Conditions: Crohn's Disease
Keywords: Crohn's Disease ABBV-154
Allocation: RANDOMIZED | Intervention model: SEQUENTIAL
Enrollment: 176
Healthy volunteers: no

Brief summary:
Crohn's disease (CD) is a long-lasting condition causing inflammation that can affect any part of the gut. CD may cause tiredness, loose stools with or without bleeding, abdominal pain, weight loss, and fever. This study evaluates how safe and effective ABBV-154 is in participants treated for moderately to severely active CD. Adverse events and change in the disease activity will be assessed.

ABBV-154 is an investigational drug being evaluated for the treatment of CD. In the induction period, there is a 1 in 5 chance that participants will be assigned to placebo. Depending on the dose received in the induction period, there is a 1 in 2 or 1 in 3 chance that participants will be assigned to placebo in the maintenance period. Around 265 participants 18-75 years of age with moderately to severely active CD will be enrolled in the study at approximately 200 sites worldwide.

The study is comprised of a 12-week double-blind, placebo-controlled induction period, followed by either a 12-week double-blind re-induction period for non-responders or a 40-week double-blind placebo-controlled maintenance period for responders. In the maintenance period, responders will be randomized to receive subcutaneous placebo or ABBV-154 in 2 different doses every other week. Participants in the placebo group who are initial responders will receive ABBV-154 in the maintenance period.

There may be higher treatment burden for participants in this trial compared to their standard of care due to study procedures. Participants will attend regular visits during the study at a hospital or clinic. The effect of the treatment will be checked by medical assessments, blood tests, checking for side effects and completing questionnaires.

Detailed description:

Arms:
arm 1: Varying doses of ABBV-154 as described in the protocol. arm 2: Varying doses of ABBV-154 as described in the protocol. arm 3: Varying doses of ABBV-154 as described in the protocol. arm 4: Varying doses of ABBV-154 as described in the protocol. arm 5: Fixed dose placebo as described in the protocol. arm 6: Varying doses of ABBV-154 as described in the protocol. arm 7: Varying doses of ABBV-154 as described in the protocol. arm 8: Fixed dose ABBV-154 every other week. arm 9: Fixed dose ABBV-154 every other week. arm 10: Fixed dose placebo every other week.

Interventions: intervention 1: ABBV-154 intervention 2: Placebo intervention 3: ABBV-154 intervention 4: Placebo
Intervention descriptions: intervention 1: Intravenous (IV) Infusion; Subcutaneous Injection intervention 2: Intravenous (IV) infusion; Subcutaneous Injection intervention 3: Subcutaneous Injection intervention 4: Subcutaneous Injection

Protocol document:
Prot_000.pdf: 


  
STUDY M20-371  |  Version 4.0  |  EudraCT 2021-002869-18
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
TABLE OF CONTENTS
1
SYNOPSIS
5
2
INTRODUCTION
9
2.1
BACKGROUND AND RATIONALE
9
2.2
BENEFITS AND RISKS TO SUBJECTS
10
3
OBJECTIVES AND ENDPOINTS
11
3.1
OBJECTIVES, HYPOTHESES, AND ESTIMANDS
11
3.2
PRIMARY ENDPOINT
12
3.3
SECONDARY ENDPOINT(S)
12
3.4
ADDITIONAL EFFICACY ENDPOINTS
12
3.5
SAFETY MEASURES
14
3.6
PHARMACOKINETIC ENDPOINTS
14
3.7
EXPLORATORY BIOMARKER RESEARCH
14
4
INVESTIGATIONAL PLAN
15
4.1
OVERALL STUDY DESIGN AND PLAN
15
4.2
DISCUSSION OF STUDY DESIGN
19
5
STUDY ACTIVITIES
20
5.1
ELIGIBILITY CRITERIA
20
5.2
CONTRACEPTION RECOMMENDATIONS
26
5.3
PROHIBITED MEDICATIONS AND THERAPY
28
5.4
PRIOR AND CONCOMITANT THERAPY
29
5.5
WITHDRAWAL OF SUBJECTS AND DISCONTINUATION OF STUDY
32
5.6
FOLLOW-UP AFTER SUBJECT DISCONTINUATION OF STUDY DRUG OR FROM STUDY
34
5.7
STUDY DRUG
35
5.8
RANDOMIZATION/DRUG ASSIGNMENT
35
5.9
PROTOCOL DEVIATIONS
37
5.10 DATA MONITORING COMMITTEE
37
5.11 GLUCOCORTICOID ADJUDICATION COMMITTEE
37
6
SAFETY CONSIDERATIONS
38
Page 2 of 145
 


  
STUDY M20-371  |  Version 4.0  |  EudraCT 2021-002869-18
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
6.1
COMPLAINTS AND ADVERSE EVENTS
38
6.2
TOXICITY MANAGEMENT
42
7
STATISTICAL METHODS & DETERMINATION OF SAMPLE SIZE
47
7.1
STATISTICAL AND ANALYTICAL PLANS
47
7.2
DEFINITION FOR ANALYSIS POPULATIONS
47
7.3
HANDLING POTENTIAL INTERCURRENT EVENTS FOR THE PRIMARY AND SECONDARY ENDPOINTS
48
7.4
STATISTICAL ANALYSES FOR EFFICACY
48
7.5
STATISTICAL ANALYSIS FOR PHARMACOKINETICS AND IMMUNOGENICITY
49
7.6
STATISTICAL ANALYSIS OF BIOMARKER DATA
50
7.7
STATISTICAL ANALYSES FOR SAFETY
50
7.8
INTERIM ANALYSIS
50
7.9
OVERALL TYPE I ERROR CONTROL
50
7.10 SAMPLE SIZE DETERMINATION
51
8
ETHICS
51
8.1
INDEPENDENT ETHICS COMMITTEE/INSTITUTIONAL REVIEW BOARD (IEC/IRB)
51
8.2
ETHICAL CONDUCT OF THE STUDY
51
8.3
SUBJECT CONFIDENTIALITY
52
9
SOURCE DOCUMENTS AND CASE REPORT FORM COMPLETION
52
10 DATA QUALITY ASSURANCE
52
11 START AND COMPLETION OF THE STUDY
53
12 REFERENCES
53
LIST OF TABLES
TABLE 1.
EXAMPLES OF COMMONLY USED STRONG CYP3A INHIBITORS
29
TABLE 2.
INVESTIGATIONAL PRODUCT
35
TABLE 3.
SPECIFIC TOXICITY MANAGEMENT GUIDELINES FOR ABNORMAL LABORATORY VALUES
46
Page 3 of 145
 


  
STUDY M20-371  |  Version 4.0  |  EudraCT 2021-002869-18
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
LIST OF FIGURES
FIGURE 1.
STUDY SCHEMATIC
18
LIST OF APPENDICES
APPENDIX A.
STUDY-SPECIFIC ABBREVIATIONS AND TERMS
55
APPENDIX B.
RESPONSIBILITIES OF THE INVESTIGATOR
59
APPENDIX C.
LIST OF PROTOCOL SIGNATORIES
60
APPENDIX D.
ACTIVITY SCHEDULE
61
APPENDIX E.
PROTOCOL SUMMARY OF CHANGES
73
APPENDIX F.
OPERATIONS MANUAL
76
Page 4 of 145
 






  
STUDY M20-371  |  Version 4.0  |  EudraCT 2021-002869-18
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
considered non-responders, regardless of clinical response or 
endoscopic response (per local read) at Week 12 and will be 
re-randomized in a 1:1 ratio into 2 ABBV-154 treatment groups in the 
12-Week Re-Induction Period as follows:
1.
Re-Induction Group 1:  Loading dose of 300 mg IV at Week 0, 
followed by 230 mg SC at Week 2 and EOW;
2.
Re-Induction Group 2:  Loading dose of 600 mg IV at Week 0, 
followed by 530 mg SC at Week 2 and EOW. 
Subjects who achieve clinical response AND/OR endoscopic response 
(per local read) at Week 12 of the Re-Induction Period will be re-
randomized into the Maintenance Period as described above for 
subjects achieving clinical response AND/OR endoscopic response (per 
local read) at Week 12 of the Induction Period.  Subjects who do not 
achieve either clinical response or endoscopic response (per local read) 
after the Re-Induction Period will be discontinued and will have a 
follow-up visit scheduled 70 days after last study drug administration.
To determine endoscopic response status for re-randomization into the 
Maintenance Period, the SES-CD score per local read at Week 12 of the 
Induction/Re-Induction Period and the SES-CD score per central read at 
Baseline will be used.  In the case of missing data where either clinical 
response or endoscopic response cannot be determined, subjects will 
be considered non-responders for the re-randomization criteria 
evaluation.
Subjects who have an inadequate response at or after Week 4 in the 
Maintenance Period will be eligible to receive Rescue Therapy with a 
single dose of ABBV-154 600 mg IV followed by ABBV-154 230 mg SC 
EOW.  Subjects who have received rescue therapy with ABBV-154 for 
at least 4 weeks and who continue to demonstrate inadequate 
response may receive additional Rescue Therapy with oral 
glucocorticoids, aminosalicylates, or immunomodulators.
The primary analysis for the Induction Period and Re-Induction Period
will be performed after all subjects have either completed Week 12 of 
the Induction Period and Re-Induction Period, respectively, or 
prematurely discontinued study participation.  The final analysis will be 
conducted after all subjects have either completed Week 40 of the 
Maintenance Period plus the follow-up visit or prematurely 
discontinued study participation.  To ensure the integrity of the trial, 
the study sites and subjects will remain blinded until the final database 
lock is completed.
The Wearable Device Substudy will enroll up to approximately 
75 subjects in countries and sites where the digital health technology 
device is deployed and available.  For subjects participating in the 
substudy, data for sleep parameters, daily physical activity, and SF data 
will be collected continuously throughout the 12-Week Induction 
Period.
Page 7 of 145
 




  
STUDY M20-371  |  Version 4.0  |  EudraCT 2021-002869-18
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
2 INTRODUCTION
2.1 Background and Rationale
Why Is This Study Being Conducted?
There are a number of anti-inflammatory biologic therapies available to treat patients with Crohn's 
disease (CD), including infliximab, adalimumab, certolizumab pegol, vedolizumab, natalizumab, and 
ustekinumab.  In particular, the efficacy and safety of anti-tumor necrosis factor (anti-TNF) monoclonal 
antibodies, including adalimumab, in CD is well established.1,2,3  Adalimumab demonstrated superior 
efficacy for inducing and maintaining clinical remission compared to placebo in moderate to severe CD 
patients who failed conventional therapies and infliximab.4,5  However, while the available biologic 
treatments have provided therapeutic options for CD patients, there remain high treatment failure rates 
associated with existing agents.6  Patients with CD treated with anti-TNF agents do not respond at rates 
of 10% to 40% to initial treatment (primary nonresponse) and additional subjects are observed to lose 
response over time (secondary loss of response).7  Similar patterns of primary nonresponse and 
secondary loss of response have been observed with other classes of anti-inflammatory biologics used 
to treat CD.8,9  Despite the availability of multiple advanced therapies for the treatment of CD patients, 
the overall burden of surgery remains high in this population at 3.8 intestinal resections per 100 person-
years.  Therefore, a large unmet need remains for the treatment of CD.10
Glucocorticoids have been shown to be efficacious for inducing clinical remission in CD.  While 
nontargeted glucocorticoids with systemic exposure and limited systemic exposure have not been 
shown to be effective for maintenance treatment,11 approximately 25% of CD patients are 
glucocorticoid-dependent receiving chronic or recurrent systemic glucocorticoids.12,13,14,15  However, the 
administration of glucocorticoids is limited due to their long-term side effect profile including (but not 
limited to) hypothalamic-pituitary-adrenal axis (HPA) suppression, osteoporosis, hyperglycemia, 
glaucoma, and skin atrophy.16  Thus, the full efficacy of glucocorticoid therapy is often limited with 
existing agents due to systemic side effects.
ABBV-154 is an anti-TNF antibody-drug conjugate (ADC) composed of adalimumab (the active 
component of Humira®) conjugated to phosphorylated A-1677770, a proprietary glucocorticoid receptor 
modulator (GRM, also referred to as the GRM payload) via an 
 linker.  Binding of the 
adalimumab portion of the ABBV-154 ADC to activated immune cells that express transmembrane TNF is 
intended to deliver the anti-inflammatory payload intracellularly.  The monoclonal antibody portion of 
the ADC provides targeted delivery of the GRM payload to minimize systemic exposure to the free GRM 
payload.  Therefore, ABBV-154 is a promising novel therapeutic agent which may achieve 
transformational efficacy while reducing side effects caused by systemic glucocorticoid exposure.
This is a dose-ranging study to explore the efficacy and safety of ABBV-154 in subjects with moderately 
to severely active CD who continue to have unmet medical need, and to inform subsequent clinical 
studies in the indication.
Page 9 of 145
 


  
STUDY M20-371  |  Version 4.0  |  EudraCT 2021-002869-18
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
2.2 Benefits and Risks to Subjects
The clinical efficacy of TNF inhibitors and glucocorticoids in the treatment of CD is well established.  By 
utilizing expression of transmembrane TNF on activated immune cells, ABBV-154 has the potential to 
deliver an anti-inflammatory payload intracellularly, while minimizing systemic exposure to the free 
GRM payload.  Based on the data discussed in the ABBV-154 Investigator's Brochure, ABBV-154 is 
expected to demonstrate a positive benefit-risk profile for the treatment of CD.
Medical review of the safety data from the Phase 1, single ascending dose study did not identify any
unexpected risk or trend in the healthy volunteer population (including Japanese and Chinese subjects).  
For further details, please see the ABBV-154 Investigator's Brochure.
In clinical settings, TNF antagonists and glucocorticoids have been associated with increased risk for 
serious infections due to bacterial, mycobacterial, invasive fungal, viral, parasitic, or other opportunistic 
pathogens.  Subjects with a recent history of these events will be excluded from the study.  Other known 
adverse events (AE) for glucocorticoids include hypertension, hypothalamic pituitary-adrenal axis (HPA) 
suppression, decreased bone-formation, diabetes, glaucoma, and cataracts.  Signs of infection, blood 
pressure changes, blood glucose levels, HPA axis suppression, and bone mineral density will be closely 
monitored during the study.
TNF antagonists have also been associated with an increased risk for serious allergic reactions, including 
anaphylaxis; infusion reactions; malignancy (including nonmelanoma skin cancer [NMSC], lymphoma, 
and leukemia); worsening or new onset heart failure; and rarely hepatitis B virus (HBV) reactivation, 
central nervous system events, demyelinating disease, pancytopenia (including aplastic anemia), and 
lupus-like syndrome.  Subjects with a history of these events, other than successfully treated NMSC or 
localized carcinoma in situ of the cervix, will be excluded from the study.  Signs and symptoms of these 
events will be closely monitored.
The safety profile specific to the adalimumab component of ABBV-154 is well-established for marketed 
doses.  In addition, adalimumab has been studied at doses up to 10 mg/kg intravenously (IV), which is 
higher than the doses planned in this study, with a safety profile consistent to Humira® product labeling.  
Potential risks will be minimized through the selection of appropriate study subjects defined by the 
eligibility criteria and subject safety will be monitored by an unblinded independent data monitoring 
committee (DMC) and regular blinded review of safety data by the study team (see Section 5.10).  In 
addition, guidance for toxicity management and stopping rules are provided to ensure subject safety 
(see Section 6.2).
Based on the totality of the data, ABBV-154 is expected to demonstrate therapeutic benefit in the 
treatment of CD with a positive benefit-risk profile for development in the treatment of this disease.
In view of the coronavirus pandemic 2019 (COVID-19), the benefit-risk profile of various 
immunomodulatory therapies on COVID-19 are being evaluated.  Currently, the effects of ABBV-154 on 
the course of COVID-19 are not well defined.  Guidance regarding severe acute respiratory syndrome 
coronavirus 2 (SARS-CoV-2) vaccination is provided for investigators in Section 5.4.
The safety and effectiveness of the device component (non-investigational device) for use as described 
in labeling has been demonstrated through literature review, pre-clinical, and clinical data as 
Page 10 of 145
 


  
STUDY M20-371  |  Version 4.0  |  EudraCT 2021-002869-18
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
appropriate, and the device is certified, cleared, approved, or registered for marketing.  The benefits of 
the device in use, as labeled and as planned for this clinical study, have been demonstrated to outweigh 
the residual risks.
3 OBJECTIVES AND ENDPOINTS
3.1 Objectives, Hypotheses, and Estimands
Primary
The primary objective of the study is to assess the efficacy, safety, and tolerability of ABBV-154 in 
comparison with placebo in subjects with moderately to severely active CD who had inadequate 
response to or were intolerant of prior biologics.

Primary Efficacy Objective:  The primary efficacy objective of the study is to demonstrate a 
higher rate of endoscopic response after 12 weeks of treatment with ABBV-154 when compared 
to placebo in subjects with moderately to severely active CD who had inadequate response to or 
were intolerant of prior biologics.
The hypothesis corresponding to the primary efficacy objective is the proportion of subjects achieving 
endoscopic response with ABBV-154 is greater than that with placebo at Week 12.  The estimand for the 
primary endpoint is defined as the difference in the proportion of subjects that achieve endoscopic 
response at Week 12 without use of concomitant medication that could confound the efficacy (see 
Section 7.3) and regardless of premature discontinuation of study drug, in each of the ABBV-154 dose 
groups compared with the placebo group in subjects with moderately to severely active CD who had 
inadequate response to or were intolerant of prior biologics.

Secondary Efficacy Objectives:  The secondary efficacy objectives of the study are to 
demonstrate greater efficacy with ABBV-154 treatment when compared with placebo treatment 
with respect to the secondary endpoints specified in Section 3.3, in subjects with moderately to 
severely active CD who had inadequate response to or were intolerant of prior biologics.

The estimands corresponding to the secondary efficacy endpoints are as follows:

For endpoints in the Induction Period:  The difference in the proportion of subjects that 
achieve a response without use of concomitant medication that could confound the efficacy 
(see Section 7.3) and regardless of premature discontinuation of study drug, in each of the 
ABBV-154 dose groups compared with the placebo group in subjects with moderately to 
severely active CD who had inadequate response to or were intolerant of prior biologics.

For endpoints in the Maintenance Period:  The difference in the proportion of subjects that 
achieve a response without use of concomitant medication that could confound the efficacy 
(see Section 7.3) and regardless of premature discontinuation of study drug, in each of the 
ABBV-154 dose groups compared with the placebo group in subjects with moderately to 
severely active CD who had inadequate response to or were intolerant of prior biologics and 
achieved response after the 12-week induction treatment with ABBV-154.
Page 11 of 145
 


  
STUDY M20-371  |  Version 4.0  |  EudraCT 2021-002869-18
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
Secondary Objectives
The secondary objectives are to assess the pharmacokinetics (PK), pharmacodynamics (PD), and 
immunogenicity of ABBV-154.
3.2 Primary Endpoint
The primary endpoint is the achievement of endoscopic response at Week 12 in the Induction Period 
defined as a decrease in Simple Endoscopic Score for Crohn's Disease (SES-CD17) > 50% from Baseline (or 
for subjects with isolated ileal disease and a Baseline SES-CD of 4, at least a 2-point reduction from 
Baseline).
3.3 Secondary Endpoint(s)
Secondary Endpoint(s)

Achievement of clinical remission per Crohn's Disease Activity Index (CDAI) at Week 12 in the 
Induction Period defined as CDAI < 150.

Achievement of clinical remission per average daily liquid or very soft stool frequency (SF) and 
average daily abdominal pain (AP) score (SF/AP) at Week 12 in the Induction Period defined as 
average daily liquid or very soft SF ≤ 2.8 and not worse than Baseline AND average daily AP score 
≤1 and not worse than Baseline.

Achievement of endoscopic response per SES-CD at Week 40 in the Maintenance Period.

Achievement of clinical remission per CDAI at Week 40 in the Maintenance Period.

Achievement of clinical remission per SF/AP at Week 40 in the Maintenance Period.
3.4 Additional Efficacy Endpoints
In the Induction/Re-Induction/Maintenance Periods, the additional endpoints below will be analyzed at 
timepoints specified in the schedule of events table of the protocol (in this section, "Baseline" refers to 
the Baseline [Week 0, Day 1] of the Induction Period):

Achievement of clinical remission per CDAI.

Achievement of clinical remission per SF/AP.

Achievement of clinical response defined as a decrease of CDAI ≥ 100 points from Baseline 
(CR100).

Achievement of clinical response per SF/AP defined as ≥ 30% decrease in average daily liquid or 
very soft SF and/or ≥ 30% decrease in average daily AP score and both not worse than Baseline.

Achievement of enhanced clinical response per SF/AP defined as ≥ 60% decrease in average 
daily liquid or very soft SF and/or ≥ 35% decrease in average daily AP score and both not worse 
than Baseline, and/or clinical remission per SF/AP.
Page 12 of 145
 


  
STUDY M20-371  |  Version 4.0  |  EudraCT 2021-002869-18
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.

Achievement of endoscopic remission defined as SES-CD ≤ 4 and at least a 2-point reduction 
versus Baseline and no subscore > 1 in any individual variable.

Change from Baseline in Inflammatory Bowel Disease Questionnaire (IBDQ18,19) total score.

Change from Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F20).

Change from Baseline in the Bowel Incontinence Scale.

Change from Baseline in CDAI.

Change from Baseline in individual IBDQ domain scores (bowel, emotional, social, systemic).

Change from Baseline in individual IBDQ items under Bowel Symptom domain (for Q1, Q5, Q9, 
Q13, Q17, Q20, Q22, Q24, Q26, and Q29).

Achievement of IBDQ remission defined as IBDQ ≥ 170 points.

Achievement of IBDQ response defined as increase in IBDQ ≥ 16 points from Baseline.

Change from Baseline in 36-Item Short Form Health Survey (SF-3621,22).

Change from Baseline in fecal calprotectin (FCP).

Change from Baseline in high-sensitivity C-Reactive Protein (hs-CRP).

Change from Baseline in average daily AP score.

Change from Baseline in average daily liquid or very soft SF.

Change from Baseline in SES-CD.

Achievement of SES-CD ulcerated surface subscore ≤ 1 in each segment in subjects with a 
SES-CD ulcerated surface subscore ≥ 2 at Baseline.

Achievement of ulcer-free endoscopy:  SES-CD ulcerated surface subscore of 0 in subjects with 
SES-CD ulcerated surface subscore ≥ 1 at Baseline.

Change from Baseline in daily physical activity for subjects participating in the Wearable Device 
Substudy.

Change from Baseline in sleep parameters for subjects participating in the Wearable Device 
Substudy.

Change from Baseline in stool frequency, as captured from the wearable device, for subjects 
participating in the Wearable Device Substudy.

Patient Global Impression of Change – Crohn's Disease+ (PGIC-CD+).

Change from Baseline in Patient Global Impression of Severity – Crohn's Disease+ (PGIS-CD+).

Achievement of absence of bowel urgency.

Change from Baseline in average daily bowel urgency frequency.

Achievement of absence of rectal bleeding.
All endoscopic endpoints will be scored by a central reviewer.
Page 13 of 145
 


  
STUDY M20-371  |  Version 4.0  |  EudraCT 2021-002869-18
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
SF/AP-based efficacy endpoints will be analyzed in the subset of subjects with an average daily liquid or 
very soft SF score ≥ 4 and/or average daily AP score ≥ 2 at Baseline.
3.5 Safety Measures

Treatment emergent adverse events (TEAEs), serious adverse events (SAEs), AEs leading to 
discontinuation of the study drug;

Occurrence of possible glucocorticoid-related AEs;

Potentially clinically significant laboratory, vital signs, and electrocardiogram (ECG) variables.
3.6 Pharmacokinetic Endpoints
Serum or plasma concentrations of the conjugated ADC, total antibody, free payload A-1677770 will be 
determined at Baseline (pre-dose) of the Induction Period and at timepoints during the treatment 
period as specified in the Activity Schedule (Appendix D).
Development of anti-drug antibody (ADA) to ABBV-154 will be evaluated and if confirmed positive, titers 
will be measured.  Samples that are confirmed positive may be further characterized in a validated 
neutralizing antibody (nAb) assay.  Immunogenicity samples will be collected at Baseline (pre-dose) of 
the Induction Period and at timepoints as specified in the Activity Schedule (Appendix D).
3.7 Exploratory Biomarker Research
The effect of the ADC compound on glucocorticoid-related endpoints will be assessed by blood samples 
and intestinal tissue biopsies collected throughout the study at timepoints as specified in the Activity 
Schedule (Appendix D).  The biomarkers to be analyzed include, but are not limited to the following:

Neuroendocrine biomarkers (total and free cortisol and adrenocorticotropic hormone [ACTH])

Bone formation (osteocalcin, procollagen type 1 N-propeptide [P1NP]), and bone resorption 
(C-terminal telopeptide of type I [CTX-I]) biomarkers

Biopsy tissue only - Histological, proteomic, or genomic biomarkers (may include but not limited 
to glucocorticoid-related genes and proteins).
Provision of these biospecimens for biomarker research is mandatory, but they will not be collected 
from sites where local regulations do not allow for the collection, use, and storage of samples described 
in the protocol.
Additional optional biospecimens (whole blood for serum, plasma, peripheral blood mononuclear cells 
[PBMC], RNA, and DNA) will be collected throughout the study at timepoints as specified in the Activity 
Schedule (Appendix D) to evaluate known and/or novel disease-related or drug-related biomarkers in 
circulation.  Types of biomarkers may include nucleic acids, proteins, cell populations, lipids, and/or 
metabolites, either free or in association with particular cell types.  The analyses may include but are not 
limited to soluble proteins, genomic transcripts, blood leukocyte populations, and genetic analysis to 
Page 14 of 145
 


  
STUDY M20-371  |  Version 4.0  |  EudraCT 2021-002869-18
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
evaluate biomarker endpoints related to safety, disease state, and target pathway.  Results from this 
optional biomarker research results may not be included in the clinical study report.  Further details 
regarding the biomarker research rationale and collection time points are provided in the Operations 
Manual, Appendix F, Section 3.21.
4 INVESTIGATIONAL PLAN
4.1 Overall Study Design and Plan
This is a randomized, double-blind, placebo-controlled Phase 2b study to assess the safety, tolerability, 
PK, PD, immunogenicity, and efficacy of ABBV-154 in subjects with moderately to severely active CD 
who had inadequate response to or were intolerant of prior biologics.  The enrollment for subjects with 
prior adalimumab use is capped at approximately 30% of the total enrolled subjects.  The study 
comprises 3 periods:  a 12-Week Double-Blind Placebo-Controlled Induction Period, a 12-Week 
Double-Blind Re-Induction Period (for subjects considered to be clinical non-responders and endoscopic 
non-responders), and a 40-Week Double-Blind Placebo-Controlled Maintenance Period.
At the Baseline Visit of the Induction Period, approximately 265 subjects will be randomized in a 
1:1:1:1:1 ratio into 4 ABBV-154 treatment groups or placebo:
1.
Induction Group 1:  Loading dose of 150 mg IV at Week 0, followed by 80 mg subcutaneous (SC) 
at Week 2 and every other week (EOW);
2.
Induction Group 2:  Loading dose of 300 mg IV at Week 0, followed by 230 mg SC at Week 2 and 
EOW;
3.
Induction Group 3:  Loading dose of 600 mg IV at Week 0, followed by 530 mg SC at Week 2 and 
EOW;
4.
Induction Group 4:  Loading dose of 600 mg IV at Week 0, followed by 530 mg SC at Weeks 4 
and 8, and placebo at Weeks 2, 6, and 10; and
5.
Induction Group 5:  Matching placebo (IV and SC).
At Week 12 of the Induction Period, subjects achieving clinical response, defined as a decrease in CDAI 
≥100 points from Baseline (CR100) AND/OR endoscopic response (per local read) will receive treatment 
in the 40-Week Maintenance Period as follows:
1.
Induction Group 1:  Re-randomized in a 1:1 ratio to receive ABBV-154 80 mg SC EOW or 
matching placebo;
2.
Induction Groups 2 to 4:  Re-randomized in a 1:1:1 ratio to receive ABBV-154 80 mg SC EOW, 
ABBV-154 230 mg SC EOW, or matching placebo;
3.
Induction Group 5:  ABBV-154 80 mg SC EOW.
At Week 12 of the Induction Period, subjects who are categorized as clinical non-responders and 
endoscopic non-responders (per local read) will be re-randomized into the Re-Induction Period.
Page 15 of 145
 


  
STUDY M20-371  |  Version 4.0  |  EudraCT 2021-002869-18
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
Subjects who demonstrate inadequate response at or after Week 8 in the Induction Period may receive 
Rescue Therapy with oral glucocorticoids as defined in Section 5.4.
Subjects who receive Rescue Therapy, fail to complete glucocorticoid tapering by Week 6, or increase 
doses of or initiate treatment with aminosalicylates or immunomodulators in the Induction Period will 
be considered non-responders, regardless of clinical response or endoscopic response (per local read) 
per the definitions above at Week 12 and will be re-randomized in a 1:1 ratio into 2 ABBV-154 treatment 
groups in the 12-Week Re-Induction Period as follows:
1.
Re-Induction Group 1:  Loading dose of 300 mg IV at Week 0, followed by 230 mg SC at Week 2 
and EOW;
2.
Re-Induction Group 2:  Loading dose of 600 mg IV at Week 0, followed by 530 mg SC at Week 2 
and EOW.
Subjects who achieve clinical response AND/OR endoscopic response (per local read) at Week 12 of the 
Re-Induction Period will be re-randomized into the Maintenance Period as described above for subjects 
achieving clinical response AND/OR endoscopic response (per local read) after Week 12 of the Induction 
Period.  Subjects who do not achieve either clinical response or endoscopic response (per local read) 
after the Re-Induction Period will be discontinued and will have a follow-up visit scheduled 70 days after 
last study drug administration.
To determine endoscopic response status for re-randomization into the Maintenance Period, the SES-CD 
score per local read at Week 12 of the Induction/Re-Induction Period and the SES-CD score per central 
read at Baseline will be used.  In the case of missing data where either clinical response or endoscopic 
response cannot be determined, subjects will be considered non-responders for the re-randomization 
criteria evaluation.
Subjects who have an inadequate response at or after Week 4 in the Maintenance Period will be eligible 
to receive Rescue Therapy with a single dose of ABBV-154 600 mg IV followed by ABBV-154 230 mg SC 
EOW. Subjects who have received rescue therapy with ABBV-154 for at least 4 weeks and who continue 
to demonstrate inadequate response may receive additional Rescue Therapy with oral glucocorticoids, 
aminosalicylates, or immunomodulators.  Rescue Therapy options for the Maintenance Period are 
further described in Section 5.4.
The last dose of study drug will be given at Week 38 of the Maintenance Period.  A follow-up visit will be 
scheduled 70 days after the last study drug administration.
The Primary Analysis for the Induction Period and Re-Induction Period will be performed after all 
subjects have either completed Week 12 of the Induction Period and Re-Induction Period, respectively, 
or prematurely discontinued study participation.  The final analysis will be conducted after all subjects 
have completed Week 40 of the Maintenance Period plus the 70-day Follow-up Visit or prematurely 
discontinued study participation. To ensure the integrity of the trial, the study sites and subjects will 
remain blinded until the final database lock is completed (see Section 7.1).
Interim analyses may be performed as outlined in Section 7.8.
Page 16 of 145
 


  
STUDY M20-371  |  Version 4.0  |  EudraCT 2021-002869-18
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
The Wearable Device Substudy will enroll up to approximately 75 subjects in countries and sites where 
the digital health technology device is deployed and available.  For subjects participating in the 
substudy, data for sleep parameters, daily physical activity, and stool frequency will be collected 
continuously throughout the Induction Period.
The schematic of the study is shown in Figure 1.  Further details regarding study procedures are located 
in the Operations Manual.  See Section 5.1 for information regarding eligibility criteria.
Page 17 of 145
 


  
STUDY M20-371  |  Version 4.0  |  EudraCT 2021-002869-18
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
Figure 1.
Study Schematic
DB = double-blind; EOW = every other week; IV = intravenous; SC = subcutaneous; Wk = week
*
Responders are defined as clinical responders AND/OR endoscopic responders (per local read), and non-responders are 
defined as clinical non-responders AND endoscopic non-responders (per local read).  Clinical responder is defined at Week 
12 of the Induction Period or Re-Induction Period as a decrease in CDAI ≥100 points from Baseline (CR100).  Endoscopic 
responder is defined at Week 12 of the Induction Period or Re-Induction Period as a decrease in SES-CD > 50% from 
Baseline (or for subjects with isolated ileal disease and a Baseline SES-CD of 4, at least a 2-point reduction from Baseline) 
(per local read).  In the case of missing data where clinical response and endoscopic response cannot be calculated, 
subjects will be considered as non-responders for the re-randomization criteria evaluation.
**
Only subjects who are considered to be clinical non-responders and endoscopic non-responders (per local read) at Week 
12 of the Induction Period will be re-randomized into the Re-Induction Period.
*** Subjects with inadequate response at/after Week 4 of the Maintenance Period will be eligible to receive Rescue Therapy 
consisting of ABBV-154 600 mg IV followed by ABBV-154 230 mg SC EOW.
Page 18 of 145
 
  
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
  
 
 
 
  
 
  
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


  
STUDY M20-371  |  Version 4.0  |  EudraCT 2021-002869-18
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
4.2 Discussion of Study Design
Choice of Control Group
Placebo has been selected as the appropriate control group to evaluate the primary and secondary 
efficacy endpoints as double-blind, placebo-controlled study designs are generally acknowledged as 
standard for unbiased estimates of treatment differences.  There is no anticipated medical risk for 
subjects randomized to placebo given that subjects have already demonstrated inadequate response or 
intolerance to at least one of the available biologic treatment options and may receive Rescue Therapy 
during the Induction and Maintenance Periods if they demonstrate inadequate response as per 
protocol-specified criteria.
Appropriateness of Measurements
Standard statistical, clinical, and laboratory procedures will be utilized in this study.  Most efficacy and 
safety-related measurements in this study are standard for assessing disease activity in subjects with CD.  
In addition, a new wearable device for data collection and exploratory patient-reported outcome (PRO) 
measures will be evaluated to inform use in future clinical studies.  Furthermore, possible 
glucocorticoid-reported related AEs will be adjudicated as specified in Section 5.11.  All clinical and 
laboratory procedures in this study are standard and generally accepted.
Suitability of Subject Population
The mechanism of action of ABBV-154 has the potential to improve disease activity in CD subjects.  
While this is the first study to test ABBV-154 in CD subjects, safety results of ABBV-154 in healthy 
volunteers indicate no safety issues of concern and no dose limiting toxicity.
Selection of Doses in the Study
As shown in Figure 1, four 12-week ABBV-154 induction regimens, two 12-week ABBV-154 re-induction 
regimens, two 40-week ABBV-154 maintenance regimens, and one ABBV-154 rescue therapy regimen 
have been selected for evaluation in this Phase 2b dose-ranging study in subjects with CD who have had 
prior inadequate response to or intolerance of biologics.
All induction regimens in the study have an IV loading dose at Week 0 to enable faster achievement of 
steady-state levels, followed by SC doses administered EOW from Week 2 or every 4 weeks (E4W) at 
Week 4 and Week 8.  The low induction regimen is expected to result in total antibody exposures that 
are comparable to the approved adalimumab CD dosing regimen, and additional efficacy is expected 
from the delivery of the GRM payload into activated immune cells.  All selected induction regimens are 
adequately separated from each other with minimal overlapping exposures and cover a wide dose range 
to enable robust characterization of the dose/exposure-response relationship and selection of Phase 3 
induction doses.  The E4W regimen provides the optionality of exploring an alternate dosing frequency.  
The selected induction regimens are predicted to result in exposures that are similar to or lower than 
the maximum exposures safely tested in the ABBV-154 first-in-human study and are projected to be 
covered by adequate safety margins relative to no-observed-adverse-effect level exposures observed at 
a dose of 80 mg/kg/week SC in the 26-week Good Laboratory Practice -compliant toxicology study in 
cynomolgus monkeys.  Projected ABBV-154 and payload safety margins for the highest induction dosing 
Page 19 of 145
 


STUDY M20-371  |  Version 4.0  |  EudraCT 2021-002869-18
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
regimen are at least 6×, based on predicted ABBV-154 human exposures and the observed toxicokinetic 
data in the 26-week cynomolgus monkey study.
For the Re-Induction Period, subjects will be re-randomized to the mid and high EOW induction dosing 
regimens to increase the chances of initial non-responders achieving clinical response AND/OR 
endoscopic response.
During the Maintenance Period, 2 dosing regimens of ABBV-154, 80 and 230 mg SC EOW will be 
evaluated which are equivalent to the EOW dose level of the low and mid doses during the Induction 
Period.  The selected doses are expected to be sufficient to maintain response and to enable selection of 
Phase 3 maintenance doses.
Subjects who have an inadequate response at or after Week 4 in the Maintenance Period will be eligible 
to receive Rescue Therapy with a single dose of ABBV-154 600 mg IV followed by 
ABBV-154 230 mg SC EOW, to assess whether their response status can be recaptured.
5 STUDY ACTIVITIES
5.1 Eligibility Criteria
Subjects must meet all of the following criteria in order to be included in the study.  Anything other than 
a positive response to the questions below will result in exclusion from study participation.  (In this 
section, "Baseline" refers to the Baseline [Week 0, Day 1] of the Induction Period.)
Consent
1. Subject must be able to understand and willing to adhere to all protocol requirements and 
voluntarily sign and date an informed consent, approved by an independent ethics committee 
(IEC)/institutional review board (IRB), prior to the initiation of any screening or study-specific 
procedures.
Demographic and Laboratory Assessments
2. Adult male or female, at least 18 years old and not more than 75 years of age at the time of 
Screening.
3. Body Mass Index (BMI) ≥ 18.0 to ≤ 39.9 kg/m2 after rounding to the nearest tenth at the time 
of Screening.  BMI is calculated as weight in kg divided by the square of height measured in 
meters.
4. Laboratory values must meet the following criteria within the Screening Period:

Serum aspartate aminotransferase (AST) ≤2.5 × upper limit of normal (ULN);

Serum alanine transaminase (ALT) ≤2.5 × ULN;

Total bilirubin ≤1.5 × ULN;

Estimated glomerular filtration rate (eGFR) by simplified 4-variable Modification of Diet in 
Renal Disease formula ≥ 60 mL/min/1.73 m2;
Page 20 of 145


STUDY M20-371  |  Version 4.0  |  EudraCT 2021-002869-18
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.

Absolute neutrophil count (ANC) ≥ 1,500/µL;

Absolute lymphocyte count (ALC) ≥ 800/µL;

Platelet count ≥ 75,000/µL;

Glycated hemoglobin (hemoglobin A1c [HbA1c] ≤ 8.5%);

Serum potassium >3.0 mmol/L and < 5.5 mmol/L; and

Thyroid-stimulating hormone <10.0 mlU/L.
Disease/Condition Activity
5. Subject must have a confirmed diagnosis of CD for at least 3 months prior to Baseline.  
Appropriate documentation of biopsy results consistent with the diagnosis of CD, in the 
assessment of the Investigator, must be available.
6. Subject must have a CDAI score of 220 to 450 at Baseline.
7. Subject must have endoscopic evidence of mucosal inflammation as documented by an 
SES-CD of ≥ 6 for ileocolonic or colonic disease or SES-CD of ≥ 4 for isolated ileal disease as 
scored by a central reader.  All eligible scores must exclude the presence of narrowing 
component.
8. Subject must not have evidence of current fistulizing disease, abscess (abdominal or perianal), 
symptomatic bowel strictures, fulminant colitis, toxic megacolon, or any other manifestation of 
CD that might require surgery while enrolled in the study.
9. Subject must not have ostomy or ileoanal pouch.
10. Subject must not have a diagnosis of short gut or short bowel syndrome.
11. Subject must not have a history of surgical bowel resection within the past 3 months prior to 
Baseline, history of > 3 bowel resections due to progression of CD (note:  ostomy reversal and 
hernia repair are not considered related to progression of CD), or > 2 missing segments of the 
following 5 segments:  terminal ileum, right colon, transverse colon, sigmoid and left colon, and 
rectum.
Subject History
12. Subject must have demonstrated intolerance or inadequate response to one or more of the 
following biologic agents as defined below.  Subjects who discontinued biologic agents only for 
reasons other than inadequate response or intolerance (e.g., change of insurance) are not 
eligible to enroll.  Subjects with prior intolerance to adalimumab are not eligible to enroll.  
Where mandated by local requirements: subjects with prior exposure to adalimumab must not 
have evidence of anti-adalimumab antibodies prior to Baseline.

Demonstration of intolerance requires no minimum dose or duration of use.

Inadequate response defined as signs and symptoms of persistently active disease (in the 
opinion of the Investigator) despite a history of one or more of the following:

At least one 6-week induction regimen of infliximab (≥ 5 mg/kg IV at Weeks 0, 2, and 6);
Page 21 of 145


STUDY M20-371  |  Version 4.0  |  EudraCT 2021-002869-18
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.

At least one 4-week induction regimen of adalimumab (one 160 mg SC dose at Week 0, 
followed by one 80 mg SC dose at Week 2 [or one 80 mg SC dose at Week 0, followed by 
one 40 mg SC dose at Week 2, in countries where this dosing regimen is approved]);

At least one 4-week induction regimen of certolizumab pegol (400 mg SC at Weeks 0, 2, 
and 4);

At least one 6-week induction regimen of vedolizumab (300 mg IV at Weeks 0, 2, and 6);

At least one 12-week induction regimen of natalizumab (300 mg IV every 4 weeks);

At least one 8-week induction regimen of ustekinumab (260 mg [≤ 55 kg] or 390 mg 
[> 55 to ≤ 85 kg] or 520 mg [> 85 kg] IV, followed by 90 mg SC at Week 8);

At least one 8-week induction regimen of risankizumab (600 mg IV at Weeks 0, 4, and 8);

Recurrence of symptoms during scheduled maintenance dosing following prior clinical 
benefit of the above biologic agents.
13. Subject must not have a current or history of infection including:

Chronic recurring infections(s) and/or active viral infection that, based on the investigator's 
clinical assessment, makes the subject an unsuitable candidate for the study;

Active infection(s) requiring hospitalization or treatment with parenteral anti-infectives 
within 30 days, or oral anti-infectives within 14 days prior to the first dose of study drug 
administration;

Active tuberculosis (TB) or meets TB exclusionary parameters (See specific requirements for 
TB testing and prophylaxis in the Operations Manual);

Positive Clostridium difficile stool assay during the Screening Period;

Subjects in Japan only:  positive result of beta-D-glucan (screening for Pneumocystis jirovecii 
infection) or two consecutive indeterminate results of beta-D-glucan during the Screening 
period;

Confirmed COVID-19 infection:  the Baseline visit must be at least 10 days from onset of 
signs/symptoms or positive SARS-CoV-2 test; symptomatic subjects must have recovered, 
defined as resolution of fever without use of antipyretics and improvement of symptoms;

Suspected COVID-19 infection:  subjects with signs/symptoms suggestive of COVID-19 
infection, should undergo molecular testing (e.g., polymerase chain reaction [PCR]) or have 
2 negative antigen test results at least 24 hours apart to rule out SARS-CoV-2 infection or 
must be asymptomatic for at least 10 days without use of antipyretics.

Subject must not have evidence of the following:

Hepatitis B virus (HBV):  A positive test result for hepatis B surface antigen (HBs Ag) or 
detectable HBV DNA PCR qualitative test for subjects who are hepatitis B core antibody 
(HBc Ab) positive (and for hepatitis B surface antibody [HBs Ab] positive subjects where 
mandated by local requirements);

Hepatitis C virus (HCV):  A detectable HCV RNA in any subject with anti-HCV antibody 
(HCV Ab);
Page 22 of 145


STUDY M20-371  |  Version 4.0  |  EudraCT 2021-002869-18
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.

Human Immunodeficiency virus (HIV) infection defined as confirmed positive anti-HIV 
antibody (HIV Ab) test.
14. Subject must not have a history of the following medical diseases or disorders:

Suspected or confirmed adrenal insufficiency;

Hypothyroidism for which the subject is not receiving physiological replacement therapy.

Moderate to severe congestive heart failure (New York Heart Association Class III or IV).

Uncontrolled hypertension defined as confirmed systolic blood pressure > 160 mm Hg or 
diastolic blood pressure > 100 mm Hg at rest despite regular treatment under standard of 
care.

Glaucoma, osteonecrosis, or osteoporosis with high risk of fracture (e.g., T score ≤ -2.5 with 
history of fragility fracture).

Organ transplant which requires continued immunosuppression.

Demyelinating disease (including myelitis) or neurologic symptoms suggestive of 
demyelinating disease.

Active or suspected malignancy or history of any malignancy within the last 5 years, except 
for successfully treated nonmelanoma skin cancer (NMSC) or localized carcinoma in situ of 
the cervix.  Regardless of the time since remission, subjects with any history of lymphoma, 
leukemia, melanoma, Merkel cell carcinoma, colon carcinoma, or small bowel carcinoma.

History of any medical condition other than CD that is likely to require systemic 
glucocorticoid treatment during the study (e.g., asthma and chronic obstructive pulmonary 
disease [COPD]) per investigator judgement.

Allergic reaction or significant sensitivity to constituents of the study drug (and its 
excipients) and/or other products in the same class.  This includes anaphylactic reaction to 
any agent (e.g., food products or bee sting), hereditary fructose intolerance, or a reaction to 
any immunoglobulin G (IgG) containing product.

Dysplasia of the gastrointestinal tract or found to have dysplasia, other than completely 
removed low-grade dysplastic lesions, in any biopsy performed during the Screening 
endoscopy.

Hepatic cirrhosis.
15. For subjects in the Wearable Device Substudy, subjects with history of pre-existing sleep 
disorders, including insomnia requiring regular sleep medication, obstructive sleep apnea, 
restless leg syndrome, or currently on prescription sleep medications should not participate in 
the Wearable Device Substudy but may participate in the study as a whole if meeting all other 
eligibility criteria.
16. Subject must not have a history of clinically significant (per investigator's judgment) drug or 
alcohol abuse within the last 12 months prior to Baseline.
Page 23 of 145


STUDY M20-371  |  Version 4.0  |  EudraCT 2021-002869-18
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
17. There must be no reason the investigator believes that the subject is an unsuitable 
candidate to participate in the study, receive study drug, or would be placed at risk by 
participating in the study (e.g., because of a medical condition or illness other than CD that is 
not well controlled regardless of treatment).
Contraception
18. Females of childbearing potential must not have a positive serum pregnancy test at the 
Screening Visit and must have a negative urine pregnancy test at Baseline, prior to the first dose 
of study drug.  Local practices may require a serum pregnancy test at Baseline.  Subjects with a 
borderline serum pregnancy test at Screening must not have a clinical suspicion of pregnancy or 
other pathological cause of a borderline result and a serum pregnancy test ≥ 3 days later to 
document continued lack of a positive result (unless prohibited by local requirements).
19. Female subjects of childbearing potential must practice at least 1 protocol-specified method 
of birth control, that is highly effective from Baseline through at least 70 days after the last dose 
of study drug.  Local practices may require 2 methods of birth control.  Female subjects of 
non-childbearing potential do not need to use birth control.  Where mandated by local 
requirements:  Female subjects of childbearing potential must practice at least 1 protocol-
specified method of birth control, that is highly effective from Study Day 1 through at least 
150 days after the last dose of study drug.
20. Females must not be pregnant, breastfeeding, or considering becoming pregnant and may 
not donate eggs during the study or for approximately 70 days (150 days where mandated by 
local requirements) after the last dose of study drug.
21. If male, and subject is sexually active with female partner(s) of childbearing potential, he 
must agree, from Baseline through at least 70 days (150 days where mandated by local 
requirements) after the last dose of study drug, to practice the protocol-specified contraception.
22. If male, must not be considering fathering a child or donating sperm during the study or for 
approximately 70 days (150 days where mandated by local requirements) after the last dose of 
study drug.
Concomitant Medications
23. Subject must have discontinued CD-related antibiotics or be on a stable dose of CD-related 
antibiotics for at least 14 days prior to Baseline.
24. Subject must have discontinued oral aminosalicylates (e.g., balsalazide, mesalamine, 
olsalazine, sulfasalazine, aminosalicylate) or be on a stable dose of oral aminosalicylates for at 
least 14 days prior to Baseline.
25. Subject must have discontinued oral glucocorticoids for at least 14 days prior to Baseline OR 
must have been on ≤ 1 of the following oral glucocorticoids for at least 14 days prior to Baseline 
and on a stable dose as specified below for at least 7 days prior to Baseline:

Budesonide ≤ 9 mg/day;

Beclomethasone ≤ 5 mg/day;
Page 24 of 145


STUDY M20-371  |  Version 4.0  |  EudraCT 2021-002869-18
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.

Prednisone or equivalent ≤ 20 mg/day.
If enrolling on oral glucocorticoids subject must be willing and able to follow the protocol 
defined prespecified glucocorticoid-tapering regimen.
26. Subject must not have been treated with any of the following:

Intra-articular, intramuscular, IV, trigger point or tender point, intra-bursa, or intra-tendon 
sheath glucocorticoid in the preceding 8 weeks prior to the first dose of the study drug; or

Super high potency and/or high potency topical glucocorticoids in the preceding 1 week 
prior to the first dose of study drug.
27. If subject is using inhaled glucocorticoids for a stable medical condition, must be at stable 
dose ≥ 4 weeks prior to the Baseline visit.
28. Subject on azathioprine (AZA), 6-mercaptopurine (6-MP), or methotrexate (MTX) must:

Be on the current course for ≥ 42 days prior to Baseline, and on a stable dose for ≥ 30 days 
prior to Baseline, OR

Have discontinued these therapies ≥ 30 days prior to Baseline.
29. Subject must not have received cyclosporine, tacrolimus, or mycophenolate mofetil within 
30 days prior to Baseline.
30. Subject must have discontinued all biologic therapies used for the treatment of CD or with 
potential for additive immunosuppressive effect prior to the first dose of study drug.  Subjects 
may not have prior exposure to ABBV-154.  Use of biologic therapies for indications other than 
CD may be approved by the AbbVie TA MD on a case-by-case basis.  If there is documentation of 
an undetectable drug level measured by a commercially available assay for any of the biologics 
given in eligibility criterion #12, there is a no minimum washout period prior to Baseline.  The 
washout periods required prior to the Baseline Visit are specified below or at least 5 times the 
mean terminal elimination half-life for other biologic therapies:

≥ 8 weeks for infliximab, adalimumab, certolizumab, vedolizumab, and natalizumab;

≥ 12 weeks for ustekinumab and risankizumab.
31. Subject must not have been treated with any investigational drug within 30 days or 
5 half-lives of the drug (whichever is longer) prior to Baseline and must not be currently enrolled 
in another interventional clinical study.  The eligibility criterion applies to any drug that was
investigational at the time of protocol approval regardless of regulatory approval status of the 
drug for the treatment of CD.
32. Subject must not have received any live vaccine with replicating potential within 28 days
prior to Baseline (or longer if required locally) or be expected to need a live vaccination with any 
live vaccine with replicating potential during study participation including at least 70 days after 
the last dose of the study drug.  Live vaccines that are incapable of replicating (e.g., JYNNEOS 
monkeypox vaccine) are permitted.
Page 25 of 145


STUDY M20-371  |  Version 4.0  |  EudraCT 2021-002869-18
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
33. Subject must have discontinued nonsteroidal anti-inflammatory drugs (NSAIDs) with the 
exception of low-dose aspirin daily and selective COX-2 inhibitors at least 14 days prior to the 
Screening endoscopy and may not use NSAIDS other than low-dose aspirin and selective COX-2 
inhibitors during the remainder of the Screening Period.  Subjects entering on low-dose aspirin 
or selective COX-2 inhibitors must be on stable dose ≥ 1 week prior to the first dose of study 
drug.
34. Subject must not have received exclusive enteral nutrition or any parenteral nutrition within 
14 days prior to Baseline.
35. Subject must not have received fecal microbial transplantation within 30 days prior to 
Baseline.
36. Subject must not have received therapeutic enema or suppository, other than required for 
endoscopy, within 14 days prior to endoscopy used for Screening or during the Screening 
Period.
37. Subject must not have received apheresis (e.g., Adacolumn apheresis) within 60 days prior 
to Screening or during the Screening Period.
38. Subject must not have been treated with oral traditional Chinese medicine within 4 weeks 
prior to Baseline.
39. Subject must have no systemic use of known strong cytochrome P450 3A (CYP3A) inhibitors 
from Screening through the end of study drug administration (refer to Table 1 in Section 5.3 for 
examples of commonly used strong CYP3A inhibitors).  Subjects may not use herbal therapies or 
other traditional medicines with unknown effects on CYP3A from Screening through the end of 
study drug administration.
5.2 Contraception Recommendations
Contraception Requirements for Females
Subjects must follow the following contraceptive guidelines as specified (in this section, "Baseline" 
refers to the Baseline [Week 0, Day 1] of the Induction Period):

Females, Non-Childbearing Potential
Females do not need to use birth control during or following study drug treatment if considered 
of non-childbearing potential due to meeting any of the following criteria:
1.
Premenopausal female with permanent sterility or permanent infertility due to one of the 
following:

Permanent sterility due to a hysterectomy, bilateral salpingectomy, bilateral 
oophorectomy;

Non-surgical permanent infertility due to Mullerian agenesis, androgen insensitivity, or 
gonadal dysgenesis; investigator discretion should be applied to determining study entry 
for these individuals.
Page 26 of 145


  
STUDY M20-371  |  Version 4.0  |  EudraCT 2021-002869-18
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
2.
Postmenopausal female

Age > 55 years with no menses for 12 or more months without an alternative medical 
cause.

Age ≤ 55 years with no menses for 12 or more months without an alternative medical 
cause AND a follicle-stimulating hormone (FSH) level ≥30 IU/L.

Females, Childbearing Potential

Females of childbearing potential must avoid pregnancy while taking study drug(s) and for 
at least 70 days (150 days where mandated by local requirements) after the last dose of 
study drug.

Females must commit to one of the following methods of birth control:

Combined (estrogen and progestogen containing) hormonal birth control (oral, 
intravaginal, transdermal, injectable) associated with inhibition of ovulation-initiated at 
least 30 days prior to Baseline.

Progestogen-only hormonal birth control (oral, injectable, implantable) associated with 
inhibition of ovulation initiated at least 30 days prior to Baseline.

Bilateral tubal occlusion/ligation (can be via hysteroscopy, provided a 
hysterosalpingogram confirms success of the procedure).

Intrauterine device.

Intrauterine hormone-releasing system.

Vasectomized partner (provided the partner has received medical confirmation of the 
surgical success of the vasectomy and is the sole sexual partner of the trial subject).

Practice true abstinence, defined as:  Refraining from heterosexual intercourse when 
this is in line with the preferred and usual lifestyle of the subject (periodic abstinence 
[e.g., calendar, ovulation, symptothermal, post-ovulation methods] and withdrawal are 
not acceptable).
If required per local practices, male or female condom with or without spermicide OR cap, diaphragm or 
sponge with spermicide should be used in addition to one of the birth control methods listed above 
(excluding true abstinence).
Contraception recommendations related to use of concomitant therapies prescribed (e.g., MTX) should 
be based on the local label.
During the course of the study, female subjects may change from "of Childbearing Potential" to "of Non-
Childbearing Potential" if meeting criteria outlined above under "Females, Non-Childbearing Potential."  
If needed to confirm post-menopausal status after the screening visit, follicle-stimulating hormone level 
may be obtained at any time during the study.
Page 27 of 145
 


  
STUDY M20-371  |  Version 4.0  |  EudraCT 2021-002869-18
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
Contraception Requirements for Males
Male subjects who are sexually active with a female partner of childbearing potential, must agree to use 
male condoms, even if the male subject has undergone a successful vasectomy, from Baseline through 
at least 70 days (150 days where mandated by local requirements) after the last dose of study drug.
5.3 Prohibited Medications and Therapy
Subjects must be able to safely discontinue any prohibited medications as specified in Section 5.1 and 
Section 5.4.  Subjects must be consented for the study prior to discontinuing any prohibited medications 
for the purpose of meeting study eligibility.
The following medications are prohibited through the end of study drug administration:

All biologic therapies used for the treatment of CD or with potential for additive 
immunosuppressive effect including but not limited to the following (including biosimilars):  
abatacept (Orencia®), adalimumab (Humira®), anakinra (Kineret®), belimumab (Benlysta®), 
certolizumab pegol (Cimzia®), etanercept (Enbrel®), golimumab (Simponi®), infliximab 
(Remicade®), natalizumab (Tysabri®), rituximab (Rituxan®), tocilizumab (Actemra®), 
ustekinumab (Stelara®), vedolizumab (Entyvio®), and risankizumab (Skyrizi®).

Investigational agents

All other therapies with a potential therapeutic impact on CD (except for those allowed per 
protocol) including but not limited to the following:  Janus kinase (JAK) inhibitors such as 
tofacitinib, cyclosporine, tacrolimus, or mycophenolate mofetil.

Live vaccination (see Section 5.4).

Rectal therapy, with the exception of those required for endoscopy.

IV, intramuscular, intra-articular, epidural, intra-bursal, intra-tendon sheath, trigger or tender 
point, or rectal administration of glucocorticoids; 

Super high potency and/or high potency topical glucocorticoids (see Operations Manual 
[Appendix F], Section 3.5).  From Weeks 0 to 28 of the Maintenance Period super high potency 
and/or high potency topical glucocorticoids are permitted for non-CD-related adverse events.

Corticotropin gel injection (e.g., Acthar®)

Apheresis (e.g., adacolumn apheresis).

Exclusive enteral nutrition or any parenteral nutrition.

NSAIDs with the exception of low dose aspirin daily and selective COX-2 inhibitors.

Traditional oral Chinese medicine (e.g., tripterygium glycosides, sinomenine, total glucosides of 
white paeony).
Strong CYP3A Inhibitors
Systemic use of known strong cytochrome P450 3A (CYP3A) inhibitors (includes over-the-counter or 
prescription medicines, vitamins and/or herbal supplements) is not permitted from Screening through 
Page 28 of 145
 


  
STUDY M20-371  |  Version 4.0  |  EudraCT 2021-002869-18
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
the end of study drug administration.  Table 1 includes examples of commonly used strong CYP3A 
inhibitors.  In addition, herbal therapies and other traditional medicines with unknown effects on CYP3A 
are not permitted from Screening through the end of study drug administration.
Table 1.
Examples of Commonly Used Strong CYP3A Inhibitors
Strong CYP3A Inhibitors
Boceprevir
Cobicistat
Clarithromycin
Conivaptan
Grapefruit (fruit or juice)
Indinavir
Itraconazole
Ketoconazole
Lopinavir/Ritonavir
Mibefradi
Nefazodone
Nelfinavir
Posaconazole
Ritonavir
Saquinavir
Telaprevir
Telithromycin
Troleandomycin
Voriconazole
CYP3A = cytochrome P450 3A
5.4 Prior and Concomitant Therapy
Aminosalicylates, immunomodulators, CD-related antibiotics:  Dose adjustment is prohibited during the 
Induction Period, the Re-Induction Period, and after Week 28 of the Maintenance Period except in the 
event of moderate-to-severe treatment-related toxicities and after discussion with the AbbVie 
Therapeutic Area Medical Director (TA MD) or if subject meets protocol defined rescue criteria.  All 
subjects receiving CD-related antibiotics may discontinue treatment after the Induction Period or Re-
Induction Period at the discretion of the investigator.  Subjects who continue CD-related antibiotics at 
Week 0 of the Re-Induction Period will maintain their CD-related antibiotics and respective doses 
through the Re-Induction Period.  CD-related antibiotics may be initiated at any time for the treatment 
of an AE.
Page 29 of 145
 


  
STUDY M20-371  |  Version 4.0  |  EudraCT 2021-002869-18
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
Inhaled glucocorticoids:  Subjects may take inhaled glucocorticoids if used for a stable medical condition 
and at stable dose ≥ 4 weeks prior to the Baseline Visit (Week 0, Day 1 of the Induction Period).  
Short-term use (≤ 14 days) of an inhaled glucocorticoid at an increased dose/frequency for treatment of 
an AE unrelated to CD is permissible.
Use of concomitant biologic therapies for indications other than CD (e.g., denosumab or intravitreal 
administration of VEGF inhibitors such as brolucizumab) may be approved by the AbbVie TA MD on a 
case-by-case basis.
Any medication (including over-the-counter or prescription medicines, vitamins, and/or herbal 
supplements) that the subject is receiving at the time of enrollment or receives during the study must be 
recorded from 30 days prior to study drug administration through the post-treatment visit (70-day 
follow-up visit).
Any questions regarding concomitant or prior therapy should be raised to the AbbVie TA MD.  
Information regarding potential drug interactions with ABBV-154 can be located in the ABBV-154 
Investigator's Brochure.
Subjects must be able to safely discontinue any prohibited medications as specified in eligibility criteria 
in Section 5.1 or 5 half-lives or 4 weeks, whichever is longer, prior to initial study drug administration.  
Subjects must be consented for the study prior to discontinuing any prohibited medications for the 
purpose of meeting study eligibility.
Vaccines
If the subject and investigator choose to receive/administer live vaccines with replicating potential, 
these vaccinations must be completed (per local label) at least 28 days (or longer if required locally) 
before first dose of study drug.  Live vaccines (except non-replicating live vaccines – e.g., JYNNEOS 
monkeypox vaccine) are prohibited during the study and for at least 70 days after the last dose of study 
drug.  Examples of live vaccines with replicating potential include, but are not limited to, the following:

Monovalent live influenza A (H1N1) (intranasal);

Seasonal trivalent live influenza (intranasal);

Zostavax (herpes zoster, live attenuated);

Rotavirus;

Varicella (chicken pox);

Measles-mumps-rubella or measles-mumps-rubella-varicella;

Oral polio vaccine;

Smallpox/monkeypox vaccine capable of replicating (ACAM2000®);

Yellow fever;

Bacille Calmette-Guérin (BCG);

Typhoid (oral).
Page 30 of 145
 


  
STUDY M20-371  |  Version 4.0  |  EudraCT 2021-002869-18
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
Administration of inactivated (non-live) vaccines is permitted prior to or during the study according to 
local practice guidelines.  Examples of common vaccines that are inactivated, toxoid, or biosynthetic 
include, but are not limited to the following:  injectable influenza vaccine, pneumococcal, Shingrix 
(zoster vaccine, recombinant, adjuvanted), and pertussis (Tdap) vaccines.
COVID-19 Pandemic-Related Vaccination Guidance
Given the ongoing COVID-19 pandemic, selected non-live vaccines (e.g., mRNA, non-replicating viral 
vector, protein subunit, etc.) to prevent SARS-CoV-2 infection may be administered during screening or 
the treatment period, as long as components of the vaccine are not contraindicated.
The decision to receive a locally available vaccine should be based on local guidance and an individual 
discussion between the treating physician and the subject.
The potential impact of ABBV-154 on SARS-CoV-2 vaccination is unknown.  Therefore, study drug should 
be administered as follows:

The first dose of study drug, when possible, is preferred to be given at least ± 7 days from the 
SARS-CoV-2 vaccine administration.
Note:  The above guidance applies to all SARS-CoV-2 vaccine doses given as part of the complete 
treatment course.
These recommendations may be subject to change based on the evolving knowledge around the use of 
SARS-CoV-2 vaccines and as more data are collected in real-world scenarios and clinical trials.
Any SARS-CoV-2 vaccine information must be documented on the COVID-19 vaccine electronic case 
report form (eCRF).  Refer to the Operations Manual for instructions on reporting any AEs associated 
with the COVID-19 vaccine.
Rescue Concomitant Medications/Therapy
Unless qualifying for Rescue Therapy or undergoing mandatory tapering for glucocorticoids as described 
below, no changes may be made to oral glucocorticoids, aminosalicylates, or immunomodulators during 
the Induction and Re-Induction Periods, or after Week 28 of the Maintenance Period.
In the Induction Period, starting at or after the completion of the Week 8 Visit and thereafter (Week 8 
through Week 12), subjects who demonstrate inadequate response as defined below may receive 
Rescue Therapy with oral glucocorticoids (≤ 20 mg/day prednisone or equivalent, ≤ 9 mg/day 
budesonide, or ≤ 5 mg/day beclomethasone).  Changes in aminosalicylates, or immunomodulators are 
not permitted during the Induction Period.
In the Maintenance Period, starting at or after the completion of the Week 4 Visit and thereafter
(Week 4 through Week 40), subjects who demonstrate inadequate response as defined below will be 
eligible to receive rescue therapy with a single dose of ABBV-154 600 mg IV at the respective visit, 
followed by ABBV-154 230 mg SC after 2 weeks and EOW thereafter.
In the Maintenance Period, subjects who have received rescue therapy with ABBV-154 for at least 
4 weeks and who continue to demonstrate inadequate response, as defined below, may receive 
Page 31 of 145
 


  
STUDY M20-371  |  Version 4.0  |  EudraCT 2021-002869-18
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
additional rescue therapy with oral glucocorticoids (≤ 20 mg/day prednisone or equivalent, ≤ 9 mg/day 
budesonide, or ≤ 5 mg/day beclomethasone), aminosalicylates, or immunomodulators.
In the Induction Period after the Week 8 Visit and in the Maintenance Period after the Week 4 Visit, 
inadequate response may also be confirmed at unscheduled visits and visits where collection of CDAI 
components was not planned.
Rescue Therapy is not permitted in the Re-Induction Period.
Subjects who receive protocol-defined glucocorticoid Rescue Therapy, initiate glucocorticoids (other 
than inhaled) after Baseline without qualifying for Rescue Therapy, fail to complete glucocorticoid 
tapering by Week 6, or who increase doses of or initiate treatment with aminosalicylates or 
immunomodulators during the Induction Period will be considered non-responders and will be 
re-randomized into the Re-Induction Period.  All subjects who fulfill the clinical response AND/OR 
endoscopic response (per local read) definition at Week 12 of the Re-Induction Period will be 
re-randomized into the Maintenance Period.
The criteria for inadequate response are the following:

Induction Period:  Presence of clinical symptoms defined as CDAI ≥ 220 and not achieving a 
decrease in CDAI ≥ 35 points from Baseline of the Induction Period.

Maintenance Period:  Presence of clinical symptoms defined as CDAI ≥220 and an increase in 
CDAI ≥70 points from Baseline of the Maintenance Period.

And, for both the Induction Period and Maintenance Period, presence of at least 1 of the 
following objective markers of inflammation:

hs-CRP ≥ ULN, and worse than the lowest value assessed during the study, or

FCP ≥250 µg/g, and worse than the lowest value assessed during the study, or

SES-CD, excluding the narrowing component, ≥ 6 (≥ 4 for isolated ileal disease), as scored by 
the site investigator at an endoscopy.
The last available values for hs-CRP and FCP will be used for assessment of inadequate response.
Use of Rescue Therapy in subjects who qualify is at the investigator's discretion and not mandatory.
5.5 Withdrawal of Subjects and Discontinuation of Study
AbbVie may terminate this study prematurely at any time, either in its entirety or partially (discontinue 
one or more treatment groups) or at any site.  The study may be discontinued or terminated in case of 
an unacceptable risk, any relevant toxicity, or a negative change in the risk/benefit assessment.  This 
might include the occurrence of AEs with a character, severity or frequency that is new in comparison to 
the existing risk profile.  In addition, data derived from other clinical trials or toxicological studies which 
negatively influence the benefit-risk assessment might cause discontinuation or termination of the 
study.  The investigator may also stop the study at his/her site if he/she has safety concerns.  If AbbVie 
terminates the study for safety reasons, AbbVie will promptly notify the investigator.  Advance notice is 
not required by either party if the study is stopped due to safety concerns.
Page 32 of 145
 


  
STUDY M20-371  |  Version 4.0  |  EudraCT 2021-002869-18
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
A subject may voluntarily withdraw from the study at any time for any reason.  An investigator may 
discontinue a subject's participation at any time for any reason.  The AbbVie TA MD may mandate 
individual subject discontinuation from study drug in case of a safety concern.
Subjects must have study drug discontinued immediately if any of the following occur:

Abnormal laboratory result or AE that meets the criteria for discontinuation of study drug as 
stated in Section 6.2, or rule out safe continuation of the study drug, as determined by the 
investigator or the AbbVie TA MD.

Serious infection (e.g., sepsis) that cannot be adequately controlled within 2 weeks by 
anti-infective treatment or would put the subject at risk with continuation of study drug.

Subject is noncompliant with TB prophylaxis (if applicable) or develops active TB at any time 
during the study.

Malignancy or high-grade dysplasia of the gastrointestinal tract, except for localized NMSC or 
carcinoma in-situ of the cervix.

The subject develops an anaphylactic reaction or anaphylactic shock.

The investigator believes it is in the best interest of the subject.

The subject requests withdrawal from study drug or the study.

Eligibility criteria violation was noted after the subject started study drug and continuation of 
the study drug would place the subject at risk.

Introduction of prohibited medications or dosages and continuation of the study drug would 
place the subject at risk.

The subject becomes pregnant while on study drug.

Subject is significantly noncompliant with study procedures, which would put the subject at risk 
for continued participation in the trial as determined by the investigator or AbbVie TA MD.

Subject is prematurely unblinded to study drug assignment by the investigator or AbbVie TA 
MD.
State of Emergency or Pandemic-Related Acceptable Protocol Modification
During states of emergency or pandemic situations, it might be necessary to employ mitigation 
strategies to enable the investigator to ensure subject safety and continuity of care.  Acceptable 
mitigation strategies are identified and included in the Operations Manual in Appendix F.
The investigator should contact the AbbVie TA MD before discontinuing a subject from the study for a 
reason other than described in the protocol to ensure all acceptable mitigation steps have been 
explored.
Page 33 of 145
 


  
STUDY M20-371  |  Version 4.0  |  EudraCT 2021-002869-18
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
5.6 Follow-Up After Subject Discontinuation of Study Drug or from 
Study
Discontinuation of Study Drug and Continuation of Study Participation
To minimize missing data for efficacy and safety assessments, subjects who prematurely discontinue 
study drug treatment should be encouraged to continue to be followed for all regularly scheduled visits 
as outlined in the Protocol Activities tables in the Operations Manual (Appendix F, Section 2) and adhere 
to all study procedures except for administration of study drug, endoscopy, annual TB testing, PK, and 
plasma/serum or other biomarker or exploratory research sample collection unless a subject decides to 
discontinue study participation entirely (withdrawal of informed consent).  Subjects should continue to 
be advised on the scientific importance of their data even if they discontinue treatment with study drug 
early.  Following the discontinuation of study drug, the subject should be treated in accordance with the 
investigator's best clinical judgment irrespective of whether the subject decides to continue 
participation in the study.
In addition, a 70-Day Follow-up Visit after the last dose of study drug is required to ensure all 
treatment-emergent AEs/SAE have been resolved.  All attempts must be made to determine the date of 
the last study drug dose and the primary reason for discontinuation of study drug or study participation.  
This information will be recorded on the appropriate eCRF page.  For subjects who discontinue study 
drug but continue study participation, the 70-Day Follow-up Visit is not required if at least one visit has 
occurred at least 70 days since the last dose of study drug.
Premature Discontinuation of Study (Withdrawal of Informed Consent)
If a subject prematurely discontinues study participation (withdrawal of informed consent), the 
procedures outlined for the Premature Discontinuation visit should be completed as soon as possible, 
preferably within 2 weeks, and preferably prior to initiation of another therapy.
For subjects to be considered lost to follow-up, reasonable attempts must be made to obtain 
information on the subject's final status.  At a minimum, 2 telephone calls must be made, and 1 certified 
letter must be sent and documented in the subject's source documentation.
If a subject withdraws from study follow up or withdraws permission for the collection of their personal 
data, the study staff may still use available public records to obtain information about survival status 
only, as appropriate per local regulations.
In the event a subject withdraws consent from the clinical study, biomarker research will continue 
unless the subject explicitly requests analysis to be stopped.  When AbbVie is informed the subject has 
withdrawn and no longer wishes biomarker samples research to continue, samples will not be analyzed,
and no new biomarker analysis data will be collected for the withdrawn subject or added to the existing 
data or database(s).  A subject may withdraw consent for biomarker research at any time and remain in 
the clinical study.  Data generated from clinical study and/or biomarker research, before subject 
withdrawal of consent, will remain part of the study results.
Page 34 of 145
 


  
STUDY M20-371  |  Version 4.0  |  EudraCT 2021-002869-18
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
5.7 Study Drug
ABBV-154 and matching placebo will be manufactured and provided by AbbVie (Table 2).  Each dose will 
be administered by a healthcare professional either intravenously or as a subcutaneous injection in the 
abdomen or thigh.  Blinded study drug will be administered at approximately the same time of day, 
preferably between 7 am and 11 am, beginning at the Baseline Visit (Week 0, Day 1) of each period.  The 
study drug can be taken with or without food.  Refer to Section 6.2 for required observation periods 
after each IV and SC doses.  The last dose of study drug will be given at Week 38 of the Maintenance 
Period.
ABBV-154 and matching placebo syringes and vials will be packaged in cartons with quantities sufficient 
to accommodate the study design.  Each pre-filled syringe (PFS), vial, and carton will be labeled per local 
requirements and these labels must remain affixed to the syringe, vial, and carton.  Each kit will contain 
a unique kit number.  This kit number is assigned to a subject via Interactive response technology (IRT) 
and encodes the appropriate study drug to be dispensed at the subject's corresponding study visit.  
Study drug must not be dispensed without contacting the IRT system.  Site staff will complete all blank 
spaces on the label before dispensing study drug for the subject.  Study drug is for investigational use 
only and will only be used for the conduct of this study.
Upon completion of or discontinuation from study treatment, all original study drug units (containing 
unused study drugs) will be returned to the sponsor (or designee) or destroyed on site.  All return or 
destruction procedures will be according to instructions from the sponsor and according to local 
regulations following completion of drug/device accountability procedures.
Table 2.
Investigational Product
Study Drug
Dosage Form
Strength
Route of 
Administration
Manufacturer
ABBV-154
Lyophilized powder for 
solution for infusion in vials
50 mg (50 mg/mL when 
reconstituted with 1.2 mL of 
sterile water for injection)
Intravenous
AbbVie
Matching 
Placebo
Lyophilized powder for 
solution for infusion in vials
N/A
Intravenous
AbbVie
ABBV-154
0.8 mL, 1.5 mL solution for 
injection in PFS
100mg/ml
SC Injection in 
abdomen or thigh
AbbVie
Matching 
Placebo
Placebo solution for 
injection in PFS
N/A
SC Injection in 
abdomen or thigh
AbbVie
N/A = not applicable; PFS = prefilled syringe; SC = subcutaneous
5.8 Randomization/Drug Assignment
All subjects will be assigned a unique identification number by the IRT at the screening visit.  For 
subjects who rescreen, the screening number assigned by the IRT at the initial screening visit should be 
used.  The IRT will assign a randomization number that will encode the subject's treatment group 
Page 35 of 145
 


  
STUDY M20-371  |  Version 4.0  |  EudraCT 2021-002869-18
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
assignment according to the randomization schedule.  Randomization into the 12-Week Double-Blind 
Induction Period, the 12-Week Double-Blind Re-Induction Period, and the 40-Week Double-Blind 
Maintenance Period is outlined in Section 4.1.
Randomization at Baseline (Week 0, Day 1) of the Induction Period will be stratified as follows:

Baseline glucocorticoid use (yes/no);

Endoscopic disease severity (SES-CD < 15; SES-CD ≥15); and

Inadequate response to adalimumab (yes/no).
Re-randomization at Baseline (Week 0, Day 1) of the Re-Induction Period will be stratified as follows:

Treatment group in the Induction Period
Re-randomization at Baseline (Week 0, Day 1) of the Maintenance Period will be stratified as follows:

Achievement of CR100 at entry of the Maintenance Period (Week 12 of the 
Induction/Re-Induction Period)

For subjects who enter from the Induction Period:  ABBV-154 dose groups in the Induction 
Period

For subjects who enter from Re-Induction Period:

ABBV-154 dose groups in the Re-Induction Period

Induction Period treatment:  ABBV-154 (any dose group) versus placebo
All AbbVie personnel with direct oversight of the conduct and management of the trial (with the 
exception of AbbVie Drug Supply Management Team) will remain blinded to each subject's treatment-
assignment in each study period until the Primary Analysis of the respective period.  The investigator, 
study site personnel, and the subject will remain blinded to each subject's assignment throughout the 
study.  Selected AbbVie personnel may be unblinded to treatment assignment after an interim analysis 
to support regulatory interactions; details will be included in the interim unblinding plan (IUP).  To 
maintain the blind, the ABBV-154 and placebo PFS and vials provided for the study will be identical in 
appearance.  The IRT will provide access to unblinded subject treatment information in the case of a 
medical emergency.
In the event of a medical emergency that requires unblinding of the study drug assignment, the 
investigator is requested to contact the AbbVie TA MD prior to breaking the blind.  However, if an 
urgent therapeutic intervention is necessary which warrants breaking the blind prior to contacting the 
AbbVie TA MD, the investigator can directly access the IRT system to break the blind without AbbVie 
notification or agreement.  Unblinding is available in the IRT system via the Subject Unblinding by Site 
transaction, which is available only to the investigator.  If the IRT system is unavailable, unblinding may 
occur by contacting the technical support of the IRT vendor via either phone (preferred) or email 
(support@endpointclinical.com).  For country-specific phone numbers, please see the following website: 
http://www.endpointclinical.com/help-desk.  In the event the blind is broken before notification to the 
AbbVie TA MD, the AbbVie TA MD should be notified within 24 hours of the blind being broken.  The 
Page 36 of 145
 


  
STUDY M20-371  |  Version 4.0  |  EudraCT 2021-002869-18
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
date and reason that the blind was broken must be conveyed to AbbVie and recorded on appropriate 
eCRF.
5.9 Protocol Deviations
AbbVie does not allow intentional/prospective deviations from the protocol except when necessary to 
eliminate an immediate hazard to study subjects.  The investigator is responsible for complying with all 
protocol requirements, written instructions, and applicable laws regarding protocol deviations.  If a 
protocol deviation occurs (or is identified including those that may be due to the COVID-19 pandemic), 
the investigator is responsible for notifying independent ethics committee (IEC)/independent review 
board (IRB), regulatory authorities (as applicable), and AbbVie.
5.10 Data Monitoring Committee
An external DMC will be established to safeguard the interest of trial subjects by assessing the safety of 
the interventions during the trial as well as for monitoring of the integrity and interpretability of the 
trial.  A separate DMC charter will be prepared outside of the protocol and will further describe the roles 
and responsibilities of the DMC members, frequency, and scope of the data reviews, and expectations 
for blinded communications.  The first DMC review of unblinded safety data will occur after 
approximately 30 subjects (6 subjects/treatment group) have reached Week 8.  The DMC will be 
requested to review the unblinded safety data at an earlier timepoint if the sponsor notes on blinded 
data review any of the following:

Fatal or life-threatening event considered to have a reasonable possibility of being related to 
study drug by the investigator or sponsor;

Serious hypersensitivity reaction considered to have a reasonable possibility of being related to 
study drug by the investigator or sponsor;

Higher than anticipated rate of serious infection as compared to the rate for serious infection in 
subjects with CD receiving adalimumab in the Humira clinical trials.
5.11 Glucocorticoid Adjudication Committee
An independent adjudication committee will be established to adjudicate systemic glucocorticoid AEs.  A 
separate charter will be prepared outside of the protocol and will describe the roles and responsibilities 
of the adjudication committee members, frequency of data reviews, and expectations for blinded 
communications.
Page 37 of 145
 


  
STUDY M20-371  |  Version 4.0  |  EudraCT 2021-002869-18
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
6 SAFETY CONSIDERATIONS
6.1 Complaints and Adverse Events
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.  Complaints associated with any component of this investigational 
product must be reported to AbbVie.
Product Complaint
A product complaint is any complaint 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 (e.g., printing illegible), missing components/product, device damage or not 
working properly, or packaging issues.
Product complaints concerning the investigational product and/or device must be reported to AbbVie 
within 24 hours of the study site's knowledge of the event.
Product complaints occurring during the study will be followed up to a satisfactory conclusion.
Medical Complaints/ Adverse Events and Serious Adverse Events
An adverse event is defined as any untoward medical occurrence in a subject or clinical investigation 
subject administered a pharmaceutical product and which does not necessarily have a causal 
relationship with this treatment.  An adverse event can therefore be any unfavorable and unintended 
sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use 
of a medicinal (investigational) product, whether or not the event is considered causally related to the 
use of the product.
Such an event can result from use of the drug as stipulated in the protocol or labeling, as well as from 
"special situations" such as accidental or intentional overdose, medication error, occupational or 
accidental exposure, off-label use, drug abuse, drug misuse, or drug withdrawal, all which must be 
reported whether associated with an adverse event or not.  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, meets protocol-specific criteria (see Section 6.2 regarding toxicity management), and/or if 
the investigator considers them to be adverse events.
The investigators will monitor each subject for clinical and laboratory evidence of adverse events on a 
routine basis throughout the study.  All adverse events will be followed to a satisfactory conclusion.
Page 38 of 145
 




  
STUDY M20-371  |  Version 4.0  |  EudraCT 2021-002869-18
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
If an adverse event, whether associated with study drug or not, meets any of the following criteria, it is 
to be reported to AbbVie clinical pharmacovigilance or contract research organization (as appropriate) 
as a serious adverse event within 24 hours of the site being made aware of the serious adverse event 
(refer to Section 4.2 of the Operations Manual for reporting details and contact information):
Death of Subject
An event that results in the death of a subject.
Life-Threatening
An event that, in the opinion of the investigator, 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.
All adverse events reported from the time of study drug administration until 70 days after 
discontinuation of study drug administration will be collected, whether solicited or spontaneously 
reported by the subject.  In addition, study procedure-related serious and nonserious adverse events 
will be collected from the time the subject signs the study-specific informed consent.
The following definitions will be used for Serious Adverse Reactions (SARs) and Suspected Unexpected 
Serious Adverse Reaction (SUSAR):
Page 40 of 145
 


  
STUDY M20-371  |  Version 4.0  |  EudraCT 2021-002869-18
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
SAR
Defined as all noxious and unintended responses to an Investigational Medicinal 
Product (IMP) related to any dose administered that result in an SAE as defined 
above.
SUSAR
Refers to individual SAE case reports from clinical trials where a causal 
relationship between the SAE and the IMP was suspected by either the sponsor 
or the investigator, is unexpected (not listed in the applicable Reference Safety 
Information), and meets one of the above serious criteria.
AbbVie will be responsible for Suspected Unexpected Serious Adverse Reactions (SUSAR) reporting for 
the Investigational Medicinal Product (IMP) in accordance with global and local requirements.
Adverse events will be monitored throughout the study to identify any safety topics of interest that may 
indicate a trend or risk to subjects.
Safety Topics of Interest
The following Safety Topics of Interest will be monitored during the study:

Serious infections;

Opportunistic infections;

Active TB;

Hypersensitivity reactions;

Serious allergic reactions;

Malignancies;

Systemic glucocorticoid side effects;

Adrenal insufficiency;

Iatrogenic Cushing's syndrome.
Adverse Event Severity and Relationship to Study Drug
The investigator will rate the severity of each adverse event according to the National Cancer Institute 
Common Terminology Criteria for Adverse Events (NCI CTCAE Version 5.0), which can be accessed at:  
https://ctep.cancer.gov/protocoldevelopment/electronic_applications/docs/CTCAE_v5_Quick_Referenc
e_5x7.pdf.
The investigator will use the following definitions to assess the relationship of the adverse event to the 
use of study drug:
Page 41 of 145
 


  
STUDY M20-371  |  Version 4.0  |  EudraCT 2021-002869-18
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
Reasonable Possibility
After consideration of factors including timing of the event, biologic 
plausibility, clinical judgment, and potential alternative causes, there is 
sufficient evidence (information) to suggest a causal relationship.
No Reasonable Possibility
After consideration of factors including timing of the event, biologic 
plausibility, clinical judgment, and potential alternative causes, there is 
insufficient evidence (information) to suggest a causal relationship.
Pregnancy
While not an adverse event, pregnancy in a study subject must be reported to AbbVie within 24 hours 
after the site becomes aware of the pregnancy.  Subjects who become pregnant during the study must 
be discontinued (Section 5.5).  If a pregnancy occurs in a study subject or in the partner of a study 
subject, information regarding the pregnancy and the outcome will be collected.
In the event of pregnancy occurring in a subject's partner during the study, written informed consent 
from the partner must be obtained prior to collection of any such information.  AbbVie will provide a 
separate consent form for this purpose.  Pregnancy in a subject's partner will be collected from the date 
of the first dose through 70 days following the last dose of study drug.
The pregnancy outcome of an elective or spontaneous abortion, stillbirth or congenital anomaly is 
considered a SAE and must be reported to AbbVie within 24 hours after the site becomes aware of the 
event.
6.2 Toxicity Management
For subjects who discontinue study drug but continue study participation and are on standard of care 
therapies, these toxicity management requirements do not apply (including alerts from the central 
laboratory) and any intolerability to standard of care therapies should be managed by the prescribing 
physician.
Elective surgery is not allowed during the Induction and Re-Induction Periods of the study.  If the subject 
undergoes elective surgery, study drug should be interrupted at least 2 weeks prior to the planned 
surgery. If the subject must undergo emergency surgery, the study drug should be interrupted at the 
time of the surgery.  After surgery, allow reintroduction of study drug once the physician has examined 
the surgical site and determined that it has healed and there is no sign of infection.
Management of Hypersensitivity and Serious Allergic Reactions
Subjects should be closely monitored and assessed for the development of signs and symptoms of 
hypersensitivity reactions, including anaphylaxis.  For any hypersensitivity reaction, appropriate therapy 
should be instituted per standard of care.  Study drug should be discontinued if a subject develops 
anaphylaxis.
Emergency medical equipment and personnel trained to evaluate and manage infusion-related reactions 
and anaphylaxis should be immediately available during dosing and the post-treatment observational 
period.
Page 42 of 145
 


  
STUDY M20-371  |  Version 4.0  |  EudraCT 2021-002869-18
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
In the event of a suspected systemic postdose hypersensitivity reaction, if the clinical situation allows, 
every effort should be made to obtain a serum sample within 2 hours but no later than 6 hours from 
symptom onset for additional blood tests specified in the Operations Manual, Section 3.19 
Hypersensitivity Testing.
IV infusion of study drug for loading dose:  The following infusion times should be applied dependent 
on the subject's individual body weight:
Subject's Body Weight
Infusion Time
≥54 kg
60 min
44 to 53 kg
75 min
36 to 43 kg
90 min
27 to 35 kg
120 min
Subjects should be closely monitored for signs and symptoms of hypersensitivity reactions, including 
anaphylaxis.
Study drug should be interrupted and appropriate therapy instituted if an infusion reaction occurs.  If 
symptoms are mild (e.g., flushing without respiratory symptoms or vital sign changes) and quickly 
improve with cessation of the infusion, re-starting study drug at a lower infusion rate may be an option.  
Study drug should be discontinued if a subject develops a severe infusion reaction or anaphylaxis (refer 
to definitions of severity of Infusion Related Reaction given below and in CTCAE v5.0).

Mild to Moderate:  transient symptoms, responds to minimal intervention (e.g., antihistamines, 
IV fluids)

Severe:  prolonged symptoms, multiple organ systems affected, life-threatening
Subjects should be observed for at least 30 minutes after infusion.  If new onset of symptoms occurs 
during or after completion of the infusion, subjects should receive standard of care or remain at the site 
for further observation until symptoms have resolved.  Subjects with mild to moderate infusion 
reactions who are able to complete the IV infusion should be observed for at least 1 hour after infusion.  
These subjects may receive additional IV infusion loading doses during the Re-Induction Period and for 
ABBV-154 Rescue Therapy during the Maintenance Period (as applicable per the protocol) at the 
discretion of the investigator.
SC injection of study drug:  After SC study drug injection, a 15- to 30-minute post-injection 
observational period is required.
Management of Serious Infections
Subjects should be closely monitored for the development of signs and symptoms of infection during 
and after treatment with study drug.  Study drug should be interrupted if a subject develops a serious 
infection or a serious opportunistic infection.  A subject who develops a new infection during treatment 
with study drug should undergo prompt diagnostic testing appropriate for an immunocompromised 
subject.  As appropriate, antimicrobial therapy should be initiated, and the subject should be closely 
Page 43 of 145
 


  
STUDY M20-371  |  Version 4.0  |  EudraCT 2021-002869-18
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
monitored.  Study drug may be restarted once the infection has been successfully treated.  Subjects who 
develop active TB must be permanently discontinued from study drug.
Management of Malignancy
Subjects who develop high-grade dysplasia of the gastrointestinal tract or malignancy other than 
localized NMSC or carcinoma in-situ of the cervix must be discontinued from the study drug.  
Information including histopathological results should be queried for the confirmation of the diagnosis.
Management of Demyelinating Disease
Subjects must be discontinued from study drug with new onset of symptoms and/or radiographic 
evidence of central nervous system demyelinating disease (including multiple sclerosis), optic neuritis, 
or peripheral demyelinating disease (including Guillain Barré syndrome).
Management of Hypertension
Subjects should be closely monitored for the development of hypertension.  Investigators should 
consider stopping the study drug if hypertension is not successfully controlled under standard of care.
Management of Hyperglycemia
Subjects should be closely monitored for the development of hyperglycemia.  Investigators should 
manage the hyperglycemia with appropriate standard of care.
Management of Glucocorticoid Induced Adrenal Insufficiency
Subjects should be closely monitored for signs and symptoms of adrenal insufficiency (e.g., nausea, 
vomiting, lightheadedness, pale skin, unexplained weight loss, low blood pressure, electrolyte 
abnormalities [e.g., hyponatremia < 135 mmol/L, hyperkalemia > 5.5 mmol/L]) and if adrenal 
insufficiency is suspected, further assessment and management should follow local standard of care, 
which may include measuring cortisol levels and/or ACTH stimulation testing at a local laboratory.  
Glucocorticoid therapy with physiologic doses should be considered.  After withdrawal of glucocorticoid 
therapy, adrenal insufficiency may persist for months; therefore, glucocorticoid therapy should be 
considered in any situation of stress (e.g., serious infection) occurring or in the months following 
withdrawal of study drug.
Management of COVID-19
Subjects should be closely monitored for COVID-19.  Study drug should be interrupted if a subject has a 
confirmed diagnosis of COVID-19.  Consider the interruption of study drug in subjects with signs and/or 
symptoms and suspicion of COVID-19.
Management of Select Laboratory Abnormalities
For any given laboratory abnormality, the investigator should assess the subject, apply the standard of 
care for medical evaluation and treatment following any local guidelines.  Specific toxicity management 
guidelines for selected abnormal laboratory values are described in Table 3, and may require a 
supplemental eCRF to be completed.  For subjects with ongoing laboratory abnormalities which require 
data entry into an eCRF, an additional eCRF related to subsequent laboratory abnormalities is only 
required if the subject has relevant changes in history (e.g., new onset signs or symptoms) or laboratory 
Page 44 of 145
 


  
STUDY M20-371  |  Version 4.0  |  EudraCT 2021-002869-18
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
values which have returned to normal reference range or its Baseline value followed by subsequent 
laboratory abnormalities meeting toxicity guidelines (considered a new event).  All abnormal laboratory 
tests that are considered clinically significant by the investigator will be followed to a satisfactory 
resolution.  If a repeat test is required, the repeat testing must occur as soon as possible.
Page 45 of 145
 


  
STUDY M20-371  |  Version 4.0  |  EudraCT 2021-002869-18
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
Table 3.
Specific Toxicity Management Guidelines for Abnormal Laboratory Values
Laboratory 
Parameter
Toxicity Management Guideline
ANC
If confirmed < 1000/µL by repeat testing with new sample, interrupt study drug dosing 
until ANC value returns to normal reference range or its BL value.
Discontinue study drug if confirmed < 500/µL by repeat testing with new sample.
ALC
If confirmed < 500/µL by repeat testing with new sample, interrupt study drug dosing 
until ALC returns to normal reference range or its BL value.
Platelet count
If confirmed < 50,000/µL by repeat testing with new sample, interrupt study drug dosing 
until platelet count returns to normal reference range or its BL value.
AST or ALT
Interrupt study drug if confirmed ALT or AST > 3 × ULN by repeat testing with new sample 
and either a total bilirubin > 2 × ULN or an INR > 1.5.
A separate blood sample for INR testing will be needed to measure INR at the time of 
repeat testing for ALT or AST.  A repeat test of INR is not needed for determination if 
above toxicity management criteria are met.

Interrupt study drug if confirmed ALT or AST > 3 × ULN by repeat testing with new 
sample along with appearance of fatigue, nausea, vomiting, right upper quadrant 
pain or tenderness, fever, rash, and/or eosinophilia (> 5% increase from BL).

Interrupt study drug if confirmed ALT or AST > 5 × ULN by repeat testing with new 
sample for more than 2 weeks.

If ALT or AST > 8 × ULN, interrupt study drug immediately, confirm by repeat testing 
with a new sample, and contact the TA MD.
Subjects with HBc Ab+ (irrespective of HBs Ab status) or HBs Ab+ (without a history of 
vaccination) and negative HBV DNA PCR testing at Screening who develop the following 
laboratory findings should have HBV DNA PCR testing performed within one week (based 
on initial elevated value):

ALT> 5 × ULN OR

ALT or AST > 3 × ULN if an alternative cause is not readily identified.

Note:  A separate blood sample for HBV DNA PCR testing will be needed at the 
time of repeat testing for ALT or AST.
A positive result for HBV DNA PCR testing will require immediate interruption of study 
drug (unless not acceptable by local practices) and a hepatologist consultation should 
occur within 1 week for recommendation regarding subsequent treatment.
Subjects who meet any of the above criteria should be evaluated for an alternative 
etiology of the ALT or AST elevation and managed as medically appropriate.  If applicable, 
the alternative etiology should be documented in the eCRF.  If ALT or AST values return to 
the normal reference range or its BL value, study drug may be restarted.  If restarting 
study drug, documentation should include reason that rechallenge is expected to be safe.  
If after clinically appropriate evaluation, no alternative etiology for ALT or AST elevation is 
found or the ALT or AST elevation has not resolved or is not trending down toward 
normal, the subject should be discontinued from study drug.
For any confirmed ALT or AST elevations > 3 ULN, complete the appropriate supplemental 
hepatic eCRF(s).
Page 46 of 145
 


  
STUDY M20-371  |  Version 4.0  |  EudraCT 2021-002869-18
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
Laboratory 
Parameter
Toxicity Management Guideline
Serum Creatinine
If serum creatinine is > 1.5 × the BL value and > ULN, repeat the test for serum creatinine 
(with subject in an euvolemic state) to confirm the results.  If the results of the repeat 
testing still meet this criterion, then interrupt study drug and re-start study drug once 
serum creatinine returns to ≤ 1.5 × BL value and ≤ ULN.  For the above serum creatinine 
elevation scenario, complete the appropriate supplemental renal eCRF(s).
ALC = Absolute lymphocyte counts; ALT = alanine aminotransferase; ANC = absolute neutrophil count; AST = aspartate 
aminotransferase; BL = baseline; DNA = deoxyribonucleic acid; eCRF = electronic case report form; HBc Ab = Hepatitis B core 
antibody; HBs Ab = Hepatitis B surface antibody; HBV = hepatitis B virus; INR = international normalized ratio; PCR = polymerase 
chain reaction; TA MD = Therapeutic Area Medical Director; ULN = upper limit of normal
Note:
Baseline value refers to the Baseline (Week 0, Day 1) visit of the Induction Period.
7 STATISTICAL METHODS & DETERMINATION OF SAMPLE SIZE
7.1 Statistical and Analytical Plans
The statistical methods provided in this protocol are focused on primary and secondary analyses.  
Complete and specific details of the statistical analysis will be described in the Statistical Analysis Plan 
(SAP).
The Primary Analysis for the Induction Period and Re-Induction Period will be conducted after all 
subjects have completed Week 12 of the Induction Period and Re-Induction Period, respectively, or 
prematurely discontinued from the study.
A final analysis will be conducted after all subjects have completed Week 40 of the Maintenance Period 
plus the 70-day Follow-up Visit or prematurely discontinued from the study.
7.2 Definition for Analysis Populations
The following populations will be used for analyses:

Intent-to-treat (ITT) Population:  The ITT Population includes all subjects who were randomized 
and received at least 1 dose of study drug.  The ITT Population will be analyzed as randomized 
(i.e., according to the randomized treatment assignment).

ITT1 Population:  The subset of the ITT population who were randomized and received at 
least one dose of study drug in the Induction Period.  The ITT1 Population is the primary 
analysis population for efficacy analyses of the Induction Period.

ITT2 Population:  The subset of the ITT population who were randomized and received at 
least one dose of study drug in the Re-Induction Period.  The ITT2 Population is the analysis 
population for efficacy analyses of the Re-Induction Period.

ITT3 Population:  The subset of the ITT population who received ABBV-154 for 12 weeks 
before entering the Maintenance Period (including subjects were randomized to ABBV-154 
Page 47 of 145
 


  
STUDY M20-371  |  Version 4.0  |  EudraCT 2021-002869-18
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
dose groups in the Induction Period and entered the Maintenance Period from the Induction 
Period OR were randomized to the placebo group in the Induction Period and entered the 
Maintenance Period from the Re-Induction Period) AND were randomized and received at 
least one dose of study drug in the Maintenance Period.  The ITT3 Population is the primary 
analysis population for efficacy analyses of the Maintenance Period.

Safety Population:  The Safety Population includes all subjects who received at least 1 dose of 
study drug.  The Safety Population will be analyzed as treated (i.e., according to the actual 
treatment received).
7.3 Handling Potential Intercurrent Events for the Primary and 
Secondary Endpoints
Primary endpoint/Categorical secondary endpoints in the Induction Period:

Subjects will be considered as not achieving response after receiving medications that could 
confound the assessment of efficacy, including protocol-defined Rescue Therapy for the 
Induction Period, initiating glucocorticoids after Baseline, failing to complete glucocorticoid 
taper by Week 6, and initiating/increasing doses of aminosalicylates or immunomodulators.

Available data collected after study drug discontinuation will be used until the initiation of 
medications that could confound the assessment of efficacy.
Categorical secondary endpoints in the Maintenance Period:

Subjects will be considered as not achieving response after receiving medications that could 
confound the assessment of efficacy, including protocol-defined Rescue Therapy for the 
Maintenance Period.

Available data collected after study drug discontinuation will be used until the initiation of 
medications that could confound the assessment of efficacy.
7.4 Statistical Analyses for Efficacy
Efficacy analysis will be performed by the subject's randomized treatment group.  All statistical tests will 
be performed at a 2-sided significance level of 0.1.  A 95% confidence interval (CI) of the treatment 
difference between each ABBV-154 dose and placebo will be provided.  The actual value of stratification 
factors will be used in the analysis.
For categorical variables, pairwise comparison will be made between each ABBV-154 dose and placebo 
using the Cochran-Mantel-Haenszel (CMH) test, adjusting for stratification factors (Section 5.8).  
Non-responder imputation incorporating multiple imputation (NRI-MI) to handle COVID-19 will be the 
primary approach to handle missing data for categorical endpoints.
For continuous variables, the comparison will be made between each ABBV-154 dose and placebo based 
on the mixed effect model repeated measures (MMRM) adjusting for visit, interaction between 
Page 48 of 145
 


  
STUDY M20-371  |  Version 4.0  |  EudraCT 2021-002869-18
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
treatment and visit, actual values of stratification factors as fixed factors, and baseline value (of the 
Induction Period) as a covariate.  The MMRM will be the primary approach to handle missing values for 
continuous endpoints.
Summary and Analysis of the Primary Endpoint
The primary endpoint is the achievement of endoscopic response at Week 12 of the Induction Period.  
Comparison of the primary endpoint will be made between each ABBV-154 dose and placebo using CMH 
test adjusting for stratification factors.  The points and CI estimate of the treatment difference for each 
ABBV-154 dose versus placebo will be presented.
One supplementary analysis for the primary endpoint is to test a prespecified set of dose-response 
models among ABBV-154 dose groups and the placebo group at Week 12 of the Induction Period using 
the Multiple Comparison Procedure – Modeling (MCP-Mod) method.
Summary and Analysis of Secondary Endpoints
Analysis of secondary efficacy endpoints is described above.
Summary and Analysis of Additional Efficacy Endpoints
Analysis of additional efficacy endpoints is described above.
Subgroup Analysis for Efficacy
To evaluate the consistency of efficacy across demographic and other baseline characteristics, the 
following subgroup analysis will be performed on the primary endpoint: Baseline glucocorticoid use (yes; 
no)

Endoscopic disease severity (SES-CD < 15; SES-CD ≥ 15)

Inadequate response to adalimumab (yes; no)

Sex (female; male)

Race (White; Non-white)

Age (≥18 years to < 40 years, ≥40 years to < 65 years, ≥ 65 years)

Inadequate response to prior anti-TNF biologics (yes; no)
If deemed necessary, additional subgroup analyses may be performed with details described in the SAP.
7.5 Statistical Analysis for Pharmacokinetics and Immunogenicity
Concentrations of conjugated ADC, total antibody, and free payload (A-1677770) will be summarized at 
each time point using descriptive statistics.
Population PK analyses combining the data from this study and other studies may be performed and 
reported outside of the clinical study report.
Page 49 of 145
 


  
STUDY M20-371  |  Version 4.0  |  EudraCT 2021-002869-18
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
Anti-drug antibody (ADA) and nAb incidence and ADA titer values will be summarized for each group 
using descriptive statistics.
7.6 Statistical Analysis of Biomarker Data
Analyses may be conducted on biomarker data for the purpose of identification of prognostic, 
predictive, surrogate, and pharmacodynamic biomarkers associated with efficacy or safety.  The 
association of biomarkers to the efficacy or safety endpoints may be explored for each biomarker one at 
a time, and also for combinations of biomarkers via some multivariate predictive modeling approaches.  
Analyses may be reported outside of the clinical study report.
7.7 Statistical Analyses for Safety
All safety analyses will be performed using the Safety Population, as defined in Section 7.2.  Data will be 
analyzed based on the actual treatment subjects received.  TEAEs, laboratory assessments, and vital 
signs will be summarized.  Details will be described in the SAP.
A TEAE for the Safety Population is defined as an AE newly occurred or worsened after the first dose of 
study drug and within 70 days after the last dose of study drug.  The number and percentage of subjects 
experiencing TEAEs will be tabulated using the Medical Dictionary for Regulatory Activities (MedDRA) 
system organ class and preferred term, by severity, and by relationship to the study drug as assessed by 
the investigator.  Summaries (including percentages and events per 100 patient years) of SAEs, deaths, 
and AEs leading to discontinuation will also be provided.  Procedure related pretreatment AEs will be 
summarized separately.
For selected laboratory parameters, a listing of all subjects with any laboratory value that is Grade ≥3 of 
NCI CTCAE will be provided.  Mean change in laboratory and vital signs variables will be summarized.  
Additional details for the safety analysis will be provided in the SAP.
7.8 Interim Analysis
An interim analysis will be performed when approximately 66% of the subjects (35 subjects per group) 
have reached Week 12 of the Induction Period or have prematurely discontinued the study to inform 
the development of future studies.
An additional interim analysis in the Maintenance Period might be performed to inform the 
development of future studies.  The results from this analysis will not impact the conduct of the current 
study.
Selected AbbVie personnel may be unblinded to treatment assignment after an interim analysis to 
support regulatory interactions and future development decisions; details will be included in the IUP.
7.9 Overall Type I Error Control
Overall Type I error control is not planned in this Phase 2 study.
Page 50 of 145
 


  
STUDY M20-371  |  Version 4.0  |  EudraCT 2021-002869-18
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
7.10 Sample Size Determination
Approximately 265 subjects will be randomized into 4 ABBV-154 treatment groups or placebo in a 
1:1:1:1:1 ratio at Baseline of the Induction Period.  There will be a cap of approximately 30% the total 
enrolled of subjects who had prior use of adalimumab treatment.
A total of 265 subjects (53 subjects per group) will provide more than 90% power to detect a 26% 
difference in endoscopic response rates at Week 12 of the Induction Period between an ABBV-154 
group and the placebo group (assuming the response rate in the placebo group is 11%) using a 
Chi-square test at α level of 0.1 (two-sided).
Under the response rate assumptions for ABBV-154 and placebo in the Induction Period, it is expected 
that at least 40 subjects per group will be available for the analysis of endoscopic response at Week 40 
in the Maintenance Period.  This sample size (40 subjects per group) will provide more than 80% power 
to detect a 26% difference between ABBV-154 and placebo (assuming the response rate in the placebo 
group at Week 40 of the Maintenance Period is 11%) using a Chi-square test at α level of 0.1 
(two-sided).
The total sample size (planned as 265 subjects) for the Induction Period may be adjusted to ensure at 
least 40 subjects per group for the analysis in the Maintenance Period.
8 ETHICS
8.1 Independent Ethics Committee/Institutional Review Board 
(IEC/IRB)
The protocol, informed consent form(s), recruitment materials, and all subject materials will be 
submitted to the IEC/IRB for review and approval.  Approval of both the protocol and the informed 
consent form(s) must be obtained before any subject is enrolled.  Any amendment to the protocol will 
require review and approval by the IEC/IRB before the changes are implemented to the study.  In 
addition, all changes to the consent form(s) will be IEC/IRB approved.
8.2 Ethical Conduct of the Study
The study will be conducted in accordance with the protocol, Operations Manual, International Council 
for Harmonisation (ICH) guidelines, applicable regulations, and guidelines governing clinical study 
conduct and the ethical principles that have their origin in the Declaration of Helsinki.  Responsibilities of 
the investigator are specified in Appendix B.  Investigators should notify AbbVie if any urgent safety 
measures are taken to protect the subjects against any immediate hazard.
In the event a significant disaster/crisis (e.g., epidemic/pandemic, natural disaster, conflict/combat) 
occurs leading to difficulties in performing protocol-specified procedures, AbbVie may engage with 
study site personnel in efforts to ensure the safety of subjects, maintain protocol compliance, and 
minimize risks to the integrity of the study while trying to best manage subject continuity of care.  This 
may include alternative methods for assessments (e.g., phone contacts or virtual site visits), alternative 
Page 51 of 145
 


  
STUDY M20-371  |  Version 4.0  |  EudraCT 2021-002869-18
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
locations for data collection (e.g., use of a local lab instead of a central lab), and shipping investigational 
product and/or supplies direct to subjects to ensure continuity of treatment where allowed.  In all cases, 
these alternative measures must be allowed by local regulations and permitted by IRB/IEC.
8.3 Subject Confidentiality
For the protection of personal data, AbbVie has developed a robust security program focused on due 
diligence in design, managed change, and information security governance.  Information Security 
policies govern the Information Security functions including identity and access management, 
operations, infrastructure, application, and third-party security requirements.  The risk-based AbbVie 
Data Classification Tool dictates the level of scrutiny and control required for the relevant activities per 
AbbVie's Information Security policies taking into account the sensitivity of the data.
Before subject's data is shared with AbbVie, the study investigator and staff will replace any information 
that could directly identify a subject (such as name, address, and contact information) with an assigned 
numerical study identifier or "code" which AbbVie cannot link to that subject's identity in order to 
protect the confidentiality of the data.
AbbVie has a data protection impact assessment program to ensure and document the appropriate 
controls and safeguards stated above are in place for clinical trial data that it controls and maintains and 
these processing activities respect privacy of clinical trial subjects. AbbVie also maintains robust security 
incident response policies and procedures, including requirements for the containment of any data 
related incidents, the mitigation measures where needed, and notification to authorities or affected
individuals where required.
9 SOURCE DOCUMENTS AND CASE REPORT FORM 
COMPLETION
The investigator is responsible for ensuring the accuracy, completeness, legibility, and timeliness of the 
data reported.  All source documents should be attributable, legible, contemporaneous, original, 
accurate, and complete to ensure accurate interpretation of data.  Clinical site monitoring is conducted 
to ensure that the rights and well-being of human subjects are protected, that the reported trial data 
are accurate, complete, and verifiable, and that the conduct of the trial is in compliance with the 
currently approved protocol, ICH Good Clinical Practice (GCP), and applicable local regulatory 
requirement(s).  During states of emergency or pandemic situations, remote data review/verification 
may be employed if allowed by the local regulatory authority, IRB/IEC, and the study site.
10
DATA QUALITY ASSURANCE
AbbVie will ensure that the clinical trial is conducted with a quality management system that will define 
quality tolerance limits in order to ensure human subject protection and reliability of study results.  Data 
will be generated, documented, and reported in compliance with the protocol, ICH GCP, and applicable 
regulatory requirements.
Page 52 of 145
 


  
STUDY M20-371  |  Version 4.0  |  EudraCT 2021-002869-18
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
11
START AND COMPLETION OF THE STUDY
The start-of-study is defined as the date of the first site activated.
The end-of-study is defined as the date of the last subject's last visit or the actual date of follow-up 
contact, whichever is later; and in the last country where the study was conducted.
12
REFERENCES
1.
Hanauer SB, Feagan BG, Lichtenstein GR, et al. Maintenance infliximab for Crohn's disease: the 
ACCENT I randomised trial. Lancet. 2002;359(9317):1541-9.
2.
Hanauer SB, Sandborn WJ, Rutgeerts P, et al. Human anti-tumor necrosis factor monoclonal 
antibody (adalimumab) in Crohn's disease: the CLASSIC-I trial. Gastroenterology. 2006;130(2):323-
33; quiz 591.
3.
Sandborn WJ, Feagan BG, Stoinov S, et al. Certolizumab pegol for the treatment of Crohn's disease. 
N Engl J Med. 2007;357(3):228-38.
4.
Colombel JF, Sandborn WJ, Rutgeerts P, et al. Adalimumab for maintenance of clinical response and 
remission in patients with Crohn's disease: the CHARM trial. Gastroenterology. 2007;132(1):52-65.
5.
Sandborn WJ, Rutgeerts P, Enns R, et al. Adalimumab induction therapy for Crohn disease previously 
treated with infliximab: a randomized trial. Ann Intern Med. 2007;146(12):829-38.
6.
Gordon JP, McEwan PC, Maguire A, et al. Characterizing unmet medical need and the potential role 
of new biologic treatment options in patients with ulcerative colitis and Crohn's disease: a 
systematic review and clinician surveys. Eur J Gastroenterol Hepatol. 2015;27(7):804-12.
7.
Ben-Horin S, Kopylov U, Chowers Y. Optimizing anti-TNF treatments in inflammatory bowel disease. 
Autoimmun Rev. 2014;13(1):24-30.
8.
Gutierrez A, Rodriguez-Lago I. How to Optimize Treatment With Ustekinumab in Inflammatory 
Bowel Disease: Lessons Learned From Clinical Trials and Real-World Data. Front Med (Lausanne). 
2021;8:640813.
9.
Shmidt E, Kochhar G, Hartke J, et al. Predictors and Management of Loss of Response to 
Vedolizumab in Inflammatory Bowel Disease. Inflamm Bowel Dis. 2018;24(11):2461-7.
10. Ma C, Moran GW, Benchimol EI, et al. Surgical Rates for Crohn's Disease are Decreasing: A 
Population-Based Time Trend Analysis and Validation Study. Am J Gastroenterol. 
2017;112(12):1840-8.
11. Lichtenstein GR, Abreu MT, Cohen R, et al. American Gastroenterological Association Institute 
medical position statement on corticosteroids, immunomodulators, and infliximab in inflammatory 
bowel disease. Gastroenterology. 2006;130(3):935-9.
Page 53 of 145
 


  
STUDY M20-371  |  Version 4.0  |  EudraCT 2021-002869-18
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
12. Faubion WA, Jr., Loftus EV, Jr., Harmsen WS, et al. The natural history of corticosteroid therapy for 
inflammatory bowel disease: a population-based study. Gastroenterology. 2001;121(2):255-60.
13. Munkholm P, Langholz E, Davidsen M, et al. Frequency of glucocorticoid resistance and dependency 
in Crohn's disease. Gut. 1994;35(3):360-2.
14. Chhaya V, Saxena S, Cecil E, et al. Steroid dependency and trends in prescribing for inflammatory 
bowel disease - a 20-year national population-based study. Aliment Pharmacol Ther. 
2016;44(5):482-94.
15. Bokemeyer B, Ghiani M, Fuchs A, et al. Indicators of active disease and steroid dependency in 
patients with inflammatory bowel diseases not treated with biologics in a German real-world-
setting. Int J Colorectal Dis. 2020;35(8):1587-98.
16. Schacke H, Docke WD, Asadullah K. Mechanisms involved in the side effects of glucocorticoids. 
Pharmacol Ther. 2002;96(1):23-43.
17. Daperno M, D'Haens G, Van Assche G, et al. Development and validation of a new, simplified 
endoscopic activity score for Crohn's disease: the SES-CD. Gastrointest Endosc. 2004;60(4):505-12.
18. Higgins PD, Schwartz M, Mapili J, et al. Patient defined dichotomous end points for remission and 
clinical improvement in ulcerative colitis. Gut. 2005;54(6):782-8.
19. Irvine EJ, Feagan B, Rochon J, et al. Quality of life: a valid and reliable measure of therapeutic 
efficacy in the treatment of inflammatory bowel disease. Canadian Crohn's Relapse Prevention Trial 
Study Group. Gastroenterology. 1994;106(2):287-96.
20. Chandran V, Bhella S, Schentag C, et al. Functional assessment of chronic illness therapy-fatigue 
scale is valid in patients with psoriatic arthritis. Ann Rheum Dis. 2007;66(7):936-9.
21. Ware JE, Jr. SF-36 health survey update. Spine (Phila Pa 1976). 2000;25(24):3130-9.
22. Ware JE, Jr., Sherbourne CD. The MOS 36-item short-form health survey (SF-36). I. Conceptual 
framework and item selection. Med Care. 1992;30(6):473-83.
Page 54 of 145
 


  
STUDY M20-371  |  Version 4.0  |  EudraCT 2021-002869-18
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
APPENDIX A. STUDY-SPECIFIC ABBREVIATIONS AND TERMS
Abbreviation
Definition
6-MP
6-mercaptopurine
Ab
antibody
ACTH
adrenocorticotropic hormone
ADA
anti-drug antibody
ADC
antibody-drug conjugate
AE
adverse event
ALC
absolute lymphocyte count
ALT
alanine aminotransferase
ANC
absolute neutrophil count
AP
abdominal pain
AST
aspartate aminotransferase
AZA
azathioprine
BCG
bacilli Calmette-Guérin
BL
Baseline
BMD
bone mineral density
BMI
body mass index
C diff
Clostridium difficile
CD
Crohn's Disease
CDAI
Crohn's Disease Activity Index
CI
confidence interval
CMH
Cochran-Mantel-Haenszel
CO2
carbon dioxide
COPD
chronic obstructive pulmonary disease
COVID-19
Coronavirus disease-2019
CR100
A decrease in CDAI ≥100 points from Baseline
CR70
A decrease in CDAI ≥70 points from Baseline
CTCAE
Common Terminology Criteria for Adverse Events
CTX
C-terminal telopeptide
CXR
chest x-ray
CYP3A
cytochrome P450 3A
DB
double-blind
Page 55 of 145
 


  
STUDY M20-371  |  Version 4.0  |  EudraCT 2021-002869-18
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
Abbreviation
Definition
DMC
data monitoring committee
DNA
deoxyribonucleic acid
DSUR
Development Safety Update Report
DXA
dual-energy x-ray absorptiometry
E4W
every 4 weeks
ECG
electrocardiogram
eCRF
electronic case report form
EDC
electronic data capture
eGFR
Estimate glomerular filtration rate
EIM
extra intestinal manifestation
EOW
every other week
ePRO
electronic patient-reported outcome
FACIT-F
Functional Assessment of Chronic Illness Therapy-Fatigue
FCP
fecal calprotectin
FSH
follicle stimulating hormone
GCP
good clinical practice
GRM
glucocorticoid receptor modulator
HbA1c
Hemoglobin A1c
HBc
Hepatitis B core
HBc Ab
Hepatitis B core antibody
HBs
Hepatitis B surface
HBs Ab
Hepatitis B surface antibody
HBs Ag
hepatis B surface antigen
HBV
hepatitis B virus
Hct
hematocrit
HCV
hepatitis C virus
HCV Ab
HCV antibody
HDL
high density lipoprotein
HIV
human immunodeficiency virus
HIV
human immunodeficiency virus
HPA
Hypothalamic-pituitary-adrenal axis
hs-CRP
high-sensitivity C-reactive protein
Page 56 of 145
 


  
STUDY M20-371  |  Version 4.0  |  EudraCT 2021-002869-18
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
Abbreviation
Definition
IBDQ
Inflammatory Bowel Disease Questionnaire
ICH
International Council for Harmonisation
IEC
independent ethics committee
IgE
Immunoglobulin E
IgG
immunoglobulin G
IMP
Investigational Medicinal Product
IRB
institutional review board
IRT
Interactive response technology
ITT
Intent-to-treat
IU
International units
IUP
interim unblinding plan
IV
Intravenous (ly)
JAK
Janus kinase
LCMS
Liquid chromatography-mass spectrometry
LDL
low density lipoprotein
MACE
major adverse cardiac event
MCP-Mod
Multiple Comparison Procedure - Modeling
MedDRA
Medical Dictionary for Regulatory Activities
MMRM
Mixed Effect Model Repeated Measurements
mRNA
messenger RNA
MTX
methotrexate
N/A
not applicable
nAb
neutralizing antibody
NCI
National Cancer Institute
NMSC
nonmelanoma skin cancer
NRI-MI
Non-responder imputation incorporating multiple imputation
NSAID
nonsteroidal anti-inflammatory drug
OC
osteocalcin
P1NP
procollagen type 1 N-propeptide
PBMC
peripheral blood mononuclear cells
PCR
polymerase chain reaction
PD
pharmacodynamics
Page 57 of 145
 


  
STUDY M20-371  |  Version 4.0  |  EudraCT 2021-002869-18
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
Abbreviation
Definition
PFS
pre-filled syringe
PGIC-CD+
Patient Global Impression of Change – Crohn's Disease+
PGIS-CD+
Patient Global Impression of Severity – Crohn's Disease+
PK
pharmacokinetic(s)
PPD
purified protein derivative
PPE
Personal Protective Equipment
PRO
Patient-reported outcome
PRO
patient-reported outcome
RNA
ribonucleic acid
RSI
reference safety information
SAE
serious adverse event
SAP
statistical analysis plan
SAR
serious adverse reaction
SARS-CoV-2
severe acute respiratory syndrome coronavirus 2
SC
subcutaneous
SES-CD
Simplified Endoscopic Score for CD
SF
stool frequency
SF-36
short form-36
SUSAR
suspected unexpected serious adverse reaction
TA MD
Therapeutic Area Medical Director
TB
tuberculosis
TEAE
treatment-emergent adverse event
TNF
tumor necrosis factor
TSH
thyroid stimulating hormone
ULN
upper limit of normal
Wk
week
Page 58 of 145
 


  
STUDY M20-371  |  Version 4.0  |  EudraCT 2021-002869-18
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
APPENDIX B. RESPONSIBILITIES OF THE INVESTIGATOR
Protocol M20-371:  A Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety and Efficacy of 
ABBV-154 in Subjects with Moderately to Severely Active Crohn's Disease (CD):  AIM-CD
Protocol Date:  20 December 2022
Clinical research studies sponsored by AbbVie are subject to the International Council for Harmonisation of 
Technical Requirements for Pharmaceuticals for Human Use (ICH) Good Clinical Practices (GCP) and local 
regulations and guidelines governing the study at the site location.  In signing the Investigator Agreement, the 
investigator is agreeing to the following:
1.
Conducting the study in accordance with ICH GCP, the applicable regulatory requirements, current 
protocol and operations manual, and making changes to a protocol only after notifying AbbVie and the 
appropriate Institutional Review Board (IRB)/Independent Ethics Committee (IEC), except when necessary 
to protect the subject from immediate harm.
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., 
IEC or IRB) review and approval of the protocol and its amendments.
4.
Reporting complaints that occur in the course of the investigation(s) to AbbVie.
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 
protocol and all of its amendments.
9.
Reporting promptly (within 1 calendar day to AbbVie, the ethics committees/institutional review boards 
(as required) and other appropriate individuals (e.g., coordinating investigator, institution director):

Any departure from relevant clinical trial law or regulation, GCP, or the trial protocol that 
has the potential to affect the following:

Rights, safety, physical or mental integrity of the subjects in the clinical trial.

Scientific value of the clinical trial, reliability or robustness of data generated.
10. Providing direct access to source data documents for study-related monitoring, audits, IEC/IRB review, 
and regulatory inspection(s).
Signature of Principal Investigator
Date
Name of Principal Investigator (printed or typed)
Page 59 of 145
 


  
STUDY M20-371  |  Version 4.0  |  EudraCT 2021-002869-18
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
APPENDIX C. LIST OF PROTOCOL SIGNATORIES
Name
Title
Functional Area
Study Project Manager
Clinical Study Leadership
Principal Medical Writer
Medical Writing
Global Development Lead
Therapeutic Area - Immunology
Medical Director
Therapeutic Area Medical Director
Statistics Director
Statistics
Director
Clinical Pharmacology & Pharmacometrics
Page 60 of 145
 


  
STUDY M20-371  |  Version 4.0  |  EudraCT 2021-002869-18
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
APPENDIX D. ACTIVITY SCHEDULE
The following table shows the required activities across the 12-Week Induction Period, the 12-Week 
Re-Induction Period, and the 40-Week Maintenance Period subject encounters.  The individual activities 
are described in detail in the Operations Manual (Appendix F).  Allowed modifications due to state of 
emergency or pandemic situations are detailed in the Operations Manual.
Page 61 of 145
 
























  
STUDY M20-371  |  Version 4.0  |  EudraCT 2021-002869-18
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
APPENDIX E. PROTOCOL SUMMARY OF CHANGES
Previous Protocol Versions
Protocol
Date
Version 1.0
29 August 2021
Version 2.0
11 October 2021
Version 1.1 (German Only)
28 January 2022
Version 2.1 (Belgium Only)
11 February 2022
Version 2.2 (German Only)
25 February 2022
Version 3.0
18 May 2022
The purpose of this version is to update the following sections:
Protocol

Synopsis, Investigational Plan and Section 4.1, removed text that subjects who complete the 
study have an option to continue in a Long-Term Extension study.
Rationale:  The clinical development plan was updated to remove the Long-Term Extension 
study.

Synopsis, Key Eligibility Criteria updated to include a subject history of inadequate response or 
intolerance to risankizumab.
Rationale:  Risankizumab has recently received regulatory approval for the treatment of CD.  
Updated language to include subjects with a history of inadequate response to or intolerance of 
treatment with risankizumab.

Section 2.2, added a statement about the benefit-risk ratio of the device which is used in the 
study and clarified that the device is non-investigational.
Rationale:  To clarify the pre-filled syringe used in the study is a non-investigational device.

Section 3.1, updated the wording for the population attribute of the estimand description.
Rationale:  To align with the evolving guidelines of the estimand framework, defining the 
population attribute as the target population instead of the analysis population.  This update 
does not affect either the trial conduct or the statistical analysis.

Section 5.1, updated eligibility criterion #11 to state that subjects must not have a disease
history of > 3 bowel resections due to progression of CD.
Rationale: To change the maximum number of prior bowel resections from ≥3 to >3 and specify 
the criterion applies only to prior bowel resections related to progression of CD in order to 
exclude subjects for whom limited benefit from study drug is anticipated. This change will allow 
the results of the study to be more generalizable to clinical practice, is aligned with another 
clinical development program, and does not affect the benefit-risk for subject participation.
Page 73 of 145
 


  
STUDY M20-371  |  Version 4.0  |  EudraCT 2021-002869-18
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.

Section 5.1, updated eligibility criterion #12 to add subject history of at least one 8-week 
induction regimen of risankizumab (600 mg IV at Weeks 0, 4, and 8).
Rationale: Risankizumab has recently received regulatory approval for the treatment of CD.  
Language updated to include subjects with a history of inadequate response to or intolerance of 
treatment with risankizumab and specify the minimum induction regimen required.

Section 5.1, for eligibility criterion #28 added that subjects on azathioprine, 6-mercaptopurine, 
or methotrexate must have discontinued these therapies or be on a stable dose for ≥ 30 days 
prior to Baseline.
Rationale: To clarify the washout period for the immunosuppressants azathioprine, 
6-mercaptopurine, or methotrexate is ≥ 30 days prior to Baseline for a subject who has 
previously used and discontinued these therapies.

Section 5.1, for eligibility criterion #30 added that the washout period required prior to the 
Baseline Visit is ≥ 12 weeks for risankizumab.
Rationale: To specify a washout period for subjects treated with risankizumab.

Section 5.1, for eligibility criterion #31 added that the eligibility criterion applies to any drug that 
was investigational at the time of protocol approval regardless of regulatory approval status of 
the drug for the treatment of CD.
Rationale: To clarify this criterion applies to all drugs which were investigational for the 
treatment of CD at the time of protocol approval as additional drugs may receive regulatory 
approval for the treatment of CD during the conduct of this clinical trial.

Section 5.1, for eligibility criterion #32 and Section 5.4, added language to specify that live 
vaccines with replicating potential are prohibited and that the JYNNEOS vaccine for prevention 
of monkeypox disease is permitted.
Rationale: Monkeypox disease has emerged as a health issue during the conduct of the study.  
Administration of all live vaccines with replicating potential remains as prohibited during the 
study.  However, administration of the JYNNEOS vaccine is allowed.  The JYNNEOS vaccine, is 
used for the prevention of smallpox and monkeypox.  It is a third-generation vaccine based on a 
live, attenuated non-replicating orthopoxvirus, Modified Vaccinia Ankara (MVA).  MVA is a live 
virus that does not have the ability to replicate efficiently in humans and therefore can be given 
to immune compromised patients without the risk of developing a monkeypox infection.

Section 5.3, added Risankizumab to the prohibited medications.
Rationale: Risankizumab has recently received regulatory approval for the treatment of CD.

Section 5.6, added "at least 70 days" to align with the 70-Day Follow-up Visit requirement as 
correctly described in Section 2.5 of the Operations Manual.
Rationale: To add text which had been erroneously left out.

Section 5.7, added language to detail study drug return or destruction procedures following 
subject completion or discontinuation from study treatment.
Rationale:  Language added per EU CT regulatory guidance.

Section 7.3, updated the handling strategy for the intercurrent event of study drug 
discontinuation.
Page 74 of 145
 


  
STUDY M20-371  |  Version 4.0  |  EudraCT 2021-002869-18
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
Rationale: To clarify the handling strategy after switching to other medications for CD following 
study drug discontinuation, since the use of other medications may confound assessments 
collected afterwards.

Section 8.3, updated language to outline AbbVie information security policies and 
de-identification of subject health information.
Rationale:  To clarify details for subject confidentiality and protection of personal data to align 
with EU CT regulatory guidance.

Appendix C, updated protocol signatories.
Rationale:  To update due to study personnel changes for this protocol amendment.
Operations Manual

Section 1 and Section 4.2, removed the safety team contact number.
Rationale: The phone number previously provided will no longer be supported.

Section 2.3 and Section 3.14, for Maintenance Period Week 40, updated footnote "e" and 
respective section text to remove guidance for the assessment of endoscopy before the 
administration of the first dose of study drug in the Long-Term Extension study.
Rationale: The Long-Term Extension study was removed from the investigational plan.

Section 3.15, added for subject with an endoscopy that was performed before the Screening 
visit, no intestinal biopsy sample(s) are required to be collected at Screening.
Rationale: To clarify that intestinal biopsies will not be collected at Screening if the endoscopy 
is not performed during the screening period.

Section 4.2, updated language that the sponsor will be responsible for SUSAR reporting for the 
IMP in accordance with global and local requirements (not Directive 2001/20/EC).
Rationale:  To clarify SUSAR reporting per EU CT regulatory guidance.
Page 75 of 145
 

SAP_001.pdf: 
ABBV-154
M20-371 – Statistical Analysis Plan
Version 2.0 – 10 February 2023
1
Statistical Analysis Plan for Study M20-371
A Randomized, Double-Blind, Placebo-Controlled 
Study to Evaluate the Safety and Efficacy of 
ABBV-154 in Subjects with Moderately to Severely 
Active Crohn's Disease (CD):  AIM-CD
Date:  10 February 2023
Version 2.0
 
NCT05068284


ABBV-154
M20-371 – Statistical Analysis Plan
Version 2.0 – 10 February 2023
2
Table of Contents
1.0
Introduction...........................................................................5
2.0
Study Design and Objectives ................................................5
2.1
Objectives, Hypotheses and Estimands................................................... 5
2.2
Study Design Overview.......................................................................... 7
2.3
Treatment Assignment and Blinding..................................................... 11
2.4
Sample Size Determination .................................................................. 12
3.0
Endpoints.............................................................................12
3.1
Primary Endpoint ................................................................................. 13
3.2
Secondary Endpoints............................................................................ 14
3.3
Other Efficacy Endpoints ..................................................................... 14
3.4
Safety Endpoints .................................................................................. 15
4.0
Analysis Populations ...........................................................15
5.0
Subject Disposition..............................................................18
6.0
Study Drug Duration and Compliance ..............................18
7.0
Demographics, Baseline Characteristics, Medical 
History, and Prior/Concomitant Medications ...................19
7.1
Demographics and Baseline Characteristics.......................................... 19
7.2
Medical History.................................................................................... 22
7.3
Prior and Concomitant Medications...................................................... 22
8.0
Handling of Potential Intercurrent Events for the 
Primary and Key Secondary Endpoints ............................23
8.1
Intercurrent Event 1 (IE1): CD-Related Confounding Medications ....... 23
8.2
Intercurrent Event 2 (IE2): Premature Discontinuation of Study 
Drug..................................................................................................... 24
9.0
Efficacy Analyses.................................................................25
9.1
General Considerations......................................................................... 25
9.2
Handling of Missing Data..................................................................... 27
9.2.1
Categorical Endpoints .......................................................................... 28
9.2.2
Continuous Endpoints .......................................................................... 30
9.2.3
Additional Analyses ............................................................................. 30
9.3
Primary Efficacy Endpoint and Analyses.............................................. 31
 


ABBV-154
M20-371 – Statistical Analysis Plan
Version 2.0 – 10 February 2023
3
9.3.1
Primary Efficacy Endpoint ................................................................... 31
9.3.2
Primary Analysis of Primary Efficacy Endpoint ................................... 31
9.3.3
Sensitivity and Supplementary Analyses of the Primary Efficacy 
Endpoint............................................................................................... 32
9.4
Secondary Efficacy Analyses ............................................................... 33
9.4.1
Main Analyses of Ranked Secondary Efficacy Endpoints..................... 33
9.4.2
Sensitivity and Supplementary Analyses for Secondary Efficacy 
Endpoints ............................................................................................. 35
9.5
Additional Efficacy Analyses ............................................................... 35
9.6
Dose-Response Modeling for ABBV-154............................................. 35
9.7
Efficacy Subgroup Analyses................................................................. 37
9.8
Efficacy Analyses for ABBV-154 Rescue Therapy............................... 38
10.0
Safety Analyses....................................................................38
10.1
General Considerations......................................................................... 38
10.2
Adverse Events..................................................................................... 39
10.2.1
Treatment-Emergent Adverse Events.................................................... 40
10.2.2
Adverse Event Overview...................................................................... 41
10.2.3
Treatment-Emergent Adverse Events by SOC and/or PT...................... 42
10.2.4
Treatment-Emergent Adverse Events per Patient-Years of 
Exposure .............................................................................................. 43
10.2.5
SAEs (Including Deaths) and Adverse Events Leading to Study 
Drug Discontinuation ........................................................................... 44
10.2.6
Adverse Events of Special Interest........................................................ 44
10.3
Analysis of Laboratory Data................................................................. 44
10.4
Analysis of Vital Signs......................................................................... 46
11.0
Interim Analyses..................................................................47
11.1
Data Monitoring Committee................................................................. 48
12.0
Overall Type-I Error Control.............................................48
13.0
Version History ...................................................................48
14.0
References............................................................................51
 


ABBV-154
M20-371 – Statistical Analysis Plan
Version 2.0 – 10 February 2023
4
List of Tables
Table 1.
Summary of the Estimand Attributes of the Primary Efficacy 
Endpoint............................................................................................... 32
Table 2.
Summary of the Estimand Attributes of the Key Secondary 
Efficacy Endpoints ............................................................................... 34
Table 3.
Candidate Models................................................................................. 36
Table 4.
Subgroups for Efficacy Analysis .......................................................... 38
Table 5.
SAP Version History Summary ............................................................ 48
List of Figures
Figure 1.
Study M20-371 Study Schematic.......................................................... 10
List of Appendices
Appendix A.
Protocol Deviations .............................................................................. 52
Appendix B.
Crohn's Disease Activity Index (CDAI)................................................ 53
Appendix C.
Simple Endoscopic Score – CD (SES-CD) ........................................... 57
Appendix D.
Patient Reported Outcomes Questionnaires Descriptions ...................... 58
Appendix E.
Random Seeds...................................................................................... 62
Appendix F.
Crohn's Disease Location Per SES-CD................................................. 63
Appendix G.
List of Adverse Events of Special Interest (AESIs)............................... 64
 


ABBV-154
M20-371 – Statistical Analysis Plan
Version 2.0 – 10 February 2023
5
1.0
Introduction
This Statistical Analysis Plan (SAP) describes the statistical analyses for ABBV-154 
Study M20-371, "A Randomized, Double-Blind, Placebo-Controlled Study to Evaluate 
the Safety and Efficacy of ABBV-154 in Subjects with Moderately to Severely Active 
Crohn's Disease (CD):  AIM-CD."
The pharmacokinetic/pharmacodynamic endpoints, pharmacogenetic endpoints, selected 
biomarkers, Patient Global Impression of Change –- Crohn's Disease+ (PGIC-CD+) and 
Change from Baseline in Patient Global Impression of Severity –- Crohn's Disease+ 
(PGIS-CD+) for variable validation purposes, and data collected in the Wearable Device 
Substudy will be analyzed separately and are not described in this SAP.
The SAP will not be updated in case of administrative changes or amendments to the 
protocol unless the changes impact the analysis.
Unless noted otherwise, all analyses will be performed using SAS Version 9.4 
(SAS Institute Inc., Cary, NC  27513) or later under the UNIX operating system.
2.0
Study Design and Objectives
2.1
Objectives, Hypotheses and Estimands
The objective of Study M20-371 is to assess the efficacy, safety, and tolerability of 
ABBV-154 in comparison with placebo in subjects with moderately to severely active 
Crohn's Disease (CD) who had inadequate response to or were intolerant of prior 
biologics.
Primary Efficacy Objective
The primary efficacy objective of Study M20-371 is to demonstrate a higher rate of 
endoscopic response after 12 weeks of treatment with ABBV-154 when compared to 
placebo in subjects with moderately to severely active CD who had inadequate response 
to or were intolerant of prior biologics.
 


ABBV-154
M20-371 – Statistical Analysis Plan
Version 2.0 – 10 February 2023
6
Hypothesis corresponding to the primary efficacy objective is:
●
The proportion of subjects achieving endoscopic response (see Section 3.0) 
with ABBV-154 is greater than that with placebo at Week 12 in the Induction 
Period.
The estimand corresponding to the primary efficacy objectives are defined as follows:
●
The difference in the proportion of subjects that achieve endoscopic response 
at Week 12 without use of concomitant medication that could confound the 
efficacy (see Section 8.1) and regardless of premature discontinuation of study 
drug (see Section 8.2), in each of the ABBV-154 dose groups compared with 
the placebo group in subjects with moderately to severely active CD who had 
inadequate response to or were intolerant of prior biologics.
Secondary Efficacy Objectives
The secondary efficacy objectives of the Study M20-371 are to demonstrate greater 
efficacy with ABBV-154 treatment when compared with placebo treatment with respect 
to the secondary endpoints specified in Section 3.2, in subjects with moderately to 
severely active CD who had inadequate response to or were intolerant of prior biologics.
Hypotheses corresponding to the ranked secondary efficacy objectives are:  for each of the 
secondary endpoints specified in Section 3.2, greater proportion of subjects with 
improvement is achieved with ABBV-154 when compared to that of placebo.
The estimands corresponding to the secondary efficacy objectives are defined for each of 
the secondary endpoints as follows:
●
For endpoints in the Induction Period:  The difference in the proportion of 
subjects that achieve response/remission without use of concomitant 
medication that could confound the efficacy (see Section 8.1) and regardless of 
premature discontinuation of study drug (see Section 8.2), in each of the 
ABBV154 dose groups compared with the placebo group in subjects with 
 


ABBV-154
M20-371 – Statistical Analysis Plan
Version 2.0 – 10 February 2023
7
moderately to severely active CD who had inadequate response to or were 
intolerant of prior biologics.
●
For endpoints in the Maintenance Period:  The difference in the proportion of 
subjects that achieve response/remission without use concomitant medication 
that could confound the efficacy (see Section 8.1) and regardless of premature 
discontinuation of study drug (see Section 8.2), in each of the ABBV154 dose 
groups compared with the placebo group in subjects with moderately to 
severely active CD who had inadequate response to or were intolerant of prior 
biologics and achieved response after the 12-week induction treatment with 
ABBV-154.
2.2
Study Design Overview
This is a randomized, double-blind, placebo-controlled Phase 2b study to assess the 
safety, tolerability, PK, PD, immunogenicity, and efficacy of ABBV-154 in subjects with 
moderately to severely active CD who had inadequate response to or were intolerant of 
prior biologics.  The enrollment for subjects with prior adalimumab use is capped at 
approximately 30% of the total enrolled subjects.  The study comprises 3 periods:  a 
12-Week Double-Blind Placebo-Controlled Induction Period, a 12-Week Double-Blind 
Re-Induction Period (for subjects considered to be clinical non-responders and endoscopic 
non-responders), and a 40-Week Double-Blind Placebo-Controlled Maintenance Period.
At the Baseline Visit of the Induction Period, approximately 265 subjects will be 
randomized in a 1:1:1:1:1 ratio into 4 ABBV-154 treatment groups or placebo:
●
Induction Group 1:  Loading dose of 150 mg IV at Week 0, followed by 80 mg 
subcutaneous (SC) at Week 2 and every other week (EOW);
●
Induction Group 2:  Loading dose of 300 mg IV at Week 0, followed by 
230 mg SC at Week 2 and EOW;
●
Induction Group 3:  Loading dose of 600 mg IV at Week 0, followed by 
530 mg SC at Week 2 and EOW;
●
Induction Group 4:  Loading dose of 600 mg IV at Week 0, followed by 
530 mg SC at Weeks 4 and 8, and placebo at Weeks 2, 6, and 10; and
 


ABBV-154
M20-371 – Statistical Analysis Plan
Version 2.0 – 10 February 2023
8
●
Induction Group 5:  Matching placebo (IV and SC).
At Week 12 of the Induction Period, subjects achieving clinical response, defined as a 
decrease in Crohn's Disease Activity Index (CDAI) ≥100 points from Baseline (CR100) 
AND/OR endoscopic response defined as a decrease in SES-CD > 50% from Baseline (or 
for subjects with isolated ileal disease and a Baseline SES-CD of 4, at least a 2-point 
reduction from Baseline) (per local read) will receive treatment in the 40-Week 
Maintenance Period as follows:
●
Induction Group 1:  Re-randomized in a 1:1 ratio to receive ABBV-154 80 mg 
SC EOW or matching placebo;
●
Induction Groups 2 to 4:  Re-randomized in a 1:1:1 ratio to receive ABBV-154 
80 mg SC EOW, ABBV-154 230 mg SC EOW, or matching placebo;
●
Induction Group 5:  ABBV-154 80 mg SC EOW.
At Week 12 of the Induction Period, subjects who are categorized as clinical non-
responders and endoscopic non-responders (per local read) will be re-randomized into the 
Re-Induction Period.  Subjects who receive Rescue Therapy, fail to complete 
glucocorticoid tapering by Week 6, or increase doses of or initiate treatment with 
aminosalicylates or immunomodulators in the Induction Period will be considered non-
responders, regardless of clinical response or endoscopic response (per local read) per the 
definitions above at Week 12 and will be re-randomized in a 1:1 ratio into 2 ABBV-154 
treatment groups in the 12-Week Re-Induction Period as follows:
●
Re-Induction Group 1:  Loading dose of 300 mg IV at Week 0, followed by 
230 mg SC at Week 2 and EOW;
●
Re-Induction Group 2:  Loading dose of 600 mg IV at Week 0, followed by 
530 mg SC at Week 2 and EOW.
Subjects who achieve clinical response AND/OR endoscopic response (per local read) at 
Week 12 of the Re-Induction Period will be re-randomized into the Maintenance Period as 
described above for subjects achieving clinical response AND/OR endoscopic response 
 


ABBV-154
M20-371 – Statistical Analysis Plan
Version 2.0 – 10 February 2023
9
(per local read) after Week 12 of the Induction Period.  Subjects who do not achieve either 
clinical response or endoscopic response (per local read) after the Re-Induction Period 
will be discontinued and will have a follow-up visit scheduled 70 days after last study 
drug administration.
To determine endoscopic response status for re-randomization into the Maintenance 
Period, the SES-CD score per local read at Week 12 of the Induction/Re-Induction Period 
and the SES-CD score per central read at Baseline will be used.  In the case of missing 
data where either clinical response or endoscopic response cannot be determined, subjects 
will be considered non-responders for the re-randomization criteria evaluation.
Subjects who have an inadequate response at or after Week 4 in the Maintenance Period 
will be eligible to receive Rescue Therapy with a single dose of ABBV-154 600 mg IV 
followed by ABBV-154 230 mg SC EOW. Subjects who have received rescue therapy 
with ABBV-154 for at least 4 weeks and who continue to demonstrate inadequate 
response may receive additional Rescue Therapy with oral glucocorticoids, 
aminosalicylates, or immunomodulators.
The last dose of study drug will be given at Week 38 of the Maintenance Period.  A 
follow-up visit will be scheduled 70 days after the last study drug administration.
The Primary Analysis for the Induction Period and Re-Induction Period will be performed 
after all subjects have either completed Week 12 of the Induction Period and Re-Induction 
Period, respectively, or prematurely discontinued study participation.  The final analysis 
will be conducted after all subjects have completed Week 40 of the Maintenance Period 
plus the 70-day Follow-up Visit or prematurely discontinued study participation. To 
ensure the integrity of the trial, the study sites and subjects will remain blinded until the 
final database lock is completed.
The schematics of the overall study design are shown in Figure 1.
 


ABBV-154
M20-371 – Statistical Analysis Plan
Version 2.0 – 10 February 2023
10
Figure 1.
Study M20-371 Study Schematic
DB = double-blind; EOW = every other week; IV = intravenous; SC = subcutaneous; Wk = week
*
Responders are defined as clinical responders AND/OR endoscopic responders (per local read), and non-
responders are defined as clinical non-responders AND endoscopic non-responders (per local read).  Clinical 
responder is defined at Week 12 of the Induction Period or Re-Induction Period as a decrease in CDAI ≥ 100 points 
from Baseline (CR100).  Endoscopic responder is defined at Week 12 of the Induction Period or Re-Induction 
Period as a decrease in SES-CD > 50% from Baseline (or for subjects with isolated ileal disease and a Baseline 
SES-CD of 4, at least a 2-point reduction from Baseline) (per local read).  In the case of missing data where clinical 
response and endoscopic response cannot be calculated, subjects will be considered as non-responders for the re-
randomization criteria evaluation.
**
Only subjects who are considered to be clinical non-responders and endoscopic non-responders (per local read) at 
Week 12 of the Induction Period will be re randomized into the Re-Induction Period.
*** Subjects with inadequate response at/after Week 4 of the Maintenance Period will be eligible to receive Rescue 
Therapy consisting of ABBV-154 600 mg IV followed by ABBV-154 230 mg SC EOW.
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
  
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 


ABBV-154
M20-371 – Statistical Analysis Plan
Version 2.0 – 10 February 2023
11
2.3
Treatment Assignment and Blinding
All subjects will be assigned a unique identification number by the Interactive response 
technology (IRT) at the screening visit.  For subjects who rescreen, the screening number 
assigned by the IRT at the initial screening visit should be used.  The IRT will assign a 
randomization number that will encode the subject's treatment group assignment 
according to the randomization schedule.  Randomization into the 12-Week Double-Blind 
Induction Period, the 12-Week Double-Blind Re-Induction Period, and the 40-Week 
Double-Blind Maintenance Period is outlined in Section 2.2.
Randomization at Baseline (Week 0, Day 1) of the Induction Period will be stratified as 
follows:
●
Baseline glucocorticoid use (yes/no);
●
Endoscopic disease severity (SES-CD < 15; SES CD ≥ 15); and
●
Inadequate response to adalimumab (yes/no).
Re-randomization at Baseline (Week 0, Day 1) of the Re-Induction Period will be 
stratified as follows:
●
Treatment group in the Induction Period
Re-randomization at Baseline (Week 0, Day 1) of the Maintenance Period will be 
stratified as follows:
●
Achievement of CR100 at entry of the Maintenance Period (Week 12 of the 
Induction/Re Induction Period)
●
For subjects who enter from the Induction Period:  ABBV-154 dose groups in 
the Induction Period
●
For subjects who enter from Re-Induction Period:
○
ABBV-154 dose groups in the Re-Induction Period
○
Induction Period treatment:  ABBV-154 (any dose group) versus placebo.
 


ABBV-154
M20-371 – Statistical Analysis Plan
Version 2.0 – 10 February 2023
12
2.4
Sample Size Determination
Approximately 265 subjects will be randomized into 4 ABBV-154 treatment groups or 
placebo in a 1:1:1:1:1 ratio at Baseline of the Induction Period.  There will be a cap of 
approximately 30% the total enrolled of subjects who had prior use of adalimumab 
treatment.
A total of 265 subjects (53 subjects per group) will provide more than 90% power to 
detect a 26% difference in endoscopic response rates at Week 12 of the Induction Period 
between an ABBV-154 group and the placebo group (assuming the response rate in the 
placebo group is 11%) using a Chi square test at α level of 0.1 (two-sided).
Under the response rate assumptions for ABBV-154 and placebo in the Induction Period, 
it is expected that at least 40 subjects per group will be available for the analysis of 
endoscopic response at Week 40 in the Maintenance Period.  This sample size 
(40 subjects per group) will provide more than 80% power to detect a 26% difference 
between ABBV-154 and placebo (assuming the response rate in the placebo group at 
Week 40 of the Maintenance Period is 11%) using a Chi-square test at α level of 0.1 
(two sided).
The total sample size (planned as 265 subjects) for the Induction Period may be adjusted 
to ensure at least 40 subjects per group for the analysis in the Maintenance Period.
3.0
Endpoints
In Section 3.0, please note 
1.
"Baseline" refers to the last available measurement on/before Baseline [Week 0, 
Day 1] of the Induction Period;
2.
All endoscopic endpoints will be scored by central review; 
3.
Average daily liquid or very soft stool frequency (SF) and average daily 
abdominal pain (AP) score (SF/AP)-based efficacy endpoints will be analyzed in 
 


ABBV-154
M20-371 – Statistical Analysis Plan
Version 2.0 – 10 February 2023
13
the subset of subjects with an average daily liquid or very soft SF score ≥ 4 and/or 
average daily AP score ≥2 at Baseline.
The following endpoint definitions apply to the efficacy variables described below:
●
Endoscopic response:  decrease in Simple Endoscopic Score for Crohn's 
Disease (SES-CD) > 50% from Baseline (or for subjects with isolated ileal 
disease and a Baseline SES-CD of 4, at least a 2-point reduction from 
Baseline)
●
Clinical remission per CDAI:  CDAI < 150
●
Clinical response (CR100):  a decrease of CDAI ≥ 100 points from Baseline 
●
Clinical remission per SF/AP:  average daily very soft or liquid SF ≤ 2.8 and 
not worse than Baseline AND average daily AP score ≤ 1 and not worse than 
Baseline 
●
Enhanced Clinical Response per SF/AP:  ≥ 60% decrease in average daily 
very soft or liquid SF and/or ≥ 35% decrease in average daily AP score and 
both not worse than baseline, and/or clinical remission per SF/AP
●
Clinical response per SF/AP:  ≥ 30% decrease in average daily liquid or very 
soft SF and/or ≥ 30% decrease in average daily AP score and both not worse 
than Baseline 
●
Endoscopic remission:  SES-CD ≤ 4 and at least a 2-point reduction versus 
Baseline and no subscore > 1 in any individual variable 
●
Ulcer-free endoscopy:  SES-CD ulcerated surface subscore of 0 in subjects 
with SES-CD ulcerated surface subscore ≥ 1 at Baseline 
Details of CDAI, SES-CD and patient-reported outcome (PRO) questionnaires are 
provided in Appendix B, Appendix C and Appendix D respectively.
3.1
Primary Endpoint
The primary endpoint is:
●
Achievement of endoscopic response at Week 12 in the Induction Period.
 


ABBV-154
M20-371 – Statistical Analysis Plan
Version 2.0 – 10 February 2023
14
3.2
Secondary Endpoints
The following endpoints will be included as secondary endpoints:
●Achievement of:
○
clinical remission per CDAI at Week 12 in the Induction Period.
○
clinical remission per SF/AP at Week 12 in the Induction Period.
○
endoscopic response at Week 40 in the Maintenance Period.
○
clinical remission per CDAI at Week 40 in the Maintenance Period.
○
clinical remission per SF/AP at Week 40 in the Maintenance Period.
3.3
Other Efficacy Endpoints
In the Induction/Re-Induction/Maintenance Periods, the additional endpoints below will 
be analyzed at timepoints specified in the schedule of events table of the protocol, except 
for those specified as primary/secondary endpoints above.
●
Achievement of clinical remission per CDAI.
●
Achievement of clinical remission per SF/AP.
●
Achievement of CR100.
●
Achievement of clinical response per SF/AP.
●
Achievement of enhanced clinical response per SF/AP.
●
Achievement of endoscopic remission.
●
Change from Baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) 
total score.
●
Change from Baseline in Functional Assessment of Chronic Illness Therapy-
Fatigue (FACIT-F).
●
Change from Baseline in the Bowel Incontinence Scale.
●
Change from Baseline in CDAI.
●
Change from Baseline in individual IBDQ domain scores (bowel, emotional, 
social, systemic).
 


ABBV-154
M20-371 – Statistical Analysis Plan
Version 2.0 – 10 February 2023
15
●
Change from Baseline in individual IBDQ items under Bowel Symptom 
domain (for Q1, Q5, Q9, Q13, Q17, Q20, Q22, Q24, Q26, and Q29).
●
Achievement of IBDQ remission defined as IBDQ ≥ 170 points.
●
Achievement of IBDQ response defined as increase in IBDQ ≥ 16 points from 
Baseline.
●
Change from Baseline in 36-Item Short Form Health Survey (SF-36).
●
Change from Baseline in fecal calprotectin (FCP).
●
Change from Baseline in high-sensitivity C-Reactive Protein (hs-CRP).
●
Change from Baseline in average daily AP score.
●
Change from Baseline in average daily liquid or very soft SF.
●
Change from Baseline in SES-CD.
●
Achievement of SES-CD ulcerated surface subscore ≤ 1 in each segment with 
a SES-CD ulcerated surface subscore ≥ 2 at Baseline.
●
Achievement of Ulcer-free endoscopy.
●
Achievement of absence of bowel urgency.
●
Change from Baseline in average daily bowel urgency frequency.
●
Achievement of absence of rectal bleeding.
3.4
Safety Endpoints
The following endpoints will be included in the safety analyses:
●
Treatment emergent adverse events (TEAEs), serious adverse events (SAEs), 
AEs leading to discontinuation of the study drug;
●
Occurrence of possible glucocorticoid-related AEs;
●
Potentially clinically significant laboratory, vital signs, and electrocardiogram 
(ECG) variables.
4.0
Analysis Populations
The following population sets will be used for the analyses.
 


ABBV-154
M20-371 – Statistical Analysis Plan
Version 2.0 – 10 February 2023
16
ITT Populations
ITT population:  The ITT Population includes all subjects who were randomized and 
received at least 1 dose of study drug.
ITT1 population:  The subset of the ITT Population who were randomized and received 
at least 1 dose of study drug in the Induction Period.  The ITT1 Population is the primary 
analysis population for efficacy analyses of the Induction Period.
ITT2 population:  The subset of the ITT population who were randomized and received 
at least one dose of study drug in the Re-Induction Period.  The ITT2 Population is the 
analysis population for efficacy analyses of the Re-Induction Period.
ITT3 population:  The subset of the ITT population who received ABBV-154 for 
12 weeks before entering the Maintenance Period (including subjects were randomized to 
ABBV-154 dose groups in the Induction Period and entered the Maintenance Period from 
the Induction Period OR were randomized to the placebo group in the Induction Period
and entered the Maintenance Period from the Re-Induction Period) AND were 
randomized and received at least one dose of study drug in the Maintenance Period.  The 
ITT3 Population is the primary analysis population for efficacy analyses of the 
Maintenance Period.
ITT3-RN population:  The subset of the ITT population who were enrolled and received 
at least one dose of study drug in the randomized portion of the Maintenance Period.
ITT3-NRN population:  The subset of the ITT population who were enrolled and 
received at least one dose of study drug in the non-randomized portion of the Maintenance 
Period.
ITT3-RES population:  The subset of the ITT population who received at least one dose 
of ABBV-154 rescue therapy in the Maintenance Period.
 


ABBV-154
M20-371 – Statistical Analysis Plan
Version 2.0 – 10 February 2023
17
The ITT Populations (including ITT1, ITT2, ITT3, ITT3-RN, ITT3-NRN populations) 
will be analyzed as randomized (i.e., according to the randomized/assigned treatment 
assignment).
Safety Populations
The safety population for the Induction Period (denoted by SA1) includes all subjects who 
received at least one dose of the study drug in the Induction Period.
The safety population for the Re-Induction Period (denoted by SA2) includes all subjects 
who received at least one dose of the study drug in the Re-Induction Period.
The safety population for the Maintenance Period (denoted by SA3) includes all subjects 
who received at least one dose of the study drug in the Maintenance Period.
The all ABBV-154 safety population (SA-ALL154) includes all subjects who received at 
least one dose of ABBV-154 in the Induction Period, or the Re-Induction Period, or the 
Maintenance Period.
The all ABBV-154 rescue safety population (SA-RES) includes all subjects who received 
at least one dose of ABBV-154 rescue therapy in the Maintenance Period.
The following safety populations are defined for safety analyses based on data from 
multiple study periods:
SA-IN2:  all subjects who received at least one dose of ABBV-154 in both Induction 
Period and Re-Induction Period.
SA-INMN:  all subjects who received at least one dose of ABBV-154 in either Induction 
Period or Re-Induction Period AND at least one dose of ABBV-154 in the Maintenance 
Period.
 


ABBV-154
M20-371 – Statistical Analysis Plan
Version 2.0 – 10 February 2023
18
SA-IN2MN:  all subjects who received at least one dose of ABBV-154 in the Induction 
Period AND at least one dose of ABBV-154 in the Re-Induction Period AND at least one 
dose of ABBV-154 in the Maintenance Period.
For the safety populations, subjects are assigned to a treatment group based on the "as 
treated" treatment group, regardless of the treatment randomized.
5.0
Subject Disposition
A summary of subject accountability will be provided where the number of subjects in 
each of the following categories will be summarized by treatment group for each period 
separately, among the corresponding ITT population:
●
Subjects enrolled (randomized) in the study;
●
Subjects who took at least one dose of study drug;
●
Subjects who completed protocol-specified treatment;
●
Subjects who prematurely discontinued study drug;
●
Subjects who withdrew from study.
Number and percentage of subjects who discontinued study drug and who withdrew from 
the study will be summarized by reason (primary reason and all reasons) and by treatment 
group for each period separately.  Subjects with multiple reasons for premature 
discontinuation will be counted once in the calculation of the number and percentage of 
total discontinuations.
In addition, subjects who reported at least one of the protocol deviation categories 
(Appendix A) will be summarized for each treatment group.
6.0
Study Drug Duration and Compliance
For the safety populations (SA1, SA2 and SA3), duration of treatment will be summarized 
by each treatment group for each period. Duration of treatment is defined for each subject 
as last dose date of blinded study drug minus first dose date + 14.  Duration of treatment 
 


ABBV-154
M20-371 – Statistical Analysis Plan
Version 2.0 – 10 February 2023
19
will be summarized for each treatment group using the number of subjects treated, mean, 
standard deviation, median, minimum, and maximum.  In addition, the number and 
percentage of subjects in the following treatment duration intervals will be summarized.
Induction/Re-Induction Period: < 2 weeks [14 days], ≥ 2 weeks [14 days], ≥ 4 weeks 
[28 days], ≥ 8 weeks [56 days], and ≥ 12 weeks [84 days] 
Maintenance Period: < 2 weeks [14 days], ≥ 2 weeks [14 days], ≥ 4 weeks [28 days], 
≥8 weeks [56 days], ≥ 12 weeks [84 days], ≥ 24 weeks [168 days], ≥ 36 weeks 
[252 days], and ≥ 40 weeks [280 days]
Treatment compliance will be summarized by treatment group for each period for the 
safety population.  Treatment compliance is defined as the number of infusions/injections 
actually taken divided by the number of infusions/injections that should have been taken.  
Percent compliance will be summarized. 
7.0
Demographics, Baseline Characteristics, Medical 
History, and Prior/Concomitant Medications
Demographics, baseline or disease characteristics, medical history, and prior and 
concomitant medications will be summarized overall and by treatment group, and overall 
for each of the ITT1/ITT2/ITT3/ITT3-RN/ITT3-NRN population.  Categorical variables 
will be summarized with the number and percentage of subjects; percentages will be 
calculated based on the number of non-missing observations.  Continuous variables will 
be summarized with descriptive statistics (number of non-missing observations, mean, 
standard deviation, median, minimum, and maximum).
7.1
Demographics and Baseline Characteristics
Demographic/vital Signs
●
Sex (Male, Female)
●
Age (Years)
●
Age Category (≥ 18 years - < 40 years, ≥ 40 years - < 65 years, ≥ 65 years)
 


ABBV-154
M20-371 – Statistical Analysis Plan
Version 2.0 – 10 February 2023
20
●
Ethnicity (Hispanic/Latino, Non-Hispanic/Latino)
●
Race category (White, Black or African American, American Indian or Alaska 
Native, Native Hawaiian or Other Pacific Islander, Asian, Multiple)
●
Geographic Region category (US, ex-US)
●
Geographic Region category (Asia, Eastern Europe, Western Europe, North 
America, South/Central America, Other)
●
Tobacco/Nicotine Use (currently smokes, ex-smoker, never smoked, 
unknown)
●
Alcohol use (current drinker, former drinker, non-drinker, unknown)
●
Body weight (kg) – overall and by sex
●
Body Mass Index (BMI, kg/m2)
●
BMI category
○
[< 18 kg/m2]
○
[≥ 18 and < 25 kg/m2]
○
[≥ 25 and < 30 kg/m2]
○
[≥ 30 kg/m2]
Patient Reported Outcome Questionnaires at Baseline
●
IBDQ total and domain scores
●
FACIT-F total score
●
SF-36 - 8 domain scores, PCS and MCS
●
PGIS-CD+
Other Baseline Characteristics
●
CDAI
●
Average Daily very soft or liquid SF
●
Average Daily AP score
●
SES-CD
●
SES-CD category (< 15, ≥ 15)
 


ABBV-154
M20-371 – Statistical Analysis Plan
Version 2.0 – 10 February 2023
21
●
Crohn's disease Duration (years)
●
Crohn's disease Duration category (≤ 5 years, > 5 years)
●
hs-CRP (mg/L)
●
hs-CRP category (< 5, ≥ 5 mg/L)
●
FCP (µg/g)
●
FCP category (≤ 250 µg/g, > 250 µg/g)
●
CD Location Per SES-CD (ileal, ileocolonic, colonic; Appendix F)
Prior and Concomitant Treatment use
●
Baseline CD-related glucocorticoid use (yes, no)
●
Baseline CD-related immunomodulator use (yes, no)
●
Baseline CD-related aminosalicylates use (yes, no)
●
Prior inadequate response and/or intolerance to biologics
○
Number of prior biologics with inadequate response and/or intolerance 
(≤1, 2, > 3)
○
Prior inadequate response and/or intolerance to an anti-TNF agent (yes, no)
●
Inadequate response to an anti-TNF agent (yes, no)
●
Intolerance to an anti-TNF agent (yes, no)
●
Inadequate response to adalimumab (yes, no)
○
Prior inadequate response and/or intolerance to vedolizumab/natalizumab
(yes, no)
○
Prior inadequate response and/or intolerance to ustekinumab (yes, no)
In addition, clinical tests at baseline such as TB test, pregnancy test and electrocardiogram 
assessment will be summarized.  Crohn's disease history (Montreal classification) and 
Crohn's disease surgical history will be summarized separately as well.
 


ABBV-154
M20-371 – Statistical Analysis Plan
Version 2.0 – 10 February 2023
22
7.2
Medical History
Medical history data will be coded using the Medical Dictionary for Regulatory Activities 
(MedDRA).  The actual version of the MedDRA coding dictionary will be noted in the 
statistical tables and clinical study report.  The number and percentage of subjects in each 
medical history category [by MedDRA system organ class (SOC) and preferred term 
(PT)] will be summarized overall and by treatment group.  The SOC will be presented in 
alphabetical order, and the preferred terms will be presented in alphabetical order within 
each SOC.  Subjects reporting more than one condition/diagnosis will be counted only 
once in each row (SOC or PT).
7.3
Prior and Concomitant Medications
Prior and concomitant medications will be summarized by generic name (ITT1 population 
for prior medications; ITT1, ITT2 and ITT3/ITT3-RN/ITT3-NRN populations for 
concomitant medications).  A prior medication is defined as any medication taken prior to 
the date of the first dose of study drug in the Induction Period.
A concomitant medication for the Induction Period is defined as any medication other 
than study drug that (1) was started prior to the first dose study drug in the Induction 
Period and continued to be taken after the first dose of study drug in the Induction Period, 
or (2) was started after the first dose of study drug in the Induction Period, but (i) prior to 
the first dose of study drug in the Re-Induction Period (if applicable), or (ii) prior to the 
first dose of study drug in the Maintenance Period (if applicable), or (iii) within the last 
dose in the Induction Period + 14 days, whichever is earlier.
A concomitant medication for the Re-Induction Period is defined as any medication other 
than study drug that (1) was started prior to the first dose study drug in the Re-Induction 
Period and continued to be taken after the first dose of study drug in the Re-Induction 
Period, or (2) was started after the first dose of study drug in the Re-Induction Period, but 
(i) prior to the first dose of study drug in the Maintenance Period (if applicable), or 
(iii) within the last dose in the Re-Induction Period + 14 days, whichever is earlier.
 


ABBV-154
M20-371 – Statistical Analysis Plan
Version 2.0 – 10 February 2023
23
A concomitant medication for the Maintenance Period is defined as any medication other 
than study drug that (1) was started prior to the first dose study drug in the Maintenance 
Period and continued to be taken after the first dose of study drug in the Maintenance 
Period, or (2) was started after the first dose of study drug in the Maintenance Period, but 
(i) within the last dose in the Maintenance Period + 14 days, or (ii) prior to initiation of 
ABBV-154 rescue therapy, whichever is earlier.
The number and percentage of subjects taking medications will be summarized by generic 
drug name based on the World Health Organization (WHO) Drug Dictionary for both 
prior and concomitant medications.
8.0
Handling of Potential Intercurrent Events for the 
Primary and Key Secondary Endpoints
Potential intercurrent events considered in the Study M20-371 include 1) premature 
discontinuation of study drug and 2) CD-related confounding medications defined in 
Section 8.1.  As suggested by Qu et al. (2021), a mix of strategies will be used to handle 
different intercurrent events for the efficacy analysis.
8.1
Intercurrent Event 1 (IE1): CD-Related Confounding 
Medications
The CD-related confounding medications intercurrent event is defined as follows.
In the Induction Period:
1.
Initiation of protocol-defined Rescue Therapy for the Induction Period;
2.
Initiation of glucocorticoids after Baseline of the Induction Period;
3.
Fail to complete glucocorticoid taper by Week 6 of the Induction Period;
4.
Initiation/increasing doses of aminosalicylates or immunomodulators.
 


ABBV-154
M20-371 – Statistical Analysis Plan
Version 2.0 – 10 February 2023
24
In the Maintenance Period:
●
Initiation of protocol-defined Rescue Therapy for the Maintenance Period.
Within each period, the time point of the CD-related confounding medications 
intercurrent event is defined as the date when one of the scenarios above occurs for a 
subject.
Binary endpoints:  A composite strategy will be used in the efficacy analysis: the subject 
will be considered as non-responders at all visits on/after the CD-related confounding 
medications intercurrent event.
Continuous endpoints:  A hypothetical strategy will be used in the efficacy analysis.  
Data collected on/after the initiation of CD-related confounding medications will not be 
used in the analysis.  Efficacy analysis will be handled by using corresponding statistical 
models (e.g., the Mixed-Effect Model Repeated Measurement [MMRM] model).
8.2
Intercurrent Event 2 (IE2): Premature Discontinuation of 
Study Drug
Following the intent-to-treat (ITT) principle, a treatment policy strategy will be used to 
handle the IE2.  Data collected on/after premature discontinuation of study drug will be 
used for all efficacy endpoints.
The only exception is when data are collected on/after the date subjects switching to other 
treatments for CD, which will be handled as follows:
●
Binary endpoints: A composite strategy will be used in the efficacy analysis: 
the subject will be considered as non-responder at all visits after the initiation 
of other CD-related treatments.
●
Continuous endpoints: A hypothetical strategy will be used in the efficacy 
analysis. Data collected after the initiation of other CD-related treatments will 
not be used in the analysis.  Efficacy analysis will be handled by using 
corresponding statistical models (e.g., MMRM model).
 


ABBV-154
M20-371 – Statistical Analysis Plan
Version 2.0 – 10 February 2023
25
The other CD-related medications include:
●
Biologics approved for CD (Adalimumab, Certolizumab, Infliximab, 
Ustekinumab, Vedolizumab, Natalizumab)
●
Any investigational compound
●
Systemic glucocorticoids and rectal glucocorticoids
●
Immunomodulators
9.0
Efficacy Analyses
9.1
General Considerations
All efficacy analyses will be conducted in the ITT Populations in each period.  All tests 
will be 2-sided at an alpha level of 0.1.
For all efficacy endpoints, the descriptive statistics will be provided by treatment group 
for each of the study period.  The statistics include number of observations, mean, 
standard deviation, 95% CI, minimum, median, and maximum for continuous variables, 
and number, percent and two-sided 95% CI for discrete variables.  And number of 
subjects with missing data due to COVID-19 pandemic will be summarized for primary 
and secondary efficacy endpoints.
Unless otherwise specified, any subject will be analyzed according to the actual stratum 
the subject belongs to.
The Primary Analysis for the Induction Period and Re-Induction Period will be performed 
after all subjects have completed Week 12 of the Induction Period and Re-Induction 
Period, respectively, or prematurely discontinued study participation.  This is the final 
efficacy analysis for the Induction Period and Re-Induction Period, respectively.
The final analysis will be conducted after all subjects have completed Week 40 of the 
Maintenance Period plus the 70 day Follow-up Visit or prematurely discontinued study 
participation.  This is the final efficacy analysis for the Maintenance Period. To ensure the 
 


ABBV-154
M20-371 – Statistical Analysis Plan
Version 2.0 – 10 February 2023
26
integrity of the trial, the study sites and subjects will remain blinded until the final 
database lock is completed.
In Section 9.0, "Baseline" refers to the last non-missing observation prior to the 
first administration of study drug in the Induction Period, unless specified otherwise.  
"Comparison of treatment groups" refers to (i) comparison of each ABBV-154 group and 
placebo group in the Induction Period; (ii) comparison of Re-Induction Group 2 and 
Re-Induction Group 1 in the Re-Induction Period; (iii) comparison of each ABBV-154 
group and placebo group for the randomized portion in the Maintenance Period. 
"Stratification factors for the corresponding period" refers to randomization stratification 
factors specified in Section 2.3 except for the Maintenance Period, the randomization 
stratification factors used in efficacy analyses for the Maintenance Period are
●
Achievement of CR100 at entry of the Maintenance Period (Week 12 of the 
Induction/Re-Induction Period): Yes vs No;
●
Entry to the Maintenance Period:  Induction Period vs Re-Induction Period.
For the comparison between ABBV-154 80 mg SC EOW and Placebo in the Maintenance 
Period, all data from subjects of the corresponding ITT3/ITT3-RN population will be 
included.
For the comparison between ABBV-154 230 mg SC EOW and Placebo in the 
Maintenance Period, data from subjects of the corresponding ITT3/ITT3-RN population 
will be included with the exception that data from subjects who are randomized to 
Induction Group 1 (ABBV-154 150 mg IV + 80 mg SC EOW), considered as responder at 
Week 12 of the Induction Period and entered the Maintenance Period will not be included.
Analysis of Categorical Variables:
For categorical variables, frequencies and percentages will be reported for each treatment 
group in each of the study period.  In each period, comparison of treatment groups will be 
performed using the Cochran Mantel-Haenszel (CMH) test adjusting for stratification 
 


ABBV-154
M20-371 – Statistical Analysis Plan
Version 2.0 – 10 February 2023
27
factors for the corresponding period.  If there is a stratum that has no subject in it, a value 
of 0.1 will be added to the denominator to the corresponding stratum in order to prevent 
dividing by 0, as suggested in Greenland and Robins (1985).1  Point estimates and 95% 
confidence intervals (CI) for the difference in proportions between treatment groups will 
be provided.  Construction of CI for the common risk difference will be based on the 
Mantel-Haenszel estimate adjusting for stratification factors for the corresponding study 
period.
Analysis of Continuous Variables:
For continuous variables, the model based mean and standard error will be provided.  The 
mean value of the variable at baseline and each scheduled visit will also be presented for 
each treatment group.  Continuous variables collected longitudinally will be using a 
Mixed-Effect Model Repeated Measurement (MMRM) model.  Continuous efficacy 
variables which are collected at only one post-baseline visit (such as SES-CD) will be 
analyzed using an Analysis of Covariance (ANCOVA) model.  Point estimates and 95% 
CIs of mean change from baseline within each treatment group, and the difference 
between treatment groups for each period will be provided.
9.2
Handling of Missing Data
Missing data could occur due to various reasons, including missing visits/assessments, 
early withdrawal from the clinical trials, or missing due to COVID-19 infection or logistic 
restrictions during the pandemic.  Assessments on or after any intercurrent event will be 
handled as specified in Section 8.0.
The COVID-19 pandemic is interfering with the conduct of many ongoing trials, with 
potential impacts on treatment duration and the collection, analysis, and the interpretation 
of clinical trial data.  For example, some scheduled visits may be missed due to 
self-quarantine or local government restrictions on travel; some visits may also be delayed 
or canceled due to healthcare resource constraints during the pandemic.  Impacted visits 
due to COVID-19 will be recorded in the database.  The probability of having missed 
 


ABBV-154
M20-371 – Statistical Analysis Plan
Version 2.0 – 10 February 2023
28
visits and missing data due to COVID-19 infection or logistical restrictions related to the 
COVID-19 pandemic can be reasonably assumed to be unrelated to the unobserved 
values.  Therefore, for the purpose of statistical analysis, it is reasonable to assume that 
these missing data are missing at random (MAR) and the statistical models that require 
MAR assumption are appropriate.  The intent is to provide reliable estimates of the 
treatment effects under the scenario without the impact of COVID-19 pandemic.
Missing data for the efficacy analyses will be handled using the methods described below.
9.2.1
Categorical Endpoints
For binary efficacy endpoints, missing data will be handled using the following 
approaches:
●
The primary approach for handling missing data in the analysis of binary 
endpoints will use Non-Responder Imputation (NRI) while incorporating 
Multiple Imputation (MI) to handle missing data due to COVID-19 (NRI-C).
○
The NRI-C will categorize any subject who does not have an evaluation 
during a pre-specified visit window (either due to missing assessment or 
due to early withdrawal from the study) as a non-responder for the visit.  
The only exception is that missing data due to COVID-19 infection or 
logistical restriction will be handled by MI.  At each visit, subjects will be 
characterized as responders or non-responders based on MI imputed values 
if missing due to COVID-19; otherwise, subjects will be considered as 
non-responders for missing due to other reasons in the NRI-C approach.  In 
addition, at and after the CD-related confounding medications intercurrent 
event (see Section 8.1) and on/after the date of initiation of CD-related 
medications after premature discontinuation of study drug (see Section 8.2)
in the corresponding study period, subjects will be considered as non-
responders and will not be imputed by MI.
●
A sensitivity analysis for binary endpoints will use NRI with No special data 
handling for missing due to COVID-19 (NRI-NC).
○
NRI-NC will be performed in the same way as NRI-C without the 
exception above.  Missing due to COVID-19 infection or logistical 
 


ABBV-154
M20-371 – Statistical Analysis Plan
Version 2.0 – 10 February 2023
29
restriction will also be counted as non-responders.  Subjects on or after the 
occurrence of the CD-related confounding medications intercurrent event 
and on/after the date of initiation of CD-related medications after 
premature discontinuation of study drug will still be considered as 
non-responders.
●
Details on MI method in NRI-C are described below:
○
Markov Chain Monte Carlo (MCMC) will be first applied to augment data 
into monotonic missing pattern (where applicable) and PROC MI will be 
used to generate 30 datasets using the regression method.  If the binary 
endpoints are derived from the continuous variables, PROC MI will be 
applied to the continuous variables.  The variables to be included in the 
imputation model are:  treatment group, randomization stratification factors 
for the corresponding period, age, gender, weight, baseline measurement 
(if applicable) and post-baseline measurements at each visit for the 
respective analysis period up to the end of the analysis period.  The random 
seed for MCMC and the random seed for PROC MI are specified in 
Appendix E.  The imputed post-baseline measurements will be rounded to 
the same precision as the observed data before the determination of 
responder status.  Subjects will be characterized as responders or non-
responders based on MI imputed data.  Using the CMH model adjusted by 
randomization stratification factors, the endpoints will be analyzed using 
each of the 30 imputed datasets.  SAS PROC MIANALYZE will be used 
to generate the final inferences of the risk difference between treatment 
groups, using Rubin's rule.2  Note that measurements will be set to missing 
1) at or after the occurrence of the CD-related confounding medications 
intercurrent event, or 2) on/after the date of initiation of CD-related 
medications after premature discontinuation of study drug before applying 
MI.  After the MI imputation, an NRI override will be implemented for 
missing values 1) missing values due to reasons other than COVID-19 
infection or logistic reasons, or 2) at or after the occurrence of the CD-
related confounding medications or 3) on/after the date of initiation of CD-
related medications after premature discontinuation of study drug, that is, 
regardless of MI imputed values, subjects satisfying 1) or 2) or 3) will be 
considered as "non-responder" for binary efficacy endpoints.
 


ABBV-154
M20-371 – Statistical Analysis Plan
Version 2.0 – 10 February 2023
30
9.2.2
Continuous Endpoints
For continuous efficacy endpoints where Mixed-Effect Model Repeat Measurement 
(MMRM) analysis or Analysis of Covariance (ANCOVA) is performed, missing data will 
be handled using the following approaches.
●
MMRM:  The repeat measurement analysis will be conducted using a mixed 
model including observed measurements at all post-baseline visits for the 
respective analysis period up to the end of the analysis period.  The mixed 
model includes the categorical fixed effects of treatment, visit and treatment-
by-visit interaction, stratification factors at randomization, and the continuous 
fixed covariates of baseline measurement.  An unstructured variance 
covariance matrix will be used.  If the model cannot converge, an appropriate 
variance-covariance structure matrix (e.g., autoregressive or compound 
symmetry) will be used.  Parameter estimation is based on the method of 
restrictive maximum likelihood (REML).  MMRM will be the primary 
approach in the analysis of continuous variables with repeated measurements.
●
ANCOVA:  For continuous efficacy variables that are collected at only one 
post-baseline visit (such as SES-CD), ANCOVA will be used.  The model 
includes the categorical fixed effects of treatment, stratification factors at 
randomization, and the continuous fixed covariates of baseline and 
measurement.
9.2.3
Additional Analyses
In addition, As Observed (AO) analysis will be performed as supplementary for 
categorical endpoints.
●
AO:  The AO analysis will not impute values for missing evaluations, and thus 
a subject who does not have an evaluation on a scheduled visit will be 
excluded from the AO analysis for that visit.  AO will include all values 
collected in the study (except data collected after initiation of ABBV-154 
rescue therapy for the analyses in the Maintenance Period).
 


ABBV-154
M20-371 – Statistical Analysis Plan
Version 2.0 – 10 February 2023
31
9.3
Primary Efficacy Endpoint and Analyses
9.3.1
Primary Efficacy Endpoint
The primary endpoint for the primary analysis of efficacy is:
●
Achievement of endoscopic response at Week 12 of the Induction Period
9.3.2
Primary Analysis of Primary Efficacy Endpoint
The attributes of the estimand corresponding to the primary efficacy endpoint are 
summarized in Table 1.
The primary endpoint will be analyzed between each ABBV-154 group and placebo 
group in the Induction Period using the CMH test, stratified by the randomization factors 
(baseline glucocorticoid use (yes/no); endoscopic disease severity (SES-CD < 15; SES 
CD ≥ 15); inadequate response to adalimumab (yes/no)) based on ITT1 population.
 


ABBV-154
M20-371 – Statistical Analysis Plan
Version 2.0 – 10 February 2023
32
Table 1.
Summary of the Estimand Attributes of the Primary Efficacy 
Endpoint
Estimand 
Label
Attributes of the Estimand
Treatment
Endpoint
Population
Intercurrent Events
Statistical 
Summary
Primary
Each 
ABBV-154 
group vs. 
placebo in 
the 
Induction 
Period
Achievement 
of endoscopic 
response at 
Week 12 of 
the Induction 
Period
Subjects with 
moderately to 
severely 
active CD 
who had 
inadequate 
response to or 
were 
intolerant of 
prior 
biologics
IE1: Initiation or dose 
escalation of 
CD-related 
confounding 
medications
IE2:  premature 
discontinuation of 
study drug 
All subjects will be 
considered as 
non-responders at or 
after IE1
All data after IE2 will 
be used until initiation 
of CD-related 
medications
Difference 
in the
proportion 
of subjects 
achieving 
endoscopic 
response
The primary efficacy endpoint will be tested at two-sided significance level of 0.1.  
A CMH based two-sided 95% CI for the difference between treatment groups will be 
constructed.
The NRI-C approach for handling missing data will be used for main analysis for the 
primary endpoint.
9.3.3
Sensitivity and Supplementary Analyses of the Primary 
Efficacy Endpoint
Sensitivity analyses of the primary analysis of the primary efficacy endpoint is NRI-NC.
A supplementary analysis of the primary endpoint corresponded to the AO analysis 
specified in Section 9.2 will be performed in which all data after IE1 and IE2 will be used.  
CMH analysis as detailed in Section 9.1 will be repeated using AO data handling without 
 


ABBV-154
M20-371 – Statistical Analysis Plan
Version 2.0 – 10 February 2023
33
any imputation as an additional analysis.  The analysis will be conducted on the 
ITT1 population who have the efficacy measurement at Week 12 visit.
9.4
Secondary Efficacy Analyses
9.4.1
Main Analyses of Ranked Secondary Efficacy Endpoints
The attributes of the estimands corresponding to the ranked secondary efficacy endpoints 
are summarized in Table 2.
In general, secondary efficacy variables will be analyzed using the CMH test controlling 
for stratification factors for the corresponding period.  A CMH based two-sided 95% CI 
for the difference between treatment groups will be constructed.
The NRI-C method will be the primary approach for missing data handling.
 


ABBV-154
M20-371 – Statistical Analysis Plan
Version 2.0 – 10 February 2023
34
Table 2.
Summary of the Estimand Attributes of the Key Secondary Efficacy 
Endpoints
Attributes of the Estimand
Treatment
Endpoint
Population
Handling 
Intercurrent 
Events
Statistical 
Summary
Secondary 
endpoints in 
the Induction 
Period
Each 
ABBV-
154 group 
vs. placebo
Achievement 
of clinical 
remission per 
CDAI at Week 
12 in the 
Induction 
Period, clinical 
remission per 
SF/AP at 
Week 12 in the 
Induction 
Period 
Subjects with 
moderately to 
severely active 
CD who had 
inadequate 
response to or 
were intolerant 
of prior 
biologics
IE1: Initiation or 
dose escalation of 
CD-related 
confounding 
medications
IE2:  premature 
discontinuation of 
study drug 
All subjects will 
be considered as 
non-responders at 
or after IE1
All data after IE2 
will be used until 
initiation of CD-
related 
medications
Difference in 
the proportion 
of subjects 
achieving each 
binary 
secondary 
endpoint in the 
Induction 
Period
Secondary 
endpoints in 
the 
Maintenance 
Period
Each 
ABBV-
154 group 
vs. placebo
Achievement 
of clinical 
remission per 
CDAI at Week 
40 in the 
Maintenance 
Period, clinical 
remission per 
SF/AP at 
Week 40 in the 
Maintenance 
Period, 
endoscopic 
response at 
Week 40 in the 
Maintenance 
Period  
subjects with 
moderately to 
severely active 
CD who had 
inadequate 
response to or 
were intolerant 
of prior 
biologics and 
achieved 
response after 
the 12-week 
induction 
treatment with 
ABBV-154
IE1: Initiation or 
dose escalation of 
CD-related 
confounding 
medications
IE2:  premature 
discontinuation of 
study drug 
All subjects will 
be considered as 
non-responders at 
or after IE1
All data after IE2 
will be used until 
initiation of CD-
related 
medications
Difference in 
the proportion 
of subjects 
achieving each 
binary 
secondary 
endpoint in the 
Maintenance 
Period
 


ABBV-154
M20-371 – Statistical Analysis Plan
Version 2.0 – 10 February 2023
35
9.4.2
Sensitivity and Supplementary Analyses for Secondary 
Efficacy Endpoints
For secondary endpoints, sensitivity analysis of the of the main analysis is NRI-NC.
A supplementary analysis of secondary endpoints are AO analyses specified in 
Section 9.2 will be performed in which all data after IE1 and IE2 will be used.  
CMH analysis as detailed in Section 9.1 will be repeated using AO data handling without 
any imputation as an additional analysis.  The analyses will be conducted on the 
ITT1 population (for the Induction Period)/ ITT3 population (for the Maintenance Period) 
who have the efficacy measurement at corresponding visit for the endpoint.
NRI-C analysis for the secondary endpoints in the Maintenance Period will also be 
performed the ITT3-RN population.  Treatment difference between each ABBV-154 
group and placebo with point estimate and 95% CI will be presented using NRI-C 
approach with the CMH method as detailed in Section 9.1 and Section 9.2.
9.5
Additional Efficacy Analyses
Other efficacy endpoints described in Section 3.3 will be analyzed at all visits assessed 
using the same methods listed in above and Section 9.2.  For analyses for the Induction 
Period and the randomized portion of the Maintenance Period, NRI-C with CMH method 
will be performed for binary endpoints while MMRM/ANCOVA will be performed for 
continuous endpoints.
AO analyses will be performed for analyses in the Re-Induction Period.
9.6
Dose-Response Modeling for ABBV-154
The dose-response relationship among ABBV-154 dose groups and the placebo group 
will be characterized for the primary endpoint using the Multiple Comparison Procedure -
Modeling (MCP-Mod) method5,6 among the ITT1 population for the Induction Period. 
The summary level response rates based on the primary analysis approach above will be 
used, and ADDPLAN DF software will be used to perform the MCP-Mod analyses.
 




ABBV-154
M20-371 – Statistical Analysis Plan
Version 2.0 – 10 February 2023
37
Steps of MCP-Mod:
1.
Choose a candidate set of models as in Table 3.
2.
Compute the optimum contrast for each model.
3.
Use contrast test to find all significant models while preserving family-wise error 
rate (FWER).
4.
Use all significant models to make inference about the weighted target dose of 
interest.
9.7
Efficacy Subgroup Analyses
To evaluate the consistency of the efficacy over demographic and other baseline 
characteristics, subgroup analysis will be performed for the primary endpoint for the 
subgroups listed in Table 4 below using ITT1.
For subgroup analysis, point estimate and 95% CI for each treatment group as well as
point estimate and 95% CI for treatment differences between each ABBV-154 group and 
placebo group will be presented.  No p-value will be provided.  If any of the resulting 
categories for a subgroup factor listed in Table 4 (except age, sex and race), has fewer 
than 10% of the planned total sample size, subgroup analyses will not be presented for 
that category.
 


ABBV-154
M20-371 – Statistical Analysis Plan
Version 2.0 – 10 February 2023
38
Table 4.
Subgroups for Efficacy Analysis
Subgroup Factor
Categories
Sex
Age
Male, Female
≥ 18 years - < 40 years, ≥ 40 years - < 65 years, 
≥ 65 years
Race
White, non-White
Baseline Glucocorticoid Use
Endoscopic Disease Severity
Inadequate Response to adalimumab
Inadequate response to prior anti-TNF biologics
Yes or No
SES-CD < 15, SES-CD ≥ 15
Yes or No
Yes or No
9.8
Efficacy Analyses for ABBV-154 Rescue Therapy
To evaluate the efficacy for ABBV-154 rescue therapy, the following endpoints will be 
analyzed on ITT3-RES population and AO analysis will be performed:
●
Achievement of clinical remission per CDAI at Week 12 and Week 24 after
ABBV-154 rescue therapy
●
Achievement of clinical remission per SF/AP at Week 12 and Week 24 after
ABBV-154 rescue therapy
●
Achievement of CR100 at Week 12 and Week 24 after ABBV-154 rescue 
therapy
●
Mean FCP at Week 12 and Week 24 after ABBV-154 rescue therapy
●
Mean hs-CRP at Week 12 and Week 24 after ABBV-154 rescue therapy
10.0
Safety Analyses
10.1
General Considerations
Safety analyses will be performed on the safety population for the Induction Period 
(SA1), the Re-Induction Period (SA2), the Maintenance Period (SA3) and SA-RES, 
SA-ALL154 population as defined in Section 4.0.  In addition, safety summaries will be 
 


ABBV-154
M20-371 – Statistical Analysis Plan
Version 2.0 – 10 February 2023
39
performed on the safety analysis set for combined data from different periods (SA-IN2, 
SA-INMN, SA-IN2MN).
The standard safety analyses will include reporting of adverse events (AEs), adverse 
events of special interest (AESIs), laboratory, and vital signs measurements.  Frequency 
tables and exposure adjusted event rate per 100 patient-years tables of subjects with 
treatment-emergent adverse events (TEAEs) by system organ class (SOC) and by 
preferred term (PT) as in the Medical Dictionary for Regulatory Activities (MedDRA) 
dictionary will be provided by treatment group.  All continuous laboratory parameters and 
vital signs variables at each visit will also be summarized by treatment group.  Frequency 
tables of subjects meeting criteria for potentially clinically important vital sign values and 
for potentially clinically important laboratory values will be provided by treatment group.
For safety analyses (such as analyses of laboratory and vital signs measurements) in the 
Induction Period, the baseline value is defined as the last available measurement before 
study drug administration for all subjects (including subjects who received placebo).  For 
all other safety analyses, the baseline value is defined as the last available measurement 
before first administration of ABBV-154 for all subjects.
For the safety analysis, subjects are assigned to a treatment group based on the treatment 
actually received, regardless of the treatment randomized.
Missing safety data will not be imputed.
10.2
Adverse Events
AEs will be summarized and presented using primary MedDRA SOCs and PTs according 
to the version of the MedDRA coding dictionary used for the study at the time of database 
lock.  The actual version of the MedDRA coding dictionary used will be noted in the 
AE tables and in the clinical study report.  Specific AEs will be counted once for each 
subject for calculating percentages, unless stated otherwise.  In addition, if the same 
adverse event occurs multiple times within a subject, the highest severity and level of 
relationship to investigational product will be reported.
 


ABBV-154
M20-371 – Statistical Analysis Plan
Version 2.0 – 10 February 2023
40
10.2.1
Treatment-Emergent Adverse Events
Induction Period (SA1 population):  TEAEs for the Induction Period are defined as 
events that begin either on or after the first dose of the study drug in the Induction Period 
and until (i) the first dose of study drug in the Re-Induction Period (if applicable), or (ii) 
until first dose of study drug in the Maintenance Period (if applicable), or (iii) within 70 
days after the last dose administration of the study drug in the Induction Period, 
whichever is earlier.
Re-Induction Period (SA2 population):  TEAEs for the Re-Induction Period are defined 
as events that begin either on or after the first dose of the study drug in the Re-Induction 
Period and until (i) first dose of study drug in the Maintenance Period (if applicable), or 
(ii) within 70 days after the last dose administration of the study drug in the Re-Induction 
Period, whichever is earlier.
Maintenance Period (SA3 population):  TEAEs for the Maintenance Period are defined 
as events that begin either on or after the first dose of the study drug in the Maintenance 
Period and until (i) within 70 days after the last dose administration of the blinded study 
drug in the Maintenance Period, or (ii) initiation of ABBV-154 rescue therapy, whichever 
is earlier.
ABBV-154 Rescue Therapy (SA-RES population):  TEAEs for the ABBV-154 rescue 
therapy are defined as events that begin either on or after the first dose of the ABBV-154 
rescue therapy in the Maintenance Period and until 70 days after the last dose 
administration of the study drug in the Maintenance Period.
All ABBV-154 (SA-ALL154 population):  TEAEs for "All ABBV-154" are defined as 
events that begin either on or after the first dose of ABBV-154 and within 70 days after 
the last dose of ABBV-154 in the study.  Events that begin when subjects on Placebo will 
be not included.
 


ABBV-154
M20-371 – Statistical Analysis Plan
Version 2.0 – 10 February 2023
41
Safety analyses from combined periods:
Induction Period + Re-Induction Period ABBV-154 (SA-IN2 population):  TEAEs for 
"Induction Period + Re-Induction Period ABBV-154" (SA_IN2) are defined as events that 
begin either on or after the first dose of ABBV-154 in the Induction Period and until 
(i) first dose of study drug in the Maintenance Period (if applicable), or (ii) within 70 days 
after the last dose of study drug in the study, whichever is earlier.
Induction Period/Re-Induction Period + Maintenance Period ABBV-154 (SA-INMN 
population):  TEAEs for "Induction Period/Re-Induction Period + Maintenance Period 
ABBV-154" (SA_INMN) are defined as events that begin either on or after the first dose 
of ABBV-154 in the Induction Period/Re-Induction Period and until (i) within 70 days 
after the last dose of study drug in the study, or (ii) initiation of ABBV-154 rescue 
therapy, whichever is earlier.
Induction Period + Re-Induction Period + Maintenance Period ABBV-154 (SA-
IN2MN population):  TEAEs for "Induction Period + Re-Induction Period + 
Maintenance Period ABBV-154" (SA-IN2MN) are defined as events that begin either on 
or after the first dose of ABBV-154 in the Induction Period and until (i) within 70 days 
after the last dose of study drug in the study, or (ii) initiation of ABBV-154 rescue 
therapy, whichever is earlier.
If an incomplete onset date was collected for an adverse event, the event will be assumed 
to be treatment-emergent unless there is other evidence that confirms that the event was 
not treatment-emergent (e.g., the event end date was prior to the study drug start date).  
The number and percentage of subjects experiencing treatment-emergent AEs will be 
summarized.
10.2.2
Adverse Event Overview
An overview of AEs will be presented consisting of the number and percentage of 
subjects experiencing at least one event for each of the following AE categories:
 


ABBV-154
M20-371 – Statistical Analysis Plan
Version 2.0 – 10 February 2023
42
●
Any TEAE
●
Any TEAE related to COVID-19
●
Any TEAE that was rated as with reasonable possibility to study drug by the 
investigator.
●
Any TEAE with CTCAE grade ≥ 3
●
Any serious TEAE.
●
Any TEAE leading to discontinuation of study drug.
●
Any TEAE leading to death.
●
Treatment-emergent AESI (See ABBV-154 Product Safety SAP (PSSAP) for 
details).
●
All deaths
○
Deaths occurring ≤ 70 days after last dose of study drug
○
Deaths occurring > 70 days after last dose of study drug
○
Deaths related to COVID-19
In addition, an overview of AEs per 100 patient-years of study exposure will be presented 
for the AE categories defined above.  The number of TEAEs reported, the total number of 
years of study drug exposure, and the TEAE rate per 100 patient-years will be presented.
10.2.3
Treatment-Emergent Adverse Events by SOC and/or PT
TEAEs will be summarized by SOC and PT; by maximum relationship to study drug as 
assessed by the investigator (e.g., reasonable possibility or no reasonable possibility) and 
SOC and PT; by maximum severity and SOC and PT; and by subject number and SOC 
and PT.  Specific AEs will be counted once for each subject for calculating percentages, 
unless stated otherwise.  In addition, if the same AE occurs multiple times within a 
subject, the highest severity and level of relationship to investigational product will be 
reported.  The SOCs will be presented in alphabetical order, and the PTs will be presented
in alphabetical order within each SOC.
For summary by maximum severity, if a subject has an AE with an unknown severity, 
then the subject will be counted in the severity category of unknown, even if the subject 
 


ABBV-154
M20-371 – Statistical Analysis Plan
Version 2.0 – 10 February 2023
43
has another occurrence of the same event with a severity present.  The only exception is if 
the subject has another occurrence of the same AE in the same analysis period with 
grade ≥ 3.  In this case, the subject will be counted under the maximum AE grade.
For summary by maximum relationship to study drug, if a subject has an AE with an 
unknown relationship, then the subject will be counted in the relationship category of 
"unknown," even if the subject has another occurrence of the same event with a 
relationship present.  The only exception is if the subject has another occurrence of the 
same AE in the same analysis period with a relationship assessment of "Reasonable 
Possibility."  In this case, the subject will be counted under the "Reasonable Possibility" 
category.
In addition, TEAEs will be summarized by PT and sorted by decreasing frequency for the 
total ABBV-154 group.
10.2.4
Treatment-Emergent Adverse Events per Patient-Years of 
Exposure
TEAEs will be summarized by event rate per 100 subject years, defined as
Years
Patient
Total
TEAEs
of
Number

100
where total patient years is defined as the sum of the study drug exposure of all subjects, 
normalized by 365.25, and rounded to 1 decimal place.  Note that one event per preferred 
term per day per subject will be counted in the calculation of the number of AEs (i.e., a 
preferred term will not be counted twice on the same day for the same subject).
The TEAE rates per 100 patient-years of exposure will be provided for each AE category 
in the AE overview summary (defined in Section 10.2.2) and for TEAE summary by SOC 
and PT.
 


ABBV-154
M20-371 – Statistical Analysis Plan
Version 2.0 – 10 February 2023
44
The study drug exposure for each safety population is defined as last dose date plus 70 
days, minus the first dose date. For SA-All154 safety population, the duration when 
subjects on Placebo will not be included in the calculation.
10.2.5
SAEs (Including Deaths) and Adverse Events Leading to 
Study Drug Discontinuation
SAEs (including deaths) and AEs leading to study drug discontinuation will be 
summarized by SOC and PT and in listing format.
10.2.6
Adverse Events of Special Interest
Treatment-emergent AESIs will be summarized by SOC and PT and will be based on 
standardized or company MedDRA queries (SMQs or CMQs), or based on adjudication 
results, as specified in Appendix G.
Treatment-emergent AESIs will be summarized by SOC and PT and listing format.  
Additionally, the event rate per 100 patient years of exposure will be provided for 
provided by SOC and PT for each AESI in the AE overview summary.
10.3
Analysis of Laboratory Data
Data collected from central and local laboratories, including additional laboratory testing 
due to an SAE, will be used in the analyses.  Baseline values collected for SAE-related 
laboratory assessments on or before the first dose of study drug will be excluded.  Data 
collected more than 70 days after the last dose of study drug of the analysis period (See 
Section 10.2.1) for the corresponding analysis populations will be excluded.
The clinical laboratory tests defined in the protocol (e.g., hematology and clinical 
chemistry) will be summarized.
Analysis of Quantitative Laboratory Parameters
Each laboratory variable will be summarized at all time points (starting at baseline) with 
the number of observations, mean, standard deviation, median, minimum and maximum 
 


ABBV-154
M20-371 – Statistical Analysis Plan
Version 2.0 – 10 February 2023
45
for non-missing observations.  The change from Baseline at each applicable post-baseline 
visit will be summarized for selected laboratory variables, with the number of 
observations, baseline mean, and visit mean.  The mean, standard error, and 95% CI will 
be presented for the change from Baseline for each treatment group.
For each period, treatment group differences for the changes from baseline will be 
analyzed using a one-way Analysis of Variance (ANOVA) model with treatment as a 
fixed factor and 95% CI for treatment difference will be presented for selected laboratory 
parameters.
Shift Table Analyses
Changes in laboratory parameters will be tabulated using shift tables categorized as low, 
normal, or high based on the normal ranges of the laboratory used for each sample.  A 
shift table summarizes shifts from baseline to minimum and maximum values (based on 
normal range) will be created.  A similar shift table will be provided to summarize shifts 
from baseline to the final post-baseline value.
Potentially Clinically Significant Laboratory Values
The criteria for potentially clinically significant laboratory values will be determined by 
CTCAE criteria of Grade 3, Grade 4 and ≥ Grade 3, with a grade worsening compared to 
baseline.  Toxicity grading scale is based on National Cancer Institute Common Toxicity 
Criteria (NCI CTC) AE version 5.0.  The number and percentage of subjects meeting the 
criteria for potentially clinically significant laboratory values will be summarized by 
treatment group.  Listings of subject-level laboratory data will be provided for subjects 
meeting the criteria.
Assessment of Liver Elevations
The liver-specific laboratory tests include the serum glutamic pyruvic transaminase 
(SGPT/ALT), serum glutamic-oxaloacetic transaminase (SGOT/AST), alkaline 
phosphatase (ALP), and total bilirubin (TBL).  The frequencies and percentages of 
 


ABBV-154
M20-371 – Statistical Analysis Plan
Version 2.0 – 10 February 2023
46
subjects with post baseline liver specific function test values that meet the following 
criteria of potential clinical interest will be summarized by treatment group:
●
ALT > 3 × ULN
●
ALT > 5 × ULN
●
ALT > 10 × ULN
●
ALT > 20 × ULN
●
AST > 3 × ULN
●
AST > 5 × ULN
●
AST > 10 × ULN
●
AST > 20 × ULN
●
TBL > 1.5 × ULN
●
TBL > 2 × ULN
●
ALP > 1.5 × ULN
●
ALT and/or AST > 3 × ULN and TBL > 1.5 × ULN
●
ALT and/or AST > 3 × ULN and TBL > 2 × ULN
●
ALT > 3 × ULN and TBL > 1.5 × ULN
●
ALT > 3 × ULN and TBL > 2 × ULN,
where ULN is the upper normal limit.  The maximum ratio relative to the ULN will be 
used to determine if subjects meet any of the criteria listed above.
A listing of subjects, defined as those meeting the following criteria will also be provided:
●
ALT and/or AST > 3 × ULN and/or ALP > 1.5 × ULN and TBL > 1.5 × ULN
10.4
Analysis of Vital Signs
Vital sign measurements of systolic and diastolic blood pressure, pulse rate, body weight, 
respiratory rate and body temperature will be summarized.  Data collected more than 70 
 


ABBV-154
M20-371 – Statistical Analysis Plan
Version 2.0 – 10 February 2023
47
days after the last dose of study drug of the analysis period (See Section 10.2.1) for the 
corresponding analysis populations will not be included.
Each vital sign variable will be summarized at all time points (starting with Baseline) with 
the number of observations, mean and standard deviation, median, minimum and 
maximum for non-missing observations.  Change from Baseline at each applicable post-
baseline visit will be summarized for each vital sign variable, with the number of 
observations, Baseline mean, and visit mean.  The mean, standard error, and 95% CI will 
be presented for the change from Baseline for each treatment group.
For each period, treatment group differences for changes from Baseline will be analyzed 
using a one-way Analysis of Variance (ANOVA) with treatment as a fixed factor and 
95% CI for treatment difference will be presented for each vital sign variable.
Vital sign variables will be evaluated based on potentially clinically important (PCI) 
criteria (See ABBV-154 PSSAP).  For each vital sign PCI criterion, the number and 
percentage of subjects who have a vital sign value meeting the criteria will be 
summarized.  Listings will be provided to summarize subject-level vital sign data for 
subjects meeting PCI criteria.
11.0
Interim Analyses
An interim analysis will be performed when approximately 66% of the subjects 
(35 subjects per group) have reached Week 12 of the Induction Period or have 
prematurely discontinued the study to inform the development of future studies.  The 
interim analysis will be conducted by an independent AbbVie team outside of the blinded 
M20-371 study team.  The interim analysis result will be reviewed by Internal Executive 
Review Committee (IERC) from AbbVie.
IERC members are not involved in this study but have the scientific and technical 
expertise and experiences for making decisions based on the interim analysis results.  The 
interim analysis result will not be reviewed by external Data Monitoring Committee 
(DMC).
 


ABBV-154
M20-371 – Statistical Analysis Plan
Version 2.0 – 10 February 2023
48
A separate interim unblinding plan will be developed to describe the detailed interim 
analysis plan, including the interim unblinding team, decision rules, execution logistics, 
and data chain of custody to protect the integrity of the clinical study.  The interim 
analysis plan will not be documented in the DMC charter.
An additional interim analysis in the Maintenance Period might be performed to inform 
the development of future studies. The results from this analysis will not impact the 
conduct of the current study.
11.1
Data Monitoring Committee
An external data monitoring committee (DMC) composed of persons independent of 
AbbVie and with relevant expertise in their field will review unblinded safety data from 
the ongoing study.  The primary responsibility of the DMC is to protect the safety of the 
subjects participating in this study.
A separate DMC charter describes the roles and responsibilities of the DMC members, 
frequency of data reviews, relevant data to be assessed, and general operations.
12.0
Overall Type-I Error Control
Overall Type I error control is not planned for this Phase 2 study.
13.0
Version History
Table 5.
SAP Version History Summary
Version
Date
Summary
1.0
17 April 2022
Original version
2.0
10 February 2023

Provided clarification that PGIC-CD+, PGIS-CD+,  
and data collected in the Wearable Device Substudy 
are not in the scope of the SAP, removed endpoints 
related to PGIC-CD+, PGIS-CD+ and the endpoints 
from the Wearable Device Substudy from SAP 
(Section 1.0, Section 3.4).

To be more precise in terms of definition of study 
populations.
 


ABBV-154
M20-371 – Statistical Analysis Plan
Version 2.0 – 10 February 2023
49
Version
Date
Summary
o
Updated the population attribute to target 
population (Section 2.1, Table 1, Table 2)
o
Specified the terminology of ITT1 population 
(Section 4.0)
o
Provided additional clarifications on the 
definition of ITT3 population (Section 4.0)

The following changes have occurred to reflect 
changes in the protocol amendment to add Rescue 
Therapy option with ABBV-154 during the 
Maintenance Period and removal of the Long-Term 
Extension study.
o
Provided description of ABBV-154 rescue 
therapy (Section 2.2, Figure 1)
o
Added ITT3-RES and SA-RES for the 
efficacy/safety analyses on the subjects who 
receive Rescue Therapy option with ABBV-154 
(Section 4.0, Section 10.1)
o
Added the analyses to evaluate the efficacy of 
ABBV-154 rescue therapy (Section 9.8)
o
Provided clarification that TEAEs for the 
Maintenance Period (SA3 population) and 
combined period analyses (SA-INMN, SA-
IN2MN population) don't include AEs with onset 
date after initiation of ABBV-154 rescue therapy 
(Section 10.2.1)
o
Added the definition of TEAE for SA-RES 
population (Section 10.2.1)
o
Removed language related to the Long-Term 
Extension study (Section 2.2, Section 9.1)

Provided additional clarity for the timing of the 
primary analysis for each period (Section 2.2, 
Section 9.1).

Provided additional clarification for the summary of 
subject disposition (Section 5.0).

Provided clarification for the calculation of duration 
of treatment that only duration of blinded study drug 
will be considered for SA1/SA2/SA3 populations, and 
also provide more clarification of study drug duration 
of Induction Group 4 (Section 6.0).
 


ABBV-154
M20-371 – Statistical Analysis Plan
Version 2.0 – 10 February 2023
50
Version
Date
Summary

Provided clarification that medications started after 
initiation of ABBV-154 rescue therapy will not be 
considered as concomitant medications for the 
Maintenance Period, and updated concomitant 
medications definition following the removal of Long-
Term Extension study (Section 7.0).

Updated the handling strategy for the intercurrent 
event of premature discontinuation of study drug 
(Section 8.2, Section 9.2.1, Table 1, Table 2).

Provided additional clarity that data from subjects 
randomized to Induction Group 1, considered as 
responder at Week 12 of the Induction Period and 
entered the Maintenance Period will not be included 
in the comparison between ABBV-154 230 mg SC 
EOW versus Placebo as they are not from the same 
randomization (Section 9.1).

Provided clarification that data collected after 
initiation of ABBV-154 rescue therapy will not be 
included in the AO analysis (Section 9.2.3).

Provided clarification for the planned analysis method 
for the additional efficacy analyses (Section 9.5).

Updated the terminology "safety topics of interest" to 
"adverse events of special interest" and provided list 
of AESIs and the corresponding identification criteria 
(Section 10.1. Section 10.2.2, Section 10.2.6, 
Appendix G).

Updated TEAE definition following the removal of 
Long-Term Extension study, and also provided 
additional clarifications on TEAE definition for the 
SA-ALL154 population and patient-year duration 
calculation method for the SA-ALL154 population  
(Section 10.2.1, Section 10.2.4).

Updated AE severity grade to CTCAE grade to align 
with AE collection strategy (Section 10.2.2, 
Section 10.2.3).

Provided additional clarity that laboratory/vital sign 
collected 70 days after last dose of study drug within 
each analysis period will not be included in the 
analysis for that period (Section 10.3, Section 10.4).

Provided additional clarity that additional interim 
analysis may be performed for the Maintenance 
Period (Section 11.0).
 


ABBV-154
M20-371 – Statistical Analysis Plan
Version 2.0 – 10 February 2023
51
14.0
References
1.
Greenland S, Robins JM.  Estimation of a common effect parameter from sparse 
follow-up data.  Biometrics.  1985;41(1):55-68.
2.
Rubin DB.  Multiple imputation for nonresponse in surveys.  John Wiley & Sons, 
Inc.  1987.
3.
Holm S.  A simple sequentially rejective multiple test procedure.  Scand J Stat.  
1979;6:65-70.
4.
Qu Y, Shurzinske L, Sethuraman S.  Defining estimands using a mix of strategies 
to handle intercurrent events in clinical trials.  Pharm Stat.  2021;20(2):314-23.
5.
Pinheiro J, Bornkamp B, Bretz F.  Design and analysis of dose-finding studies 
combining multiple comparisons and modeling procedures.  J Biopharm Stat.  
2006;16(5):639-56.
6.
Bretz F, Pinheiro JC, Branson M.  Combining multiple comparisons and modeling 
techniques in dose-response studies.  Biometrics.  2005;61(3):738-48.
 


ABBV-154
M20-371 – Statistical Analysis Plan
Version 2.0 – 10 February 2023
52
Appendix A.
Protocol Deviations
The number and percentage of subjects who reported at least one of the following 
protocol deviation categories will be provided.
●
Subject entered into the study even though s/he did not satisfy entry criteria.
●
Subject developed withdrawal criteria during the study and was not 
withdrawn.
●
Subject received wrong treatment or incorrect dose of study.
●
Subject took prohibited concomitant medication.
 


ABBV-154
M20-371 – Statistical Analysis Plan
Version 2.0 – 10 February 2023
53
Appendix B.
Crohn's Disease Activity Index (CDAI)
The Crohn's Disease Activity Index (CDAI) is a composite instrument that includes 
patient symptoms evaluated over 7 days (abdominal pain, stool frequency and general 
well-being), as well as physical and laboratory findings.  These items are scored 
individually, weighted, and do not contribute equally to the overall score.  The CDAI is 
derived from summing up the weighted individual scores of eight items as detailed below:
 


ABBV-154
M20-371 – Statistical Analysis Plan
Version 2.0 – 10 February 2023
54
Factor
Subtotal
1.
Number of liquid or very soft stools 
(Record the frequency per day)
__+___+___+___+___+___+___=___
Days:  1    2    3    4    5    6    7    Sum
×
2
2.
Abdominal pain rating:
0 = none, 1 = mild, 2 = moderate,
3 = severe
__+___+___+___+___+___+___=___
Days:  1    2    3    4    5    6    7    Sum
×
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
×
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 fistula (draining/non-
                draining)
☐
Fever over 100°F (37.8°C) 
during past week
Record "0" if no categories checked
×
20
5.
Taking Lomotil/Imodium/
Loperamide/opiates for diarrhea
0 = no, 1 = yes
________
×
30
6.
Abdominal mass
0 = none, 2 = questionable,
5 = defined
________
×
10
7.
Hematocrit:  ___.__
Male:  (47 – hematocrit) =
Female:  (42 – hematocrit) =
Subtotal
If hematocrit > normal, enter "0"
×
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"
×
1
Total
Higher CDAI scores indicate more severe disease.  For the calculation of CDAI and 
components (daily stool frequency, abdominal pain score and general well-being) at each 
visit, the following rules will be applied:
 


ABBV-154
M20-371 – Statistical Analysis Plan
Version 2.0 – 10 February 2023
55
1.
Identify the visit date with CDAI components that are collected, and set it as the 
CDAI calculation date.
2.
Calculate the subtotal scores from the component 1-3 (liquid or very soft stool 
frequency, abdominal pain score and general well-being) as follows:
a.
Select the diary data from 14 days prior to the CDAI calculation date, and set 
the data from the 4 days (the day prior to, on the day of and two days after the 
endoscopy date) to missing;
b.
Take non-missing diary data from 7 most recent days from step i.  If there are 
multiple entries on the same day for the eDiary component, use the worst 
result (larger number);
c.
If there are non-missing diary data from 7 days, the subtotal score is calculated 
as the sum of the 7-day scores, and multiplying the factor for the 
corresponding component as listed in the table above;
d.
If there are non-missing diary data from less than 7 days but greater than 
3 days (4, 5, 6 days), the subtotal score is calculated as average of the dairy 
data and times 7, and multiplying the factor for the corresponding component 
as listed in the table above;
e.
If there are only less than 4 days of non-missing diary data available, the 
subtotal score will be set to missing.
Of note, Average daily SF/AP will be determined in the same way as described 
above to derive SF/AP-related endpoints (for example, clinical remission per 
SF/AP).
3.
Subtotal scores for components 4-6 (Number of 6 listed categories, usage of 
Lomotil/Imodium/Loperamide/opiates for diarrhea and abdominal mass) will be 
determined using the data collected on the CDAI calculation date and the 
corresponding formula in the table above;
 


ABBV-154
M20-371 – Statistical Analysis Plan
Version 2.0 – 10 February 2023
56
4.
Subtotal score for component 7 (Hematocrit) is calculated as follows:
a.
Identify the Hematocrit (%) value form the same visit as the CDAI calculation 
date, use the Hematocrit that is closest to the CDAI calculation date;
b.
Hematocrit values obtained from previous visits can be used.
c.
The subtotal score for Hematocrit is calculated using the formula in the table 
above.  If Hematocrit value is greater or equal to 47% for male subjects 
(greater or equal to 42% for female subjects), the subtotal score is set to 0.
5.
Subtotal score for component 8 (percentage below standard weight) is calculated as 
follows:
a.
Standard weight is calculated based on height obtained at screening, sex and 
study operations manual Section 7.2;
b.
Body weight is based on the measurement obtained on the CDAI calculation 
data, or previous visits if the measurement is missing.
c.
The subtotal score for percentage below standard weight is calculated using the 
formula in the table above.
6.
CDAI score is calculated as the sum of subtotal scores of 8 components, and the 
total CDAI score will be rounded to 1 decimal.  If any of the subtotal scores are 
missing, the CDAI score will be missing.
 


ABBV-154
M20-371 – Statistical Analysis Plan
Version 2.0 – 10 February 2023
57
Appendix C.
Simple Endoscopic Score – CD (SES-CD)
SES-CD is calculated based the sum of individual segment values for four endoscopic 
variables (presence and size of ulcers, ulcerated surface, affected surface and presence of 
narrowing).  Each variable in each segment be scored 0 to 3 resulting in SES-CD values 
ranging from 0 to 56 with higher scores indicating more severe disease.
SES-CD Scoring:
Rectum
Sigmoid and 
Left Colon
Transverse 
Colon
Right 
Colon
Ileum
Total
Size of Ulcers 
Enter:
0 if none
1 if aphthous ulcers ( 0.1 to ≤ 
0.5 cm)
2 if large ulcers ( > 0.5 to 2 cm)
3 if very large ulcers ( > 2 cm)
Ulcerated Surface
Enter:
0 if none
1 if < 10%
2 if 10% – 30%
3 if > 30%
Affected Surface
Enter:
0 if unaffected segments
1 if < 50%
2 if 50% – 75%
3 if > 75%
Presence of Narrowing
Enter:
0 if none
1 if single, can be passed
2 if multiple, can be passed
3 if cannot be passed
TOTAL =
 


ABBV-154
M20-371 – Statistical Analysis Plan
Version 2.0 – 10 February 2023
58
Appendix D.
Patient Reported Outcomes Questionnaires Descriptions
IBDQ – Inflammatory Bowel Disease Questionnaire
The IBDQ is a 32-item (ranges 1 – 7) self-report questionnaire for patients with IBD to 
evaluate the patient reported outcomes across 4 dimensions:  bowel symptoms (loose 
stools, abdominal pain), systemic symptoms (fatigue, altered sleep pattern), social 
function (work attendance, need to cancel social events), and emotional function (anger, 
depression, irritability).  The IBDQ total Score ranges from 32 to 224 with a higher score 
indicating better outcome.
The derivation of the IBDQ total score and the four IBDQ domain scores are as follows:
Domain Scores:
S1. BOWEL SYMPTOM: Q1 + Q5 + Q9 + Q13 + Q17 + Q20 + Q22 + Q24 + 
Q26 + Q29
[score ranges from 10 - 70],
 
 
 
 
 
 
 
 
 
 
 
 
 
  
  
   
 
 
 
 
 
 
 
 
 
 
  
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
   
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
  
   
 
 


ABBV-154
M20-371 – Statistical Analysis Plan
Version 2.0 – 10 February 2023
59
S2. SOCIAL FUNCTION: Q4 + Q8 + Q12 + Q16 + Q28
[score ranges from 5 - 35],
S3. SYSTEMIC SYMPTOM: Q2 + Q6 + Q10 + Q14 + Q18
[score ranges from 5 - 35],
S4. EMOTIONAL FUNCTION: Q3 + Q7 + Q11 + Q15 + Q19 + Q21 + Q23 + 
Q25 + Q27 + Q30 + Q31 + Q32
[score ranges from 12 - 84].
Total Score:
IBDQ Total Score = SUM of (bowel symptom domain score, social function domain 
score, systemic symptom domain score, emotional function domain score).
The following convention applies to IBDQ:
When not more than 20% of items in a domain of IBDQ were missing, it was substituted 
with the mean values from the items completed in the particular domain; otherwise, they 
were treated as missing.  The 20% threshold in each domain is:  bowel symptom domain:  
2 items, systemic symptom domain:  1 item, social function domain:  1 item, emotional 
function domain:  2 items.  If any of the 4 domain scores is missing, the total IBDQ score 
will be set to missing.
SF-36 – Short Form 36
The SF-36 questionnaire is a self-administered multi-domain scale with 36 items.  
Eight subscales cover a range of functioning:  physical functioning, role-physical, bodily 
pain, general health, vitality, social functioning, role-emotional, and mental health.  The 
scoring yields a physical component score, a mental component summary score, and 
subscale scores.  Higher scores represent better outcomes.  The concepts measured by the 
 


ABBV-154
M20-371 – Statistical Analysis Plan
Version 2.0 – 10 February 2023
60
SF-36 are not specific to any age, disease, or treatment group, allowing comparison of 
relative burden of different diseases and the benefit of different treatments.
FACIT-F – Functional Assessment of Chronic Illness Therapy-Fatigue
The Functional Assessment of Chronic Illness Therapy (FACIT) measurement system is a 
comprehensive compilation of questions that measure health related quality of life in 
patients with cancer and other chronic diseases (www.facit.org).  The FACIT-F scale is a 
symptom-specific subscale of FACIT and is composed of 13 fatigue-related questions as 
follows.  The response to each question is as follows: 0=Not at all, 1=A little bit, 
2=Somewhat, 3=Quite a bit, 4=Very much.
1.
I feel fatigued
2.
I feel weak all over
3.
I feel listless ("washed out")
4.
I feel tired
5.
I have trouble starting things because I am tired
6.
I have trouble finishing things because I am tired
7.
I have energy
8.
I am able to do my usual activities
9.
I need to sleep during the day
10.
I am too tired to eat
11.
I need help doing my usual activities
12.
I am frustrated by being too tired to do the things I want to do
13.
I have to limit my social activity because I am tired
 


ABBV-154
M20-371 – Statistical Analysis Plan
Version 2.0 – 10 February 2023
61
In order to have higher values representing lower level of fatigue, all of the items, except 
for item 7 "I have energy" and item 8 "I am able to do my usual activities," are assigned 
reversed scores: reversed score = 4 – raw score.  The total FACIT-F score will then be 
calculated as follows: 
●
FACIT-F score = 13[Sum of answered-item scores / Number of items 
answered]
The score ranges from 0 to 52, 52 being the lowest level of fatigue.
When there are missing data, provided that more than 50% of the items 
(i.e., at least 7 of 13 items) were answered in FACIT-F questionnaire, the total score will 
not be deemed as missing but be calculated as the mean response for all the 
non-missing-value items.  If less than 50% of the items were answered, the total score will 
have a missing value.
 


ABBV-154
M20-371 – Statistical Analysis Plan
Version 2.0 – 10 February 2023
62
Appendix E.
Random Seeds
In case of non-convergence, the random seed will be updated by adding 100000 at each 
attempt until convergence of model happens.
Table I-1.
Random Seeds for NRI-C
Variables
Random Seed
MCMC Procedure
PROC MI
CDAI
20371
30371
SES-CD (for 20 individual variables)
N/A
31371
SF 
22371
32371
AP score
23371
33371
IBDQ total score
24371
34371
Bowl Urgency
25371
35371
Rectal Bleeding
26371
36371
 


ABBV-154
M20-371 – Statistical Analysis Plan
Version 2.0 – 10 February 2023
63
Appendix F.
Crohn's Disease Location Per SES-CD
For isolated ileal disease in the analysis using SES-CD:  Patients who have SES-CD = 0 
in all segments other than ileum are considered to have isolated ileitis.
For ileocolonic disease in the analysis using SES-CD:  Patients who have SES-CD 
different than 0 in the ileum and at least one of the colonic segments.
For colonic disease in the analysis using SES-CD:  Patients who have SES-CD = 0 in the 
ileum and SES-CD different than 0 in at least one of the colonic segments.
 


ABBV-154
M20-371 – Statistical Analysis Plan
Version 2.0 – 10 February 2023
64
Appendix G.
List of Adverse Events of Special Interest (AESIs)
AESI 
Criteria for Identification of Events
Serious infections
"Infections" CMQ (subset for SAEs)
Opportunistic infections
"Opportunistic Infection" CMQ for Opportunistic
Infections excluding Tuberculosis and Herpes Zoster 
Active TB
"Active Tuberculosis" CMQ
Hypersensitivity reactions
"Hypersensitivity" SMQ narrow
Serious allergic reactions
"Anaphylactic Reaction" SMQ (Narrow) or
"Angioedema" SMQ (Narrow) (subset to SAEs)
Malignancies
Malignant Tumours SMQ (Narrow) 
Malignancies excluding 
non-melanoma skin cancer 
(NMSC)
Malignant Tumours SMQ (Narrow) excluding (Skin 
malignant tumors SMQ Broad excluding PTs identified 
by Melanoma CMQ)
NMSC
Skin Malignant Tumours SMQ (Broad) excluding PTs 
identified by Melanoma CMQ
Lymphoma
Malignant Lymphomas SMQ (Narrow)
Systemic glucocorticoid side 
effects
Based on adjudicated results (the identification of 
events to be adjudicated are described in the GC 
Adjudication Charter)
Adrenal insufficiency
"Tertiary Adrenal Insufficiency (ABBV-154 Product 
Specific)" CMQ
Iatrogenic Cushing's 
syndrome
"Iatrogenic Cushing's Syndrome (ABBV-154 Product 
Specific)" CMQ