Clinical trial NCT05044234
Conditions: Psoriasis
Keywords: Psoriasis Plaque Psoriasis Cedirogant ABBV-157
Sponsor: AbbVie
Start date: 2021-11-16; Completion date: 2022-11-30
Enrollment: 156 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
Psoriasis is a chronic disease characterized by marked inflammation and thickening of the skin that results in thick, scaly skin plaques. This study assessed how safe and effective cedirogant (ABBV-157) was compared to placebo in adult participants with moderate to severe psoriasis. Efficacy and safety-related measurements assessed disease activity in participants with plaque psoriasis.

Cedirogant (ABBV-157) is an investigational drug being developed for the treatment of chronic plaque psoriasis. Participants were put into 1 of 4 groups, called treatment arms and each group received a different treatment. There was a 1 in 4 chance that participants were assigned to placebo.

Participants received oral daily doses of cedirogant or placebo capsules for 16 weeks.

There may have been a higher burden for participants in this study compared to usual standard of care. Participants attended regular visits per routine clinical practice. The effect of the treatment was checked by medical assessments, checking for side effects, and questionnaires.

Detailed description:

Arms: arm 1: Participants received placebo capsules for cedirogant orally once daily (QD) for 16 weeks. arm 2: Participants received 75 mg cedirogant orally once daily (QD) for 16 weeks. arm 3: Participants received 150 mg cedirogant orally once daily (QD) for 16 weeks. arm 4: Participants received 375 mg cedirogant orally once daily (QD) for 16 weeks.
Interventions: intervention 1: Cedirogant intervention 2: Placebo
Intervention descriptions: intervention 1: Capsule, Oral intervention 2: Capsule, Oral

Protocol documents:
Prot_000.pdf: 


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TABLE OF CONTENTS
1
SYNOPSIS
5
2
INTRODUCTION
7
2.1
BACKGROUND AND RATIONALE
7
2.2
BENEFITS AND RISKS TO SUBJECTS
8
3
OBJECTIVES AND ENDPOINTS
9
3.1
OBJECTIVES, HYPOTHESES, AND ESTIMANDS
9
3.2
PRIMARY ENDPOINT
9
3.3
SECONDARY ENDPOINTS
9
3.4
ADDITIONAL EFFICACY ENDPOINTS
10
3.5
SAFETY MEASURES
10
3.6
PHARMACOKINETIC ENDPOINTS
10
3.7
BIOMARKER RESEARCH ENDPOINTS
11
4
INVESTIGATIONAL PLAN
11
4.1
OVERALL STUDY DESIGN AND PLAN
11
4.2
DISCUSSION OF STUDY DESIGN
12
5
STUDY ACTIVITIES
13
5.1
ELIGIBILITY CRITERIA
13
5.2
CONTRACEPTION RECOMMENDATIONS
17
5.3
PROHIBITED MEDICATIONS AND THERAPY
18
5.4
PRIOR AND CONCOMITANT THERAPY
19
5.5
WITHDRAWAL OF SUBJECTS AND DISCONTINUATION OF STUDY
20
5.6
FOLLOW-UP AFTER SUBJECT DISCONTINUATION OF STUDY DRUG OR FROM STUDY
22
5.7
STUDY DRUG
23
5.8
RANDOMIZATION/DRUG ASSIGNMENT
24
5.9
PROTOCOL DEVIATIONS
24
5.10 DATA MONITORING COMMITTEE
24
6
SAFETY CONSIDERATIONS
25
6.1
COMPLAINTS AND ADVERSE EVENTS
25
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6.2
TOXICITY MANAGEMENT
29
7
STATISTICAL METHODS & DETERMINATION OF SAMPLE SIZE
30
7.1
STATISTICAL AND ANALYTICAL PLANS
30
7.2
DEFINITION FOR ANALYSIS POPULATIONS
31
7.3
HANDLING POTENTIAL INTERCURRENT EVENTS FOR THE PRIMARY ENDPOINT
31
7.4
STATISTICAL ANALYSES FOR EFFICACY
31
7.5
STATISTICAL ANALYSES FOR PHARMACOKINETICS
32
7.6
STATISTICAL ANALYSES FOR SAFETY
32
7.7
INTERIM ANALYSIS
32
7.8
OVERALL TYPE I ERROR CONTROL
33
7.9
SAMPLE SIZE DETERMINATION
33
8
ETHICS
33
8.1
INDEPENDENT ETHICS COMMITTEE/INSTITUTIONAL REVIEW BOARD
33
8.2
ETHICAL CONDUCT OF THE STUDY
33
8.3
SUBJECT CONFIDENTIALITY
34
9
SOURCE DOCUMENTS AND CASE REPORT FORM COMPLETION
34
10 DATA QUALITY ASSURANCE
34
11 COMPLETION OF THE STUDY
34
12 REFERENCES
34
LIST OF TABLES
TABLE 1.
IDENTITY OF INVESTIGATIONAL PRODUCTS
23
LIST OF FIGURES
FIGURE 1.
STUDY SCHEMA
12
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LIST OF APPENDICES
APPENDIX A.
STUDY-SPECIFIC ABBREVIATIONS AND TERMS
36
APPENDIX B.
RESPONSIBILITIES OF THE INVESTIGATOR
39
APPENDIX C.
LIST OF PROTOCOL SIGNATORIES
40
APPENDIX D.
ACTIVITY SCHEDULE
41
APPENDIX E.
PROTOCOL SUMMARY OF CHANGES
45
APPENDIX F.
OPERATIONS MANUAL
49
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2 INTRODUCTION
2.1 Background and Rationale
Why Is This Study Being Conducted?
Psoriasis is a chronic debilitating immunologic disease characterized by marked inflammation and 
thickening of the epidermis that result in thick, scaly skin plaques.  In most developed countries, the 
prevalence in adults is between approximately 1.5 and 5%.1 About 20% of patients have moderate to 
severe disease with a considerable negative impact on psychosocial and economic status.2,3  It is 
increasingly recognized that psoriasis is more than a superficial disease, with 30% of patients having 
joint involvement; additionally, high correlations exist between psoriasis and obesity, diabetes, 
depression, metabolic syndrome, and cardiovascular events.4,5
Currently available oral systemic agents provide modest efficacy in plaque psoriasis patients; therefore, 
patients are increasingly being treated with biologic agents, such as Tumor Necrosis Factor-alpha 
inhibitors (etanercept and adalimumab), an interleukin (IL)-12/23 inhibitor (ustekinumab),5 and IL-17A 
inhibitors (secukinumab and ixekizumab).  In addition, other recently approved systemic agents for the 
treatment of psoriasis include an IL-17RA inhibitor (brodalumab) and IL-23p19 inhibitors (risankizumab, 
guselkumab and tildrakizumab).
While the clinical efficacy of ustekinumab indicates a role for both IL-12 and IL-23 in the pathogenesis of 
psoriasis,6 more recent data suggest that IL-23 is disproportionately involved in the maintenance of 
chronic psoriasis.7  IL-23 is thought to be involved in the pathophysiology of psoriasis via induction and 
maintenance of T helper 17 (Th17) type cells, and other IL-23 responsive cells.  This is supported by 
recent clinical data indicating that monoclonal antibodies that block IL-17A (the cytokine produced by 
Th17 cells), IL-17RA, and direct blockade of IL-23 with IL-23p19 inhibitors, have high efficacy in 
psoriasis.6,8-10  
There is still clinical need for increased efficacy as the most effective anti-TNF and anti-IL-12/23 agents 
provide approximately 75% improvement in psoriasis in about 50 to 80% of patients and these 
responses can be lost over time.  Although the anti-IL-17A, -IL-17RA, and -IL-23p19 agents 
(i.e., secukinumab, ixekizumab, brodalumab and guselkumab) may provide better efficacy than anti-TNF 
therapies and ustekinumab, they require monthly, every other month, or quarterly injections.6,8-10  There 
remains an unmet medical need for an oral medication targeting the validated IL-17 pathway to 
potentially deliver efficacious intervention in dermatological indications.
Cedirogant is an inverse agonist of retinoic acid-related orphan receptor gamma, thymus (RORγt), a key 
transcription factor responsible for IL-17 synthesis in vivo and the master regulator of the Th17 cell 
lineage program.  RORγt expression is driven by IL-23 and directly supports IL-17 production in multiple 
immune cell types, particularly Th17 cells; thus, RORγt bridges the gap between these 2 important 
cytokines.  Targeting RORγt has the potential to directly block cellular function (i.e., RORγt-dependent 
genes), a different strategy from the neutralization of effector molecules (such as IL-17) by biologics.
This dose ranging study is designed to explore the range of efficacious and tolerated doses in adult 
subjects with moderate to severe chronic plaque psoriasis for determination of the dose(s) to be 
selected for a pivotal Phase 3 program in psoriasis.
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Clinical Hypothesis
Cedirogant is superior to placebo in achieving ≥75% reduction from baseline in the Psoriasis Area and 
Severity Index score (PASI 75) at Week 16 in patients with moderate to severe plaque psoriasis who are 
candidates for systemic therapy or phototherapy.
2.2 Benefits and Risks to Subjects
Based on the available preclinical and clinical data, cedirogant is expected to demonstrate therapeutic 
benefit in the treatment of chronic plaque psoriasis.  Study drugs may be associated with adverse events 
(AEs) as detailed in the subject informed consent form(s).  Not all of the potential side effects of the 
study drugs may be known.  In addition, subjects may experience discomfort or inconvenience related to 
study procedures.
Medical review of the safety data from the Phase 1 program with cedirogant (including Study M17-239, 
a single ascending dose study; Study M17-238, a multiple ascending dose [MAD] study; Study M18-809, 
a multiple dose study; and Study M19-371, a single and multiple dose study) did not identify any 
unexpected risk or trend in the healthy volunteer population or patients with chronic plaque psoriasis.  
No drug related ocular events, such as those observed in a different compound of the same chemical 
class, have been observed in the Phase 1 studies of cedirogant.
In Study M21-560, conducted in healthy volunteers to evaluate the effects of cedirogant on QT interval,
no clinically relevant QT prolongation was observed following the administration of 375 mg or 750 mg
doses of cedirogant, with mean placebo-corrected change from baseline in Fridericia-corrected QT
interval of 4 and 6 milliseconds, respectively. Based on these results, standard electrocardiogram (ECG)
eligibility criteria (Section 5.1) are considered appropriate.
In Study M18-809, conducted in healthy volunteers to evaluate the modulatory effects of cedirogant on 
cytochrome P450 (CYP) enzymes, cedirogant showed moderate CYP3A and CYP2C19 induction potential 
with a 375 mg QD regimen, and a limited effect was observed on CYP2C9 while no clinically relevant 
effects were observed on CYP1A2 or CYP2D6.
In Study M20-115, conducted in healthy volunteers to evaluate potential drug-drug interactions 
between cedirogant and statins at steady state, co-administration of 375 mg QD cedirogant resulted in a 
160% and 70% increase in Cmax and AUC0-24 of rosuvastatin, respectively; resulted in no change in AUC 
and 40% increase in Cmax of atorvastatin; and resulted in an 85% and 40% increase in Cmax and AUC0-24 of 
the active metabolite of atorvastatin (ortho-hydroxy atorvastatin), respectively.  Taken together, the 
safety and efficacy data from the Phase 1 program support further development of cedirogant in 
Phase 2 in subjects with psoriasis. Refer to Section 5.1 for instructions on daily use limits of concomitant 
statins.
For further details, please see findings from completed studies, including safety data, in the current 
cedirogant Investigator's Brochure.
In view of the Coronavirus Disease - 2019 (COVID-19) pandemic, the benefit: risk profile of various 
immunomodulatory therapies on COVID-19 is being evaluated.  At this time, the effects of cedirogant on 
the course of COVID-19 are not well defined.
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3 OBJECTIVES AND ENDPOINTS
3.1 Objectives, Hypotheses, and Estimands
Primary Objective
The primary objective of this study is to assess the safety and efficacy of cedirogant versus placebo for 
the treatment of moderate to severe plaque psoriasis in adult subjects who are candidates for systemic 
therapy or phototherapy.

Primary efficacy objective: The primary efficacy objective of the study is to demonstrate a higher 
rate of subjects achieving PASI 75 at Week 16 with cedirogant compared to placebo in the 
Intent-to-Treat (ITT) population, which consists of all randomized subjects (further described in 
Section 7.2).
The hypothesis corresponding to the primary endpoint is the proportion of subjects achieving PASI 75 at 
Week 16 with cedirogant is greater than that with placebo.  The estimand corresponding to the primary 
endpoint is defined as the difference in the proportion of subjects achieving PASI 75 at Week 16, 
regardless of treatment discontinuation, between each of the cedirogant dose groups compared with 
placebo in the ITT Population.
Secondary Objectives
The secondary efficacy objectives are to demonstrate higher rates of subjects who achieve the 
secondary endpoints specified in Section 3.3 below in the ITT population.
3.2 Primary Endpoint
The primary endpoint is the achievement of ≥75% reduction from baseline in PASI score (PASI 75) at 
Week 16.
3.3 Secondary Endpoints
Secondary Endpoints

Achievement of a static Physician Global Assessment (sPGA) score of clear or almost clear at 
Week 16

Achievement of ≥50% reduction from baseline in PASI score (PASI 50) at Week 16

Achievement of ≥90% reduction from baseline in PASI score (PASI 90) at Week 16

Achievement of 100% reduction from baseline in PASI score (PASI 100) at Week 16

Achievement of Psoriasis Symptoms Scale (PSS) total score of 0 at Week 16 for subjects with 
PSS >0 at Baseline

Achievement of itch Numerical Rating Scale (NRS) ≥4-point improvement from Baseline at 
Week 16 for subjects with itch NRS ≥4 at Baseline
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3.4 Additional Efficacy Endpoints
Additional efficacy endpoints include the primary and all secondary endpoints assessed at visits other 
than the Week 16 Visit as noted in the Study Activities Table (Appendix D).  Additional efficacy endpoints 
include the following measurements assessed at visits as specified in the Study Activities Table:

Change from baseline in Dermatology Life Quality Index (DLQI) score

Achievement of a DLQI score of 0 or 1

Achieving a change of ≥4 points from baseline in DLQI score (for patients whose DLQI score at 
baseline is ≥4)

Treatment Satisfaction Questionnaire for Medication Version 9 (TSQM-9) domain scores 
(effectiveness, convenience and global satisfaction domains) 

Change from baseline in Hospital Anxiety and Depression Scale (HADS)-Anxiety score

Change from baseline in HADS-Depression score

Change from Baseline in Work Productivity and Activity Impairment (WPAI):  Psoriasis 
Questionnaire measures:

Percent work time missed (Absenteeism)

Percent impairment while working (Presenteeism)

Percent overall work impairment

Percent activity impairment
3.5 Safety Measures
Safety evaluations include AE monitoring, physical examinations, vital sign measurements, 
electrocardiogram (ECG) variables, and clinical laboratory testing (hematology, chemistry, and urinalysis) 
as measures of safety and tolerability for the entire study duration.
3.6 Pharmacokinetic Endpoints
Plasma cedirogant concentrations, possible metabolite(s), and if warranted, relevant concomitant 
medications will be obtained at the visits indicated in the Activity Schedule (Appendix D).  A nonlinear 
mixed effects modeling approach will be used to estimate the population central values and the 
empirical Bayesian estimates of the individual values of cedirogant oral clearance (apparent clearance) 
and volume of distribution (V/F).  Additional parameters may be estimated if useful in the interpretation 
of the data.
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3.7 Biomarker Research Endpoints
Optional biospecimens (e.g., whole blood for plasma, serum, peripheral blood mononuclear cell [PBMC], 
RNA, DNA, and tissue biopsy) will be collected at specified time points (Appendix D) throughout the 
study to evaluate known and/or novel disease-related or drug-related biomarkers in circulation or at 
tissue sites.  Types of biomarkers may include nucleic acids, proteins, lipids, and/or metabolites, either 
free or in association with particular cell types.  The analyses may include but are not limited to:  blood 
leukocyte subpopulations, serum and plasma cytokine evaluations, transcriptomic, genetic, epigenetic 
analysis, and tissue genomic and histopathological analysis to evaluate biomarker endpoints related to 
safety, disease state, response to treatment, and target pathway.  The biomarker research results may 
not be included with the clinical study report.  Further details regarding the biomarker research 
rationale and collection time points are located in the Operations Manual, Section 2.1 and Section 3.16.
4 INVESTIGATIONAL PLAN
4.1 Overall Study Design and Plan
This is a Phase 2, multicenter, randomized, double-blind, parallel-group, placebo-controlled dose 
ranging study that will evaluate the safety and efficacy of cedirogant in approximately 200 adult subjects 
with moderate to severe plaque psoriasis and who are candidates for systemic therapy or phototherapy.
The study is comprised of a 28-day Screening Period, a 16-week double-blind Treatment Period, and a 
30-day Follow-up Period.
Subjects who meet eligibility criteria at Baseline will be randomized in a 1:1:1:1 ratio to 1 of 4 treatment 
groups:

Cedirogant 375 mg once daily (QD) (N = 50)

Cedirogant 150 mg QD (N = 50)

Cedirogant 75 mg QD (N = 50)

Placebo QD (N = 50)
The schematic of the study is shown in Figure 1.  Clinical assessments, laboratory tests, collection of 
samples for cedirogant concentration, optional biomarker samples and optional skin biopsies will be 
performed at specified clinic visits as noted in the Study Activities Table (Appendix D).  Further details 
regarding study procedures are located in the Operations Manual (Appendix F).  See Section 5 for 
information regarding eligibility criteria.
An interim analysis will be conducted after the first 140 subjects have either completed the Week 16 
assessments or withdrawn from the study.  Study sites and subjects will remain blinded for the duration 
of the study.
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Figure 1.
Study Schema
BL = baseline; PASI = Psoriasis Area Severity Index; PBO = placebo; QD = once daily
4.2 Discussion of Study Design
Choice of Control Group
Placebo has been selected as the appropriate control group to evaluate the efficacy endpoints as 
double-blind, placebo-controlled study designs are generally acknowledged as standard for unbiased 
estimates of treatment (cedirogant versus placebo) differences.
Appropriateness of Measurements
Standard (i.e., widely used and generally recognized as reliable, accurate, and relevant [able to 
discriminate between effective and ineffective agents]) statistical, clinical, and laboratory procedures 
will be utilized in this study.  All efficacy and safety-related measurements in this study are standard for 
assessing disease activity in subjects with plaque psoriasis.  All clinical and laboratory procedures in this 
study are standard and generally accepted.
Suitability of Subject Population
This Phase 2 study will provide essential efficacy and safety data for cedirogant for the indication of 
moderate to severe plaque psoriasis.  Efficacy results of cedirogant in a Phase 1 study of subjects with 
plaque psoriasis showed a potential therapeutic effect to improve disease activity.  Safety results of 
cedirogant in healthy volunteers and subjects with plaque psoriasis indicate no safety issues of concern 
and no dose limiting toxicity.
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Selection of Doses in the Study
The cedirogant doses to be administered in this study are 75, 150, and 375 mg QD.  Based on analyses of 
ex-vivo IL-17A inhibition by cedirogant in Phase 1 studies, the 75 mg QD dose is predicted to have a 
submaximal therapeutic effect.  The 150 mg QD dose is predicted to approach the plateau and the 
375 mg QD dose is predicted to be approximately at the plateau for inhibition of ex-vivo IL-17A by 
cedirogant.  All three doses are expected to have plasma exposures in PsO patients which are within the 
exposures previously evaluated in Phase 1 single ascending dose and MAD studies, and those achieved
in preclinical toxicology studies up to 16 weeks in duration.
Based on the pharmacokinetic (PK) data at cedirogant doses of 75 to 375 mg in the MAD study in 
healthy subjects (Study M17-238 Substudy 1), the cedirogant dose of 75 mg is expected to provide 
steady-state cedirogant AUCtau of approximately 51 μg•hr/mL.
Based on the PK data from the multiple dose study in psoriasis patients (Study M17-238 Substudy 2), the 
highest planned dose of 375 mg QD is expected to provide steady-state cedirogant AUCtau of 
approximately 206 μg•hr/mL.
Cedirogant safety margins at the highest planned dose of 375 QD are approximately 8-fold based on the 
exposure (area under the curve [AUC]) at the no-observed-adverse-effect-level (NOAEL) in the rat, and 
11-fold based on the dog NOAEL in the 4-week toxicity study (no NOAEL defined in the 16-week dog 
study).
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.
Consent
1. Subjects or their legally authorized representative must 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 65 years of age at the time of 
Screening.
3. Laboratory values meeting the following criteria within the screening period prior to the 
first dose of study drug:

Serum aspartate transaminase (AST) < 2 × upper limit of normal (ULN);

Serum alanine transaminase (ALT) < 2 × ULN;

Total Bilirubin ≤1.5 × ULN
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
Total white blood cell (WBC) count > 3,000/µL;

Absolute neutrophil count > 1,500/µL;

Platelet count > 100,000/µL;

Hemoglobin > 9 g/ (dL);
4. Are willing and able to comply with procedures required in this protocol.
Disease/Condition Activity
5. Subjects must have a clinical diagnosis of moderate to severe chronic plaque psoriasis with a 
disease duration of at least 6 months as determined by subject interview of his/her medical 
history and confirmation of diagnosis through physical examination by the investigator.
6. Subjects must be a candidate for systemic therapy or phototherapy and meet the following 
disease activity criteria at both Screening and Baseline visits:

Subjects must have a PASI score ≥12;

Subjects must have a sPGA score of 3 or 4;

Subjects must have a body surface area (BSA) affected by psoriasis ≥10%.
7. Subjects must not be primary non-responders to previous anti-IL-17 (e.g., secukinumab, 
ixekizumab, brodalumab), anti-IL-23 (e.g., guselkumab, tildrakizumab, risankizumab), or 
anti-IL-12/23 (e.g., ustekinumab) treatment for chronic plaque psoriasis.
8. Subjects must not be diagnosed with erythrodermic psoriasis, generalized or localized 
pustular psoriasis, medication-induced or medication exacerbated psoriasis, or new onset 
guttate psoriasis or any other active skin disease which may interfere with assessment of 
chronic plaque psoriasis.
Subject History
9. Subjects are judged to be in good health as determined by the Principal Investigator, based 
upon the results of medical history, laboratory profile, physical examination, chest x-ray (CXR), 
and a 12-lead ECG performed during Screening.
10. No history of hepatitis B virus (HBV), hepatitis C virus (HCV), or human immunodeficiency 
virus (HIV), or active infection with tuberculosis (TB) or infections requiring intravenous (IV) 
treatment.

No evidence of HBV or HCV infection defined as the following:

HBV:  Hepatitis B surface antigen (HBs Ag) positive (+) test or detected sensitivity on the 
HBV DNA polymerase chain reaction (PCR) qualitative test for subjects who are HB core 
antibody (HBc Ab) positive (+) (and for HB surface antibody [Hbs Ab] positive (+) subjects 
where mandated by local requirements).

HCV:  HCV RNA detectable in any subject with anti HCV antibody (HCV Ab).

No evidence of HIV, defined as confirmed positive anti-HIV antibody test.
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
No evidence of active TB:  Subjects with a positive QuantiFERON-TB gold test (or interferon 
gamma release assay [IGRA] equivalent) or TB skin test may participate in the study if 
further work up (according to local practice / guidelines) establishes conclusively that the 
subject has no evidence of active TB.  If the presence of latent TB is established, subjects are 
required to be treated with prophylactic anti-TB therapy for at least 2 weeks prior to 
initiation of cedirogant.  Specific requirements for TB testing and prophylaxis are located in 
the Operations Manual, Section 3.14.

No infections (bacterial, fungal or viral) requiring IV systemic treatment within 4 weeks of 
the Baseline Visit.
11. No known active severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection:  If 
a subject has signs/symptoms suggestive of SARS-CoV-2 infection, the subject must have a 
negative molecular (e.g., PCR) test result or 2 negative antigen test results at least 24 hours 
apart.  Note:  SARS-CoV-2 diagnostic tests should be applied following local 
requirements/recommendations.
12. Subjects who do not meet SARS-CoV-2 infection eligibility criteria must be screen failed and 
may only rescreen after they meet the following SARS-CoV-2 infection viral clearance criteria:

At least 10 days since first positive test result have passed in asymptomatic patients or at 
least 10 days since recovery, defined as resolution of fever without use of antipyretics and 
improvement in symptoms.
13. No history of any malignancy within the last 5 years or documented active malignancy 
except for successfully treated non-melanoma skin cancer (NMSC) or localized carcinoma in situ 
of the cervix.
14. No history of clinically significant (per investigator's judgment) drug or alcohol abuse within 
the last 6 months, including medicinal or recreational cannabis or cannabinoids.
15. No evidence of uncontrolled thyroid disease.
16. No history of organ transplantation.
17. No major surgery performed within 12 weeks prior to randomization or planned during the 
conduct of the study (e.g., hip replacement, aneurysm removal, stomach ligation).
18. No history of an allergic reaction or significant sensitivity to constituents of the study drug 
(and its excipients) and/or other products in the same class.
19. No clinically relevant or significant ECG abnormalities or risk factors for torsade de pointes, 
including:

Evidence of second or third degree atrioventricular block at Screening or Baseline;

QT interval corrected for heart rate (QTc) using Fridericia's correction formula (QTcF) is 
> 430 msec (males) or > 450 msec (females) at Screening or Baseline;

History of QTc prolongation, bradyarrhythmia or clinically significant bradycardia or subjects 
with a resting heart rate of < 50 beats per minute;

Family history of QTc prolongation or sudden cardiac death in immediate family members 
< 30 years of age.
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20. No history of clinically significant medical conditions other than the indication being studied 
or any other reason that the investigator determines would interfere with the subject's 
participation in this study, would make the subject an unsuitable candidate to receive study 
drug, or would put the subject at risk by participating in the protocol.
Contraception
21. For all females of childbearing potential; a negative serum pregnancy test at the Screening 
Visit and a negative urine pregnancy test at baseline prior to the first dose of study drug.
22. Females of childbearing potential must practice at least 1 protocol-specified method of birth 
control, that is effective from Baseline through at least 30 days after the last dose of study drug.  
If hormonal contraception is used, an additional barrier method (such as condoms with 
spermicide) must be used.  Female subjects of non-childbearing potential do not need to use 
birth control.
23. Females who are not pregnant or breastfeeding, and are not considering becoming pregnant
or donating eggs during the study or for approximately 30 days after the last dose of study drug.
Prior and Concomitant Medications
24. Subjects must not have been treated with any prohibited medications as specified in 
Section 5.3.
25. Subjects must not require daily use of rosuvastatin at doses higher than 10 mg, pitavastatin 
at doses higher than 2 mg, pravastatin at doses higher than 40 mg, fluvastatin at doses higher 
than 20 mg, atorvastatin at doses higher than 40 mg, or lovastatin at doses higher than 40 mg.  
Use of simvastatin at any dose is allowed.
26. Subjects must not have been treated with any investigational non-biologic drug within 
30 days or 5 half-lives of the drug (whichever is longer) or 12 weeks for biologic investigational 
therapy prior to the first dose of study drug, or is currently enrolled in another clinical study.  
Examples of investigational non-biologic drugs include but are not limited to:  
phosphodiesterase 4 (PDE4) inhibitors such as orismilast, and Janus kinase (JAK) inhibitors 
(including JAK1-3 and tyrosine kinase 2 inhibitors such as tofacitinib or deucravacitinib).
27. Subjects must not have systemically used known strong CYP3A inhibitors (for example, 
clarithromycin or itraconazole) or inducers (for example, phenytoin or rifampin) from Screening 
through the end of the study.
28. Subjects must not have received any live vaccine within 28 days prior to the first dose of 
study drug (or longer if required locally) or expected need of live vaccination during study 
participation including at least 30 days after the last dose of study drug.
Other
29. Subjects must not have been previously exposed to cedirogant or any other RORγt inhibitors 
such as vimirogant.
30. Subjects must be willing and able to comply with procedures required in this protocol.
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31. In the opinion of the investigator, the subjects are suitable candidates for enrollment in this 
study.
5.2 Contraception Recommendations
Contraception Requirements for Females
Subjects must follow the following contraceptive guidelines as specified:

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 females 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.
2.
Postmenopausal females

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, of Childbearing Potential

Females of childbearing potential must avoid pregnancy while taking study drug(s) and for 
at least 30 days after the last dose of study drug.

The efficacy of hormonal contraception is potentially decreased due to interaction with 
cedirogant; therefore, a barrier contraception, such as condoms with or without spermicide, 
must be used in addition to the hormonal contraception methods (combined oral 
contraception, progestogen only hormonal contraception and Intrauterine hormone-
releasing system [IUS]) listed below.  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.
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
Bilateral tubal occlusion/ligation (can be via hysteroscopy, provided a 
hysterosalpingogram confirms success of the procedure). For Japan:  only bilateral tubal 
ligation.

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 guidelines, 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 should be based on 
the local label.
5.3 Prohibited Medications and Therapy
The following medications are prohibited within the specified timeframe prior to Baseline Visit and 
through the duration of the study:

Topical therapies for the treatment of chronic plaque psoriasis such as corticosteroids, vitamin D 
analogs, or retinoids, within 2 weeks.

Phototherapy (e.g., UVA or UVB) and Psoralen + ultraviolet light A (PUVA) phototherapy, tanning 
beds, or extended sun exposure that could affect disease severity or interfere with disease 
assessments within 4 weeks.

Systemic non-biologic therapies for the treatment of chronic plaque psoriasis (including but not 
limited to corticosteroids, oral retinoids, methotrexate, apremilast, cyclosporine) or known to 
improve chronic plaque psoriasis within 4 weeks.

Biologic therapies to treat psoriasis:

Etanercept or biosimilar versions within 6 weeks

Adalimumab, infliximab, or biosimilar versions within 12 weeks

Ixekizumab, brodalumab, or other IL-17 inhibitors (excluding secukinumab) within 16 weeks

Ustekinumab, secukinumab, risankizumab, guselkumab, tildrakizumab, bimekizumab, or 
other IL-23 inhibitors within 24 weeks.

Any investigational non-biologic for the treatment of chronic plaque psoriasis within 4 weeks or 
5 half-lives (whichever is longer).

Any investigational biologic for psoriasis within 12 weeks or 5 half-lives (whichever is longer).
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
Subjects may not use herbal therapies or other traditional medicines within 4 weeks.

Subjects may not have systemic use of drugs that are strong CYP3A inhibitors (for example, 
clarithromycin or itraconazole) or inducers (for example, phenytoin or rifampin) within 4 weeks.

Vaccines:  Live vaccines are prohibited within 28 days prior to the first dose of study drug or 
during study participation and including at least 30 days (or longer if required locally) after the 
last dose of study drug.  If the subject and investigator choose to receive / administer live 
vaccines, these vaccinations must be completed at least 28 days (or longer if required locally) 
before the first dose of study drug with appropriate precautions.  Although not mandated by the 
protocol, vaccines recommended by local guidelines should be considered.  Examples of live 
vaccines include but are not limited to the following:

Monovalent live attenuated influenza A (H1N1) (intranasal);

Seasonal trivalent live attenuated influenza (intranasal);

Zostavax (herpes zoster, live attenuated);

Rotavirus;

Varicella (chicken pox);

Measles-mumps-rubella or measles-mumps-rubella varicella;

Oral polio vaccine;

Smallpox;

Yellow fever;

Bacille Calmette-Guérin;

Typhoid (oral)

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);

Pertussis (Tdap) vaccine
5.4 Prior and Concomitant Therapy
Any medication or vaccine (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 
(30 day Follow-up Visit).
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Any questions regarding concomitant or prior therapy should be raised to the AbbVie emergency 
contact.  Information regarding potential drug interactions with cedirogant can be located in the 
cedirogant Investigator's Brochure.
Subjects must be able to safely discontinue any prohibited medications within 30 days or 5 half-lives 
(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.
Cedirogant showed moderate induction of CYP3A and CYP2C19 at a dose of 375 mg QD.  Therefore, 
concomitant administration of cedirogant may decrease the plasma concentrations and efficacy of drugs 
that are sensitive substrates for CYP3A or CYP2C19 (e.g., simvastatin, omeprazole).
SARS CoV-2 Vaccination
Given the ongoing COVID-19 pandemic, selected non-live vaccines (e.g., messenger RNA [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 cedirogant on SARS-CoV-2 vaccination is unknown.
COVID-19 Vaccine:  Whenever-possible, subjects should not have received a COVID-19 vaccination in the 
7 days prior to randomization or plan to receive a COVID-19 vaccination within the first 7 days after 
initiation of study drug.
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 in patients with psoriasis 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.
5.5 Withdrawal of Subjects and Discontinuation of Study
AbbVie may terminate this study prematurely, either in its entirety or partially (discontinue one or more 
treatment group[s]), 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.  In the event the study is partially terminated, all subjects in the terminated arm(s) will be asked 
to return for a PD visit and to perform a 30-day follow-up phone call after the last dose of study drug.  
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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.
A subject may voluntarily withdraw or be withdrawn 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 
Therapeutic Area Medical Director (TA MD) may mandate individual subject discontinuation from study 
drug in case of a safety concern.  Subjects may be discontinued for reasons including, but not limited to, 
the following:

Clinically significant abnormal laboratory results or AEs, which rule out continuation of the study 
drug, as determined by the investigator or the AbbVie TA MD.

Grade 2 or higher ocular AEs considered related to study drug administration (this is referenced 
in the 6.2 toxicity management section of the protocol).

The investigator believes it is in the best interest of the subject.

The subject requests withdrawal from 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.  Note:  intentional/prospective deviations from 
the protocol are NOT allowed, see Section 5.9.

Introduction of prohibited medications or dosages and continuation of the study drug would 
place the subject at risk.

Subject is diagnosed with a malignancy; exception localized NMSC or carcinoma in situ of the 
cervix where discontinuation is at the discretion of the investigator.

Subject is noncompliant with TB prophylaxis (if applicable) or develops active TB at any time 
during the study.

The subject becomes pregnant while on study drug.

Subject is significantly noncompliant with study procedures.

Any subject administered study drug having confirmed ECG changes that are considered 
clinically significant and considered related to study drug, or a confirmed absolute 
QTcF value > 500 msec, or a confirmed absolute QTcF value change from baseline > 60 msec.
Subjects who withdraw from the study will not be replaced.
State of Emergency or Pandemic-Related Acceptable Protocol Modification
During states of emergency or pandemic situations, it has been necessary to employ mitigation 
strategies to enable the investigator to ensure subject safety and continuity of care.  Acceptable 
mitigation strategies are identified and included in the Operations Manual in Appendix F.
The investigator should contact the sponsor medical contact 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.
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Interruption/Discontinuation of Study Drug Due to COVID-19 Infection
During the study drug dosing period, a subject with confirmed (viral test positive) or suspected 
COVID-19 infection can only be dosed with study drug if the following COVID-19 viral clearance criteria 
are met:

At least 10 days since first positive test result have passed in asymptomatic patients or at least
10 days since recovery, defined as resolution of fever without use of antipyretics and 
improvement in symptoms.
Delays in study drug dosing due to the above COVID-19 testing guidance for subjects must be discussed 
with the AbbVie medical contact, along with the possibility of premature discontinuation from the study 
drug dosing period.  Follow subsequent protocol Section 5.6 for subjects who discontinued study drug.  
Frequency or timing of COVID-19 testing and intervals between testing for the above viral clearance 
criteria may be adjusted to account for epidemiologic trends, updated information regarding infectivity, 
and local/institutional guidelines.
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 continue to be followed for all regularly scheduled visits as outlined in the 
Protocol Activities Schedule in the Operations Manual (Appendix F, Section 2) and adhere to all study 
procedures except for administration of study drug and PK sample collection unless a subject decides to 
discontinue study participation entirely (withdrawal of informed consent).  Subjects should be advised 
on the continued scientific importance of their data even if they discontinue treatment with study drug 
early.  Subjects who prematurely discontinue study drug treatment should remain compliant with the 
prohibited medication requirements while participating in the study.
Premature Discontinuation of Study (Withdrawal of Informed Consent)
If a subject prematurely discontinues study participation, the procedures outlined for the Premature 
Discontinuation Visit should be completed as soon as possible, preferably within 2 weeks.  In addition, a 
30-day follow-up phone call after the last dose of study drug will be completed to ensure all 
treatment-emergent AEs/serious adverse event (SAE) have been resolved.
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.
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, 
no new biomarker analysis data will be collected for the withdrawn subject or added to the existing data 
or database(s), and the samples will be destroyed.  A subject may withdraw consent for optional 
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biomarker research at any time and remain in the clinical study.  Data generated from clinical study 
and/or optional biomarker research, before subject withdrawal of consent, will remain part of the study 
results.
5.7 Study Drug
Cedirogant and matching placebo will be manufactured by AbbVie (Table 1).  Each dose will be taken 
orally QD beginning on Day 1 (Baseline) and should be taken at approximately the same time each day.  
The study drug can be taken with or without food.  If subjects should forget to take their cedirogant or 
matching placebo dose at their regularly scheduled dosing time, they should take the forgotten dose as 
soon as they remember as long as it is at least 12 hours before their next scheduled dose.  Otherwise, 
they should skip the missed dose and take the next dose at the next scheduled dosing time.  The 
phototoxic potential of cedirogant is unknown; therefore, pending further evaluation, subjects will be 
cautioned to limit sunlight exposure during the study and for 30 days after the last dose of study drug.
Subject dosing will be recorded on a subject dosing diary.  The subject will be instructed to return all 
blister cards (even if empty) to the study site personnel at each study visit.  The study site personnel will 
document compliance.
AbbVie will provide study drug for cedirogant or matching placebo.  If a subject is unable to come to the 
study site to pick up their study drug due to a pandemic or emergency situation, a direct-to-patient 
(DTP) study drug shipment can be made from the study site to the subject if allowed by local 
regulations.  AbbVie will submit any required notifications to the regulatory authority as applicable.  
Refer to the Operations Manual in Appendix F for details on DTP shipment of study drug.
Cedirogant and matching placebo will be packaged in blister cards with quantities sufficient to 
accommodate study design.  Each kit will be labeled per local requirements and this label must remain 
affixed to the kit.  Upon receipt, study drug should be stored as specified on the label and kept in a 
secure location.  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.  Site staff will complete all blank spaces on the label before 
dispensing to subjects.  Study drug will only be used for the conduct of this study.
Table 1.
Identity of Investigational Products
Cedirogant
Placebo for Cedirogant
Dosage form
Capsule
Capsule
Strength
75 mg
N/A
Dosage
75, 150, and 375 mg
N/A
Route of administration
Oral
Oral
Manufacturer
AbbVie
AbbVie
N/A = not applicable
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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 
assignment according to the randomization schedule.
All AbbVie personnel with direct oversight of the conduct and management of the trial (with the 
exception of AbbVie Drug Supply Management Team), the investigator, study site personnel, and the 
subject will remain blinded to each subject's treatment throughout the study.  To maintain the blind, the 
cedirogant capsules and placebo capsules 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 
(global.helpdesk@cenduit.com).  For country-specific phone numbers, please see the following website: 
https://www.cenduit.com/support-247-global-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 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 states of emergency or 
pandemic situations), the investigator is responsible for notifying IEC/independent review board (IRB), 
regulatory authorities (as applicable), and AbbVie.
5.10 Data Monitoring Committee
An internal data monitoring committee (DMC) composed of clinicians and statisticians independent of 
any cedirogant clinical trials outside their role on the DMC, with relevant expertise in their field will 
review unblinded data from the ongoing study.  The DMC is responsible for safeguarding the interests of 
trial subjects by assessing the safety of the interventions during the trial, as well as for monitoring the 
integrity and interpretability of the trial.  When needed, high-level unblinded efficacy data may also be 
requested by the DMC and reviewed so that the DMC can assess benefit/risk of any emerging safety 
differences.  A separate DMC charter will be prepared outside of the protocol and will further describe 
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the roles and responsibilities of the DMC members, frequency and scope of the data reviews, and 
expectations for blinded communications.  The DMC will provide recommendations to the study team 
regarding ongoing trial conduct or modifications to the trial as described in the separate DMC charter.  
Communications from the DMC to the study team will not contain information that could potentially 
unblind the primary study team to subject treatment assignments.
In order to maintain blinding, a statistical data analysis center (SDAC) is responsible for performing the 
analyses described in the DMC charter as well as additional analyses requested by the DMC and 
facilitating interpretation and answering questions that arise before, during or after DMC review.
The DMC will review unblinded safety data from the ongoing study according to the schedule provided 
in the DMC charter, including AEs, laboratory values, vitals sign values and ECG results.
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 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 AE is defined as any untoward medical occurrence in a subject or clinical investigation subject 
administered a pharmaceutical product and which does not necessarily have a causal relationship with 
this treatment.  An AE can therefore be any unfavorable and unintended sign (including an abnormal 
laboratory finding), symptom, or disease temporally associated with the use of a medicinal 
(investigational) product, whether or not the event is considered causally related to the use of the 
product.
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Such an event can result from use of the drug as stipulated in the protocol or labeling, as well as from 
"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 AE or not.  Any worsening of a pre-existing condition or illness 
including chronic plaque psoriasis is considered an AE.  Worsening in severity of a reported AE should be 
reported as a new AE.  Laboratory abnormalities and changes in vital signs are considered to be AEs only 
if they result in discontinuation from the study, necessitate therapeutic medical intervention, meets 
protocol-specific criteria (see Section 6.2 regarding toxicity management), and/or if the investigator 
considers them to be AEs.
The investigators will monitor each subject for clinical and laboratory evidence of AEs on a routine basis 
throughout the study.  All AEs will be followed to a satisfactory conclusion.
An elective surgery/procedure scheduled to occur during a study will not be considered an AE if the 
surgery/procedure is being performed for a pre-existing condition and/or the surgery/procedure has 
been pre-planned prior to study entry.  However, if the pre-existing condition deteriorates unexpectedly 
during the study (e.g., surgery performed earlier than planned), then the deterioration of the condition 
for which the elective surgery/procedure is being done will be considered an AE.
If any of the following Safety Topics of Interest events are reported, then the following supplemental 
report must be completed.
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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 AEs reported from the time of study drug administration until 30 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 AEs will be collected from the time the subject 
signs the study-specific informed consent.
Safety Topics of Interest
Adverse events will be monitored throughout the study to identify any safety topics of interest that may 
indicate a trend or risk.
The potential for abdominal distention, gastrointestinal pain, vomiting, diarrhea and eye pain, redness 
or blurred vision has been identified.
No ocular findings were seen in the preclinical studies conducted with cedirogant and no ocular AEs 
considered related to drug have been reported in the cedirogant Phase 1 studies to date.  There have 
been no reports of ocular findings in the literature with other products in development of the same 
mechanism of action.
Adverse Event Severity and Relationship to Study Drug
The investigator will rate the severity of each AE according to the National Cancer Institute (NCI) 
Common Terminology Criteria for Adverse Events (CTCAE) (Version 5.0).
The investigator will use the following definitions to assess the relationship of the AE to the use of study 
drug:
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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 AE, 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, information regarding the 
pregnancy and the outcome will be collected.
The pregnancy outcome of an elective or spontaneous abortion, stillbirth or congenital anomaly is 
considered an SAE and must be reported to AbbVie within 24 hours after the site becomes aware of the 
event.
6.2 Toxicity Management
The toxicity management of the AEs including safety topics of interest consists of safety monitoring 
(review of AEs on an ongoing basis, and periodic/ad hoc review of safety issues by an independent Data 
Monitoring Committee), and, if applicable, interruption of study drug dosing with appropriate clinical 
management and/or discontinuation of the subjects from study drug.  The management of specific AEs 
and laboratory parameters is described below.
Serious Infections:  Study drug should be interrupted if a subject develops a serious infection.  Study 
drug may be restarted once the infection has been successfully treated.  Subjects who develop active TB 
must be permanently discontinued from study drug.
Ocular Events:  Any subject with CTCAE Grade 2 or higher AE ocular event or considered to be necessary 
by investigator must follow up with an ophthalmologist as soon as possible, but within 7 days at the 
latest.  Grade 2 or higher ocular AEs considered related to study drug administration qualify for 
withdrawal criteria.
Management of Laboratory Abnormalities:

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 is to occur as 
soon as possible.

In case of confirmed creatine phosphokinase > 5 × ULN accompanied by muscle related 
symptoms and without a clear alternate etiology (e.g., trauma), interrupt study drug and 
evaluate.

Study drug should be discontinued for the following laboratory abnormalities:
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
Occurrence of one or more of the following hepatic test abnormalities (confirmed on a 
second separate sample):

ALT or AST > 8 × ULN;

ALT or AST > 5 × ULN for more than 2 weeks;

ALT or AST > 3 × ULN and Total Bilirubin > 2 × ULN or international normalized ratio 
[INR] > 1.5;

ALT or AST > 3 × ULN with the appearance of fatigue, nausea, vomiting, right upper 
quadrant pain or tenderness, fever, rash, and/or eosinophilia (> 5%).
Elective and Emergency Surgeries
For elective and emergency surgeries the following rules will apply:
If the subject must undergo emergency surgery, the study drug should be interrupted at the time of the 
surgery.  After emergency surgery, allow reintroduction of study drug once the physician has examined 
the surgical site and determined that study drug may be safely restarted.
Elective surgery, and interruption of study drug for such a surgery, will not be allowed until after the 
Week 16 visit has been completed.  If the subject undergoes elective surgery, the study drug should be 
interrupted at least 1 week prior to the planned surgery.  Allow reintroduction of study drug once the 
physician has examined the surgical site and determined that study drug may be safely restarted.
7 STATISTICAL METHODS & DETERMINATION OF SAMPLE SIZE
7.1 Statistical and Analytical Plans
The statistical methods provided in this protocol will be focused on analyses of primary and secondary 
endpoints.  Complete and specific details of the statistical analysis will be described in the statistical 
analysis plan (SAP).
The Primary Analysis will be conducted after all subjects have completed Week 16 of the treatment 
period or withdrawn from the study, data has been cleaned and a database lock has occurred.
An interim analysis will be conducted after the first 140 subjects have either completed the Week 16 
assessments or withdrawn from the study.  The study team will remain blinded during the conduct of 
the interim analysis and the analysis results will not be released to the study team.  Study sites and 
subjects will remain blinded for the duration of the study.
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7.2 Definition for Analysis Populations
The following populations will be used for analyses:

Intent-to-Treat (ITT) Population:  The ITT Population includes all randomized subjects.  The 
efficacy analyses, summary of demographic, and baseline disease characteristics will be carried 
out with the ITT Population.  Subjects will be analyzed as randomized.

Safety Population:  The Safety Population includes all subjects who are randomized and received 
at least 1 dose of study drug.  All safety analyses will use the Safety Population.  Subjects will be 
analyzed as treated (i.e., according to the actual treatments received), regardless of the 
treatment assigned.
7.3 Handling Potential Intercurrent Events for the Primary Endpoint
The primary endpoint (Section 3.2) will be analyzed in the ITT Population and no intercurrent events will 
impact the analysis.  All data collected, regardless of premature discontinuation of study drug, will be 
used in the analysis.
7.4 Statistical Analyses for Efficacy
The efficacy analysis will be conducted in the ITT Population and all statistical tests will be performed at 
a 2-sided significance level of 0.1.  The 95% confidence interval of the treatment effect will be provided.
For categorical endpoints, comparisons will be made between each dose of cedirogant and placebo 
using Fisher's exact test.  Non-responder imputation (NRI) incorporating multiple imputation (MI) to 
handle missing data due to COVID-19 (NRI-MI) will be the primary approach to handle missing values for 
categorical endpoints.
For continuous variables, comparisons of change and/or percent change from Baseline will be made 
between each dose of cedirogant and placebo based on the Mixed Model Repeated Measures (MMRM) 
adjusting for treatment, visit, and treatment-by-visit interaction as fixed factors, and Baseline value 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 PASI 75 score at Week 16.  Analysis of the primary endpoint 
will be conducted on the ITT Population based on treatment as randomized.  Comparison of the primary 
endpoint will be made between each cedirogant dose and placebo using Fisher's exact test at a 2-sided 
significance level of 0.1.
The NRI-MI method will be the primary approach to handle missing values.  A sensitivity analysis will be 
performed for the primary endpoint, using MI to handle all missing values.
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Summary and Analysis of Secondary Endpoints
Categorical endpoints will be analyzed using Fisher's exact test.  The comparisons of all the secondary 
endpoints will be made between each cedirogant dose and placebo at a 2-sided significance level of 0.1.
Summary and Analysis of Additional Efficacy Endpoints
Additional endpoints, as described in Section 3.4, will also be analyzed.  Analysis details will be provided 
in the SAP.
Subgroup Analysis for Efficacy
To evaluate the consistency of efficacy across demographic and other baseline characteristics, 
summaries and analyses will be performed for selected subgroups for the primary endpoints.  The 
subgroups will be defined in SAP.
7.5 Statistical Analyses for Pharmacokinetics
Plasma concentrations will be tabulated for each subject and summarized using descriptive statistics.
Data from this study may be combined with data from other studies for the population PK and 
exposure-response analyses.  Population PK and exposure-response analyses of only data from this 
study may not be conducted.
7.6 Statistical Analyses for Safety
All safety analyses will be performed on the Safety Population, based on the actual treatment received.  
Treatment-emergent adverse events (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 30 days after the last dose of study drug.  The number and percentage of subjects 
experiencing TEAEs and exposure-adjusted number of events (events per 100 year) will be tabulated 
using the 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.
Mean change in laboratory and vital signs variables will be summarized.  For selected laboratory 
parameters, a listing of all subjects with any laboratory value that is Grade ≥3 of NCI CTCAE v4.03 will be 
provided.  Additional details for the safety analysis will be provided in the SAP.
7.7 Interim Analysis
An interim analysis will be performed by an independent team at AbbVie after the first 140 subjects 
have either completed the Week 16 assessments or withdrawn from the study.  The objective of this 
analysis is to assess the benefit and risk profile of the treatment regimens and initiate preparation of 
cedirogant to the next development stage.  As this interim analysis is not intended for the claim of 
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success of this study, there will be no alpha spending for this interim analysis.  An Interim Unblinding 
Plan will be developed to describe the analyses to be performed and will include execution logistics, 
unblinded analysis team, and the data chain of custody to protect the integrity of the study.  An Internal 
Executive Review Committee (IERC) will review the interim unblinded results following the IERC charter.  
The study team will remain blinded.
7.8 Overall Type I Error Control
Overall Type I error control is not planned in this Phase 2 study.
7.9 Sample Size Determination
Given the planned total sample size of 200 subjects (50 subjects in each arm), the study has more than 
95% power to detect the treatment differences of 60% in PASI 75 in at least one cedirogant group versus 
placebo (PASI 75 response rate of 11%) using a two-sided significance level of 0.1 based on the 2-sample 
Chi-Squared test.
8 ETHICS
8.1 Independent Ethics Committee/Institutional Review Board
The protocol, informed consent form(s), recruitment materials, and all subject materials will be 
submitted to the Independent Ethics Committee/Institutional Review Board (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.
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 
locations for data collection (e.g., use of a local lab instead of a central lab), and shipping investigational 
product and/or supplies direct to subjects to ensure continuity of treatment where allowed.  In all cases, 
these alternative measures must be allowed by local regulations and permitted by IRB/IEC.  Investigators 
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should notify AbbVie if any urgent safety measures are taken to protect the subjects against any 
immediate hazard.
8.3 Subject Confidentiality
To protect subjects' confidentiality, all subjects and their associated samples will be assigned numerical 
study identifiers or "codes."  No identifiable information will be provided to AbbVie.
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 complies with the currently 
approved protocol, ICH Good Clinical Practice (GCP), and applicable local regulatory requirement(s).  
During states of emergency or pandemic situations, remote source 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.
11
COMPLETION OF THE STUDY
The end-of-study is defined as 30 days after the last study drug administration.
12
REFERENCES
1.
World Health Organization. Global report on psoriasis. Geneva, Switzerland: WHO; 2016 [cited 2017 
Sep 17]. Available from: http://apps.who.int/iris/handle/10665/204417.
2.
Menter A, Griffiths CE. Current and future management of psoriasis. Lancet. 2007;370(9583):272-84.
3.
Helmick CG, Lee-Han H, Hirsch SC, et al. Prevalence of psoriasis among adults in the U.S.: 2003-2006 
and 2009-2010 National Health and Nutrition Examination Surveys. Am J Prev Med. 2014;47(1):37-
45.
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4.
Mease PJ, Gladman DD, Papp KA, et al. Prevalence of rheumatologist-diagnosed psoriatic arthritis in 
patients with psoriasis in European/North American dermatology clinics. J Am Acad Dermatol. 
2013;69(5):729-35.
5.
Davidovici BB, Sattar N, Prinz J, et al. Psoriasis and systemic inflammatory diseases: potential 
mechanistic links between skin disease and co-morbid conditions. J Invest Dermatol. 
2010;130(7):1785-96.
6.
Lebwohl M, Strober B, Menter A, et al. Phase 3 Studies Comparing Brodalumab with Ustekinumab in 
Psoriasis. N Engl J Med. 2015;373(14):1318-28.
7.
Reich K, Puig L, Paul C, et al. One-year safety and efficacy of ustekinumab and results of dose 
adjustment after switching from inadequate methotrexate treatment: the TRANSIT randomized trial 
in moderate-to-severe plaque psoriasis. Br J Dermatol. 2014;170(2):435-44.
8.
Smith RL, Warren RB, Eyre S, et al. Polymorphisms in the IL-12beta and IL-23R genes are associated 
with psoriasis of early onset in a UK cohort. J Invest Dermatol. 2008;128(5):1325-7.
9.
Gordon KB, Blauvelt A, Papp KA, et al. Phase 3 Trials of Ixekizumab in Moderate-to-Severe Plaque 
Psoriasis. N Engl J Med. 2016;375(4):345-56.
10. Reich K, Armstrong AW, Foley P, et al. Efficacy and safety of guselkumab, an anti-interleukin-23 
monoclonal antibody, compared with adalimumab for the treatment of patients with moderate to 
severe psoriasis with randomized withdrawal and retreatment: Results from the phase III, double-
blind, placebo- and active comparator-controlled VOYAGE 2 trial. J Am Acad Dermatol. 
2017;76(3):418-31.
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APPENDIX A. STUDY-SPECIFIC ABBREVIATIONS AND TERMS
Abbreviation
Definition
AE
adverse event
ALT
alanine transaminase
AST
aspartate transaminase
AUC
area under the curve
AUCinf
area under the concentration-time curve from time 0 to infinite time
AUCtau
area under the concentration-time curve over the dosing interval
BSA
body surface area
COVID-19
Coronavirus Disease – 2019
CTCAE
Common Terminology Criteria for Adverse Events
CXR
chest x-ray
CYP
cytochrome P450
CYP3A
cytochrome P450 3A isoform subfamily
DLQI
Dermatology Life Quality Index
DMC
data monitoring committee
DNA
deoxyribonucleic acid
DTP
direct-to-patient
ECG
electrocardiogram
eCRF
electronic case report form
EDC
electronic data capture
FSH
follicle-stimulating hormone
GCP
Good clinical practice
HADS
Hospital Anxiety and Depression Scale
HB
hepatitis B
HBc Ab
hepatitis B core antibody
HBs Ab
hepatitis B surface antibody
HBs Ag
hepatitis B surface antigen
HBV
hepatitis B virus
HCV
hepatitis C virus
HCV Ab
HCV antibody
HIV
human immunodeficiency virus
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ICH
International Council for Harmonisation of Technical Requirements for Pharmaceuticals 
for Human Use
IEC
Independent Ethics Committee
IERC
Internal Executive Review Committee
IGRA
interferon gamma release assay
IL
interleukin
IMP
Investigational Medicinal Product
INR
international normalized ratio
IRB
Institutional Review Board
IRT
interactive response technology
ITT
Intent-to-Treat
IUS
Intrauterine hormone-releasing system
IV
intravenous
JAK
Janus kinase
MAD
multiple ascending dose
MedDRA
Medical Dictionary for Regulatory Activities
MI
multiple imputation
MMRM
Mixed Model Repeated Measures
mRNA
messenger RNA
NCI
National Cancer Institute
NMSC
non-melanoma skin cancer
NRI
Non-Responder Imputation
NRS
Numerical Rating Scale
OR
odds ratio
PASI
Psoriasis Area Severity Index
PBMC
peripheral blood mononuclear cell
PCR
polymerase chain reaction
PDE4
phosphodiesterase 4
PK
pharmacokinetic(s)
PPD
purified protein derivative
PRO
patient-reported outcome
PSS
Psoriasis Symptoms Scale
PUVA
psoralen-UV-A
QD
once daily
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QTc
QT interval corrected for heart rate
QTcF
QT interval corrected for heart rate using Fridericia's formula
RNA
ribonucleic acid
RSI
reference safety information
SAE
serious adverse event
SAP
statistical analysis plan
SARS-CoV-2
severe acute respiratory syndrome coronavirus 2
SDAC
Statistical Data Analysis Center
SUSAR
Suspected Unexpected Serious Adverse Reactions
sPGA
static Physician Global Assessment
TA MD
Therapeutic Area Medical Director
TB
tuberculosis
TEAE
treatment-emergent adverse event(s)
Th17
T helper 17
TSH
thyroid-stimulating hormone
TSQM-9
Treatment Satisfaction Questionnaire for Medication Version 9
ULN
upper limit of normal
V/F
apparent volume of distribution
WBC
white blood cell
WPAI
Work Productivity and Activity Impairment
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APPENDIX B. RESPONSIBILITIES OF THE INVESTIGATOR
Protocol M18-816:  A Phase 2b, Multicenter, Randomized, Double-Blind, Placebo-Controlled, 
Dose-Ranging Study to Evaluate the Safety and Efficacy of Cedirogant (ABBV-157) in Adult Subjects with 
Moderate to Severe Psoriasis.
Protocol Date:  13 May 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.
1.
Personally conducting or supervising the described investigation(s).
2.
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.
3.
Reporting complaints that occur in the course of the investigation(s) to AbbVie.
4.
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).
5.
Informing all associates, colleagues, and employees assisting in the conduct of the study about 
their obligations in meeting the above commitments.
6.
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.
7.
Maintaining records demonstrating that an ethics committee reviewed and approved the initial 
clinical protocol and all of its amendments.
8.
Reporting promptly, all changes in the research activity and all unanticipated problems involving 
risks to human subjects or others, to the appropriate individuals (e.g., coordinating investigator, 
institution director) and/or directly to the ethics committees and AbbVie.
9.
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)
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APPENDIX C. LIST OF PROTOCOL SIGNATORIES
Name
Title
Functional Area
Clinical Study Leadership
Clinical Study Leadership
Medical Writing
Therapeutic Area Medical Monitor
Global Pharmaceutical R & D
Statistics 
Clinical Pharmacology and 
Pharmacometrics
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APPENDIX D. ACTIVITY SCHEDULE
The following table shows the required activities across the 11 subject encounters.  The individual 
activities are described in detail in the Operations Manual (Appendix F).  Allowed modifications due 
states of emergency or pandemic situations are detailed in the Operations Manual.
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APPENDIX E. PROTOCOL SUMMARY OF CHANGES
Previous Protocol Versions
Protocol
Date
Version 1.0
28 July 2021
Version 1.1 (Japan Only)
02 December 2021
Protocol Appendix (Japan Only)
01 November 2021
The purpose of this version is to update the following sections below. 
Summary of Protocol Changes: 

Protocol Title Page and Synopsis:  Updated number of sites to approximately 50.
Rationale:  To align with the number of sites currently participating.

Protocol Section 2.2, Benefits and Risks to Subjects:  Revised Study M19-371 description to 
indicate that it is a single "and multiple" dose study.
Rationale:  To correct the inadvertent omission.

Protocol Section 2.2, Benefits and Risks to Subjects:  Added a paragraph regarding QT 
prolongation results from Study M21-560 to support the appropriateness of standard ECG 
eligibility criteria in Study M18-816.
Rationale:  To justify the appropriateness of eligibility criteria #19, which includes exclusion of 
subjects with risk factors for torsade de pointes.

Protocol Section 2.2, Benefits and Risks to Subjects:  Added a paragraph regarding results from 
Study M20-115, conducted in healthy volunteers to evaluate potential drug-drug interactions 
between cedirogant and statins at steady state.
Rationale:  To provide current PK data regarding the interactions between cedirogant and 
studied statins to support the changes made to the daily use limits of concomitant statin in 
Section 5.1.

Protocol Section 2.2, Benefits and Risks to Subjects:  Added a paragraph regarding results from 
Study M18-809, conducted in healthy volunteers to evaluate the modulatory effects of 
cedirogant on CYP enzymes.
Rationale:  To provide current PK data regarding the modulatory effects of cedirogant on CYP 
enzymes, which provides support to the language added in Section 5.4 noting a potential 
decreased efficacy of concomitant CYP3A and CYP2C19 substrate medications.

Protocol Section 3.4, Additional Efficacy Endpoints; Operations Manual Section 3.19, 
Unscheduled Visits; Section 7.6, Skin Biopsy Procedure:  Updated wording for the activities table 
to "Study Activities Table."
Rationale:  Updated for consistency throughout both documents.
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
Protocol Section 3.6, Pharmacokinetic Endpoints; Operations Manual Section 3.15.  
Pharmacokinetic Sampling:  Added ", possible metabolite(s), and if warranted, relevant 
concomitant medications" to plasma cedirogant concentrations.
Rationale:  To provide clarification.

Protocol Section 3.7, Biomarker Research Endpoints:  Corrected Operations Manual Section 
number from 3.8 to 3.16.
Rationale:  To correct typographical error.

Protocol Section 4.1, Overall Study Design and Plan:  Added "BL = baseline" to the abbreviations 
list for Figure 1, Study Schema.
Rationale:  To add missing abbreviation.

Protocol Section 4.2, Selection of Doses in the Study:  Updated the dose language based on final 
data from multiple ascending dose (MAD) Study M17-238, as well as safety margin based on 
most recent rat and dog toxicity results.
Rationale:  To update language based on final data from completed MAD and animal studies.

Protocol Section 5.1, Eligibility Criteria:  Added "at both Screening and Baseline visits" to 
criterion #6.
Rationale:  To provide clarification.

Protocol Section 5.1, Eligibility Criteria:  Added "active" to describe skin disease in criterion #8. 
Rationale:  To provide clarification.

Protocol Section 5.1, Eligibility Criteria:  Added "or 2 negative antigen test results at least 24 
hours apart" to criterion #11. 
Rationale:  Updated to reflect the current protocol template language regarding COVID-19 
testing.

Protocol Section 5.1, Eligibility Criteria; Section 5.5, Interruption/Discontinuation of Study Drug 
Due to COVID-19 Infection:  Revised criterion #12 to "at least 10 days since first positive 
molecular test result have passed in asymptomatic patients or at least 10 days since recovery…"
Rationale:  To align with current SARS-CoV-2 guidelines.

Protocol Section 5.1 Eligibility Criteria:  Updated pitavastatin dose from 1 mg to 2 mg and 
atorvastatin dose from 20 mg to 40 mg in criterion #25.
Rationale:  Pitavastatin PK is mainly affected by OATP1B1 (organic anion transporting 
polypeptide 1B1).  An estimated < 100% increase in OATP1B1 substrate by co-administered 
cedirogant (375 mg QD) is expected based on the results from the statin drug-drug interaction 
(DDI) Study M20-115.  The atorvastatin dose was adjusted based on observed 85% increase in 
Cmax of ortho-hydroxy atorvastatin (active metabolite of atorvastatin) by cedirogant (375 mg 
QD) in the statin DDI Study M20-115.

Protocol Section 5.1 Eligibility Criteria: Revised "cytochrome P450 (CYP) 3A" to "CYP3A" in 
criterion #27.
Rationale: Changed to abbreviation since already defined at first use. 
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
Protocol Section 5.3, Prohibited Medications and Therapy:  Added "including but not limited to 
corticosteroids, oral retinoids…" to the list of systemic non-biologic therapies for the treatment 
of chronic plaque psoriasis.
Rationale:  To provide clarification.

Protocol Section 5.3, Prohibited Medications and Therapy:  Deleted "with unknown effects on 
CYP3A" regarding the prohibition of herbal therapies or other traditional medicines.
Rationale:  To ensure no potential DDI.  

Protocol Section 5.4, Prior and Concomitant Therapy:  Added language regarding moderate
induction of CYP3A and CYP2C19 by cedirogant 375 mg QD, and the potential effects on drugs 
that are sensitive substrates with concomitant administration of cedirogant.

Rationale:  To note a potential decreased efficacy of concomitant CYP3A and CYP2C19 substrate 
medications given the inductive effects of cedirogant on these two CYP enzymes observed in 
Study M18-809.

Protocol Section 5.5, Withdrawal of Subjects and Discontinuation of Study:  Added "partially 
discontinue one or more treatment group(s)" regarding study termination.  Added sentence to 
state that all subjects in the terminated arm(s) will be asked to return for a PD visit and to 
perform a 30-day follow-up phone call after the last dose of study drug.
Rationale:  To provide clarification in the event that only partial termination of the study is 
required.

Protocol Section 6.1, Complaints and Adverse Events:  Added herpes zoster and hypersensitivity 
to supplemental report form table. 
Rationale:  Herpes Zoster will be included as an additional search as an opportunistic infection as 
the risk is increased with subjects with psoriasis.  Hypersensitivity reactions have been reported 
in healthy volunteer studies.

Protocol Section 6.2, Toxicity Management, Ocular Events:  Expanded definition of AE ocular 
event to include investigator discretion when event does not meet the specified criterion of 
CTCAE Grade 2 or higher.  Mandatory follow up with an ophthalmologist was changed from 
occurring within 7 days (± 1 day) to occurring as soon as possible, but within 7 days at the latest.
Rationale:  Although current data demonstrates the risk of ocular toxicity with cedirogant to be 
low, a conservative approach for monitoring and reporting ocular AEs will be followed. Updated 
for consistency with Japan Only protocol amendment version 1.1.

Protocol Appendix B, Responsibilities of the Investigator:  Updated title to include ABBV-157.
Rationale:  Added for consistency with the title page.

Protocol Appendix C, List of Protocol Signatories:  Updated list of protocol signatories.
Rationale:  To reflect current personnel and roles.

Operations Manual Section 3.14, Tuberculosis Screening and Prophylaxis:  For tuberculosis 
screening, added "which is the preferred testing method," to QuantiFERON-TB Gold Test (or 
IGRA equivalent). For tuberculosis testing, added "and the QUANTIFERON-TB Gold test should 
be utilized unless it is not possible or both tests are required by local regulations."
Page 47 of 100
 


STUDY M18-816  |  Version 2.0
CONFIDENTIAL INFORMATION
No use or disclosure outside AbbVie is permitted without prior written authorization from AbbVie.
Rationale:  To provide clarification and clearer guidance for sites to follow.

Operations Manual Section 3.15, Pharmacokinetic Sampling:  Added "The date and timing of the 
last two doses administered prior to the blood sample collection and the date and timing of the 
blood sample collection should be recorded to the nearest minute."
Rationale:  To provide clarification.

Operations Manual Section 7.1, Static Physician Global Assessment (sPGA):  Corrected the
numbering from sequential to individual score values (0 through 4) by descriptor.  
Rationale:  To correct the typographical errors.

Operations Manual Section 7.2, Psoriasis Area and Severity Index (PASI) and Assessment of Total 
Body Surface Area:  Corrected formula from "Dh" to "Dh."
Rationale:  To correct the typographical error.
Page 48 of 100
 

SAP_001.pdf: 
ABBV-157
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Version 2.0 – 15 December 2022
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Statistical Analysis Plan for Study M18-816
Phase 2b, Multicenter, Randomized, Double-Blind, 
Placebo-Controlled, Dose-Ranging Study to Evaluate 
the Safety and Efficacy of Cedirogant (ABBV-157) in 
Adult Subjects with Moderate to Severe Psoriasis
Date: 15 December 2022
Version 2.0
 
NCT05044234


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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.......................................................................... 6
2.3
Treatment Assignment and Blinding....................................................... 7
2.4
Sample Size Determination .................................................................... 8
3.0
Endpoints...............................................................................8
3.1
Primary Endpoint ................................................................................... 8
3.2
Secondary Endpoints.............................................................................. 8
3.3
Other Efficacy Endpoints ....................................................................... 9
3.4
Safety Endpoints .................................................................................... 9
4.0
Analysis Populations ...........................................................10
5.0
Subject Disposition..............................................................10
6.0
Study Drug Duration and Compliance ..............................11
7.0
Demographics, Baseline Characteristics, Medical 
History, and Prior/Concomitant Medications ...................11
7.1
Demographics and Baseline Characteristics.......................................... 11
7.2
Medical History.................................................................................... 12
7.3
Prior and Concomitant Medications...................................................... 12
8.0
Handling of Potential Intercurrent Events for the 
Primary and Secondary Endpoints ....................................13
9.0
Efficacy Analyses.................................................................13
9.1
General Considerations......................................................................... 13
9.2
Handling of Missing Data..................................................................... 14
9.3
Primary Efficacy Endpoint and Analyses.............................................. 14
9.3.1
Primary Efficacy Endpoint ................................................................... 14
9.3.2
Main Analysis of Primary Efficacy Endpoints ...................................... 14
9.3.3
Sensitivity and Supplementary Analyses of the Primary Efficacy 
Endpoint............................................................................................... 14
9.4
Secondary Efficacy Endpoints and Analyses ........................................ 14
9.4.1
Secondary Efficacy Endpoints.............................................................. 14
 


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9.4.2
Main Analyses of Secondary Efficacy Endpoints.................................. 14
9.4.3
Sensitivity and Supplementary Analyses for Secondary Efficacy 
Endpoints ............................................................................................. 15
9.5
Additional Efficacy Analyses ............................................................... 15
9.6
Efficacy Subgroup Analyses................................................................. 15
10.0
Safety Analyses....................................................................15
10.1
General Considerations......................................................................... 15
10.2
Adverse Events..................................................................................... 16
10.2.1
Treatment-Emergent Adverse Events.................................................... 16
10.2.2
Adverse Event Overview...................................................................... 16
10.2.3
Treatment-Emergent Adverse Events by SOC and/or PT...................... 17
10.2.4
Treatment-Emergent Adverse Events per Patient-Years of 
Exposure .............................................................................................. 17
10.2.5
SAEs (Including Deaths) and Adverse Events Leading to Study 
Drug Discontinuation ........................................................................... 18
10.2.6
Safety Topics of Interest....................................................................... 18
10.3
Analysis of Laboratory Data................................................................. 18
10.4
Analysis of Vital Signs......................................................................... 20
10.5
Safety Subgroup Analyses.................................................................... 20
10.6
Other Safety Analyses .......................................................................... 20
11.0
Other Analyses ....................................................................20
12.0
Interim Analyses..................................................................21
12.1
Data Monitoring Committee................................................................. 21
13.0
Overall Type-I Error Control.............................................21
14.0
Version History ...................................................................22
15.0
References............................................................................23
List of Tables
Table 1.
SAP Version History Summary ............................................................ 22
 


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List of Figures
Figure 1.
Study Schematic..................................................................................... 7
List of Appendices
Appendix A.
Protocol Deviations .............................................................................. 24
Appendix B.
Definition of Safety Topics of Interest for cedirogant ........................... 25
Appendix C.
Potentially Clinically Important Criteria for Safety Endpoints .............. 31
 


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1.0
Introduction
This Statistical Analysis Plan (SAP) describes the statistical analyses for ABBV-157 
Study M18-816 A Phase 2b, Multicenter, Randomized, Double-Blind, Placebo-
Controlled, Dose-Ranging Study to Evaluate the Safety and Efficacy of Cedirogant 
(ABBV-157) in Adult Subjects with Moderate to Severe Psoriasis.
Study M18-816 examines the efficacy and safety of ABBV-157 in adult subjects with 
moderate to severe psoriasis.
The analyses of pharmacokinetic endpoints will not be covered 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 primary objective of this study is to assess the safety and efficacy of cedirogant 
versus placebo for the treatment of moderate to severe plaque psoriasis in adult subjects 
who are candidates for systemic therapy or phototherapy.
The primary objective of the study is to demonstrate a higher rate of subjects achieving 
Psoriasis Area and Severity Index (PASI) 75 (defined as ≥75% reduction from Baseline 
in PASI) at Week 16 with at least one cedirogant dosing group compared to placebo in the 
Intent-to-Treat (ITT) population, which consists of all randomized subjects.
The primary endpoint is the achievement of PASI 75 at Week 16.
The secondary efficacy objective of the study is to demonstrate a higher rate of subjects 
achieving static Physicians Global Assessment (sPGA) score of clear or almost clear, 
 


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PASI 50/90/100, Psoriasis Symptoms Scale (PSS) total score of 0 for subjects with PSS>0 
at Baseline, and itch Numerical Rating Scale (NRS)≥4-point improvement from Baseline 
for subjects with itch NRS≥4 at Baseline, at Week 16 with cedirogant compared to 
placebo in the ITT population.
As the study was terminated prematurely before the planned number of subjects could be 
randomized, all efficacy data will be summarized using descriptive summary statistics 
without statistical comparison or statistical testing. No hypotheses or estimands are 
defined for the primary and secondary efficacy endpoints.
2.2
Study Design Overview
This is a Phase 2, multicenter, randomized, double-blind, parallel-group, placebo-
controlled dose ranging study that will evaluate the safety and efficacy of cedirogant in 
approximately 200 adult subjects with moderate to severe plaque psoriasis and who are 
candidates for systemic therapy or phototherapy.
The study is comprised of a 28-day Screening Period, a 16-week double-blind Treatment 
Period, and a 30-day Follow-up Period.
The schematic of the study is shown in Figure 1.
This study was terminated early by AbbVie due to preclinical findings in the cedirogant 
39-week dog toxicity study. The interim analysis pre-defined in the protocol will not be 
conducted. The final database lock will occur after the last on-going subject completes the 
follow-up phone call or withdraws from the study.
 


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Figure 1.
Study Schematic
PASI = Psoriasis Area Severity Index; PBO = placebo; QD = once daily
2.3
Treatment Assignment and Blinding
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 assignment according to the randomization schedule.
Subjects who meet eligibility criteria at Baseline will be randomized in a 1:1:1:1 ratio to 1 
of the 4 treatment groups:
●
Cedirogant 375 mg once daily (QD) (N = 50)
●
Cedirogant 150 mg QD (N = 50)
●
Cedirogant 75 mg QD (N = 50)
 
 
 
 
 
 
 
 
 
 
   
 
   
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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●
Placebo QD (N = 50)
All active and placebo treatment will be taken orally (cedirogant 75 mg tablets and 
matching placebo). There is no stratification factor for the randomization.
2.4
Sample Size Determination
Given the planned total sample size of 200 subjects (50 subjects in each arm), the study 
has more than 95% power to detect the treatment differences of 60% in PASI 75 in at least 
one cedirogant group versus placebo (PASI 75 response rate of 11%) using a two-sided 
significance level of 0.1 based on the 2-sample Chi-Squared test.
3.0
Endpoints
3.1
Primary Endpoint
The primary endpoint is the achievement of ≥ 75% reduction from baseline in PASI score 
(PASI 75) at Week 16.
3.2
Secondary Endpoints
The secondary endpoints are:
●
Achievement of a static Physician Global Assessment (sPGA) score of clear or 
almost clear at Week 16
●
Achievement of ≥ 50% reduction from baseline in PASI score (PASI 50) at 
Week 16
●
Achievement of ≥90% reduction from baseline in PASI score (PASI 90) at 
Week 16
●
Achievement of 100% reduction from baseline in PASI score (PASI 100) at 
Week 16
●
Achievement of Psoriasis Symptoms Scale (PSS) total score of 0 at Week 16 
for subjects with PSS >0 at Baseline
●
Achievement of itch Numerical Rating Scale (NRS) ≥ 4-point improvement 
from Baseline at Week 16 for subjects with itch NRS ≥ 4 at Baseline
 


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3.3
Other Efficacy Endpoints
Additional efficacy endpoints include the primary and all secondary endpoints assessed at 
visits other than the Week 16 Visit as noted in the Study Activities table (Appendix D of 
the protocol). Additional efficacy endpoints include the following measurements assessed 
at visits as specified in the Study Activities table:
●
Change from baseline in Dermatology Life Quality Index (DLQI) score
●
Achievement of a DLQI score of 0 or 1
●
Achieving a change of ≥ 4 points from baseline in DLQI score (for patients 
whose DLQI score at baseline is ≥ 4)
●
Treatment Satisfaction Questionnaire for Medication Version 9 (TSQM-9) 
domain scores (effectiveness, convenience and global satisfaction domains)
●
Change from baseline in Hospital Anxiety and Depression Scale (HADS)-
Anxiety score
●
Change from baseline in HADS-Depression score
●
Change from Baseline in Work Productivity and Activity Impairment (WPAI): 
Psoriasis Questionnaire measures:
○
Percent work time missed (Absenteeism)
○
Percent impairment while working (Presenteeism)
○
Percent overall work impairment
○
Percent activity impairment
3.4
Safety Endpoints
Safety evaluations include AE monitoring, physical examinations, vital sign 
measurements, electrocardiogram (ECG) variables, and clinical laboratory testing 
(hematology, chemistry, and urinalysis) as measures of safety and tolerability for the 
entire study duration.
 


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4.0
Analysis Populations
The following population sets will be used for the analyses.
The Intent-to-Treat (ITT) Population includes all randomized subjects. The efficacy 
analyses, summary of demographic, and baseline disease characteristics will be carried 
out with the ITT Population. Subjects will be analyzed as randomized.
The Safety Population includes all subjects who are randomized and received at least 
1 dose of study drug. All safety analyses will use the Safety Population. Subjects will be 
analyzed as treated (i.e., according to the actual treatments received), regardless of the 
treatment assigned. The 'as-treated' treatment group is determined by the treatment the 
subject received during the majority of the subject's drug exposure time in the analysis 
period.
5.0
Subject Disposition
The number of subjects for each of the following categories will be summarized, for 
overall and for each group in ITT Population:
●
Subjects randomized;
●
Subjects who took at least one dose of study drug;
●
Subjects who completed study;
●
Subjects who completed study drug;
●
Subjects who prematurely discontinued study drug;
●
Subjects who prematurely discontinued study.
Number and percentage of subjects who discontinue study drug or who discontinue from
study will be summarized by primary reason for each treatment group and overall.
In addition, the above summaries (except for the reason for premature discontinuation)
will also be summarized by center in the accountability table.
 


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6.0
Study Drug Duration and Compliance
For the Safety population, duration of treatment will be summarized for each treatment 
group and for all active investigational study drug dose groups combined. Duration of 
treatment is defined for each subject as last dose date minus first dose date +1. Duration 
of treatment will be summarized using the number of subjects treated, mean, standard 
deviation, median, minimum and maximum. In addition, the number and percentage of 
subjects in each treatment duration interval (≥ 1 dose, ≥ 4 weeks, ≥ 12 weeks, ≥ 16 weeks) 
will be summarized.
Treatment compliance in the treatment period will be summarized by treatment group 
based on the Safety population. Treatment compliance for each subject is defined as the 
number of tablets actually taken divided by the number of tablets that should have been 
taken. For subjects who prematurely discontinued the study drug, the planned tablets will 
only be counted prior to that scheduled visit of discontinuation. The compliance rate will 
be summarized by treatment group.
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 for the ITT population overall and by 
treatment group. 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 and standard deviation, median, minimum 
and maximum).
7.1
Demographics and Baseline Characteristics
Continuous demographic variables include age, weight, height, and body mass index 
(BMI). Categorical demographic variables include sex, ethnicity, race, age (< 40, 
40 – 65), weight (< 100 or ≥ 100 kg), BMI (< 25 or ≥ 25 kg/m2), region (North America, 
 


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rest of world), tobacco user (current, former, never, unknown), and alcohol user (current, 
former, never, unknown).
Disease characteristics include the following: Baseline PASI, Baseline sPGA, Baseline 
PSS, Baseline BSA, Baseline NRS, Baseline DLQI, Baseline HADS, Baseline WPAI, 
history of psoriatic arthritis, prior biologic and disease duration in years as a continuous 
and categorical (< 5 or ≥ 5 years) variable.
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 and preferred term) will be 
summarized overall and by treatment group. The system organ class (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 preferred term).
7.3
Prior and Concomitant Medications
Prior and concomitant medications will be summarized by generic name. A prior 
medication is defined as any medication taken prior to the date of the first dose of study 
drug. A concomitant medication is defined as any medication that started prior to the date 
of the first dose of study drug and continued to be taken after the first dose of study drug 
or any medication that started on or after the date of the first dose of study drug, but not 
after the date of the last dose of study drug. 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.
 


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8.0
Handling of Potential Intercurrent Events for the 
Primary and Secondary Endpoints
The primary and secondary endpoints (Section 3.1 and Section 3.2) will be analyzed in 
the ITT Population and no intercurrent events will impact the analysis. All data collected, 
regardless of premature discontinuation of study drug, will be used in the analysis.
9.0
Efficacy Analyses
9.1
General Considerations
All efficacy analyses will be conducted in the ITT Population.
The only and final analysis for the primary and secondary efficacy endpoints as well as all 
other efficacy endpoints will be performed after the last on-going subject completes the 
follow-up phone call or withdraws from the study and the database has been locked.
Descriptive summary statistics will be provided for efficacy endpoints at each visit by 
treatment groups based on the ITT population. There will be no statistical testing.
Categorical efficacy endpoints at each visit will be summarized by number of subjects, the 
number and percentage of subjects who achieve the endpoint, as well as the 95% 
confidence interval (CI) based on normal approximation.
Continuous efficacy endpoints at each visit and change from baseline at each visit will be 
summarized by descriptive summary statistics including number of subjects, mean, 
standard deviation, median, minimum, maximum. The 95% CI based on normal 
approximation will be provided for the mean change from baseline.
"Baseline" refers to the last non-missing observation before the first administration of 
study drug or randomization if no study drug is given.
 


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9.2
Handling of Missing Data
Observed Cases (OC) approach will be the only approach to handle missing data for both 
categorical and continuous efficacy endpoints in the study. The OC 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 OC analysis for that visit. OC will not 
include values after a subject prematurely discontinues from study treatment.
9.3
Primary Efficacy Endpoint and Analyses
9.3.1
Primary Efficacy Endpoint
The primary endpoint is the achievement of ≥ 75% reduction from baseline in PASI score 
(PASI 75) at Week 16.
9.3.2
Main Analysis of Primary Efficacy Endpoints
Descriptive summary statistics of the primary efficacy endpoint will be provided based on 
the ITT Population as described in Section 9.1.
9.3.3
Sensitivity and Supplementary Analyses of the Primary 
Efficacy Endpoint
No sensitivity and supplementary analyses of the primary efficacy endpoint will be 
conducted.
9.4
Secondary Efficacy Endpoints and Analyses
9.4.1
Secondary Efficacy Endpoints
The secondary endpoints are as defined in Section 3.2.
9.4.2
Main Analyses of Secondary Efficacy Endpoints
Descriptive summary statistics of the secondary efficacy endpoints will be provided based 
on the ITT Population as described in Section 9.1.
 


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9.4.3
Sensitivity and Supplementary Analyses for Secondary 
Efficacy Endpoints
There will be no sensitivity analysis for the secondary efficacy endpoints.
9.5
Additional Efficacy Analyses
Descriptive summary statistics of the additional efficacy endpoints will be provided based 
on the ITT Population as described in Section 9.1.
9.6
Efficacy Subgroup Analyses
Descriptive summary statistics of each subgroup defined below will be provided for PASI 
75 at Week 16, among the ITT Population:
●
Age group (< 40 years, ≥40)
●
Sex (male, female)
●
BMI (< 25, ≥25)
●
Baseline PASI (< median, ≥median)
●
Baseline sPGA (3, 4)
●
Baseline PSS (0, > 0)
●
Baseline NRS (< 4, ≥4)
●
Psoriatic arthritis (yes, no)
●
Prior biologic (yes, no)
10.0
Safety Analyses
10.1
General Considerations
Safety data will be summarized for the Safety Population. Safety summaries will be 
presented by treatment group, including a total group for all subjects on active study drug. 
For the safety analysis, subjects are assigned to a treatment group based on the treatment 
actually received, regardless of the treatment randomized.
 


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The overview of TEAEs, and potentially clinically important (PCI) findings in laboratory 
variables and vital sign variables will also be summarized among the Safety Populations.
Missing safety data will not be imputed.
10.2
Adverse Events
Adverse events (AEs) will be summarized and presented using primary MedDRA System 
Organ Classes (SOCs) and preferred terms (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 adverse events 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.
10.2.1
Treatment-Emergent Adverse Events
Treatment-emergent AEs are defined as any AE with the onset that is after the first dose 
of study drug and within 30 days after the last dose of study drug.
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 in the 
Safety Population:
●
Any treatment-emergent AE
●
Any treatment-emergent AE related to study drug according to the investigator
●
Any severe treatment-emergent AE
●
Any serious treatment-emergent AE
●
Any treatment-emergent AE leading to discontinuation of study drug
●
Any treatment-emergent AE leading to death
●
Any treatment-emergent Safety topic of interest (STI)
 


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●
All deaths
●
Deaths occurring ≤ 30 days after last dose of study drug
●
Deaths occurring > 30 days after last dose of study drug.
10.2.3
Treatment-Emergent Adverse Events by SOC and/or PT
The number and percentage of subjects experiencing TEAEs will be tabulated using the 
MedDRA system organ class and preferred term, by maximum severity by SOC and PT, 
and by relationship to the study drug as assessed by the investigator by SOC and PT. 
Specific adverse events 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.
In addition, treatment-emergent adverse events will be summarized by PT and sorted by 
decreasing frequency for the total active group.
10.2.4
Treatment-Emergent Adverse Events per Patient-Years of 
Exposure
Exposure-adjusted AEs per 100 patient-years will be provided, where AEs per 
100 patient-years of exposure are defined as the number of AEs divided by the total 
exposure in 100 patient-years.
Note that one event per preferred term per day per subject will be counted in the 
calculation of the number of TEAEs (i.e., a preferred term will not be counted twice on 
the same day for the same subject). The exposure-adjusted TEAE rate per 100 patient-
years is calculated as:
100 × Number of TEAEs 
Total Patient Years,
 


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where total patient years is defined as the sum of individual patient year, which is defined 
as the minimum of (the last dose date + 30 days, the end of study date) minus the first 
dose date +1, normalized by 365.25 and rounded to one decimal place.
10.2.5
SAEs (Including Deaths) and Adverse Events Leading to 
Study Drug Discontinuation
Treatment-emergent SAEs (including deaths) and AEs leading to discontinuation of study 
drug will be summarized by SOC and PT and in listing format.
A listing of pre-treatment SAEs with onset dates prior to the first dose of study drug will 
be provided.
10.2.6
Safety Topics of Interest
Safety topics of interest will be summarized according to the search criteria are provided 
in Appendix B.
The final list will be based on the most updated final version of cedirogant Product Safety 
Statistical Analysis Plan.
Treatment-emergent Safety Topics of Interest will be summarized by SOC and PT and 
listing format. Additionally, STI rates per 100 patient years of exposure will be provided 
for each STI category (Appendix B) in the AE overview summary.
Listings of safety topics of interest will also be provided.
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 all analyses, except for Baseline where SAE-related 
laboratory assessments on or before the first dose of study drug will be excluded. The 
clinical laboratory tests defined in the protocol operations manual (e.g., hematology and 
clinical chemistry) will be summarized.
 


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The raw laboratory variable values and change from baseline to each applicable post-
baseline visit will be summarized by treatment group, with number of subjects, mean, 
standard deviation, median, minimum, maximum. The 95% CI based on normal 
approximation will be provided for the mean change from baseline.
Laboratory abnormalities meeting CTC criteria grade 3, 4 and '≥3' will be summarized.
Laboratory abnormalities will be evaluated based on Potentially Clinically Important 
(PCI) criteria (Appendix C). For each laboratory PCI criterion, the number and percentage 
of subjects who have a laboratory value meeting the criteria will be summarized. Listings 
will be provided to summarize subject-level laboratory data for subjects meeting PCI 
criteria.
Assessment of Liver Enzyme and Bilirubin Elevations
The frequencies and percentages of subjects with post baseline liver specific function test 
values in ALT/SGPT, AST/SGOT, alkaline phosphatase, and total bilirubin meeting the 
following criteria will be summarized:
●
ALT > 3 × ULN, > 5 × ULN, > 10 × ULN, > 20 × ULN
●
AST > 3 × ULN, > 5 × ULN, > 10 × ULN, > 20 × ULN
●
TBL > 1.5 × ULN, > 2 × 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
●
Alkaline phosphatase > 1.5 × ULN
A listing of possible Hy's Law cases, defined as those who meet all of the following 
conditions simultaneously, will be provided: ALT > 3 × ULN or AST > 3 × ULN that is 
associated with an increase in total bilirubin ≥ 2 × ULN and alkaline phosphatase 
< 2 × ULN.
 


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An Evaluation of Drug Induced Serious Hepatotoxicity (eDISH) plot1 of the maximum 
post-baseline ALT value (as a multiple of the ULN) vs. the maximum post-baseline total 
bilirubin value (as a multiple of the ULN), not necessarily concurrent, will also be created. 
Reference lines will be included at 3 × ULN for ALT and at 2 × ULN for total bilirubin. A 
similar eDISH plot will be provided for the maximum post-baseline AST value (as a 
multiple of the ULN) vs. the maximum post-baseline total bilirubin value (as a multiple of 
the ULN).
10.4
Analysis of Vital Signs
Vital sign measurements of systolic and diastolic blood pressure will be summarized.
The raw value of each vital sign variable and change from baseline at each time point will 
be summarized by treatment group with number of subjects, mean, standard deviation, 
median, minimum and maximum. The 95% CI based on normal approximation will be 
provided for the mean change from baseline.
Vital sign variables will be evaluated based on potentially clinically important (PCI) 
criteria (Appendix C) among the Safety Population. 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.
10.5
Safety Subgroup Analyses 
There will be no safety subgroup analyses for this study.
10.6
Other Safety Analyses
There will be no other safety analyses for this study.
11.0
Other Analyses
There will be no other analyses for this study.
 


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12.0
Interim Analyses
There were plans for an interim analysis which was to be conducted after the first 140 
subjects had either completed the Week 16 assessments or withdrawn from the study. Due 
to preclinical findings in the cedirogant 39-week dog toxicity study, Study M18-816 was 
terminated early and no interim analysis will be conducted.
12.1
Data Monitoring Committee
An internal data monitoring committee (DMC) composed of clinicians and statisticians 
independent of any cedirogant clinical trials outside their role on the DMC, and with 
relevant expertise in their field will review unblinded safety data from the ongoing study. 
The primary responsibility of the DMC will be 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.
Since there are no efficacy analyses for early stopping, no alpha adjustment is needed.
13.0
Overall Type-I Error Control
There will be no comparison or statistical testing for this Phase 2 study. Overall type I 
error control is not applicable.
 


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14.0
Version History
Table 1.
SAP Version History Summary
Version
Date
Summary
1.0
18 Jan 2022
Original version
2.0
15 Dec 2022
1. Section 2.0 Study Objectives and Design, due to early 
termination of the study, the planned interim analysis will 
not be conducted. The Final database lock will occur after 
the last on-going subject completes the follow-up phone 
call.
2. Section 7.1 Demographics and Baseline Characteristics, 
removed Baseline TSQM-9, as TSQM-9 is not collected at 
baseline.
3. Section 9.0 Efficacy Analyses, due to early termination of 
the study, there will be no comparison or statistical testing 
for all efficacy endpoints, only summary statistics will be 
provided. OC will be the approach to handle missing data 
for categorical and continuous efficacy endpoints instead 
of NRI-MI and MMRM, respectively.
4. Section 10.2 Adverse Events, total patient years is defined 
as the sum of individual patient year, which is defined as 
the minimum of (the last dose date + 30 days, the end of 
study date) minus the first dose date +1, normalized by 
365.25 and rounded to one decimal place.
5. Section 10.3 added eDISH Plot of AST and removed shift 
tables.
6. Section 12.0 Interim Analyses, due to early termination of 
the study, the planned interim analysis will not be 
conducted.
 


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15.0
References
1.
Watkins PB, Desai M, Berkowitz SD, et al. Evaluation of drug-induced serious 
hepatotoxicity (eDISH): application of this data organization approach to phase III 
clinical trials of rivaroxaban after total hip or knee replacement surgery. Drug Saf. 
2011;34(3):243-52.
 


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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.
 


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Appendix B.
Definition of Safety Topics of Interest for cedirogant
Safety topics of interest (STI) will be identified using the following search criteria:
 


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Safety Topic of 
Interest
Basis for Inclusion
Criteria for 
Identification of 
Event
Are events adjudicated 
(yes/no)? If yes, external or 
internal adjudication?
Special Collection 
Forms or Safety 
Studies
Relevant Restrictions#
Identified Risks - None
Important Potential Risks
Serious infection*
Based on the mechanism of action and 
data from the biomedical literature, as well 
as information from nonclinical 
pharmacology and toxicity studies, 
ABBV-157 administration is expected to 
produce effects on white blood cells and 
cytokines. These immunomodulatory 
properties may result in an increased risk 
of infection.
Serious events only 
from the Infections 
and Infestations SOC
No
No
Exclusion of subjects 
with HIV, hepatitis B or 
hepatitis C viral 
infection. Exclusion of 
subjects with active 
severe acute respiratory 
syndrome coronavirus 2 
(SARS-CoV-2) 
infection.
Other Safety Topics of Interest
GI tract altered 
mobility
In rats, GI effects were present at ≥100 
mg/kg/day in the 4-week GLP study and 
led to marked body weight loss and 
dehydration, necessitating euthanasia in 
two animals due to moribund condition.
There was also histopathologic evidence 
of intestinal tract dilation in rats. In the 
GLP dog study, ABBV-157 produced 
emesis and loose to watery stools that 
were well tolerated throughout the study at 
doses of 40, 120, and 300 mg/kg/day.
Gastrointestinal 
nonspecific 
symptoms and 
therapeutic 
procedures 
SMQ_Narrow
No
No
None
Herpes zoster
Manipulating the inflammation cascade 
with any immune-modulating biologic 
may increase the risk of infections. Cases 
of Herpes Zoster is not included in OI 
CMQ
Herpes Zoster CMQ
No
Yes
None
 


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Safety Topic of 
Interest
Basis for Inclusion
Criteria for 
Identification of 
Event
Are events adjudicated 
(yes/no)? If yes, external or 
internal adjudication?
Special Collection 
Forms or Safety 
Studies
Relevant Restrictions#
Opportunistic 
infection excluding 
tuberculosis and 
herpes zoster
On the basis of MOA and data from the 
medical literature, as well as information 
from nonclinical pharmacology and 
toxicity studies, Cedirogant administration 
is expected to produce effects on white 
blood cells and cytokines. These 
immunomodulatory properties may result 
in an increased risk of infection.
Opportunistic 
Infection Excluding 
Tuberculosis and 
Herpes Zoster CMQ
No
No
Exclusion of subjects 
with infection (bacterial, 
fungal or viral) requiring 
systemic treatment 
within 4 weeks of the 
Baseline Visit.
Active tuberculosis
On the basis of MOA and data from the 
medical literature, as well as information 
from nonclinical pharmacology and 
toxicity studies, Cedirogant administration 
is expected to produce effects on white 
blood cells and cytokines. These 
immunomodulatory properties may result 
in an increased risk of infection.
Active Tuberculosis 
CMQ
No
Yes
Exclusion of subjects 
with active TB and 
prophylaxis of subjects 
with latent TB.
Hepatic Disorders
Though there are no signals, preclinical or 
clinical, of hepatotoxicity associated with 
ABBV-157 therapy to date, hepatic events 
are routinely monitored for any drug in 
development.
Drug Related Hepatic 
Disorders –
Comprehensive 
Search SMQ _narrow
No
Yes
Exclusion of subjects 
with AST ≥2 x ULN or 
ALT ≥2 x ULN or total 
bilirubin > 1.5 x ULN.
Exclusion of subjects 
with history or evidence 
of HBV or HCV 
infection.
 


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Safety Topic of 
Interest
Basis for Inclusion
Criteria for 
Identification of 
Event
Are events adjudicated 
(yes/no)? If yes, external or 
internal adjudication?
Special Collection 
Forms or Safety 
Studies
Relevant Restrictions#
Lymphopenia
Non-clinical Findings:  Decreased 
numbers of lymphocyte in the thymus, 
Peyer's patch, and lymph nodes, along 
with decreases in thymus weights, were 
present in rats and dogs and were related 
to ABBV-157 administration.
Hematological 
Toxicity -
Lymphopenia 
(Upadacitinib 
Product Specific) 
CMQ
No
No
None.
Anemia
Non-clinical Findings: Minimal to mild 
decreases in RBC mass were present in 
dogs and rats and were reversible after 4 
weeks of recovery.
Non-Hemolytic and 
Non-Aplastic 
Anemias CMQ
No
No
Exclusion of subjects 
with hemoglobin 
≤9 g/dl.
MACE
There is an increased risk of 
cardiovascular disease in the psoriasis 
patient population.
Other Ischaemic 
heart disease 
SMQ_narrow
Central nervous 
system hemorrhages 
and cerebrovascular 
conditions 
SMQ_narrow
Myocardial 
infarction 
SMQ_narrow
Death and Sudden 
Death - HLT
No
Yes
None
 


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Safety Topic of 
Interest
Basis for Inclusion
Criteria for 
Identification of 
Event
Are events adjudicated 
(yes/no)? If yes, external or 
internal adjudication?
Special Collection 
Forms or Safety 
Studies
Relevant Restrictions#
Ocular events
In a healthy volunteer study of an RORγt 
compound related to ABBV-157, 3 of 9 
subjects developed eye related events after 
multiple doses, including one subject who 
was seen by eye specialists and required 
prolonged treatment with steroid eye drops 
and an oral NSAID (aspirin-like drug).
Conjunctival 
disorders 
SMQ_narrow
Corneal disorders 
SMQ
Scleral disorders 
SMQ_narrow
No
Yes
Current phase 2b 
protocol requires any 
subject with CTCAE 
Grade 2 or higher AE 
ocular event must follow 
up with an
ophthalmologist within 7 
days. Grade 2 or higher 
ocular AEs considered 
related to study drug
administration qualify 
for withdrawal criteria.
Possible 
malignancies
Comorbidity with patient population, 
NMSC most common. Theoretical 
possibility of decreased immune 
surveillance against malignancies with 
alteration of immune pathways.
- Malignant tumours 
SMQ - narrow 
No
No
Exclusion of subjects 
with a history of any 
malignancy within the 
last 5 years or 
documented active 
malignancy except for 
successfully treated non-
melanoma skin cancer 
(NMSC) or localized 
carcinoma in situ of the 
cervix.
Non-melanoma skin 
cancer (NMSC)
Comorbidity with patient population, 
NMSC most common. Theoretical 
possibility of decreased immune 
surveillance against malignancies with 
alteration of immune pathways.
Skin malignant 
tumours SMQ Broad
excluding preferred 
terms identified by 
the Melanoma CMQ 
No
No
Exclusion of subjects 
with a history of 
untreated non-melanoma 
skin cancer (NMSC).
 


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Safety Topic of 
Interest
Basis for Inclusion
Criteria for 
Identification of 
Event
Are events adjudicated 
(yes/no)? If yes, external or 
internal adjudication?
Special Collection 
Forms or Safety 
Studies
Relevant Restrictions#
Malignant tumours
excluding non-
melanoma skin 
cancer (NMSC)
Comorbidity with patient population. 
Theoretical possibility of decreased 
immune surveillance against malignancies 
with alteration of immune pathways.
Malignant Tumours 
SMQ Narrow 
EXCLUDING (Skin 
malignant tumors 
SMQ Broad 
excluding PTs 
identified by 
Melanoma CMQ)
No
No
Exclusion of subjects 
with a history of any 
malignancy within the 
last 5 years or 
documented active 
malignancy except for 
successfully treated non-
melanoma skin cancer 
(NMSC) or localized 
carcinoma in situ of the 
cervix.
*
Important risk.
#
e.g., protocol exclusion criteria or risk minimization actions limiting data on certain patient populations.
 


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Appendix C.
Potentially Clinically Important Criteria for Safety Endpoints
The criteria for Potentially Clinically Important (PCI) laboratory findings are described in 
Table C-1 and Table C-2, and the PCI criteria for vital sign findings are described in 
Table C-3.
Table C-1.
Criteria for Potentially Clinically Important Hematology Values
Hematology Variables
Units
Definition of Potentially Clinically Important
NCI CTCAE (Version 4.03) Grade 3 or greater
Very Low
Hemoglobin
g/dL
< 8.0
Platelets count
109/L
< 50.0
WBC count
109/L
< 2.0
Neutrophils
109/L
< 1.0
Lymphocytes
109/L
< 0.5
Note:
A post-baseline value must be more extreme than the baseline value to be considered a potentially clinically 
important finding.
 


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Table C-2.
Criteria for Potentially Clinically Important Chemistry Values
Chemistry Variables
Units
Definition of Potentially Clinically 
Important NCI CTCAE (Version 4.03) 
Grade 3 or greater
Very Low
Very High
TBL
mcmol/L
> 3.0 × ULN
ALP
U/L
> 5.0 × ULN
SGOT/AST
U/L
> 5.0 × ULN
SGPT/ALT
U/L
> 5.0 × ULN
Albumin
g/L
< 20
Glucose
mmol/L
< 2.2
> 13.9
Triglycerides
mmol/L
> 5.7
Creatinine
mcmol/L
> 3.0 × ULN
(> 3.0 × BL)
Sodium
mmol/L
< 130
> 155
Potassium
mmol/L
< 3.0
> 6.0
Calcium
mmol/L
< 1.75
> 3.1
CPK
U/L
> 5.0 × ULN
Total Cholesterol
mmol/L
> 10.34
GGT
> 5.0 × ULN
Note:
A post-baseline value must be more extreme than the baseline value to be considered a potentially clinically 
important finding.
Table C-3.
Criteria for Potentially Clinically Important Vital Sign Values
Vital Signs Variables
Criterion
Definition of Potentially Clinically Important
Systolic Blood 
Pressure (mmHg)
Low
Value ≤ 90 mmHg and decrease ≥ 20 mmHg from Baseline
High
Value ≥ 160 mmHg and increase ≥ 20 mmHg from Baseline
Diastolic Blood 
Pressure (mmHg)
Low
Value ≤ 50 mmHg and decrease ≥ 10 mmHg from Baseline
High
Value ≥ 100 mmHg and increase ≥ 10 mmHg from Baseline