjusted height falls in-between 2 values listed in the Adjusted Height column, the closest height listed 
on the chart should be selected.

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Appendix E.
Sample Injection Instructions for Onsite Administration –
Pre-Filled Syringe
Subject Instructions
0.8 mL dose
(Administered as a single dose-pre-filled syringe)
Protocol M14-233
Tables of Contents

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Injection Procedures (PFS)
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 prefilled syringe(s) of adalimumab from the refrigerator.  
Do not use a pre-filled syringe that has been frozen or if it has been left in 
direct sunlight.
●
Return any unused syringe(s) to the refrigerator.
You will need the following items for each dose:
●
study medication in pre-filled syringe(s)
●
alcohol prep(s)
●
cotton ball or gauze pad(s)
●
Use only the items provided in the box adalimumab comes in.
●
Make sure the liquid in the pre-filled syringe is clear and colorless.  Do not use 
a prefilled syringe 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.

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For 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 the thighs or stomach area (abdomen).  If you 
choose your abdomen, you should avoid the area 2 inches or 5 cm around your 
belly button (navel).
●
Choose a different site each time you give an injection.  Each new injection 
should be given at least one inch or 2.5 cm from a site used before.  Never 
inject into areas where the skin is tender, bruised, red or hard or where you 
have scars or stretch marks.
●
If the subject has 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 the 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 Pre-filled Syringe
●
Hold the syringe upright with the needle facing down.  The top of the liquid 
may be curved.  If the syringe does not have the correct amount of liquid, do 
not use that syringe.  Call your study monitor.

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●
Remove the needle cover taking care not to touch the needle with your fingers 
or allow it to touch any surface.
●
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.
●
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.
●
Press a cotton ball or gauze pad over the injection site and hold it for 
10 seconds.  Do not rub the injection site.  There might be slight bleeding.  
This is normal.
●
Dispose of the syringe right away into your special sharps container.

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Appendix F.
Sample Injection Instructions for at Home Dosing – Pre-Filled 
Syringe
Subject Instructions
0.8 mL dose
(Administered as a single dose-pre-filled syringe)
Protocol M14-233
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 injections throughout the study.
You will receive the following number of injections during the study:
●
Baseline Visit (the first visit to receive study medication for this study), you 
will receive 4 injections (2 kits) at the clinic.
●
Week 2 you will receive 2 injections (1 kit) at the clinic.
●
At Week 4 you will receive 4 injections at the clinic.
●
At Week 6 you will receive 2 injections at the clinic.
●
At Week 8 you will receive 1 injection at the clinic.
●
Week 10 you will administer 1 injection at home.
●
At Weeks 12, 16, and 20 you will receive 1 injection at the clinic if you have 
not dose escalated.  If you have dose escalated then you will receive
2 injections at the clinic.
●
At Weeks 14, 18, 22, and 24 you will administer 1 injection at home if you 
have not dose escalated.  If you have dose escalated then you will administer 
2 injections at home.
For all doses, kits must be used in the order dispensed.  All doses of study medication 
must be taken in order, starting with the syringe labeled with a "1," then at the next dose, 
using the syringe labeled with a "2."
Please return all used and unused syringes and empty boxes to the clinic on your next 
visit.  Used syringes should be placed in the special sharps container provided.  All 
unused syringes should be returned in the original box.
If an injection is missed or something occurs where the full dose cannot be injected, 
contact your study center immediately for further instructions.  Please record any missed 
doses on your subject dosing diary.

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Remember to complete your dosing diary 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
●
Pre-filled syringes will be labeled "Adalimumab" versus Placebo.
●
Store all adalimumab pre-filled syringes in your refrigerator NOT in the 
freezer.  Should the syringes 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 SYRINGE EVERY INJECTION DAY.  There may be 
medication left in the syringe.  DO NOT RE-USE.
●
Save all study medications.  Pre-filled syringes (used and unused) & 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.
●
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.

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Injection Procedures (PFS)
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 prefilled syringe(s) of adalimumab from the refrigerator.  
Do not use a prefilled syringe that has been frozen or if it has been left in direct 
sunlight.
●
Return any unused syringe(s) to the refrigerator.
You will need the following items for each dose:
●
study medication in pre-filled syringe(s)
●
alcohol prep(s)
●
cotton ball or gauze pad(s)

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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 prefilled syringe is clear and colorless.  Do not use 
a prefilled syringe 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 or 5 cm around 
your belly button (navel).
●
Choose a different site each time you give yourself an injection.  Each new 
injection should be given at least one inch or 2.5 cm 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.

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●
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 Prefilled Syringe
●
Hold the syringe upright with the needle facing down.  Check to make sure 
that the amount of liquid in the syringe is the same or close to the 0.8 mL line 
for the 40 mg prefilled syringe.  The top of the liquid may be curved.  If the 
syringe does not have the correct amount of liquid, do not use that syringe.  
Call your study doctor.
●
Remove the needle cover taking care not to touch the needle with your fingers 
or allow it to touch any surface.
●
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.

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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.
●
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.
●
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 special sharps container.

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Appendix G.
Sample Quality of Life in Inflammatory Bowel Disease 
Questionnaire (IBDQ)

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Appendix H.
70-Day Follow-Up Phone Call – Sample
Site Name/Number:
____________________________
Subject Number:
____________________________
Please contact subjects that 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 one attempt.)
☐
No Events Reported.
☐
N/A subject continued adalimumab therapy after the end of their study participation.
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.
Please fax all completed forms to:
[Name] at XXX-XXX-XXXX

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Appendix I.
Protocol Amendment:  List of Changes
Specific Protocol Changes
The summary of changes is listed in Section 1.1.
Section 1.0  Title Page
"Sponsor/Emergency Contact:" previously read:
Has been changed to read:

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Section 1.1  Synopsis
Subsection Diagnosis and Main Criteria for Inclusion/Exclusion:
Heading "Main Inclusion:"
Criterion 4, third bullet previously read:
At least a consecutive 42-day course of azathioprine, 6-mercaptopurine (6-MP), or 
injectable methotrexate (MTX) prior to Baseline (Week 0), with a minimum dose of
azathioprine ≥0.75 mg/kg/day or 6-MP ≥ 0.5 mg/kg/day (rounded to the nearest available 
tablet formulation) or MTX ≥ 15 mg (subcutaneous [SC]/intramuscular [IM]) per week, or 
a dose that is the highest tolerated by the subject (e.g., due to leukopenia, elevated liver 
enzymes, nausea) during that time.
Has been changed to read:
At least a consecutive 42-day course of azathioprine, 6-mercaptopurine (6-MP), or 
injectable methotrexate (MTX) prior to Baseline (Week 0), with a minimum dose of 
azathioprine ≥0.75 mg/kg/day or 6-MP ≥ 0.5 mg/kg/day (rounded to the nearest available 
tablet or half tablet formulation) or MTX ≥ 15 mg/week (subcutaneous 
[SC]/intramuscular [IM]), or a dose that is the highest tolerated by the subject (e.g., due to 
leukopenia, elevated liver enzymes, nausea) during that time.
Section 1.1  Synopsis
Subsection Diagnosis and Main Criteria for Inclusion/Exclusion:
Heading "Main Inclusion:"
"Note:" following third bullet previously read:
Note: If a subject is on both an oral corticosteroid and an immunosuppressant 
BOTH of the drugs need to meet the above criteria.
Has been changed to read:
Note: If a subject is on both an oral corticosteroid and an immunosuppressant listed 
above, BOTH of the drugs need to meet the above criteria.

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Section 1.1  Synopsis
Subsection Diagnosis and Main Criteria for Inclusion/Exclusion:
Heading "Main Exclusion:"
Criterion 12 previously read:
Subject with prior exposure to medications that have a potential or known association 
with progressive multifocal leukoencephalopathy, including participation in a clinical trial 
of investigational agents targeting white cell trafficking (e.g., natalizumab [Tysabri®], 
efalizumab [Raptiva®], or rituximab [Rituxan®]).
Has been changed to read:
Subject with prior exposure to medications that have a potential or known association 
with progressive multifocal leukoencephalopathy, including participation in a clinical trial 
of investigational agents targeting white cell trafficking (e.g., natalizumab [Tysabri®] or 
rituximab [Rituxan®]).
Section 1.1  Synopsis
Subsection Diagnosis and Main Criteria for Inclusion/Exclusion:
Heading "Main Exclusion:"
Criterion 31 previously read:
Subject with a previous history of dysplasia of the gastrointestinal tract.
Has been changed to read:
Subject with a previous history of gastric dysplasia.
Section 3.3  Adalimumab Overview
Last paragraph, second sentence previously read:
Additional indications have been approved in the US and EU including Psoriasis (Ps), 
Psoriatic Arthritis (PsA), Ankylosing Spondyloarthritis (AS), CD, pediatric Crohn's 
Disease, polyarticular Juvenile Idiopathic Arthritis (JIA), and Ulcerative Colitis (UC).  

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Has been changed to read:
Additional indications have been approved in the US and EU including Psoriasis (Ps), 
Psoriatic Arthritis (PsA), Ankylosing Spondyloarthritis (AS), CD, Ulcerative Colitis 
(UC), polyarticular Juvenile Idiopathic Arthritis (JIA), pediatric CD, pediatric psoriasis as 
well as pediatric Enthesitis Related Arthritis and non-radiographic axial spondyloarthritis 
in the EU, and intestinal Bechet's Disease in Japan.  
Section 5.1  Overall Study Design and Plan:  Description
Subsection Re-screening
Fifth sentence previously read:
If the subject had a complete initial screening evaluation including the assessment of a 
QuantiFERON-Gold, CXR (or optional chest CT scan), and electrocardiogram (ECG), 
these tests will not be required to be repeated for re-screening provided the conditions 
noted in Section 5.2 are met.  
Has been changed to read:
If the subject had a complete initial screening evaluation including the assessment of a 
QuantiFERON-TB Gold In-Tube test, CXR (or optional chest CT scan), and 
electrocardiogram (ECG), these tests will not be required to be repeated for re-screening 
provided the conditions noted in Section 5.2 are met.  If the subject had negative 
anti-HIV-1 test results from the central lab, these tests will not be required to be repeated 
if the results were obtained within 90 days of the re-screening visit.  .  If the subject had 
negative anti-HIV-1 test results from the central lab, these tests will not be required to be 
repeated if the results were obtained within 50 days of the re-screening visit provided that 
in the meanwhile nothing has changed in the patient's medical history or risk behaviors.  
Section 5.2.1  Inclusion Criteria
Criterion 4, third bullet previously read:
At least a consecutive 42-day course of azathioprine, 6-mercaptopurine (6-MP), or 
injectable methotrexate (MTX) prior to Baseline (Week 0), with a minimum dose of 
azathioprine ≥ 0.75 mg/kg/day or 6-MP ≥ 0.5 mg/kg/day (rounded to the nearest available 

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tablet formulation) or MTX ≥ 15 mg (subcutaneous [SC]/intramuscular [IM]) per week, or 
a dose that is the highest tolerated by the subject (e.g., due to leukopenia, elevated liver 
enzymes, nausea ) during that time.
Has been changed to read:
At least a consecutive 42-day course of azathioprine, 6-mercaptopurine (6-MP), or 
injectable methotrexate (MTX) prior to Baseline (Week 0), with a minimum dose of 
azathioprine ≥ 0.75 mg/kg/day or 6-MP ≥ 0.5 mg/kg/day (rounded to the nearest available 
tablet or half tablet formulation) or MTX ≥ 15 mg/week (subcutaneous 
[SC]/intramuscular [IM]), or a dose that is the highest tolerated by the subject (e.g., due to 
leukopenia, elevated liver enzymes, nausea ) during that time.
Section 5.2.1  Inclusion Criteria
Criterion 4
"Note:" following third bullet previously read:
Note: If a subject is on both an oral corticosteroid and an immunosuppressant 
BOTH of the drugs need to meet the above criteria.
Has been changed to read:
Note: If a subject is on both an oral corticosteroid and an immunosuppressant listed 
above, BOTH of the drugs need to meet the above criteria.
Section 5.2.2  Exclusion Criteria
Criterion 12 previously read:
Subject with prior exposure to medications that have a potential or known association 
with progressive multifocal leukoencephalopathy, including participation in a clinical trial 
of investigational agents targeting white cell trafficking (e.g., natalizumab [Tysabri ®], 
efalizumab [Raptiva®], or rituximab [Rituxan®]).

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Has been changed to read:
Subject with prior exposure to medications that have a potential or known association 
with progressive multifocal leukoencephalopathy, including participation in a clinical trial 
of investigational agents targeting white cell trafficking (e.g., natalizumab [Tysabri®] or 
rituximab [Rituxan®]).
Section 5.2.2  Exclusion Criteria
Criterion 31 previously read:
Subject with a previous history of dysplasia of the gastrointestinal tract.
Has been changed to read:
Subject with a previous history of gastric dysplasia.
Section 5.2.3.3  Prohibited Therapy
Delete:  eighth sub-bullet following first bullet
Efalizumab (Raptiva®);

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Table 1.  Study Activities
Activity "Pregnancy Testsm" previously read:
Activity
Screening 
(35 Days)
Day 
–21a Day 
–7a Baseline 
(Wk 0)b Wk 
2
Wk 
4
Wk 
6
Wk 
8
Wk 
10
Wk 
12
Wk 
14
Wk 
16
Wk 
18
Wk 
20
Wk 
22
Wk 
24
Wk 26/
Premature 
Discontinuation
Unscheduled 
Visit
70-Day
Follow-Up 
Callc
Pregnancy Testsm
Xm
X
X
X
Has been changed to read:
Activity
Screening 
(35 Days)
Day 
–21a Day 
–7a Baseline 
(Wk 0)b Wk 
2
Wk 
4
Wk 
6
Wk 
8
Wk 
10
Wk 
12
Wk 
14
Wk 
16
Wk 
18
Wk 
20
Wk 
22
Wk 
24
Wk 26/
Premature 
Discontinuation
Unscheduled 
Visit
70-Day 
Follow-Up 
Callc
Pregnancy Testsm
X
X
X
X

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Table 1.  Study Activities
Table note "n.," ninth and tenth sentence previously read:
Re-screen subjects with a negative anti-HIV-1 test results from the central lab within 
90 days of initial Screening are not required to repeat HIV testing.  Subjects with a 
negative anti-HIV-1 test results from the central lab within 90 days of Screening are not 
required to repeat HIV testing.
Has been changed to read:
If the subject had negative anti-HIV-1 test results from the central lab, these tests will not 
be required to be repeated if the results were obtained within 50 days of the re-screening 
visit provided that in the meanwhile nothing has changed in the patient's medical history 
or risk behaviors.  If the subject had negative HBV and Anti-Hepatitis C test results from 
the central lab, these tests will not be required to be repeated if the results were obtained 
within 35 days of the re-screening visit.  
Section 5.3.1.1  Study Procedures
Subsection TB Testing
First bullet previously read:
QuantiFERON-TB Gold In-Tube (QTF),
Has been changed to read:
QuantiFERON-TB Gold In-Tube test (QTF),
Section 5.3.1.1  Study Procedures
Subsection Crohn's Disease Activity Index (CDAI)
Seventh paragraph previously read:
Standard height is calculated by using the height obtained at Screening (without shoes) 
plus one inch.

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Has been changed to read:
Standard height is calculated by using the height obtained at Screening (without shoes) 
plus one inch or 2.5 cm.
Section 5.3.1.1  Study Procedures
Subsection Hepatitis and HIV Testing
Third paragraph, last sentence previously read:
Subjects with negative anti-HIV-1 test results from the central lab within 90 days of 
Screening are not required to repeat HIV testing.
Has been changed to read:
If the subject had negative anti-HIV-1 test results from the central lab, these tests will not 
be required to be repeated if the results were obtained within 50 days of the re-screening 
visit provided that in the meanwhile nothing has changed in the patient's medical history 
or risk behaviors.  
If the subject had negative HBV and Anti-Hepatitis C test results from the central lab, 
these tests will not be required to be repeated if the results were obtained within 35 days 
of the re-screening visit.  
Section 5.3.1.1  Study Procedures
Subsection Other Laboratory Assessments
Heading "ANA/anti-dsDNA"
First paragraph, last sentence previously read:
Anti-double-stranded DNA (anti-dsDNA) assessments will be performed if ANA is 
positive (> 1/80).
Has been changed to read:
Anti-double-stranded DNA (anti-dsDNA) assessments will be performed if ANA is 
positive.

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Section 5.3.1.2  Blood Samples for Pharmacogenetic Analysis
Second paragraph, second, third and fourth sentence previously read:
Samples will be shipped frozen to the central laboratory in China and then to AbbVie in 
China for long-term storage.  Samples should not be allowed to thaw prior to arrival at 
AbbVie or the designated laboratory.  Arrangements will be made with the central 
laboratory for the shipment of PG samples to AbbVie or specified lab for testing in China.
Has been changed to read:
Samples will be shipped frozen to the central laboratory in China and then to an AbbVie 
designated laboratory in China for long-term storage.  Samples should not be allowed to 
thaw prior to arrival at the designated laboratory.  Arrangements will be made with the 
central laboratory for the shipment of PG samples to the specified lab for testing in China.
Section 5.3.1.3  Blood Samples for Biomarkers Analysis
Subsection Collection of Samples for mRNA Analysis
Second paragraph, second, third and fourth sentence previously read:
Samples will be shipped frozen to the central laboratory in China and then to AbbVie in 
China for long-term storage.  Samples should not be allowed to thaw prior to arrival at 
AbbVie or the designated laboratory.  Arrangements will be made with the central 
laboratory for the shipment of PG samples to AbbVie or specified lab for testing in China.
Has been changed to read:
Samples will be shipped frozen to the central laboratory in China and then to an AbbVie 
designated laboratory in China for long-term storage.  Samples should not be allowed to 
thaw prior to arrival at the designated laboratory.  Arrangements will be made with the 
central laboratory for the shipment of mRNA samples to the specified lab for testing in 
China.

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Section 5.3.5  Pharmacokinetic Variables
Add:  new section
5.3.5
Pharmacokinetic Variables
Serum adalimumab concentrations will be determined from samples collected just prior to 
dosing at Baseline (Week 0), Week 4, Week 8, Week 12, and Week 26/Premature 
Discontinuation.  Blood samples for the measurement of serum adalimumab 
concentrations at Week 14, Week 16, Week 18, Week 20, Week 22 and Week 24 will be 
collected prior to dosing only if the subject qualifies for dose escalation.
Serum anti-adalimumab antibody (AAA) will be determined from the samples collected 
just prior to dosing at Baseline (Week 0), Week 4, Week 12 and Week 26/Premature 
Discontinuation.  Blood samples for the measurement of serum AAA at Week 14, 
Week 16, Week 18, Week 20, Week 22 and Week 24 will be collected prior to dosing 
only if the subject qualifies for dose escalation.
Blood samples will also be collected for measurement of infliximab serum levels and 
HACA just prior to dosing at Baseline (Week 0).
Section 5.4.1  Discontinuation of Individual Subjects
Ninth bullet, first sentence previously read:
Subject has dysplasia of the gastrointestinal tractor a malignancy, except for localized 
non-melanoma skin cancer.  
Has been changed to read:
Subject has dysplasia or a malignancy, except for localized non-melanoma skin cancer.  
Section 5.4.1  Discontinuation of Individual Subjects
Add:  new second sentence to fourth paragraph
The information will be recorded on the appropriate eCRF page.

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Section 6.1.5  Adverse Event Reporting
First paragraph, last sentence previously read:
Serious adverse events and non-serious events of malignancy in subjects 30 years of age 
and younger that occur prior to the site having access to the RAVE® system or if RAVE is 
not operable should use the SAE Non-CRF paper forms and send them to Clinical 
Pharmacovigilance within 24 hours of being made aware of the serious adverse event.
Has been changed to read:
Serious adverse events and non-serious events of malignancy in subjects 30 years of age 
and younger that occur prior to the site having access to the RAVE® system or if RAVE is 
not operable should be documented on the SAE Non-CRF forms and emailed (preferred 
route) or faxed to Clinical Pharmacovigilance within 24 hours of being made aware of the 
serious adverse event.
Section 6.1.5  Adverse Event Reporting
Contact information following first paragraph previously read:
Or

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Or
FAX to:
Section 6.1.5  Adverse Event Reporting
Fourth paragraph previously read:
For any subject safety concerns, please contact the physician listed below:
Has been changed to read:

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Section 7.0  Protocol Deviations
First paragraph, first sentence previously read:
AbbVie does not allow intentional/prospective deviations from the protocol.  
Has been changed to read:
AbbVie does not allow intentional/prospective deviations from the protocol unless when 
necessary to eliminate an immediate hazard to study subjects.  
Appendix B.  List of Protocol Signatories
Previously read:
Name
Title
Functional Area
Clinical
Statistics
Pharmacokinetics/Pharmacodynamics
Clinical
Clinical
Clinical
Functional Area
Clinical
Statistics
Pharmacokinetics/Pharmacodynamics
Clinical
Clinical
Clinical

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Appendix D.  Standard Weights
Header row previously read:
Standard Height and Weight Tables – Use to Calculate CDAI Score
Actual Height
cm (Inches)
Standard Weight (Men)
kg (Pounds)
Standard Weight (Women) 
kg (Pounds)
Has been changed to read:
Standard Height and Weight Tables – Use to Calculate CDAI Score
Adjusted Height*
cm (Inches)
Standard Weight (Men)
kg (Pounds)
Standard Weight (Women) 
kg (Pounds)
Appendix D.  Standard Weights
Table notes previously read:
Notes:
Height in the Standard Height and Weight Tables includes the 1" or 2.5 cm added to the height obtained 
during screening.
If the actual measured height falls in-between 2 values listed under in the actual height column, the closest 
height listed on the chart should be selected.
Has been changed to read:
Notes:
* Values in the Adjusted Height column includes the 1" or 2.5 cm added to the height obtained during 
screening.
If the adjusted height falls in-between 2 values listed in the Adjusted Height column, the closest height listed 
on the chart should be selected.
Appendix E.  Sample Injection Instructions for Onsite Administration – Pre Filled 
Syringe
Subsection Injection Procedures (PFS)
Item 2, second and third bullet previously read:
●
Choose a site on the front of the thighs or stomach area (abdomen).  If you 
choose your abdomen, you should avoid the area 2 inches around your belly 
button (navel).
●
Choose a different site each time you give an injection.  Each new injection 
should be given at least one inch from a site used before.  Never inject into 

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areas where the skin is tender, bruised, red or hard or where you have scars or 
stretch marks.
Has been changed to read:
●
Choose a site on the front of the thighs or stomach area (abdomen).  If you 
choose your abdomen, you should avoid the area 2 inches or 5 cm around your 
belly button (navel).
●
Choose a different site each time you give an injection.  Each new injection 
should be given at least one inch or 2.5 cm from a site used before. Never 
inject into areas where the skin is tender, bruised, red or hard or where you 
have scars or stretch marks.
Appendix F.  Sample Injection Instructions for at Home Dosing – Pre-Filled Syringe
Subsection Injection Procedures (PFS)
Item 2, second and third bullet previously read:
●
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).
●
Choose a different site each time you give yourself an injection.  Each new 
injection should be given at least one 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.
Has been changed to read:
●
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 or 5 cm around 
your belly button (navel).
●
Choose a different site each time you give yourself an injection.  Each new 
injection should be given at least one inch or 2.5 cm 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.