Conditions: Crohn Disease
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 48
Healthy volunteers: no

Brief summary:
The purpose of this study is to evaluate the efficacy of JNJ-active as measured by the change in the Crohn's Disease Activity Index (CDAI) score and Simplified Endoscopic Score for Crohn's disease (SES-CD) from baseline at Week 12.

Detailed description:

Arms:
arm 1: Participants will receive oral tablets of JNJ-67864238 twice daily for 12 weeks. arm 2: Participants will receive oral tablets of matching placebo twice daily for 12 weeks.

Interventions: intervention 1: JNJ-67864238 intervention 2: Placebo
Intervention descriptions: intervention 1: Participants will receive oral tablets of JNJ-67864238 twice daily. intervention 2: Participants will receive oral tablets of matching placebo twice daily.

Protocol document:
Prot_000.pdf: 
1
Status: Approved,  Date: 11 May 2021
Janssen Research & Development *
Clinical Protocol
Intervention Specific Appendix to Master Clinical Protocol PLATFORMPACRD2001
PRISM-SCARLET
Protocol 67864238PACRD2001; Phase 2a
AMENDMENT 5
JNJ-67864238  
*Janssen Research & Development is a global organization that operates through different legal entities in
various countries. Therefore, the legal entity acting as the sponsor for Janssen Research & Development
studies may vary, such as, but not limited to Janssen Biotech, Inc.; Janssen Products, LP; Janssen
Biologics, BV; Janssen-Cilag International NV; Janssen, Inc; Janssen Pharmaceutica NV; Janssen
Sciences Ireland UC; Janssen Biopharma Inc.; or Janssen Research & Development, LLC. The term
“sponsor” is used throughout the protocol to represent these various legal entities; the sponsor is
identified on the Contact Information page that accompanies the protocol.
US sites of this study will be conducted under US Food & Drug Administration IND regulations 
(21 CFR Part 312).
EudraCT NUMBER:         2019-003335-37
Status:
Approved
Date:
11 May 2021
Prepared by:
Janssen Research & Development, LLC 
EDMS number:
EDMS-ERI-154159369, 7.0
GCP Compliance: This study will be conducted in compliance with Good Clinical Practice, and applicable regulatory 
requirements. 
Confidentiality Statement
The information in this document contains trade secrets and commercial information that are privileged or confidential and 
may not be disclosed unless such disclosure is required by applicable law or regulations. In any event, persons to whom the 
information is disclosed must be informed that the information is privileged or confidential and may not be further disclosed 
by them. These restrictions on disclosure will apply equally to all future information supplied to you that is indicated as 
privileged or confidential.
NCT04102111


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PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE
DOCUMENT HISTORY
Document
Date
Amendment 5
11 May 2021
Amendment 4
14 December 2020
Amendment 3
17 September 2020
Amendment COVID-19 Appendix 
20 May 2020
Amendment 2
13 November 2019  
Amendment 1
14 August 2019
Original Protocol
06 June 2019
Amendment 5: 11 May 2021
Overall Rationale for the Amendment: The overall rationale for the amendment is to allow for additional
ad hoc interim analyses to augment decision making for this JNJ-67864238 cohort.
Section number
and Name
Description of Change
Brief Rationale
Synopsis;
4.1 Overall Design; 
9.2.1 Decision-Making 
Framework; 
9.5. Interim Analysis   
Additional ad hoc interim analyses may be 
conducted if deemed necessary.  
To augment decision making for 
this JNJ-67864238 intervention
cohort.
Synopsis;
9.2.1 Decision-Making 
Framework; 
9.5. Interim Analysis    
The number of participants to be included in 
the interim analysis was updated from at least 
45 participants to approximately 45 
participants.  
To provide flexibility regarding the 
number of participants required to 
conduct the interim analysis.    
9.2.2.2 Decision-Making 
Specifics at the 
Completion of the 
Intervention Cohort;
A decision-making framework based solely on 
Crohn’s Disease Activity Index scores was 
added.  
To add decision-making criteria 
based on the primary endpoint of 
the change in the Crohn’s Disease 
Activity Index from baseline at 
Week 12.  
5.2 Exclusion Criteria, 
A01;
10.8. Appendix 8: 
Definition of Minimal 
Exposure to 
Ustekinumab
Exclusion criterion A01 was updated to 
indicate that participants who have had limited 
exposure to ustekinumab as defined in 
Appendix 8 may be eligible for this 
JNJ-67864238 intervention cohort.
Appendix 8 was added to specify the 
definition of minimal exposure to 
ustekinumab.  
To clarify that limited prior 
exposure to ustekinumab may not 
disqualify a participant from 
participating in this JNJ-67864238
intervention cohort.    
5.1 Inclusion Criteria
6.5 Concomitant 
Therapy
Inclusion criterion A06 was added to address 
the use of COVID-19 vaccines.
Guidance was added to address the use of 
COVID-19 vaccines.  
COVID-19 vaccines are 
provisionally authorized (ie, 
emergency-use authorization or 
conditional marketing 
authorization) and are in use.  
10.4 Appendix 4:  Liver 
Safety: Suggested 
Actions and Follow-up 
Assessments   
The liver safety stopping algorithm and 
follow-up assessments were updated.  
To align with health authority 
guidance for liver safety.  
8.3.7. Adverse Events of 
Special Interest; 
The definition of a possible Hy’s law case was 
added.
To align with health authority 
guidance for liver safety.  


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Section number
and Name
Description of Change
Brief Rationale
10.5 Appendix 5: 
Clinical Laboratory 
Tests
8.3.7. Adverse Events of 
Special Interest; 
Text was updated to indicate that adverse 
events of special interest should be reported to 
the sponsor in an expedited manner.  
To clarify the procedures for 
reporting adverse events of special 
interest.  
1.3 Schedule of 
Activities 
Footnote bb was added to indicate that at
the screening visit only, the CDAI will be 
calculated using participant recall. The 
investigator will complete the variable 
assessments required to calculate the CDAI 
total score as conducted in the other visits.  
To clarify the procedures for 
obtaining the components of the 
CDAI.
1.3 Schedule of 
Activities
Footnote cc was added to indicate that for 
visits other than Week 0, the most recent 
hematocrit value obtained before a visit will be 
used to calculate the CDAI for that visit.  
To clarify the procedures for the 
calculation of CDAI using the 
hematocrit value.  
5.2 Exclusion Criteria, 
A01;
7.1 Discontinuation of 
Study Intervention
Experimental compound MEDI2070 is now 
named brazikumab.
To align with current compound 
names.  
5.2 Exclusion Criteria, 
A01; 
Experimental compound LY3074828 is now 
named mirikizumab.
To align with current compound 
names.  
Synopsis;
4.1 Overall Design
For the single database lock, the term study 
was updated to intervention cohort.  
To clarify that the single database 
lock applies to this JNJ-67864238 
intervention cohort. 
Throughout the protocol
Minor grammatical, formatting, or spelling 
changes were made.
Minor errors were noted.


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TABLE OF CONTENTS
PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE ............................................................... 2
TABLE OF CONTENTS ............................................................................................................................... 4
LIST OF IN-TEXT TABLES AND FIGURES................................................................................................ 6
1.
PROTOCOL SUMARY ........................................................................................................................ 7
1.1.
Synopsis........................................................................................................................................... 7
1.2.
Schema .......................................................................................................................................... 11
1.3.
Schedule of Activities..................................................................................................................... 12
2.
INTRODUCTION................................................................................................................................ 16
2.1.
Study Rationale.............................................................................................................................. 17
2.2.
Background .................................................................................................................................... 18
2.3.
Benefit-Risk Assessment ............................................................................................................... 20
2.3.1.
Risks for Study Participation....................................................................................................... 21
2.3.2.
Benefits for Study Participation .................................................................................................. 22
2.3.3.
Benefit-Risk Assessment for Study Participation ....................................................................... 23
3.
OBJECTIVES AND ENDPOINTS ..................................................................................................... 24
4.
STUDY DESIGN ................................................................................................................................ 24
4.1.
Overall Design................................................................................................................................ 24
4.2.
Scientific Rationale for Study Design............................................................................................. 25
4.2.1.
Study-Specific Ethical Design Considerations ........................................................................... 25
4.3.
Justification for Dose...................................................................................................................... 25
4.4.
End of Study Definition................................................................................................................... 26
5.
STUDY POPULATION ...................................................................................................................... 26
5.1.
Inclusion Criteria ............................................................................................................................ 27
5.2.
Exclusion Criteria ........................................................................................................................... 30
5.3.
Lifestyle Considerations................................................................................................................. 35
5.4.
Screen Failures .............................................................................................................................. 35
6.
STUDY INTERVENTION................................................................................................................... 35
6.1.
Study Interventions Administered .................................................................................................. 35
6.2.
Preparation/Handling/Storage/Accountability ................................................................................ 37
6.3.
Measures to Minimize Bias: Randomization and Blinding............................................................. 37
6.4.
Study Intervention Compliance...................................................................................................... 38
6.5.
Concomitant Therapy..................................................................................................................... 38
6.5.1.
Rescue Medication ..................................................................................................................... 39
6.5.2.
Crohn’s Disease-Specific Therapies .......................................................................................... 39
6.5.3.
Prohibited Medications ............................................................................................................... 40
6.6.
Dose Modification........................................................................................................................... 41
6.7.
Study Intervention After the End of the Study................................................................................ 41
7.
DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL ............................................................................................... 41
7.1.
Discontinuation of Study Intervention ............................................................................................ 41
7.2.
Participant Discontinuation/Withdrawal From the Study................................................................ 43
7.3.
Lost to Follow-up............................................................................................................................ 43
8.
STUDY ASSESSMENTS AND PROCEDURES ............................................................................... 43
8.1.
Efficacy Assessments .................................................................................................................... 44
8.2.
Safety Assessments....................................................................................................................... 44
8.2.1.
Physical Examinations................................................................................................................ 44
8.2.2.
Vital Signs................................................................................................................................... 44


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8.2.3.
Electrocardiograms..................................................................................................................... 44
8.2.4.
Clinical Safety Laboratory Assessments .................................................................................... 44
8.2.5.
Signs of Infection ........................................................................................................................ 45
8.3.
Adverse Events and Serious Adverse Events ............................................................................... 45
8.3.1.
Time Period and Frequency for Collecting Adverse Event and Serious Adverse Event 
Information.................................................................................................................................. 45
8.3.2.
Follow-up of Adverse Events and Serious Adverse Events ....................................................... 46
8.3.3.
Regulatory Reporting Requirements for Serious Adverse Events ............................................. 46
8.3.4.
Pregnancy................................................................................................................................... 46
8.3.5.
Concomitant Medication Review ................................................................................................ 47
8.3.6.
Disease-Related Events and Disease-Related Outcomes Not Qualifying as Adverse 
Events or Serious Adverse Events ............................................................................................. 47
8.3.7.
Adverse Events of Special Interest............................................................................................. 47
8.4.
Treatment of Overdose .................................................................................................................. 47
8.5.
Pharmacokinetics........................................................................................................................... 48
8.5.1.
Evaluations ................................................................................................................................. 48
8.5.2.
Analytical Procedures................................................................................................................. 49
8.5.3.
Pharmacokinetic Parameters and Evaluations........................................................................... 49
8.6.
Pharmacodynamics........................................................................................................................ 49
8.7.
Genetics ......................................................................................................................................... 49
8.8.
Biomarkers ..................................................................................................................................... 49
8.8.1.
RNA Transcriptome Research.................................................................................................... 50
8.8.2.
Proteome Research.................................................................................................................... 51
8.8.3.
Metabolomic Research............................................................................................................... 51
8.9.
Immunogenicity Assessments ....................................................................................................... 51
8.10.
Medical Resource Utilization and Health Economics .................................................................... 51
8.11.
Tuberculosis Assessments ............................................................................................................ 51
9.
STATISTICAL CONSIDERATIONS.................................................................................................. 53
9.1.
Statistical Hypotheses.................................................................................................................... 53
9.2.
Sample Size Determination ........................................................................................................... 53
9.2.1.
Decision-Making Framework ...................................................................................................... 53
9.2.2.
Decision-Making Specifics.......................................................................................................... 54
9.2.2.1.
Decision-Making Specifics at the Interim Analysis.................................................................. 54
9.2.2.2.
Decision-Making Specifics at the Completion of the Intervention Cohort ............................... 54
9.2.3.
Sample Size................................................................................................................................ 55
9.2.3.1.
Operating Characteristics of the Intervention Cohort .............................................................. 55
9.2.3.2.
Power for Detecting Treatment Difference in Change in the CDAI......................................... 55
9.3.
Populations for Analyses................................................................................................................ 55
9.4.
Statistical Analyses ........................................................................................................................ 55
9.4.1.
General Considerations.............................................................................................................. 55
9.4.1.1.
Multiplicity Control ................................................................................................................... 56
9.4.2.
Primary Endpoint ........................................................................................................................ 56
9.4.3.
Secondary Endpoints.................................................................................................................. 56
9.4.4.
Safety Analyses .......................................................................................................................... 56
9.4.5.
Other Analyses ........................................................................................................................... 56
9.5.
Interim Analysis.............................................................................................................................. 58
9.6.
Data Monitoring Committee or Other Review Board ..................................................................... 58
10.
SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS ............................ 59
10.1.
Appendix 1: Abbreviations ............................................................................................................. 59
10.2.
Appendix 2:  Contraceptive and Barrier Guidance and Collection of Pregnancy 
Information ..................................................................................................................................... 60
10.3.
Appendix 3: Tuberculin Skin Testing ............................................................................................. 63
10.4.
Appendix 4:  Liver Safety: Suggested Actions and Follow-up Assessments................................. 64
10.4.1.
Stopping Algorithm ..................................................................................................................... 64
10.4.2.
Follow-up Assessments.............................................................................................................. 65
10.5.
Appendix 5:  Clinical Laboratory Tests .......................................................................................... 68


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10.6.
Appendix 6: Data Simulation.......................................................................................................... 69
10.7.
Appendix 7: COVID-19 APPENDIX ............................................................................................... 70
10.8.
Appendix 8: Definition of Minimal Exposure to Ustekinumab ........................................................ 73
10.9.
Appendix 9: Protocol Amendment History ..................................................................................... 76
11.
REFERENCES................................................................................................................................... 81
INVESTIGATOR AGREEMENT ................................................................................................................. 82
LIST OF IN-TEXT TABLES AND FIGURES 
TABLES
Table 1:
Consolidated Schedule of Activities - PLATFORMPACRD2001 and 
67864238PACRD2001 ............................................................................................................. 12
Table 2:
Dosage and Administration Specifics for JNJ-67864238 and Matching Placebo .................... 36
FIGURES
Figure 1:
Schematic Overview of Study Design....................................................................................... 11




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OVERALL DESIGN, INTERVENTION COHORT AND DURATION, AND NUMBER OF 
PARTICIPANTS
The overall study design and target population are presented in the synopsis of the Master protocol 
PLATFORMPACRD2001.  This ISA is designed to assess the effects of a predominantly gastrointestinal-
restricted anti-IL-23R compound, JNJ-67864238, for moderately to severely active Crohn’s disease. This 
12-week Phase 2a study is focused on proof-of-concept and will assess the safety and efficacy of an orally 
administered high dose of JNJ-67864238 compared with placebo in participants with Crohn’s disease. Since 
the inhibition of the IL-23 pathway has been validated as a mechanism for treating Crohn’s disease, a high 
dose was chosen to assess the efficacy of a locally acting anti-IL-23 inhibitor.  
Participants may be biologic intolerant or refractory (Bio-IR) or biologic nonfailures (Bio-NF) populations 
as defined in the synopsis of the Master protocol PLATFORMPACRD2001.    
A target of 90 Bio-IR and Bio-NF participants will be randomized to receive JNJ-67864238 
 
 or placebo in a 3:2 ratio using permuted block randomization, stratified by baseline Crohn’s Disease 
Activity Index (CDAI) score (≤300, >300) and biological refractory status (Bio-IR, Bio-NF).  The treatment 
arms for this study will be as follows:

JNJ-67864238 
 (N=54)

Placebo (N=36)
Of note, the sample size has been chosen to assess a level of efficacy consistent with that observed with 
systemically available biological therapies for Crohn’s disease.
There is 1 database lock planned at the end of this intervention cohort. In addition, there will be a planned
Interim Analysis (IA) to enable early termination of the intervention cohort if JNJ-67864238 (
 
) is futile.  Additional ad hoc IA(s) may be conducted if deemed necessary.   No database locks are 
planned for any of the IA(s).
Refer to the synopsis of the Master protocol PLATFORMPACRD2001 for a description of the Data 
Monitoring Committee. 
End of Study Definition
The end of the JNJ-67864238 intervention cohort is considered as the last visit for the last participant in the 
intervention cohort. Refer to the synopsis of the Master protocol PLATFORMPACRD2001 for the end of 
study definition.       
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IMMUNOGENICITY EVALUATIONS
Immunogenicity will not be assessed in the JNJ-67864238 intervention cohort.  Samples collected for 
immunogenicity would only be analyzed if required to assess other data or analyses, such as 
pharmacokinetics or adverse events.   
PHARMACODYNAMIC AND BIOMARKER EVALUATIONS
Pharmacodynamic assessments will be made to examine the biological response to treatment and to 
identify genes and proteins that are relevant to JNJ-67864238 treatment and/or Crohn’s disease.  Serum, 
fecal, and whole blood samples will be collected from all participants to study the effect of JNJ-67864238 
on proteins (serum and fecal samples) and RNA expression (whole blood and biopsy samples). Stool and 
saliva samples will also be collected to evaluate the effects of JNJ-67864238 on the microbiome.    
PHARMACOGENOMIC (DNA) EVALUATIONS
Among participants who consent separately to this component of the study, whole genome analyses will be 
performed to detect associations between specific gene polymorphisms to the disease or JNJ-67864238 
response. DNA analysis will be restricted to JNJ-67864238-related effects or to the diseases for which 
JNJ-67864238 is being developed.
SAFETY EVALUATIONS
Participants will be screened for tuberculosis (TB) at study entry. In addition, to aid in the early detection 
of TB reactivation or new TB infection during study participation, participants must be evaluated for signs 
and symptoms of active TB at scheduled visits.    
Refer to the synopsis of the Master protocol PLATFORMPACRD2001 for other safety evaluations.  
STATISTICAL METHODS
Sample Size Determination
The decision-making framework is applied to a total of 5000 virtual studies with simulated CDAI and 
change in the Simplified Endoscopic Score for Crohn’s disease (SES-CD) data. With 90 participants 
(54 participants receiving JNJ-67864238 
 and 36 participants receiving placebo), under 
the alternative hypothesis, the probability of JNJ-67864238 meeting the success criteria is approximately 
87%, and the probability of dropping JNJ-67864238 for futility is approximately 1%. When there is no 
treatment difference, the probability of JNJ-67864238 meeting the success criteria is approximately 5% and 
the probability of dropping JNJ-67864238 for futility is approximately 77%.  There is approximately a 32% 
chance that the futility criteria are met at the IA.  
For reference, without factoring in the interim futility analysis, the sample size of 90 participants 
(54 participants in the JNJ-67864238 
 treatment arm and 36 participants in the placebo 
treatment arm) will provide 90% power to detect a treatment difference at α=0.1 (2-sided) when the true 
treatment difference is 60 (placebo – JNJ-67864238) in the change in CDAI at Week 12 for both Bio-IR 
and Bio-NF populations.
Efficacy Analyses
There are no JNJ-67864238-specific efficacy analyses. Refer to the synopsis of the Master protocol 
PLATFORMPACRD2001 for efficacy analyses.   
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Safety Analyses
There are no JNJ-67864238-specific safety analyses. Refer to the synopsis of the Master protocol 
PLATFORMPACRD2001 for safety analyses.   
Interim Analyses
One IA is planned. It will take place when approximately 45 participants have completed their Week 12 
assessments or have withdrawn early from the intervention cohort. Additional ad hoc IA(s) may be 
conducted if deemed necessary. The objective of the IA(s) is to enable early termination of the intervention 
cohort if JNJ-67864238 is futile and plan for future intervention cohorts. At the time of the IA(s), the study 
team will remain blinded. The planned IA (and any additional IA[s]) will be described in the IA SAP.
1.2.
Schema   
Figure 1:
Schematic Overview of Study Design   








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visit, it must be performed at least 8 days before the Week 0 visit and no more than 8 days before the Week 12 visit or early termination visit. The Simplified 
Endoscopic Score for Crohn’s disease (SES-CD) will be calculated by the central reader. 
q.
The PROMIS surveys should be administered before any clinical procedures or tests are performed. PROMIS surveys will only be collected in countries where 
translations are available. 
r.
Hematology and chemistry tests at Week 0 are not required if screening laboratory tests were performed within 2 weeks before the Week 0 visit.
s.
Blood samples should be collected after PROs are administered and vital signs collected. All reasonable attempts should be made to collect samples at the 
scheduled timepoints and record the actual times of sample collections.
t.
All reasonable attempts should be made to collect samples at the scheduled timepoints and record the actual dates and times of sample collections. 
u.
Requires completion of a separate informed consent. 
67864238PACRD2001 specific
v.
All participants will undergo QuantiFERON-TB testing. In countries where the QuantiFERON-TB test is not registered/approved, TB skin testing will also be 
required (recommended but not required for study centers in Ukraine if tuberculin is not available).
w.
Chest radiograph (posterior-anterior view) must be obtained within 3 months before the Week 0 visit. 
x.
If TB is suspected at any time, a chest radiograph and QuantiFERON-TB test should be performed. In countries where the QuantiFERON-TB test is not 
registered/approved, TB skin testing should also be performed (recommended but not required for study centers in Ukraine if tuberculin is not available). 
y.
Biopsy samples will also be used for the measurement of JNJ-67864238 tissue concentration.
z.
Venous blood samples of sufficient volume for the measurement of JNJ-67864238 plasma concentrations and to assess serum antibodies to JNJ-67864238 will be 
collected from all randomized participants as follows:

Before study intervention administration (ie, predose) at Week 0, Week 2, Week 4, Week 8, and Week 12
i.
The Weeks 2 and 8 sample should be of sufficient volume to assess the plasma concentration of JNJ-67864238 (and a backup sample).  
ii.
The Weeks 0, 4, and 12 samples should be of sufficient volume to assess the plasma concentration of JNJ-67864238 (and a backup sample) 
and to assess serum antibodies to JNJ-67864238.  

After study intervention administration (ie, postdose) at Week 12 within 2 to 4 hours 

At the early termination visit (if applicable)  
aa.
A single stool sample (ie, bowel movement) will be collected at each visit to assess JNJ-67864238 stool concentration and biomarkers.    
bb.
At the screening visit only, the CDAI will be calculated using participant recall. The investigator will complete the variable assessments required to calculate the 
CDAI total score as conducted in the other visits.  
cc.
For visits other than Week 0, the most recent hematocrit value obtained before a visit will be used to calculate the CDAI for that visit.  


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2.
INTRODUCTION
Background
There is significant unmet medical need for patients with Crohn’s disease. To rapidly identify 
efficacious and novel treatment options for these patients, a large number of Phase 2 therapies 
need to be evaluated. 
A platform study is a study with multiple targeted therapies investigated in a single disease in a 
perpetual manner, with therapies allowed to enter or leave the platform on the basis of a decision 
algorithm.14 Therefore, Crohn’s disease is ideally suited for a platform study, as the general design 
and endpoints required for Phase 2 development are common across compounds.
Master protocol PLATFORMPACRD2001 describes the common study design elements in the 
sponsor’s platform program in participants with moderately to severely active Crohn’s disease.  
This Intervention Specific Appendix describes the Phase 2a 67864238PACRD2001 study for
JNJ-67864238 and additional protocol elements specific to this Intervention Specific Appendix
(ISA). For complete study information, refer to both the PLATFORMPACRD2001 and the 
67864238PACRD2001 protocols. 
JNJ-67864238 is an oral antagonist of the interleukin (IL)-23 receptor (IL-23R) being developed 
for the treatment of moderately to severely active Crohn’s disease. 
 
 
  Targeting of the IL-23 pathway has shown to be effective in the treatment of Crohn’s 
disease in clinical studies.11,6,4,12
JNJ-67864238, also known as PTG-200, is being jointly developed by Janssen Research &
Development and Protagonist Therapeutics and will be referred to as JNJ-67864238 in this ISA
protocol.  
For the most comprehensive nonclinical and clinical information regarding JNJ-67864238, refer 
to the latest version of the Investigator's Brochure (IB) and Addenda for JNJ-67864238.   
Terminology
The following terms are used throughout the Master protocol PLATFORMPACRD2001 and this 
67864238PACRD2001 protocol:

"Participant" refers to the common term "subject"

“Study intervention” refers to study agent, either active or placebo

“Intervention cohort” refers to a cohort of adult participants with moderately to severely active 
Crohn’s disease who receive a specific active study intervention or the comparator (ie, placebo 
and/or an active comparator) and in whom the efficacy and safety of that active study
intervention is evaluated
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
“JNJ-active” and “placebo” refer to the active study intervention and the inactive study 
intervention, respectively, being tested in an intervention cohort  

In this intervention cohort, JNJ-active is JNJ-67864238

“Treatment arm” refers to the treatment assignment within an intervention cohort, eg, 
JNJ-active, an active comparator, or placebo  

“Control arm” refers to the comparator for JNJ-active, either an active comparator or placebo 

“Intervention Specific Appendix (ISA)” refers to this 67864238PACRD2001 companion 
protocol to Master protocol PLATFORMPACRD2001, which describes the background 
information for JNJ-67864238 (eg, preclinical and clinical data), JNJ-67864238 entry criteria 
or assessments, JNJ-67864238 statistical assessments (eg, sample size, randomization method 
and ratio), and JNJ-67864238 dosage and administration information.  

"Sponsor" refers to the entities listed in the Contact Information page(s), which will be 
provided as a separate document.  
2.1.
Study Rationale
Initial observations from genetic and animal model data suggest that Crohn’s disease is mediated 
by IL-12 and/or IL-23, potentially through the induction of Th1 and Th17 pathways.10 However, 
increasing evidence suggests a predominant role for IL-23 in Crohn’s disease. Genome-wide 
association studies identified polymorphisms in the IL-23R gene that are associated with Crohn’s 
disease.2 The role of IL-23 in driving intestinal inflammation has been shown in several mouse 
models of inflammatory bowel disease (IBD). Mice treated with anti-IL-23 antibodies exhibited 
attenuated inflammation,10 and mice with a genetic deletion of the p19 subunit of IL-23 are 
protected in several models of intestinal inflammation.9
The potential therapeutic role of IL-23 in Crohn’s disease was first established by clinical studies 
of the IL-12/23p40 antagonist ustekinumab.13 While these studies demonstrated that blockade of 
both IL-12 and IL-23 is effective in treating Crohn’s disease, it could not ascertain the relative 
contributions of the 2 cytokines. More recent studies of 2 anti-IL-23 antagonists risankizumab4,5
and brazikumab12 reported Phase 2 results demonstrating efficacy of IL-23 blockade alone in 
participants with moderately to severely active Crohn’s disease. 
Selective inhibition of IL-23R with an oral compound offers an additional opportunity to uniquely 
inhibit IL-23 driven pathology.  JNJ-67864238, an IL-23 receptor (IL-23R) antagonist, is being 
developed as an oral treatment for patients with IBD.  In vitro studies have shown that 
JNJ-67864238 binds selectively to IL-23R, blocks IL-23 mediated phosphorylation of Stat3 in a 
transformed cell line and in whole blood, and reduces the production of cytokines in primary cells.  
In vivo studies in a rat colitis model showed dose-dependent and significant attenuation of disease 
parameters with high concentrations of JNJ-67864238 detected in the gastrointestinal (GI) tissue 
and stool and with low systemic exposure. 
Following oral administration,
 
 
  Thus, 
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JNJ-67864238 offers an opportunity for differentiation from the injectable monoclonal antibody 
therapeutics and represents an innovative approach to the treatment of patients with IBD. 
2.2.
Background
Nonclinical Studies 
Pharmacologic Profile 
In vitro and in vivo studies have been conducted to assess the activity, pharmacokinetics (PK) and 
toxicology of JNJ-67864238.  In vitro, JNJ-67864238 is a potent and selective antagonist of the 
IL-23 receptor and blocks IL-23 mediated phosphorylation of Stat3 in a transformed cell line and 
in whole blood and reduces the production of cytokine in primary cells (refer to Section 3 of the 
IB for details). 
 
 
In vitro stability studies and the 
 
  
In vivo, JNJ-67864238 is efficacious in attenuating colitis in a 2,4,6 trinitrobenzene sulfonic acid 
(TNBS)-induced rat model of IBD by reducing the ratio of colon weight to length and improving 
the gross pathology and histopathology of the diseased colon comparable to treatment with an anti-
IL-23p19 monoclonal antibody.  The efficacy of JNJ-67864238 in the colitis model was associated 
with detectable drug in the stool corresponding with high concentrations of the drug in the GI 
tissue but low systemic exposure.
Safety Pharmacology 
JNJ-67864238 has been evaluated for cardiovascular safety in the in vitro human ether-à-go-go-
related gene (hERG) assay and by an in vivo radio telemetry study in monkeys. 
JNJ-67864238 did not induce any meaningful inhibition of the hERG potassium current.  
Cardiovascular assessments were also included in a 90-day monkey study near the end of the 
dosing period and no treatment-related changes were seen in electrocardiogram (ECG) parameters, 
heart rate, blood pressure, and body temperature.  Effects on respiratory and neurobehavioral 
function were also assessed in rats and no adverse changes were reported. 
Toxicology
The potential toxicity of JNJ-67864238 was evaluated in repeated dose studies in rats (up to 
6 months in duration) and monkeys (for up to 9 months in duration) and in a standard battery of 
safety pharmacology and genetic toxicity studies. Potential effects on reproductive safety were 
assessed in rats and rabbits. No JNJ-67864238-related adverse changes were observed in any 
study, and the no observed effect level (NOEL) or the no observed adverse effect level (NOAEL) 
in each study was typically the highest dose level evaluated.  
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Embryo-fetal developmental safety was evaluated in rats and rabbits, and no untoward effects were 
detected at 
 (the highest dose tested). JNJ-67864238 was evaluated in 
rats for effects on male and female fertility and no adverse findings were noted at 
 
 (the highest dose tested). JNJ-67864238 was not genotoxic in a standard panel of 
genotoxicity assays.
Pharmacokinetic Profile 
After a single oral dose to rats and monkeys, absorption was rapid, with a Tmax of ≤0.5 hour and 1 
hour in the rat and monkey, respectively. Absolute bioavailability was less than 0.15% and 0.03% 
in the rat and monkey, respectively.  
The retention of JNJ-67864238 in selected GI tissues was assessed after repeated oral dosing in 
rats and monkeys.  These studies demonstrated a comparatively high GI tissue exposure and low 
plasma exposure of JNJ-67864238.  The observed high tissue:plasma ratios after repeated doses 
(in rat) supports the assumption that the activity of JNJ-67864238 will be restricted to the GI tract.
JNJ-67864238 was also assessed for its ability to inhibit the cytochrome (CYP) drug metabolizing 
isozymes. JNJ-67864238 is not an inhibitor of CYP activity and, coupled with the very low 
systemic exposure after oral administration, that there is no concern for drug-drug interactions 
through CYP inhibition.  
In vitro studies evaluated JNJ-67864238 as a potential inhibitor of human P-glycoprotein (P-gp or 
Multidrug Resistance 1 [MDR1] protein), the efflux transporter involved in the intestinal 
absorption and biliary and renal excretion of drugs. The inhibitory effect of JNJ-67864238 on the 
MDR1-mediated efflux of digoxin was determined at seven concentrations of JNJ-67864238 
(0.82-600 μM). JNJ-67864238 did not decrease the net efflux ratio of digoxin, a P-gp substrate, 
indicating that JNJ-67864238 is not an inhibitor of MDR1/P-gp. It is concluded that drug-drug 
interactions with co-administered drugs which are P-gp substrates are unlikely.
Immunogenicity was not tested in animals.  
Clinical Studies
Human Pharmacokinetics, Pharmacokinetics, Safety, and Tolerability
Study PTG-200-01
Study PTG-200-01 was a Phase 1, randomized, double-blind, placebo-controlled, first-in-human 
(FIH) study to assess the safety, tolerability, and PK of JNJ-67864238 in healthy study participants. 
The study was done in 2 parts: Part 1 Single Ascending Dose and Part 2 Multiple Ascending Dose.
Safety Summary
Part 1 Single Ascending Dose:  Thirty-one healthy male participants enrolled in 3 single ascending 
dose cohorts: 
. There were no deaths or serious adverse events (SAEs) 
reported. With the exception of 1 adverse event (AE; nausea) that was reported to be moderate in 
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2.3.1.
Risks for Study Participation
Potential Risks of Clinical 
Significance
Summary of Data/
Rationale for Risk
Mitigation Strategy
Non-response to oral anti-IL23. 
This is the first study examining 
JNJ-67864238 in participants with 
Crohn’s disease.  
Participants should continue 
treatment of Crohn’s disease with 
certain concomitant medications 
(Section 5.1 of this ISA). 
Participants will be withdrawn from 
the study if continuation is not in 
their best interest or if they need to 
initiate protocol-prohibited 
medications including certain 
biologics or immunomodulators 
(Section 7.1 of this ISA).
Risks Due to JNJ-67864238
Risk of infection, including 
tuberculosis (TB).
Available animal and human data 
suggest that systemic blockade of 
IL-23 may be associated with an 
increased infection risk. However, 
unlike a systemically administered 
anti-IL-23 molecule, JNJ-67864238 
is designed to be GI restricted and 
exhibits minimal plasma exposure. 
Therefore, the potential that 
JNJ-67864238 may increase the 
risk of infections or reactivation of 
latent infections is considered to be 
low (Section 5.8 of the IB). 
Systemic exposure with JNJ-
67864238 is far below that required 
for pharmacodynamic (PD) effect, 
therefore risk of infection or TB 
reactivation is not expected.
Participants with either a chronic 
infection, a prior history of 
recurrent infection, or a clinically 
important active infection should 
not receive JNJ-67864238. 
Participants will be instructed to 
seek medical advice if signs or 
symptoms suggestive of an 
infection occur. If a participant 
develops a serious infection they 
will be closely monitored and 
JNJ-67864238 will not be 
administered during the infection. 
Following resolution of a serious 
infection, JNJ-67864238 may be 
reinitiated at the discretion of the 
investigator and/or the medical 
monitor.
Participants with evidence of active 
or latent TB will be excluded.


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Potential Risks of Clinical 
Significance
Summary of Data/
Rationale for Risk
Mitigation Strategy
Vaccine responsiveness may be 
blunted by concurrent anti-IL-23 
treatment.
The theoretical risk of systemic 
anti-IL-23 reducing primary or 
secondary vaccine responses has 
been considered but has not been 
demonstrated to date.
Prior to initiating therapy, 
participants should have completed 
all age-appropriate immunizations 
according to current immunization 
guidelines. Immunization history 
will be assessed at screening.  
Participants must agree not to 
receive a live attenuated virus 
vaccination during the study and for 
30 days after receiving the last dose 
of JNJ-67864238. 
Risks Due to Study Procedures 
A colonoscopy procedure will be 
performed at enrollment and at 
12 weeks post dosing (the primary 
endpoint time point).
Serious complications of 
colonoscopy such as a perforation 
are rare (less than 1/1000); other 
risks associated with colonoscopies 
include abdominal pain, diarrhea, 
bleeding, flatulence, anal bleeding, 
and bloating.
All participants must sign a consent 
form to have a colonoscopy as part 
of this study, which will include an 
explanation of the risks and benefits 
of the procedure. Standard of care 
will be practiced by the investigator 
performing the procedure to 
minimize risks.
2.3.2.
Benefits for Study Participation
JNJ-67864238 is predominantly GI restricted, thereby minimizing the risk of systemic side effects 
that could occur due to systemic exposure to high concentrations of an IL-23 inhibitor.  This 
potentially gives oral JNJ-67864238 an advantage over the injectable therapeutics that target the 
same immune pathway (IL-23) because most of it does not enter or last in the systemic circulation 
at high concentrations. Thus, JNJ-67864238 offers an opportunity for differentiation from the 
injectable, systemic anti-IL-23 monoclonal antibody therapeutics and represents an innovative 
approach to the treatment of patients with IBD. 
The clinical efficacy of JNJ-67864238 has not been evaluated in patients with Crohn’s disease. 
Therefore, the benefit of JNJ-67864238 in Crohn’s disease is not yet known. However, studies of 
systemic anti-IL-23 compounds have shown efficacy for both clinical and endoscopic 
improvement in up to ~30% of patients. In addition, approved anti-IL-12/23 or anti-IL-23 drugs 
(ie, STELARA® [ustekinumab], TREMFYA® [guselkumab]) have been generally safe and well 
tolerated by patients in the approved indications of psoriasis and Crohn’s disease for STELARA
and psoriasis for TREMFYA. Thus, the potential benefit of participating in this study is that 
JNJ-67864238 could induce clinical response and remission of Crohn’s disease. Participants will 
also have regular follow-up with their physician during this study, and this type of monitoring (ie, 
physical exams and laboratory assessments) may result in improved care of their disease.  


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JNJ-67864238 is not an injectable medication (ie, not a subcutaneous [SC] injection or intravenous
[IV] infusion) but is an oral tablet that will be administered at 
 
. If approved, it will be a convenient treatment for patients, reducing the burden of missing 
school or work for a drug infusion or dealing with the pain and inconvenience of injections. 
Participants in the study will also help in furthering development of this and other oral drugs 
specifically designed to treat Crohn’s disease.  Thus, the knowledge gained from this study has the 
potential to benefit many more patients suffering with Crohn’s disease by developing better, more 
potent, and safer medications for this disease.
2.3.3.
Benefit-Risk Assessment for Study Participation
The dose regimen of JNJ-67864238 selected for this study demonstrated a favorable safety profile 
in a Phase 1 FIH healthy volunteer study. There were no adverse drug reactions reported.
Available animal and human data support the critical role of IL-23 in the pathogenesis of Crohn’s 
disease, and studies with other anti-IL-23 monoclonal antibodies (mAbs) suggest that selective 
targeting of IL-23 may achieve higher levels of efficacy than that observed with other mechanisms 
of action in patients with moderately to severely active Crohn’s disease. Participants with Crohn’s 
disease with evidence of active disease and an inadequate response or loss of response to biologics 
(ie, anti-tumor necrosis factor [TNF] agents, anti-integrins) or immunomodulators (ie, 
6-mercaptopurine, azathioprine, or methotrexate) are eligible for this study. Given their history 
with other agents, many of these participants may have few other treatment options to induce 
and/or maintain remission of active disease. Anti-IL-12/23 drug therapy (ustekinumab) has 
demonstrated efficacy in patients who are naïve to anti-TNF therapy or who have received anti-
TNF therapy. Due to the unique design of JNJ-67864238, most of it is concentrated in the GI tract 
with very little of it reaching the systemic circulation. Thus, the low risk of infection associated 
with the systemic anti-IL23 drug compounds, as described in Section 5.8 of the IB, are 
significantly minimized with JNJ-67864238. Although an efficacy response with JNJ-67864238 
in Crohn’s disease has not been established, given the low systemic exposure and risk of infection, 
there is a potential benefit to participants who may respond to treatment with investigational JNJ-
67864238.  
Some participants will receive placebo for the duration of the study, which will eliminate exposure 
to JNJ-67864238 and any possible benefit or adverse effects associated with it.  All participants 
should continue to receive protocol-permitted, existing background medications for Crohn’s 
disease.  In addition, if participants experience worsening of their Crohn’s disease, they have the 
option to discontinue the study intervention and initiate other treatment at the discretion of their 
physician.  
Taking into account the measures taken to minimize risk to participants participating in this study, 
the potential risks identified in association with JNJ-67864238 are justified by the anticipated 
benefits that may be afforded to participants with Crohn’s disease.  
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3.
OBJECTIVES AND ENDPOINTS
Refer to Section 3 of the Master protocol PLATFORMPACRD2001 for study objectives and 
endpoints.  
HYPOTHESIS
Refer to Section 3 of the Master protocol PLATFORMPACRD2001 for the study hypothesis.   
4.
STUDY DESIGN
4.1.
Overall Design
This ISA is designed to assess the effects of a predominantly gastrointestinal-restricted anti-
IL-23R compound for moderately to severely active Crohn’s disease. This 12-week Phase 2a study 
is focused on proof-of-concept and will assess the safety and efficacy of an orally administered
high dose of JNJ-67864238 compared with placebo in participants with Crohn’s disease. Since the 
inhibition of the IL-23 pathway has been validated as a mechanism for treating Crohn’s disease, a 
high dose was chosen to assess the efficacy of a locally acting anti-IL-23 inhibitor.  
The target population for this intervention cohort is defined in Section 4.1.2 of the Master protocol 
PLATFORMPACRD2001 (ie, men or women 18 to 75 years of age with moderately to severely 
active Crohn’s disease of at least 3 months’ duration, defined as a Crohn’s Disease Activity Index 
(CDAI) score ≥220 but ≤450 at Week 0, with a Simplified Endoscopic Score for Crohn’s disease
(SES-CD) score ≥3 by central endoscopy read OR an elevated C-reactive protein (CRP; >0.3 
mg/dL or 3.0 mg/L) or elevated fecal calprotectin (>250 µg/mg). In this intervention cohort, 
however, participants with a screening SES-CD score <3 who have an elevated CRP or elevated 
fecal calprotectin will be limited to 20% of the participant population.
Participants may be biologic intolerant or refractory (Bio-IR) or biologic nonfailures (Bio-NF) 
populations as defined in Section 4.1.2 of the Master protocol PLATFORMPACRD2001. 
A target of 90 Bio-IR and Bio-NF participants will be randomized to receive JNJ-67864238 
or placebo in a 3:2 ratio using permuted block randomization, stratified by 
baseline CDAI score (≤300, >300) and biological refractory status (Bio-IR, Bio-NF).  The 
treatment arms for this study will be as follows:

JNJ-67864238
 (N=54)

Placebo (N=36)
Of note, the sample size has been chosen to assess a level of efficacy consistent with that observed 
with systemically available biological therapies for Crohn’s disease (Section 2.1 of this ISA).
There is 1 database lock (DBL) planned at the end of this intervention cohort. In addition, there 
will be a planned Interim Analysis (IA) to enable early termination of the intervention cohort if 
JNJ-67864238 (
) is futile. Additional ad hoc IA(s) may be conducted if deemed 
necessary.  No DBLs are planned for any of the IA(s).
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The Data Monitoring Committee (DMC) and Interim Analysis Committee for the study are
described in Section 9.5.1, Section 9.6 and Appendix 5, Regulatory, Ethical, and Study Oversight 
Considerations, all in the Master protocol PLATFORMPACRD2001.  
A diagram of the study design is provided in Section 1.2 of this ISA, Schema.  
4.2.
Scientific Rationale for Study Design
JNJ-67864238 is the first JNJ-active compound in the Crohn’s disease platform study described in 
the Master protocol PLATFORMPACRD2001. 
Refer to Section 4.2 of the Master protocol PLATFORMPACRD2001 for a full description of the 
scientific rationale for the study design.     
4.2.1.
Study-Specific Ethical Design Considerations
The primary ethical concern is that participants enrolled in an intervention cohort will be randomized 
to receive either active study intervention or placebo for 12 weeks, with no therapeutic benefit for 
this portion of the study. While patients with Crohn’s disease do traditionally benefit from inclusion 
in clinical studies independent of the assigned therapy and many improve even while on placebo (up 
to 30-50%), the duration of the placebo-controlled induction period has been limited to the extent 
possible while still maintaining sufficient scientific rigor for meaningful evaluation of critical 
endoscopic endpoints. Also, participants will be closely monitored during this 12-week period and 
will continue to receive existing background therapy for Crohn’s disease. Participants with 
worsening Crohn’s disease can discontinue the study intervention at any time, and the study 
intervention should be discontinued if a participant requires additional therapy for Crohn’s disease.   
The total blood volume to be collected is considered to be an acceptable amount of blood to be 
collected over this time period from the population in this study and is described Section 8 of this
ISA.  
Refer to Section 4.2.1 of the Master protocol PLATFORMPACRD2001 for other study-specific
ethical design considerations. 
4.3.
Justification for Dose
JNJ-67864238 is administered orally for local action in the intestinal tract with very little systemic 
exposure (absolute bioavailability approximately 0.1% in the rat and approximately 0.03% in the 
monkey). The human equivalent dose approach and relative in vitro (IC50 for IL 23R) and ex vivo 
(white blood cell pSTAT3 IC50) potency in preclinical species versus humans was used to select 
the JNJ-67864238 doses evaluated in the FIH study (PTG-200-01). The JNJ-67864238 doses 
evaluated in the single ascending dose part were 
; the 
doses evaluated in the multiple ascending dose part were 
 
 The dosage selected for this proof-
of-concept study is the highest dosage tested in the FIH study (ie, 
). This dosage
also produced consistent fecal JNJ-67864238 concentrations in humans which, on average, greatly 
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exceed the estimated EC80 concentrations or the 50% probability of obtaining a favorable colonic 
score shown to be efficacious in a TNBS-induced rat model of colitis.
The FIH study in healthy subjects demonstrated that 
 
 are safe and generally well tolerated. After multiple dosing, 
fecal samples showed that only those subjects administered JNJ-67864238 
had
substantially higher (~24-fold) median fecal JNJ-67864238 concentrations than the 15,000 ng/mL
threshold target. 
In view of these results and to maximize the likelihood of a positive outcome in this study, the 
JNJ-67864238 dose selected is 
. This dose is also supported by a preclinical 
exposure-response analysis of the efficacy of JNJ-67864238 in treating rats with TNBS-induced 
colitis, as well as safety data following daily dosing for up to 6 months in rats and 9 months in 
monkeys. 
In summary, a dosage of JNJ-67864238 
is selected for this study, as it is 
supported by preclinical exposure-response modeling, human safety/tolerability from the FIH 
study, and the toxicology margins established in the Good Laboratory Practice studies.
4.4.
End of Study Definition
The end of the JNJ-67864238 intervention cohort is considered as the last visit for the last 
participant in the intervention cohort. Refer to Section 4.4
of the Master protocol 
PLATFORMPACRD2001 for a full description of the end of study definition.  
5.
STUDY POPULATION
To be eligible to participate in the JNJ-67864238 intervention cohort, potential participants must 
meet all inclusion and exclusion criteria described in Section 5.1 and Section 5.2, respectively, of
the Master protocol PLATFORMPACRD2001, which are also listed below. Potential participants 
must also meet the additional JNJ-67864238-specific inclusion and exclusion criteria presented in
Section 5.1 and Section 5.2 of this ISA, respectively, to participate in the JNJ-67864238 
intervention cohort. 
Considerations specific to JNJ-67864238 include the following:   

Participants who have failed anti-IL-12/23 and anti-IL-23 agents will be excluded.

Participants with known allergies, hypersensitivity, or intolerance to JNJ-67864238 or its 
excipients will be excluded.

As reactivation of latent tuberculosis (TB) has been reported with systemic IL-23 inhibition, 
participants with evidence of active or latent TB will be excluded. However, because systemic 
exposure with JNJ-67864238 is far below that required for a pharmacodynamic (PD) effect, 
the risk for TB reactivation is expected to be low.
Screening for eligible participants will be performed within 5 weeks before administration of the 
study intervention. Refer to Section 5.4 of this ISA, Screen Failures, for conditions under which
the repeat of any screening procedures are allowed.
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The inclusion and exclusion criteria for enrolling participants in the Master protocol 
PLATFORMPACRD2001 and this ISA are described below. If there is a question about these
criteria, the investigator must consult with the appropriate sponsor representative and resolve any 
issues before enrolling a participant in the study.  Waivers are not allowed. 
5.1.
Inclusion Criteria
Each potential participant must satisfy all of the following Master PLATFORMPACRD2001 
protocol and these ISA-specific criteria to be enrolled in the JNJ-67864238 intervention cohort.     
Master PLATFORMPACRD2001 protocol inclusion criteria are listed below.
1.
Male or female
2.
18 to 75 years of age, inclusive
Disease Characteristics
3.
Have Crohn’s disease or fistulizing Crohn’s disease of at least 3 months’ duration, with 
colitis, ileitis, or ileocolitis confirmed at any time in the past by radiography, histology, 
and/or endoscopy    
4.
Have active Crohn’s disease, defined as a baseline CDAI score of ≥220 and ≤450
5.
Have evidence of active ileocolonic Crohn’s disease as assessed by: 
a.
An SES-CD score ≥3 at screening by central endoscopy reading 
OR 
b. An elevated screening CRP (>0.3 mg/dL or 3.0 mg/L) or an elevated screening 
fecal calprotectin (>250 µg/mg)
6.
A participant with a family history of colorectal cancer, personal history of increased risk 
of colorectal cancer, age >50 years, or other known risk factor must be up-to-date on 
colorectal cancer surveillance (may be performed during screening). Adenomatous 
polyps must be removed before the first administration of the study intervention. 


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7.
A participant who has had extensive colitis for ≥8 years, or disease limited to the left side 
of the colon for ≥12 years, must either have had a colonoscopy to assess for the presence 
of dysplasia within 1 year before the first administration of the study intervention or a 
colonoscopy to assess for the presence of malignancy at the screening visit, with no 
evidence of malignancy  
Concomitant or Previous Medical Therapies Received
8.
Meet the following requirements for prior or current medications for Crohn’s disease: 
a. Has previously demonstrated inadequate response to, loss of response to, or 
intolerance to an approved biologic therapy (unless otherwise specified in the JNJ-
67864238 intervention cohort specific criteria below, ie, anti-TNFα agents [eg, 
infliximab, adalimumab, certolizumab pegol], anti-IL-12/23 agents [eg, 
ustekinumab], or anti-integrin agents [eg, vedolizumab]), ie, the Bio-IR 
population (Appendix 2 of the Master protocol PLATFORMPACRD2001
[Definition of Inadequate Initial Response, Loss of Response, or Intolerance to 
TNF Antagonist Therapies (Infliximab, Adalimumab, or Certolizumab Pegol), 
Vedolizumab, or Ustekinumab] and Section 5.2 of this ISA)
OR
b. Has previously demonstrated an inadequate response to or failed to tolerate 
corticosteroids or immunomodulators (ie, 6-MP, AZA, and MTX) but not a 
biologic, ie, the Bio-NF population (Appendix 3 of the Master protocol 
PLATFORMPACRD2001, Definitions of Inadequate Response to or Intolerance 
of Corticosteroids or AZA/6 MP and Corticosteroid Dependence)    
9.
Therapy for the treatment of Crohn's disease must include at least 1 of the following 
medications, which should have been maintained at stable doses prior to the baseline 
(Week 0) visit:   
a. Oral 5-aminosalicylic acid (5-ASA) compounds 
b. Oral corticosteroids at a prednisone-equivalent dose ≤25 mg/day, or 9 mg/day of 
budesonide, or 5 mg/day beclomethasone dipropionate  
c. Antibiotics being used as a primary treatment of Crohn's disease   
d. Conventional immunomodulators (ie, AZA, 6-MP, or MTX) if participants have 
been taking them for at least 12 weeks and have been at a stable dose for at least 
4 weeks prior to baseline 
Laboratory Parameters
10. Have screening laboratory test results within the following parameters:
a. Hemoglobin ≥8.0 g/dL 


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b. White blood cell count (WBCs) ≥3.0 × 103/μL 
c. Neutrophils ≥1.5 × 103/μL 
d. Platelets ≥100 × 103/μL 
e. Serum creatinine <1.7 mg/dL 
f. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) 
concentrations must be within 2 times the upper limit of the normal range for the 
laboratory conducting the test 
g. Direct (conjugated) bilirubin <1.0 mg/dL
Pregnancy Testing 
11. A woman of childbearing potential must have a negative highly sensitive serum (-human 
chorionic gonadotropin [-hCG]) pregnancy test result at screening and a negative urine 
pregnancy test result at Week 0.  
Other
12. Must sign an informed consent form (ICF) indicating that he or she understands the 
purpose of, and procedures required for, the study and is willing to participate in the study
13. Must sign a separate ICF if he or she agrees to provide optional DNA samples for research 
(where local regulations permit). Refusal to give consent for the optional DNA research 
samples does not exclude a participant from participation in the study   
14. Willing and able to adhere to the lifestyle restrictions specified in this protocol
JNJ-67864238 intervention cohort specific inclusion criteria start with the letter A and are listed 
below.  
A01.
A woman using oral contraceptives must use an additional contraceptive method (above 
that required in Inclusion Criterion A02).  
A02.
A woman must be (as defined in Appendix 2 of this ISA, Contraceptive and Barrier 
Guidance and Collection of Pregnancy Information)
a.
Not of childbearing potential
b.
Of childbearing potential and
o
Practicing a highly effective method of contraception (failure rate of <1% 
per year when used consistently and correctly) and agrees to remain on a 
highly effective method while receiving study intervention and until 30 days 


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after last dose - the end of relevant systemic exposure. Examples of highly 
effective methods of contraception are located in Appendix 2 of this ISA,
Contraceptive and Barrier Guidance and Collection of Pregnancy 
Information. 
A03.
A woman must agree not to donate eggs (ova, oocytes) for the purposes of assisted 
reproduction during the study and for a period of 30 days after receiving the last dose of 
study intervention.
A04.
A male participant must wear a condom when engaging in any activity that allows for 
passage of ejaculate to another person.    
A05.
A male participant must agree not to donate sperm for the purpose of reproduction during 
the study and for a minimum 90 days after receiving the last dose of study intervention.
A06.
It is recommended that participants are up to date on age-appropriate vaccinations prior 
to screening as per routine local medical guidelines. For study participants who received 
locally approved (and including emergency use-authorized) COVID-19 vaccines recently 
prior to study entry, follow applicable local vaccine labeling, guidelines, and standards of 
care for patients  receiving immune-targeted therapy when determining an appropriate 
interval between vaccination and study enrollment (see also Section 6.5 Concomitant 
Therapy).  
5.2.
Exclusion Criteria
Any potential participant who meets any of the following Master PLATFORMPACRD2001 
protocol and these ISA-specific criteria will be excluded from participating in the JNJ-67864238 
intervention cohort.
Master PLATFORMPACRD2001 protocol exclusion criteria are listed below.
Disease Characteristics
1.
Has complications of Crohn’s disease such as symptomatic strictures or stenoses, short 
gut syndrome, or any other manifestation that might be anticipated to require surgery, 
could preclude the use of the CDAI to assess response to therapy, or would possibly 
confound the ability to assess the effect of treatment with JNJ-67864238
2.
Currently has or is suspected to have an abscess. Recent cutaneous and perianal 
abscesses are not exclusionary if drained and adequately treated at least 3 weeks before 
baseline, or 8 weeks before baseline for intra-abdominal abscesses, provided that there 
is no anticipated need for any further surgery. Participants with active fistulas may be 
included if there is no anticipation of a need for surgery and there are currently no 
abscesses identified.  
3.
Has had any kind of bowel resection within 6 months or any other intra-abdominal 
surgery within 3 months before baseline  


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4.
Has a draining (ie, functioning) stoma or ostomy   
Concomitant or Previous Medical Therapies Received
5.
Has received any of the following prescribed medications or therapies within the 
specified period: 
Compound
Exclusionary Period
a.
Intravenous corticosteroids 
<3 weeks before baseline  
b.
Oral immunomodulatory 
agents including 6-
thioguanine (6-TG), 
cyclosporine, tacrolimus, 
sirolimus, or mycophenolate 
mofetil, tofacitinib and other 
Janus kinase (JAK) inhibitors
<6 weeks or within 5 half-lives of agent 
before baseline, whichever is longer    
c.
Natalizumab or biologic 
agents that deplete B or T 
cells (eg, rituximab or 
alemtuzumab) 
<12 weeks before baseline
6.
Has received a TNFα-antagonist biologic agents (eg, monoclonal antibody therapies) 
within 8 weeks prior the first administration of the study intervention or vedolizumab 
within 16 weeks prior to the first administration of the study intervention OR has
received an anti-IL-12/23 (eg, ustekinumab) within 16 weeks prior to the first 
administration of the study intervention OR has detectable serum concentrations of an 
advanced therapy (ie, TNFα-antagonist biologic agents, vedolizumab, and tofacitinib)  
7.
Initiation of total (complete) or partial (supplemental) parenteral nutrition administered 
through any indwelling catheter <3 weeks before baseline or anticipated to require 
parenteral nutrition administered through an indwelling catheter during enrollment in 
the study
8.
Initiation of enteral therapy for Crohn’s disease (liquid nutritional formula comprising 
≥80% of total caloric intake administered through the gastrointestinal tract) <3 weeks 
before baseline. Subjects who are on a stable regimen of enteral feeds ≥3 weeks before 
baseline may be considered for enrollment if they plan to continue enteral feeds as 
treatment for Crohn’s disease through the duration of the study.
Infections or Predisposition to Infections  
9.
Has a history of serious infection (eg, sepsis, pneumonia, or pyelonephritis), including 
any infection requiring hospitalization or IV antibiotics, within 8 weeks before baseline 
10. Has a stool culture or other examination positive for an enteric pathogen, including 
Clostridium difficile toxin, in the last 4 months unless a repeat examination is negative 
and there are no signs of ongoing infection with that pathogen, or has had a fecal 
transplant in the last 4 months 


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11. Has a history of, or ongoing, chronic or recurrent infectious disease, including but not 
limited to, chronic renal infection, chronic chest infection, recurrent urinary tract 
infection (eg, recurrent pyelonephritis or chronic nonremitting cystitis), or open, 
draining, or infected skin wounds or ulcers 
12. Has current signs or symptoms of infection. Established nonserious infections (eg, acute 
upper respiratory tract infection, simple urinary tract infection) need not be considered 
exclusionary at the discretion of the investigator 
13. Has or ever has had a systemic nontuberculous mycobacterial infection or serious 
opportunistic infection (eg, cytomegalovirus colitis, Pneumocystis carinii, aspergillosis) 
14. Is infected with human immunodeficiency virus (HIV; positive serology for HIV 
antibody). If seropositive, consultation with a physician with expertise in the treatment 
of HIV is recommended
15. Is seropositive for antibodies to hepatitis C virus (HCV) without a history of successful 
treatment, defined as being negative for HCV RNA at least 24 weeks after completing 
antiviral treatment  
16. Is infected with hepatitis B virus (HBV; Appendix 4 of the Master protocol 
PLATFORMPACRD2001, Hepatitis B Virus Screening). For participants who are not 
eligible for this study due to HBV test results, consultation with a physician with 
expertise in the treatment of HBV infection is recommended.  
Malignancy or Increased Potential for Malignancy  
17. Has a known history of lymphoproliferative disease, including monoclonal 
gammopathy of unknown significance, lymphoma, or signs and symptoms suggestive 
of possible lymphoproliferative disease, such as lymphadenopathy and/or splenomegaly 
18. Known malignancy or a history of malignancy before screening (with the exception of 
basal cell carcinoma; squamous cell carcinoma in situ of the skin; or cervical carcinoma 
in situ that has been treated with no evidence of recurrence; or squamous cell carcinoma 
of the skin that has been treated with no evidence of recurrence within 5 years before 
screening)  
Coexisting Medical Conditions or Past Medical History  
19. History of liver or renal insufficiency (estimated creatinine clearance below
60 mL/min); significant cardiac, vascular, pulmonary, endocrine, neurologic, 
hematologic, rheumatologic, psychiatric, or metabolic disturbances 
20. Has a transplanted organ (with exception of a corneal transplant >12 weeks before 
screening) 


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Other  
21. Is unable or unwilling to undergo multiple venipunctures because of poor tolerability or 
lack of easy access to veins   
22. Is currently or intending to participate in any other study using an investigational agent 
or procedure during participation in this study  
23. Received an investigational treatment or used an invasive investigational medical 
device within 5 half-lives of the investigational treatment before baseline before the 
planned first dose of study intervention  
24. Any condition for which, in the opinion of the investigator, participation would not be 
in the best interest of the participant (eg, compromise the well-being) or that could 
prevent, limit, or confound the protocol-specified assessments  
25. Employee of the investigator or study site, with direct involvement in the proposed 
study or other studies under the direction of that investigator or study site, as well as 
family members of the employees or the investigator.  
26. Participants must not have a history of drug or alcohol abuse according to the Diagnostic 
and Statistical Manual of Disorders (5th edition) criteria within the last 12 months
JNJ-67864238 intervention cohort specific exclusion criteria start with the letter A and are listed 
below.  
A01.
Updated per Amendment 5.
A01.1. Prior exposure to an anti-IL-12/23 (ie, ustekinumab) or anti-IL-23 agents or 
related compound (including risankizumab, brazikumab, guselkumab, mirikizumab, 
and related compounds). Exception is made for participants who have had minimal
exposure to ustekinumab at its approved labeled dosage AND have met the required 
wash-out criteria AND have not demonstrated inadequate response or intolerance to 
ustekinumab as defined in Appendix 8 of this ISA.  
A02.
Known allergies, hypersensitivity, or intolerance to JNJ-67864238 or its excipients 
(refer to IB for JNJ-67864238)
A03.
Pregnant, or breast-feeding, or planning to become pregnant while enrolled in this study 
or within 30 days after the last dose of study intervention.
A04.
Plans to father a child while enrolled in this study or within 90 days after the last dose 
of study intervention  
A05.
Unable or unwilling to swallow
intact study intervention tablets 
 with 
approximately 240 mL (8 ounces) of water
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Tuberculosis Exclusion Criteria
A06
Have a history of latent or active TB prior to screening
A07
Have signs or symptoms suggestive of active TB upon medical history and/or physical 
examination
A08
Have had recent close contact with a person with active TB
A09
QuantiFERON®-TB test criteria:
a.
Within 2 months prior to the first administration of study agent, have a 
positive QuantiFERON®-TB test result; Within 2 months, a positive 
tuberculin skin test (Appendix 3 of this ISA, Tuberculin Skin Testing) prior 
to the first administration of study agent is exclusionary if the 
QuantiFERON®-TB test is not approved/registered in that country or the 
tuberculin skin test is mandated by local health authorities.   
b.
Indeterminate results should be handled as outlined in Section 8.11 of this 
ISA.  Participants with persistently indeterminate QuantiFERON®-TB test 
results may be enrolled without treatment for latent TB, if active TB is ruled 
out, a chest radiograph shows no abnormality suggestive of TB (active or 
old, inactive TB), and the participant has no additional risk factors for TB 
as determined by the investigator. This determination must be promptly 
reported to the sponsor’s medical monitor and recorded in the participant’s 
source documents and initialed by the investigator.   
A10
Have a chest radiograph (posterior-anterior view) taken within 3 months prior to the 
first administration of study agent and read by a qualified radiologist, with evidence of 
current, active TB or old, inactive TB or that shows an abnormality suggestive of a 
malignancy or current active infection  
A11
Have a history of active granulomatous infection, including histoplasmosis or 
coccidioidomycosis, prior to screening
A12
Have had a Bacille Calmette-Guérin (BCG) vaccination within 12 months of screening 
or any other live bacterial or live viral vaccination within 12 weeks before baseline
NOTE: Investigators should ensure that all study enrollment criteria have been met at screening. 
If a participant's clinical status changes (including any available laboratory results or receipt of 
additional medical records) after screening but before the first dose of study intervention is given 
such that he or she no longer meets all eligibility criteria, then the participant should be excluded 
from participation in the study. Section 5.4 of this ISA and Section 5.4 of the Master protocol 
PLATFORMPACRD2001, Screen Failures, describe options for retesting. The required source 
documentation to support meeting the enrollment criteria are noted in Appendix 5 of the Master 
protocol PLATFORMPACRD2001, Regulatory, Ethical, and Study Oversight Considerations.


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5.3.
Lifestyle Considerations
Potential participants must be willing and able to adhere to the following lifestyle restrictions 
during the course of the study to be eligible for participation:
1.
Refer to Section 6.5 of this ISA, Concomitant Therapy for details regarding prohibited 
and restricted therapy during the study.
2.
Agree to follow all requirements that must be met during the study as noted in the 
Inclusion and Exclusion Criteria (eg, contraceptive requirements).
3.
Must agree not to receive a live attenuated virus vaccination during the study and for 
30 days after receiving the last dose of study intervention.
4.
Must agree not to receive a BCG vaccination during the study and for 30 days after 
receiving the last dose of study intervention.
5.4.
Screen Failures
Refer to Section 5.4 of the Master protocol PLATFORMPACRD2001 for screening failure 
considerations.
Participants
who meet the entry criteria for inclusion per
the Master protocol 
PLATFORMPACRD2001 but do not meet the entry criteria for participation per this ISA may be 
rescreened to this or another ISA, depending on the reason for screen failure. Participants who 
meet exclusion criteria A01 or A02 (Section 5.2 of this ISA) may not be rescreened to this ISA.  
6.
STUDY INTERVENTION
6.1.
Study Interventions Administered
JNJ-67864238 will be provided as
 for oral administration. Participants will be 
instructed to take their assigned dose of the study intervention (JNJ-67864238 or matching placebo
tablets) 
orally 
. 
The study intervention is to be taken with approximately 240 mL (8 ounces) of water. The tablets 
should be swallowed intact with no attempt to dissolve them in water. 
The dosage and administration specifics for JNJ-67864238 tablets and the matching placebo
tablets are described in Table 2.
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6.2.
Preparation/Handling/Storage/Accountability
Preparation/Handling/Storage
All study intervention must be stored at controlled temperatures ranging from 36°F to 46°F (2°C 
to 8°C) and protected from moisture. 
Refer to the pharmacy manual/study site investigational product and procedures manual for 
additional guidance on study intervention preparation, handling, and storage. 
Accountability
The investigator is responsible for ensuring that all study intervention received at the site is 
inventoried and accounted for throughout the study. The dispensing of study intervention to the 
participant, and the return of study intervention from the participant (if applicable), must be 
documented on the study intervention accountability form. Participants must be instructed to return 
all original containers, whether empty or containing study intervention. All study intervention will 
be stored and disposed of according to the sponsor's instructions. Study-site personnel must not 
combine contents of the study intervention containers.
Study intervention must be handled in strict accordance with the protocol and the container label, 
and must be stored at the study site in a limited-access area or in a locked cabinet under appropriate 
environmental conditions. Unused study intervention, and study intervention returned by the 
participant, must be available for verification by the sponsor's study site monitor during on-site 
monitoring visits. The return to the sponsor of unused study intervention, or used returned study 
intervention for destruction, will be documented on the study intervention return form. When the 
study site is an authorized destruction unit and study intervention supplies are destroyed on-site, 
this must also be documented on the study intervention return form.
Study intervention should be dispensed under the supervision of the investigator or a qualified 
member of the study-site personnel, or by a hospital/clinic pharmacist. Study intervention will be 
supplied only to participants enrolled in the study. Returned study intervention must not be 
dispensed again, even to the same participant. Whenever a participant brings his or her study 
intervention to the study site for pill count, this is not seen as a return of supplies. Study 
intervention may not be relabeled or reassigned for use by other participants. The investigator 
agrees neither to dispense the study intervention from, nor store it at, any site other than the study 
sites agreed upon with the sponsor.
6.3.
Measures to Minimize Bias: Randomization and Blinding
JNJ-67864238 Intervention Cohort
Randomization
Central randomization will be implemented in this study. Participants assigned to this intervention 
cohort and eligible to enroll will be randomized to 1 of 2 treatment arms in a 3:2 ratio 


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(JNJ-67864238:placebo) based on a computer-generated randomization schedule prepared before 
the study by or under the supervision of the sponsor. 
Stratification
The study intervention randomization in this cohort will be balanced by using randomly permuted 
blocks and will be stratified by the baseline CDAI score (<300 and ≥300) and population (Bio-IR 
and Bio-NF).  The interactive web response system (IWRS) will assign a unique treatment code, 
which will dictate the study intervention treatment arm and matching study intervention kit for the 
participant. The requestor must use his or her own user identification and personal identification 
number when contacting the IWRS and will then give the relevant participant details to uniquely 
identify the participant.
Blinding
After all 90 randomized participants have either completed the Week 12 visit or have terminated 
study participation before Week 12, the Week 12 DBL will occur and the treatment assignment 
information will be unblinded to the sponsor for all participants and released to the sponsor for 
analysis. The final safety DBL will occur when all randomized participants have either completed 
the final safety visit or have terminated study participation.   
Refer to Section 6.3 of the Master protocol PLATFORMPACRD2001 for additional blinding 
considerations.   
6.4.
Study Intervention Compliance
Participant compliance with the protocol-specified administration of the study intervention (
 by mouth 
) will be assessed by the site at each clinic visit 
following baseline (Day 1) up to the end of treatment. 
Study-site personnel will maintain a log of all study intervention administered. Drug supplies for 
each participant will be inventoried and accounted for.  
6.5.
Concomitant Therapy
Concomitant therapies must be recorded throughout the study beginning with the signing of the 
ICF to the last study visit (including the follow-up visit).
Concomitant therapies should also be recorded beyond the follow-up visit only in conjunction with 
new or worsening AEs and SAEs that meet the criteria outlined in Serious Adverse Events in 
Section 8.3.1 of this ISA.
All therapies (prescription or over-the-counter medications, including vaccines, vitamins, herbal 
supplements; non-pharmacologic therapies such as electrical stimulation, acupuncture, special 
diets, exercise regimens) different from the study intervention must be recorded in the CRF. 
Recorded information will include a description of the type of treatment, treatment period, dosing 
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regimen, route of administration, and its indication.  Modification of an effective pre-existing 
therapy should not be made for the explicit purpose of entering a participant into the study. 
Participants are not to receive the prohibited prestudy therapies listed in Exclusion Criteria 5, 6, 
and A01.  
When considering use of locally approved (and including emergency use-authorized) COVID-19 
vaccines in study participants, follow applicable local vaccine labelling, guidelines, and standards 
of care for participants receiving immune-targeted therapy.
The sponsor must be notified in advance (or as soon as possible thereafter) of any instances in 
which prohibited therapies are administered.
6.5.1.
Rescue Medication
Participants may transiently use (ie, for <4 weeks) increased doses of corticosteroids for reasons 
other than loss of response to treatment for Crohn’s disease (eg, stress doses of corticosteroids for 
surgery, asthma, adrenocortical insufficiency, etc).
Although enrolled participants should not initiate or increase the dose of oral or rectal 5-ASA 
compounds, immunomodulators (ie, AZA, 6-MP, or MTX), corticosteroids, or antibiotics as a 
treatment for Crohn’s disease so as not to confound the efficacy assessments, it is recognized that 
the use of such compounds may be medically necessary.  In such cases, participants may continue 
to receive the study intervention, but would be considered a treatment failure. This would not 
represent a deviation from the study protocol.
6.5.2.
Crohn’s Disease-Specific Therapies
Participants must continue to receive their concomitant, background oral 5-ASA compounds, the 
immunomodulators AZA, 6-MP, and MTX, oral corticosteroids, and/or antibiotics for the 
treatment of Crohn’s disease during the study (as defined in the inclusion criteria). Concomitant 
medications for Crohn’s disease at study enrollment should be maintained at a stable dose 
throughout this study.
Enrolled participants should not initiate any of the following Crohn’s disease-specific medical 
therapies during their participation in the study: 

Oral or rectal 5-ASA compounds

Immunomodulators (ie, AZA, 6-MP, or MTX)

Parenteral or rectal corticosteroids  

Antibiotics as a treatment for Crohn’s disease

Total parenteral nutrition as a treatment for Crohn’s disease 
Because protection of human research participants is paramount, it is recognized that initiating or 
modifying the dose of the above therapies may be medically required. If the above medications 
are initiated or medication doses are changed, participants may continue to receive the study


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intervention, and should continue to attend all study visits and have all assessments. If due to 
medical necessity in the opinion of the investigator, the above medications are initiated or 
medication doses are changed, this does not represent a deviation from the study protocol, but may 
be considered a treatment failure.
Oral corticosteroid should not be initiated during the study.  
Concomitant corticosteroids must remain stable through Week 8.  Participants receiving 
corticosteroids at baseline must begin tapering corticosteroids at Week 8. When corticosteroid 
tapering is commenced, the daily dose of prednisone or the equivalent should be decreased by 
5 mg/week until the daily dose is 20 mg, and then by 2.5 mg/week until the daily dose is 0 mg.  
Participants receiving budesonide must begin tapering starting at Week 8. When budesonide 
tapering is commenced, the daily dose of budesonide should be decreased by 3 mg every 3 weeks 
until the daily dose is 0 mg.  For participants who experience a worsening of disease activity while 
tapering oral corticosteroid or budesonide, further dose decreases may be suspended and/or their 
dose increased if deemed necessary by the investigator. The oral corticosteroid or budesonide dose, 
however, may not be increased above the baseline dose unless due to medical necessity.  These 
participants will not be considered treatment failures unless their dose of oral corticosteroids or 
budesonide is increased above the baseline dose.   
6.5.3.
Prohibited Medications
Participants must not initiate any of the following prohibited medications:  

Immunomodulatory non-biologic agents other than 6-MP, AZA, or MTX (including but not 
limited to 6-TG, cyclosporine, tacrolimus, sirolimus, mycophenolate mofetil, tofacitinib, and 
other JAK inhibitors)  

Immunomodulatory biologic agents (including but not limited to TNFα antagonists, 
natalizumab, vedolizumab, and ustekinumab)

Experimental Crohn’s disease medications 
Because protection of human research participants is paramount, it is recognized that initiating 
such therapies may be required due to medical necessity. However, initiation of these prohibited 
medications should be documented as a deviation from the study protocol, and the participant will 
be discontinued from receiving further study intervention.
Participants must not enroll in any other clinical study with an investigational agent while in this 
study and must terminate study participation if they do. A participant who intends to enroll in any 
other clinical study with an investigational agent should undergo an early termination visit before 
he or she withdraws from study participation. 
The sponsor must be notified in advance (or as soon as possible thereafter) of any instances in 
which prohibited therapies are administered.


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6.6.
Dose Modification
Dose modification is not permitted in this intervention cohort.  
6.7.
Study Intervention After the End of the Study
Investigators may recontact the participant to obtain long-term follow-up information regarding 
the participant's safety or survival status as noted in the ICF (refer to Informed Consent in 
Appendix 5 of the Master protocol PLATFORMPACRD2001, Regulatory, Ethical, and Study 
Oversight Considerations).   
Participants will be instructed that study intervention will not be made available to them after they 
have completed/discontinued the study intervention and that they should return to their primary 
physician to determine standard of care.
7.
DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL
7.1.
Discontinuation of Study Intervention
Participants will not be automatically withdrawn from the study if they discontinue the study
intervention before the end of the dose regimen.
A participant's study intervention must be discontinued if:

The participant withdraws consent to receive study intervention.

The investigator believes that for safety reasons or tolerability reasons (eg, an AE) it is in the 
best interest of the participant to discontinue study intervention.

The participant becomes pregnant. Refer to Appendix 2 of this ISA, Contraceptive and Barrier 
Guidance and Collection of Pregnancy Information.

The participant is deemed ineligible according to the following TB screening criteria:

A diagnosis of active TB is made.

A participant has symptoms suggestive of active TB based on follow-up assessment 
questions and/or physical examination or has had recent close contact with a person with 
active TB, and cannot or will not continue to undergo additional evaluation. 

A participant undergoing evaluation has a chest radiograph with evidence of current 
active TB and/or a positive QuantiFERON®-TB test result and/or an indeterminate 
QuantiFERON®-TB test result on repeat testing (refer to Section 5.2 of this ISA); and/or 
a positive tuberculin skin test result in countries in which the QuantiFERON®-TB test is 
not approved/registered or the tuberculin skin test is mandated by local health authorities.

The participant develops an opportunistic infection, ie, an infection by an organism that 
usually causes disease only in a host whose resistance is lowered (eg, Pneumocystis jirovecii, 
coccidioidomycosis, Mycobacterium avium).


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
The participant develops a malignancy including squamous cell skin cancer. Consideration 
may be given to allow participants who develop ≤2 basal cell skin cancers that are adequately 
treated with no evidence of residual disease to continue to receive study agent.

The participant initiates any of the following protocol-prohibited medications at any time 
during the study:

Immunomodulatory agents other than AZA, 6-MP, or MTX (including, but not limited 
to, 6-TG, cyclosporine, mycophenolate mofetil, tacrolimus, and sirolimus).

Immunomodulatory biologic agents (including, but not limited to, TNF antagonists, 
abatacept, anakinra, rituximab, vedolizumab, natalizumab, ustekinumab).

Experimental Crohn’s disease medications (including, but not limited to, tofacitinib, 
etrolizumab, guselkumab, risankizumab, brazikumab, or other experimental anti-IL-23 
agents).

Thalidomide or related agents.

The participant has any Crohn’s disease-related surgeries that represent a lack of efficacy of 
study agent or will preclude the future ability to assess efficacy through the CDAI 

Other permitted Crohn’s disease-related surgeries (eg, to resolve long-standing 
complications such as strictures or for symptomatic nonhealing fistulas, in participants 
experiencing improvement on the study intervention) other than minor procedures (eg, 
placement of a seton or cutaneous drainage of an abscess) should be postponed until after 
the Week 12 visit, unless necessary to ensure the participant’s well-being and/or safety.

The participant develops severe hepatic function abnormalities, as described in Section 8.2.4
and Appendix 4, Liver Safety: Suggested Actions and Follow-up Assessments, both of this
ISA

Adverse events of National Cancer Institute Common Terminology Criteria for Adverse 
Events (NCI-CTCAE) grade ≥3 will be evaluated by the investigator and the study medical 
monitor to make a determination on discontinuation of the study intervention. Discontinuation 
of the study intervention should be considered in participants with worsening Crohn’s disease 
where continuation of the study drug is not in the best interest of the participant. 

Total (complete) or partial (supplemental) parenteral nutrition is initiated through an 
indwelling catheter at any time during the study.

A participant has symptoms of anaphylaxis, such as bronchospasm with wheezing and/or 
dyspnea that requires ventilatory support OR that results in symptomatic hypotension with a 
decrease in systolic blood pressure >40 mm Hg or blood pressure <90/60 mm Hg following 
study intervention administration. This may include events of NCI-CTCAE toxicity grade ≥3.    

A participant has a serious adverse allergic reaction that is possibly related to the study
intervention.

The participant (or the participant’s representative) withdraws consent for administration of 
the study intervention.
In the event of any serious infection, the intervention must be held and may not be resumed until 
the investigator has discussed the case with the study medical monitor.


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Study intervention assigned to the participant who discontinued study intervention may not be 
assigned to another participant. Additional participants will not be entered to ensure the protocol-
specified number of participants complete the study.    
Refer to Section 7.1 of the Master protocol PLATFORMPACRD2001 for additional
considerations for discontinuation of study intervention. 
7.2.
Participant Discontinuation/Withdrawal From the Study
Refer to Section 7.2 of the Master protocol PLATFORMPACRD2001 for participant 
discontinuation or withdrawal considerations. 
7.3.
Lost to Follow-up
Refer to Section 7.3 of the Master protocol PLATFORMPACRD2001 for follow-up 
considerations.  
8.
STUDY ASSESSMENTS AND PROCEDURES
Overview
Participants in the JNJ-67864238 intervention cohort will be assessed using the study evaluations 
described in Section 8 of the Master protocol PLATFORMPACRD2001.  Participants will also be 
assessed using the following JNJ-67864238-specific assessments and procedures. 
The Schedule of Activities (Table 1) summarizes the frequency and timing of efficacy, PK,
immunogenicity, PD, biomarker, pharmacogenomic, and safety measurements applicable to this 
intervention cohort.  
Contraception
Women of childbearing potential must have a negative serum β-hCG pregnancy test result at 
screening as described in the Schedule of Activities (Table 1). Participants must be reminded that 
they are required to use a highly effective method of contraception during the study and must 
continue using contraception as directed after receiving the last administration of the study 
intervention (Section 5.1 of this ISA). The method(s) of contraception used by each participant 
must be documented.  Additional serum or urine pregnancy tests may be performed, as determined 
necessary by the investigator or required by local regulation, to establish the absence of pregnancy 
at any time during the participation in the study. 
Blood Volume
For each participant, the maximum amount of blood drawn from each participant in this study will 
not exceed 500 mL.  
The total blood volume to be collected is considered to be an acceptable amount of blood to be 
collected over this time period from the population in this study based upon the World Health 
Organization’s Blood Donor Selection: Guidelines on Assessing Donor Suitability for Blood 
Donation, which state that whole blood donation should not exceed 13% of blood volume (ie, 


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350 mL ± 10% for a donor with a body weight of 45 kg and 450 mL ± 10% for a donor with a 
body weight of 50 kg).  The total blood volume collected in this study is below the amounts 
recommended for a single blood donation.14
Repeat or unscheduled samples may be taken for safety reasons or for technical issues with the 
samples.
8.1.
Efficacy Assessments
Refer to Section 8.1 of the Master protocol PLATFORMPACRD2001 for efficacy assessments.  
8.2.
Safety Assessments 
Refer to Section 8.2 of the Master protocol PLATFORMPACRD2001 for safety assessments.  
Participants in the JNJ-67864238 intervention cohort will also have the safety assessments in the 
following sections. The study will include the following evaluations of safety and tolerability 
according to the time points provided in the Schedule of Activities (Table 1).    
8.2.1.
Physical Examinations
Physical examination will be performed as indicated in the Schedule of Activities (Table 1).
Clinically significant findings should be reported as AEs.
8.2.2.
Vital Signs
Temperature, pulse/heart rate, blood pressure, respiratory rate, and body weight will be assessed.
8.2.3.
Electrocardiograms
During ECGs, participants should be in a quiet setting without distractions (eg, television, cell 
phones). Participants should rest in a supine position for at least 5 minutes before the ECG and 
should refrain from talking or moving arms or legs. If blood sampling or vital sign measurement 
is scheduled for the same time point as ECG recording, the procedures should be performed in the 
following order: ECG(s), vital signs, blood draw.
Electrocardiograms will be performed at screening, Week 12, and the final safety visit.
8.2.4.
Clinical Safety Laboratory Assessments
Clinical laboratory assessments will include hematology assessments, blood chemistry 
assessments, pregnancy testing, serology (HIV antibody; HBV surface antigen [HBsAg; 
Appendix 4 of the Master protocol PLATFORMPACRD2001, Hepatitis B Virus Screening]; and 
HCV antibody), and liver function tests (Appendix 4 of this ISA, Liver Safety: Suggested Actions 
and Follow-up Assessments) for additional information on monitoring and assessment of abnormal 
liver function tests.
Pregnancy testing (serum or urine) should be conducted as indicated in the Schedule of Activities 
(Table 1).


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Blood samples for serum chemistry and hematology will be collected as noted in Appendix 5 of
this ISA, Clinical Laboratory Tests. The investigator must review the laboratory results, document 
this review, and record any clinically relevant changes occurring during the study in the Adverse 
Event section of the CRF. The laboratory reports must be filed with the source documents.
8.2.5.
Signs of Infection
The study intervention should not be administered to a participant with a clinically important, 
active infection. Investigators are required to evaluate participants for any signs or symptoms of 
infection, and also review participant’s diary entries for signs of infection, at scheduled visits in 
the Schedule of Activities (Table 1). If a participant develops a serious infection, including but not 
limited to sepsis or pneumonia, discontinuation of the study intervention (ie, no further study 
intervention administrations) must be considered.
8.3.
Adverse Events and Serious Adverse Events
Refer to Section 8.3 of the Master protocol PLATFORMPACRD2001 for considerations for 
collecting AEs and SAEs.  
8.3.1.
Time Period and Frequency for Collecting Adverse Event and Serious 
Adverse Event Information
All Adverse Events
All AEs and special reporting situations (Appendix 6
of the Master protocol 
PLATFORMPACRD2001, Adverse Events: Definitions and Procedures for Recording, 
Evaluating, Follow-up, and Reporting), whether serious or nonserious, will be reported from the 
time a signed and dated ICF is obtained until completion of the participant's last study-related 
procedure, which may include contact for follow-up of safety. Serious adverse events, including 
those spontaneously reported to the investigator within 30 days after the last dose of study
intervention, must be reported using the Serious Adverse Event Form. The sponsor will evaluate 
any safety information that is spontaneously reported by an investigator beyond the time frame 
specified in the protocol.  
Beyond the protocol-specified follow-up period, the investigator should report any AEs they 
consider associated with the use of the study intervention (ie, possibly, probably, or very likely 
related to the study intervention according to the Attribution Definitions in Appendix 6 of the 
Master protocol PLATFORMPACRD2001, Adverse Events: Definitions and Procedures for 
Recording, Evaluating, Follow-up, and Reporting) to Janssen Global Medical Safety.  
Serious Adverse Events
All SAEs occurring during the study must be reported to the appropriate sponsor contact person 
by study-site personnel within 24 hours of their knowledge of the event. 
Information regarding SAEs will be transmitted to the sponsor using the Serious Adverse Event 
Form and Safety Report Form of the CRF, which must be completed and reviewed by a physician 


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from the study site and transmitted to the sponsor within 24 hours. The initial and follow-up reports 
of an SAE should be transmitted electronically or by facsimile (fax).
8.3.2.
Follow-up of Adverse Events and Serious Adverse Events
Adverse events, including pregnancy, will be followed by the investigator as specified in 
Appendix 6 of the Master protocol PLATFORMPACRD2001, Adverse Events: Definitions and 
Procedures for Recording, Evaluating, Follow-up, and Reporting.
8.3.3.
Regulatory Reporting Requirements for Serious Adverse Events
The sponsor assumes responsibility for appropriate reporting of AEs to the regulatory authorities. 
The sponsor will also report to the investigator (and the head of the investigational institute where 
required) all suspected unexpected serious adverse reactions (SUSARs). The investigator (or 
sponsor where required) must report SUSARs to the appropriate Independent Ethics 
Committee/Institutional Review Board (IEC/IRB) that approved the protocol unless otherwise 
required and documented by the IEC/IRB. A SUSAR will be reported to regulatory authorities 
unblinded. Participating investigators and IEC/IRB will receive a blinded SUSAR summary, 
unless otherwise specified. 
An anticipated event is an AE that commonly occurs in the study population independent of 
exposure to the drug under investigation.  For the purposes of this study the following SAEs will 
be considered anticipated events: 

Adverse events related to symptoms of Crohn’s disease 

Adverse events related to worsening or progression of Crohn’s disease
These anticipated events will be periodically analyzed in aggregate by the sponsor during study 
conduct.  The sponsor will prepare a safety report in narrative format if the aggregate analysis 
indicates that the anticipated event occurs more frequently in the treatment group than in the 
control group and the sponsor concludes there is a reasonable possibility that the drug under 
investigation caused the anticipated event.
The plan for monitoring and analyzing the anticipated events is specified in a separate Anticipated 
Events Safety Monitoring Plan.  The assessment of causality will be made by the sponsor’s 
unblinded safety assessment committee.
The sponsor assumes responsibility for appropriate reporting of the listed anticipated events 
according to the requirements of the countries in which the studies are conducted. 
8.3.4.
Pregnancy
All initial reports of pregnancy in female participants or partners of male participants must be 
reported to the sponsor by the study-site personnel within 24 hours of their knowledge of the event 
using the appropriate pregnancy notification form. Abnormal pregnancy outcomes (eg, 
spontaneous abortion, fetal death, stillbirth, congenital anomalies, ectopic pregnancy) are 


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considered SAEs and must be reported using the Serious Adverse Event Form. Any participant 
who becomes pregnant during the study must discontinue further study intervention. 
Because the effect of the study drug on sperm is unknown, pregnancies in partners of male 
participants included in the study will be reported as noted above.
Follow-up information regarding the outcome of the pregnancy and any postnatal sequelae in the 
infant will be required.
8.3.5.
Concomitant Medication Review
Concomitant medications will be reviewed as indicated in the Schedule of Activities (Table 1).
8.3.6.
Disease-Related Events and Disease-Related Outcomes Not 
Qualifying as Adverse Events or Serious Adverse Events
All events that meet the definition of an SAE will be reported as SAEs, regardless of whether they 
are protocol-specific assessments.
The cause of death of a participant in a study, whether or not the event is expected or associated 
with the study treatment, is considered an SAE.
8.3.7.
Adverse Events of Special Interest 
Any newly identified malignancy or case of active TB occurring after the first study intervention 
administration(s) in participants participating in this clinical study are considered AEs of special 
interest and must be reported by the investigator in an expedited manner according to the 
procedures in Appendix 6 of the Master protocol PLATFORMPACRD2001, Adverse Events: 
Definitions and Procedures for Recording, Evaluating, Follow-up, and Reporting. Investigators 
are also advised that active TB is considered a reportable disease in most countries. These events 
are to be considered serious only if they meet the definition of an SAE.
A possible Hy’s law case is defined by the occurrence of ALT/AST ≥3 x the upper limit of 
normal (ULN), alkaline phosphatase <2 x ULN together with Tbili ≥2 x ULN or international 
normalized ratio >1.5 (if measured). Any possible Hy’s Law case is considered an important 
medical event and should be reported to the sponsor in an expedited manner using the adverse 
events of special interest form, even before all other possible causes of liver injury have been 
excluded (FDA 2009).
A confirmed Hy’s law case must be reported as a SAE.
8.4.
Treatment of Overdose
For this study, any dose of JNJ-67864238 greater than the assigned treatment within a 24-hour 
time period ±8 hours will be considered an overdose.


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In the event of an overdose, the investigator or treating physician should:

Contact the medical monitor immediately. 

Document the quantity of the excess dose as well as the duration of the overdosing in the CRF.
Decisions regarding dose interruptions or modifications will be made by the investigator in 
consultation with the medical monitor based on the clinical evaluation of the participant.  
Note that overdose is a special reporting situation (Appendix 6 of the Master protocol 
PLATFORMPACRD2001, Adverse Events: Definitions and Procedures for Recording, 
Evaluating, Follow-Up, and Reporting).
8.5.
Pharmacokinetics
Pharmacokinetic assessments will be used to understand the disposition of JNJ-67864238 in 
participants with moderately to severely active Crohn’s disease.  Plasma and fecal samples will be 
used to evaluate the systemic and local colon exposure, respectively, of JNJ-67864238. Plasma
collected for PK may additionally be used to evaluate safety or efficacy aspects that address 
concerns arising during or after the study period. Genetic analyses will not be performed on these
plasma samples. In addition, biopsy samples will also be used for the measurement of 
JNJ-67864238 tissue concentration.
Participant confidentiality will be maintained.  
8.5.1.
Evaluations
Venous blood samples and fecal samples will be collected for the determination of plasma and 
fecal concentrations of JNJ-67864238 according to the Schedule of Activities (Table 1).
Blood samples for the measurement of JNJ-67864238 plasma concentrations will be collected 
from all randomized participants as follows: 

Before study intervention administration at Week 0, Week 2, Week 4, Week 8, and Week 12 

After study intervention administration at Week 12 within 2 to 4 hours 

The early termination visit (if applicable)  
The exact dates and times of PK blood sampling must be recorded on the laboratory requisition 
form. Additional information about the collection, handling, and shipment of biological samples 
can be found in the applicable Laboratory Manual.
Stool samples for the measurement of JNJ-67864238 concentrations will be collected from all 
randomized participants as follows: 

At Week 2, Week 4, Week 8, and Week 12 

The early termination visit (if applicable)  


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Biopsy samples collected during video ileocolonoscopy will be used for the measurement of 
JNJ-67864238 tissue concentration.
8.5.2.
Analytical Procedures 
Plasma, fecal, and biopsy tissue samples will be analyzed to determine concentrations of 
JNJ-67864238 
using 
validated, 
specific, 
and 
sensitive 
liquid 
chromatography-mass 
spectrometry/mass spectrometry methods by or under the supervision of the sponsor.
If required, some plasma samples may be analyzed to document the presence of circulating 
metabolites using a qualified research method. In addition, plasma PK samples may be stored for 
future analysis of other co-administered treatments and protein binding and the metabolite profile.  
8.5.3.
Pharmacokinetic Parameters and Evaluations
Parameters
Sparse samples will be collected for the determination of plasma concentrations of JNJ-67864238. 
Since a population PK model is not available for JNJ-67864238, PK parameters cannot be 
estimated.
Pharmacokinetic/Pharmacodynamic Evaluations
The relationship between plasma, fecal, and biopsy tissue concentrations of JNJ-67864238 and PD 
and/or clinical endpoints may be examined if appropriate.  
8.6.
Pharmacodynamics
Pharmacodynamic assessments will be made to examine the biological response to treatment and
to identify genes and proteins that are relevant to JNJ-67864238 treatment and/or Crohn’s disease.  
The results will be used to inform Phase 3 study design.  
8.7.
Genetics
A pharmacogenomic blood sample will be collected from participants who consent separately to 
this component of the study to allow for pharmacogenomic research, as necessary, where local 
regulations permit. 
Whole genome analyses will be performed to detect associations between specific gene 
polymorphisms to the disease or JNJ-67864238 response. DNA research will be performed only 
on samples from participants consenting to DNA analysis and will be restricted to JNJ-67864238-
related effects or to the diseases for which JNJ-67864238 is being developed.
A participant may withdraw such consent at any time without affecting their participation in other 
aspects of the study, or their future participation in the study.  
8.8.
Biomarkers
Serum, fecal, and whole blood samples will be collected from all participants to study the effect 
of JNJ-67864238 on proteins (serum and fecal samples) and RNA expression (whole blood and 


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biopsy samples).  Protein and RNA expression data will be used to assess and predict effects on 
clinical disease activity and will support study interpretation and disease understanding.  
Computational analysis will be performed on a subset of analytes shown by the sponsor to relate 
to disease activity in IBD to compare effects of JNJ-67864238 to placebo.
Stool and saliva samples will also be collected to evaluate the effects of JNJ-67864238 on the 
microbiome.  
Results will be presented in a separate technical report.  
Serum-based Biomarkers
Blood samples for serum-based biomarker analyses will be collected from all participants. Assays 
to be performed may include the following: 
 
 
 
Whole Blood-based Biomarkers
Whole blood samples will be collected from all participants to study the effect of JNJ-67864238 
on RNA expression. Whole blood analyses may also examine RNA expression associated with the 
pathogenesis of Crohn’s disease.  
Biopsy-based Biomarkers
Biopsy samples will be collected during video ileocolonoscopy to study the effect of 
JNJ-67864238 on gene and protein expression and for the histologic assessment of disease and 
healing. Biopsy analyses may also examine gene and protein expression associated with the 
pathogenesis of Crohn’s disease.
Stool-based Biomarkers
Stool samples will be collected according to the Schedule of Activity (Table 1).  Gut biomarkers
(ie, the microbiome and other fecal-based protein markers) will be investigated in relation to 
JNJ-67864238 and/or pathogenesis of Crohn’s disease.
Oral Biomarkers
Oral microbiome samples will be collected from saliva and analyzed from all participants to further 
the understanding of Crohn’s disease and the potential connection between Crohn’s disease 
activity and changes in oral microbiome.3,8,1
8.8.1.
RNA Transcriptome Research 
Transcriptome studies may be conducted using, but not limited to, microarray, and/or alternative 
technologies, which facilitates the simultaneous measurement of the relative abundances of RNA 
species resulting in a transcriptome profile. This will enable the evaluation of changes in 
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transcriptome profiles that may correlate with biological response relating to IBD and medically 
related conditions or the action of JNJ-67864238.  
The same samples may also be used to confirm findings by application of alternative technologies.
8.8.2.
Proteome Research  
Plasma, serum, stool, or biopsy proteome studies may be performed. Proprietary algorithms and 
standard statistical techniques, such as analysis of variance (ANOVA) and analysis of covariance 
(ANCOVA), may be used to identify individual proteins exhibiting statistically significantly 
different changes in their levels between samples and/or between groups of samples. This may 
enable the evaluation of changes in proteome profiles that may correlate with biological response 
relating to IBD and medically related conditions or the action of JNJ-67864238.  
The samples may also be used to confirm findings by application of alternative technologies.
8.8.3.
Metabolomic Research 
Plasma, serum, stool, or biopsy metabolome studies may be performed by, but not limited to, 
nuclear magnetic resonance, mass spectrometry, liquid chromatography – mass spectrometry, gas 
chromatography – mass spectrometry, and/or Fourier transform mass spectrometry, or other 
methods. This may include analysis of identified or uncharacterized metabolites and lipids that are 
known to be or emerge in the future as important in the pathogenesis of IBD or a related medical 
condition, or the participant’s response to JNJ-67864238, or AE.  
8.9.
Immunogenicity Assessments 
Immunogenicity will not be assessed in the JNJ-67864238 intervention cohort.  Samples collected
per the consolidated Schedule of Activities (Table 1) for immunogenicity would only be analyzed 
if required to assess other data or analyses, such as PK or AEs.   
8.10.
Medical Resource Utilization and Health Economics
Medical Resource Utilization and Health Economics parameters are not evaluated in this study.  
8.11.
Tuberculosis Assessments 
Screening Assessments
Participants must undergo testing for TB (see Section 5.2 and Appendix 3, Tuberculin Skin 
Testing, both of this ISA) and their medical history assessment must include specific questions 
about a history of TB or known occupational or other personal exposure to individuals with active 
TB.  The participant should be asked about past testing for TB, including chest radiograph results 
and responses to tuberculin skin or other TB testing.  Investigators have the option to use both the 
QuantiFERON®-TB test and the tuberculin skin test to screen for latent TB if they believe, based 
on their judgment, that the use of both tests is clinically indicated in order to evaluate a participant 
who has high risk of having latent TB.  If either the QuantiFERON®-TB test or the tuberculin skin 
test is positive, the participant is considered to have latent TB infection for the purposes of 
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Participants with a negative QuantiFERON®-TB test result (and a negative tuberculin skin test 
result in countries in which the QuantiFERON®-TB test is not approved/registered or the 
tuberculin skin test is mandated by local health authorities) are eligible to continue with 
prerandomization procedures.  Participants with a newly identified positive QuantiFERON®-TB 
(or tuberculin skin) test result must be excluded from the study. 
Treatment Phase
Early Detection of Active Tuberculosis 
To aid in the early detection of TB reactivation or new TB infection during study participation, 
participants must be evaluated for signs and symptoms of active TB at scheduled visits (refer to 
the Schedule of Activities [Table 1]) or by telephone contact approximately every 8 to 12 weeks.  
The following series of questions is suggested for use during the evaluation: 

“Have you had a new cough of > 14 days’ duration or a change in a chronic cough?”

“Have you had any of the following symptoms:
– Persistent fever?
– Unintentional weight loss?
– Night sweats?”

“Have you had close contact with an individual with active TB?”  (If there is uncertainty as 
to whether a contact should be considered “close,” a physician specializing in TB should be 
consulted.)
If the evaluation raises suspicion that a participant may have TB reactivation or new TB infection, 
an immediate and thorough investigation should be undertaken, including, where possible, 
consultation with a physician specializing in TB. 
Investigators should be aware that TB reactivation in immunocompromised participants may 
present as disseminated disease or with extrapulmonary features.  Participants with evidence of 
active TB should be referred for appropriate treatment.
Participants who experience close contact with an individual with active TB during the conduct of 
the study must have a repeat chest radiograph, a repeat QuantiFERON® TB test, a repeat 
tuberculin skin test in countries in which the QuantiFERON®-TB test is not approved/registered 
or the tuberculin skin test is mandated by local health authorities, and, if possible, referral to a 
physician specializing in TB to determine the participant’s risk of developing active TB and 
whether treatment for latent TB is warranted.  If the QuantiFERON® TB test result is 
indeterminate, the test should be repeated as outlined in the manufacturer’s instructions.  
Participants should be encouraged to return for all subsequent scheduled study visits according to 
the protocol.


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9.
STATISTICAL CONSIDERATIONS
Statistical analyses for the JNJ-67864238 intervention cohort will be performed using the 
statistical methods described in Section 9 of the Master protocol PLATFORMPACRD2001.  In 
addition, JNJ-67864238-specific statistical considerations are described below.   
Statistical analysis will be done by the sponsor or under the authority of the sponsor. A general 
description of the statistical methods to be used to analyze the efficacy and safety data is outlined 
below. Specific details will be provided in the Statistical Analysis Plan (SAP).
9.1.
Statistical Hypotheses
The statistical hypothesis is that JNJ-67864238 is superior to placebo as measured by the reduction 
from baseline in the CDAI at Week 12 in participants with moderately to severely active Crohn’s 
disease.
9.2.
Sample Size Determination
Sample size is determined to achieve desirable operating characteristics of the decision-making 
framework for JNJ-67864238 through simulated CDAI and SES-CD data. More details on data 
simulation are provided in Appendix 6 of this ISA, Data Simulation.
9.2.1.
Decision-Making Framework
There are a minimum of 2 decision points planned for this ISA protocol:
1.
At the IA: The IA will take place when approximately 45 participants have completed 
their Week 12 assessments or have withdrawn from the study before Week 12.  If the 
futility criteria are met, the decision to terminate enrollment will be made based on a 
benefit-risk assessment of the totality of data, including overall efficacy assessments, 
analysis of biomarker and PD data, and a safety review by the external DMC. If the futility 
criteria are not met and the DMC has not raised any safety issue, enrollment will continue 
until the planned sample size is reached.  To augment decision-making, all available data 
at this IA, including from those participants without Week 12 assessments, will be 
analyzed.  An Interim Analysis Committee will review the unblinded interim data and 
formulate
recommendations 
(Section 
9.5.1 
of 
the 
Master 
protocol 
PLATFORMPACRD2001).  
2.
At the completion of this intervention cohort:  The overall study success or futility is 
defined in the Master protocol. 
Additional ad hoc IA(s) may be conducted if deemed necessary; any ad hoc IA(s) will be part of 
the decision-making framework and will follow the same decision-making rules as those of the 
planned IA.
This decision-making framework is suggestive but not binding. The final decision will be made 
based on the totality of data. 


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9.2.2.
Decision-Making Specifics
9.2.2.1.
Decision-Making Specifics at the Interim Analysis  
If neither change in CDAI nor change in SES-CD of the JNJ-67864238 
treatment arm meets the success criteria, the futility of the JNJ-67864238 
 
treatment arm will be considered.   The futility is defined as follows:

Futility in change in CDAI: if upper bound (UB) (95%) <60 and lower bound (LB) (10%) 
<40, ie, the 95% upper confidence bound of the true mean treatment difference at Week 12 is 
less than 60 and its 90% lower confidence bound less than 40; and 

Futility in change in SES-CD: if UB (95%) <1.6 and LB (10%) <0.4, ie, the 95% upper 
confidence bound of the true median treatment difference at Week 12 is less than 1.6 and its 
90% lower confidence bound less than 0.4. 
The thresholds chosen for futility at the IA correspond to an active study intervention profile with 
limited benefit.  
9.2.2.2.
Decision-Making Specifics at the Completion of the Intervention 
Cohort
The success of the JNJ-67864238 
treatment arm is defined as follows:

Success in change in CDAI: if LB (20%) ≥40, ie, the 80% lower confidence bound of the true 
mean treatment difference at Week 12 is at least 40; or

Success in change in SES-CD: if LB (20%) ≥0.4, ie, the 80% lower confidence bound of the 
true median treatment difference at Week 12 is at least 0.4. 
The threshold of 40 is selected to provide confidence that a therapy is at least as effective as 
currently approved therapies (STELARA® [ustekinumab] or adalimumab), where a CDAI change 
of 40 represents the lower confidence bound for success of the treatment difference between JNJ-
67864238 and placebo.
If neither change in CDAI nor change in SES-CD of the JNJ-67864238 
 
treatment arm meets the success criteria, the futility of the JNJ-67864238 
 
treatment arm will be considered.  The futility of is defined as follows:

Futility in change in CDAI: if UB (80%) <60 and LB (20%) <40, ie, the 80% upper confidence 
bound of the true mean treatment difference at Week 12 is less than 60 and its 80% lower 
confidence bound less than 40; and 

Futility in change in SES-CD: if UB (90%) <1.6 and LB (20%) <0.4, ie, the 90% upper 
confidence bound of the true median treatment difference at Week 12 is less than 1.6 and its 
80% lower confidence bound less than 0.4. 
In addition, a decision-making framework based solely on CDAI scores will also be assessed by 
combining a benefit-risk assessment of the totality of the data, including analyses of biomarker 
and PD data. For the case of futility criteria based solely on CDAI scores, the UB of 80% based 
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on a change in the CDAI for the final analysis will be updated to 95% (ie, UB 95% <60) and the 
LB will remain the same (ie, LB 20% <40). Details will be provided in the SAP.  
9.2.3.
Sample Size
9.2.3.1.
Operating Characteristics of the Intervention Cohort
The decision-making framework outlined in Section 9.2.2 of this ISA is applied to a total of 5000 
virtual studies with simulated CDAI and change in SES-CD data. With 90 participants 
(54 participants receiving JNJ-67864238 
and 36 participants receiving
placebo), under the alternative hypothesis (Appendix 6 of this ISA, Data Simulation), the 
probability of JNJ-67864238 meeting the success criteria is approximately 87%, and the 
probability of dropping JNJ-67864238 for futility is approximately 1%. When there is no treatment 
difference, the probability of JNJ-67864238 meeting the success criteria is approximately 5% and 
the probability of dropping JNJ-67864238 for futility is approximately 77%. There is 
approximately a 32% chance that the futility criteria are met at the IA when there is no treatment 
difference.
9.2.3.2.
Power for Detecting Treatment Difference in Change in the CDAI 
For reference, without factoring in the interim futility analysis, the sample size of 90 participants 
(54 participants in the JNJ-67864238 
 treatment arm and 36 participants in the 
placebo treatment arm) will provide 90% power to detect a treatment difference at α=0.1 (2-sided) 
when the true treatment difference is 60 (placebo – JNJ-67864238) in the change in CDAI at Week 
12 for both Bio-IR and Bio-NF populations.  The detailed assumptions of the CDAI scores are 
outlined in Appendix 6 of this ISA, Data Simulation. This evaluation is based on an analysis of 
covariance model with change in the CDAI score at Week 12 as the response variable and baseline 
CDAI score as a covariate, with population (Bio-IR and Bio-NF), treatment, and their interaction 
as fixed factors in the model.   
9.3.
Populations for Analyses
Refer to Section 9.3 of the Master protocol PLATFORMPACRD2001 for populations for analyses.   
9.4.
Statistical Analyses
9.4.1.
General Considerations
Refer to Section 9.4.1 of the Master protocol PLATFORMPACRD2001 for general 
considerations.   
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9.4.1.1.
Multiplicity Control  
An overall type I error rate of 0.1 (2-sided) will be used. 
The hypothesis testing will be conducted in a hierarchical manner with the test on the primary 
endpoint conducted first and the tests on major secondary endpoints conducted next.  Within the 
major secondary endpoints, the gatekeeping approach in conjunction with graphical multiplicity 
control procedures will be applied. More details will be provided in the ISA SAP.  
As the IA will not lead to an early ISA completion due to success, multiplicity adjustment is not 
required.
Nominal p-values will be calculated for all treatment comparisons. 
9.4.2.
Primary Endpoint
Refer to Section 9.4.2 of the Master protocol PLATFORMPACRD2001 for the primary endpoint.  
9.4.3.
Secondary Endpoints 
Refer to Section 9.4.3 of the Master protocol PLATFORMPACRD2001 for the secondary 
endpoints. 
9.4.4.
Safety Analyses
Refer to Section 9.4.4 of the Master protocol PLATFORMPACRD2001 for safety analyses.   
9.4.5.
Other Analyses
Refer to Section 9.4.5 of the Master protocol PLATFORMPACRD2001 for additional information 
for other analyses.   
Pharmacokinetic Analyses 
Data will be listed for all participants with available plasma, fecal, and biopsy tissue concentrations 
per treatment arm. Participants will be excluded from the descriptive statistics if their data do not 
allow for accurate assessment of the concentration data (eg, incomplete administration of the study 
intervention; missing information of dosing and sampling times).
All concentrations below the lowest quantifiable concentration or missing data will be labeled as 
such in the concentration database. All participants and samples excluded from the analysis will 
be clearly documented in the study report.
For each treatment arm, descriptive statistics, including arithmetic mean, standard deviation, 
coefficient of variation, median, minimum, and maximum will be calculated.
Biomarkers Analyses 
Refer to Section 9.4.5 of the Master protocol PLATFORMPACRD2001 for biomarker analyses.   


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Immunogenicity Analyses 
The incidence of anti-JNJ-67864238 antibodies will be summarized for all participants who 
receive at least 1 dose of JNJ-67864238 and have appropriate samples for detection of antibodies 
to JNJ-67864238 (ie, participants with at least 1 sample obtained after their first dose of
JNJ-67864238). Antibodies may be summarized as induced or pre-existing if a predose sample at 
Week 0 is obtained.  
A listing of participants who are positive for antibodies to JNJ-67864238 will be provided. The 
maximum titers of antibodies to JNJ-67864238 will be summarized for participants who are 
positive for antibodies to JNJ-67864238.
Systemic JNJ-67864238 concentrations and clinical efficacy/safety endpoints may be summarized 
by antibody to JNJ-67864238 status if sufficient numbers of participants are positive for 
antibodies.   Other immunogenicity analyses may be performed to further characterize the immune 
responses that are generated.
Pharmacodynamic and Disease-specific Analyses
Planned biomarker analyses may be deferred if emerging study data show no likelihood of 
providing useful scientific information. Any PD samples received by the contract vendor or 
sponsor after the cutoff date will not be analyzed, and therefore, excluded from the PD analysis.
Changes in serum/RNA or other biomarkers over time will be summarized by treatment arm. 
Associations between baseline levels and changes from baseline in select markers and clinical 
response will be explored. RNA analyses will be summarized in separate technical reports.  
Pharmacokinetic/Pharmacodynamic Analyses
Refer to Section 9.4.5 of the Master protocol PLATFORMPACRD2001 for PK/PD analyses.   
Pharmacogenomic Analyses 
Complete genomic testing will be done to search for links of specific genes to disease or response 
to drug. Only DNA research related to JNJ-67864238 or to the diseases for which this drug is being 
developed will be performed.
Genome-wide pharmacogenomic testing will be undertaken in participants who have signed a 
separate informed consent to participate in this portion of the study. Further, a participant may 
withdraw such consent at any time without affecting their participation in other aspects of the 
study, or their future participation in the study.
Results will be presented in a separate report.
DNA samples will be analyzed for links to specific genes to disease or the response to 
JNJ-67864238. Additional analyses may be conducted if it is hypothesized that this may help 
resolve issues with the clinical data. 


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DNA samples will be used for research related to links to specific genes to disease or the response 
to JNJ-67864238.  They may also be used to develop tests/assays related to JNJ-67864238 and 
Crohn’s disease. Pharmacogenomic research may consist of the analysis of one or more candidate 
genes or analysis of the entire genome (as appropriate) in relation to JNJ-67864238 or Crohn’s 
disease clinical endpoints.
9.5.
Interim Analysis
One IA is planned. It will take place when approximately 45 participants have completed their 
Week 12 assessments or have withdrawn early from the intervention cohort. Additional ad hoc 
IA(s) may be conducted if deemed necessary.   The objective of the IA(s) is to enable early 
termination of the intervention cohort if JNJ-67864238 (
) is futile and plan for 
future intervention cohorts. At the time of the IA(s), the study team will remain blinded. The 
planned IA (and any additional IA[s]) will be described in the IA SAP.
9.6.
Data Monitoring Committee or Other Review Board
Refer to Section 9.6 of the Master protocol PLATFORMPACRD2001 for information regarding 
the DMC.       
CCI


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10.
SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS
10.1.  Appendix 1: Abbreviations 
6-MP 
6-mercaptopurine
AE
adverse event
AUC
area under the curve
AZA
azathioprine 
Bio-IR
biologic intolerant or refractory
Bio-NF
biologic nonfailures, ie, inadequate response to or failed to tolerate corticosteroids or 
immunomodulators, but not a biologic
CDAI
Crohn’s Disease Activity Index
CRF
case report form 
CRP
C-reactive protein
DMC
Data Monitoring Committee 
DNA 
deoxyribonucleic acid
ECG
electrocardiogram 
FIH
first-in-human
HBV
hepatitis B virus 
HCV
hepatitis C virus 
hERG
human ether-à-go-go-related gene 
HIV
human immunodeficiency virus 
IA
interim analysis
IB
Investigator’s Brochure
ICF
informed consent form
IEC
Independent Ethics Committee
IL
interleukin
IRB
Institutional Review Board 
ISA
Intervention Specific Appendix
IV
intravenous
IWRS
interactive web response system
LB
lower bound
MTX
methotrexate
NCI-CTCAE
National Cancer Institute Common Terminology Criteria for Adverse Events 
NRS
numeric rating scale
PD
pharmacodynamic
PGIC
Patient’s Global Impression of Change
PGIS
Patient’s Global Impression of Severity
P-gp
P-glycoprotein
PK
pharmacokinetic(s)
PRO
patient-reported outcome
PROMIS
Patient-Reported Outcomes Measurement Information System
RNA 
ribonucleic acid
SAE
serious adverse event
SAP
Statistical Analysis Plan
SC
subcutaneous 
SES-CD
Simplified Endoscopic Score for Crohn’s Disease
TB
tuberculosis 
TNBS
trinitrobenzene sulfonic acid
TNF
tumor necrosis factor 
UB
upper bound 
ULN
upper limit of normal


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10.2.  Appendix 2: Contraceptive and Barrier Guidance and Collection of 
Pregnancy Information
Participants must follow contraceptive measures as outlined in Section 5.1 of this ISA, Inclusion 
Criteria. Pregnancy information will be collected and reported as noted in Section 8.3.4 of this ISA
Pregnancy, and Appendix 6 of the Master protocol PLATFORMPACRD2001, Adverse Events: 
Definitions and Procedures for Recording, Evaluating, Follow-up, and Reporting.  
Definitions
Woman of Childbearing Potential (WOCBP)
A woman is considered fertile following menarche and until becoming postmenopausal unless 
permanently sterile (see below).
Woman Not of Childbearing Potential

premenarchal
A premenarchal state is one in which menarche has not yet occurred.

postmenopausal
A postmenopausal state is defined as no menses for 12 months without an alternative medical 
cause. A high follicle stimulating hormone (FSH) level (>40 IU/L or mIU/mL) in the 
postmenopausal range may be used to confirm a postmenopausal state in women not using 
hormonal contraception or hormonal replacement therapy (HRT), however in the absence of 
12 months of amenorrhea, a single FSH measurement is insufficient.

permanently sterile (for the purpose of this study)
Permanent sterilization methods include hysterectomy, bilateral salpingectomy, and bilateral 
oophorectomy.
Note: If the childbearing potential changes after start of the study (eg, a premenarchal woman 
experiences menarche) or the risk of pregnancy changes (eg, a woman who is not heterosexually 
active becomes active), a woman must begin a highly effective method of contraception, as 
described throughout the inclusion criteria.
Contraceptive (birth control) use by men or women should be consistent with local regulations 
regarding the acceptable methods of contraception for those participating in clinical studies.
Typical use failure rates may differ from those when used consistently and correctly. Use should 
be consistent with local regulations regarding the use of contraceptive methods for participants in 
clinical studies.
Examples of Contraceptives
EXAMPLES OF CONTRACEPTIVESa ALLOWED DURING THE STUDY INCLUDE:
USER INDEPENDENT 
Highly Effective Methods That Are User Independent Failure rate of <1% per year when used 
consistently and correctly.

Implantable progestogen-only hormone contraception associated with inhibition of ovulationb

Intrauterine device (IUD)


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
Intrauterine hormone-releasing system (IUS)

Bilateral tubal occlusion

Vasectomized partner
(Vasectomized partner is a highly effective contraceptive method provided that the partner is the 
sole sexual partner of the woman of childbearing potential and the absence of sperm has been 
confirmed. If not, additional highly effective method of contraception should be used. 
Spermatogenesis cycle is approximately 74 days.)
USER DEPENDENT
Highly Effective Methods That Are User Dependent Failure rate of <1% per year when used 
consistently and correctly.

Combined (estrogen- and progestogen-containing) hormonal contraception associated with 
inhibition of ovulationb
oral
intravaginal
transdermal
injectable

Progestogen-only hormone contraception associated with inhibition of ovulationb
oral
injectable

Sexual abstinence
(Sexual abstinence is considered a highly effective method only if defined as refraining from 
heterosexual intercourse during the entire period of risk associated with the study intervention. 
The reliability of sexual abstinence needs to be evaluated in relation to the duration of the study 
and the preferred and usual lifestyle of the participant.)
NOT ALLOWED AS SOLE METHOD OF CONTRACEPTION DURING THE STUDY (not 
considered to be highly effective - failure rate of ≥1% per year)

Progestogen-only oral hormonal contraception where inhibition of ovulation is not the primary 
mode of action.

Male or female condom with or without spermicidec

Cap, diaphragm, or sponge with spermicide

A combination of male condom with either cap, diaphragm, or sponge with spermicide (double-
barrier methods)c

Periodic abstinence (calendar, symptothermal, post-ovulation methods)

Withdrawal (coitus-interruptus)

Spermicides alone

Lactational amenorrhea method (LAM)
a) Typical use failure rates may differ from those when used consistently and correctly. Use should be 
consistent with local regulations regarding the use of contraceptive methods for participants in 
clinical studies.
b) Hormonal contraception may be susceptible to interaction with the study intervention, which may 
reduce the efficacy of the contraceptive method. In addition, consider if the hormonal contraception 
may interact with the study intervention.
c) Male condom and female condom should not be used together (due to risk of failure with friction).


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Pregnancy During the Study
All initial reports of pregnancy in female participants or partners of male participants must be 
reported to the sponsor by the study-site personnel within 24 hours of their knowledge of the event 
using the appropriate pregnancy notification form. Abnormal pregnancy outcomes (eg, 
spontaneous abortion, fetal death, stillbirth, congenital anomalies, ectopic pregnancy) are 
considered serious adverse events and must be reported using the Serious Adverse Event Form. 
Any participant who becomes pregnant during the study must discontinue further study 
intervention. 
Follow-up information regarding the outcome of the pregnancy and any postnatal sequelae in the 
infant will be required.


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10.3.   Appendix 3: Tuberculin Skin Testing
Administering the Mantoux Tuberculin Skin Test
The Mantoux tuberculin skin test (CDC, 2000) is the standard method of identifying persons infected with 
Mycobacterium tuberculosis.  Multiple puncture tests (Tine and Heaf) should not be used to determine whether a 
person is infected because the amount of tuberculin injected intradermally cannot be precisely controlled.  Tuberculin 
skin testing is both safe and reliable throughout the course of pregnancy.  The Mantoux tuberculin test is performed
by placing an intradermal injection of 0.1 mL of tuberculin into the inner surface of the forearm.  The test must be 
performed with tuberculin that has at least the same strength as either 5 tuberculin units (TU) of standard purified 
protein derivative (PPD)-S or 2 TU of PPD-RT 23, Statens Serum Institut, as recommended by the World Health 
Organization.  PPD strengths of 1 TU or 250 TU are not acceptable (Menzies, 2000).  Using a disposable tuberculin 
syringe with the needle bevel facing upward, the injection should be made just beneath the surface of the skin.  This 
should produce a discrete, pale elevation of the skin (a wheal) 6 mm to 10 mm in diameter.  To prevent needle-stick 
injuries, needles should not be recapped, purposely bent or broken, removed from disposable syringes, or otherwise 
manipulated by hand.  After they are used, disposable needles and syringes should be placed in puncture-resistant 
containers for disposal.  Institutional guidelines regarding universal precautions for infection control (eg, the use of 
gloves) should be followed.  A trained health care worker, preferably the investigator, should read the reaction to the 
Mantoux test 48 to 72 hours after the injection.  Subjects should never be allowed to read their own tuberculin skin 
test results.  If a subject fails to show up for the scheduled reading, a positive reaction may still be measurable up to 
1 week after testing.  However, if a subject who fails to return within 72 hours has a negative test, tuberculin testing 
should be repeated.  The area of induration (palpable raised hardened area) around the site of injection is the reaction 
to tuberculin.  For standardization, the diameter of the induration should be measured transversely (perpendicular) to 
the long axis of the forearm.  Erythema (redness) should not be measured.  All reactions should be recorded in 
millimeters, even those classified as negative.
Interpreting the Tuberculin Skin Test Results
In the US and many other countries, the most conservative definition of positivity for the tuberculin skin test is 
reserved for immunocompromised patients, and this definition is to be applied in this study to maximize the likelihood 
of detecting latent TB, even though the subjects may not be immunocompromised at baseline.
In the US and Canada, an induration of 5 mm or greater in response to the intradermal tuberculin skin test is considered 
to be a positive result and evidence for either latent or active TB.
In countries outside the US and Canada, country-specific guidelines for immunocompromised patients should be 
consulted for the interpretation of tuberculin skin test results.  If no local country guidelines for immunocompromised 
patients exist, US guidelines must be followed.
Treatment of Latent Tuberculosis
Local country guidelines for immunocompromised patients should be consulted for acceptable antituberculous 
treatment regimens for latent TB.  If no local country guidelines for immunocompromised patients exist, US guidelines 
must be followed.
References
Centers for Disease Control and Prevention.  Core curriculum on tuberculosis:  What the clinician should know 
(Fourth Edition).  Atlanta, GA:  Department of Health and Human Services; Centers for Disease Control and 
Prevention; National Center for HIV, STD, and TB Prevention; Division of Tuberculosis Elimination; 2000:25-86. 
Menzies RI.  Tuberculin skin testing.  In:  Reichman LB, Hershfield ES (eds). Tuberculosis, a comprehensive 
international approach.  2nd ed.  New York, NY:  Marcel Dekker, Inc; 2000:279-322.


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10.4.
Appendix 4: Liver Safety: Suggested Actions and Follow-up Assessments 
10.4.1.
Stopping Algorithm
Study intervention will be discontinued for a participant if liver chemistry stopping criteria are 
met.


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10.4.2.
Follow-up Assessments
Phase 2 liver chemistry stopping criteria are designed to assure participant safety and to evaluate 
liver event etiology.
Liver Chemistry Stopping Criteria
ALT/AST--
absolute
ALT or AST- 5xULN
ALT/AST-
Increase
If cannot monitor:
ALT or AST- 3xULN and cannot be monitored weekly for 4 weeks
Or if able to monitor:
ALT or AST- 3xULN persists for 4 weeks
Total 
bilirubin1, 2
ALT or AST- 3xULN and total bilirubin 2xULN (or at least a doubling 
of direct bilirubin in known Gilbert’s syndrome)
INR2
ALT or AST- 3xULN and international normalized ratio (INR) >1.5, if 
INR measured
Symptomatic3
ALT or AST- 3xULN associated with symptoms (new or worsening) 
believed to be related to liver injury or hypersensitivity
Suggested Actions, Monitoring and Follow-up Assessments
Actions
Follow-up Assessments
Immediately stop study intervention
Report the event to the sponsor within 
24 hours
Complete the AE form and the SAE data 
collection tool if the event also met the criteria 
for an SAE2
Perform follow-up assessments as described in 
the Follow Up Assessment column
Monitor the participant until liver chemistry 
test abnormalities resolve, stabilize, or return 
to baseline (see MONITORING)
MONITORING:
If ALP <2xULN, ALT or AST - 3xULN AND 
total bilirubin 2xULN (or at least a doubling 
of direct bilirubin in known Gilbert’s 
syndrome) or INR >1.5 (if measured): 
Repeat liver chemistry tests (include ALT, 
AST, ALP, total and direct bilirubin, and INR) 
and perform liver event follow-up assessments 
within 24 hours
Monitor participant twice weekly until liver 
chemistry test abnormalities resolve, stabilize, 
or return to baseline
Viral hepatitis serology4
Obtain INR and recheck with each 
liver chemistry assessment until the 
transaminases values show downward 
trend
Obtain blood sample for 
pharmacokinetic (PK) analysis 72 
hours after the most recent dose5
Obtain serum creatine phosphokinase 
(CPK), lactate dehydrogenase (LDH), 
gamma-glutamyltransferase (GGT), 
glutamate dehydrogenase (GLDH), 
and serum albumin
Fractionate bilirubin
Obtain complete blood count with 
differential to assess eosinophilia
Record the appearance or worsening of 
clinical symptoms of liver injury, or 
hypersensitivity, on the AE and SAE 
forms. 
Record use of concomitant 
medications (including 
acetaminophen, herbal remedies, 


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A specialist or hepatology consultation is 
recommended
If ALT or AST - 3xULN AND total bilirubin 
<2xULN and INR 1.5: 
Repeat liver chemistry tests (include ALT, 
AST, ALP, total and direct bilirubin, and INR) 
and perform liver chemistry follow-up 
assessments within 24 to 72 hours
Monitor participants weekly until liver 
chemistry abnormalities resolve, stabilize, or 
return to baseline
RESTART/RECHALLENGE
Do not restart/rechallenge participant with 
study intervention 
recreational drugs and other over-the-
counter medications)
Record alcohol use on the substance 
use alcohol form   
If ALT or AST 3xULN AND total 
bilirubin 2xULN or INR >1.5 (if 
measured) obtain the following in 
addition to the assessments listed above:
Anti-nuclear antibody, anti-smooth 
muscle antibody, Type 1 anti-liver 
kidney microsomal antibodies, and 
quantitative total immunoglobulin G 
(IgG) or gamma globulins
Serum acetaminophen adduct assay, 
when available, to assess potential 
acetaminophen contribution to liver 
injury in participants with definite or 
likely acetaminophen use in the 
preceding week
Liver imaging (ultrasound, magnetic 
resonance, or computerized 
tomography) and/or liver biopsy to 
evaluate liver disease; complete the 
medical encounter form  
Liver biopsy may be considered and 
discussed with local specialist if 
available:
In participants when serology raises 
the possibility of autoimmune 
hepatitis 
In participants when suspected 
drug-induced liver injury
progresses or fails to resolve on 
withdrawal of study intervention
In participants with acute or chronic 
atypical presentation
If liver biopsy conducted complete the 
medical encounter form  
1. Serum bilirubin fractionation should be performed if testing is available. If serum bilirubin fractionation is not 
immediately available, discontinue study intervention if ALT 3xULN and total bilirubin 2xULN. 
Additionally, if serum bilirubin fractionation testing is unavailable, record the absence/presence of detectable 
urinary bilirubin on dipstick which is indicative of direct bilirubin elevations suggesting liver injury. 
2. All events of ALP <2xULN, ALT or AST - 3xULN and total bilirubin 2xULN (or at least a doubling of 
direct bilirubin in known Gilbert’s syndrome) or ALP <2xULN , ALT or AST - 3xULN and INR >1.5 (if 


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measured) may indicate severe liver injury (possible ‘Hy’s Law’) and must be reported to sponsor in an 
expedited manner and as an SAE if SAE criteria are met (excluding studies of hepatic impairment or 
cirrhosis). The INR stated threshold value will not apply to participants receiving anticoagulants.
3. New or worsening symptoms believed to be related to liver injury (such as fatigue, nausea, vomiting, right upper 
quadrant pain or tenderness, or jaundice) or hypersensitivity (such as fever, rash or eosinophilia).
4. Includes: hepatitis A immunoglobulin M (IgM) antibody; HBsAg and hepatitis B Core Antibody; hepatitis C 
RNA; cytomegalovirus IgM antibody; Epstein-Barr viral capsid antigen IgM antibody (or if unavailable, 
heterophile antibody or monospot testing); and hepatitis E IgM antibody.
5. PK sample may not be required for participants known to be receiving placebo or non-comparator interventions. 
Record the date/time of the PK blood sample draw and the date/time of the last dose of study intervention prior 
to the blood sample draw on the CRF. If the date or time of the last dose is unclear, provide the participant’s best 
approximation. If the date/time of the last dose cannot be approximated OR a PK sample cannot be collected in 
the time period indicated above, do not obtain a PK sample. Instructions for sample handling and shipping are in 
the Laboratory Manual.  




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10.6.
Appendix 6: Data Simulation 
To evaluate the operating characteristics of the study design, the following assumptions are made 
based 
on 
3 
completed 
clinical 
studies 
(C0743T26, 
CNTO1275CRD3001, 
and 
CNTO1275CRD3002) conducted by the sponsor:   

The compositions of Bio-IR and Bio-NF populations are 50% each

For Bio-IR population, the CDAI scores of the JNJ-67864238 
 treatment 
arm and placebo treatment arm at Weeks 0, 2, 4, 8, and 12 are assumed to be 
(323,285,259,247,238) ` and (323,305,300,299,298) `, respectively. Similarly, for Bio-NF 
population, the CDAI scores of the JNJ-67864238 
 treatment arm and 
placebo treatment arm at Weeks 0, 2, 4, 8 and 12 are assumed to be (302,245,208,180,176) ` 
and (302,271,254,241,236) `, respectively. 

The covariance matrix is assumed to be 
















11025
7030
5250
5670
3255
7030
10609
7210
6489
3193
5250
7210
10000
7200
3100
5670
6489
7200
8100
3069
3255
3193
3100
3069
3844
   and
















11025
7166
4988
4725
2520
7166
11025
6484
5670
3646
4988
6484
9025
5558
2565
4725
5670
5558
8100
2970
2520
3646
2565
2970
3600
        for the Bio-IR and Bio-NF populations, respectively.  

In CNTO1275CRD3001 and CNTO1275CRD3002, an optional endoscopy substudy was 
conducted in a subset of study participants. Based on the collected data, change in SES-CD is 
assumed to have a mixture distribution - excessive zeros (no change) and a normal 
distribution. Therefore, 2 steps were utilized to simulate the change in SES-CD data. 

Step 1: no change in SES-CD is simulated for 19% of JNJ-67864238 
 
treated participants and 32% placebo treated participants. 

Step 2: changes in SES-CD based on the normal distributions with mean changes from 
baseline of -3.26 and -0.22 are generated for the JNJ-67864238 
 and 
placebo arms, respectively. The common standard deviation is 3.8. As the change in SES-
CD of a participant is an integer, the simulated value then is rounded to the nearest integer. 
The above assumptions are for the Bio-IR population. The change in SES-CD responses 
for the Bio-NF population can be simulated similarly with the following assumptions: the 
proportion of the excessive zeros is 12% for both the active and placebo treatment arm in 
Step 1. The means of the normal distributions are -4.68 and -2.71 for the JNJ-67864238 
 and placebo arms, respectively. The common standard deviation is 
5.9. 

The correlation coefficients between the change in SES-CD and the CDAI scores are assumed 
to be -0.15, 0, 0, 0.15, and 0.15 at Weeks 0, 2, 4, 8, and 12 for the Bio-IR population. They 
are assumed to be 0, 0, 0, 0.15 and 0.15 at Weeks 0, 2, 4, 8, and 12 for the Bio-NF population.
CCI
CCI
CCI
CCI
CCI


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10.7. Appendix 7: COVID-19 APPENDIX
GUIDANCE ON STUDY CONDUCT DURING THE COVID-19 PANDEMIC
It is recognized that the Coronavirus Disease 2019 (COVID-19) pandemic may have an impact on 
the conduct of this clinical study due to, for example, self-isolation/quarantine by participants and 
study-site personnel; travel restrictions/limited access to public places, including hospitals; study 
site personnel being reassigned to critical tasks.
In alignment with recent health authority guidance, the sponsor is providing options for 
study -related participant management in the event of disruption to the conduct of the study. This 
guidance does not supersede any local or government guidelines or requirements or the clinical 
judgement of the investigator to protect the health and well-being of participants and site staff. If,
at any time, a participant’s safety is considered to be at unacceptable risk, study intervention will 
be discontinued, and study follow-up will be conducted.
Scheduled visits that cannot be conducted in person at the study site will be performed to the extent 
possible remotely/virtually or delayed until such time that on-site visits can be resumed. At each 
contact, participants will be interviewed to collect safety data. Key efficacy endpoint assessments 
should be performed if required and as feasible. Participants will also be questioned regarding 
general health status to fulfill any physical examination requirement. 
Every effort should be made to adhere to protocol-specified assessments for participants on study 
intervention, including follow up. Modifications to protocol-required assessments may be 
permitted via COVID-19 Appendix after consultation between the participant and investigator, 
and with the agreement of the sponsor (see below). 
The sponsor will continue to monitor the conduct and progress of the clinical study, and any 
changes will be communicated to the sites and to the health authorities according to local guidance.
If a participant has tested positive for COVID-19, the investigator should contact the sponsor’s 
responsible medical officer to discuss plans for study intervention and follow-up. Modifications 
made to the study conduct as a result of the COVID-19 pandemic should be summarized in the 
clinical study report.


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ADDITIONAL ELEMENTS, WHERE APPLICABLE:

Certain protocol-mandated visits to the study site may not be possible during the COVID-19 
outbreak. Therefore, temporary measures may be implemented if considered appropriate by 
the sponsor and investigator to maintain continuity of participant care and study integrity. 
Certain measures, such as those listed below, may be necessary and should be instituted in 
accordance with applicable (including local) laws, regulations, guidelines, and procedures:
o
remote (eg, by phone / telemedicine) or in-person, off-site (eg, in-home) interactions 
between site staff (or designees) and participants for study procedures e.g. those related 
to safety monitoring / efficacy evaluation / study intervention storage and 
administration (including training where pertinent)
o
laboratory assessments using a suitably accredited local laboratory; for selected 
measures (eg, urine pregnancy), home testing may be employed
o
other procedures, eg, imaging, may be conducted at an appropriate facility

Missed assessments/visits will be captured in the clinical trial management system for 
protocol deviations.  Discontinuations of study interventions and withdrawal from the 
study should be documented with the prefix “COVID-19-related” in the case report form 
(CRF).  
o
other relevant study data elements impacted by the pandemic should also be 
documented / labeled as “COVID-19-related” in CRFs and / or other study systems, 
as directed by detailed sponsor guidance. These may include missed / delayed / 
modified study visits / assessments / dosing, and instances where temporary 
measures such as those above are implemented.  

The sponsor will evaluate the totality of impact of COVID-19 on collection of key study 
data and additional data analyses will be outlined in study SAP(s). 

Exclusion: a potential participant with the following features will be excluded from 
participating in the study protocol:
o
During the 6 weeks prior to baseline, have had ANY of (a) confirmed SARS-CoV-
2 (COVID-19) infection (test positive), OR (b) suspected SARS-CoV-2 infection 
(clinical features without documented test results), OR (c) close contact with a 
person with known or suspected SARS-CoV-2 infection 

Exception: may be included with a documented negative result for a 
validated SARS-CoV-2 test
(i) obtained at least 2 weeks after conditions (a), (b), (c) above (timed from 
resolution of key clinical features if present, e.g. fever, cough, dyspnea)


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AND
(ii) with absence of ALL conditions (a), (b), (c) above during the period 
between the negative test result and the baseline study visit 

NOTES on COVID-related exclusion:
1. If a participant is excluded due to recent COVID-19-related features, the reason for 
screen failure should be documented in the case report form under the exclusion 
criterion of having a condition for which participation would not be in the participant’s 
interest or could confound study assessments. 
2. The field of COVID-related testing (for presence of, and immunity to, the SARS-CoV-
2 virus) is rapidly evolving. Additional testing may be performed as part of screening 
and/or during the study if deemed necessary by the investigator and in accordance with 
current regulations / guidance from authorities / standards of care. 

Precaution: for those who may carry a higher risk for severe COVID-19 illness (eg, those 
aged over 65 years), follow guidance from local health authorities when weighing the 
potential benefits and risks of enrolling in the study, and during participation in the study. 


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10.8.
Appendix 8: Definition of Minimal Exposure to Ustekinumab
Participants who have had limited exposure to ustekinumab at its approved labeled dosage AND have met 
the required washout criterion AND have not demonstrated inadequate response or intolerance to 
ustekinumab as defined further below are eligible for entry into this intervention cohort.    
Participants who have had exposure to ustekinumab as an investigational agent (ie, exposure to ustekinumab 
from participation in prior ustekinumab clinical studies) or exposure to ustekinumab as an off-label 
treatment at their physician’s discretion are ineligible for entry into this intervention cohort.
Participants with prior exposure to an anti-IL-12/23 (ie, ustekinumab) or anti-IL-23 agents or related 
compound (including risankizumab, brazikumab, guselkumab, mirikizumab, and related compounds) are 
ineligible for entry into this intervention cohort.   Exception is made for participants who have had minimal 
exposure to ustekinumab as defined by the 3 criteria below.  
Participants MUST meet all of criteria 1, 2, and 3 below to qualify for entry into this intervention 
cohort as having had minimal exposure to ustekinumab, and provided that all other entry criteria as 
described in Section 5.1 and 5.2 have been satisfied.
1.
The criteria for minimal exposure to ustekinumab at its approved label dosage is defined as 
follows:
a.
No more than one induction dose of ustekinumab (ie, an IV dose of 260 mg, 390 mg or 520 mg)     
b.
No more than one maintenance dose of ustekinumab (ie, a 90 mg SC dose) 8 weeks after the 
single induction dose
2.
The required washout period from ustekinumab is defined as follows:
Participants must have been discontinued from ustekinumab for at least 16 weeks prior to the Week 0 
dosing visit of this intervention cohort 
3.
The following documentation to confirm the discontinuation of ustekinumab treatment for 
Crohn’s disease for reasons other than inadequate response or intolerance MUST be provided:
Examples of acceptable documents include medical records, letter provided by a referring physician, 
or other “reason for referral” documents (eg, insurance authorization / denial notifications) that:
a.
Provide the dates and doses of ustekinumab for the treatment of Crohn’s disease; AND
b.
Provide the date of discontinuation of ustekinumab for the treatment of Crohn’s disease; AND
c.
Indicate the participant had discontinued ustekinumab treatment for reasons other than inadequate 
response and/or intolerance (eg, loss of insurance); AND
d.
Indicate the participant did not discontinue ustekinumab treatment for Crohn’s disease due to 
inadequate response and/or intolerance. See further details under the NOTE section below for 
evidence indicative of inadequate response and/or intolerance.
NOTE:
The following are considered evidence of inadequate response and/or intolerance to ustekinumab treatment 
for Crohn’s disease.  Participants who meet these criteria are ineligible to enter this intervention cohort.  
Evidence of inadequate response to ustekinumab that had precluded continuation of previous 
treatment with ustekinumab for Crohn’s disease:

Lack of improvement or worsening in stool frequency

Lack of improvement or worsening in daily abdominal pain


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
Occurrence, lack of improvement, or worsening of fever thought to be related to Crohn’s disease

Lack of improvement or worsening in a draining fistula or development of a new draining fistula

Lack of improvement or worsening in rectal bleeding

Initiation or increase in antidiarrheal medication
These signs and symptoms of Crohn’s disease are offered only as a benchmark and acknowledges that the 
Crohn’s Disease Activity Index is not routinely recorded in clinical practice.
Evidence of intolerance to ustekinumab that had precluded continuation of previous treatment with 
ustekinumab for Crohn’s disease:
Have had an adverse reaction that meets 1 of the following 3 criteria: 1) significant acute 
infusion/administration reaction; 2) significant delayed infusion/administration reaction (for example, 
delayed hypersensitivity or serum sickness-like reaction); or 3) significant injection-site reaction.  
Definitions of these 3 criteria are provided below.

A significant acute infusion/administration reaction is defined as an adverse reaction that:
a.
Was manifested through 1 of the following symptoms.
o
Fever greater than 100F (37.8C)
o
Chills or rigors
o
Itching
o
Rash
o
Flushing
o
Urticaria or angioedema
o
Breathing difficulties (dyspnea, chest paint or tightness, shortness of breath, wheezing, 
stridor)
o
Clinical hypotension (pallor, diaphoresis, faintness, syncope), blood pressure <90 mm Hg 
systolic and 60 mm Hg diastolic, or a systemic or orthostatic drop in systolic blood pressure 
>20 mm Hg
AND
b.
Occurred 24 hours after infusion/administration of ustekinumab
AND
c.
Was considered related to the infusion/administration of ustekinumab

A significant delayed infusion/administration reaction is defined as an adverse reaction that:
a.
Was manifested through 1 or more of the following symptoms:
o
Myalgias
o
Arthralgias
o
Fever greater than 100F (37.8C)
o
Malaise
o
Rash


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AND
b.
Occurred >24 hours and <15 days after infusion/administration of ustekinumab
AND
c.
Was considered related to the infusion/administration of ustekinumab

A significant injection-site reaction is defined as an adverse reaction that:
a.
Was manifested through 1 or more of the following symptoms:
o
Significant bruising
o
Erythema
o
Hemorrhage
o
Irritation
o
Pain
o
Pruritus
o
“Injection-site reaction”
AND
b.
Occurred within 24 hours of an SC injection of ustekinumab.
AND
c.
Was considered related to the SC injection of ustekinumab.


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10.9. Appendix 9: Protocol Amendment History
The Protocol Amendment Summary of Changes Table for the current amendment is located 
directly before the Table of Contents.
Amendment 4 (14 Dec 2020)
Overall Rationale for the Amendment:  The overall rationale for the amendment is to incorporate the 
Coronavirus Disease 2019 (COVID-19) appendix into the protocol.  
Section Number
and Name
Description of Change
Brief Rationale
Section 10.7. 
Appendix 7 
COVID-19 
Appendix
The previously approved and submitted 
COVID-19 appendix was added as Section 
10.7 of the protocol.  The Protocol 
Amendment History, previously Section 
10.7, is Section 10.8.   
The stand-alone COVID-19 appendix was a 
prior amendment that was added to the 
body of the protocol to consolidate all 
protocol amendments.  
Cover Page 
The version number of the protocol was
updated from 4.0 to 6.0.  
Protocol amendment 3 dated 17 September 
2020 was inadvertently labeled version 4.0 
instead of version 5.0.  
Amendment 3 (17 Sep 2020)
Overall Rationale for the Amendment:  The overall rationale for the amendment is to update fecal 
samples for the microbiome to fecal samples for biomarkers. Biomarkers is a more inclusive term, and 
proteins and the microbiome will be analyzed from the same sample.
Section Number
and Name
Description of Change
Brief Rationale
1.1. Synopsis;
2 Introduction 
The definition of a platform study and the 
reference were added.   
The term platform study was not defined.  
The definition of an intervention cohort 
was updated to indicate that an 
intervention cohort may include 
participants receiving placebo or an active 
comparator. 
The definition of an intervention cohort 
was clarified.  
1.1 Synopsis;
1.3 Schedule of 
Activities;
8.8 Biomarkers
Fecal samples for microbiome was 
updated to fecal samples for biomarkers. 
Footnote dd was also removed to align 
with this change.  
Biomarkers is a more inclusive term, and 
proteins and the microbiome will be 
analyzed from the same sample.
1.3 Schedule of 
Activities
An optional screening follicle stimulating 
hormone assessment at the discretion of 
the investigator was added.  
This optional screening assessment was 
inadvertently omitted from the Schedule 
of Activities.
A fecal sample for stool concentrations 
and a plasma sample for systemic 
concentrations of JNJ-67864238 were 
added at Week 2.
These samples at Week 2 were 
inadvertently omitted from the Schedule 
of Activities. 
Footnote t was removed as it was a Master 
protocol footnote and had the sample 
schedule for pharmacokinetics (PK) and 
The PK sampling schedule was 
inadvertently included in the master 
protocol.  


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Section Number
and Name
Description of Change
Brief Rationale
immunogenicity, which are ISA specific.  
The lettering of the remaining footnotes 
was subsequently updated.    
Footnote u (updated to footnote t with this 
amendment) was revised as it was a 
Master protocol footnote and had 
references to PK sampling, which are ISA 
specific.  
The PK sampling information was 
inadvertently included in the Master 
protocol.  
Footnote aa (updated to footnote z with 
this amendment) was revised to include 
the relevant sampling information that was 
in footnotes t and u.  
Footnote bb was removed since the 
information is in footnote aa (updated to 
footnote z).    
Footnote t was removed and footnote u 
(updated to footnote t with this 
amendment) was revised to remove 
references to PK and antibody 
assessments.  
Footnote bb was removed as the antibody 
sampling schedule was incorporated into 
footnote aa (updated to footnote z with
this amendment).  
Footnote bb was redundant.  
2.2 Background; 
Pharmacokinetic 
Profile; 
6.5 Concomitant 
Therapy
Text indicating that narrow therapeutic 
index drugs that are P-glycoprotein (P-gp)
substrates should be avoided was 
removed.
Data from a sponsor preclinical study 
(Report FK13558, In vitro Interaction 
Studies of JNJ-67864238 with human 
MDR1 Efflux [ABC] Transporter, issued 
08 JUL 2019) indicate that there was no 
effect of JNJ-67864238 on digoxin (a P-
gp substrate) efflux and therefore drug 
interactions with drugs that are P-gp 
substrates are unlikely.
7.1 Discontinuation of 
Study Intervention
Text regarding follow-up visits for 
participants who discontinuation study 
intervention prior to Week 12 was 
removed.  
Detailed instructions were added to 
Section 7.1 of Master protocol 
PLATFORMPACRD2001 to clarify the 
follow-up visit schedule for participants
who discontinuation study intervention 
prior to Week 12.  
8.5.1 Evaluations
A plasma sample for systemic 
concentrations of JNJ-67864238 was 
added at Week 2.
This sample at Week 2 was inadvertently 
omitted. 
Details regarding the collection of stool 
samples for measurement of JNJ-67864238 
stool concentrations as outlined in the 
Schedule of Activities were added.  
Details regarding the collection of stool 
samples were added to align with the 
Schedule of Activities.  
1.1. Synopsis;
8.9 Immunogenicity 
Assessments
Immunogenicity will not be assessed in 
the JNJ-67864238 intervention cohort.  
Samples for immunogenicity will be 
collected and would only be analyzed if 
required to assess other data or analyses, 
such as for PK or AEs.
Appendix 2
The bilateral tubal occlusion/ligation 
procedures were removed from the 
definition of permanently sterile.  
The text was updated to align the 
definition of permanently sterile with that 
of the European Union Clinical Trials 
Facilitation and Coordination Group.  


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Section Number
and Name
Description of Change
Brief Rationale
Appendix 5
An optional screening follicle stimulating 
hormone assessment at the discretion of 
the investigator was added.  
This optional screening assessment was 
inadvertently omitted.
Throughout the 
protocol
Minor grammatical, formatting, or spelling 
changes were made.
Minor errors were noted.


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Amendment 2 (13 November 2019)
Overall Rationale for the Amendment:  To address health authority requested changes.  
Section number
and Name
Description of Change
Brief Rationale
5.1. Inclusion Criteria, 
#9
Text was added to indicate that subjects 
must be receiving treatment for Crohn’s 
disease at study entry. 
In this early phase study where some 
participants will receive placebo and 
the efficacy of JNJ-67864238 is 
unknown, participants must receive 
appropriate therapy for Crohn’s 
disease.
2.3.1. Risks for Study 
Participation;
2.3.3. Benefit-Risk 
Assessment for Study 
Participation;
6.5.2. Crohn’s Disease-
Specific Therapies
Text was added to indicate that concomitant 
background therapies should be continued 
throughout the study. 
In this early phase study where some 
participants will receive placebo and 
the efficacy of JNJ-67864238 is 
unknown, participants should 
continue to receive appropriate 
concomitant therapy for Crohn’s 
disease.
5.2. Exclusion Criteria
Exclusion criterion #26 was added to clarify 
that participants must not have a history of 
drug or alcohol abuse.  
The exclusion criterion was added to 
exclude participants with a history of 
drug or alcohol abuse.
6.3. Measures to 
Minimize Bias: 
Randomization and 
Blinding 
Text was added to specify that 
treatment assignment will be unblinded to 
the sponsor at the Week 12 database lock.  
The text was updated to clarify 
unblinding to the sponsor.  
9.2.2.2. Decision-
Making Specifics at the 
Completion of the 
Intervention Cohort
Futility criteria for the change in SES-CD 
were updated. 
The futility criteria were corrected for 
internal document consistency.
9.5. Interim Analysis  
Text was added to indicate that the study 
team will remain blinded at the Interim 
Analysis.  
The text was updated to clarify that 
the study team will not be unblinded 
for the Interim Analysis.  
4.1. Overall Design;
5.1. Inclusion Criteria
The units for fecal calprotectin were 
changed from >250 mg/mL to >250 µg/mg.  
The units for fecal calprotectin were 
corrected.  
5.2 Exclusion Criteria
Duplication of exclusion criteria #A05 was 
corrected. 
The number A05 was used twice and 
was corrected to sequential 
numbering.
6.2. 
Preparation/Handling/
Storage/Accountability
Text regarding the disposition of needles and 
syringes was removed. 
Since JNJ-67864238 is an oral 
intervention, the text is not 
applicable. 
7.1. Discontinuation of 
Study Intervention
Text regarding severe injection-site or 
infusion reactions was removed. 
Since JNJ-67864238 is an oral 
intervention, the text is not 
applicable.
1.2 Scheme; 
1.3 Schedule of 
Activities
The Patient’s Global Impression of Change 
(PGIC) at Week 0 was removed.  
PGIC is not applicable at Week 0.
Throughout the protocol
Minor grammatical, formatting, or spelling 
changes were made.
Minor errors were noted.  
Amendment 1 (14 August 2019) 
Overall Rationale for the Amendment:  To update the protocol with a newly assigned EudraCT number 
to allow for re-submission of a request for the Voluntary Harmonisation Procedure (VHP) in the European 
Union.  


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Section number
and Name
Description of Change
Brief Rationale
Title page
Replacement of the previous EudraCT
number (2018-000649-38) with a newly 
assigned EudraCT number (2019-003335-
37).  
To allow the re-submission of a request for 
the VHP for the assessment of the Clinical 
Trial Authorisation application in the 
European Union, following rejection of the 
initial VHP application for administrative 
reasons. 
10.7, Appendix 7 
Protocol 
Amendment History
Update text to indicate that the Protocol 
Amendment Summary of Changes Table 
for this current amendment is located 
before the Table of Contents.
To update the amendment history to 
indicate that there are amendments for this 
protocol.  


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11.
REFERENCES
1.
Atarashi K, Suda W, Luo C, et al.  Ectopic colonization of oral bacteria in the intestine drives TH1 cell 
induction and inflammation. Science. 2017;358(6361):359-365. DOI: 10.1126/science.aan4526.   
2.
Barrett JC, Hansoul S, Nicolae DL, et al. Genome-wide association defines more than 30 distinct susceptibility 
loci for Crohn’s disease. Nat Genet. 2008;40(8):955-962.   
3.
Docktor MJ, Paster BJ, Abramowicz S, et al.  Alterations in Diversity of the Oral Microbiome in Pediatric 
Inflammatory Bowel Disease. Inflamm Bowel Dis. 2012;18(5):935–942. Doi:  10.1002/ibd.21874
4.
Feagan BG, Sandborn WJ, D’Haens G, et al. Induction therapy with the selective interleukin-23 inhibitor 
risankizumab in patients with moderate-to-severe Crohn’s disease: a randomised, double-blind, placebo-
controlled phase 2 study. Lancet. 2017;389(10080)1699-1709. 
5.
Feagan BG, Sandborn WJ, Panés J, et al. Efficacy and safety of re-induction treatment with the selective IL-23 
inhibitor risankizumab in patients with moderate-to-severe Crohn’s disease. United European Gastroenterol J. 
2016a;4(6):806.  
6.
Feagan BG, Sandborn WJ, Gasink C, et al. Ustekinumab as induction and maintenance therapy for Crohn’s 
disease [UNITI–IM-UNITI Study Group]. N Engl J Med. 2016b;375(20):1946-1960.  
7.
Food and Drug Administration Center for Drugs Evaluation Research, Center for Biologics Evaluation and 
Research (2009). Guidance for Industry Drug-Induced Liver Injury: Premarketing Clinical Evaluation.
8.
Gevers D, Kugathasan S, Denson LA, et al.  The treatment-naïve microbiome in new-onset Crohn’s disease. 
Cell Host Microbe. 2014;15(3):382–392. Doi:  10.1016/j.chom.2014.02.005.   
9.
Hue S, Ahern P, Buonocore S, et al. Interleukin-23 drives innate and T cell-mediated intestinal inflammation. J 
Exp Med. 2006; 203:2473-2483.  
10.
Maxwell JR, Zhang Y, Brown WA, et al. Differential roles for interleukin-23 and interleukin-17 in intestinal 
immunoregulation. Immunity. 2015;43(4):739-750.  
11.
Sandborn WJ, Gasink C, Gao LL, et al. Ustekinumab induction and maintenance therapy in refractory Crohn’s 
disease. N Engl J Med. 2012;367(16):1519-1528.  
12.
Sands BE, Chen J, Feagan BG, et al. Efficacy and safety of MEDI2070, an antibody against interleukin 23, 
patients with moderate to severe Crohn's disease: A Phase 2a Study. Gastroenterology. 2017;153(1):77-86.e6.  
13.
STELARA Package Insert. Horsham, PA: Janssen Biotech, Inc. 2012. 
14.
Woodcock J and LaVange LM. Master Protocols to Study Multiple Therapies, Multiple Diseases, or Both. N 
Engl J Med. 2017;377:62-70.  
15.
World Health Organization. Blood Donor Selection: Guidelines on Assessing Donor Suitability for Blood 
Donation. WHO, Geneva, Switzerland, 2012.




CONFIDENTIAL – FOIA Exemptions Apply in U.S.
1
Status: Approved ,  Date: 20 May 2020
Janssen Research & Development *
Clinical Protocol
COVID-19 Appendix
Intervention Specific Appendix to Master Clinical Protocol PLATFORMPACRD2001
PRISM-SCARLET
Protocol 67864238PACRD2001; Phase 2a
JNJ-67864238
*Janssen Research & Development is a global organization that operates through different legal entities in
various countries. Therefore, the legal entity acting as the sponsor for Janssen Research & Development
studies may vary, such as, but not limited to Janssen Biotech, Inc.; Janssen Products, LP; Janssen Biologics,
BV; Janssen-Cilag International NV; Janssen, Inc; Janssen Pharmaceutica NV; Janssen Sciences Ireland
UC; Janssen Biopharma Inc.; or Janssen Research & Development, LLC. The term “sponsor” is used
throughout the protocol to represent these various legal entities; the sponsor is identified on the Contact
Information page that accompanies the protocol.
United States (US) sites of this study will be conducted under US Food & Drug Administration
Investigational New Drug (IND) regulations (21 CFR Part 312).
EudraCT NUMBER:         2019-003335-37
Status:
Approved 
Date:
20 May 2020
Prepared by:
Janssen Research & Development, LLC;  
EDMS number:
EDMS-RIM-62480, 1.0 
THIS APPENDIX APPLIES TO ALL CURRENT APPROVED VERSIONS OF PROTOCOL
GCP Compliance: This study will be conducted in compliance with Good Clinical Practice, and applicable regulatory 
requirements. 
Confidentiality Statement
The information provided herein contains Company trade secrets, commercial or financial information that the Company 
customarily holds close and treats as confidential.  The information is being provided under the assurance that the recipient
will maintain the confidentiality of the information under applicable statutes, regulations, rules, protective orders or 
otherwise.
NCT04102111


COVID-19 Appendix
JNJ-67864238
Clinical Protocol 67864238PACRD2001
CONFIDENTIAL – FOIA Exemptions Apply in U.S.
2
Status: Approved ,  Date: 20 May 2020
COVID-19 APPENDIX
GUIDANCE ON STUDY CONDUCT DURING THE COVID-19 PANDEMIC
It is recognized that the Coronavirus Disease 2019 (COVID-19) pandemic may have an impact on 
the conduct of this clinical study due to, for example, self-isolation/quarantine by participants and 
study-site personnel; travel restrictions/limited access to public places, including hospitals; study 
site personnel being reassigned to critical tasks.
In alignment with recent health authority guidance, the sponsor is providing options for 
study -related participant management in the event of disruption to the conduct of the study. This 
guidance does not supersede any local or government guidelines or requirements or the clinical 
judgement of the investigator to protect the health and well-being of participants and site staff. If,
at any time, a participant’s safety is considered to be at unacceptable risk, study intervention will 
be discontinued, and study follow-up will be conducted.
Scheduled visits that cannot be conducted in person at the study site will be performed to the extent 
possible remotely/virtually or delayed until such time that on-site visits can be resumed. At each 
contact, participants will be interviewed to collect safety data. Key efficacy endpoint assessments 
should be performed if required and as feasible. Participants will also be questioned regarding 
general health status to fulfill any physical examination requirement. 
Every effort should be made to adhere to protocol-specified assessments for participants on study 
intervention, including follow up. Modifications to protocol-required assessments may be 
permitted via COVID-19 Appendix after consultation between the participant and investigator, 
and with the agreement of the sponsor (see below). 
The sponsor will continue to monitor the conduct and progress of the clinical study, and any 
changes will be communicated to the sites and to the health authorities according to local guidance.
If a participant has tested positive for COVID 19, the investigator should contact the sponsor’s 
responsible medical officer to discuss plans for study intervention and follow-up. Modifications 
made to the study conduct as a result of the COVID-19 pandemic should be summarized in the 
clinical study report.


COVID-19 Appendix
JNJ-67864238
Clinical Protocol 67864238PACRD2001
CONFIDENTIAL – FOIA Exemptions Apply in U.S.
3
Status: Approved ,  Date: 20 May 2020
ADDITIONAL ELEMENTS, WHERE APPLICABLE:

Certain protocol-mandated visits to the study site may not be possible during the COVID-19 
outbreak. Therefore, temporary measures may be implemented if considered appropriate by 
the sponsor and investigator to maintain continuity of participant care and study integrity. 
Certain measures, such as those listed below, may be necessary and should be instituted in 
accordance with applicable (including local) laws, regulations, guidelines, and procedures:
o
remote (eg, by phone / telemedicine) or in-person, off-site (eg, in-home) interactions 
between site staff (or designees) and participants for study procedures e.g. those related 
to safety monitoring / efficacy evaluation / study intervention storage and 
administration (including training where pertinent)
o
laboratory assessments using a suitably accredited local laboratory; for selected 
measures (eg, urine pregnancy), home testing may be employed
o
other procedures, eg, imaging, may be conducted at an appropriate facility

Missed assessments/visits will be captured in the clinical trial management system for 
protocol deviations.  Discontinuations of study interventions and withdrawal from the 
study should be documented with the prefix “COVID-19-related” in the case report form 
(CRF).  
o
other relevant study data elements impacted by the pandemic should also be 
documented / labeled as “COVID-19-related” in CRFs and / or other study systems, 
as directed by detailed sponsor guidance. These may include missed / delayed / 
modified study visits / assessments / dosing, and instances where temporary 
measures such as those above are implemented.  

The sponsor will evaluate the totality of impact of COVID-19 on collection of key study 
data and additional data analyses will be outlined in study SAP(s). 

Exclusion: a potential participant with the following features will be excluded from 
participating in the study protocol:
o
During the 6 weeks prior to baseline, have had ANY of (a) confirmed SARS-CoV-
2 (COVID-19) infection (test positive), OR (b) suspected SARS-CoV-2 infection 
(clinical features without documented test results), OR (c) close contact with a 
person with known or suspected SARS-CoV-2 infection 

Exception: may be included with a documented negative result for a 
validated SARS-CoV-2 test
(i) obtained at least 2 weeks after conditions (a), (b), (c) above (timed from 
resolution of key clinical features if present, e.g. fever, cough, dyspnea)


COVID-19 Appendix
JNJ-67864238
Clinical Protocol 67864238PACRD2001
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Status: Approved ,  Date: 20 May 2020
AND
(ii) with absence of ALL conditions (a), (b), (c) above during the period 
between the negative test result and the baseline study visit 

NOTES on COVID-related exclusion:
1. If a participant is excluded due to recent COVID-19-related features, the reason for 
screen failure should be documented in the case report form under the exclusion 
criterion of having a condition for which participation would not be in the participant’s 
interest or could confound study assessments. 
2. The field of COVID-related testing (for presence of, and immunity to, the SARS-CoV-
2 virus) is rapidly evolving. Additional testing may be performed as part of screening 
and/or during the study if deemed necessary by the investigator and in accordance with 
current regulations / guidance from authorities / standards of care. 

Precaution: for those who may carry a higher risk for severe COVID-19 illness (eg, those 
aged over 65 years), follow guidance from local health authorities when weighing the 
potential benefits and risks of enrolling in the study, and during participation in the study. 



SAP_001.pdf: 
1
Approved, Date: 29 June 2021
Janssen Research & Development 
Statistical Analysis Plan
Phase 2, Multicenter, Randomized, Double-blind, Placebo-controlled, Platform Study 
Evaluating the Efficacy and Safety of Interventions in Subjects with Moderately to 
Severely Active Crohn’s Disease - Intervention Specific Appendix to Master Clinical 
Protocol PLATFORMPACRD2001PRISM-SCARLET
Protocol 67864238PACRD2001; Phase 2a
JNJ-67864238  
Status:
Approved
Date:
June 29th 2021
Prepared by:
[Janssen Research & Development, LLC]  
Document No.:
EDMS-RIM-201693
Compliance: The study described in this report was performed according to the principles of Good Clinical Practice (GCP). 
Confidentiality Statement
The information in this document contains trade secrets and commercial information that are privileged or confidential and may 
not be disclosed unless such disclosure is required by applicable law or regulations. In any event, persons to whom the 
information is disclosed must be informed that the information is privileged or confidential and may not be further disclosed by 
them. These restrictions on disclosure will apply equally to all future information supplied to you that is indicated as privileged or 
confidential.
NCT04102111


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TABLE OF CONTENTS
TABLE OF CONTENTS ............................................................................................................................... 2
VERSION HISTORY..................................................................................................................................... 4
INTRODUCTION.................................................................................................................................. 5
1.1.
Objectives and Endpoint...................................................................................................................... 5
1.2.
Study Design.................................................................................................................................... 6
STATISTICAL HYPOTHESES............................................................................................................ 7
SAMPLE SIZE DETERMINATION...................................................................................................... 8
POPULATIONS (ANALYSIS SETS) FOR ANALYSIS....................................................................... 8
STATISTICAL ANALYSES ................................................................................................................. 8
5.1.
General Considerations ................................................................................................................... 8
5.1.1.
Analysis Window........................................................................................................................... 9
5.2.
Participant Dispositions.................................................................................................................... 9
5.3.
Primary Endpoint Analysis ............................................................................................................. 10
5.3.1.
Definition of Endpoint.................................................................................................................. 10
Treatment Failure Rules:............................................................................................................................. 11
5.3.2.
Estimand..................................................................................................................................... 12
5.3.2.1.
Primary Estimand (Estimand 1)............................................................................................... 12
5.3.3.
Analysis Methods........................................................................................................................ 14
5.3.3.1.
Main Estimator (Analysis) for the Primary Estimand ............................................................... 14
5.3.3.2.
Sensitivity and Supplementary Estimand for Primary Endpoint .............................................. 14
5.3.3.3.
Supplementary Estimand for Primary Endpoint ...................................................................... 15
Estimand 2 ................................................................................................................................................. 15
Estimand 3 ................................................................................................................................................. 15
Estimand 4 ................................................................................................................................................. 16
5.3.4.
Subgroup Analysis...................................................................................................................... 17
5.3.5.
Multiplicity Adjustment for Secondary Endpoints ....................................................................... 17
5.4.
Secondary Endpoint(s) Analysis .................................................................................................... 17
5.4.1.
Key Confirmatory Secondary Endpoint ...................................................................................... 17
5.4.1.1.
Definition of Endpoint(s) .......................................................................................................... 17
5.4.1.2.
Estimands................................................................................................................................ 18
5.4.1.3.
Analysis Methods for the Estimands for the Major Secondary Endpoints .............................. 20
5.4.2.
Supportive Endpoint(s) ............................................................................................................... 20
5.4.2.1.
Analysis Methods .................................................................................................................... 21
5.5.
Tertiary/Exploratory Endpoint(s) Analysis...................................................................................... 21
5.6.
Safety Analyses ............................................................................................................................. 21
5.6.1.
Extent of Exposure ..................................................................................................................... 21
5.6.2.
Adverse Events........................................................................................................................... 22
5.6.3.
Additional Safety Assessments .................................................................................................. 22
5.6.3.1.
Clinical Laboratory Tests......................................................................................................... 22
5.6.3.2.
Vital Signs and Physical Examination Findings....................................................................... 25
5.6.3.3.
Electrocardiogram ................................................................................................................... 25
5.7.
Other Analyses............................................................................................................................... 25
5.7.1.
Pharmacokinetics ....................................................................................................................... 25
5.7.1.1.
PTG-200 Concentrations......................................................................................................... 25
5.7.1.2.
Data Handling Rules................................................................................................................ 26
5.7.1.3.
PK vs Efficacy.......................................................................................................................... 26
5.7.2.
Immunogenicity........................................................................................................................... 27
5.7.2.1.
Antibodies to PTG-200 ............................................................................................................ 27
5.7.2.2.
Neutralized Antibodies to PTG-200......................................................................................... 27


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5.7.2.3.
Antibody vs Efficacy/PK........................................................................................................... 27
5.7.3.
Pharmacogenomic...................................................................................................................... 27
5.7.4.
Pharmacokinetic/Pharmacodynamic Relationships ................................................................... 27
5.7.5.
Biomarker Analyses.................................................................................................................... 28
5.7.6.
Health Economics....................................................................................................................... 28
5.7.6.1.
PROMIS 29.............................................................................................................................. 28
5.7.6.2.
Analysis Method ...................................................................................................................... 28
5.7.7.
Other Variables and/or Parameters............................................................................................ 28
5.7.8.
Definition of Subgroups .............................................................................................................. 29
5.8.
Interim Analyses............................................................................................................................. 29
5.8.1.
Data Monitoring Committee (DMC) or Other Review Board ...................................................... 30
SUPPORTING DOCUMENTATION .................................................................................................. 31
6.1.
Appendix 1 List of Abbreviations.................................................................................................... 31
6.2.
Appendix 2 Changes to Protocol-Planned Analyses ..................................................................... 32
6.3.
Appendix 3 Demographics and Baseline Characteristics.............................................................. 33
6.4.
Appendix 4 Protocol Deviations ..................................................................................................... 35
6.5.
Appendix 5 Prior and Concomitant Medications............................................................................ 36
6.6.
Appendix 6 Medical History ........................................................................................................... 37
6.7.
Appendix 7 Intervention Compliance ............................................................................................. 38
6.8.
Appendix 8 Adverse Events of Special Interest............................................................................. 39
6.9.
Appendix 9 Medications of Special Interest................................................................................... 40
6.10.
Appendix 10 Laboratory Toxicity Grading...................................................................................... 41
REFERENCES................................................................................................................................... 42
Attachment 1
Decision-Making Framework...................................................................................... 43
Attachment 2:
Data Simulation .......................................................................................................... 45
Attachment 3:
Crohn’s Disease Activity Index................................................................................... 46
Attachment 4:
Sample score sheet and scoring definitions for the Simple Endoscopic Score 
for Crohn’s Disease (SES-CD)................................................................................... 47
Attachment 5:
STANDARD WEIGHT TABLE.................................................................................... 48


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VERSION HISTORY
Table [xx] – SAP Version History Summary
SAP Version
Approval Date
Change
Rationale
1
Not Applicable
Initial release


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INTRODUCTION
This statistical analysis plan (SAP) contains the definitions of analysis sets, key derived variables, 
and statistical methods to evaluate the safety and efficacy of JNJ‑67864238 (also known as PTG-
200), an experimental drug, in adult participants with moderately to severely active Crohn's disease 
for Intervention-Specific Appendix (ISA) Protocol JNJ-67864238PACRD2001 that refers to 
Master Protocol PLATFORMPACRD2001. Analysis results titles, mock-ups and programming 
instructions for all statistical outputs (tables, figures and listings) will be provided in a separate 
document entitled Data Presentation Specifications (DPS).  
1.1.
Objectives and Endpoint
Objectives 
Primary Objective

The primary objective is to evaluate the efficacy of JNJ‑67864238 as measured by the 
change in the Crohn’s Disease Activity Index (CDAI) score from baseline at Week 12.
Secondary Objectives

To investigate the safety and tolerability of JNJ‑67864238 in patients with moderately to 
severely active Crohn’s disease 

To evaluate the efficacy of JNJ‑67864238 to reduce the Simplified Endoscopic Score for 
Crohn’s disease (SES-CD), induce clinical remission, clinical response, and endoscopic 
healing of the mucosa   

To evaluate the pharmacokinetics (PK), pharmacodynamics (PD), immunogenicity (if 
applicable), and biomarker response of JNJ‑67864238
Other Objectives

to evaluate the efficacy of JNJ‑67864238 on patient-related outcomes as measured by the 
Patient-Reported Outcomes Measurement Information System (PROMIS)-29 score
Endpoints
Primary Endpoint

Change from baseline in the CDAI score at Week 12.
Secondary Endpoints

Change in the SES-CD from baseline

Clinical response as measured by CDAI (≥100-point reduction from baseline in CDAI or 
CDAI <150)

Clinical remission rate as measured by CDAI (CDAI <150)

PRO-2 remission defined as abdominal pain (AP) mean daily score (AP component of 
the CDAI) at or below 1 AND stool frequency (SF) mean daily score at or below 3, i.e., 
AP ≤1 and SF ≤3


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
Endoscopic response (defined as at least a 50% improvement from baseline in the SES-
CD)

Endoscopic remission (defined as an SES-CD score ≤2)
Other Endpoints
Other endpoints to be evaluated across all post-baseline visits include but are not limited to:

Change in AP from baseline based on a 0 to 10 numerical rating scale (NRS)

Change in number of daily loose or watery stools

Changes from baseline in the CDAI, PRO-2 (the sum of AP and SF subscores of the 
CDAI score), PRO-3 (the sum of AP, stool frequency, and general well-being subscores 
of the CDAI score), C-reactive protein (CRP), and fecal calprotectin

Clinical remission (CDAI <150), PRO-2 remission (AP ≤1 and SF ≤3), and clinical 
response based on CDAI

Endoscopic improvement based on a reduction from baseline in the SES-CD score (≥3 
points, 25%, 50%)

Endoscopic healing (defined as the absence of mucosal ulcerations)

Patient’s Global Assessment of Crohn’s Disease Activity

Change from baseline in multivariate score of biomarkers measured in mucosal biopsy
samples, whole blood, serum, and/or stool

Change in PROs as measured by the PROMIS-29 score
1.2.
Study Design
The clinical development program for experimental drug in Crohn’s disease will be conducted 
under a platform protocol, which consists of a Master protocol and multiple ISAs.  The Master 
protocol describes the design elements that are common across the whole platform study without 
any compound information. The ISA describes the specific JNJ-active compound information to 
evaluate the safety and efficacy of JNJ-active in Participants with moderately to severely active 
Crohn’s disease who have demonstrated an inadequate response or failure to tolerate previous 
conventional therapy or biologic therapy. This SAP will be in-line follow platform protocol 
starting from the first ISA phase 2a Proof-of-concept study first. The first ISA is a Phase 2a, 
multicenter, randomized, double-blind, placebo-controlled study designed to assess the effects of 
a predominantly gastrointestinal-restricted anti-IL 23R compound for moderately to severely 
active Crohn’s disease. This 12-week Phase 2a study is focused on proof-of-concept and will 
assess the safety and efficacy of an orally administered high dose of JNJ-67864238 compared with 
placebo in participants with Crohn’s disease. Since the inhibition of the IL-23 pathway has been 
validated as a mechanism for treating Crohn’s disease, a high dose was chosen to assess the 
efficacy of a locally acting anti-IL-23 inhibitor.
Participants may be biologic intolerant or refractory (Bio-IR) or biologic nonfailures (Bio-NF)
populations as defined below:

Bio-IR Population: Those participants who have received infliximab, adalimumab,
certolizumab pegol, vedolizumab, or ustekinumab at a dose approved for the treatment of 
Crohn’s disease, and either did not respond initially, responded initially but then lost 
response, or were intolerant to the medication.


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
Bio-NF Population: Those participants who have demonstrated an inadequate response to 
or have failed to tolerate corticosteroids or the immunomodulators 6-MP, AZA, or MTX. 
Participants who have demonstrated corticosteroid dependence (ie, an inability to 
successfully taper corticosteroids without a return of the symptoms of Crohn’s disease) are 
also eligible. Bio-NF participants may also have received biologic therapy but only if it 
was discontinued for reasons other than lack of efficacy or intolerance (eg, a drug holiday).
A target of 90 Bio-IR and Bio-NF participants will be randomized to receive JNJ 67864238 
 
 or placebo in a 3:2 ratio using permuted block randomization, stratified by baseline 
Crohn’s Disease Activity Index (CDAI) score (≤300, >300) and biological refractory status (Bio-
IR, Bio-NF).  The treatment arms for this study will be as follows: JNJ-67864238 
 
 (N=54) and Placebo (N=36). Of note, the sample size has been chosen to assess a level of 
efficacy consistent with that observed with systemically available biological therapies for Crohn’s 
disease.
An overview of this study design is presented in Figure 1 below:
Figure 1:
Schematic Overview of Study Design
STATISTICAL HYPOTHESES 
The hypothesis is that JNJ‑67864238 is superior to placebo as measured by the reduction from 
baseline in the CDAI at Week 12 in Participants with moderately to severely active Crohn’s 
disease. 
Primary Objective
The primary objective is to evaluate the efficacy of experimental drugJNJ‑67864238 as measured 
by the change in the CDAI score from baseline at Week 12.
CCI
CCI


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Secondary Objectives
The major secondary objectives are as follows:

To investigate the safety and tolerability of experimental drugJNJ‑67864238 in participants 
with moderately to severely active Crohn’s disease

To evaluate the efficacy of experimental drugJNJ‑67864238 to reduce the SES-CD, induce 
clinical remission, clinical response, and endoscopic healing of the mucosa

To evaluate the PK, PD, immunogenicity (if applicable), and biomarker response of 
JNJ‑67864238
SAMPLE SIZE DETERMINATION
The sample size determination is based on the overall population, including both Bio-IR and Bio-
NF participants. To examine the hypothesis that JNJ-active is superior to placebo as measured by 
CDAI, sample size is planned to achieve desirable operating characteristics of a predefined 
decision-making framework through simulation. A 90 Bio-IR or Bio-NF participants will provide 
about 90% power when the true treatment difference is 60 (placebo – JNJ-67864238) with standard 
deviation of 93 in the change in CDAI at Week 12 for both Bio-IR and Bio-NF populations.
POPULATIONS (ANALYSIS SETS) FOR ANALYSIS
For purposes of analysis, the following analysis sets are defined:
Analysis Sets
Description
Randomized
The randomized analysis set includes all participants 
who were randomized in the study.
Full Analysis Set (FAS)
All participants who are randomized to a treatment arm 
within an intervention cohort and receive at least 1 dose 
of the study intervention
Per Protocol (PP)
The per protocol analysis set (PP) includes a subset of 
participants in the full analysis set (FAS) who were in 
compliance with the protocol. Compliance is defined 
after reviewing by study physician and statistician 
Safety
All randomized participants who take at least 1 dose of 
the study intervention within an intervention cohort. 
Participants will be analyzed according to the study 
intervention they actually received
Pharmacokinetics Analysis Set
The PK analysis set is defined as participants who 
received at least 1 dose JNJ‑67864238 and have at least 
1 valid blood sample drawn for PK analysis.
Immunogenicity Analysis Set
The Immunogenicity analysis set is defined as 
participants who received at least 1 dose JNJ‑67864238
and have at least 1 valid blood sample drawn for 
Immunogenicity analysis.
STATISTICAL ANALYSES
5.1.
General Considerations
Descriptive statistics (eg, mean, median, SD, minimum, and maximum) will be used to summarize 
continuous variables. Counts and percentages will be used to summarize categorical variables. 
Graphic data displays may also be used to summarize the data. Analyses suitable for categorical 
data (eg, chi-square tests, Cochran-Mantel-Haenszel chi-square tests, or logistic regression, as 
appropriate) will be used to compare the proportions of participants achieving selected endpoints 


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(eg, clinical remission). In cases of sparse events, Fisher’s exact test will be considered for 
treatment comparisons. Continuous response parameters will be compared using a longitudinal 
model, an analysis of variance (ANOVA) model, or an analysis of covariance (ANCOVA) model. 
If non-normality is observed, then van der Waerden normal scores will be used to fit a model. For 
primary endpoint change from baseline in the CDAI score will be fit through a MMRM with 
categorical effects of population, treatment, time and treatment-by-time, and baseline CDAI score 
as a continuous covariate as needed, an appropriate external prior information will be incorporated 
in the form of a prior probability distribution function to evaluate various study hypotheses in a 
Bayesian framework. In such a framework, inference will be based on posterior probability 
distributions.
5.1.1.
Analysis Window
The study date and corresponding study visit/week will be captured on each case report form 
(CRF). Visit windows will be created around the study day of each scheduled visit. It will be used 
to aggregate data, which are to be summarized by visit. The visit windows and the targeted study 
day are indicated in Table 1. Details will be added later if more than one assessment falls within 
the same visit window. If an assessment is not scheduled for every visit, windows will be combined 
so that the interval between targeted study days is split evenly and consistently between visits. 
Table 1. Visit Windows
Scheduled Study Day 
Visit Window 
Screening
-999, -1
Week 0 Day 1* 
1, 7
Week 2 Day 1 (Day 15) 
8, 21
Week 4 Day 1 (Day 29) 
22, 42
Week 8 (Day 57) 
43, 70
Week 12 (Day 85) 
71, 98
Safety Follow-up (Week 16)
99, 999
* Study Day 1 begins on the day of randomization. Each Week consists of 7 days. 
5.2.
Participant Dispositions
The number of participants in the following disposition categories will be summarized throughout 
the study by intervention group and overall:

Participants who received study intervention

Participants who completed the study

Participants who discontinued study intervention

Reasons for discontinuation of study intervention

Participants who terminated study prematurely

Reasons for termination of study
The distribution of the time to [study termination/discontinuation of study intervention] will be 
displayed with Kaplan-Meier curves. Participants who terminate study participation 


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prematurely/discontinue study intervention at any time will be considered an ‘Event’ and their date 
of study termination/study intervention discontinuation will be used in the time to event 
calculation. Participants who complete [the study/study intervention] will be censored and the date 
of [study completion/last dose of study intervention] will serve as the time of censoring.
A listing of participants will be provided for the following categories:

Participants who discontinued study intervention

Participants who terminated study prematurely

Participants who were unblinded during the study period

Participants who were randomized yet did not receive study intervention.
5.3.
Primary Endpoint Analysis
Level of Significance: In general, all tests will be performed at a 2-sided significance level of 0.1, 
unless otherwise specified. All interval estimations will be reported using 2-sided 90% confidence 
intervals (CIs).
Multiplicity adjustment consideration will be based on an overall type I error rate of 0.1 (2-sided).
The hypothesis testing will be conducted in a hierarchical manner with the test on the primary
endpoint conducted first and the tests on major secondary endpoints conducted next. Within the
major secondary endpoints, the sequential gatekeeping approach in conjunction with graphical 
multiplicity control procedures will be applied. As the interim analysis (IA) will not lead to an 
early completion due to success, multiplicity adjustment is not required. Nominal p-values will be 
calculated for all treatment comparisons.
The efficacy analysis of the primary will be based on the full analysis set. Regardless of the 
actual treatments the participants received, efficacy data will be analyzed according to the initial 
randomization assignment for the treatment phase. 
5.3.1. Definition of Endpoint
The primary endpoint will be change from baseline in the CDAI score at Week 12 based on full 
analysis set. This will apply for both interim analysis and final analysis.
The CDAI is a validated multi-item measure of severity of illness derived as a weighted sum of 8 
different Crohn’s disease-related variables1. These 8 variables are: 

extra-intestinal manifestations

abdominal mass

weight

hematocrit

use of antidiarrheal drug(s) and/or opiate

total number of liquid or very soft stools

abdominal pain/cramps


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
general well-being. 
The last 3 variables are scored over 7 days by the participant on a diary card. For the total number 
of liquid or very soft stools, abdominal pain/cramps, and general well-being, if only 5 days or 6 
days of data are available for the calculation, the weights of 7/5 and 7/6, respectively, will be used 
for the calculation; if the values are recorded for less than 5 days, the component will not be 
calculated. 
At each timepoint, the CDAI score will only be calculated if ≥ 4 of the 8 components are available. 
If the CDAI score cannot be calculated (ie, <4 components available), the CDAI score will be 
considered missing. When at least 4 of the 8 components are available, any missing components 
will be imputed by carrying forward the last non-missing component.
The weight component of the CDAI will be based on the standard weight table (Attachment 5).
Subjects who do not return for evaluation or have a missing CDAI score at Week 12 will be considered 
to have no change at Week 12 from their baseline CDAI score.
Treatment Failure Rules:
Treatment failure rules will be applied for all efficacy endpoints unless otherwise specified. In 
such a case, baseline values (at Week 0) will be assigned from the point of treatment failure 
onward, regardless of the observed data, for continuous endpoints, and participants will be 
considered as not achieving the respective endpoints for dichotomous endpoints. Treatment failure 
rules override other data handling rules.
For dichotomous endpoints, participants who have a treatment failure are considered as not 
achieving the respective endpoints after treatment failure. For continuous endpoints, participants 
who have a treatment failure will have their baseline values carried forward after treatment failure 
onwards.
The treatment failure rules will be applied to determine the final CDAI score. The treatment failure 
rules override the actual observation of the CDAI score. Participants who have any of the following 
events prior to the Week 12 visit will be considered a treatment failure and will be considered to 
have no change at Week 12 from their baseline CDAI score, regardless of the actual CDAI score:

A Crohn’s disease-related surgery (with the exception of drainage of an abscess or seton 
placement) 

Discontinuation of study intervention due to lack of efficacy or due to an adverse event (AE) 
of worsening Crohn’s disease 

Specified changes in concomitant Crohn’s disease medications described below.
The treatment failure rules for physician prescribed concomitant medication changes between
Week 0 and Week 12 are:


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1. Corticosteroids:
a.
Initiation of oral corticosteroids (excluding budesonide) due to worsening Crohn’s disease.
b. Initiation of oral corticosteroids (excluding budesonide) for more than 7 days due to
reasons other than worsening Crohn’s disease.
c.
Initiation of oral budesonide due to worsening Crohn’s disease.
d. Initiation of oral budesonide for more than 7 days due to reasons other than worsening
Crohn’s disease.
e.
Increase by >= 5 mg above baseline in the prednisone equivalent dosage of oral
corticosteroids (excluding budesonide) due to worsening Crohn’s disease.
f.
Increase by >= 5 mg above baseline in the oral prednisone equivalent dosage of oral
corticosteroids (excluding budesonide) for more than 7 days due to reasons other than
worsening Crohn’s disease.
g. Increase by >= 3 mg above baseline in the dose of oral budesonide due to worsening
Crohn’s disease.
h. Initiation of IV corticosteroids due to worsening Crohn’s disease.
i.
Initiation of rectal corticosteroids due to worsening Crohn’s disease.
2. 5-ASA compounds:
a.
Initiation or increase of oral 5-ASA compounds due to worsening Crohn’s disease.
3. Immunomodulator agents:
a.
Initiation of oral 6-MP/AZA due to worsening Crohn’s disease.
b. Initiation of oral, subcutaneous, or intramuscular MTX due to worsening Crohn’s disease.
c.
Increase above baseline in the dose of oral 6-MP/AZA due to worsening Crohn’s disease.
d. Increase above baseline in the dose of oral, subcutaneous, or intramuscular MTX due to
worsening Crohn’s disease (with the same route).
4. Protocol-prohibited medications:
      An initiation of any of the following after baseline due to worsening Crohn’s disease:
a.
Immunomodulatory agents other than 6-MP/AZA or MTX (including but not limited to 6-
TG, cyclosporine, tacrolimus, sirolimus, mycophenolate mofetil).
b. Immunomodulatory biologic agents (including but not limited to TNF antagonists,
natalizumab, abatacept).
c.
Experimental Crohn’s disease medications (including but not limited to thalidomide,
briakinumab, vedolizumab, traficet, AMG 827).
5. Crohn’s disease related antibiotics:
a.
Initiation or change of antibiotics due to worsening Crohn’s disease.
5.3.2.
Estimand 
5.3.2.1.
Primary Estimand (Estimand 1)
The primary estimand uses a Composite Strategy that considers meeting the treatment failure (TF) 
criteria as an unfavorable outcome. This strategy aims to achieve an objective treatment effect.


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The primary estimand, the main clinical quantity of interest to be estimated in the study, is defined 
by the following components:
Treatment: Oral tablets 
 for a 12 week period 

Experimental: JNJ‑67864238 (PTG-200),
 
 

Control: Matching Placebo tablets 
Population: Participants with moderately to severely active Crohn’s disease, The target 
population consists of men or women 18 to 75 years of age with moderately to severely active
Crohn’s disease of at least 3 months’ duration, defined as a CDAI score ≥220 but ≤450 at Week 
0, with an SES-CD score ≥3 by central endoscopy read. Participants with a screening SES-CD 
score <3 can be randomized and received at least one study dose if they have an elevated CRP
(>0.3 mg/dL or 3.0 mg/L) or elevated fecal calprotectin (>250 μg/g). Participants must have colitis, 
ileitis, or ileocolitis previously confirmed at any time in the past by radiography, histology, and/or 
endoscopy.  Participants must be biologic intolerant or refractory (Bio-IR) or biologic nonfailures 
(Bio-NF) and must be on a stable dose of at least 1 protocol-permitted therapy for the treatment of 
Crohn’s disease prior to baseline and not receiving any protocol-prohibited therapies.  For more 
details and for a complete list of inclusion/exclusion criteria, please refer to the protocol. 
Variable (Endpoint): Change from baseline in the CDAI score at Week 12. Participants who have 
intercurrent events in categories 1-3 (defined below) prior to the Week 12 visit will have their 
baseline CDAI score assigned, regardless of the observed data.
Intercurrent Events and Corresponding Strategies: 
The following are the intercurrent events considered for this trial:
1. A Crohn’s disease-related surgery (with the exception of minor procedures such as 
drainage of a superficial abscess or seton placement, etc.);
2. A prohibited change in CD medication;
3. Discontinuation of study intervention due to lack of efficacy or an AE of worsening 
Crohn’s disease;
4. Discontinuation of study intervention due to COVID-19 related reasons (like missing the 
assessment visit due to COVID-19 quarantine, but excluding COVID-19 infection)
5. Discontinuation of study intervention due to reasons other than lack of efficacy or an AE 
of worsening Crohn’s disease (including AE/SAE due to COVID-19 infection).
Intercurrent events (ICEs) in categories 1-3 will be handled by the composite strategy, and ICE 
category 4 will be handled by the hypothetical strategy (as if subjects would have not experienced 
this intercurrent event), and ICE category 5 will be handled by the treatment policy strategy.  The 
composite strategy assesses the treatment effects not only based on the variable measurements, but 
also based on intercurrent events. This estimand acknowledges that having an intercurrent event
in categories 1-3 is an unfavorable outcome, ie. baseline value will be used after ICEs. For subjects 
experiencing ICE category 4, CDAI data at all visits after an ICE will be set to missing with 
CCI
CCI
CCI


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assumption of missing at random. For ICE category 5, treatment policy strategy, the observed 
values after ICEs will be used, if available.  
Population-level summary: The difference of change in the CDAI score at Week 12 between the 
Experimental treatment group and the placebo treatment group.
5.3.3. Analysis Methods
5.3.3.1.
Main Estimator (Analysis) for the Primary Estimand
The primary analysis will be based on the full analysis set which will include all participants 
randomized and who receive at least 1 dose of the study intervention. Participants in the efficacy 
analyses will be summarized according to their assigned treatment arm regardless of whether or 
not they receive the assigned study intervention. The primary endpoint will be analyzed based on 
the primary estimand.
Data used in the primary analysis (i.e. the main estimator for the primary estimand) include all 
values for change from baseline in CDAI score collected up to and including Week 12 for all 
participants in the primary efficacy analysis set (ie, those who were randomly assigned to study 
intervention and received at least one dose of study intervention.  Any CDAI score collected after 
experiencing intercurrent event categories 1-3 will be replaced by the baseline observation for 
CDAI. For subjects experiencing ICE category 4, CDAI data at all visits after an ICE will be set 
to missing with assumption of missing at random. For ICE category 5, treatment policy strategy, 
the observed values after ICEs will be used, if available.
The main estimator for the primary estimand is based on the Mixed Effects Model for Repeated 
Measures (MMRM), under the Missing at Random (MAR) assumption for the missing responses, 
the missing data will be accounted for through correlation of repeated measures in the model, to 
test the difference between the experimental group and the placebo group. The analysis will use 
change in CDAI scores at post-baseline time points through Week 12 as dependent variables. The 
explanatory variables of the MMRM model will include the fixed, categorical effects of treatment, 
time, and treatment-by-time interaction, as well as the continuous, fixed covariates of baseline and 
baseline-by-time interaction. If the intervention cohort includes both Bio-IR and Bio-NF 
participants, then the biologic therapy status will be included in the MMRM model as well. An 
unstructured variance-covariance structure will be used to model the within-participant errors. The 
treatment comparison at Week 12 in terms of the least square mean difference and confidence 
intervals for decision making will be estimated based on this model.
The estimates for the primary estimand of the treatment difference between each experimental
group and the placebo group will be provided by the difference in the least squares means 
(LSmeans). The 90% confidence interval (CI) for the differences in LSmeans and p-values will be 
calculated based on the MMRM. An unstructured covariance matrix for repeated measures within 
a subject will be used.  
5.3.3.2.
Sensitivity and Supplementary Estimand for Primary Endpoint
To examine the robustness of the primary estimator under the different assumption from the main 
estimator. Sensitivity estimators will be conducted for primary estimand


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Sensitivity Estimator 1:

Assumption: Consider different analysis population

Sensitivity Estimator Per-protocol analysis: participants with major deviations/identified by 
SRP (study responsible physician) will be excluded. 
Sensitivity Estimator 2:

Assumption: Consider different statistical model ANCOVA

Sensitivity Estimator An ANCOVA model will be applied with the change from baseline in 
the CDAI at Week 12 as the response variable, treatment and population status (Bio-IR and 
Bio-NF) as fixed factors, and baseline CDAI score as a covariate.
Sensitivity Estimator 3:

Assumption: Consider background concomitant medication steroids tapering as treatment 
failure

Sensitivity Estimator: Imputing CDAI score based on last value carried forward (LVCF)
method for participates who have any steroids tapering prior to week 8. 
Other exploratory estimators may be conducted as necessary including but are not limited to 

Completer analysis for participant who completed week 12 treatment

Imputing the CDAI score using the values prior to the treatment failure (ICE category 1-3) or 
prior to COVID-19 related ICE categories 4 and 5, 

Observed CDAI without incorporating treatment failure 
5.3.3.3.
Supplementary Estimand for Primary Endpoint
Estimand 2
Composite strategy: This supplementary estimand will be same as Estimand 1 except for ICE 
categories 4 and 5, ICE categories 4 and 5 will be handled same as ICEs categories 1-3: baseline 
CDAI values will be used at all visits after an ICE.  
Analysis for Estimand 2:
For testing of the primary endpoint using the supplementary estimand 3, the change from baseline 
in the CDAI score at Week 12 will be compared between experimental group and the placebo 
group using MMRM with categorical effects of population, treatment, time and treatment-by-time, 
and baseline CDAI score as a continuous covariate, with assumption of missing at random.
Estimand 3
Hypothetical strategy: This supplementary estimand will be handled by the hypothetical strategy
for ICE categories 1-5: CDAI data at all visits after an ICE will be set to missing and assuming 
missing at random.  
Analysis for Estimand 3:


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For testing of the primary endpoint using the supplementary estimand 3, the change from baseline 
in the CDAI score at Week 12 will be compared between experimental group and the placebo 
group using MMRM with categorical effects of population, treatment, time and treatment-by-time, 
and baseline CDAI score as a continuous covariate, with assumption of missing at random.
Estimand 4
Tipping point method: This supplementary estimand will be used to assess the robustness of 
primary estimand using tipping point method to assess COVID-19 ICE impact as appropriate. For 
the change from baseline in CDAI, a delta adjustment multiple imputation method will be 
performed to evaluate the impact of missing data when deviating from the MAR assumption.
This method will employ the following 3 steps:
Step 1 - Multiple Imputation (MI)
Preparing monotone missing data pattern, and then run MAR-based multiple imputation with the 
regression option to impute missing values. For subjects with a non-monotone missing data 
pattern, ie, subjects may have ‘intermediate missing’ data between non-missing observations, 
imputing the intermediate missing values using the MCMC (Markov Chain Monte Carlo) 
method. This will be done using SAS PROC MI.
Step 2 - Delta Adjustments
The imputed values for subjects who discontinued will be adjusted by adding Delta () to the 
results from step 1. Delta-adjusted fully imputed datasets will be generated for different 
combinations of values for active treatment group and place group as defined below:

= 0 to tipping point value of Δ by incremental of 1 to active treatment only

= 0 to tipping point value of Δ by incremental of 1 to active treatment; for control 
group, = half of active treatment adjustment

= 0 to tipping point value of Δ by incremental of 1 for both active treatment and 
placebo groups
Step 3 – Analysis and Pooling
For each combination described in step 2:

Run MMRM model for each set of the adjusted datasets, the p-values for testing the 
treatment difference will be obtained.

Multiple imputation combining rules in PROC MIANALYZE will be applied to the 
MMRM
The delta adjustment method will be applied for two scenarios:

To all subjects who discontinued due to ICE categories 4 and 5. 

To all subjects who discontinued, except those with a discontinuation reason that was not 
considered related to the study drug, ie. lost to follow-up. 


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Analysis for Estimand 4:
For testing of the treatment benefit impacted by COVID-19, a turning point threshold will be 
explored based on PTG-200 treatment effect.
5.3.4. Subgroup Analysis  
The consistency of treatment effect for the primary endpoint will be evaluated for the subgroups 
defined in Section 5.7.8.  For each of these subgroups, the difference of experimental group vs 
placebo in the change from baseline in the CDAI score at Week 12 and the associated 90% 
confidence interval will be provided. The same data handling rules will be applied as the primary 
efficacy analysis. 
5.3.5. Multiplicity Adjustment for Secondary Endpoints
Inferential hypothesis testing will be conducted in a hierarchical manner with the test on the 
primary endpoint conducted first. Major secondary endpoints will be conducted only if the primary
analysis of CDAI change from baseline achieves statistical significance. Within the major 
secondary endpoints, the gatekeeping approach in conjunction with graphical multiplicity control 
procedures will be applied. All statistical significance levels are defined at a 2-sided alpha of 0.1.
5.4.
Secondary Endpoint(s) Analysis 
5.4.1. Key Confirmatory Secondary Endpoint
5.4.1.1.
Definition of Endpoint(s)
The major secondary endpoints include the following at Week 12: 

Change in the SES-CD from baseline

Clinical response as measured by CDAI (≥100-point reduction from baseline in CDAI or 
CDAI <150)

Clinical remission rate as measured by CDAI (CDAI <150)

PRO-2 remission defined as abdominal pain (AP) mean daily score (AP component of 
the CDAI) at or below 1 AND stool frequency (SF) mean daily score at or below 3, ie, 
AP ≤1 and SF ≤3

Endoscopic response (defined as at least a 50% improvement from baseline in the SES-
CD)

Endoscopic remission (defined as an SES-CD score ≤2)
The (SES-CD) is a scoring system developed to provide a more granular evaluation of endoscopic 
disease severity in patients with Crohn’s disease. It is constructed based on the evaluation of 4 
endoscopic components across 5 predefined ileocolonic segments. The 4 endoscopic components 
within each segment are:  the presence/ size of ulcers, the proportion of mucosal surface covered 
by ulcers, the proportion of mucosal surface affected by any other lesions, and the presence/ type 
of narrowing (also commonly referred to as strictures/ stenosis clinically).  Each endoscopic 
component is scored from 0 to 3 for each segment, and a total score is calculated as a sum of all 
the component scores across all the segments, as outlined in Attachment 4. The total SES-CD score 
ranges from 0 to 56.


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Calculation of the SES-CD score:
Main approach (SES-CD calculated based on all segments available): 
The total SES-CD score at a visit will be calculated based on all segments scored at the visit. If the 
total SES-CD score cannot be calculated (i.e., no segment is scored) at a visit, the total SES-CD 
score will be considered missing.  
Alternative approach (baseline segments matched approach):
To calculate the SES-CD score at a visit, the sum of the segments that were present at baseline 
will be used. For segments that were present at baseline but missing post-baseline, the baseline 
score for the missing segment(s) will be carried forward.  In the event that a segment is missing at 
baseline but non-missing at post-baseline, the non-missing post-baseline score is not used in the 
calculation of SES-CD. 
The Week 12 SES-CD Total score will be calculated only if the participant has a Week 12 
endoscopy and at least one segment is evaluable.  For segments evaluated and scored at baseline 
but not at Week 12, associated baseline segment scores will be carried forward to calculate the 
Total SES-CD score at Week 12.  Otherwise, the Week 12 Total SES-CD will be missing.
Participants who meet 1 or more treatment failure rules (as specified for the primary endpoint) 
before Week 12 will be considered not to be in clinical remission, clinical response or clinical-
biomarker response, either based on CDAI or PRO-2. For endoscopic response, the same treatment 
failure rules will be applied as appropriate. Any missing values at week 12 will be considered as 
no responder/remitter.
5.4.1.2.
Estimands 
The following describes the attributes of the estimands for the major secondary endpoints:
Treatment by Week 12: Same as Estimand 1, ie:
Treatment: 
 for a 12 weeks period 

Experimental: JNJ‑67864238 (PTG-200), 
 
 

Control: Matching Placebo tablets 
Population: Participants with moderately to severely active Crohn’s disease, 
Variables and Population-level Summary (for Estimands 5-10)
Table 2: 
Variables and Population-level Summary for the estimand for each Major Secondary Endpoint
Estimand
Variable (Endpoint)
Population-level summary
5
Change in the SES-CD from baseline
(both main approach and alternative 
approach analyses will be performed)
Change from baseline in the SES-CD score at 
Week 12 or early withdrawal visit between 
experimental group and placebo.
CCI
CCI
CCI


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6
Clinical response as measured by CDAI 
(≥100-point reduction from baseline in 
CDAI or CDAI <150)
Difference in percentage of subjects who achieved 
clinical response at Week 12 between experimental 
group and placebo.
7
Clinical remission rate as measured by 
CDAI (CDAI <150)
Difference in percentage of subjects who achieved 
clinical remission at Week 12 between 
experimental group and placebo.
8
PRO-2 remission defined as abdominal 
pain (AP) mean daily score (AP 
component of the CDAI) at or below 1 
AND stool frequency (SF) mean daily 
score at or below 3, ie, AP ≤1 and SF ≤3
Difference in percentage of subjects who achieved 
PRO-2 remission at Week 12 between 
experimental group and placebo.
9*
Endoscopic response (defined as at least a 
50% improvement from baseline in the 
SES-CD)
(both main approach and alternative 
approach analyses will be performed)
Difference in percentage of subjects who achieved 
endoscopic response at Week 12 between 
experimental group and placebo.
10
Endoscopic remission (defined as an SES-
CD score ≤2)
(both main approach and alternative 
approach analyses will be performed)
Difference in percentage of subjects who achieved 
endoscopic remission at Week 12 between 
experimental group and placebo.
* For Endoscopic response, please refer to below prohibited medications for ICE category 2

Immunomodulatory agents other than AZA, 6-MP, or MTX (including, but not limited to, 6-TG, cyclosporine, mycophenolate mofetil, 
tacrolimus, and sirolimus).

Immunomodulatory biologic agents (including, but not limited to, TNF antagonists, natalizumab, ustekinumab, rituximab, vedolizumab). 
Ustekinumab is permitted in this study only in participants randomly assigned to ustekinumab and only as stipulated in this protocol.

Experimental Crohn’s disease medications (including, but not limited to, upadacitinib, filgotinib, ozanimod, etrolizumab, brazikumab, 
mirakizumab [formerly LY-3074828], risankizumab, GS-5745)

Thalidomide or related agents.
Intercurrent Events and Corresponding Strategies: 
The intercurrent events for all major secondary endpoints other than endoscopic response at Week 
12 will be same as those used in the primary estimand, and are as follows: 
1. A Crohn’s disease-related surgery (with the exception of minor procedures such as drainage 
of a superficial abscess or seton placement, etc.);
2. A prohibited change in CD medication;
3. Discontinuation of study intervention due to lack of efficacy or an AE of worsening Crohn’s 
disease;
4. Discontinuation of study intervention due to COVID-19 related reasons (like missing the 
assessment visit due to COVID-19 quarantine, but excluding COVID-19 infection)
5. Discontinuation of study intervention due to reasons other than lack of efficacy or an AE of 
worsening Crohn’s disease (including AE/SAE due to COVID-19 infection).


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ICEs will be handled by the same Estimands strategies as the primary Estimands strategies for the 
major secondary endpoints including clinical remission, clinical response, PRO-2 remission, 
endoscopic response (refer to Table 2 footnotes for ICE category 2), or endoscopic remission.
5.4.1.3.
Analysis Methods for the Estimands for the Major Secondary 
Endpoints
The major secondary endpoints of clinical remission (either based on CDAI, SES-CD, or PRO-2), 
clinical response, endoscopic response, and clinical-biomarker response at Week 12 will be 
compared between PTG-200 group and the placebo group. 
A logistic regression model will be used in the responder analyses with the treatment arm and 
population status (Bio-IR or Bio-NF), if applicable, as fixed factors, at 2-sided significance level of 
0.1. In this model, baseline measurements may be included as covariates as appropriate. The 
change from baseline in the SES-CD score at Week 12 will be evaluated using MMRM model in 
comparing treatment difference by LS Mean (SD), LS mean (90% CI). P-Value was based on 
comparison with placebo model. And other statistical analysis as appropriate.
5.4.2.
Supportive Endpoint(s)
Other endpoints to be evaluated across all post-baseline visits as appropriate:

Change in AP from baseline based on a 0 to 10 numerical rating scale (NRS)

Change in number of daily loose or watery stools

Changes from baseline in the CDAI, PRO-2 (the sum of AP and SF subscores of the 
CDAI score), PRO-3 (the sum of AP, stool frequency, and general well-being subscores 
of the CDAI score), C-reactive protein (CRP), and fecal calprotectin

Clinical remission (CDAI <150), PRO-2 remission (AP ≤1 and SF ≤3), and clinical 
response based on CDAI

Endoscopic improvement based on a reduction from baseline in the SES-CD score (≥3 
points, 25%, 50%), (both main approach and alternative approach analyses will be 
performed)

Endoscopic healing (defined as the absence of mucosal ulcerations), (both main approach 
and alternative approach analyses will be performed)

Patient’s Global Assessment of Crohn’s Disease Activity

Change from baseline in multivariate score of biomarkers measured in mucosal biopsy 
samples, whole blood, serum, and/or stool

Change in PROs as measured by the PROMIS-29 score
ICEs will be handled by the same Estimands strategies as the primary Estimands strategies for the 
supportive secondary endpoints.  Participants who do not return for evaluation or have missing AP 
or SF scores at Week 12 will be considered not to be in PRO-2 remission (ie, clinical remission
measured by AP and SF). Participants who do not return for evaluations or have missing CRP or 
fecal calprotectin values at Week 12 will be considered not to be in clinical-biomarker response 
unless the non-missing values at Week 12 already confirm a clinical-biomarker response. Any 
missing values at week 12 will be considered as no responder/remitter.


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5.4.2.1.
Analysis Methods
Descriptive statistics (i.e., mean, median, SD, IQ range, minimum, and maximum) will be used to 
summarize continuous variables. Counts and percentages will be used to summarize categorical 
variables. Graphical data displays (e.g., line plots) may also be used to summarize the data. The 
statistical model specified in the major secondary section will be applied for the other efficacy 
endpoints as appropriate.
5.5.
Tertiary/Exploratory Endpoint(s) Analysis
Exploratory analysis will be performed to understand the potential factors of regional and/or 
subpopulation variability such as covariate-adjusted analyses, subgroup summaries if it is 
necessary.
5.6.
Safety Analyses
Safety summaries will be based on the safety analysis set and participants will be analyzed based 
on the treatment the participants received. 
For all continuous safety variables, descriptive statistics by intervention group will include the N, 
mean, standard deviation, median, minimum, and maximum. Categorical variables will be 
summarized by intervention group using frequency counts and percentages.
Safety analyses will be based on observed data (i.e., no data imputation).
5.6.1.
Extent of Exposure
The number and percentage of participants who receive study intervention will be summarized by 
intervention group.
Study intervention duration is defined as (date of last dose of study intervention – date of first dose 
of study intervention) +1. Descriptive statistics for duration of study intervention (N, mean, SD, 
median, and range (minimum, maximum)) will be summarized by intervention group.
Total dose days of intervention is defined as the total number of days that study intervention was 
administered to the participant (excluding days off study intervention).
The number (%) of participants with a dose adjustment will be summarized by intervention group.
Reasons for dose adjustments will also be summarized intervention group.
Descriptive statistics will be presented for the following parameters:

Number of administrations

Cumulative total dose

Mean daily dose
The mean daily dose of study intervention is calculated as (sum of total daily dose during the 
intervention phase)/total dose days of intervention.


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5.6.2.
Adverse Events
The verbatim terms used in the CRF by investigators to identify adverse events will be coded using 
the Medical Dictionary for Regulatory Activities (MedDRA). Any AE occurring at or after the 
initial administration of study intervention through the day of last dose plus 30 days is considered 
to be treatment emergent. If the event occurs on the day of the initial administration of study 
intervention, and either event time or time of administration are missing, then the event will be 
assumed to be treatment emergent. If the event date is recorded as partial or completely missing, 
then the event will be considered to be treatment emergent unless it is known to be prior to the first 
administration of study intervention based on partial onset date or resolution date. All reported 
treatment-emergent adverse events will be included in the analysis.  For each adverse event, the 
number and percentage of participants who experience at least 1 occurrence of the given event will 
be summarized by intervention group.
Summary tables will be provided for treatment-emergent adverse events:

AEs

Serious adverse events (SAEs)

AEs leading to discontinuation of study agent

Reasonably related AEs.

Infections, including infections requiring with an oral or parenteral antibiotic treatment.

Serious infections.
An infection is defined as any AE that was characterized by the investigator as an infection on the 
eCRF.
In addition to the summary tables, listings will be provided for participants who:

Had SAEs

Had AEs leading to discontinuation of study intervention/termination of study participation
A listing of participants who died will be provided.
Incidence of other treatment-emergent adverse events of [clinical, special] interest will be 
summarized as necessary.
5.6.3.
Additional Safety Assessments
5.6.3.1.
Clinical Laboratory Tests
Clinical laboratory tests will be displayed for the participants included in the safety analysis set.
Clinical laboratory values are to be graded using National Cancer Institute Common Terminology 
Criteria for Adverse Events (NCI-CTCAE) version 5.0 (see Table 3). Descriptive statistics and 
graphical displays will be presented for chemistry and hematology at scheduled time points.
Change/percent change from baseline to time point will be summarized for chemistry, hematology, 
tests and displayed by intervention group. 


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
Summary of the observed values and changes from baseline over time through the final 
efficacy & safety visit for clinical laboratory parameters. 

Summary of maximum NCI-CTCAE toxicity grade for postbaseline laboratory values through 
Week 12 and through the final efficacy & safety visit for clinical laboratory parameters listed 
in Table . For toxicity grades, treatment emergent (TE) will be concluded if the postbaseline 
value is worse than the baseline value.

Shift tables for selected clinical laboratory parameters (ALT, AST, alkaline phosphatase and 
total bilirubin) at Week 12.

For abnormalities based on normal range and/or criteria: If the postbaseline value is above the 
upper limit and the baseline value is below the upper limit (eg, Normal or Low), then the 
postbaseline abnormality will be considered TE. The same applies to the postbaseline value 
being below the lower limit with the baseline value being above the lower limit (eg, Normal 
or High).

If the baseline value is missing, a postbaseline abnormality will always be considered as TE.
Listings of participants with any abnormal postbaseline laboratory values of CTCAE grade ≥2 will 
also be provided. 
The laboratory data to be summarized are as follows:

Hematology assessments: hematocrit, hemoglobin, platelet count, total leukocytes and 
differential WBC count (neutrophils, lymphocytes, monocytes, eosinophils, and basophils) 

Blood chemistry assessments: ALT, AST, alkaline phosphatase, albumin, total and direct 
bilirubin, blood urea nitrogen, calcium, chloride, creatinine, phosphate, potassium, total 
protein, and sodium.
The baseline value for a participant is the value closest to but prior to the first dose of study agent 
(Week 0). Change from baseline is defined to be the assessment at the postbaseline visit minus the 
assessment at baseline. Summaries of laboratory data will be completed using all the available 
laboratory data at the time point of interest without imputing missing data. Shift tables summarize 
the number of participants with low, normal, and high values (determined by the laboratory normal 
ranges) at the post baseline visit for each of the classifications of low, normal, and high at baseline. 


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Table 3:
Grading Criteria for Clinical Laboratory Tests [CTCAE Version 5.0]
Table 3:Grading Criteria for Clinical Laboratory Tests [CTCAE Version 5.0]
Hematology Tests
Criteria
Test
Direction
1
2
3
4
Hemoglobin (g/dL)
Increase
>0 - 2 
>2 - 4
>4
Hemoglobin (g/dL)
Decrease
<LLN - 10.0 
<10.0 - 8.0 
<8.0 
Lymphocytes (/mm3)
Increase
>4000 -
20,000
>20,000
Lymphocytes (/mm3)
Decrease
<LLN - 800
<800 - 500
<500 - 200
<200
Neutrophils (/mm3)
Decrease
<LLN - 1500 
<1500 - 1000 
<1000 - 500
<500
Platelets (/mm3)
Decrease
<LLN - 75,000
<75,000 -
50,000
<50,000 -
25,000
<25,000
Total WBC count 
(/mm3)
Increase
>100,000
Total WBC count
(/mm3)
Decrease
<LLN - 3000
<3000 - 2000
<2000 - 1000
<1000 
Chemistry Tests
Criteria
Test
Direction
1
2
3
4
ALT
Increase
>ULN - 3.0 x 
ULN if 
baseline was 
normal; 1.5 -
3.0 x baseline 
if baseline was 
abnormal
>3.0 - 5.0 x 
ULN if 
baseline was 
normal; >3.0 -
5.0 x baseline 
if baseline 
was abnormal
>5.0 - 20.0 x 
ULN if 
baseline was 
normal; >5.0 -
20.0 x 
baseline if 
baseline was 
abnormal
>20.0 x ULN 
if baseline 
was normal; 
>20.0 x 
baseline if 
baseline was 
abnormal
AST
Increase
>ULN - 3.0 x 
ULN if 
baseline was 
normal; 1.5 -
3.0 x baseline 
if baseline was 
abnormal
>3.0 - 5.0 x 
ULN if 
baseline was 
normal; >3.0 -
5.0 x baseline 
if baseline 
was abnormal
>5.0 - 20.0 x 
ULN if 
baseline was 
normal; >5.0 -
20.0 x 
baseline if 
baseline was 
abnormal
>20.0 x ULN 
if baseline 
was normal; 
>20.0 x 
baseline if 
baseline was 
abnormal
Albumin (g/L)
Decrease
≥30 - <LLN
≥20 - <30
<20
Alkaline Phosphatase
Increase
>ULN - 2.5 x 
ULN if 
baseline was 
normal; 2.0 -
2.5 x baseline 
if baseline was 
abnormal
>2.5 - 5.0 x 
ULN if 
baseline was 
normal; >2.5 -
5.0 x baseline 
if baseline 
was abnormal
>5.0 - 20.0 x 
ULN if 
baseline was 
normal; >5.0 -
20.0 x 
baseline if 
baseline was 
abnormal
>20.0 x ULN 
if baseline 
was normal; 
>20.0 x 
baseline if 
baseline was 
abnormal
Bilirubin (total)
Increase
>ULN - 1.5 x 
ULN if 
baseline was 
normal; > 1.0 -
1.5 x baseline 
if baseline was 
abnormal
>1.5 - 3.0 x 
ULN if 
baseline was 
normal; >1.5 -
3.0 x baseline 
if baseline 
was abnormal
>3.0 - 10.0 x 
ULN if 
baseline was 
normal; >3.0 -
10.0 x 
baseline if 
baseline was 
abnormal
>10.0 x ULN 
if baseline 
was normal; 
>10.0 x 
baseline if 
baseline was 
abnormal
Corrected Calcium* 
(mmol/L)
Increase
>ULN - ≤2.9
>2.9 - ≤3.1
>3.1 - ≤3.4
>3.4


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Corrected Calcium 
(mmol/L)
Decrease
≥2.0 - <LLN
<2.0 - ≥1.75
<1.75 - ≥1.5
<1.5
Creatinine
Increase
>ULN - ≤1.5 
xULN
>1.5 - 3.0 x 
baseline; >1.5 
- 3.0 x ULN
>3.0 x 
baseline; >3.0 
- 6.0 x ULN
>6.0 xULN
Glucose (mmol/L)
Decrease
<LLN - 3.0 
<3.0 - 2.2 
<2.2 - 1.7 
<1.7 
Potassium (mmol/L)
Increase
>ULN - ≤5.5
>5.5 - 6.0
>6.0 - 7.0
>7.0
Potassium (mmol/L)
Decrease
<LLN - 3.0
<3.0 - 2.5
<2.5
Sodium (mmol/L)
Increase
>ULN - 150
>150 - 155
>155 - 160
>160
Sodium (mmol/L)
Decrease
<LLN - 130
129 - 125
124 - 120
<120
5.6.3.2.
Vital Signs and Physical Examination Findings
Vital signs are measured at every visit. The listing for participants with clinically important results 
will be provided as appropriate. 
Continuous vital sign parameters collected will be summarized at each assessment time point. 
Descriptive statistics (mean, standard deviation, median, minimum and maximum) will be 
presented by intervention groups.
5.6.3.3.
Electrocardiogram
The listing for participants with clinically important results will be provided as appropriate.
5.7.
Other Analyses
5.7.1.
Pharmacokinetics
PK analyses will be based on the Pharmacokinetics Analysis Set (Section 4).
5.7.1.1.
PTG-200 Concentrations
Blood, colonic tissue and fecal samples for determining PTG-200 concentrations will be collected 
from all participants according to the schedule in the Protocol Schedule of Activities. Plasma, 
colonic tissue and fecal PTG-200 concentrations will be used to evaluate local and systemic drug 
exposure.
Plasma, colonic tissue and fecal PTG-200 concentrations will be summarized using descriptive 
statistics (i.e., n, arithmetic mean, standard deviation [SD], coefficient of variation [%CV],
median, range [minimum and maximum], and interquartile [IQ] range) at each visit. PK data may 
be displayed graphically. 
The following analyses will be performed as appropriate.

Summary of plasma PTG-200 concentration over time 

Proportion of participants with plasma PTG-200 concentration below the lowest quantifiable 
concentration in a sample at each visit  

Summary of plasma PTG-200 concentrations over time by baseline body weight (quartiles). 
Other covariates may also be applied.

Plots of median plasma PTG-200 concentrations over time 


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
Plots of median plasma PTG-200 concentrations over time by baseline body weight (≤median, 
>median).
As applicable, a similar approach as described above for plasma PTG-200 concentration will also 
be applied to colonic tissue and fecal PTG-200 concentrations.
5.7.1.2.
Data Handling Rules
Unless otherwise specified, the following data handling rules will apply to PK sample analyses:

Plasma concentration summaries will be based on the actual treatment received. 

All plasma, colonic tissue and fecal concentration summaries for a particular timepoint will 
include data obtained from treated participants at the timepoint of interest without imputing 
any missing data. 

A concentration not quantifiable (below the lower limit of quantification) will be treated as 0 
in the summary statistics and shown as the lower limit of quantification (< LLOQ) in the data 
listings. 

The data from a participant who meets 1 of the following dosing deviation criteria will be 
excluded from the by-visit data analyses from that point onwards:

Discontinued study agent administrations

Skipped an administration

Received an incomplete/ incorrect dose 

Received an incorrect study agent

Received an additional dose

Received an administration outside the dosing window specified in Table .
Table 4:
Dosing Window
Visit
Window
Week 0 through Week 12
± 5 days from scheduled visit day
Final Safety and Efficacy Follow-up visits
± 14 days from scheduled visit day
All participants and samples excluded from the analysis will be clearly documented in the Clinical 
Study Report.
5.7.1.3.
PK vs Efficacy
To explore the relationship between PTG-200 plasma, colonic tissue or fecal concentrations and 
efficacy endpoints, the following analyses may be explored: 

The relationship between PTG-200 plasma, colonic tissue or fecal concentrations (quartiles) 
and change from baseline in CDAI score, clinical response and clinical remission status at 


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Week 8 or Week 12 may be explored. Summaries by Bio-IR status (yes or no) (i.e., Bio-IR 
and Bio-NF) and by SNP status (positive or negative) may also be provided.
5.7.2.
Immunogenicity
5.7.2.1.
Antibodies to PTG-200
Immune response analyses will be based on the Immunogenicity Analysis Set.
The antibody to PTG-200 status (positive at any time, negative) and titers will be summarized by 
treatment group for participants who receive a dose of PTG-200 and have appropriate samples for 
detection of antibodies to PTG-200 (ie, participants with at least 1 sample obtained after their first 
dose of PTG-200). The maximum titers of antibodies to PTG-200 will be provided for participants 
who are positive for antibodies to PTG-200.
A listing of participants who are positive for antibodies to PTG-200 will be provided. The sample 
antibody status, the titer, and the neutralizing antibody status to PTG-200 will be listed by visit. 
This listing will also provide information regarding dose administered, PTG-200 plasma 
concentration, and CDAI for all applicable visits. In addition, a list of antibody to PTG-200 status 
in participants who discontinued study agent early will be provided.
5.7.2.2.
Neutralized Antibodies to PTG-200
The incidence of neutralizing antibodies (NAbs) to PTG-200 will be summarized for participants 
who are positive for antibodies to PTG-200 and have samples evaluable for NAbs to PTG-200.
5.7.2.3.
Antibody vs Efficacy/PK
Plasma PTG-200 concentrations, clinical remission/response status, and change from baseline in 
the CDAI score over time may be summarized by antibody to PTG-200 status if sufficient numbers 
of participants are positive for antibodies. Plots of median plasma PTG-200 concentrations over 
time by antibody to PTG-200 status may also be provided. The evaluation between colonic tissue 
PTG-200 concentration and the identified efficacy parameters will be performed as appropriate.
5.7.3.
Pharmacogenomic 
A whole blood sample collection for SNPs and DNA analysis will be collected from all participants 
at Screening who have signed an optional pharmacogenomics consent form. DNA testing will be 
done to search for links of specific genes to disease or response to JNJ-67864238 drug. Exploratory 
genetic analyses on DNA collection from participants who signed the optional DNA consent will 
be presented in a separate technical report.
5.7.4.
Pharmacokinetic/Pharmacodynamic Relationships
The relationship between plasma concentration of PTG-200 and PD may be analyzed graphically. 
Similarly, the relationship between colonic tissue or fecal PTG-200 concentration and PD 
endpoints listed above may be analyzed graphically. If any visual trend is observed, a suitable 
PK/PD model may be developed to describe the exposure-response relationship. In the latter case, 
the results of the PK/PD modeling analysis will be presented in a separate technical report.


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5.7.5.
Biomarker Analyses
Biomarker assessments will be conducted to examine the biological response to treatment and to 
identify biomarkers that are relevant to PTG-200 treatment and/or Crohn’s disease. Assessments 
include the evaluation of relevant biomarkers in serum, whole blood (for RNA analysis), stool, 
and mucosal biopsy samples (for protein, RNA and histology analysis) collected according to the 
Schedule of Activities in the protocol.
Biomarker analyses will characterize the effects of PTG-200 on the measured biomarkers to 
identify biomarkers relevant to treatment and to determine if these biomarkers can predict response 
to PTG-200. Results will be reported in separate technical reports.
5.7.6.
Health Economics
5.7.6.1.
PROMIS 29
The PROMIS-29 profile instrument is intended for adults (ages 18 years and older). It is a
collection of short forms containing 4 items for each of 7 PROMIS domains: Depression, Anxiety, 
Physical Function, Pain Interference, Fatigue, Sleep Disturbance, and Ability to Participate in 
Social Roles and Activities. The PROMIS-29 instrument also includes a Pain Intensity 0-10 NRS 
in addition to the 7 domains. PROMIS-29 is a universal rather than disease-specific instrument. It 
assesses all domains over the past 7 days, except for the Physical Function domain, which has no 
specified timeframe. The raw score of each domain is converted into a standardized score with a 
mean of 50 and a standard deviation (SD) of 10 (T-Score). The standardized T-score is reported 
as the final score for each participant. Pain Intensity is presented as raw responses (0-10). For the 
PROMIS domains of Depression, Anxiety, Physical Function, Pain Interference, and Fatigue, a 
score of 50 is the mean for the United States general population with an SD of 10 (validated with 
a large sample of the general US population). Since the other 2 domains (Ability to Participate in
Social Roles and Activities and Sleep Disturbance) were not validated with a national sample, a 
score of 50 represents the mean of the calibration sample (which was enriched for chronic illness 
so a score of 50 represents a sicker population). A higher PROMIS T-score represents more of the 
domain being measured. For negatively-worded domains like Anxiety, a T-score of 60 is 1 SD 
worse than average. By comparison, an Anxiety T-score of 40 is 1 SD better than average. 
However, for positively-worded domains like Physical Function, a T-score of 60 is better than 
average.
PROMIS surveys will only be collected in countries where translations are available.
5.7.6.2.
Analysis Method
The analysis will be performed at Week 12. The analysis will include descriptively summarizing 
change from baseline in PROMIS-29 score. Using MMRM model in comparing treatment 
difference by LS Mean (SD), LS mean (90% CI). p-Value was based on comparison with placebo
model. And other statistical analysis as appropriate.
5.7.7.
Other Variables and/or Parameters
Not applicable.


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5.7.8.
Definition of Subgroups
Subgroups of interest in this study include but not limited to:
1.
Population
a.
BIO-IR vs BIO-NF
2.
Demographics at baseline:
a.
Age (≤median age, >median age)
b.
Sex (male, female)
c.
Race (White, non-White)
d.
Weight at baseline (≤ median, > median; ≤ 1st quartile, >1st quartile and ≤ 2nd quartile, 
>2nd quartile and ≤ 3rd quartile, >3rd quartile) 
e.
Center location (North America, Rest of World)
3.
Disease characteristics at baseline:
a.
Crohn’s disease duration (5 years, > 5 years to 15 years, or > 15 years)
b.
Involved gastrointestinal areas (ileum only, colon only, ileum & colon)
c.
CDAI score (<300, ≥300 
d.
CRP (≤ 3 mg/L, > 3 mg/L)
e.
Fecal Calprotectin (≤250 µg/g, > 250 µg/g)
4.
Concomitant Crohn’s-disease medication at baseline:
a.
Oral corticosteroids (including budesonide and beclomethasone dipropionate) 
(receiving, not receiving)
b.
Oral 5-ASA compounds (receiving, not receiving)
c.
Immunomodulators (6-MP/AZA/MTX) (receiving, not receiving)
d.
Oral corticosteroids (including budesonide and beclomethasone dipropionate) and 
Immunomodulators (receiving, not receiving)
5.
Other:
a.
Current fistula at baseline (yes, no)
5.8.
Interim Analyses
An interim analysis is planned when approximately 50% of planned Participants reach their Week 
12 visit, which is approximately 45 Participants who received at least one administration of study 
agent (including a partial dose), have completed their Week 12 visit, or have terminated their study 
participation before Week 12. Additional ad hoc IA(s) may be conducted if deemed necessary. 
The objective of the IA(s) is to enable early termination of the intervention cohort if JNJ-67864238 
is futile and plan for future intervention cohorts. At the time of the IA(s), the study team will 
remain blinded. No DBL is planned for the IA. The statistical model specified in master protocol 
Section 9.4.2 and this document Section 5 will be used to evaluate the treatment difference at Week 


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12 using all available data. The interim analysis criteria are discussed in attachment 1. Interim 
analyses will be based on data that are as clean as possible.
An internal interim analysis committee independent of the study team will be established to review 
the interim data and formulate recommended decisions/actions in accordance with predefined 
decision rules. The details of interim analyses procure will be included in a separate interim 
analysis plan.
Interim Analysis Decision-Making Rules:
If neither change in CDAI nor change in SES-CD of the JNJ-67864238 
 
treatment arm meets the success criteria, the futility of the JNJ-67864238 
 
treatment arm will be considered. The futility is defined as follows:

Futility in change in CDAI: if upper bound (UB) (95%) <60 and lower bound (LB) (10%) <40, 
ie, the 95% upper confidence bound of the true mean treatment difference at Week 12 is less 
than 60 and its 90% lower confidence bound less than 40; and

Futility in change in SES-CD: if UB (95%) <1.6 and LB (10%) <0.4, ie, the 95% upper 
confidence bound of the true mean treatment difference at Week 12 is less than 1.6 and its 90% 
lower confidence bound less than 0.4.
If the futility criteria are met, the decision to terminate enrollment will be made based on a benefit risk 
assessment of the totality of data, including overall efficacy assessments, analysis of biomarker and 
PD data, and a safety review by the external data monitoring committee (DMC). If the futility criteria 
are not met and the DMC has not raised any safety issue, enrollment will continue until the planned 
sample size is reached. To augment decision-making, all available data at this IA, including from those 
participants without Week 12 assessments, will be analyzed. An Interim Analysis Committee will 
review the unblinded interim data and formulate recommendations (Section 9.5.1 of the Master 
protocol PLATFORMPACRD2001).
5.8.1.
Data Monitoring Committee (DMC) or Other Review Board
An external DMC will be established to monitor safety data on an ongoing basis to ensure the
continuing safety of participants enrolled in the study as noted in Committees Structure in platform 
protocol Appendix 5, Regulatory, Ethical, and Study Oversight Considerations. Please refer to 
DMC charter for details.
CCI
CCI


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SUPPORTING DOCUMENTATION
6.1.
Appendix 1 List of Abbreviations
5-ASA
5-aminosalicylate
6-MP
6-mercaptopurine
AE
adverse event
ANCOVA
analysis of covariance
AZA
Azathioprine
Bio-IR
biologic intolerant or refractory
Bio-NF
biologic nonfailure, ie, inadequate response to or failed to tolerate corticosteroids or 
immunomodulators, but not a biologic
CDAI
Crohn’s Disease Activity Index
CI
confidence interval
CRF
case report form
CRP
C-reactive protein
DPS
Data presentation specifications
MedDRA
Medical Dictionary for Regulatory Activities
MTX
Methotrexate
SAE
serious adverse event
SAP
Statistical Analysis Plan
SDC
Sponsor Decision Committee
SES-CD
Simple Endoscopic Score for Crohn’s Disease
SNP
Single Nucleotide Polymorphism
SSG
Statistical Support Group
TNF
tumor necrosis factor
ISA
DPS
PK
PD
DBL
DMC
IA
Intervention-Specific Appendix
Data Presentation Specifications
pharmacokinetics
pharmacodynamics
database lock
data monitoring committee
interim analysis


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6.2.
Appendix 2 Changes to Protocol-Planned Analyses
Based on protocol amendment to incorporate COVID-19 infection event, for primary endpoint 
point analysis, intercurrent events (ICEs) caused by COVID-19 infection will be addressed by 
treatment police strategy for primary estimator. In addition, hypothetical strategy to assume
missing at random after this ICE and tipping point method will be applied to assess the impact 
after COVID-19 ICEs in a sensitivity analysis as appropriate. Please refer to section 5.3.2 for 
details. For subject information and safety analyses, COVID-19 infection event will be tabulate in 
the corresponding tables and listings.


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6.3.
Appendix 3 Demographics and Baseline Characteristics
The number of participants in each analysis set will be summarized and listed by intervention 
group, and overall. In addition, the distribution of participants by region, country, and site ID will 
be presented unless otherwise noted.
Table 5 presents a list of the demographic variables that will be summarized by intervention group, 
and overall.  Demographics will also be summarized by region using the full analysis set.
To assess the comparability of participants, the following data will be summarized by treatment 
group based on the randomized analysis set:

Participants’ demographic data (i.e. age, gender, race, height, weight, and region)

Baseline disease characteristics (including endoscopic disease), and baseline use and history of 
Crohn’s disease medications 

Medical history of interest
Table 5:
Demographic and Baseline Disease Characteristic Variables
Continuous Variables:
Summary Type
Age (years)
Descriptive statistics (N, mean, 
standard deviation [SD], median 
and range [minimum and 
maximum], and IQ range).
Weight (kg)
Height (cm)
Crohn’s Disease Duration (yrs)
CDAI
PRO-2 (defined as the sum of the abdominal pain and stool frequency 
subscores of the CDAI score)
SES-CD
CRP Concentration (mg/L)
Fecal Calprotectin (mg/kg)
Categorical Variables
Race ([White, Black or African American, Asian, American Indian or 
Alaska Native, Native Hawaiian or Other Pacific Islander, Other, Not 
Reported and Unknown])
Frequency distribution with the 
number and percentage of 
Participants in each category.
Sex ([Male, Female])
Involved GI areas ([Ileum only, Colon only, Ileum and colon, Proximal 
gastrointestinal tract, and Perianal])
Extra intestinal manifestations ([Absent, Present])
Endoscopic disease severity (SES-CD score) ([Remission (0-2), Mild 
inflammation (3-6), Moderate inflammation (7-16) and Severe 
inflammation (>16)])
Abnormal CRP (>3 mg/L) ([Yes, No])
Abnormal fecal calprotectin (>250 mg/kg) ([Yes, No])
Crohn’s disease complications (Intra-abdominal abscess, Sinus tracts 
/perforation, Fistula, Bowel Stricturing]
Study Day and Relative Day: Study Day 1 or Day 1 refers to the day of the first study agent 
administration on or after the randomization date. All efficacy and safety assessments at all visits 
will be assigned a day relative to this date.


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Study day or relative day for a visit is defined as:

Visit date - (date of Study Day 1) +1, if visit date is ≥date of Day 1

Visit date - Date of Day 1, if visit date <date of Day 1
There is no 'Day 0'.
Baseline: Baseline is defined as the last observation prior to the first study agent administration
unless otherwise specified.


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6.4.
Appendix 4 Protocol Deviations
Major protocol deviations will be summarized by treatment group in the following categories:  
participants who entered the trial but did not satisfy entry criteria, participants who received the 
wrong medication or incorrect dose, participants who received disallowed medication, and other
as appropriate.


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6.5.
Appendix 5 Prior and Concomitant Medications
Summaries of Crohn’s-specific concomitant medications at baseline (including corticosteroids, 
Immunomodulators, antibiotics and Aminosalicylates) will be summarized. 


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6.6.
Appendix 6 Medical History
Medical History will be summarized as needed..


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6.7.
Appendix 7 Intervention Compliance
The number of Participants receiving each scheduled administration will be summarized by 
treatment group.
Drug compliance is calculated as the percent of number of tablets actually taken during the course 
of study. Specifically, for patient i
The number and percentage of patients who completed the specified range of compliance rate, 
starting at ≤ 75% compliance to a maximum of 100% in increments of 5% will be summarized by 
treatment as appropriate.  For Participants who discontinue study agent prior to week 12, the 
expected number of tablets is counted through the time of study agent discontinuation. 
100
 taken
be
 to
supposed
 tablets
of
number 
Total
 taken 
 tablets
of
number 
Actual








i
Compliance


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6.8.
Appendix 8 Adverse Events of Special Interest
Adverse Events of Special Interest will be summarized as needed. Any newly identified 
malignancy or case of active TB occurring after the first study intervention administration(s) in 
participants participating in this clinical study are considered AEs of special interest.
A possible Hy’s law case is defined by the occurrence of ALT/AST ≥3 x the upper limit of 
normal (ULN), alkaline phosphatase <2 x ULN together with Tbili ≥2 x ULN or international 
normalized ratio >1.5 (if measured). Any possible Hy’s Law case is considered an important 
medical event and should be reported to the sponsor in an expedited manner using the adverse 
events of special interest form, even before all other possible causes of liver injury have been 
excluded (FDA 2009).  A confirmed Hy’s law case must be reported as a SAE.


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6.9.
Appendix 9 Medications of Special Interest
Not applicable.


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6.10.
Appendix 10 Laboratory Toxicity Grading
Laboratory Toxicity Grading related analysis will be performed as needed.
The grading scale use for lab assessments is based on ‘Common Terminology Criteria for Adverse 
Events (CTCAE) v5.0’.
If a laboratory value falls within the grading as specified below but also within the local laboratory 
normal limits, the value is considered to be normal and will be reset to grade 0.
Pre-baseline measurements will use the same grading ranges as applied to baseline measurements. 
In case a test has two sets of ranges – one for baseline normal and one for baseline abnormal, the 
one for baseline normal will be applied for all measurements taken pre-baseline and on baseline.


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REFERENCES
1.
Best WR, Becktel JM, Singleton JW, Kern F Jr. Development of a Crohn’s disease activity index. National 
Cooperative Crohn’s Disease Study. Gastroenterology. 1976;70(3):439-444.
2.
D'haens G, Van Deventer S, Van Hogezand R, et al. Endoscopic and histological healing with infliximab anti-
tumor necrosis factor antibodies in Crohn's disease: A European multicenter trial. Gastroenterology. 
1999;116(5):1029-1034.
3.
D'Haens GR, Geboes K, Peeters M, Baert F, Penninckx F, Rutgeerts P. Early lesions of recurrent Crohn's 
disease caused by infusion of intestinal contents in excluded ileum. Gastroenterology. 1998;114(2):262-267.
4.
Irvine EJ, Feagan B, Rochon J, et al.  Quality of life: a valid and reliable measure of therapeutic efficacy in the 
treatment of inflammatory bowel disease.  Canadian Crohn’s Relapse Prevention Trial Study Group. 
Gastroenterology. 1994; 106(2):287-296.
5.
Laharie D, Reffet A, Belleannée G, et al. Mucosal healing with methotrexate in Crohn's disease: a prospective 
comparative study with azathioprine and infliximab. Aliment Pharmacol Ther. 2011;33(6):714-721.
6.
Mantzaris GJ, Christidou A, Sfakianakis M, et al. Azathioprine is superior to budesonide in achieving and 
maintaining mucosal healing and histologic remission in steroid-dependent Crohn's disease. Inflamm Bowel 
Dis. 2009;15(3):375-382.
7.
Mojtahed A, Khanna R, Sandborn WJ, et al. Assessment of histologic disease activity in Crohn's disease: a 
systematic review. Inflamm Bowel Dis. 2014;20(11):2092-2103.


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Attachment 1
Decision-Making Framework
There are 2 decision points planned for this ISA protocol:

At the IA: This IA will take place when approximately 45 participants have completed their 
Week 12 assessments or have withdrawn from the study before Week 12. If the futility criteria 
are met, the decision to terminate enrollment will be made based on a benefit risk assessment 
of the totality of data, including overall efficacy assessments, analysis of biomarker and PD 
data, and a safety review by the external DMC. If the futility criteria are not met and the DMC 
has not raised any safety issue, enrollment will continue until the planned sample size is 
reached. To augment decision-making, all available data at this IA, including from those 
participants without Week 12 assessments, will be analyzed. An Interim Analysis Committee 
will review the unblinded interim data and formulate recommendations (Section 9.5.1 of the 
Master protocol PLATFORMPACRD2001).

At the completion of this intervention cohort: The overall study success or futility is defined in 
the Master protocol. This decision-making framework is suggestive but not binding. The final 
decision will be made based on the totality of data.
Decision-Making Specifics at the Interim Analysis
If neither change in CDAI nor change in SES-CD of the PTG-200
 treatment arm 
meets the success criteria, the futility of the PTG-200
 treatment arm will be 
considered. The futility is defined as follows:

Futility in change in CDAI: if upper bound (UB) (95%) <60 and lower bound (LB) (10%) <40, 
ie, the 95% upper confidence bound of the true mean treatment difference at Week 12 is less 
than 60 and its 90% lower confidence bound less than 40; and

Futility in change in SES-CD: if UB (95%) <1.6 and LB (10%) <0.4, ie, the 95% upper 
confidence bound of the true meantreatment difference at Week 12 is less than 1.6 and its 90% 
lower confidence bound less than 0.4.
The thresholds chosen for futility at the IA correspond to PTG-200 profile with limited benefit.
Decision-Making Specifics at the Completion of the Intervention Cohort
The success of the PTG-200
 treatment arm is defined as follows:

Success in change in CDAI: if LB (20%) ≥40, ie, the 80% lower confidence bound of the true 
mean treatment difference at Week 12 is at least 40; or

Success in change in SES-CD: if LB (20%) ≥0.4, ie, the 80% lower confidence bound of the 
true meantreatment difference at Week 12 is at least 0.4.
The threshold of 40 is selected to provide confidence that a therapy is at least as effective as currently 
approved therapies (STELARA® [ustekinumab] or adalimumab), where a CDAI change of 40 
represents the lower confidence bound for success of the treatment difference between JNJ-67864238 
and placebo.
If neither change in CDAI nor change in SES-CD of the PTG-200
 treatment arm 
meets the success criteria, the futility of the PTG-200
 treatment arm will be 
considered. The futility of is defined as follows: 
CCI
CCI
CCI
CCI
CCI


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
Futility in change in CDAI: if UB (80%) <60 and LB (20%) <40, ie, the 80% upper confidence 
bound of the true mean treatment difference at Week 12 is less than 60 and its 80% lower 
confidence bound less than 40; and

Futility in change in SES-CD: if UB (90%) <1.6 and LB (20%) <0.4, ie, the 90% upper 
confidence bound of the true meantreatment difference at Week 12 is less than 1.6 and its 80% 
lower confidence bound less than 0.4. 


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Attachment 2: Data Simulation
To evaluate the operating characteristics of the study design, the following assumptions are made
based on 3 completed clinical studies (C0743T26/CNTO1275 Ph2b, CNTO1275CRD3001, and
CNTO1275CRD3002) conducted by the sponsor:

The compositions of Bio-IR and Bio-NF populations are 50% each

For Bio-IR population, the CDAI scores of the JNJ-67864238 
 
treatment arm and placebo treatment arm at Weeks 0, 2, 4, 8, and 12 are assumed to be 
(323,285,259,247,238)` and (323,305,300,299,298)`, respectively. Similarly, for Bio-NF 
population, the CDAI scores of the JNJ-67864238 
 treatment arm and 
placebo treatment arm at Weeks 0, 2, 4, 8 and 12 are assumed to be 
(302,245,208,180,176)` and (302,271,254,241,236)`, respectively.

The covariance matrix is assumed to be
for the Bio-IR and Bio-NF populations, respectively.

In CNTO1275CRD3001 and CNTO1275CRD3002, an optional endoscopy substudy was 
conducted in a subset of study participants. Based on the collected data, change in SES-
CD is assumed to have a mixture distribution - excessive zeros (no change) and a normal 
distribution. Therefore, 2 steps were utilized to simulate the change in SES-CD data.
o
Step 1: no change in SES-CD is simulated for 19% of JNJ-67864238 
 
 treated participants and 32% placebo treated participants.
o
Step 2: changes in SES-CD based on the normal distributions with mean changes 
from baseline of -3.26 and -0.22 are generated for the JNJ-67864238 
 
 and placebo arms, respectively. The common standard deviation is 
3.8. As the change in SES-CD of a participant is an integer, the simulated value 
then is rounded to the nearest integer. The above assumptions are for the Bio-IR 
population. The change in SES-CD responses for the Bio-NF population can be 
simulated similarly with the following assumptions: the proportion of the 
excessive zeros is 12% for both the active and placebo treatment arm in Step 1. 
The means of the normal distributions are -4.68 and -2.71 or the PTG-200
 
 and placebo arms, respectively. The common standard deviation is 
5.9.

The correlation coefficients between the change in SES-CD and the CDAI scores are 
assumed to be -0.15, 0, 0, 0.15, and 0.15 at Weeks 0, 2, 4, 8, and 12 for the Bio-IR 
population. They are assumed to be 0, 0, 0, 0.15 and 0.15 at Weeks 0, 2, 4, 8, and 12 for 
the Bio-NF population.
CCI
CCI
CCI
CCI
CCI


67864238PACRD2001
Statistical Analysis Plan
46
Approved, Date: 29 June 2021
Attachment 3: Crohn’s Disease Activity Index
DISEASE ACTIVITY INDEX
SUM
X FACTOR
SUBTOTAL
Total number of liquid or very soft stools in the 
previous 7 days
x
2
=
Sum abdominal pain/cramps ratings
(total for previous 7 days):
x
5
=
0 = none
2 = moderate
1 = mild
3 = severe
General well being (total for previous 7 days):
x
7
=
0 = generally well
3 = very poor
1 = slightly under par
4 = terrible
2 = poor
Categories currently present and
presumed to be related to Crohn’s disease:  0 = no; 1 = yes 
=
arthritis/arthralgia
x
20
=
=
iritis/uveitis
x
20
=
=
erythema nodosum/pyoderma 
gangrenosum/aphthous stomatitis
x
20
=
=
anal fissure, fistula or abscess
x
20
=
=
other fistula
x
20
=
=
fever over 100° F (37.8° C) during the 
previous 7 days.
x
20
=
During the previous 7 days has participant received 
antidiarrheal therapy at least once:
OR
x
30
=
During the previous 7 days has participant received
opiate therapy on each of the 7 days:
0 = no
1 = yes
Abdominal mass:
x
10
=
0 = none
2 = questionable
5 = definite
Hematocrit:
x
6
=
Males: (47-Hct) = SUM
(add or subtract by sign)
Females: (42-Hct) = SUM
(Standard Weight - Actual Body Weight)
x 100 =
*
x
1
=
Standard Weight
(add or subtract by sign,  round to 3 decimal places)
* If this value is less than -10 then enter -10 here.
Standard weight and actual weight must be in same units (kg or lb)
TOTAL = 
(round total to integer)


67864238PACRD2001
Statistical Analysis Plan
47
Approved, Date: 29 June 2021
Attachment 4: Sample score sheet and scoring definitions for the Simple Endoscopic Score for 
Crohn’s Disease (SES-CD)
Ileum
Right 
Colon
Transverse 
Colon
Left 
Colon
Rectum
Total
1. Presence and size of ulcers (0-3)
15 max
2. Extent of ulcerated surface (0-3)
15 max
3. Extent of affected surface (0-3)
15 max
4. Presence and type of narrowings (0-3)
11 max*
Total 1 + 2 + 3 + 4 =
SES-CD
(56 max)
Score = 0
Score = 1
Score = 2
Score = 3
Size of ulcers
None
Aphthous ulcers 
(ø 0.1 – 0.5 cm)
Large ulcers 
(ø 0.5 – 2.0 cm)
Very large ulcers
(ø > 2.0 cm)
Ulcerated surface
None
<10%
10-30%
>30%
Affected surface
Unaffected segment
<50%
50-75%
>75%
Narrowings
None
Single, can be passed
Multiple, can be passed
Cannot be passed
* The maximum sub-score for narrowings (i.e. stricturing) is 11 points. The presence of a narrowing that cannot be 
passed can be only observed once.
ø =Diameter.