A Phase 2 Open-label Trial to Evaluate Safety, Efficacy, Tolerability, and Pharmacodynamics of a Combination of JNJ-73763989, Nucleos(t)Ide Analogs, and a PD-1 Inhibitor in Chronic Hepatitis B Patients
Phase: PHASE2
Conditions: Hepatitis B, Chronic
Sponsor: Janssen Research & Development, LLC

CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
1
Status: Approved, Date: 30 June 2023
Janssen Research & Development *
Clinical Protocol
Intervention-specific Appendix 7 to Clinical Protocol PLATFORMPAHPB2001
A Phase 2 Open-label Trial to Evaluate Safety, Efficacy, Tolerability, and
Pharmacodynamics of a Combination of JNJ-73763989, Nucleos(t)ide Analogs, and a PD-1
Inhibitor in Chronic Hepatitis B Patients.
OCTOPUS-1Study
Protocol 73763989PAHPB2008; Phase 2
Version: Amendment 3
JNJ-73763989
*Janssen Research & Development is a global organization that operates through different legal entities in
various countries/territories. 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.
EudraCT NUMBER: 2021-005132-33
Status: 
Approved
Date: 
30 June 2023
Prepared by: Janssen Research & Development, a division of Janssen Pharmaceutica NV
EDMS number: 
EDMS-RIM-511735, 6.0
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.
NCT05275023

JNJ-73763989 
Clinical Protocol 73763989PAHPB2008 Amendment 3
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
2
Status: Approved, Date: 30 June 2023
PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLES
DOCUMENT HISTORY
Document 
Date
Amendment 3 
30 June 2023
Amendment 2  
28 March 2023
Amendment 1 
30 June 2022
Original Protocol 
21 December 2021
Amendment 3 (30 June 2023)
Overall Rationale for the Amendment: The main reason for the protocol amendment is the
discontinuation of PD-1 inhibitor (nivolumab) as study intervention as of 20 June 2023 as an urgent safety
measure (USM). Based on the observation of two cases of potential hyperthyroidism, the sponsor decided
on 20 June 2023, to halt further nivolumab dosing effective immediately. Both cases occurred in
participants in treatment arm 1 who were randomized to receive a single dose of nivolumab administered
at treatment week 16 of JNJ-3989 treatment. At treatment week 24, thyroid-stimulating hormone (TSH)
was reduced in both patients. While the first patient had normal free T3 and free T4 values and TSH values
returned to normal at follow-up visits, the second patient had fully suppressed TSH with elevation of free
T3 and free T4. The testing frequency for thyroid parameters in the Schedule of Activities will not be
changed. At the time of the USM, two participants in arm 2 were still scheduled for their third infusion with
nivolumab. Both planned infusions were cancelled via direct communication with the study sites. Treatment
with JNJ-3989 and/or nucleos(t)ide analog was continued as planned.
Also, additional clarifications were provided to the protocol sections about gastrointestinal adverse events
and hematologic abnormalities.
Section number 
and Name
Description of Change 
Brief Rationale
2.3.2.2 Potential Risks 
Discontinuation of PD-1 inhibitor (nivolumab) 
as study intervention as of 20 June 2023 for
the last two participants enrolled in treatment
arm 2 who still had outstanding doses of
nivolumab scheduled.
Two cases of potential
hyperthyroidism were observed
and therefore an urgent safety
measure was implemented.
5.4 Screen Failures 
It was clarified that the investigator will
generate screening and enrollment logs.
To align with the company’s
most recent protocol template.
8.3.6.2.1 Gastrointestinal 
Adverse Events 
It was clarified what is meant by lower
endoscopy. In addition, bowel perforation was
added as a contraindication to endoscopy.
For clarity and completeness
8.3.6.3.1 Hematologic 
Abnormalities 
Autoimmune hemolytic anemia was added to
the list of hematologic abnormalities reported
with nivolumab in the oncology setting
For completeness

JNJ-73763989 
Clinical Protocol 73763989PAHPB2008 Amendment 3
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
3
Status: Approved, Date: 30 June 2023
TABLE OF CONTENTS
PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLES............................................................. 2
TABLE OF CONTENTS ............................................................................................................................... 3
LIST OF IN-TEXT TABLES AND FIGURES................................................................................................ 6
1. 
PROTOCOL SUMMARY..................................................................................................................... 7
1.1. 
Synopsis........................................................................................................................................... 7
1.2. 
Schema.......................................................................................................................................... 18
1.3. 
Schedule of Activities..................................................................................................................... 19
1.3.1. 
Schedule of Activities –Screening Phase and Study Intervention Phase ................................. 19
1.3.2. 
Schedule of Activities –Follow-up Phase................................................................................... 25
2. 
INTRODUCTION................................................................................................................................ 28
2.1. 
Study Rationale.............................................................................................................................. 28
2.2. 
Background .................................................................................................................................... 32
2.2.1. 
Primary Pharmacology ............................................................................................................... 32
2.2.2. 
Nonclinical Studies ..................................................................................................................... 32
2.2.2.1. 
JNJ-3989................................................................................................................................. 32
2.2.2.2. 
Nivolumab................................................................................................................................ 35
2.2.2.3. 
Combination Nivolumab + JNJ-3989....................................................................................... 36
2.2.3. 
Clinical Studies ........................................................................................................................... 36
2.2.3.1. 
JNJ-3989................................................................................................................................. 36
2.2.3.2. 
Combination of JNJ-3989 and Entecavir, Tenofovir Disoproxil, or Tenofovir
Alafenamide............................................................................................................................. 38
2.3. 
Benefit-Risk Assessment............................................................................................................... 39
2.3.1. 
Benefits for Study Participation .................................................................................................. 39
2.3.1.1. 
Known Benefits........................................................................................................................ 39
2.3.1.2. 
Potential Benefits..................................................................................................................... 39
2.3.2. 
Risks for Study Participation....................................................................................................... 39
2.3.2.1. 
Known Risks............................................................................................................................ 39
2.3.2.2. 
Potential Risks......................................................................................................................... 40
2.3.3. 
Benefit-Risk Assessment for Study Participation ....................................................................... 41
3. 
OBJECTIVES AND ENDPOINTS ..................................................................................................... 43
4. 
STUDY DESIGN ................................................................................................................................ 45
4.1. 
Overall Design................................................................................................................................ 45
4.2. 
Scientific Rationale for Study Design............................................................................................. 47
4.2.1. 
Study-Specific Ethical Design Considerations ........................................................................... 47
4.3. 
Justification for Dose and Treatment Duration .............................................................................. 48
4.4. 
End of Study Definition................................................................................................................... 49
5. 
STUDY POPULATION ...................................................................................................................... 49
5.1. 
Inclusion Criteria............................................................................................................................ 50
5.2. 
Exclusion Criteria........................................................................................................................... 52
5.3. 
Lifestyle Considerations................................................................................................................. 57
5.4. 
Screen Failures.............................................................................................................................. 57
6. 
STUDY INTERVENTION AND CONCOMITANT THERAPY............................................................ 57
6.1. 
Study Intervention(s) Administered................................................................................................ 57
6.2. 
Preparation/Handling/Storage/Accountability ................................................................................ 59
6.3. 
Measures to Minimize Bias: Randomization and Blinding............................................................. 60
6.4. 
Study Intervention Compliance...................................................................................................... 60
6.5. 
Concomitant Therapy..................................................................................................................... 61
6.6. 
Dose Modification........................................................................................................................... 62
6.7. 
Continued Access to Study Intervention After the End of the Study ............................................. 62

JNJ-73763989 
Clinical Protocol 73763989PAHPB2008 Amendment 3
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
4
Status: Approved, Date: 30 June 2023
6.8. 
Treatment of Overdose .................................................................................................................. 62
6.9. 
Background Treatment................................................................................................................... 63
7.
DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT
DISCONTINUATION/WITHDRAWAL............................................................................................... 64
7.1. 
Discontinuation of Study Intervention ............................................................................................ 64
7.1.1. 
Discontinuation of JNJ-3989....................................................................................................... 65
7.1.2. 
Discontinuation of Nivolumab..................................................................................................... 65
7.2. 
Participant Discontinuation/Withdrawal From the Study................................................................ 66
7.2.1. 
Withdrawal From the Use of Research Samples ....................................................................... 66
7.3. 
Lost to Follow-up............................................................................................................................ 67
8.
STUDY ASSESSMENTS AND PROCEDURES ............................................................................... 67
8.1. 
Efficacy Assessments .................................................................................................................... 68
8.1.1. 
Sequencing................................................................................................................................. 68
8.2. 
Safety Assessments....................................................................................................................... 69
8.2.1. 
Physical Examinations................................................................................................................ 69
8.2.2. 
Vital Signs................................................................................................................................... 69
8.2.3. 
Electrocardiograms..................................................................................................................... 69
8.2.4. 
Clinical Safety Laboratory Assessments .................................................................................... 69
8.2.5. 
Pregnancy Testing...................................................................................................................... 69
8.3. 
Adverse Events, Serious Adverse Events, and Other Safety Reporting ....................................... 70
8.3.1. 
Time Period and Frequency for Collecting Adverse Event and Serious Adverse Event
Information.................................................................................................................................. 70
8.3.2. 
Method of Detecting Adverse Events and Serious Adverse Events .......................................... 70
8.3.3. 
Follow-up of Adverse Events and Serious Adverse Events ....................................................... 70
8.3.4. 
Regulatory Reporting Requirements for Serious Adverse Events ............................................. 70
8.3.5. 
Pregnancy................................................................................................................................... 70
8.3.6. 
Guidelines for Management of Adverse Events of Special Interest Including Immune-
Related Adverse Events ............................................................................................................. 71
8.3.6.1. 
Intervention-emergent ALT/AST Elevations Including Immune-related Hepatic AEs ............. 71
8.3.6.2. 
Infusion-related Reactions and Other Immune-related Adverse Events................................. 73
8.3.6.2.1. 
Gastrointestinal Adverse Events.......................................................................................... 73
8.3.6.2.2. 
Neurological Adverse Events............................................................................................... 74
8.3.6.2.3. 
Pulmonary Adverse Events.................................................................................................. 75
8.3.6.2.4. 
Renal Adverse Events.......................................................................................................... 75
8.3.6.2.5. 
Endocrinopathies ................................................................................................................. 76
8.3.6.2.6. 
Rash..................................................................................................................................... 77
8.3.6.2.7. 
Uveitis and Visual Complaints.............................................................................................. 78
8.3.6.2.8. 
Lipase/Amylase Elevations .................................................................................................. 78
8.3.6.2.9. 
Infusion-related Reactions ................................................................................................... 79
8.3.6.2.10. 
Infections.............................................................................................................................. 79
8.3.6.3. 
Other Adverse Events of Special Interest Related to JNJ-3989............................................. 79
8.3.6.3.1. 
Hematologic Abnormalities .................................................................................................. 79
8.3.6.3.2. 
Injection Site Reactions........................................................................................................ 80
8.3.6.4. 
Other Adverse Events ............................................................................................................. 81
8.3.6.4.1. 
Acute Systemic Allergic Reactions....................................................................................... 81
8.4. 
Pharmacokinetics........................................................................................................................... 81
8.4.1. 
Evaluations ................................................................................................................................. 81
8.4.2. 
Analytical Procedures................................................................................................................. 81
8.4.3. 
Pharmacokinetic Parameters and Evaluations........................................................................... 82
8.5. 
Pharmacodynamics........................................................................................................................ 82
8.6. 
Host Genetics................................................................................................................................. 82
8.7. 
Exploratory Host Biomarkers ......................................................................................................... 83
8.8. 
Immune Assessments.................................................................................................................... 83
8.9. 
Medical Resource Utilization and Health Economics .................................................................... 84
9.
STATISTICAL CONSIDERATIONS.................................................................................................. 84

JNJ-73763989 
Clinical Protocol 73763989PAHPB2008 Amendment 3
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
5
Status: Approved, Date: 30 June 2023
9.1. 
Statistical Hypotheses.................................................................................................................... 84
9.2. 
Sample Size Determination ........................................................................................................... 85
9.3. 
Populations for Analysis Sets ........................................................................................................ 85
9.4. 
Statistical Analyses ........................................................................................................................ 85
9.4.1. 
General Considerations.............................................................................................................. 85
9.4.2. 
Efficacy Analyses........................................................................................................................ 85
9.4.2.1. 
Primary Endpoints ................................................................................................................... 86
9.4.2.2. 
Secondary Efficacy and Exploratory Endpoints ...................................................................... 86
9.4.2.3. 
Across ISAs Comparisons of Efficacy..................................................................................... 87
9.4.3. 
Safety Analyses.......................................................................................................................... 87
9.4.4. 
Other Analyses ........................................................................................................................... 87
9.5. 
Interim Analysis.............................................................................................................................. 89
10. SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS ............................ 90
10.1. 
Appendix 1: Abbreviations and Definitions .................................................................................... 90
10.2. 
Appendix 2: Clinical Laboratory Tests ........................................................................................... 93
10.3. 
Appendix 3: Regulatory, Ethical, and Study Oversight Considerations......................................... 95
10.3.1. 
Regulatory and Ethical Considerations ...................................................................................... 95
10.3.2. 
Financial Disclosure.................................................................................................................... 95
10.3.3. 
Informed Consent Process ......................................................................................................... 95
10.3.4. 
Data Protection ........................................................................................................................... 95
10.3.5. 
Long-Term Retention of Samples for Additional Future............................................................. 95
10.3.6. 
Committees Structure................................................................................................................. 96
10.3.7. 
Publication Policy/Dissemination of Clinical Study Data............................................................ 96
10.3.8. 
Data Quality Assurance.............................................................................................................. 96
10.3.9. 
Case Report Form Completion................................................................................................... 96
10.3.10. Source Documents ..................................................................................................................... 96
10.3.11. Monitoring ................................................................................................................................... 96
10.3.12. On-Site Audits............................................................................................................................. 96
10.3.13. Record Retention........................................................................................................................ 96
10.3.14. Study and Site Start and Closure ............................................................................................... 96
10.4. 
Appendix 4: Adverse Events, Serious Adverse Events, Product Quality Complaints, and
Other Safety Reporting: Definitions and Procedures for Recording, Evaluating, Follow-up,
and Reporting................................................................................................................................. 97
10.4.1. 
Adverse Event Definitions and Classifications ........................................................................... 97
10.4.2. 
Attribution Definitions.................................................................................................................. 97
10.4.3. 
Severity Criteria.......................................................................................................................... 97
10.4.4. 
Special Reporting Situations ...................................................................................................... 97
10.4.5. 
Procedures ................................................................................................................................. 97
10.4.6. 
Product Quality Complaint Handling........................................................................................... 97
10.4.7. 
Contacting Sponsor Regarding Safety, Including Product Quality............................................. 97
10.5. 
Appendix 5: Contraceptive and Barrier Guidance ......................................................................... 98
10.6. 
Appendix 6: Rash Management................................................................................................... 100
10.7. 
Appendix 7: Cardiovascular Safety –Abnormalities.................................................................... 102
10.8. 
Appendix 8: DAIDS Table with Modifications (DAIDS [Modified]) ............................................... 103
10.9. 
Appendix 9: Study Conduct During a Natural Disaster................................................................ 129
10.10. Appendix 10: Protocol Amendment History................................................................................. 133
11. REFERENCES................................................................................................................................. 137
INVESTIGATOR AGREEMENT............................................................................................................... 139

JNJ-73763989 
Clinical Protocol 73763989PAHPB2008 Amendment 3
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
6
Status: Approved, Date: 30 June 2023
LIST OF IN-TEXT TABLES AND FIGURES
TABLES
Table 1: 
Animal-to-human Exposure Ratios at NOAEL for JNJ-3989.................................................... 35
Table 2: 
Description and Administration of Study Intervention............................................................... 58
Table 3: 
Disallowed Medication .............................................................................................................. 62
Table 4: 
Description and Administration of Background Treatment....................................................... 63
Table 5: 
Management of Immune-Related Hepatic Adverse Events...................................................... 72
Table 6: 
Management of Immune-Related Gastrointestinal Adverse Events......................................... 74
Table 7: 
Management of Neurological Adverse Events ......................................................................... 74
Table 8: 
Management of Pulmonary Adverse Events ............................................................................ 75
Table 9: 
Management of Renal Adverse Events .................................................................................... 76
Table 10: Management of Immune-Related Endocrinopathies ................................................................ 76
Table 11: Management of Uveitis and Visual Complaints ........................................................................ 78
Table 12: Management of Infusion-related Reactions.............................................................................. 79
Table 13: Management of Acute Systemic Allergic Reactions................................................................. 81
Table 14: Management of Rash Events by Severity Grade ................................................................... 100
FIGURES
Figure 1: Schematic Overview of the Study............................................................................................. 18
Figure 2: TMDD-IRM Predicted Liver Concentrations of JNJ-3989 (Left) and Corresponding
Predicted Change From Baseline (CFB) in HBsAg (Right) With (Red) and Without
(Cyan) Loading Dosing (200 mg JNJ-3989 Weekly for 4 Weeks) Prior to the 200 mg
JNJ-3989 Q4W Regimen.......................................................................................................... 29
Figure 3: Receptor Occupancy: (A) Nivolumab 0.1 mg/kg or 0.3 mg/kg, and (B) Nivolumab
0.3 mg/kg + GS-4774................................................................................................................ 30
Figure 4: Individual Patient Changes in HBsAg From Baseline to Week 12 (Left) or Week 24
(Right) by Nivolumab Treatment............................................................................................... 31

JNJ-73763989 
Clinical Protocol 73763989PAHPB2008 Amendment 3
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
7
Status: Approved, Date: 30 June 2023
1. 
PROTOCOL SUMMARY
1.1. 
Synopsis
A Phase 2 Open-label Trial to Evaluate Safety, Efficacy, Tolerability, and Pharmacodynamics of a
Combination of JNJ-73763989, Nucleos(t)ide Analogs, and a PD-1 Inhibitor in Chronic Hepatitis B
Patients.
Protocol 73763989PAHPB2008 is an intervention-specific appendix (ISA) to Master Protocol
PLATFORMPAHPB2001.
JNJ-73763989 (JNJ-3989) is a liver-targeted antiviral therapeutic for subcutaneous injection designed to
treat chronic hepatitis B virus (HBV) infection via a ribonucleic acid interference (RNAi) mechanism.
Engagement of the cellular RNAi machinery by JNJ-3989 results in specific cleavage of HBV RNA
transcripts, thereby reducing the levels of HBV proteins and the pre-genomic ribonucleic acid (pgRNA),
the precursor of viral relaxed circular deoxyribonucleic acid (rcDNA). The small interfering ribonucleic
acid (siRNA) triggers in JNJ-3989, JNJ-73763976 (JNJ-3976), and JNJ-73763924 (JNJ-3924), are designed
to target all HBV RNA transcripts derived from covalently closed circular deoxyribonucleic acid
(cccDNA), as well as transcripts derived from integrated HBV DNA. The latter has been suggested to be a
significant source of hepatitis B surface antigen (HBsAg) in hepatitis B e antigen (HBeAg)-negative
patients or patients on long-term (≥2 years) treatment with nucleos(t)ide analogs (NAs), the current standard
of care.
The programmed cell death protein receptor-1 (PD-1) inhibitor is nivolumab, which  is a human
immunoglobin G4 (IgG4) monoclonal antibody that binds to the PD-1 receptor, blocking the interaction
between PD-1 and its ligand PD-L1. Nivolumab is approved for the treatment of certain cancers and for
other indications at higher doses than intended in this study. The use of nivolumab in the treatment of HBV
is investigational.
Nucleos(t)ide analogs are approved treatments of chronic HBV infection.
The term “study intervention” throughout the protocol, refers to JNJ-3989 and
nivolumab.OBJECTIVES AND ENDPOINTS
Below is the list of objectives and endpoints that will be evaluated in this study, delineating the details in
alignment with the general objectives listed in the Master Protocol PLATFORMPAHPB2001. The details
specific for this ISA are highlighted (colored fill).
Objectives 
Endpoints
Primary
To evaluate efficacy of the study intervention, based on 
HBsAg levels at Follow-up Week 24 (FU Week 24). 
 
Proportion of participants who achieve HBsAg
seroclearance at FU Week 24.
Secondary
To characterize the safety and tolerability of the study 
intervention. 
 
Proportion of participants who experienced
adverse events (AEs) of interest.
 
Safety profile of JNJ-3989 with nivolumab
throughout the study (safety parameters include
but are not limited to the frequency and severity of
AEs and immune-related AEs, vital signs
measurements, physical examinations, clinical
laboratory values, and 12-lead electrocardiograms
[ECGs]).

JNJ-73763989 
Clinical Protocol 73763989PAHPB2008 Amendment 3
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
8
Status: Approved, Date: 30 June 2023
Objectives 
Endpoints
To evaluate efficacy in terms of changes in HBsAg 
levels from baseline over time during the study 
intervention and follow-up periods.
 
Change from baseline in HBsAg levels during the
study intervention and follow-up periods.
 
Proportion of participants with HBsAg levels
below/above different cut-offs over time.
To evaluate efficacy in terms of HBsAg 
seroclearance/seroconversion during the study 
intervention and follow-up periods (as defined in the 
Definitions of Terms).
 
Proportion 
of 
participants 
with 
HBsAg
seroclearance/seroconversion during the study
intervention and follow-up periods.
 
Time 
to 
achieve 
HBsAg 
seroclearance/
seroconversion.
To evaluate the efficacy as measured by blood markers 
(such as HBV DNA and HBeAg) during the study 
intervention and follow-up periods.
 
Change from baseline in HBV DNA levels during
the study intervention and follow-up periods.
 
Proportion of participants with HBV DNA and
HBeAg levels below/above different cut-offs over
time.
To evaluate the frequency of virologic breakthrough 
throughout the study. 
 
Proportion of participants with virological
breakthrough throughout the study.
To evaluate the pharmacokinetics (PK) of JNJ-3989 
(JNJ-3924 and JNJ-3976) and optionally of NA and/or 
nivolumab.
 
PK parameters of JNJ-3989 (JNJ-3924 and
JNJ‑3976).
 
Optionally, PK parameters of NA and/or
nivolumab.
Exploratory
To characterize the pharmacodynamics (PD) of 
JNJ-3989 with nivolumab including quantification of 
receptor occupancy (RO) on peripheral T-cells.
 
Relationship of various PK parameters with
selected efficacy and safety endpoints.
 
Quantification of nivolumab RO  on peripheral
CD3+ T-cells by flow cytometry on whole blood.
To explore changes in the severity of liver disease. 
 
Changes in fibrosis (according to Fibroscan liver
stiffness measurements) at end of study
intervention (EOSI) and the end of the follow-up
period versus baseline.
To explore HBV-specific T-cell responses throughout 
the study.*  
 
Changes from baseline in HBV-specific peripheral
blood T-cell responses over time.
To explore efficacy of the study intervention in terms 
of changes in HBV RNA and hepatitis B core-related 
antigen (HBcrAg) levels throughout the study.
 
Changes from baseline in HBV RNA and HBcrAg
levels over time.
To explore the HBV genome sequence throughout the 
study. 
 
Assessment of intervention associated mutations
over time.
To explore medical resource utilization to manage 
participants throughout the study. 
 
Number and duration of medical care encounters,
including surgeries, and other selected procedures
(inpatient and outpatient).
 
Duration of hospitalization (total days length of
stay, including duration by wards, eg, intensive
care unit).
 
Number and character of diagnostic and
therapeutic tests and procedures.

JNJ-73763989 
Clinical Protocol 73763989PAHPB2008 Amendment 3
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
9
Status: Approved, Date: 30 June 2023
Objectives 
Endpoints
 
Outpatient medical encounters and treatments
(including physician or emergency room visits,
tests and procedures, and medications).
*Peripheral blood mononuclear cell (PBMC) samples for immune analyses will be collected at selected sites only.
Hypothesis
The primary hypothesis of this study is that at least one of the combination regimens of
JNJ-3989+nivolumab+NA is more efficacious than JNJ-3989+NA treatment, as measured by the primary
efficacy endpoint (ie, the proportion of participants with HBsAg seroclearance at FU Week 24). Because
the study does not include a regimen arm without nivolumab, the hypothesis is formulated assuming a fixed
response rate for JNJ-3989+NA of 1% based on previous Study 73763989HPB2001 (REEF-1).
OVERALL DESIGN
This ISA describes a Phase 2 study of the combination regimen of JNJ-3989 with nivolumab and NA. It is
a companion document to the Master Protocol PLATFORMPAHPB2001, which describes the common
design elements of the Platform study in participants with chronic HBV infection. This ISA describes
specific and/or additional protocol elements applicable to this randomized, open-label, parallel, multicenter,
interventional study to evaluate safety, efficacy, tolerability, PK and PD of a combination of JNJ-3989,
nivolumab, and NAs in virologically suppressed chronic HBV-infected adult participants.
This open-label study will be conducted in 3 periods:
 
6-week Screening Period (if necessary, eg, for operational reasons, this can be extended to a
maximum of 8 weeks decided on a case-by-case basis and in agreement with the sponsor). During
the Screening Period, the participants will continue the same NA treatment they were receiving
before screening.
 
24-week Study Intervention Period:
o 
Arm 1: JNJ-3989 once a week (Q1W) for the first 4 weeks then once every 4 weeks (Q4W)
until Week 24 + nivolumab at Week 16 + NA once daily (QD)
o 
Arm 2: JNJ-3989 Q1W for the first 4 weeks then Q4W until Week 24 + nivolumab Q4W at
Weeks 16, 20, and 24 + NA QD.
 
48-week Follow-up Period: during which NA treatment will be continued.
At baseline, participants who meet the eligibility criteria will be randomized in a 1:1 ratio to Arm 1 or
Arm 2. Randomization will be stratified by absolute HBsAg level (<100 IU/mL, 100 to <1,000 IU/mL, and
≥1,000 IU/mL) at screening, as assessed by quantitative HBsAg assay.
Assessments and sampling will be done for efficacy (eg, HBsAg, HBeAg, and HBV DNA), safety (eg,
[S]AEs, immune-related AEs, laboratory evaluations, ECGs, vital signs, physical examinations), PK,
PK/PD, viral genome sequencing, PBMC, human leukocyte antigen (HLA) typing, immunogenicity and
pharmacogenomics, and for exploratory analysis of host and viral markers.
Participants will be considered to have completed the study if they have completed all the assessments of
the final study visit (ie, FU Week 48).
If a participant prematurely discontinues treatment with JNJ-3989 before Week 24, the participant will also
discontinue further treatment with nivolumab and will have an early withdrawal (WD) visit. Follow-up
assessments should be obtained as per the Schedule of Activities until 48 weeks after the end of JNJ-3989
treatment unless the participant withdraws consent. The NA treatment will be continued until the end of the
study.

JNJ-73763989 
Clinical Protocol 73763989PAHPB2008 Amendment 3
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
10
Status: Approved, Date: 30 June 2023
If a participant prematurely discontinues nivolumab, treatment with JNJ-3989 and NA should be continued
as planned, unless a treatment discontinuation rule for JNJ-3989 is also met. In that case, JNJ-3989 will
also be discontinued but NA treatment should be continued as planned.
If a participant withdraws prematurely from the study, the reason for withdrawal (if known) should be
documented. Participants who withdraw consent will be offered an optional safety follow-up visit to occur
on the day of consent withdrawal.
An internal Data Review Committee (DRC) will be commissioned for monitoring safety of participants
enrolled in this study. In addition, an Independent Flare Expert Panel (IFLEP) will be appointed.
NUMBER OF PARTICIPANTS
Initially, 44 (22 per arm) virologically suppressed, HBeAg negative, adult chronic hepatitis B participants
≥18 (or the legal age of consent in the jurisdiction in which the study is taking place) to <56 years of age
were planned to be enrolled in this study.
Due to the decision to not extend further enrollment beyond the planned enrollment period and proceed
with a reduced sample size, the final sample size is 37 (18 in Arm 1 and 19 in Arm 2).
INTERVENTION GROUPS AND DURATION
The total duration of individual participation will be up to 72 weeks (screening not included) with a 24-week
study intervention period and a 48-week follow-up period.
Description of Background Treatment
Background treatment consists of NAs tenofovir disoproxil (245 mg), tenofovir alafenamide (TAF)
(25 mg), or entecavir (ETV) (0.5 mg) given as oral tablets QD for approximately 76 weeks (screening
included).
Investigators should follow guidance detailed in the local prescribing information of NA.
Treatment Name 
Tenofovir disoproxil 
Tenofovir alafenamide 
(TAF)* 
Entecavir (ETV)
monohydrate
Type 
Drug 
Drug 
Drug
Dose Formulation 
Film-coated tablets 
Film-coated tablets 
Film-coated tablets
Unit Dose Strength(s) 
245 mg 
25 mg 
0.5 mg
Dosage Level(s) 
245 mg QD  
25 mg QD  
0.5 mg QD
Route of Administration 
Oral 
Oral 
Oral
* 
In countries where TAF is available, it will be one of the NA treatments options.

JNJ-73763989 
Clinical Protocol 73763989PAHPB2008 Amendment 3
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
11
Status: Approved, Date: 30 June 2023
Description of Study Intervention
Study intervention consists of:
 
JNJ-3989: 200 mg given by subcutaneous (SC) injections Q1W for the first 4 weeks then Q4W
until Week 24 (10 doses)
 
Nivolumab: 0.3 mg/kg, one single intravenous (IV) infusion at Week 16 for Arm 1 or 3 IV
infusions at Weeks 16, 20, and 24 for Arm 2.
Intervention Name 
JNJ-3989 
Nivolumab
Type 
Drug 
Drug
Dose Formulation  
Solution for injection (G001) 
Concentrate for solution for infusion
Unit Dose Strength(s) 
200 mg/mL 
40 mg/4 mL
Dosage Level(s) 
200 mg Q1W for the first 4 weeks, 
then Q4W until Week 24 
0.3 mg/kg (1 intravenous [IV]
infusion for Arm 1 or 3 IV infusions
Q4W for Arm 2)**
Route ofAdministration 
Subcutaneous injection* (preferably  
in the abdomen; upper arm or thigh is
also allowed)
IV infusion over 30 minutes
Use 
Investigational intervention  
Investigational intervention
Investigational Medicinal Product 
(IMP)
Yes 
Yes
Non-investigational Medicinal 
Product/ Auxiliary Medicinal
Product (NIMP/AxMP)
No 
No
Sourcing 
Provided centrally by the sponsor 
Provided centrally by the sponsor
Packaging and Labeling 
Each unit will be labeled with unique 
medication ID number 
Commercial supplies will be
sourced. Each unit will be labeled
with unique medication ID number
Food/Fasting Instructions 
Regardless of food intake 
Not Applicable
*Note: Administration into scar tissue or areas that are reddened, inflamed or swollen should be avoided. If injecting
into the abdomen, avoid a 5 cm diameter circle around the navel.
**Note: a tolerance of +/- 5% around the theoretical dose of 0.3 mg/kg will be applied to consider the necessary
rounding and standard practice for the preparation and intravenous administration of drugs dosed by weight.
EFFICACY EVALUATIONS
All efficacy assessments will be performed at predefined time points as specified in the Schedule of
Activities.
Qualitative and quantitative HBsAg and HBeAg, and quantitative HBcrAg as well as anti-hepatitis B
surface (HBs) and anti-hepatitis B e (HBe) antibodies will be determined using validated serologic assays
in a central laboratory. Samples for the determination of HBsAg, HBeAg, anti-HBs antibodies, and

JNJ-73763989 
Clinical Protocol 73763989PAHPB2008 Amendment 3
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
12
Status: Approved, Date: 30 June 2023
anti-HBe antibodies will be processed in real-time. Samples for the determination of HBcrAg can be
analyzed in batch and at the sponsor’s request.
HBV DNA and HBV RNA will be assessed at central laboratories using validated assays for the
quantification of HBV DNA and HBV RNA. Samples for the determination of HBV DNA will be processed
in real-time. Samples for the determination of HBV RNA can be analyzed in batch and at the sponsor’s
request.
In participants enrolled at a site with access to a Fibroscan device, Fibroscan assessments will be performed
at different time points to determine changes in fibrosis levels.
Samples may be used by the sponsor for additional exploratory assessments analyzing the serologic and
virologic characteristics of HBV infection and efficacy or safety of the study intervention.
Sequencing
Viral genome sequence analysis will be performed to evaluate mutations associated with the study
intervention.
SAFETY EVALUATIONS
Safety and tolerability (AEs, clinical safety laboratory assessments, ECGs, vital signs, and physical
examinations) will be evaluated as described in Section 8.2 and Section 8.3 of the Master Protocol
PLATFORMPAHPB2001 and at predefined time points as specified in the Schedule of Activities.
Adverse events of Special Interest are significant AEs that are judged to be of special interest because of
clinical importance, known class effects or based on nonclinical signals. Guidelines are in place for
management of AEs of Special Interest.
PHARMACOKINETIC EVALUATIONS
All participants will have sparse PK sampling during the study intervention period.
Blood samples will be collected for measurement of plasma concentrations of JNJ-3989 (ie, JNJ-3976 and
JNJ-3924) and NA, and serum concentrations of nivolumab at time points specified in the Schedule of
Activities. Bioanalysis of NA and nivolumab is optional at the discretion of the sponsor. Serum collected
for PK may additionally be used to evaluate safety or efficacy aspects that address concerns arising during
or after the study period.
PHARMACOKINETIC/PHARMACODYNAMIC EVALUATIONS
Relationships of individual PK parameters for JNJ-3976 and JNJ-3924, and optionally NA and/or
nivolumab, with RO, selected efficacy and/or safety endpoints may be evaluated, if applicable.
PHARMACODYNAMIC EVALUATIONS
Whole blood samples will be collected for assessment of nivolumab RO on circulating T-cells by flow
cytometry analysis.
Pharmacodynamic biomarkers will be evaluated in all participants pretreatment, on-treatment, and
posttreatment with study intervention as detailed in Section 8.5.
HOST GENETICS
An optional sample for HLA testing will be collected from participants who consent separately to this
component of the study.

JNJ-73763989 
Clinical Protocol 73763989PAHPB2008 Amendment 3
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
13
Status: Approved, Date: 30 June 2023
An optional pharmacogenomic (host DNA) blood sample may be collected (preferably at baseline) to allow
for host pharmacogenomic research, where local regulations permit. In addition, host DNA blood samples
to allow for epigenetic analyses will be collected in participants who consent. These samples could for
example be used to assess changes in frequencies of immune cells.
Complete host genomic testing may be done to search for links of specific genes to (HBV-related) liver
disease or to the PK, PD, efficacy, safety, or tolerability of the study intervention. These samples will only
be collected from participants who consent separately to this component 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 Platform study.
In addition, other samples may be used for exploratory genetic or epigenetic research in participants
consenting separately to this part of the study. These samples can only be used to investigate the potential
association of genetic or epigenetic factors with efficacy, safety, or PK of the study intervention, or HBV
infection, or may be used to develop tests/assays related to the study intervention or HBV infection. No
genetic research will be performed on any sample in participants who have not provided the additional
separate consent for host genetic research.
EXPLORATORY HOST BIOMARKERS
The study includes collection of blood samples for exploratory analysis of host blood biomarkers at the
host RNA, protein, and cell level. Sampling will be performed at the time points indicated in the Schedule
of Activities. Leftovers of other samples might also be used for exploratory research of host and viral
markers.
Samples can only be used for research related to study intervention or HBV infection or may be used to
develop tests/assays related to study intervention or HBV infection.
A fine needle aspiration (FNA) biopsy sample may be collected from participants who consent separately
to this component of the study (as permitted by local regulations). If participants agree to undergo an
optional FNA biopsy of the liver, following local standard practice, the biopsy location will be identified
and/or guided with ultrasound and the FNA biopsy samples will be collected after application of local
anesthesia to allow for exploratory biomarker research.
IMMUNE ASSESSMENTS
At selected sites, PBMC samples for immune analyses will be collected during study intervention and
follow-up and will be analyzed centrally for HBV-specific responses by enzyme-linked immunospot
(ELISpot) and/or intracellular cytokine staining (ICS) after stimulation with HBV-specific antigens.
ELISpot detects T-cells that secrete gamma interferon (IFN-γ) in response to a specific antigenic
stimulation, whereas ICS determines the frequency of CD4+ and CD8+ T-cells secreting cytokines such as
IFN-γ, interleukin (IL)-2 and tumor necrosis factor (TNF)-α in response to a specific antigenic stimulation.
Additional PBMC samples may be taken in case of alanine aminotransferase (ALT) flares, upon discussion
with the sponsor, which may require an unscheduled visit.
Additional experiments may be performed to further phenotypically and functionally characterize PBMCs.
Leftover PBMC samples may be used at the sponsor’s discretion for additional exploratory research or to
explore new functional immune assays, or for immune assay optimalization.
Blood samples taken at the time points indicated in the Schedule of Activities, can also be used to explore
the emergence of antidrug antibodies to JNJ-3989 and/or nivolumab. Antidrug antibodies may be analyzed
using assays such as an enzyme-linked immunosorbent assay or functional assays.

JNJ-73763989 
Clinical Protocol 73763989PAHPB2008 Amendment 3
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
14
Status: Approved, Date: 30 June 2023
Medical Resource Utilization
Medical resource utilization data, associated with medical encounters, will be collected in the case report
form (CRF) by the investigator and study site personnel for all participants throughout the study.
Protocol-mandated procedures, tests, and encounters are excluded. The data collected may be used to
conduct exploratory economic analyses and will include:
 
Number and duration of medical care encounters, including surgeries, and other selected procedures
(inpatient and outpatient)
 
Duration of hospitalization (total days length of stay, including duration by wards, eg, intensive care
unit)
 
Number and character of diagnostic and therapeutic tests and procedures
 
Outpatient medical encounters and treatments (including physician or emergency room visits, tests
and procedures, and medications).
STATISTICAL METHODS
Sample Size DeterminationAccording to the initial protocol, the study aimed to have a sample size of 20
participants per intervention arm which  yielded ≥85% statistical power to detect a ≥15% and ≥20%
difference for the proportions of participants with HBsAg seroclearance at FU Week 24 in the
2 intervention arms, respectively, vs a fixed proportion of ≤1%. Statistical power to test the primary
hypothesis was assessed for each of the intervention arms, using an exact test for a single proportion with
a one-sided Type 1 error rate of 0.05 and applying the Hochberg procedure for multiple comparisons
adjustment. The fixed rate assumed for the external active control (JNJ-3989 [200 mg]+NA treatment) is
based on the data of Study 73763989HPB2001 (REEF-1).
The total study sample size was adjusted to 44 participants (22 per arm), with 1:1 randomization ratio to
each of the intervention arms, to account for an approximate 10% attrition rate.
Due to the decision to not extend further enrollment beyond the planned enrollment period and proceed
with a reduced sample size, the final sample size is 37 (18 in Arm 1 and 19 in Arm 2). Under the same
assumptions and methods of the initial protocol, an approximate sample size of 16 participants per
intervention arm (assuming 10% attrition) yields ≥75% statistical power to detect the same differences in
HBsAg seroclearance at FU Week 24.
Efficacy Analyses
The primary efficacy analysis will be performed when all participants have completed the FU Week 24
visit or discontinued earlier. The final analysis will be performed when all participants have completed the
final study visit at FU Week 48 or discontinued earlier.
To evaluate the efficacy, the primary analysis set will be the Full Analysis Set (FAS) (see Section 9.3,
Populations for Analysis Sets). The Full Analysis Set for nivolumab (FAS-N) will be used for sensitivity
analyses of selected efficacy endpoints.
Primary Efficacy Endpoint
The proportion of participants who achieved HBsAg seroclearance at FU Week 24 will be summarized for
each intervention arm paired together with a two-sided, single arm 90% confidence interval (CI) based on
the Clopper-Pearson method. The statistical comparison will be conducted using an exact binomial test
against a fixed external control value of 1% at a one-sided Type 1 error rate of 0.05 and applying the
Hochberg procedure for adjusting for multiple comparisons.

JNJ-73763989 
Clinical Protocol 73763989PAHPB2008 Amendment 3
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
15
Status: Approved, Date: 30 June 2023
Association of the stratification factors and other demographic and baseline disease characteristics with the
primary endpoint may be explored using logistic regression analyses and classification and regression tree
analysis (CART).
The Mantel-Haenszel test adjusted for the randomization stratification factors will be used in a secondary
analysis comparing the primary endpoint between the 2 study intervention arms at a one-sided alpha level
of 0.05.
Secondary Efficacy and Exploratory Endpoints
Descriptive statistics will be used for all efficacy endpoints, which will be summarized by intervention arm
and by study period. Comparisons between intervention arms and 90% CIs may be done with no adjustment
for multiplicity. Specific key selected endpoints may be analyzed using suitable categorical data approaches
(eg, Mantel-Haenszel or logistic regression for proportions or other categorical type of endpoint),
longitudinal repeated measures models (eg, for continuous types of variables), or survival analysis based
on the Kaplan-Meier estimates (for time-to-event variables), as appropriate. Details will be described in the
Statistical Analysis Plan (SAP).
Graphic data displays of different type (eg, bar charts, line plots, and waterfall plots) will also be used to
summarize the efficacy data by intervention arm and over time.
Across ISAs Comparisons of Efficacy
Indirect comparisons between different regimens across multiple ISAs may be performed in an exploratory
fashion by selecting the similar subgroup of participants who match the most important inclusion/exclusion
criteria and demographic characteristics of this ISA.
More details on this approach and its application to secondary endpoints will be provided in a separate
document (eg, SAP or the Modeling and Simulation Report).
Safety Analyses
Safety analyses will be based on the safety population. Safety will be evaluated by means of descriptive
summaries of AEs including AEs of Special Interest to any of the study interventions, clinical laboratory
tests, ECGs, vital signs, and physical examinations. The safety analysis will be done by study period.
Results will be presented in tabular format and/or graphically by intervention arm and over time, as
appropriate.
Other Analyses
Pharmacokinetic Analyses
Population PK analysis of concentration-time data of JNJ-3976 and JNJ-3924, and, optionally, of NA and/or
nivolumab may be performed using non-linear mixed effects modeling. Data may be combined with
selected Phase 1 and/or 2 studies to support a relevant structural model. Available participant characteristics
(eg, demographics, laboratory variables, genotypes) will be included in the model as necessary. Details will
be given in a population PK analysis plan and results of the population PK analysis, if applied, will be
presented in a separate report.
Pharmacokinetic/Pharmacodynamic Analyses
Relationships of PK parameters for JNJ-3976 and JNJ-3924, and, optionally, for NA and/or nivolumab,
with RO, selected efficacy and/or safety endpoints may be evaluated and graphically displayed, if
applicable.
Modeling of key PD parameters (eg, HBsAg, HBV DNA) may be performed using population PK/PD. If
PK/PD modeling of key efficacy endpoints is performed, treatment effect and possible covariates may be

JNJ-73763989 
Clinical Protocol 73763989PAHPB2008 Amendment 3
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
16
Status: Approved, Date: 30 June 2023
investigated. Other biomarkers may be explored at the sponsor’s discretion. If applicable, the results will
be described in a separate report.
Pharmacodynamic Analyses
Descriptive statistics by treatment will be used to summarize PD parameters at each applicable time point.
Statistics include sample size (n), mean, standard deviation (SD), coefficient of variation (CV), geometric
mean, median, minimum, and maximum. Additional PD analyses may be performed, as deemed necessary.
Resistance Analysis
The results of HBV viral sequencing will be evaluated by the sponsor virologist. Relevant changes of amino
acid and/or nucleic acid variations (eg, substitutions) in the HBV genome will be tabulated and described.
Additional exploratory characterization of the HBV viral sequence and phenotype may be performed and
reported separately.
Pharmacogenomic Analyses
The statistical approach for analyzing the exploratory host DNA research samples, including epigenetic
analyses, may depend on the objective of the analyses (eg, efficacy, safety, and/or PK) and possibly relevant
genes at the time of analysis. Analyses will be conducted at the sponsor’s discretion, will always be under
the sponsor’s supervision, and results will be presented either in the clinical study report or a separate report.
Host Biomarker Analyses
Statistical approaches to explore correlations between clinical outcome and blood biomarkers vary and
depend on the different data types of the applied technology platforms, as well as on the extent of observed
interindividual variability. Analyses will be conducted at the sponsor’s discretion, will always be under the
sponsor’s supervision, and results will be presented either in the clinical study report or a separate report.
Immune Analyses
Descriptive statistics (n, mean, SD, CV, geometric mean, median, minimum, and maximum) may be used
to describe the magnitude of the IFN-γ T-cell response or the CD4+ and CD8+ T-cell responses (expressing
at least 1 cytokine such as IL-2, TNF-α or IFN-γ specific to any HBV antigen) as defined by ELISpot and/or
ICS, respectively. Changes from baseline (or positivity threshold) may also be tabulated for PBMCs during
study intervention and follow-up. The proportion (%) of chronic HBV-infected patients with detectable
responses based on the magnitude of the IFN-γ T-cell response or the CD4+ or CD8+ T-cells expressing at
least 1 of the cytokines amongst IL-2, TNF α or IFN-γ for 1 of the HBV antigens as defined by ELISpot
and/or ICS, respectively, will be determined.
Medical Resource Utilization
Medical resource utilization data will be descriptively summarized by intervention arm over time.
Interim Analyses
Interim analyses (IAs) will be conducted to assess safety and evaluate the time course of different safety
and efficacy markers to support the sponsor’s interactions with health authorities, as well as to inform
internal decisions about additional studies and/or investigation of other treatment combinations.

JNJ-73763989 
Clinical Protocol 73763989PAHPB2008 Amendment 3
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
17
Status: Approved, Date: 30 June 2023
Optional IAs are planned when:
 
All randomized participants have completed Week 24 or discontinued earlier.
 
All randomized participants have completed FU Week 12 or discontinued earlier.
Depending on the enrollment rate, any of the above IAs may be skipped if it is too close to the predicted
timing of any adjacent interim cut-offs and additional IAs may be performed by the sponsor to support
interactions with health authorities.
The study is open-label, and the sponsor will conduct IA(s). Hence, the study team and the DRC will have
access to the IA results, while the investigators and participants will not.
Interim analyses will be based on all data available at the predefined cut-off time points and may include
data at later time points for those participants who have reached subsequent visits.

JNJ-73763989 
Clinical Protocol 73763989PAHPB2008 Amendment 3
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
28
Status: Approved, Date: 30 June 2023
2. 
INTRODUCTION
JNJ-73763989 (JNJ-3989) is a liver-targeted antiviral therapeutic for subcutaneous (SC) injection
designed to treat chronic hepatitis B virus (HBV) infection via a ribonucleic acid interference
(RNAi) mechanism. Engagement of the cellular RNAi machinery by JNJ-3989 results in specific
cleavage of HBV RNA transcripts, thereby reducing the levels of HBV proteins and the
pre-genomic ribonucleic acid (pgRNA), the precursor of viral relaxed circular deoxyribonucleic
acid (rcDNA). The small interfering ribonucleic acid(siRNA) triggers in JNJ-3989, JNJ-73763976
(JNJ-3976), and JNJ-73763924 (JNJ-3924), are designed to target all HBV RNA transcripts
derived from covalently closed circular deoxyribonucleic acid (cccDNA), as well as transcripts
derived from integrated HBV DNA. The latter has been suggested to be a significant source of
hepatitis B surface antigen (HBsAg) in hepatitis B e antigen (HBeAg) negative patients or patients
on long-term (≥2 years) treatment with nucleos(t)ide analogs (NAs), the current standard of care.
(Wooddell 2017)
The programmed cell death protein receptor-1 (PD-1) inhibitor is nivolumab, which is a human
immunoglobulin G4 (IgG4) monoclonal antibody that binds to the PD-1 receptor, blocking the
interaction between PD-1 and its ligand PD-L1. Nivolumab is approved for the treatment of certain
cancers at higher doses than intended in this study. The use of nivolumab in the treatment of HBV
is investigational.
The nucleos(t)ide analogs (NAs) are approved treatments of chronic HBV infection.
For the most comprehensive nonclinical and clinical information regarding JNJ-3989, refer to the
latest version of the Investigator’s Brochure (IB) and Addenda for JNJ-3989 (IB JNJ-3989). For
nonclinical and clinical information regarding nivolumab  and NA, refer to the respective
prescribing information.
The term “study intervention” throughout the protocol, refers to JNJ-3989 and nivolumab as
defined in Section 6.1, Study Intervention(s) Administered.
The term “sponsor” used throughout this document refers to the entities listed in the Contact
Information page(s), which will be provided as a separate document.
2.1. 
Study Rationale
Combination treatment with JNJ-3989 and NA has shown  to specifically decrease HBV viral
antigen levels and inhibit viral replication. Since hepatitis B surface antigen (HBsAg) is immune-
suppressive, the direct reduction of HBsAg levels by JNJ-3989 is aimed at contributing to the
restoration of the immune response that is impaired in chronic HBV infection. The restoration of
immune response may not be sufficient and therefore addition of immunomodulatory agents is
being investigated.

JNJ-73763989 
Clinical Protocol 73763989PAHPB2008 Amendment 3
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
29
Status: Approved, Date: 30 June 2023
The current study is designed to assess efficacy and safety of a treatment regimen of 24 weeks of
JNJ-3989 (200 mg administered Q1W for the first 4 weeks then Q4W until Week 24), in
combination with 1 or 3 doses of nivolumab every 4 weeks (Q4W) as of Week 16 and with NA.
Virologically suppressed chronic HBV-infected HBeAg negative patients will be enrolled in this
study.
The primary objective of the study will be to explore the proportion of participants who achieve
HBsAg seroclearance at Follow-up (FU) Week 24. The complete follow-up period will be
48 weeks.
Pharmacokinetic-pharmacodynamic (PK/PD) modeling of JNJ-3989 using a transporter-mediated
drug disposition (TMDD) and indirect response model (IRM) based on REEF-1 data suggests that
applying a loading dose (Q1W) regimen for JNJ-3989 will result in higher liver concentrations
more rapidly than with a Q4W dosing regimen. Higher liver concentrations are expected to result
in a more pronounced and faster decline in HBsAg and may improve the likelihood of achieving
functional cure. Figure 2 illustrates the model-predicted liver concentrations of JNJ-3989 and
corresponding predicted change from baseline in HBsAg, comparing a 200 mg JNJ-3989 Q4W
regimen with a 200 mg JNJ-3989 loading dose regimen (Q1W for the first 4 weeks and then Q4W).
The deterministic prediction was performed using a typical subject of the REEF-1 study, being
virologically suppressed and HBeAg negative, representative of the (median) population.
Figure 2: 
TMDD-IRM Predicted Liver Concentrations of JNJ-3989 (Left) and Corresponding Predicted
Change From Baseline (CFB) in HBsAg (Right) With (Red) and Without (Cyan) Loading
Dosing (200 mg JNJ-3989 Weekly for 4 Weeks) Prior to the 200 mg JNJ-3989 Q4W Regimen

JNJ-73763989 
Clinical Protocol 73763989PAHPB2008 Amendment 3
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
30
Status: Approved, Date: 30 June 2023
A major barrier to achieving functional cure of HBV is the dysfunctional immune response to viral
infection. In patients with chronic hepatitis B (CHB), HBV antigen-specific T-cells are depleted
or exhausted and therefore, incapable of controlling and eliminating virus. HBsAg-specific B-cells
are also deficient in producing antibodies. The primary cause of immune dysfunction is excessive
antigen (eg, HBsAg) stimulation from ongoing viral replication which induces epigenetic
reprogramming of CD8+ T-cells and subsequently increased expression of multiple inhibitory
receptors, such as PD-1. Expression of the corresponding ligands (eg, PDL-1) is also increased. In
vitro, checkpoint blockade with PD(L)-1 inhibitors can reinvigorate cytokine production  of the
immune dysfunction from HBV and proliferation potential of exhausted T-cells (Yang 2021).
In 51 CHB patients with advanced hepatocellular carcinoma (HCC) treated with the humanized
monoclonal antibody (mAb, IgG4) PD-1 inhibitor nivolumab dosed 3 mg/kg every 2 weeks (Q2W)
during the dose expansion phase of CHECKMATE 040, 3 patients (6%) had ≥1 log10 decline in
HBsAg – there were no HBsAg seroconversions or HBV reactivation in this cohort
(El-Khoueiry 2017).
In the initial dose-ranging study of nivolumab, doses of 0.1 to 10 mg/kg IV were used –no serious
adverse events (SAEs), fewer treatment-related Grade 3-4 adverse events (AEs), and no
autoimmune disorders were reported in cancer patients who received single or multiple doses
<1 mg/kg IV (Brahmer 2010, Topalian 2012). Based on these data, Gane 2019 evaluated
single-dose nivolumab 0.1 or 0.3 mg/kg IV alone or with GS-4774 (therapeutic HBV vaccine) in
virologically suppressed CHB patients who were HBeAg negative on current anti-HBV treatment.
Maximum receptor occupancy (RO) measured in peripheral blood mononuclear cell (PBMCs) was
68.9-88.2% across the 2 doses, similar to levels seen in prior evaluations of nivolumab (from 0.1
to 10 mg/kg) and were maintained up to Day 43 post-dose (see Figure 3).
Figure 3: 
Receptor Occupancy: (A) Nivolumab 0.1 mg/kg or 0.3 mg/kg, and (B) Nivolumab 0.3 mg/kg +
GS-4774

JNJ-73763989 
Clinical Protocol 73763989PAHPB2008 Amendment 3
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
31
Status: Approved, Date: 30 June 2023
No difference in HBsAg was observed after 12 weeks in the 2 patients dosed 0.1 mg/kg IV. The
mean (95% confidence interval [CI]) change in HBsAg from baseline to Week 12 was -0.30 (-0.46
to -0.14) log10 IU/mL for 12 patients treated with nivolumab 0.3 mg/kg IV and -0.16 (-0.33 to
0.01) log10 IU/mL for 10 patients treated with nivolumab 0.3 mg/kg IV and GS-4774 40 yeast units
(YU); change in HBsAg from baseline to Week 24 was -0.48 (-0.83 to -0.13) and -0.25 (-0.64 to
0.13), respectively. Individual change in HBsAg is shown in Figure 4 (Gane 2019).
Figure 4: 
Individual Patient Changes in HBsAg From Baseline to Week 12 (Left) or Week 24 (Right) by
Nivolumab Treatment
AEs were reported in 15 patients: 1 (50%) receiving nivolumab 0.1 mg/kg IV, 7 (58%) receiving
nivolumab 0.3 mg/kg IV, and 7 (70%) receiving nivolumab 0.3 mg/kg IV with GS-4774 40 YU.
Most AEs were Grade 1 in severity and were considered not related to nivolumab. One patient
receiving GS-4774 + nivolumab 0.3 mg/kg experienced an AE (injection site pain) considered by
the investigator as related to GS-4774, and 3 patients receiving nivolumab 0.3 mg/kg experienced
an AE (mild fatigue, mild headache, mild cough [1 patient each]) considered by the investigator
as related to nivolumab. The most common AEs were fatigue (3 patients [nivolumab 0.3 mg/kg
group]), upper respiratory tract infection (2 patients [GS-4774 + nivolumab 0.3 mg/kg group]),
and nasal congestion (2 patients [GS-4774 + nivolumab 0.3 mg/kg group]). There were no Grade 3
or 4 AEs or SAEs. There were no AEs of autoimmune disorders (eg, pneumonitis, colitis, rash, or
endocrinopathies). One patient in the 0.3 mg/kg nivolumab group had a baseline alanine
aminotransferase (ALT) of 49 IU/mL which increased to 275 IU/mL at Week 4 (Grade 3 elevation)
after nivolumab administration before returning to 54 IU/mL by the end of study. The ALT
elevation was accompanied by a 3-log10 reduction in HBsAg level and subsequent HBsAg
seroconversion.
Two other patients (1 in the nivolumab 0.3 mg/kg group and 1 in the GS-4774 + nivolumab group)
experienced Grade 1 ALT elevations with peak ALT values of 59 IU/mL  and 61 IU/mL,
respectively, both accompanied by >0.5 log10 reduction in serum HBsAg levels at 24 weeks. The
association of these transient ALT elevations with HBsAg responses in all 3 patients suggested
that these were immune-mediated HBV flares rather than de novo autoimmune hepatitis.
There were no clinically significant abnormal findings for electrocardiograms or vital signs
(Gane 2019).

JNJ-73763989 
Clinical Protocol 73763989PAHPB2008 Amendment 3
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
32
Status: Approved, Date: 30 June 2023
2.2. 
Background
2.2.1. 
Primary Pharmacology
JNJ-3989 is a 2:1 molar mixture of 2 synthetic, double-stranded, N-acetylgalactosamine (GalNac)
conjugated RNAi triggers (JNJ-3976 and JNJ-3924, respectively). RNAi is a naturally occurring
phenomenon by which short, double-stranded RNA oligonucleotides trigger a sequence-specific
down-modulation of gene expression. The RNAi triggers in JNJ-3989 are designed to target all
HBV transcripts derived from cccDNA and integrated viral DNA. This is made possible by the
fact that all HBV transcripts expressed from cccDNA, including the RNA transcript (pgRNA) that
is used as a template for replication of HBV DNA, are terminated by the same polyadenylation
site and share a common sequence region upstream of this site. One RNAi trigger (JNJ-3924) in
JNJ-3989 has its target within this common sequence region and thus has the potential to knock
down expression of all viral proteins as well as the pgRNA expressed from cccDNA. The second
RNAi trigger (JNJ-3976), which targets the HBsAg-encoding region, was designed to knock down
expression of HBsAg derived from integrated HBV DNA as well as all viral proteins derived from
cccDNA with the exception of HBV x protein. Silencing viral RNA will reduce HBV DNA and
viral proteins, including HBsAg.
In mice transiently harboring the human HBV genome, treatment with JNJ-3989 led to
dose-dependent reductions of serum HBsAg, HBeAg, and HBV DNA. Multiple doses of JNJ-3989
resulted in additional and prolonged antigen and HBV DNA reductions in a stepwise fashion when
compared to a single dose. This was consistent with prolonged liver persistence of antisense
strands, which, when loaded into the RNA-induced silencing complex (RISC), exert the
pharmacologic RNAi activity. The ability of JNJ-3989 to reduce serum HBV DNA was additive
to synergistic with entecavir (ETV). ETV alone had no effect on serum HBsAg levels, and no
negative effect on the ability of JNJ-3989 to reduce serum HBsAg was observed when given in
combination.
2.2.2. 
Nonclinical Studies
2.2.2.1. 
JNJ-3989
Little potential for off-target inhibition of human gene expression in participants is expected, based
on in silico human genome database screening.
The nonclinical safety profile of JNJ-3989 has been evaluated through a series of in vitro and in
vivo studies. Repeat-dose SC toxicity studies up to 24 or 37 weeks were conducted in  rat and
monkey, respectively. In the 24- or 37-week studies, JNJ-3989 was administered once weekly
(QW) for the first month, followed by once monthly thereafter. JNJ-3989 was well tolerated in
these studies.
Target organs/tissues in rats are the liver, injection site, kidney, and macrophages (in testes, lymph
nodes, injection site) and in monkeys are the liver, injection site, and macrophages (lymph nodes,
injection site). Most of the observed study intervention-related microscopic changes in these
tissues/organs are well-known modality-related findings (Janas 2018a, Janas 2018b) related to

JNJ-73763989 
Clinical Protocol 73763989PAHPB2008 Amendment 3
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
33
Status: Approved, Date: 30 June 2023
intracellular presence of siRNA. Additionally, adverse findings were noted in the liver and
subcutaneous injection site in rats.
Slight alteration of the renal tubular epithelium in rats was characterized by the presence of
basophilic granules and/or microvacuolation of the cytoplasm of renal tubules in the outer cortex.
After a recovery period of 4 months in rats, most of the kidney findings noted at the end of
treatment hadfully (tubular vacuolation) or partially (basophilic granules) resolved. These findings
were considered not toxicologically meaningful since they were related to compound accumulation
and were largely in line with published data for GalNAC-conjugated siRNA compounds
(Henry 2012; Janas 2018a). There was no evidence of cellular damage (degeneration/necrosis) and
no correlation to clinical pathology indicators of changes in renal function.
After 6 months of dosing with JNJ-3989 in both rat studies (Studies 8381085 and TOX13822),
livers showed basophilic granules in Kupffer cells and hepatocytes, hepatocellular vacuolation,
single-cell necrosis (SCN), increased mitoses, karyomegaly, and/or cytoplasmic alteration, but
also an increased incidence/severity of foci of cellular alteration (FCA), oval cell proliferation and
cholangiofibrosis. These findings accompanied with increased alkaline phosphatase (ALP) activity
levels. The FCA (in combination with the magnitude of other microscopic findings in the liver)
were considered adverse in males at ≥180 mg/kg and in females at ≥60 mg/kg. Following a
4-month treatment-free period, there was no clear evidence of recovery of the FCA in females
(also no progression).
At supra-pharmacologic doses, GalNAc-siRNA compounds are known to induce modality-related
liver findings in the rat. These findings include basophilic granules in hepatocytes and Kupffer
cells, Kupffer cell hyperplasia, hepatocellular vacuolation, degeneration, and SCN, and are
commonly associated with signs of regeneration, such as increased mitosis and karyomegaly. This
may be accompanied by mild increases in hepatic transaminases related to accumulation of
GalNAc-siRNA in the liver (Janas 2018b). Sensitivity to hepatic injury including SCN and
sequelae as a result of GalNAc-siRNA accumulations are described to be largely specific to rats
because they are not seen or occur at lower severity in other species (Janas 2018a). The hypothesis
for the presence of FCA in rat livers is that at continuously high compound exposure/accumulation
in hepatocytes, primary hepatotoxic events (supported by presence of SCN) occur at a higher
incidence/severity in rats. This leads to secondary regenerative proliferative responses (mitoses,
karyomegaly, oval cell proliferation), ultimately leading to FCA, which are potentially
preneoplastic findings (Holsapple 2006; Cattley 2013). While the mechanism for the species
differences is not known, the cascade of hepatotoxic events does not appear to occur in non-human
primates (NHPs), as supported by the 9-month chronic study (Study 8381086) and data from other
GalNAc-siRNA (Givlaari 2019; Janas 2018b). Such liver findings were not observed in NHPs
(Study 8381086) despite exhibiting higher liver concentrations, confirming the higher sensitivity
of rats to liver toxicities induced by JNJ-3989. As reported, NHPs are considered a more relevant
species for testing pharmacologically-related toxicity and potency of RNAi therapeutics as they
present better genomic homology with humans (Ebeling 2011; Janas 2018a; Setten 2019).

JNJ-73763989 
Clinical Protocol 73763989PAHPB2008 Amendment 3
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
34
Status: Approved, Date: 30 June 2023
The subcutaneous injection of JNJ-3989 in rats resulted in chronic vacuolated macrophage
response (phagocytosis of siRNA), mononuclear cell infiltration, and a low incidence of fibrosis
at the end of the dosing period caused by the chronic SC  presence of the compound, while in
monkey only minimal infiltrates of macrophages were observed. In one male rat of the 300 mg/kg
dose group (highest dose tested, Study TOX13822), a poorly differentiated sarcoma was noted at
the left flank during the recovery period. This was not seen in males up to 180 mg/kg,
corresponding to a rat/human plasma area under the plasma concentration-time curve (AUC) ratio
of 59x and 21x for JNJ-3924 and JNJ-3976, respectively (human exposures originating from Study
AROHBV1001). Subcutaneous sarcomas can occur spontaneously in rodents or can be induced
by SC injection by a range of non-carcinogenic agents after varying periods oftime. They can be
induced in laboratory rodents by implanted chemical or inert substances and are typically
associated with agents that elicit a tissue response characterized by severe inflammation, tissue
damage, a macrophage response, fibroblastic proliferation and fibroplasia (Greaves 2012). The
rats in this study were repeatedly injected at the same location (ie, 10 injections in the left flank).
In the embryofetal development (EFD) studies, JNJ-3989 was not teratogenic in rats and rabbits.
The fertility study showed no effects on parental and reproductive parameters in male and female
rats given JNJ-3989 up to a dose of 180 mg/kg/week.
JNJ-3989 was shown to be non-genotoxic when tested in the bacterial reverse mutation assay, and
in vitro and in vivo micronucleus test.
Results of the non-Good Laboratory Practice (non-GLP) in vitro studies demonstrated there is no
potential for induction of the innate immune system (cytokine and complement activation),
mitochondrial toxicity/cytotoxicity, or platelet aggregation associated with JNJ-3989 exposure at
concentrations up to 250 μg/mL.
The animal-to-human exposure ratios were calculated using rat and monkey exposures at no
observed adverse effect levels (NOAELs) from the 24-week studies in rat and the 37-week study
in monkey, respectively, and human exposures after a single SC injection of 200 mg JNJ-3989 in
human participants (AROHBV1001) (Table 1).
For rats, when combining the findings of the two 24-week studies, the most conservative NOAEL
over both studies, is retained for calculations. This resulted in a NOAEL in male rats of 
and a NOAEL in female rats of
CCI
CCI

JNJ-73763989 
Clinical Protocol 73763989PAHPB2008 Amendment 3
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
35
Status: Approved, Date: 30 June 2023
Table 1: 
Animal-to-human Exposure Ratios at NOAEL for JNJ-3989
Ratio Total Concentration
Sex 
NOAEL  
(mg/kg) 
C max 
(ng/mL) 
AUC  
a
(ng∙h/mL) 
Cmax
A/H Ratio 
AUCa
A/H Ratio
JNJ-3976 
Human exposureb 
1,315 
20,136 
- 
-
24-week ratc 
M 
 
23,500 
199,000 
17.9 
9.9
F 
 
12,200 
31,400 
9.3 
1.6
37-week monkeyd 
M 
 
73,200 
1,230,000 
55.7 
61.1
F 
 
65,800 
988,000 
50.0 
49.1
JNJ-3924 
Human exposureb 
363 
4,605 
- 
-
24-week ratc 
M 
 
14,400 
124,000 
39.6 
26.9
F 
 
7,780 
20,600 
21.4 
4.5
37-week monkeyd 
M 
 
21,600 
383,000 
59.5 
83.2
F 
 
23,000 
392,000 
63.4 
85.1
AUC: area under the plasma concentration-time curve; AUC0-24h = area under the plasma concentration-time curve from
administration to 24 h; AUC0-last = area under the plasma concentration-time curve from administration to last quantifiable
sampling point; A/H ratio = animal/human ratio; Cmax: maximum plasma concentration; F = female; M = male.
Source: 24-week rat study (Study 8381085); 24-week monkey (Study 8381086)
a 
AUC0-last for human exposure; AUC0-24h for rat exposures; AUC0-24h for monkey exposures.
b 
Single dose of 200 mg JNJ-3989 in healthy participants via subcutaneous injection (Study AROHBV1001; based on clean
dataset with data cut-off date 29 October 2019).
c 
Once weekly dosing for 5 weeks, followed by once monthly dosing up to a total of 24 weeks.
d 
Once weekly dosing for 5 weeks, followed by once monthly dosing, up to a total of 37 weeks.
For further information, refer to the latest version of the IB for JNJ-3989 (IB JNJ-3989).
2.2.2.2. 
Nivolumab
Nivolumab is a fully human IgG4 monoclonal antibody targeting PD-1. Nivolumab is able to bind
PD-1 from both humans and cynomolgus monkeys and to prevent the interaction of PD-1 with its
ligands, PD-L1 and PD-L2. This interaction plays an important role in the maintenance of
self-tolerance and the prevention of unnecessary tissue damage following immune activation after
acute infection by downregulating the immune response. General toxicology studies with
nivolumab administered either weekly (4-week study) or twice weekly (13-week study) were
conducted in cynomolgus monkeys to investigate the safety of nivolumab. In both monkey studies,
exposure of nivolumab at all dose levels tested exceeded that measured in humans at the intended
clinical dose and schedule of 3 mg/kg once every 2 weeks. Toxicities noted in these monkey
studies were limited to mild increases in monocytic and lymphocytic infiltration in tissues. These
changes are consistent with the pharmacologic activity of the antibody: blocking signaling through
the immune-inhibitory PD-1 pathway. Immunophenotyping performed on samples from monkeys
administered nivolumab during the 13-week study showed a trend towards increases in the
percentage of CD4+ and CD8+ effector and central memory cells; this trend was clearer for the
CD8+ T-cell population. Monkeys did not develop any clear signs of the autoimmune toxicity seen
in clinical trials with nivolumab; however, the generalized lymphocytic infiltration and increases
in memory T-cells do hint at the possibility of these types of toxicities. Given nivolumab’s
mechanism of action, the possibility exists that greater exposure in treated monkeys would result
in a more serious inflammatory pattern closer to that seen clinically (Memorandum 2014).
C
C
C
C
C
C
C
C

JNJ-73763989 
Clinical Protocol 73763989PAHPB2008 Amendment 3
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
36
Status: Approved, Date: 30 June 2023
2.2.2.3. 
Combination Nivolumab + JNJ-3989
Due to the distinct mechanism of action and safety profile of JNJ-3989 and nivolumab, it is not
expected that they will have additive or synergistic effects on toxicology parameters. Therefore, a
combination study with these 2 compounds is not warranted.
2.2.3. 
Clinical Studies
2.2.3.1. 
JNJ-3989
At the time ofprotocol writing, JNJ-3989 is being evaluated in 13 clinical studies. Three Phase 1
studies 
(Study 
73763989HPB1001 
in 
healthy 
adult 
Japanese 
participants,
Study 73763989HPB1002 in adult participants with or without hepatic impairment, and
Study 73763989HPB1004 in healthy adult Chinese participants) and one Phase 1/2a study
(Study AROHBV1001) with a single ascending dose part in healthy adult participants and a
multiple ascending dose part in adult participants with chronic HBV infection are completed.
Conduct of the following studies is ongoing: 2 Phase 1 studies (73763989HPB1003 [renal
impairment], 73763989HPB1005 [relative bioavailability], and 73763989PAHPB1006
[OSPREY], 5 Phase 2 studies (Studies 73763989HPB2001 [REEF-1], 73763989PAHPB2002
[REEF-2], 
73763989PAHPB2003 
[INSIGHT], 
73763989PAHPB2005 
[REEF-IT],
73763989PAHPB2006 [PENGUIN], and 73763989PAHPB2007 [PENGUIN-2]) in adult chronic
HBV-infected participants, and 1 Phase 2 study (Study 73763989HPB2004 [REEF-D]) in adult
participants co-infected with hepatitis B and D virus. In total, 64 healthy, 84 chronic HBV-infected
participants, and 8 participants with moderately impaired hepatic function have been dosed with
JNJ-3989 in completed Studies AROHBV1001, 73763989HPB1001, 73763989HPB1002, and
73763989HPB1004.
Across these completed studies, JNJ-3989 was generally safe and well tolerated with no deaths,
SAEs considered at least possibly related to the study intervention, or AEs leading to study
intervention discontinuation. All treatment-emergent AEs were mild to moderate, with exception
of 1 severe blood creatine phosphokinase increased in 1 chronic HBV-infected participant. All
reported injection site reactions (ISRs) were mild. Adverse events and laboratory abnormalities
were distributed across all dose levels and occurred also on placebo treatment, except for mild
ISRs, which were only reported in participants on JNJ-3989 treatment. Most reported laboratory
abnormalities were isolated incidences and resolved while on study intervention.
In the primary REEF-1 analysis (Week 48, end of treatment), the primary endpoint (ie, proportion
of participants meeting NA completion criteria at Week 48 [assessments performed at Week 44]:
HBsAg <10 IU/mL, <3x  upper limit of normal [ULN] ALT, HBV DNA < lower limit of
quantification [LLOQ] and HBeAg negative) was most commonly met in the HBeAg negative
virologically suppressed subgroup for all regimens containing JNJ-3989. The numerically largest
NA treatment completion rate was observed in the virologically suppressed HBeAg negative
subgroup (200 mg dose group). The main reason for not meeting the primary endpoint criteria in
the HBeAg positive subgroup was the persistence of HBeAg positivity.

JNJ-73763989 
Clinical Protocol 73763989PAHPB2008 Amendment 3
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
37
Status: Approved, Date: 30 June 2023
A dose-response pattern was shown across the 3 dose levels of JNJ-3989 in mean HBsAg (log10)
decline from baseline over time. Overall, mean HBsAg levels in treatment arms containing
JNJ-3989 show the greatest magnitude of decline during the first 24 weeks.
In the REEF-1 Week 48 analysis, no deaths were reported. Ten SAEs were reported of which
2 were considered related to study drug by the investigator. Two participants experienced SAEs
related to study treatment: 1 ALT/aspartate aminotransferase (AST) increased in the triple regimen
(JNJ-3989 100 mg + JNJ-6379 250 mg QD [capsid assembly modulator] + NA) arm and 1 CK
elevation reported as rhabdomyolysis in the JNJ-3989 200 mg + NA arm. The CK elevation was
confounded by recent strenuous exercise. The elevated CK levels returned to normal and did not
recur with subsequent administrations of study treatment.
Overall, 5 (1.1%) participants discontinued investigational treatment due to an AE:
2/95 participants in the triple regimen arm, 2/93 participants in the JNJ-3989 40mg + NA arm, and
1/48 participant in the JNJ-6379 + NA arm.
Of the 29 (6.2%) participants who experienced any Grade 3 or 4 AEs, the largest incidence was
observed in the in JNJ-6379+NA arm (14.6% [7/48]) and the triple regimen arm (7.4% [7/95]).
The most frequent (8 participants) Grade 3 or 4 AEs were alanine aminotransferase increased:
3 participants each in the triple regimen arm and the JNJ-6379 + NA arm, and 2 participants in the
JNJ-3989 200 mg + NA.
Events related to renal function were the most frequently reported AE of Special Interest (14.7%
[14/95] in triple regimen arm and 8.3% [4/48] in JNJ-6379 + NA arm), followed by ISRs (10.8%
[10/93] in JNJ-3989 100mg + NA arm) and ALT/AST elevations (8.3% [4/48] in JNJ-6379 + NA
arm and 7.4% [7/95] in triple regimen arm).
Laboratory Abnormalities and Grade 3/4 ALT Elevations
No eGFR Grade 4 abnormalities were observed. No meaningful changes over time in mean
estimated glomerular filtration rate based on serum creatinine (eGFRcr) are seen in JNJ-3989 +
NA regimens.
Overall, around 5% of the participants experienced AEs or laboratory abnormalities related to
hematologic abnormalities, the majority of mild to moderate severity. The hematologic
abnormalities resolved on continued JNJ-3989 + NA treatment.
Treatment-emergent increases in mean ALT values were mild and remained within the normal
range in all treatment arms. Currently not treated participants were required to have ALT >ULN
at study entry to be eligible while virologically suppressed participants were required to have ALT
≤2x ULN. In currently not treated participants, an increase of mean ALT values early on treatment
was observed, followed by a gradual reduction towards normal values across all treatment arms.

JNJ-73763989 
Clinical Protocol 73763989PAHPB2008 Amendment 3
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
38
Status: Approved, Date: 30 June 2023
For the virologically suppressed participants an immediate increase of mean ALT values is seen
in both arms containing JNJ-6379 and a delayed and gradual increase is seen in JNJ-3989 200 mg
group.
Thirteen cases of ALT flare (3.1% [13 of 425]) (confirmed treatment-emergent elevation of ALT
and/or AST ≥3x ULN and ≥3x nadir) were observed across the active treatment arms, primarily in
currently not treated participants (11 of 13). No ALT flares were observed in the control arm.
Seven ALT flares were observed in the JNJ-3989 200 mg + NA arm (7.3% [7 of 96]), followed by
2 flares each in the JNJ-3989 (100 mg) + NA (2.2% [2 of 93]), JNJ-3989 (100 mg) + JNJ-6379
(250 mg) + NA (2.1% [2 of 95]) and the JNJ-6379 250 mg + NA arms (4.1% [2 of 48]). Majority
of the ALT flares occurred early during the study (61.5% [8 of 13]), between 1-12 weeks, one
ALT flare occurred between 13-24 weeks (7.7% [1 of 13]) and the remainder occurred between
25-48 weeks (30.7% [4 of13]). Declines in virologic parameters were similar between participants
with and without ALT flare. The ALT elevations were without concurrent bilirubin elevations or
signs and symptoms of hepatic dysfunction. All ALT flares resolved or stabilized on continued
treatment.
2.2.3.2. 
Combination of JNJ-3989 and Entecavir, Tenofovir Disoproxil, or
Tenofovir Alafenamide
Entecavir monohydrate is an HBV NA reverse transcriptase inhibitor indicated for the treatment
of chronic HBV infection in adults and children at least 2 years of age with evidence of active viral
replication and either evidence of persistent elevations in serum aminotransferases (ALT or AST)
or histologically active disease. The most common adverse reactions (≥3% of participants) are
headache, fatigue, dizziness, and nausea.
There is no common target organ toxicity between JNJ-3989 and ETV (Memorandum 2005). The
single common toxicity target organ between JNJ-3989 and tenofovir disoproxil or tenofovir
alafenamide (TAF) is the kidney.
Tenofovir disoproxil (available in several salt forms including tenofovir disoproxil fumarate and
tenofovir disoproxil maleate) is a first-generation oral prodrug of the NA tenofovir that is indicated
for the treatment of chronic HBV infection in adult and pediatric patients at least 12 years of age.
In addition, tenofovir disoproxil in combination with other antiretrovirals is indicated for the
treatment of human immunodeficiency virus type 1 (HIV-1) infection in adult and pediatric
patients at least 2 years of age. The most common adverse reactions (≥10% of participants) are
abdominal pain, nausea, insomnia, pruritus, vomiting, dizziness, and pyrexia.
Tenofovir alafenamide is an ester prodrug of the NA tenofovir that is indicated for the treatment
of chronic HBV infection in adults and that is characterized by a better safety profile than tenofovir
disoproxil. The most common adverse reaction (≥10% of participants) is headache. The single
common toxicity target organ between JNJ-3989 and tenofovir disoproxil or TAF is the kidney
(IB JNJ-3989).
For further information regarding ETV, tenofovir disoproxil, and TAF, refer to the respective
currently approved prescribing information.

JNJ-73763989 
Clinical Protocol 73763989PAHPB2008 Amendment 3
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
39
Status: Approved, Date: 30 June 2023
Based on available clinical and nonclinical data, no clinically relevant drug-drug interactions are
expected between JNJ-3989, nivolumab, and NAs. No specific concerns about additive or
synergistic toxicities in the kidney are expected when JNJ-3989 is combined with ETV, tenofovir
disoproxil, or TAF.
2.3. 
Benefit-Risk Assessment
More detailed information about the known and expected benefits and risks of JNJ-3989 may be
found in the IB  (IB JNJ-3989). For nivolumab and NA, refer to the respective prescribing
information.
Weekly dosing of JNJ-3989 was tested in study AROHBV1001 at doses ranging from 100 mg to
300 mg Q1W for 3 doses and no safety concerns were identified. For more details, refer to the IB
(IB JNJ-3989).
2.3.1. 
Benefits for Study Participation
2.3.1.1. 
Known Benefits
The clinical benefit of JNJ-3989 remains to be established.
2.3.1.2. 
Potential Benefits
Results from clinical studies with JNJ-3989 and NAs may be useful for the development of a novel
therapeutic approach for chronic HBV infection.
JNJ-3989 on a background of NAs would target different stages of the viral life cycle. While NA
treatment reduces HBV DNA to levels close to or below the LLOQ of the HBV DNA assay, HBV
replication is not completely inhibited, resulting in replenishment of the cccDNA pool. The
addition of JNJ-3989 is expected to intensify viral suppression by downregulating pgRNA levels
and therefore also HBV DNA. In addition, JNJ-3989 reduces levels of all viral proteins including
HBsAg, which is known to interfere with the host immune responses (Fang 2015; Li 2018;
Wang 2013). By acting on both viral replication and by reducing barriers to the host immune
responses, higher functional cure rates may be achieved.
Gane et al has shown, among the 12 participants who received one dose of 0.3 mg/kg nivolumab,
92% (11/12) had a reduction in HBsAg from baseline during the study. One participant achieved
a ≥0.5 log10 IU/mL decrease in HBsAg at Week 12 that continued to decline and became
undetectable at Week 16 and had an associated ALT flare from Week 3 to Week 8. This participant
developed an anti-HBs response 10 weeks after the end of the study, which is the ultimate goal of
HBV treatment.
2.3.2. 
Risks for Study Participation
2.3.2.1. 
Known Risks
In the AROHBV1001 study, ISRs were the most frequently observed AEs assessed by the
investigator as related to JNJ-3989 administered subcutaneously.

JNJ-73763989 
Clinical Protocol 73763989PAHPB2008 Amendment 3
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
40
Status: Approved, Date: 30 June 2023
Immune checkpoint inhibitors (ICIs), such as anti-PD-1 monoclonal antibodies, target proteins
that enhance the response of the immune system to tumor cells or HBV-infected hepatocytes. By
stimulating the endogenous immune system however, there is the potential for adverse effects on
other tissues by way of immune cell activation and inflammatory mechanisms. The potential
immune-related AEs (irAEs) require close and more frequent monitoring, and early intervention
such as administration of corticosteroids.
Safety risks for nivolumab are based on results from nonclinical toxicology studies and oncology
clinical studies conducted with nivolumab, the known mechanism of action of nivolumab (ie,
anti-PD-1 antibody), and the route of administration. irAEs and infusion-related reactions (IRRs)
have been identified as important identified risks for nivolumab (ie, immune-related pneumonitis,
immune-related colitis, immune-related hepatitis, immune-related nephritis and renal dysfunction,
immune-related endocrinopathies, immune-related skin adverse reactions, other irAEs, and severe
infusion reactions (NSPC).
The safety profile of nivolumab is manageable with the majority of AEs being Grade 1 or Grade 2
in severity based on the National Cancer Institute Common Terminology Criteria for Adverse
Events (NCI-CTCAE). irAEs typically resolve after systemic treatment with corticosteroids or
discontinuation of nivolumab treatment. Immune-related endocrinopathies such as
hypothyroidism and adrenal insufficiency may require endocrine replacement therapy.
Treatment with anti-PD-1 medications is associated with a risk of HBV reactivation in CHB
patients. This risk is reduced with concurrent NA treatment or continuation of ongoing NA
treatment.
In a case series of cancer patients with HIV, HBV, or hepatitis C virus (HCV) infection treated
with ICI therapy including chemotherapy plus immunotherapy, it was found that the safety and
efficacy profile of ICI therapy is similar to that observed in those without chronic viral illness,
suggesting that ICI therapy is a safe and effective treatment option for patients with HIV, HBV,
or HCV infection suffering from advanced-stage cancer (Shah 2019).
2.3.2.2. 
Potential Risks
All therapies have the potential to cause adverse experiences.
Patients with positive HBV DNA and positive HBsAg can always experience increases in liver
transaminases which may indicate immune activation and may result in the reduction of viral
parameters such as HBV DNA and/or HBsAg. Whether this occurs at higher frequency during or
after treatment with JNJ-3989 is not known.
ALT elevation is considered an important potential risk for JNJ-3989. Two distinct patterns of
ALT elevations have been observed: a rapidly rising and resolving ALT elevation, or a sustained
pattern of ALT elevation. In a Phase 2 study involving chronic HBV-infected participants
(REEF-1), ALT flares (ALT ≥3x ULN and ≥3x nadir) were observed in 7% of participants treated
with 200 mg JNJ-3989 Q4W, compared to 0% of participants treated with NA and 0% to 2% of
participants treated with lower doses of JNJ-3989.Those ALT flares seen primarily early during

JNJ-73763989 
Clinical Protocol 73763989PAHPB2008 Amendment 3
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
41
Status: Approved, Date: 30 June 2023
treatment with JNJ-3989, were observed in currently not treated HBeAg positive participants. The
majority of the ALT flares resolved rapidly on continued treatment; 1 was considered serious. In
REEF-D, an ongoing study with HBV/hepatitis D virus (HDV) co-infected participants, 10 out of
22 (45%) participants have developed ALT elevations. Study treatment assignment remains
blinded. Three participants have experienced prolonged elevation of ALT. In 2 participants the
ALT elevation was considered serious. ALT elevation has led to discontinuation of blinded study
treatment in 2 participants. A causal association of ALT elevations with JNJ-3989 has not been
confirmed and the underlying mechanism for ALT elevations being more frequent in context of
HBV HDV co-infection is not yet understood.
Important potential risks of nivolumab include embryofetal toxicity and immunogenicity (NSPC).
Optional fine needle aspiration (FNA) biopsy of the liver will be performed during this study only
for participants who consent to this procedure. The related risks and complications will be
described in a separate informed consent form (ICF) and may include pain and discomfort located
at or near the puncture site (Tang 2003). No complications were seen in a series of more than
1000 FNA biopsies performed as part of monitoring of liver allografts (Lautenschlager 1991).
During the conduct of this OCTOPUS-1 study, two cases of possible hyperthyroidism were
reported. Both cases occurred in participants in treatment Arm 1 who were randomized to receive
a single dose of nivolumab administered at treatment week 16 of JNJ-73763989 treatment. At
treatment week 24, thyroid-stimulating hormone (TSH) was reduced in both patients. While the
first patient had normal free T3 and free T4 and TSH values returned to normal at follow-up visits,
the second patient had fully suppressed TSH with elevation of free T3 and free T4. In light of this
observation, the Sponsor decided on 20 June 2023 to not further expose any patients in the
OCTOPUS-1 study to nivolumab. Two patients were concerned by this USM and did not receive
their third dose of nivolumab.
Please refer to Section 2.2, Background, for details on the safety results in the studies conducted
to date.
2.3.3. 
Benefit-Risk Assessment for Study Participation
Based on the available data and proposed safety measures, the overall risk/benefit assessment for
JNJ-3989 and nivolumab clinical studies is deemed acceptable for the following reasons:
 
Efficacy and safety of JNJ-3989 with NA as assessed in CHB patients in the REEF-1 study
over a 48-week period was generally considered safe and well tolerated. Robust reductions of
HBsAg levels were seen in all JNJ-3989 arms, however, HBsAg seroclearance occurred only
in a few participants. In the current study, JNJ-3989 is being combined with nivolumab, a
PD-1 inhibitor, which may lead to higher seroclearance rates.
 
The toxicities associated with JNJ-3989, nivolumab and NAs are manageable with guidance
provided in this protocol, the IB, and approved prescribing information. ALT/AST elevations
is an important potential risk associated for JNJ-3989 and has been observed in the REEF-1
study. These ALT/AST elevations were not associated with signs of reduced liver function.
Nivolumab is a PD-1 inhibitor administered intravenously and is associated with irAEs and

JNJ-73763989 
Clinical Protocol 73763989PAHPB2008 Amendment 3
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
42
Status: Approved, Date: 30 June 2023
IRRs. Nivolumab may cause fetal harm when administered to pregnant women. NAs are
established treatment for chronic hepatitis B and well tolerated; discontinuation of NA
treatment may lead to reactivation of hepatitis.
 
Continued careful assessment of the safety, efficacy, and PK during treatment is included in
this study.
 
Events of Special Interest are significant AEs that are judged to be of special interest because
of clinical importance, known class effects or based on nonclinical signals. Events of Special
Interest that will be carefully monitored during the study include ALT/AST elevations
including immune-related hepatic AEs, IRRs and other irAEs (including gastrointestinal AEs,
neurological AEs, pulmonary AEs, renal AEs, endocrinopathies, rash, uveitis and visual
complaints, lipase/amylase elevations, and infection; see Section 8.3.6.1 and Section 8.3.6.2).
Other AEs of Special Interest related to JNJ-3989 that will be carefully monitored during the
study include hematological abnormalities and ISRs (see Section 8.3.6.3).
 
To minimize potential risk and stress to participants, the following measures are in place:
 
Utilization of selection criteria which exclude participants who may potentially be at
higher risk of an AE (see Section 5, Study Population).
 
Utilization of withdrawal criteria (see Section 7, Discontinuation of Study Intervention
and Participant Discontinuation/Withdrawal). If a participant drops out due to withdrawal
of consent, he/she will be offered an optional safety follow-up visit.
 
At regular time points throughout the study (see Schedule of Activities), blood samples
for biochemistry, blood coagulation, and hematology and urine samples for urinalysis,
urine chemistry, and renal biomarkers will be collected. Vital signs (systolic and diastolic
blood pressure, pulse rate, and body temperature), height (only at screening), body
weight, and electrocardiograms (ECGs) will be recorded throughout the study. Physical
examinations will be performed, and AEs will be assessed (see Section 8.2, Safety
Assessments). AEs of Special Interest will be closely monitored (Section 8.3.6,
Guidelines for Management of Adverse Events of Special Interest Including
Immune-Related Adverse Events).
 
An internal Data Review Committee (DRC) will be established forcontinuous monitoring
of safety data including SAEs, AEs leading to discontinuation, and ALT flares to ensure
the continuing safety of the participants enrolled in the current study. In addition, an
Independent Flare Expert Panel (IFLEP) will be appointed to characterize and adjudicate
each ALT flare. See Section 10.3.6, Committees Structure.
 
Participants will be regularly monitored for HBV reactivation and virologic
breakthroughs throughout the study.
 
Participants will be monitored closely during the 48-week follow-up period, with frequent
follow-up visits.
 
JNJ-3989 will be administered using a proper SC technique to decrease the risk of ISRs.
ISRs will be managed as outlined in Section 8.3.6, Guidelines for Management of
Adverse Events of Special Interest Including Immune-Related Adverse Events.
Nivolumab will be administered by IV  infusion and participants will be carefully
monitored for IRRs.

JNJ-73763989 
Clinical Protocol 73763989PAHPB2008 Amendment 3
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
43
Status: Approved, Date: 30 June 2023
 
Female participants will be monitored for pregnancy due to risk of embryofetal toxicity
associated with PD-1 inhibitors. Participants of childbearing potential are required to use
a highly effective user-independent contraceptive method while receiving study
intervention and until 5 months after the last dose of study intervention.
 
Any clinically significant abnormalities persisting at the end of the study/early
discontinuation will be followed up by the investigator until resolution (return to baseline)
or until stabilization (to be agreed upon with the sponsor).
More detailed information about the benefits and risks of JNJ-3989 may be found in the IB. For
nivolumab and NA, refer to the respective prescribing information.
3. 
OBJECTIVES AND ENDPOINTS
Below is the list of objectives and endpoints that will be evaluated in this study, delineating the
details in alignment with the general objectives listed in the Master Protocol
PLATFORMPAHPB2001. The details specific for this ISA are highlighted (colored fill).
Objectives 
Endpoints
Primary
To evaluate efficacy of the study intervention, 
based on HBsAg levels at FU Week 24. 
 
Proportion of participants who achieve
HBsAg seroclearance at FU Week 24.
Secondary
To characterize the safety and tolerability of 
the study intervention. 
 
Proportion 
of 
participants 
who
experienced AEs of interest.
 
Safety  profile 
of JNJ-3989 
with
nivolumab throughout the study (safety
parameters include but are not limited to
the frequency and severity of AEs and
immune-related 
AEs, 
vital 
signs
measurements, physical examinations,
clinical laboratory values, and 12-lead
electrocardiograms [ECGs]).
To evaluate efficacy in terms of changes in
HBsAg levels from baseline over time during
the study intervention and follow-up periods.
 
Change from baseline in HBsAg levels
during the study intervention and
follow-up periods.
 
Proportion of participants with HBsAg
levels below/above different cut-offs over
time.
To evaluate efficacy in terms of HBsAg
seroclearance/seroconversion during the study
intervention and follow-up periods (as defined
in the Definitions of Terms).
 
Proportion of participants with HBsAg
seroclearance/seroconversion during the
study intervention and follow-up periods.
 
Time to achieve HBsAg seroclearance/
seroconversion.

JNJ-73763989 
Clinical Protocol 73763989PAHPB2008 Amendment 3
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
44
Status: Approved, Date: 30 June 2023
Objectives 
Endpoints
To evaluate the efficacy as measured by blood 
markers (such as HBV DNA and HBeAg) 
during the study intervention and follow-up 
period. 
 
Change from baseline in HBV DNA
levels during the study intervention and
follow-up periods.
 
Proportion of participants with HBV DNA
and HBeAg levels below/above different
cut-offs over time.
To evaluate the frequency of virologic
breakthrough throughout the study.
 
Proportion of participants with virological
breakthrough throughout the study.
To evaluate the pharmacokinetics (PK) of
JNJ-3989 (JNJ-3924 and JNJ-3976), and
optionally of NA and/or nivolumab.
 
PK parameters of JNJ-3989 (JNJ-3924
and JNJ‑3976).
 
Optionally, PK parameters of NA and/or
nivolumab.
Exploratory
To characterize the pharmacodynamics (PD)
of JNJ-3989 with nivolumab including
quantification of RO on peripheral T-cells.
 
Relationship of various PK parameters
with 
selected 
efficacy 
and 
safety
endpoints.
 
Quantification of nivolumab RO on
peripheral 
CD3+ 
T-cells 
by flow
cytometry on whole blood.
To explore changes in the severity of liver
disease.
 
Changes in fibrosis (according to
Fibroscan liver stiffness measurements) at
end of study intervention (EOSI) and the
end of the follow-up  period versus
baseline.
To explore HBV-specific T-cell responses
throughout the study.*
 
Changes from baseline in HBV-specific
peripheral blood T-cell responses over
time.
To explore efficacy of the study intervention
in terms of changes in HBV RNA and
hepatitis B core-related antigen (HBcrAg)
levels throughout the study.
 
Changes from baseline in HBV RNA and
HBcrAg levels over time.
To explore the HBV genome sequence
throughout the study.
 
Assessment of intervention-associated
mutations over time.

JNJ-73763989 
Clinical Protocol 73763989PAHPB2008 Amendment 3
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
45
Status: Approved, Date: 30 June 2023
Objectives 
Endpoints
To explore medical resource utilization to 
manage participants throughout the study. 
 
Number and duration of medical care
encounters, including surgeries, and other
selected 
procedures 
(inpatient 
and
outpatient).
 
Duration of hospitalization (total days
length of stay, including duration by
wards, eg, intensive care unit).
 
Number and character of diagnostic and
therapeutic tests and procedures.
 
Outpatient 
medical 
encounters 
and
treatments 
(including 
physician 
or
emergency 
room 
visits, 
tests 
and
procedures, and medications).
*PBMC samples for immune analyses will be collected at selected sites only.
Refer to Section 8, Study Assessments and Procedures for evaluations related to endpoints.
HYPOTHESIS
The primary hypothesis of this study is that at least one of the combination regimens of
JNJ-3989+nivolumab+NA is more efficacious than JNJ-3989+NA treatment, as measured by the
primary efficacy endpoint (ie, the proportion of participants with HBsAg seroclearance at FU
Week 24). Because the study does not include a regimen arm without nivolumab, the hypothesis
is formulated assuming a fixed response rate for JNJ-3989+NA of 1% based on previous
Study 73763989HPB2001 (REEF-1).
4. 
STUDY DESIGN
4.1. 
Overall Design
This ISA describes a Phase 2 study of the combination regimen of JNJ-3989 with nivolumab and
NA. It is a companion document to the Master Protocol PLATFORMPAHPB2001, which
describes the common design elements of the Platform study in participants with chronic HBV
infection. This ISA describes specific and/or additional protocol elements applicable to this
randomized, open-label, parallel, multicenter, interventional study  to evaluate safety, efficacy,
tolerability, PK and PD of a combination of JNJ-3989, nivolumab, and NAs in virologically
suppressed chronic HBV-infected adult participants.
Initially, a target of approximately 44  virologically suppressed, HBeAg negative, adult chronic
hepatitis B participants ≥18 (or the legal age of consent in the jurisdiction in which the study is
taking place) to <56 years of age were planned to be randomly assigned in this study with
22 participants planned per arm.
Due to the decision to not extend further enrollment beyond the planned enrollment period and
proceed with a reduced sample size, the final sample size is 37 (18 in Arm 1 and 19 in Arm 2).

JNJ-73763989 
Clinical Protocol 73763989PAHPB2008 Amendment 3
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
46
Status: Approved, Date: 30 June 2023
This open-label study will be conducted in 3 periods:
 
6-week Screening Period (if necessary, eg, for operational reasons, this can be extended
to a maximum of 8 weeks decided on a case-by-case basis and in agreement with the
sponsor). During the Screening Period, the participants will continue the same NA
treatment they were receiving before screening.
 
24-week Study Intervention Period:
o 
Arm 1: JNJ-3989 Q1W for the first 4 weeks and then Q4W until Week 24 +
nivolumab at Week 16 + NA QD
o 
Arm 2: JNJ-3989 Q1W for the first 4 weeks and then Q4W until Week 24 +
nivolumab Q4W at Weeks 16, 20, 24 + NA QD.
 
48-week Follow-up Period, during which NA treatment will be continued.
At baseline, participants who meet the eligibility criteria will be randomized in a 1:1 ratio to Arm 1
or Arm 2. Randomization will be stratified by absolute HBsAg level (<100 IU/mL, 100 to
<1,000 IU/mL, and ≥1,000 IU/mL) at screening, as assessed by quantitative HBsAg assay.
Background treatment consists of:
- NA: tenofovir disoproxil (245 mg), TAF (25 mg), or ETV (0.5 mg) given as oral tablets
QD for approximately 76 weeks (screening included).
Study intervention consists of:
 
JNJ-3989: 200 mg given by SC injections Q1W for the first 4 weeks and then Q4W until
Week 24 (10 doses)
 
Nivolumab: 0.3 mg/kg, one single IV infusion at Week 16 for Arm 1 or 3 IV infusions at
Weeks 16, 20, and 24 for Arm 2.
Assessments and sampling will be done for efficacy (eg, HBsAg, HBeAg, and HBV DNA), safety
(eg, [S]AEs, irAEs, laboratory evaluations, ECGs, vital signs, physical examinations), PK, PK/PD,
viral genome sequencing, PBMC, human leukocyte antigen (HLA) typing, immunogenicity and
pharmacogenomics, and for exploratory analysis of host and viral markers.
The total duration of individual participation will be up to 72 weeks (screening not included).
Participants will be considered to have completed the study if they have completed all the
assessments of the final study visit (ie, FU Week 48).
If a participant prematurely discontinues treatment with JNJ-3989 before Week 24, the participant
will also discontinue further treatment with nivolumab and will have an early withdrawal (WD)
visit. Follow-up assessments should be obtained as per the Schedule of Activities until 48 weeks
after the end of JNJ-3989 treatment, unless the participant withdraws consent. The NA treatment
will be continued until the end of the study.

JNJ-73763989 
Clinical Protocol 73763989PAHPB2008 Amendment 3
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
47
Status: Approved, Date: 30 June 2023
If a participant prematurely discontinues nivolumab, treatment with JNJ-3989 and NA should be
continued as planned, unless a treatment discontinuation rule for JNJ-3989 is also met. In that case,
JNJ-3989 will also be discontinued but NA treatment should be continued as planned.
If a participant withdraws prematurely from the study, the reason for withdrawal (if known) should
be documented. Participants who withdraw consent will be offered an optional safety follow-up
visit to occur on the day of consent withdrawal.
An internal DRC will be commissioned for monitoring safety of participants enrolled in this study.
In addition, an IFLEP will be appointed. Refer to Committees Structure in Appendix 3: Regulatory,
Ethical, and Study Oversight Considerations for details.
A diagram of the study design is provided in Section 1.2, Schema.
4.2. 
Scientific Rationale for Study Design
Randomization
Randomization will be used to minimize bias in the assignment of participants to intervention
arms, to increase the likelihood that known and unknown participant attributes (eg, demographic
and baseline characteristics) are evenly balanced across intervention  arms, and to enhance the
validity of statistical comparisons across intervention arms. Randomization will occur at baseline.
Stratification Factors
Randomization will be stratified by absolute HBsAg level (<100 IU/mL, 100 to <1,000 IU/mL,
and ≥1,000 IU/mL) at screening, as assessed by quantitative HBsAg assay.
Host DNA and Exploratory Host Biomarker Collection
Refer to Section 4.2 of the Master Protocol PLATFORMPAHPB2001.
Optional FNA biopsy samples may be collected to assess intrahepatic immune responses which
can be compared to responses in PBMCs.
4.2.1. 
Study-Specific Ethical Design Considerations
Refer to Section 4.2.1 of the Master Protocol PLATFORMPAHPB2001. Differences with the
Master Protocol PLATFORMPAHPB2001 are highlighted (colored fill).
Written consent may be obtained through various sources (eg, paper or electronic such as
eConsent, eSignature, or digital signature) as determined by regulations as well as study and/or
patient preferences.
FNA biopsies may be performed during this study only for participants who consent to this
procedure. The risks and complications related to these procedures are described in Section 2.3.2.2.
These risks and complications will be described in the ICF and will be clearly explained to
potential participants prior to enrollment.

JNJ-73763989 
Clinical Protocol 73763989PAHPB2008 Amendment 3
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
48
Status: Approved, Date: 30 June 2023
4.3. 
Justification for Dose and Treatment Duration
The proposed dose and treatment duration for JNJ-3989 are selected to maximize the chance for
patients to achieve functional cure and are supported by scientific understanding of available data.
The same dose (ie, 200 mg of JNJ-3989) is currently being tested in ongoing Phase 2b studies.
Clinical data on PK, PD, safety, and efficacy of JNJ-3989 are available from the completed
Phase 1/2a AROHBV1001 study. Twenty adult healthy participants received single SC injections
of JNJ-3989 (35, 100, 200, 300, and 400 mg) and 84 adult chronic HBV-infected participants
received multiple doses of JNJ-3989 (25, 50, 100, 200, 300, and 400 mg), administered as 3 SC
injections separated by either 7-day, 14-day, or 28-day intervals. All participants either continued
or started on ETV or tenofovir disoproxil on Day 1.
JNJ-3989 was generally safe and well tolerated at all doses. No clinically relevant safety signal
was identified.
Antiviral activity data are available for 56 chronic HBV-infected participants who received 3 SC
injections of 25 to 400 mg JNJ-3989 Q4W (Gane 2019; Yuen 2019; IB JNJ-3989). In general,
mean HBsAg declines reached nadir at Day 113 (ie, 8 weeks after last JNJ-3989 injection). Mean
HBsAg levels remained suppressed (below baseline levels) at least until Day 392 (ie, 9 months
after last dose) in a substantial proportion of patients. The HBsAg levels at Day 392 were variable
with some patients having HBsAg levels close to baseline levels while a substantial proportion of
patients still had HBsAg levels >1 log10 IU/mL lower than the baseline levels. JNJ-3989 showed
activity on other viral markers (HBV DNA, HBV RNA, HBeAg and HBcrAg), frequently with
sustained reduction at least until Day 362. No apparent dose-response was observed at doses
between 100 mg and 400 mg JNJ-3989, a numerically smaller mean decline was observed at the
lower doses of 25 mg and 50 mg, mainly apparent after end of JNJ-3989 dosing.
Clinical data on efficacy and safety of JNJ-3989 are available from the Phase 2b
73763989HPB2001 (REEF-1) study. One of the objectives of this ongoing study is to assess the
dose-response relationship for antiviral activity of 3 doses (40 mg, 100 mg and 200 mg,
administered Q4W) of JNJ-3989 in combination with NA.
A dose of 200 mg JNJ-3989 is chosen based on the dose-response pattern that was observed across
the 3 dose levels of JNJ-3989 in mean HBsAg (log10) decline from baseline over time in
Study REEF-1. Furthermore, a dose of 200 mg JNJ-3989 is chosen based on the observed decline
in HBsAg in Study AROHBV1001 at this dose over 3 injections, and the lack of a substantial
incremental efficacy response at higher doses.
A JNJ-3989 dosing interval of Q1W for the first 4 weeks and then Q4W until Week 24 is chosen
based on PK/PD modeling of JNJ-3989 using a TMDD and IRM based on REEF-1 data,
suggesting that a loading dose (Q1W) regimen  for JNJ-3989 will result in higher liver
concentrations more rapidly than a Q4W dosing regimen. Higher liver concentrations are expected
to result in a more pronounced and faster decline in HBsAg and may improve the likelihood of
achieving functional cure.

JNJ-73763989 
Clinical Protocol 73763989PAHPB2008 Amendment 3
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
49
Status: Approved, Date: 30 June 2023
The proposed dose of nivolumab, 0.3 mg/kg, is based on available data for the use of nivolumab
in CHB patients (refer to Section 2.1 for further information). The frequency of dosing in Arm 2,
Q4W, is based on the estimated geometric mean half-life of nivolumab (25 days) and frequency
of administration for its approved indications in oncology (for more details, refer to the nivolumab
prescribing information).
4.4. 
End of Study Definition
End of Study Definition
The end of study is considered as the last scheduled study visit (FU Week 48 or early
discontinuation) for the last participant in the study. The final data from the study site will be sent
to the sponsor (or designee) after completion of the final participant visit at that study site, in the
time frame specified in the Clinical Trial Agreement.
Participant Study Completion Definition
A participant will be considered to have completed the study if the participant has completed
assessments of the final study visit (ie, FU Week 48).
5. 
STUDY POPULATION
Screening for eligible participants will be performed within 42 days before administration of the
study intervention. If necessary, eg, for operational reasons, the Screening Period may be extended
up to a maximum of 8 weeks decided on a case-by-case basis and in agreement with the sponsor.
The inclusion and exclusion criteria for enrolling participants in this study 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.
Exceptional and limited retesting of abnormal screening values that lead to exclusion is allowed
once, using an unscheduled visit during the Screening Period (to reassess eligibility).
For a discussion of the statistical considerations of participant selection, refer to Section 9.2,
Sample Size Determination.
Each potential participant must satisfy all inclusion and exclusion criteria from the Master Protocol
PLATFORMPAHPB2001 (numbering prefixed by “M” in the list below) and all additional
intervention-specific inclusion and exclusion criteria (numbering prefixed by “A” in the list
below). The latter inclusion and exclusion criteria are highlighted (colored fill). For the few criteria
from the Master Protocol that are specified or more restricted in this ISA, the additional text is also
highlighted (colored fill).

JNJ-73763989 
Clinical Protocol 73763989PAHPB2008 Amendment 3
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
50
Status: Approved, Date: 30 June 2023
5.1. 
Inclusion Criteria
Each potential participant must satisfy all of the following criteria to be enrolled in the study:
A01 (adapted 
from M01) 
Adult male or female participants ≥18 (or the legal age of consent in the jurisdiction in
which the study is taking place) to <56 years of age.
M02 
Participants must be medically stable based on physical examination, medical history,
vital signs, and 12-lead ECG performed at screening. If there are abnormalities, they
must be consistent with the underlying illness in the study population. This determination
must be recorded in the participant’s source documents and initialed by the investigator.
A03 (adapted 
from M03a) 
Participants must have chronic HBV infection. HBV infection must be documented by
serum HBsAg positivity at screening. In addition, chronicity must be documented by any
of the following, at least 6 months prior to screening: serum HBsAg positivity, HBeAg
positivity or HBV DNA positivity, ALT elevation >ULN without another cause than
HBV infection, documented transmission event, liver biopsy with changes consistent
with chronic HBV, or absence of marker for acute HBV infection at screening such as
positive immunoglobulin M (IgM) anti-HBc antibodies.
Participants should:
 
Be HBeAg negative at screening, AND
 
Be on stable HBV treatment, defined as currently receiving NA treatment
(ie, entecavir, tenofovir disoproxil, or tenofovir alafenamide) for at least 12 months
prior to screening, and having been on the same NA treatment regimen (at the same
dose) as used in this study (see Table 4) for at least 3 months at the time of screening,
AND
 
Have serum HBV DNA <60 IU/mL on 2 sequential measurements at least 6 months
apart (one of which is at screening), AND
 
Have documented ALT values <2.0x ULN on 2 sequential measurements at least
6 months apart (one of which is at screening).
A04 (adapted 
from M04) 
Participants must have a body mass index (BMI; weight in kg divided by the square of
height in meters) between 18.0 and 30.0 kg/m2, extremes included.
A05 (adapted 
from M05) 
Participants must sign a Master ICF (specific for the Master Protocol
PLATFORMPAHPB2001) and must sign an ICF specific for this intervention cohort,
indicating that he or she understands the purpose of, and procedures required for, the
study and is willing to participate in the study.
A06 (adapted 
from M06) 
Participants must sign a separate ICF if he or she agrees to provide additional optional
DNA samples and/or FNA biopsy samples for research (where local regulations permit).
Refusal to give consent for the optional DNA and/or FNA biopsy research samples does
not exclude a participant from participation in the study.

JNJ-73763989 
Clinical Protocol 73763989PAHPB2008 Amendment 3
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
53
Status: Approved, Date: 30 June 2023
A02 
(adapted 
from M02)
Participants with evidence of hepatic decompensation at any time point prior to or at the
time of screening:
a. 
Total bilirubin >1.5x ULNa, OR
b. Direct bilirubin >1.2x ULN b, OR
c. 
Prothrombin time >1.3x ULN (unless caused by anticoagulation therapy or vitamin
K deficiency)b, OR
d. Serum albumin <3.2 g/dLb.
M03 
History or evidence of clinical signs or symptoms of hepatic decompensation, including
but not limited to: portal hypertension, ascites, hepatic encephalopathy, esophageal
varices.
M04 
Participants with evidence of liver disease of non-HBV etiology. This includes but is not
limited to hepatitis infections mentioned in exclusion criterion A01, drug- or
alcohol-related liver disease, autoimmune hepatitis, hemochromatosis, Wilson’s disease,
α-1 antitrypsin deficiency, primary biliary cholangitis, primary sclerosing cholangitis,
Gilbert’s syndrome (mild cases are allowed) or any other non-HBV liver disease
considered clinically significant by the investigator.
A05 
(adapted 
from M05) 
Participants with history or signs of cirrhosis or portal hypertension (nodules, no smooth
liver contour, no normal portal vein, spleen size ≥12 cm) or signs of HCC or clinically
relevant renal abnormalities on an abdominal ultrasound performed within 3 months prior
to screening or at the time of screening. In case of suspicious findings on conventional
ultrasound the participant may still be eligible if HCC or clinically relevant renal
abnormalities have been ruled out by a more specific imaging procedure
(contrast-enhanced ultrasound, CT or MRI).
A06 
(adapted
from M06)
Criterion modified per Amendment 1:
A06.1 Participants with one or more of the following laboratory abnormalities at screening
as defined by the Division of Acquired Immunodeficiency Syndrome (DAIDS) Toxicity
Grading Scale (see Section 10.8, Appendix 8: DAIDS Table with Modifications):
a. 
Estimated glomerular filtration rate based on serum creatinine (eGFRcr) ≥Grade 3
(ie, <60 mL/min/1.73 m2) at screening, calculated by the Chronic Kidney Disease
Epidemiology Collaboration (CKD-EPI) formula;
b. Pancreatic lipase elevation ≥Grade 3;
c. 
Pancreatic amylase elevation ≥Grade 3;
d. Hemoglobin ≤10.9 g/dL (males), ≤10.4 g/dL (females);
e. 
Platelet count ≤lower limit of normal (LLN);
f. 
Absolute neutrophil count <1,500/mm  
3 (<1,000/mm3 for participants of African
ancestry);
g. Alpha-fetoprotein (AFP) >100 ng/mL;
a Unless explained by a clinical setting that is not hepatic decompensation.

JNJ-73763989 
Clinical Protocol 73763989PAHPB2008 Amendment 3
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
54
Status: Approved, Date: 30 June 2023
Note: Participants with AFP >ULN but ≤100 ng/mL may be eligible if HCC can be
ruled out based on a sensitive imaging study (eg, contrast-enhanced ultrasound, CT
or MRI) during screening.
h. Abnormal thyroid function (including TSH, free triiodothyronine [T3] and free
thyroxine [T4])
i. 
Positive autoantibody test results for at least one of the following:
o Anti-nuclear antibodies (ANA) titer ≥1:80;
o Anti-smooth muscle antibodies (ASMA) titer ≥1:80;
o Anti-mitochondrial antibodies (AMA) titer ≥1:80;
o Anti-thyroid peroxidase antibodies ≥35 IU/mL;
o Anti-Neutrophil Cytoplasmic Antibody (ANCA) titer ≥1:20;
o Rheumatoid factor ≥14 IU/mL.
Note:In case of ≥2 positive tests but below the exclusionary cut-off, participant may
be enrolled if approved by the sponsor before randomization.
j. 
Any other laboratory abnormality considered to be clinically significant by the
investigator (also see exclusion criterion A02).
M07 
Participants with hemoglobin A1c >8% at screening.
M08 
Participants with a history of malignancy within 5 years before screening (exceptions are
squamous and basal cell carcinomas of the skin and carcinoma in situ of the cervix, or
malignancy, which are considered cured with minimal risk of recurrence).
M09 
Participants with abnormal sinus rhythm (heart rate <45 or >100 beats per minute [bpm]);
QT interval corrected for heart rate according to Fridericia’s formula (QTcF) >450 ms for
males and >470 ms for females; QRS interval ≥120 ms; PR interval >220 ms; or any other
clinically significant abnormalities on a 12-lead ECG at screening (eg, significant
abnormal conduction).
M10 
Participants with a history of or current cardiac arrhythmias (eg, significant extrasystole
patterns, tachycardia at rest), history of risk factors for Torsade de Pointes syndrome
(eg, hypokalemia, family history of long QT Syndrome) or history or other clinical
evidence of significant or unstable cardiac disease (eg, angina, congestive heart failure,
myocardial infarction, diastolic dysfunction, significant arrhythmia and/or coronary heart
disease), moderate to severe valvular disease, or uncontrolled hypertension at screening.

JNJ-73763989 
Clinical Protocol 73763989PAHPB2008 Amendment 3
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
55
Status: Approved, Date: 30 June 2023
M11  
Participants with any current or previous illness for which, in the opinion of the
investigator and/or sponsor, 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. This may include but is not limited to significant vascular,
pulmonary (eg, chronic obstructive pulmonary disease), gastrointestinal (eg, significant
diarrhea, gastric stasis, or constipation that in the investigator’s opinion could influence
drug absorption or bioavailability), endocrine (eg, thyroid disease), neurologic,
hematologic, rheumatologic, psychiatric, neoplastic, or metabolic disturbances. Any
condition possibly affecting drug absorption (eg, gastrectomy or other significant
gastrointestinal tract surgery, such as gastroenterostomy, small bowel resection, or active
enterostomy) will also lead to exclusion.
M12  
Participants who have received an organ transplant (except for skin, hair, or cornea
transplants).
M13 
Participants with any history of or current clinically significant skin disease requiring
regular or periodic treatment.
M14  
Participants with clinically relevant alcohol or drug abuse within 12 months of screening.
M15 
Participants with history of clinically relevant drug rash.
M16 
Participants who have taken any disallowed therapies as noted in Section 6.5, Concomitant
Therapy before screening.
A17 
(adapted 
from M17) 
Participants having used any invasive investigational medical device within 6 months or
having received an investigational intervention or a biological product, immunoglobulin
or other blood product not intended for the treatment of HBV within 6 months or
5 half-lives (whichever is longer), before the planned first dose of study intervention, or is
currently enrolled in an interventional clinical study with an investigational product.
A18 
(adapted 
from M18)
Female participants who are pregnant, or breast-feeding, or planning to become pregnant
while enrolled in this study, until 5 months after last dose of study intervention.
A19 
(adapted 
from M19)
Male participants who plan to father a child while enrolled in this study, until 5 months
after last dose of study intervention.
M20 
Participants who had major surgery (eg, requiring general anesthesia), excluding
diagnostic surgery, within 12 weeks before screening; or will not have fully recovered
from surgery; or have surgery planned during the time of expected participation in the
study.
Note:Participants with planned surgical procedures to be conducted under local anesthesia
may participate.

JNJ-73763989 
Clinical Protocol 73763989PAHPB2008 Amendment 3
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
57
Status: Approved, Date: 30 June 2023
5.3. 
Lifestyle Considerations
Potential participants must be willing and able to adhere to the following lifestyle restrictions
during the study to be eligible for participation:
1. 
Agree to follow all requirements outlined in Section  6.5, Concomitant Therapy,
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).
5.4. 
Screen Failures
Refer to Section 5.4 of the Master Protocol PLATFORMPAHPB2001 for handling of screen
failures and use of participant identification, enrollment, and screening logs.
This study will use IWRS. The investigator will generate screening and enrollment logs directly
from IWRS.
6. 
STUDY INTERVENTION AND CONCOMITANT THERAPY
6.1. 
Study Intervention(s) Administered
Description of Study Intervention
The JNJ-3989 supplied for this study will be provided as an aqueous clear, colorless to light yellow
solution with 200 mg/mL of JNJ-3989 for SC injection, containing 0.5 mM sodium phosphate
monobasic and 0.5 mM sodium phosphate dibasic in water as inactive ingredients (formulation
G001). JNJ-3989 will be manufactured and provided under the responsibility of the sponsor. Refer
to the IB for a list of excipients (IB JNJ-3989).
The nivolumab formulated as concentrate for solution for infusion will be supplied for this study
by the sponsor as a 40 mg/4 mL solution for IV infusion. Refer to the prescribing information for
a list of excipients.

JNJ-73763989 
Clinical Protocol 73763989PAHPB2008 Amendment 3
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
58
Status: Approved, Date: 30 June 2023
Table 2: 
Description and Administration of Study Intervention
Intervention Name 
JNJ-3989 
Nivolumab
Type 
Drug 
Drug
Dose Formulation  
Solution for injection (G001) 
Concentrate for solution for infusion
Unit Dose Strength(s) 
200 mg/mL  
40 mg/4 mL
Dosage Level(s) 
200 mg Q1W for the first 4 weeks, 
then once every Q4W until Week 24 
0.3 mg/kg (1 intravenous [IV] infusion
for Arm 1 or 3 IV infusions Q4W for
Arm 2)**
Route of Administration 
Subcutaneous injection* (preferably 
in the abdomen; upper arm or thigh
is also allowed)
IV infusion over 30 minutes
Use 
Investigational intervention  
Investigational intervention
Investigational Medicinal Product 
(IMP)
Yes 
Yes
Non-investigational Medicinal 
Product/ Auxiliary Medicinal
Product (NIMP/AxMP)
No 
No
Sourcing 
Provided centrally by the sponsor 
Provided centrally by the sponsor
Packaging and Labeling 
Each unit will be labeled with unique 
medication ID number 
Commercial supplies will be sourced.
Each unit will be labeled with unique
medication ID number
Food/Fasting Instructions 
Regardless of food intake 
Not Applicable
*Note: Administration into scar tissue or areas that are reddened, inflamed or swollen should be avoided. If injecting
into the abdomen, avoid a 5 cm diameter circle around the navel.
**Note: a tolerance of +/- 5% around the theoretical dose of 0.3 mg/kg will be applied to consider the necessary
rounding and standard practice for the preparation and intravenous administration of drugs dosed by weight.
Packaging and Labeling of Study Intervention
All study interventions will be packaged with each unit labeled with a unique medication ID
number. Packaging and labeling of JNJ-3989 and nivolumab will be done in an open-label way.
Commercial supplies of nivolumab will be sourced, and a clinical study  label will be applied.
Study intervention labels will contain information to meet the applicable regulatory requirements.
No study interventions can be repacked or relabeled without prior approval from the sponsor.
Study Intervention Administration
Study intervention administration must be captured in the source documents and the case report
form (CRF).
JNJ-3989 injections will be administered SC (preferably in the abdomen) at the study site and the
approximate location should be recorded.

JNJ-73763989 
Clinical Protocol 73763989PAHPB2008 Amendment 3
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
59
Status: Approved, Date: 30 June 2023
Prior to starting nivolumab treatment, the participant’s most recent ALT value (tested by local or
central lab) should be <3x ULN with no change in autoimmune status. In case the administration
of nivolumab would not be in the interest of the participant, this should be discussed with the
sponsor.
Nivolumab injections will be administered as an IV infusion at the study site. The duration of the
IV infusion will be approximately 30 minutes.
When both JNJ-3989 and nivolumab are administered at the same visit, JNJ-3989 should be
administered first (preferably in abdomen) followed within approximately  30 minutes by  IV
infusion of nivolumab.
For a definition of study intervention overdose, refer to Section 6.8, Treatment of Overdose.
6.2. 
Preparation/Handling/Storage/Accountability
Preparation/Handling/Storage
All study intervention must be stored as specified on the product-specific labeling.
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 intervention accountability form. Participants must be instructed to return all
original containers, whether empty or containing study intervention. The study intervention
administered to the participant must be documented on the intervention accountability form. All
study intervention will be stored and disposed of according to the sponsor's instructions. Studysite
personnel must not combine contents of the study intervention containers.
Study intervention must be handled in strict accordance with the protocol and as indicated on 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 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 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
intervention return form.
Potentially hazardous materials containing hazardous liquids, such as used ampules, needles,
syringes and vials, must be disposed of immediately in a safe manner and therefore will not be
retained for intervention accountability purposes.

JNJ-73763989 
Clinical Protocol 73763989PAHPB2008 Amendment 3
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
60
Status: Approved, Date: 30 June 2023
Study intervention must 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 participating in the study. 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.
Further guidance and information for the final disposition of unused study intervention is provided
in the Study Reference Manual.
6.3. 
Measures to Minimize Bias: Randomization and Blinding
Intervention Allocation
Procedures for Randomization and Stratification
Participants will be randomly assigned to 1 of 2 intervention  groups based on a
computer-generated randomization schedule prepared before the study by or under the supervision
of the sponsor. The randomization will be balanced by using randomly permuted blocks and will
be stratified by absolute HBsAg level (<100 IU/mL, 100 to <1,000 IU/mL, and ≥1,000 IU/mL) at
screening, as assessed by quantitative HBsAg assay. Based on this randomization code, the study
intervention will be packaged and labeled for each participant. Participant numbers will be
preprinted on the study intervention labels and assigned as participants qualify for the study and
are assigned to intervention.
For more information on the interactive web response system (IWRS), refer to Section 6.3 of the
Master Protocol PLATFORMPAHPB2001.
Blinding
As this is an open-label study, blinding procedures are not applicable.
6.4. 
Study Intervention Compliance
JNJ-3989 and nivolumab will be administered at the study site by qualified study site personnel as
an SC injection and IV infusion, respectively, to assure compliance with study requirements. The
details of each administration will be recorded in the source document and CRF (including date,
start and stop times of the IV infusion or SC injection, volume prepared, and volume administered).
The dose of study intervention and study participant identification will be confirmed at the time of
dosing by a member of the study site personnel other than the person administering the study
intervention. The study intervention may not be used for any purpose other than that outlined in
this protocol, including other human studies, animal investigations, or in vitro testing. Study site
personnel will maintain a log of all study interventions administered. Study intervention supplies
for each participant will be inventoried and accounted for.
Every effort should be made to have the study interventions administered as indicated in the
Schedule of Activities, especially during the first 4 weeks of dosing.

JNJ-73763989 
Clinical Protocol 73763989PAHPB2008 Amendment 3
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
61
Status: Approved, Date: 30 June 2023
If a SC injection of JNJ-3989 was missed during the loading dose period (Week 1-4), the injection
should be given as soon as possible but within 3 days after the scheduled time and with a minimum
of 3 days between injections. Otherwise, the dose should be skipped and the next dose should be
given at the next scheduled time point per the initial dosing schedule.
If after the loading dose period a SC injection of JNJ-3989 was missed or an IV infusion of
nivolumab was missed, the injection or infusion should be given as soon as possible but within
2 weeks after the scheduled time. Otherwise, the dose should be skipped and the next dose should
be given at the next scheduled time point per the initial dosing schedule.
In case of ALT elevation ≥3x ULN during the first 4 weeks of dosing, administration of JNJ-3989
should be discussed with the sponsor.
If a participant’s study intervention intake is not according to the protocol, the investigator will
take the necessary measures to ensure future adherence to the protocol.
6.5. 
Concomitant Therapy
For general concomitant therapy considerations, refer to Section 6.5 of the Master Protocol
PLATFORMPAHPB2001.
An overview of ISA-specific disallowed medication is provided in Table 3.
For participants who consent to complete the optional FNA biopsy of the liver, any anticoagulants
and antiplatelets are disallowed from baseline to at least 2 weeks after the completion of the last
FNA biopsy. Use of low-dose aspirin is allowed except during the 7 days period preceding the
FNA biopsies.
Note that locally approved COVID-19 vaccines (including those that received emergency use
authorization or conditional marketing authorization) are allowed throughout the study, with the
exception of the second dose of Sputnik V (which contains rAd5). Sputnik light which is the first
dose of Sputnik V (with rAd26) is allowed.
During nivolumab treatment, the following recommendations should be applied to accommodate
COVID-19 vaccination:
 
COVID-19 vaccine and nivolumab should not be administered on the same day. If required,
nivolumab administration can be delayed by 2-5 days.
 
The next nivolumab administration should be performed at the scheduled time.
 
If required, skipping a nivolumab administration may be considered after consultation with
the sponsor.
All COVID-19 vaccination-related data (eg, COVID-19 vaccination, AEs, AE management)
should be appropriately captured in the CRF and source documents. Refer to the COVID-19
vaccine and/or nivolumab prescribing information for more details.

JNJ-73763989 
Clinical Protocol 73763989PAHPB2008 Amendment 3
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
62
Status: Approved, Date: 30 June 2023
Table 3: 
Disallowed Medication
Disallowed from 12 months prior to screening until end of follow-up:
 
IFN.
 
Any oligonucleotide-based treatment (eg, siRNA, nucleic acid polymers, antisense oligonucleotides),
other than the study intervention taken in the context of this study.
 
Any prior treatment with an anti-PD-1 antibody, anti-PD-L1 antibody or anti-PD-L2 antibody, other than
the study intervention taken in the context of this study.
Disallowed from 6 months prior to screening until end of follow-up:
 
Any investigational agent, investigational vaccine, invasive investigational medical device, or
investigational biological product (other than the study intervention taken in the context of this study).
Note: For investigational COVID-19 vaccines administered within 6 months prior to screening, an
exception will be made as long as the vaccine has been approved (or received emergency use authorization
or conditional marketing authorization) at the time of screening.
 Any systemically (eg, intravenously, intramuscularly, orally, subcutaneously) administered medication
that directly or indirectly interferes with immune responses (eg, cyclosporine, interleukins, systemic
corticosteroids at doses exceeding 5 mg/day of prednisone or its equivalent). Use of systemic
immunosuppressive medications for the management of irAEs, ISRs, or IRRs, or in participants with
contrast allergies is acceptable, ie, it will not be considered a protocol deviation, but it will lead to
nivolumab discontinuation and/or JNJ-3989 discontinuation if criteria relative to the use of prohibited
medication (including systemic corticosteroids) detailed in Sections 7.1.1 and 7.1.2 are met. In addition,
use of inhaled, topical, local, and intranasal corticosteroids is permitted.
Disallowed from screening until end of follow-up:
 
Any anti-HBV drug (including vaccines) other than the study intervention and the NA background
regimen taken in the context of this study.
Notes:
o 
Prior hepatic treatment with herbal or nutritional products is allowed but should be stopped at
screening.
 
Biotin (>1 mg daily dose), either taken alone or as part of a multivitamin formulation.
Note: The use of other vitamins is allowed.
 
Topical steroids (>7 days) under occlusive dressing.
The prescribing information for ETV, tenofovir disoproxil, TAF, and nivolumab should be
consulted for any additional prohibited medication.
Medications other than JNJ-3989 requiring SC injection (eg, insulin) should be administered away
from the JNJ-3989 injection sites.
6.6. 
Dose Modification
Any dose/dosage adjustment must be overseen by medically-qualified study site personnel
(principal or subinvestigator unless an immediate safety risk appears to be present).
6.7. 
Continued Access to Study Intervention After the End of the Study
Refer to Section 6.7 of the Master Protocol PLATFORMPAHPB2001.
6.8. 
Treatment of Overdose
For this study, any dose of JNJ-3989 exceeding the protocol-specified dose with ≥25% and any
dose of nivolumab  exceeding the protocol-specified dose (0.3 mg/kg) with >5%; refer to
Section 6.1, Study Intervention(s) Administered), will be considered an overdose.

JNJ-73763989 
Clinical Protocol 73763989PAHPB2008 Amendment 3
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
63
Status: Approved, Date: 30 June 2023
In the event of an overdose, the investigator or treating physician should:
 
Contact the Medical Monitor immediately.
 
Evaluate the participant to determine, in consultation with the Medical Monitor, whether study
intervention must be interrupted or whether the dose should be reduced.
 
Closely monitor the participant for AE/SAE and laboratory abnormalities.
 
Obtain a plasma sample for PK analysis as soon as possible from the date of the last dose of
study intervention if requested by the Medical Monitor (determined on a case-by-case basis).
 
Document the quantity of the excess dose as well as the duration of the overdosing in the CRF.
6.9. 
Background Treatment
The NAs tenofovir disoproxil, TAF, and ETV are formulated as oral film-coated tablets of 245-mg,
25-mg, and 0.5-mg strength, respectively. Refer to the prescribing information for a list of
excipients.
Table 4: 
Description and Administration of Background Treatment
Treatment Name 
Tenofovir disoproxil 
Tenofovir alafenamide 
(TAF)* 
Entecavir (ETV)
monohydrate
Type 
Drug 
Drug 
Drug
Dose Formulation 
Film-coated tablets 
Film-coated tablets 
Film-coated tablets
Unit Dose 
Strength(s)
245 mg 
25 mg 
0.5 mg
Dosage Level(s) 
245 mg QD  
25 mg QD  
0.5 mg QD
Route of 
Administration
Oral 
Oral 
Oral
* In countries where TAF is available, it will be one of the NA treatments options.
Investigators should follow guidance detailed in the local prescribing information of NA, including
special warnings and precaution for use.
Participants are instructed to take their NA at home in between study visits, and to bring their NA
with them to each study visit. Study site personnel will instruct participants on how to take their
NA at home and how to store NA for at-home use. At study visits, the NA should be taken on site
to allow biochemistry and renal biomarker samples to be taken in fasted conditions.
NA prescription should follow the standard of care. Compliance will be assessed by the
investigator based on participant interview.

JNJ-73763989 
Clinical Protocol 73763989PAHPB2008 Amendment 3
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
64
Status: Approved, Date: 30 June 2023
During the study, participants will continue the same NA treatment (ETV, tenofovir disoproxil, or
TAF) at the same dose they were receiving at the time of screening (and during at least 3 months
prior to screening). In case participants experienced toxicity to ETV, tenofovir disoproxil, or TAF
prior to screening, they should be treated with one of the other 2 NAs during this study. If clinically
indicated, switching from one NA treatment (ETV, tenofovir disoproxil, or TAF) to another NA
treatment (ETV, tenofovir disoproxil, or TAF) during the study is allowed after consultation with
the sponsor. NA combination treatment is not allowed in this study.
7. 
DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT
DISCONTINUATION/WITHDRAWAL
If a participant prematurely discontinues treatment with all study intervention (ie, before Week
24), the participant will have an early WD visit and will enter the 48-week follow-up period, unless
the participant withdraws consent from study participation. NA treatment will be continued until
the end of the study.
If the reason for withdrawal from the study is withdrawal of consent, then the participant will be
offered an optional safety follow-up visit (to occur on the day of consent withdrawal). Study
intervention assigned to the participant who discontinued study intervention should not be assigned
to another participant.
7.1. 
Discontinuation of Study Intervention
Treatment with JNJ-3989 and/or nivolumab must be discontinued if any of the discontinuation
criteria listed in Sections 7.1.1 and 7.1.2 are met. Criteria specific for this ISA are highlighted
(colored fill). For the few criteria from the Master Protocol that are specified or more restricted in
this ISA, the changes compared to the Master Protocol are also highlighted (colored fill).
 If JNJ-3989 and/or nivolumab are discontinued, NA treatment should be continued until
study completion.
 If JNJ-3989 is discontinued, further treatment with nivolumab should also be discontinued.
 If nivolumab  is discontinued, treatment with JNJ-3989 and NA should be continued as
planned unless a treatment discontinuation rule for JNJ-3989 is also met. In that case,
JNJ-3989 will also be discontinued, but NA treatment should be continued as planned.
No rechallenge is allowed after discontinuation of study intervention (JNJ-3989 and/or
nivolumab).
Note: The grades are based on the DAIDS Toxicity Grading Scale and NCI-CTCAE (see
Section 10.8, Appendix 8: DAIDS Table with Modifications).

JNJ-73763989 
Clinical Protocol 73763989PAHPB2008 Amendment 3
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
65
Status: Approved, Date: 30 June 2023
7.1.1. 
Discontinuation of JNJ-3989
Treatment with JNJ-3989 must be discontinued ifany of the following occurs:
 
The participant withdraws consent to receive study intervention.
 
The investigator believes that for safety reasons or tolerability reasons (eg, AE) it is in the
best interest of the participant to discontinue JNJ-3989.
 
The participant becomes pregnant.
 
The participant has ≥Grade 3 rash (see Section 10.6, Appendix 6: Rash Management).
 
The participant has ≥Grade 3 allergic reaction or worsening of Grade 2 allergic reaction (see
Section 8.3.6.4.1, Acute Systemic Allergic Reactions).
 
The participant has signs of hepatic decompensation (ie, clinical evidence of ascites, bleeding
varices, or hepatic encephalopathy) or an increase in direct bilirubin >1.5x ULN in
combination with INR ≥1.5x ULN or albumin <3.0 g/dL. Alternative treatment options
(outside the study) should be considered in consultation with the sponsor.
 
The participant has treatment-emergent ALT/AST elevations, as described in Section 8.3.6.1,
Intervention-emergent ALT/AST Elevations including immune-related hepatic AEs.
 
The participant has a confirmed ≥Grade 3 eGFR abnormality and a drop from baseline of
>10 mL/min/1.73 m2, based on creatinine (calculated by the CKD-EPI formula), that persists
despite changing tenofovir disoproxil to ETV or TAF (if the participant was receiving
tenofovir disoproxil) and that is considered at least possibly related to JNJ-3989.
 
The participant has a QTcF prolongation (defined as a QTcF value of >500 ms, or an increase
from baseline of >60 ms) at any given time point.
 
The participant requires ≥7 days oftreatment with any of the disallowed medications listed in
Section 6.5, Concomitant Therapy, and does not intend to discontinue treatment with the
disallowed medication.
 
The participant has confirmed HBV virologic breakthrough (ie, confirmed on-treatment HBV
DNA increase by >1 log10 IU/mL from nadir or confirmed on-treatment HBV DNA level
>200 IU/mL in participants who had HBV DNA level <LLOQ of the HBV DNA assay). If
virologic breakthrough occurs during nivolumab administration, this does not automatically
lead to stop of JNJ-3989 and/or nivolumab, but should be assessed/discussed with the sponsor.
In case of virologic breakthrough, a viral sequencing sample maybe collected at the next visit.
7.1.2. 
Discontinuation of Nivolumab
Treatment with nivolumab should be discontinued if any of the following occurs:
 
Participant meets any of the JNJ-3989 discontinuation criteria listed in Section 7.1.1.
 
The investigator believes that for safety reasons or tolerability reasons (eg, AE) it is in the
best interest of the participant to discontinue nivolumab.

JNJ-73763989 
Clinical Protocol 73763989PAHPB2008 Amendment 3
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
66
Status: Approved, Date: 30 June 2023
 
Participant experiences an irAE that requires systemic treatment with corticosteroids (refer to
Section 8.3.6.2, Infusion-related Reactions and Other Immune-related AEs) or has
treatment-emergent 
ALT/AST 
elevations, 
as 
described 
in 
Section 
8.3.6.1,
Intervention-emergent ALT/AST Elevations including immune-related hepatic AEs.
 
Participant experiences Grade 3 or 4 irAE.
 
Participant experiences Grade 3 or 4 IRR.
7.2. 
Participant Discontinuation/Withdrawal From the Study
In case a participant is withdrawn from the study intervention cohort for any of the reasons listed
in Section 7.2 of the Master Protocol PLATFORMPAHPB2001, additional participants will not
be entered.
Withdrawal of Consent
A participant declining to return for scheduled visits does not necessarily constitute withdrawal of
consent. Alternate follow-up mechanisms that the participant agreed to when signing the consent
form apply as local regulations permit.
7.2.1. 
Withdrawal From the Use of Research Samples
Withdrawal From the Study
A participant who withdraws from the ISA/Platform study will have the following options
regarding the optional research samples (ie, pharmacogenomic and FNA samples):
 The collected samples will be retained and used in accordance with the participant's original
informed consent for optional research samples.
 The participant may withdraw consent for optional research samples, in which case the samples
will be destroyed and no further testing will take place. To initiate the sample destruction
process, the investigator must notify the sponsor study site contact of withdrawal of consent
for the optional research samples and to request sample destruction. The sponsor study site
contact will, in turn, contact the biomarker representative to execute sample destruction. If
requested, the investigator will receive written confirmation from the sponsor that the samples
have been destroyed.
Withdrawal From the Optional Research Samples While Remaining in the ISA/Platform
Study
The participant may withdraw consent for optional research samples (ie, pharmacogenomic and/or
FNA samples) while remaining in the study. In such a case, the participant will have to indicate:
 Whether he/she withdraws from further collection only, and he/she agrees the previously
collected samples will be retained and used in accordance with the participant's original
informed consent for optional research samples.

JNJ-73763989 
Clinical Protocol 73763989PAHPB2008 Amendment 3
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
67
Status: Approved, Date: 30 June 2023
 Or if he/she also requires that previously collected samples are destroyed and no further testing
is done. The sample destruction process will proceed as described above.
Withdrawal From the Use of Samples in Future Research
The participant may withdraw consent for use of samples for future research (refer to the
paragraphs on long-term retention of samples for additional future research in Attachment 3 of the
Master protocol). In such a case, samples will be destroyed after they are no longer needed for the
clinical study. Details of the sample retention for future research are presented in the main ICF,
and in the separate ICF for optional research samples.
7.3. 
Lost to Follow-up
Refer to Section 7.3 of the Master Protocol PLATFORMPAHPB2001.
8. 
STUDY ASSESSMENTS AND PROCEDURES
Overview
Refer to Section 8 of the Master Protocol PLATFORMPAHPB2001.
The Schedule of Activities summarizes the frequency and timing of efficacy, safety, PK, PD,
pharmacogenomic, biomarker, medical resource utilization, and immune assessments applicable
to this study.
The total blood volume to be collected from each participant during planned assessments for the
entire study will be up to approximately 875 mL. In addition, PBMC samples (at selected sites
only; approximately 250 mL) and optional pharmacogenomic samples (approximately 15 mL)
may be collected.
Sample Collection and Handling
Refer to Section 8 of the Master Protocol PLATFORMPAHPB2001.
Study-Specific Materials
In addition to the items described in Section 8 of the Master Protocol PLATFORMPAHPB2001,
the investigator will be provided with the following supplies:
 
Prescribing Information for ETV, tenofovir disoproxil, and TAF, and nivolumab.
 
Contact information page(s).

JNJ-73763989 
Clinical Protocol 73763989PAHPB2008 Amendment 3
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
68
Status: Approved, Date: 30 June 2023
8.1. 
Efficacy Assessments
All efficacy assessments will be performed at predefined time points as specified in the Schedule
of Activities.
Qualitative and quantitative HBsAg and HBeAg, and quantitative HBcrAg as well as
anti-hepatitis B surface (HBs) and anti-hepatitis B e (HBe) antibodies will be determined using
validated serologic assays in a central laboratory. Samples for the determination of HBsAg,
HBeAg, anti-HBs antibodies, and anti-HBe antibodies will be processed in real-time. Samples for
the determination of HBcrAg can be analyzed in batch and at the sponsor’s request.
HBV DNA and HBV RNA will be assessed at central laboratories using validated assays for the
quantification of HBV DNA and HBV RNA. Samples for the determination of HBV DNA will be
processed in real-time. Samples for the determination of HBV RNA can be analyzed in batch and
at the sponsor’s request.
HBV DNA, HBsAg, HBeAg, anti-HBs, and anti-HBe antibody testing results will be provided to
the investigator and the sponsor from screening until the end of follow-up.
It is the responsibility of the investigator:
 
To monitor HBV DNA results and assess whether JNJ-3989 is discontinued in participants
with confirmed virologic breakthrough (see Section 7.1, Discontinuation of Study
Intervention).
In participants enrolled at a site with access to a Fibroscan device, Fibroscan assessments will be
performed at different time points to determine changes in fibrosis levels.
Samples may be used by the sponsor for additional exploratory assessments analyzing the
serologic and virologic characteristics of HBV infection and efficacy or safety of the study
intervention.
8.1.1. 
Sequencing
Viral genome sequence analysis will be performed to evaluate mutations associated with the study
intervention.
Sequencing of the HBV genome may be performed to monitor HBV variants using any of the
virology/serology samples collected at the time points indicated in the Schedule of Activities.
Samples may be sequenced based on the sponsor virologist’s request, considering the HBV DNA
levels. In case of a virologic breakthrough/flare, additional samples for viral sequencing may be
taken.
Samples may be used by the sponsor for additional assessments analyzing the serologic and
virologic characteristics of the HBV infection and efficacy of the study intervention, including
viral genotypic and phenotypic assessments.

JNJ-73763989 
Clinical Protocol 73763989PAHPB2008 Amendment 3
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
69
Status: Approved, Date: 30 June 2023
8.2. 
Safety Assessments
Safety and tolerability (AEs, clinical safety laboratory assessments, ECGs, vital signs and physical
examinations) will be evaluated as described in Section 8.2 and Section 8.3 of the Master Protocol
PLATFORMPAHPB2001 and at predefined time points as specified in the Schedule of Activities.
Additional clinical safety laboratory assessments specific for this protocol are described in
Section 10.2, Appendix 2: Clinical Laboratory Tests.
The study will include the following evaluations of safety and tolerability according to the time
points provided in the Schedule of Activities.
8.2.1. 
Physical Examinations
Refer to Section 8.2.1 of the Master Protocol PLATFORMPAHPB2001.
In addition, physical examination will include neck and thyroid gland check.
8.2.2. 
Vital Signs
Refer to Section 8.2.2 of the Master Protocol PLATFORMPAHPB2001.
Clinically relevant abnormalities in vital signs are defined in Section 10.7, Appendix 7:
Cardiovascular Safety –Abnormalities.
8.2.3. 
Electrocardiograms
Refer to Section 8.2.3 of the Master Protocol PLATFORMPAHPB2001.
Clinically relevant abnormalities in ECG are defined in Section 10.7, Appendix 7: Cardiovascular
Safety –Abnormalities.
8.2.4. 
Clinical Safety Laboratory Assessments
Refer to Section 8.2.4 of the Master Protocol PLATFORMPAHPB2001.
In addition, urine samples for urine chemistry and renal biomarkers will be collected as noted in
Section 10.2, Appendix 2: Clinical Laboratory Tests.
8.2.5. 
Pregnancy Testing
For women of childbearing potential, a negative screening serum pregnancy test and a negative
baseline urine pregnancy test must be obtained before the first dose of study intervention on Day 1.
Urine pregnancy tests should be done at least every 4 weeks, preferably during a scheduled site
visit. Pregnancy tests for at-home use may be provided to the participants from FU Week 24
onwards to allow 4-weekly urine pregnancy testing in between scheduled site visits. If positive,
the participant should contact the site immediately.

JNJ-73763989 
Clinical Protocol 73763989PAHPB2008 Amendment 3
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
70
Status: Approved, Date: 30 June 2023
8.3. 
Adverse Events, Serious Adverse Events, and Other Safety Reporting
Adverse events and SAEs will be evaluated as described in Section 8.3 of the Master Protocol
PLATFORMPAHPB2001, including handling of pregnancy described in Section 8.3.5.
Further details on AEs, SAEs, and Product Quality Complaints (PQCs) can be found in
Attachment 4 of the Master Protocol PLATFORMPAHPB2001.
Note: All reported AEs will be coded according to the Medical Dictionary for Regulatory
Activities (MedDRA). In addition, the following coding conventions will be applied for the AEs
reported by investigators as specified below:
 
AE reporting an ALT flare in relation to laboratory test elevation will be coded to the
MedDRA preferred term alanine aminotransferase increased.
 
AE reporting a reactivation of hepatitis B in patients who are HBV DNA suppressed and have,
when a patient is off NA treatmenta, a sudden HBV DNA increase (virologic flare) will be
coded to MedDRA preferred term hepatitis B reactivation.
 
AE reporting a viral breakthrough in the context of laboratory data will be coded to the
MedDRA preferred term viral load increased.
8.3.1. 
Time Period and Frequency for Collecting Adverse Event and Serious
Adverse Event Information
Refer to Section 8.3.1 of the Master Protocol PLATFORMPAHPB2001.
8.3.2. 
Method of Detecting Adverse Events and Serious Adverse Events
Refer to Section 8.3.2 of the Master Protocol PLATFORMPAHPB2001.
8.3.3. 
Follow-up of Adverse Events and Serious Adverse Events
Adverse events and the special reporting situation of pregnancy will be followed by the
investigator as specified in Appendix 4: Adverse Events, Serious Adverse Events, Product Quality
Complaints, and Other Safety Reporting: Definitions and Procedures for Recording, Evaluating,
Follow-up, and Reporting.
8.3.4. 
Regulatory Reporting Requirements for Serious Adverse Events
Refer to Section 8.3.4 of the Master Protocol PLATFORMPAHPB2001.
8.3.5. 
Pregnancy
Refer to Section 8.3.5 of the Master Protocol PLATFORMPAHPB2001. Differences with the
Master Protocol PLATFORMPAHPB2001 are highlighted (colored fill).
a Note that in the current study, participants will continue their NA background regimen during the study intervention
and the follow-up periods.

JNJ-73763989 
Clinical Protocol 73763989PAHPB2008 Amendment 3
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
71
Status: Approved, Date: 30 June 2023
Follow-up information regarding the outcome of the pregnancy for female participants who
become pregnant, or where the pregnancy was the result of male participant and his partner, and
any postnatal sequelae in the infant will be required.
8.3.6. 
Guidelines for Management of Adverse Events of Special Interest
Including Immune-Related Adverse Events
Adverse events of interest are significant AEs that are judged to be of special interest because of
clinical importance, known class effects or based on nonclinical signals. Immune-related AEs of
interest that will be carefully monitored during the study include ALT/AST elevations including
immune-related hepatic AEs, IRRs and other irAEs (including gastrointestinal AEs, neurological
AEs, pulmonary AEs, renal AEs, endocrinopathies, rash, uveitis and visual complaints,
lipase/amylase elevations, and infection). Other AEs of Special Interest related to JNJ-3989 that
will be carefully monitored during the study include hematological abnormalities and ISRs.
AEs of Special Interest should be identified and reported to the sponsor’s Medical Monitor and
reported as an SAE if SAE criteria are met.
8.3.6.1. 
Intervention-emergent ALT/AST Elevations Including Immune-related
Hepatic AEs
Elevated liver enzyme activity can be triggered by the underlying HBV disease as well as
potentially by the study intervention. Management of intervention-emergent ALT/AST elevations
is described below.
Hepatic AEs, including elevated liver function tests and, infrequently, drug-induced-liver-injuries
(DILI) have been observed following treatment with anti-PD-1 therapies. Early recognition and
treatment of elevated liver function tests and DILI are critical to their management. Participants
should be advised to seek medical evaluation if they notice jaundice (yellow appearance of skin or
sclera) or if they develop bruising, bleeding, or right-sided abdominal pain. Investigators should
monitor liver function tests (included in chemistry laboratory test) during the study.
Any treatment-emergent elevation of ALT and/or AST ≥3x ULN and ≥3x nadir (ie, lowest value
during study participation) should trigger an assessment of confounding factors (alcohol intake,
change in concomitant medication, and comorbidities), and should trigger a confirmatory study
visit to repeat laboratory testing of ALT, AST, ALP, bilirubin (total and direct), INR, albumin,
HBV DNA. After nivolumab initiation, antinuclear antibodies, anti-smooth muscle antibodies,
anti-neutrophil cytoplasmic antibodies, and gamma globulin should be added as part of the
confirmatory laboratory testing to assess potential immune-related hepatic AEs. Additional tests
should be considered based on clinical judgement: Hepatitis A, Delta, C, E: IgM anti-HAV; delta
IgM, IgG and polymerase chain reaction (PCR), HCV RNA, IgM and IgG anti-HEV, HEV RNA;
CMV, herpes simplex virus (HSV), Epstein-Barr virus (EBV) infection; IgM and IgG anti-CMV,
IgM and IgG anti-HSV; IgM and IgG anti-EBV, PCR; HIV; Ig electrophoresis. The confirmatory
visit should be scheduled as soon as possible within 7 days of the receipt of the initial ALT/AST
results. Additional PBMC and AFP samples may be taken in case of ALT flares, upon discussion
with the sponsor, which may require an unscheduled visit.

JNJ-73763989 
Clinical Protocol 73763989PAHPB2008 Amendment 3
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
80
Status: Approved, Date: 30 June 2023
In the Phase 1/2a AROHBV1001 study with JNJ-3989, mild (Grade 1) transient thrombocytopenia
was observed in 6 out of 84 participants receiving 3 SC injections of JNJ-3989 alone over a period
of up to 12 weeks with background of NAs. The transient thrombocytopenia was not considered
clinically significant. No thrombocytopenia or pancytopenia was observed in 12 participants when
JNJ-3989 was given in combination with JNJ-6379 over a 12-week period in the same study.
Based on the nonclinical findings, any relevant abnormalities in hematologic parameters will be
carefully monitored as described below:
 
Platelet counts: <100,000 cells/mm3 (at least Grade 2 [DAIDS]) or <100 GI/L or reduction
from baseline by at least 50%.
 
Hemoglobin: Decrease of at least 2 g/dL from baseline or at least Grade 2 (DAIDS).
 
Neutrophil count: Treatment-emergent reduction to at least Grade 2 (DAIDS).
In case any of the above criteria are met, a confirmatory visit should be scheduled as soon as
possible, preferably within 7 days of the receipt of the initial results. Confirmation of the results
will trigger weekly or biweekly (every other week) unscheduled visits until improvement or
stabilization of the respective parameter(s). Stabilization is defined as no further significant
reduction over 2 consecutive visits.
In case of confirmed Grade 3 or Grade 4 hematologic abnormalities (platelet count, hemoglobin,
and neutrophil count), discontinuation of JNJ-3989 (and nivolumab if applicable) should be
considered. In case of discontinuation, NA treatment should be continued.
8.3.6.3.2. 
Injection Site Reactions
At the time points specified in the Schedule of Activities or at an unscheduled visit if needed, an
evaluation of the injection site will be performed based on participant’s description and/or physical
examination. Evaluations will be recorded in the source documents and will include at a minimum
the time of occurrence, time of resolution and a description of the abnormality including its
maximal diameter.
For each ISR, information on pain, erythema, induration and pruritus should be obtained as
specified in Section 10.8, Appendix 8: DAIDS Table with Modifications.
All ISRs (including ISRs below Grade 1) will need to be recorded in the special events section of
the CRF.
Digital pictures will be taken when considered appropriate; all efforts should be made to collect
images in case of Grade 3 and 4 ISRs. Digital pictures will only be taken and collected from
participants who consent separately to this component of the study. If digital pictures are required,
they should be made anonymous and provided to the sponsor.

JNJ-73763989 
Clinical Protocol 73763989PAHPB2008 Amendment 3
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
82
Status: Approved, Date: 30 June 2023
8.4.3. 
Pharmacokinetic Parameters and Evaluations
Parameters
Based on the individual plasma concentration-time data, using the actual dose taken and the actual
sampling times, PK parameters and exposure information of JNJ-3989 and optionally NA and/or
nivolumab will be derived using population PK modeling. Baseline covariates (eg, body weight,
age, sex, creatinine clearance [CrCL], race) may be included in the model, if relevant.
Pharmacokinetic/Pharmacodynamic Evaluations
Relationships of individual PK parameters for JNJ-3924 and JNJ-3976, and optionally NA and/or
nivolumab, with RO, selected efficacy and/or safety endpoints may be evaluated, if applicable.
8.5. 
Pharmacodynamics
Whole blood samples will be collected for assessment of nivolumab RO on circulating T-cells by
flow cytometry analysis.
Pharmacodynamic biomarkers will be evaluated in all participants pretreatment, on-treatment, and
posttreatment with study intervention as shown in Schedule of Activities in Section 1.3.1 and
Section 1.3.2.
Refer to laboratory manuals for sample collection requirements.
8.6. 
Host Genetics
An optional sample for HLA testing will be collected from participants who consent separately to
this component of the study.
An optional pharmacogenomic (host DNA) blood sample may be collected (preferably at baseline)
to allow for host pharmacogenomic research, where local regulations permit. In addition, host
DNA blood samples to allow for epigenetic analyses will be collected in participants who consent.
These samples could for example be used to assess changes in frequencies of immune cells.
Complete host genomic testing may be done to search for links of specific genes to (HBV-related)
liver disease or to the PK, PD, efficacy, safety, or tolerability of the study intervention. These
samples will only be collected from participants who consent separately to this component 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 Platform study (see
Section 7.2.1 of the Master Protocol PLATFORMPAHPB2001).
In addition, other samples may be used for exploratory genetic or epigenetic research in
participants consenting separately to this part of the study. These samples can only be used to
investigate the potential association of genetic or epigenetic factors with efficacy, safety, or PK of
the study intervention, or HBV infection, or may be used to develop tests/assays related to the
study intervention or HBV infection. No genetic research will be performed on any sample in
participants who have not provided the additional separate consent for host genetic research.

JNJ-73763989 
Clinical Protocol 73763989PAHPB2008 Amendment 3
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
83
Status: Approved, Date: 30 June 2023
These analyses will be performed at the sponsor’s discretion, will always be under the sponsor’s
supervision, and may be reported separately.
8.7. 
Exploratory Host Biomarkers
The study includes collection of blood samples for exploratory analysis of host blood biomarkers
at the host RNA, protein, and cell level. Sampling will be performed at the time points indicated
in the Schedule of Activities. Leftovers of other samples might also be used for exploratory
research of host and viral markers.
Samples can only be used for research related to study intervention or HBV infection or may be
used to develop tests/assays related to study intervention or HBV infection.
A FNA biopsy sample may be collected from participants who consent separately to this
component of the study (as permitted by local regulations). If participants agree to undergo an
optional FNA biopsy of the liver, following local standard practice, the biopsy location will be
identified and/or guided with ultrasound and the FNA biopsy samples will be collected after
application of local anesthesia to allow for exploratory biomarker research.
The FNA biopsy procedure should be preceded and followed by standard medical monitoring
according to local medical practice. This may include an overnight stay at the investigator’s
discretion. Prior to each to FNA biopsy, a recent (≤2 weeks) coagulation and hematology panel
are required to ensure normal platelet count and normal coagulation parameters. The use of local
laboratories may be allowed at the investigator’s discretion. Optional FNA biopsy will only be
completed at selected sites that have expertise and capacity to perform FNA biopsy. Intrahepatic
immune response to treatment will be assessed in FNA biopsy samples.
Infiltrating immune cells will be used for the evaluation of immune responses, which can be
compared to responses in PBMCs.
These analyses will be performed at the sponsor’s discretion, will always be under the sponsor’s
supervision, and may be reported separately.
More information is provided in Section 8.8 of the Master Protocol PLATFORMPAHPB2001.
8.8. 
Immune Assessments
At selected sites, PBMC samples for immune analyses will be collected during study intervention
and follow-up and will be analyzed centrally for HBV-specific responses by enzyme-linked
immunospot (ELISpot) and/or intracellular cytokine staining (ICS) after stimulation with
HBV-specific antigens. ELISpot detects T-cells that secrete gamma interferon (IFN-γ) in response
to a specific antigenic stimulation, whereas ICS determines the frequency of CD4+ and CD8+
T-cells secreting cytokines such as IFN-γ, interleukin (IL)-2 and TNF-α in response to a specific
antigenic stimulation.
Additional PBMC samples may be taken in case of ALT flares, upon discussion with the sponsor,
which may require an unscheduled visit.

JNJ-73763989 
Clinical Protocol 73763989PAHPB2008 Amendment 3
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
84
Status: Approved, Date: 30 June 2023
Additional experiments may be performed to further phenotypically and functionally characterize
PBMCs. Leftover PBMC samples may be used at the sponsor’s discretion for additional
exploratory research or to explore new functional immune assays, or for immune assay
optimalization.
Blood samples taken at the time points indicated in the Schedule of Activities, can also be used to
explore the emergence of antidrug antibodies to JNJ-3989 and/or nivolumab. Antidrug antibodies
may be analyzed using assays such as an enzyme-linked immunosorbent assay or functional
assays.
These analyses will be performed at the sponsor’s discretion, will always be under the sponsor’s
supervision, and may be reported separately.
8.9. 
Medical Resource Utilization and Health Economics
Medical resource utilization data, associated with medical encounters, will be collected in the CRF
by the investigator and study site personnel for all participants throughout the study. Protocol-
mandated procedures, tests, and encounters are excluded. The data collected may be used to
conduct exploratory economic analyses and will include:
 
Number and duration of medical care encounters, including surgeries, and other selected
procedures (inpatient and outpatient).
 
Duration of hospitalization (total days length of stay, including duration by wards,
eg, intensive care unit).
 
Number and character of diagnostic and therapeutic tests and procedures.
 
Outpatient medical encounters and treatments (including physician or emergency room visits,
tests and procedures, and medications).
9. 
STATISTICAL CONSIDERATIONS
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 primary hypothesis of this study is that at least one of the combination regimens of
JNJ-3989+nivolumab+NA is more efficacious than JNJ-3989+NA treatment, as measured by the
primary efficacy endpoint (ie, the proportion of participants with HBsAg seroclearance at FU
Week 24). Because the study does not include a regimen arm without nivolumab, the hypothesis
is formulated assuming a fixed response rate for JNJ-3989+NA of 1% based on previous
Study 73763989HPB2001 (REEF-1).

JNJ-73763989 
Clinical Protocol 73763989PAHPB2008 Amendment 3
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
85
Status: Approved, Date: 30 June 2023
9.2. 
Sample Size Determination
According to the initial protocol, the study aimed to have a sample size of 20 participants per
intervention arm which yielded ≥85% statistical power to detect a ≥15% and ≥20% difference for
the proportions of participants with HBsAg seroclearance at FU Week 24 in the 2 intervention
arms, respectively, vs a fixed proportion of ≤1%. Statistical power to test the primary hypothesis
was assessed for each of the intervention arms, using an exact test for a single proportion with a
one-sided Type 1 error rate of 0.05 and applying the Hochberg procedure for multiple comparisons
adjustment. The fixed rate assumed for the external active control (JNJ-3989 [200 mg]+NA
treatment) is based on the data of Study 73763989HPB2001 (REEF-1).
The total study sample size was adjusted to 44 participants (22 per arm), with 1:1 randomization
ratio to each of the intervention arms, to account for an approximate 10% attrition rate.
Due to the decision to not extend further enrollment beyond the planned enrollment period and
proceed with a reduced sample size, the final sample size is 37 (18 in Arm 1 and 19 in Arm 2).
Under the same assumptions and methods of the initial protocol, an approximate sample size of 16
participants per intervention arm (assuming 10% attrition) yields ≥75% statistical power to detect
the same differences in HBsAg seroclearance at FU Week 24.
9.3. 
Populations for Analysis Sets
For purposes of analysis, the following populations are defined:
Screened 
All participants who signed the ICF for the Master Protocol and the ICF specific for this ISA.
Enrolled 
All participants who were enrolled in this ISA.
Full Analysis Set 
(FAS) 
All participants who were randomly assigned to an intervention arm in this ISA and received
at least 1 dose of study intervention within this ISA. Participants will be analyzed according
to the study intervention they were randomly assigned to.
Full Analysis Set 
for nivolumab 
(FAS-N) 
All participants who were randomly assigned to an intervention arm in this ISA and received
at least 1 dose of nivolumab within this ISA. Participants will be analyzed according to the
study intervention they were randomly assigned to.
Safety  
All participants who received at least 1 dose of study intervention within this ISA.
Participants will be analyzed according to the study intervention they actually received.
9.4. 
Statistical Analyses
The SAP will include a more technical and detailed description of the statistical analyses described
in this section. This section is a summary of the planned statistical analyses of the most important
endpoints including primary and key secondary endpoints.
9.4.1. 
General Considerations
Refer to Section 9.4.1 of the Master Protocol PLATFORMPAHPB2001.
9.4.2. 
Efficacy Analyses
The primary efficacy analysis will be performed when all participants have completed the FU
Week 24 visit or discontinued earlier. The final analysis will be performed when all participants
have completed the final study visit at FU Week 48 or discontinued earlier.

JNJ-73763989 
Clinical Protocol 73763989PAHPB2008 Amendment 3
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
86
Status: Approved, Date: 30 June 2023
To evaluate the efficacy, the primary analysis set will be the Full Analysis Set (see Section 9.3,
Populations for Analysis Sets). The FAS-N set will be used for sensitivity analyses of selected
efficacy endpoints.
All efficacy summaries will be presented with descriptive statistics and 90% CIs by intervention
arm, when applicable. If the endpoint is continuous, the descriptive statistics will include the
number of participants, mean, standard deviation (SD), median, and range. If the endpoint is binary
or categorical, the frequency distribution with the number and percentage of participants in each
category will be calculated. For time-to-event variables, a summary table based on the Kaplan-
Meier method including number of participants included in the analysis, number of participants
censored, 25th  and 75th  percentiles and median time-to-event will be shown by intervention arm.
Graphic displays will also be used to summarize the data. Summaries will also be presented by the
randomization stratification factor (ie, absolute HBsAg value at baseline [<100 IU/mL, 100 to
<1,000 IU/mL, and ≥1,000 IU/mL]).
The baseline measurements are defined as the measurements taken closest to, but before, the first
administration of study intervention on Day 1, unless otherwise specified.
9.4.2.1. 
Primary Endpoints
The proportion of participants who achieved HBsAg seroclearance at FU Week 24 will be
summarized for each intervention arm paired together with a two-sided, single arm 90% CI based
on the Clopper-Pearson method. The statistical comparison will be conducted using an exact
binomial test against a fixed external control value of 1% at a one-sided Type 1 error rate of0.05
and applying the Hochberg procedure for adjusting for multiple comparisons.
Association of the stratification factors and other demographic and baseline disease characteristics
with the primary endpoint may be explored using logistic regression analyses and classification
and regression tree analysis (CART).
The Mantel-Haenszel test adjusted for the randomization stratification factors will be used in a
secondary analysis comparing the primary endpoint between the 2 study intervention arms at a
one-sided alpha level of 0.05.
9.4.2.2. 
Secondary Efficacy and Exploratory Endpoints
Descriptive statistics will be used for all efficacy endpoints, which will be summarized by
intervention arm and by study period. Comparisons between intervention arms and 90% CIs may
be done with no adjustment for multiplicity. Specific key selected endpoints may be analyzed
using suitable categorical data approaches (eg, Mantel-Haenszel or logistic regression for
proportions or other categorical type of endpoint), longitudinal repeated measures models (eg, for
continuous types of variables), or survival analysis based on the Kaplan-Meier estimates (for
time-to-event variables), as appropriate. Details will be described in the SAP.
Graphic data displays of different type (eg, bar charts, line plots, and waterfall plots) will also be
used to summarize the efficacy data by intervention arm and over time.

JNJ-73763989 
Clinical Protocol 73763989PAHPB2008 Amendment 3
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
87
Status: Approved, Date: 30 June 2023
9.4.2.3. 
Across ISAs Comparisons of Efficacy
Indirect comparisons between different regimens across multiple ISAs may be performed in an
exploratoryfashion by selecting the similar subgroup of participants who match the most important
inclusion/exclusion criteria and demographic characteristics of this ISA.
More details on this approach and its application to secondary endpoints will be provided, if
applicable, in a separate document (eg, SAP or the Modeling and Simulation Report).
9.4.3. 
Safety Analyses
Safety analyses will be based on the safety population (see Section 9.3, Populations for Analysis
Sets) and are specified in Section 9.4.3 of the Master Protocol PLATFORMPAHPB2001.
Safety will be evaluated by means of descriptive summaries of AE including AEs of Special
Interest to any of the study interventions, clinical laboratory tests, ECGs, vital signs, and physical
examinations. The safety analysis will be done by study period. Results will be presented in tabular
format and/or graphically by intervention arm and over time, as appropriate.
Indirect descriptive comparisons of selected safety endpoints between different regimens across
different ISAs will be performed in an exploratory fashion by selecting the similar subgroup of
participants who match the most important inclusion/exclusion criteria and demographic
characteristics of this ISA population.
9.4.4. 
Other Analyses
Pharmacokinetic Analyses
Population PK analysis of concentration-time data of JNJ-3976 and JNJ-3924, and, optionally, of
NA and/or nivolumab may be performed using non-linear mixed effects modeling. Data may be
combined with selected Phase 1 and/or 2 studies to support a relevant structural model. Available
participant characteristics (eg, demographics, laboratory variables, genotypes) will be included in
the model as necessary. Details will be given in a population PK analysis plan and results of the
population PK analysis, if applied, will be presented in a separate report.
Pharmacokinetic/Pharmacodynamic Analyses
Relationships of PK parameters for JNJ-3976 and JNJ-3924, and, optionally, for NA and/or
nivolumab, with RO, selected efficacy and/or safety endpoints may be evaluated and graphically
displayed, if applicable.
Modeling of key PD parameters (eg, HBsAg, HBV DNA) may be performed using population
PK/PD. If PK/PD modeling of key efficacy endpoints is performed, treatment effect and possible
covariates may be investigated. Other biomarkers may be explored at the sponsor’s discretion. If
applicable, the results will be described in a separate report.

JNJ-73763989 
Clinical Protocol 73763989PAHPB2008 Amendment 3
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
88
Status: Approved, Date: 30 June 2023
Pharmacodynamic Analyses
Descriptive statistics by treatment will be used to summarize PD parameters at each applicable
time point. Statistics include sample size (n), mean, SD, coefficient of variation (CV), geometric
mean, median, minimum, and maximum. Additional PD analyses may be performed, as deemed
necessary.
Resistance Analysis
The results of HBV viral sequencing will be evaluated by the sponsor virologist. Relevant changes
of amino acid and/or nucleic acid variations (eg, substitutions) in the HBV genome will be
tabulated and described.
Additional exploratory characterization of the HBV viral sequence and phenotype may be
performed and reported separately.
Pharmacogenomic Analysis
The statistical approach for analyzing the exploratory host DNA research samples, including
epigenetic analyses, may depend on the objective of the analyses (eg, efficacy, safety, and/or PK)
and possibly relevant genes at the time of analysis. Analyses will be conducted at the sponsor’s
discretion, will always be under the sponsor’s supervision, and results will be presented either in
the clinical study report or a separate report.
Host Biomarker Analysis
Statistical approaches to explore correlations between clinical outcome and blood biomarkers vary
and depend on the different data types of the applied technology platforms, as well as on the extent
of observed interindividual variability. Analyses will be conducted at the sponsor’s discretion, will
always be under the sponsor's supervision, and results will be presented either in the clinical study
report or a separate report.
Immune Analyses
Descriptive statistics (n, mean, SD, CV, geometric mean, median, minimum, and maximum) may
be used to describe the magnitude of the IFN-γ T-cell response or the CD4+ and CD8+ T-cell
responses (expressing at least 1 cytokine such as IL-2, TNF-α or IFN-γ specific to any HBV
antigen) as defined by ELISpot and/or ICS, respectively. Changes from baseline (or positivity
threshold) may also be tabulated for PBMCs during study intervention and follow-up. The
proportion (%) of chronic HBV-infected patients with detectable responses based on the
magnitude of the IFN-γ T-cell response or the CD4+ or CD8+ T-cells expressing at least 1 of the
cytokines amongst IL-2, TNF-α or IFN-γ for 1 of the HBV antigens as defined by ELISpot and/or
ICS, respectively, will be determined.
Medical Resource Utilization
Medical resource utilization data will be descriptively summarized by intervention arm over time.

JNJ-73763989 
Clinical Protocol 73763989PAHPB2008 Amendment 3
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
89
Status: Approved, Date: 30 June 2023
9.5. 
Interim Analysis
Interim analyses (IAs) will be conducted to assess safety and evaluate the time course of different
safety and efficacy markers to support the sponsor’s interactions with health authorities, as well as
to inform internal decisions about additional studies and/or investigation of other treatment
combinations.
Optional IAs are planned when:
 
All randomized participants have completed Week 24 or discontinued earlier.
 
All randomized participants have completed FU Week 12 or discontinued earlier.
Depending on the enrollment rate, any of the above IAs may be skipped if it is too close to the
predicted timing of any adjacent interim cut-offs and additional IAs may be performed by the
sponsor to support interactions with health authorities.
The study is open-label, and the sponsor will conduct the IA(s). Hence, the study team and the
DRC will have access to the IA results, while the investigators and patients will not.
Interim analyses will be based on all data available at the predefined cut-off time points and may
include data at later time points for those participants who have reached subsequent visits.
More details are provided in Section 9.5 of the Master Protocol PLATFORMPAHPB2001.

JNJ-73763989 
Clinical Protocol 73763989PAHPB2008 Amendment 3
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
95
Status: Approved, Date: 30 June 2023
10.3. Appendix 3: Regulatory, Ethical, and Study Oversight Considerations
10.3.1. 
Regulatory and Ethical Considerations
Refer to Attachment 3 of the Master Protocol PLATFORMPAHPB2001.
10.3.2. 
Financial Disclosure
Refer to Attachment 3 of the Master Protocol PLATFORMPAHPB2001.
10.3.3. 
Informed Consent Process
Refer to Attachment 3 of the Master Protocol PLATFORMPAHPB2001.
Each participant must give consent according to local requirements after the nature of the study
has been fully explained.
Participants will be asked for consent to provide optional host DNA samples and/or FNA biopsy
samples for research (where local regulations permit). After informed consent for the study is
appropriately obtained, the participant will be asked to sign and personally date a separate ICF
indicating agreement to participate in the optional research component. Refusal to participate in
the optional research will not result in ineligibility for the study. A copy of this signed ICF will be
given to the participant.
10.3.4. 
Data Protection
Refer to Attachment 3 of the Master Protocol PLATFORMPAHPB2001.
The informed consent obtained from the participant includes information about, and where
required per applicable regulations, explicit consent for the processing of personal data and for the
investigator/institution to allow direct access to his or her original medical records (source
data/documents) for study-related monitoring, audit, IEC/IRB review, and regulatory inspection.
The informed consent also provides information to address the lawful transfer of the data to other
entities and to other countries.
The participant has the right to request through the investigator access to his or her personal data
and the right to request rectification of any data that are not correct or complete, or make requests
concerning his or her personal data in accordance with applicable data protection law. Reasonable
steps will be taken to respond to such a request, taking into consideration the nature of the request,
the conditions of the study, and the applicable laws and regulations.
In the event of a data security breach, the sponsor will apply measures to adequately manage and
mitigate possible adverse effects taking into consideration the nature of the data security breach as
necessary to address other obligations such as notifying appropriate authorities in accordance with
applicable data protection law.
10.3.5. 
Long-Term Retention of Samples for Additional Future
Refer to Attachment 3 of the Master Protocol PLATFORMPAHPB2001.

JNJ-73763989 
Clinical Protocol 73763989PAHPB2008 Amendment 3
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
96
Status: Approved, Date: 30 June 2023
10.3.6. 
Committees Structure
Data Review Committee
The internal DRC established for the Platform study will review interim data and formulate
recommendations to protect the safety and well-being of the participants. Description of the DRC
is provided in Section 9.6 of the Master Protocol PLATFORMPAHPB2001. The possible
recommendations and role of the DRC will be further detailed in the DRC charter for this ISA.
Independent Flare Expert Panel
An IFLEP will be appointed. The IFLEP is composed of 3 independent medical experts with
experience and expertise in HBV and its treatment. The IFLEP will monitor ALT flares and will
make recommendations regarding flare management based on an analysis of aggregate data.
In order to allow for an unbiased assessment, members of the committee will not serve as study
investigators or as members of the DRC.
Further details on the IFLEP process will be included in the IFLEP charter.
10.3.7. 
Publication Policy/Dissemination of Clinical Study Data
Refer to Attachment 3 of the Master Protocol PLATFORMPAHPB2001.
10.3.8. 
Data Quality Assurance
Refer to Attachment 3 of the Master Protocol PLATFORMPAHPB2001.
10.3.9. 
Case Report Form Completion
Refer to Attachment 3 of the Master Protocol PLATFORMPAHPB2001.
10.3.10. 
Source Documents
Refer to Attachment 3 of the Master Protocol PLATFORMPAHPB2001.
10.3.11. 
Monitoring
Refer to Attachment 3 of the Master Protocol PLATFORMPAHPB2001.
10.3.12. 
On-Site Audits
Refer to Attachment 3 of the Master Protocol PLATFORMPAHPB2001.
10.3.13. 
Record Retention
Refer to Attachment 3 of the Master Protocol PLATFORMPAHPB2001.
10.3.14. 
Study and Site Start and Closure
Refer to Attachment 3 of the Master Protocol PLATFORMPAHPB2001.
The first participant screened is considered the first act of recruitment and it becomes the study
start date.

JNJ-73763989 
Clinical Protocol 73763989PAHPB2008 Amendment 3
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
97
Status: Approved, Date: 30 June 2023
10.4. Appendix 4: Adverse Events, Serious Adverse Events, Product Quality
Complaints, and Other Safety Reporting: Definitions and Procedures for
Recording, Evaluating, Follow-up, and Reporting
10.4.1. 
Adverse Event Definitions and Classifications
Refer to Attachment 4 of the Master Protocol PLATFORMPAHPB2001.
10.4.2. 
Attribution Definitions
Refer to Attachment 4 of the Master Protocol PLATFORMPAHPB2001.
10.4.3. 
Severity Criteria
Refer to Attachment 4 of the Master Protocol PLATFORMPAHPB2001.
10.4.4. 
Special Reporting Situations
Refer to Attachment 4 of the Master Protocol PLATFORMPAHPB2001.
A participant pregnancy or participant partner(s) pregnancy is also considered a special reporting
situation in this ISA.
10.4.5. 
Procedures
Refer to Attachment 4 of the Master Protocol PLATFORMPAHPB2001.
10.4.6. 
Product Quality Complaint Handling
Refer to Attachment 4 of the Master Protocol PLATFORMPAHPB2001.
10.4.7. 
Contacting Sponsor Regarding Safety, Including Product Quality
Refer to Attachment 4 of the Master Protocol PLATFORMPAHPB2001.

JNJ-73763989 
Clinical Protocol 73763989PAHPB2008 Amendment 3
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
98
Status: Approved, Date: 30 June 2023
10.5. Appendix 5: Contraceptive and Barrier Guidance
Participants must follow contraceptive measures as outlined in Section 5.1, Inclusion Criteria.
Pregnancy information will be collected and reported as noted in Section 8.3.5, Pregnancy and
Appendix 4: Adverse Events, Serious Adverse Events, Product Quality Complaints, and Other
Safety Reporting: 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.
If there is a question about menopausal status in women on HRT, the woman will be required
to use one of the non-estrogen-containing hormonal highly effective contraceptive methods if
she wishes to continue HRT during the study.
 
permanently sterile (for the purpose of this study)
- Permanent sterilization methods include hysterectomy, or bilateral salpingectomy, or
bilateral oophorectomy.
- Has congenital abnormalities resulting in sterility.
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.
If reproductive status is questionable, additional evaluation should be considered.
Contraceptive (birth control) use by men or women must 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 must be
consistent with local regulations regarding the use of contraceptive methods for participants in
clinical studies.

JNJ-73763989 
Clinical Protocol 73763989PAHPB2008 Amendment 3
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
99
Status: Approved, Date: 30 June 2023
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 ovulation
 Intrauterine device (IUD)
 Intrauterine hormone-releasing system (IUS)
 Tubal closure (eg, bilateral tubal occlusion, bilateral tubal ligation)
 Azoospermic partner (vasectomized or due to medical cause)
(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 must be used.
Spermatogenesis cycle is approximately 74 days.)
USER DEPENDENTb
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 ovulation
 oral
 intravaginal
 transdermal
 injectable
 Progestogen-only hormone contraception associated with inhibition of ovulation
 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.)
a. Typical use failure rates may differ from those when used consistently and correctly. Use must
be consistent with local regulations regarding the use of contraceptive methods for
participants in clinical studies.
b. User-dependent, highly effective forms of contraception are not acceptable as the sole method
ofcontraception for female study participants of childbearing potential. They are acceptable
as the sole method of contraception only for female partners of male study participants.

JNJ-73763989 
Clinical Protocol 73763989PAHPB2008 Amendment 3
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
100
Status: Approved, Date: 30 June 2023
10.6. Appendix 6: Rash Management
Table 14: 
Management of Rash Events by Severity Grade
Activities by Daya
In case of suspicion of immune-related rash events
Grade 1 rash
(with or without pruritus)b
Day 0: Optional on-site visit for initial rash evaluation may be performed at the
investigator’s discretion.
Safety laboratory assessments may be performed at the investigator’s discretion
(recommended if visit occurs).
Digital picturesc of skin lesions may be taken at the investigator’s discretion.
Day 1 and thereafter: Appropriate follow-up visits at the investigator’s
discretion until resolution of rash.
Safety laboratory assessments and digital picturesc of skin lesions may be
performed at the investigator’s discretion.
Study intervention may be continued at the investigator’s discretion
Treat with topical emollients and/or mild-moderate potency
topical corticosteroids.
Counsel patients to avoid skin irritants and sun exposure
Grade 2 rash
(with or without pruritus)b
Day 0: Required on-site visit (if a visit is not possible, telephone contact with the
participant should take place to collect information and give advice on the
necessary measures to be taken).
Safety laboratory assessments may be performed at the investigator’s discretion
(recommended).
The participant may be referred to a dermatologist at the investigator’s discretiond,
who may perform a biopsy.
Digital picturesc of skin lesions may be taken at the investigator’s discretion.
Digital picturesc of skin lesions are recommended in case consultation of a
dermatologist is required.
Day 1 and thereafter: Appropriate follow-up visits at the investigator’s
discretion until resolution of rash or until clinical stability is reached.
Safety laboratory assessments are required on Day 1 and are required thereafter
only if the previous values were abnormal (but may be performed at the
investigator’s discretion). If the rash progresses to a higher grade, safety
laboratory assessments of the higher grade should be followed.
Digital picturesc of skin lesions may be taken at the investigator’s discretion.
Study intervention may be continued at the investigator’s discretion
Immediately: Symptomatic therapy (eg, antihistamines, topical
steroids)
Persistence ≥2 weeks or recurrence: consider skin biopsy;
consider 0.5-1.0 mg/kg/d methylprednisolone IV or oral
equivalent; consider prophylactic antibiotics
Improvement to ≤Grade 1: taper steroids over at least 4 weeks
Worsening to >Grade 2: treat as Grade 3-4
In case of treatment with systemic corticosteroids initiated,
nivolumab must be discontinued.

JNJ-73763989 
Clinical Protocol 73763989PAHPB2008 Amendment 3
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
101
Status: Approved, Date: 30 June 2023
Table 14: 
Management of Rash Events by Severity Grade
Activities by Daya
In case of suspicion of immune-related rash events
Grade 3 rashb
Day 0: Required on-site visit.
Safety laboratory assessments required to be performed.
Referral to a dermatologist requiredd, who may perform a biopsy.
Digital picturesc of skin lesions may be taken at the investigator’s discretion
(recommended).
Day 1 and thereafter: Appropriate follow-up required until resolution of rash or
until clinical stability is reached.
Safety laboratory assessments and photography (digital picturesc of skin lesions)
are recommended to be performed until the rash severity resolves to Grade 2 or
Grade 1.
Must permanently discontinue study intervention; no rechallenge allowed
Immediately: consult dermatologist; consider skin biopsy; start
0.5-1.0 mg/kg methylprednisolone IV or IV equivalent; add
prophylactic antibiotics
Improvement to ≤Grade 1: taper steroids over at least 4 weeks
Grade 4 rash  
Day 0: required on-site visit. 
Safety laboratory assessments required to be performed. 
Referral to a dermatologist requiredd and biopsy to be performed as soon as
possible after onset of rash.
Digital picturesc of skin lesions may be taken at the investigator’s discretion
(recommended).
Day 1 and thereafter: appropriate follow-up required until resolution of rash or
until clinical stability is reached.
Safety laboratory assessments and photography (digital picturesc of skin lesions)
are recommended to be performed until the rash severity resolves to Grade 2 or
Grade 1.
Must permanently discontinue study intervention; no rechallenge allowed
Immediately: referral to a dermatologist requiredd; biopsy to be
performed as soon as possible after onset of rash; start
1.0-2.0 mg/kg/d methylprednisolone IV or IV equivalent; add
prophylactic antibiotics
Improvement to ≤Grade 1: taper steroids over at least 4 weeks
AE: adverse event; ALT: alanine aminotransferase; AST: aspartate aminotransferase; NA: nucleos(t)ide analog.
a 
Day 0 of the rash is the first day of investigator assessment and not the first day of rash as reported by the participant. The initial visit should be conducted as soon as possible after
the participant contacts the investigator to report the AE (ie, preferably on Day 0). The initial visit and subsequent visits to manage the rash may require unscheduled visit(s).
b 
The participant should be advised to contact the investigator immediately if there is any worsening of the rash, if any systemic signs or symptoms appear, or if mucosal involvement
develops. In case the rash evolves to a higher grade than that first observed, management of the rash should follow the guidelines indicated for the higher grade.
c 
Digital pictures to be taken at the clinical site upon consent of the participant.
d 
If applicable, dermatologist visit should occur preferably within 24 hours after onset of rash.
Notes:
 
Local laboratory assessments are to be used for rash management. The values of the local laboratory assessments need to be transcribed in the CRF by the study site personnel.
 
A copy of the dermatologist’s report, biopsy, and/or digital pictures if performed, should be made anonymous and will be provided to the sponsor.
 
The grades are based on the DAIDS Toxicity Grading Scale and NCI-CTCAE (see Section 10.8, Appendix 8: DAIDS Table with Modifications).

JNJ-73763989 
Clinical Protocol 73763989PAHPB2008 Amendment 3
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
102
Status: Approved, Date: 30 June 2023
10.7. Appendix 7: Cardiovascular Safety –Abnormalities
ECG
All important abnormalities from the ECG readings will be listed.
Abnormality Code 
ECG Parameter
Heart Rate 
PR  
QRS  
QTcorrected
Abnormalities on actual values
Abnormally low  
<45 bpm  
NAP  
- 
-
Abnormally high  
120 bpm  
>220 ms 
120 ms 
-
Borderline prolonged QT  
- 
- 
- 
450 ms < QTc ≤480 ms
Prolonged QT  
- 
- 
- 
480 ms < QTc <500 ms
Pathologically prolonged QT 
- 
- 
- 
QTc >500 ms
Abnormalities on changes from baseline (∆QTc)
Normal QTc change 
- 
- 
- 
∆QTc <30 ms
Borderline QTc change 
- 
- 
- 
30 ms < ∆QTc <60 ms
Abnormally high QTc change 
- 
- 
- 
∆QTc >60 ms
ECG: electrocardiogram; NAP = not applicable
For absolute QTc parameters the categories are defined based on the International Council for Harmonisation of
Technical Requirements for Pharmaceuticals for Human Use (ICH) E14 Guidancea
Vital Signsb
The following abnormalities will be defined for vital signs:
Abnormality Code 
Vital Signs Parameter
Pulse 
DBP 
SBP
Abnormalities on actual values
Abnormally low  
45 bpm  
50 mmHg 
90 mmHg
Grade 1 or mild 
- 
>90 mmHg - <100 mmHg 
>140 mmHg - <160 mmHg
Grade 2 or moderate 
- 
100 mmHg - <110 mmHg 
160 mmHg - <180 mmHg
Grade 3 or severe 
- 
110 mmHg 
180 mmHg
Abnormally high  
120 bpm  
- 
-
DBP: diastolic blood pressure; SBP: systolic blood pressure
a The clinical evaluation of QT/QTc interval prolongation and proarrhythmic potential for non-antiarrhythmic drugs
CHMP/ICH/2/04, May 2005.
b The classification of AEs related to hypotension and hypertension will be done according to the DAIDS  grading
scale.

JNJ-73763989 
Clinical Protocol 73763989PAHPB2008 Amendment 3
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
103
Status: Approved, Date: 30 June 2023
10.8. Appendix 8: DAIDS Table with Modifications (DAIDS [Modified])
DIVISION OF AIDS (DAIDS) TABLE FOR GRADING THE SEVERITY OF ADULT
AND PEDIATRIC ADVERSE EVENTS, VERSION 2.1, PUBLISH DATE: JULY, 2017
The DAIDS grading table is a descriptive terminology to be utilized for AE reporting in this study.
A grading (severity) scale is provided for each AE term.
General Instructions
Grading Adult and Pediatric Adverse Events
When a single parameter is not appropriate for grading an AE in both adult and pediatric
populations, separate parameters with specified age ranges are provided. If there is no distinction
between adult and pediatric populations, the listed parameter should be used for grading an AE in
both populations.
Determining Severity Grade for Parameters Between Grades
If the severity of an AE could fall under either 1 of 2 grades (eg, the severity of an AE could be
either Grade 2 or Grade 3), sites should select the higher of the 2 grades.
Laboratory normal ranges should be taken into consideration to assign gradings to a laboratory
value.
Definitions
Basic self-care functions 
Adults: activities such as bathing, dressing, toileting,
transfer/movement, continence, and feeding
Young children: activities that are age and culturally appropriate
(eg, feeding self with culturally appropriate eating implements)
Usual social & functional 
activities 
Activities which adults and children perform on a routine basis and
those which are part of regular activities of daily living, for
example:
Adults: adaptive tasks and desirable activities, such as going to
work, shopping, cooking, use of transportation, or pursuing a
hobby
Young Children: activities that are age and culturally appropriate
(eg, social interactions, play activities, learning tasks)
Intervention 
Medical, surgical, or other procedures recommended or provided
by a healthcare professional for the treatment of an AE
Estimating Severity Grade for Parameters not Identified in the Grading Table
The functional table below should be used to grade the severity of an AE that is not specifically
identified in the grading table. In addition, all deaths related to an AE are to be classified as
Grade 5.

JNJ-73763989 
Clinical Protocol 73763989PAHPB2008 Amendment 3
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
129
Status: Approved, Date: 30 June 2023
10.9. Appendix 9: Study Conduct During a Natural Disaster
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, isolation or quarantine ofparticipants and
study site personnel; travel restrictions/limited access to public places, including hospitals; study
site personnel being unavailable, isolated, or reassigned to critical tasks.
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
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 travel to the study site is considered to be
dangerous, study participation may be interrupted, and study follow-up conducted. If it becomes
necessary to discontinue participation in the study, the procedures outlined in the protocol for
discontinuing study intervention will be followed.
If, as a result of the COVID-19 pandemic scheduled visits cannot be conducted in person at the
study site, they 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 after consultation with the participant, investigator, and the sponsor. Missed
assessments/visits will be captured in the clinical trial management system for protocol deviations.
Discontinuations of study intervention and withdrawal from the study should be documented with
the prefix “COVID-19-related” in the CRF.
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.
Modifications made to the study conduct as a result of the COVID-19 should be summarized in
the clinical study report.
If the participant has tested positive for the COVID-19, the investigator should contact the
sponsor’s responsible medical officer to discuss plans for administration of study intervention,
performing. study assessments, and follow-up. Modifications made to the study conduct as a result
of the COVID-19 should be summarized in the clinical study report.

JNJ-73763989 
Clinical Protocol 73763989PAHPB2008 Amendment 3
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
130
Status: Approved, Date: 30 June 2023
GUIDANCE SPECIFIC TO THIS PROTOCOL
The following emergency provisions are meant to ensure participant safety on study while site
capabilities are compromised by COVID-19-related restrictions. Remote medical consultation and
alternatives to study intervention dispensing, administration, and clinical laboratory assessments
may allow continued study participation for participants in this trial. Before implementing any of
these emergency provisions, the sponsor should be consulted to perform a benefit-risk analysis
and to ensure the measures are executed and documented correctly.
As restrictions are lifted and the acute phase of the COVID-19 pandemic resolves, sites should
revert to original protocol conduct as soon as feasible and in accordance with any country-specific
regulatory requirements.
Screening and Randomization:
 Enrollment of new participants may continue based on the investigator’s assessment of risks
versus benefits, depending on the situation at a particular site, and the ability to monitor
participant safety.
 Baseline visits for participants recently screened for this study should be postponed if the
current situation does not allow for an orderly conduct of the study.
Dispensing/Administration of Study Intervention and NA Background Regimen:
 For participants able to visit the study site, but who request to reduce visit frequency, or for
whom limited access to the site is expected, an additional supply of NA background treatment,
where allowed per local regulations, can be provided.
 For participants unable to visit the study site, shipment or handover to a caregiver or delegate
of NA background treatment, may be implemented, where allowed per local regulations and if
requested by the treating study physician. Where shipments or handover to delegates are
deemed necessary, the process must be coordinated between the site and participant for
arranging shipment and adhering to associated approvals and documentation requirements.
 JNJ-3989 and nivolumab should always be administered by a nurse at the study site or, if site
visits are not possible, at the participant’s home. Refer to Section 6.4, Study Intervention
Compliance, in case a scheduled administration of study intervention (JNJ-3989 and
nivolumab) or NA background treatment is missed.
Continuation of Study Intervention and/or NA Background Treatment:
 Any issue with continuation and/or provision of study intervention  and/or NA background
treatment should be discussed with the sponsor and should be well documented.
 Study intervention should be continued if, in the assessment of the investigator, it does not
result in risk to the participant. If at any time the participant’s safety is considered at risk due
to study intervention, study intervention will be temporarily or permanently discontinued,
while every effort should be made to maintain follow-up on study. The benefit of continuing
study intervention should be assessed by the investigator for each individual participant,
considering the potential impact of reduced direct clinical supervision on participant safety.

JNJ-73763989 
Clinical Protocol 73763989PAHPB2008 Amendment 3
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
131
Status: Approved, Date: 30 June 2023
 If a participant develops a SARS-CoV-2 infection, the investigator should contact the sponsor
to discuss plans for study intervention and follow-up. A decision to continue study intervention
should be made by the investigator depending on symptoms and concomitant medication(s)
used for the treatment of COVID-19. Study intervention must be discontinued if prohibited
medication is used.
 When a participant, for whom study intervention has been interrupted, recovers from suspected
or confirmed SARS-CoV-2 infection or related disease and all AEs related to SARS-CoV-2
infection improve to Grade ≤1, the investigator should discuss with the sponsor about resuming
study intervention.
COVID-19 Vaccination During the Study:
Locally approved COVID-19 vaccines (including those that received emergency use authorization
or conditional marketing authorization) are allowed throughout the study with the exception of the
second dose of Sputnik V.
During nivolumab treatment, the following recommendations should be applied to accommodate
COVID-19 vaccination:
 
COVID-19 vaccine and nivolumab should not be administered on the same day. If required,
nivolumab administration can be delayed by 2-5 days.
 
The next nivolumab administration should be performed at the scheduled time.
 
If required, skipping a nivolumab administration may be considered after consultation with
the sponsor.
All COVID-19 vaccination-related data (eg, COVID-19 vaccination, AEs, AE management)
should be appropriately captured in the CRF and source documents. Refer to the COVID-19
vaccine prescribing information for more details.
Study Visits and Assessments:
 If possible, central laboratory testing as outlined in the Schedule of Activities is to be
continued. If central laboratory tests cannot be performed, the use of a local laboratory is
allowed for study evaluations. A copy of the local laboratory report should be reviewed by the
investigator and filed with the source documents, along with reference ranges.
 To safely maintain participants on study intervention while site capabilities are compromised
by COVID-19-related restrictions, study visits may be performed by a nurse (who received
study-specific training) at the patient’s home (home health nurse) until such time that on-site
visits can be resumed. The following activities may be completed as required per the Schedule
of Activities and as feasible:
 Sampling, processing and shipping of laboratory samples (as described above).
 Performing electrocardiograms (ECGs).
 If JNJ-3989 is administered at the patient’s home, it will need to be done by a nurse (who
received study-specific training).

JNJ-73763989 
Clinical Protocol 73763989PAHPB2008 Amendment 3
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
132
Status: Approved, Date: 30 June 2023
 Any data related to AEs, concomitant medication, vital signs, and ECGs will be reviewed and
assessed by the investigator.
 In addition, participants may have tele-health visits conducted by qualified site personnel via
phone or video conversation as per local regulation. Assessments may include review of AEs
(including ISRs), concomitant medications, and study intervention accountability. Participants
will also be questioned regarding general health status to fulfill any physical examination
requirement.
 Procedures and timings should follow the Schedule of Activities as closely as possible.
Standard AE/serious adverse event (SAE) reporting requirements apply.
 Ultrasound (and Fibroscan where applicable) should be done as close as possible to the time
points specified in the Schedule of Activities. However, if this is not possible due to
COVID-19-related restrictions, the imaging test should be performed as soon as possible.
Informed Consent:
 Consenting and re-consenting of participants (including also remote consenting by phone or
video consultation) will be performed as applicable for the measures taken and according to
local guidance for informed consent applicable during the COVID-19 pandemic. The process
is to be documented in the source documents.
Source Data Verification/Monitoring:
 In case on-site monitoring visits are not possible, the site monitor may contact the investigator
to arrange monitoring activities remotely (in accordance with site and local requirements).
Additional on-site monitoring visits may be needed in the future to catch up on source data
verification.
Site Audits:
 During the COVID-19 pandemic and at the impacted sites, study site Good Clinical Practice
(GCP) audits with direct impact/engagement from the investigator and study site personnel
would not be conducted in order to comply with national, local, and/or organizational social
distancing restrictions. Additional quality assurance activities such as remote audits or focused
review of study-related documents may take place with limited impact/engagement if possible.

JNJ-73763989 
Clinical Protocol 73763989PAHPB2008 Amendment 3
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
133
Status: Approved, Date: 30 June 2023
10.10. Appendix 10: Protocol Amendment History
Amendment 2 (28 March 2023)
Overall Rationale for the Amendment: The main reason for the protocol amendment is that due to
difficult recruitment a strategic decision was taken to not extend further enrollment beyond the planned
enrollment period and continue the study with a reduced sample size. There is no change in the benefit/risk
for the participants.
Section number
and Name
Description of Change 
Brief Rationale
1.1. Synopsis
1.2. Schema
4.1. Overall Design
9.2. Sample Size
Determination
Reduction of sample size. 
Due to difficult recruitment.
1.1. Synopsis
9.5. Interim Analysis
Reduction of number of planned interim
analyses.
The remaining optional interim
analyses at Week 24 and FU
Week 12, in addition to the final
analysis (at FU Week 48),
provide sufficient information to
assess safety and evaluate the
time course of different safety
and efficacy markers during
study conduct.
1.3.1. Schedule of Activities
–Screening Phase and
Study Intervention Phase
1.3.2. Schedule of Activities
–Follow-up Phase
8.7. Exploratory Host
Biomarkers
Removed the sentence: ‘For participants’
convenience, the coagulation test may be
collected at the visit preceding the scheduled
FNA biopsy.’
Correction.
1.3.2. Schedule of Activities
–Follow-up Phase
8. STUDY
ASSESSMENTS AND
PROCEDURES
Reduction of samples collection and analyses
during the follow-up period. Therefore, the
total blood volume was updated accordingly.
Protocol simplification without
impacting participant’s safety
and maintaining scientific value.
1.1. Synopsis
6.1. Study Intervention(s)
Administered
6.8. Treatment of Overdose
Added flexibility for nivolumab dosing and
updated the overdose definition.
To consider the necessary
rounding and standard practice
for the preparation and
intravenous administration of
drugs dosed by weight.
2.3.2.1. Known Risks 
Added: ‘Treatment with anti-PD-1
medications is associated with a risk of HBV
reactivation in CHB patients. This risk is
reduced with concurrent NA treatment or
continuation of ongoing NA treatment.’
Clarification. 
2.3.3. Benefit-Risk 
Assessment for Study 
Participation  
Added: ‘Participants will be regularly 
monitored for HBV reactivation and virologic
breakthroughs throughout the study.’
Clarification.
5.2. Exclusion Criteria 
Exclusion criteria M09 and M10 were further 
clarified.
Clarification.
7.1.1. Discontinuation of 
JNJ-3989 
Added: ‘based on creatinine (calculated by the 
CKD-EPI formula)’.
Clarification.
8.2.1. Physical 
Examinations
Added thyroid check to physical examination. 
Clarification.

JNJ-73763989 
Clinical Protocol 73763989PAHPB2008 Amendment 3
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
134
Status: Approved, Date: 30 June 2023
Section number 
and Name
Description of Change 
Brief Rationale
8.3. Adverse Events, 
Serious Adverse Events, 
and Other Safety Reporting
Added coding conventions for the AEs 
reported by investigators.
Clarification.
8.3.6.3.1. Hematologic 
Abnormalities 
Added hematological abnormalities for 
nivolumab when used in the oncology setting.
Clarification.
10.8. Appendix 8: DAIDS 
Table with Modifications 
(DAIDS [Modified]) 
Updated the CTCAE Severity Grading for 
irAEs table by adding severity grading for
myocarditis.
For investigator convenience.
11. REFERENCES  
Update of IB version. 
Update of IB version
INVESTIGATOR 
AGREEMENT  
Update of Sponsor’s Responsible Medical 
Officer. 
Update of Sponsor’s
Responsible Medical Officer.
Throughout the protocol 
Minor grammatical, formatting, or spelling 
changes were made.
Minor errors were noted.
Amendment 1(30 June 2022)
Overall Rationale for the Amendment: The rationale of this amendment is to allow inclusion of
participants with low titers of autoantibodies, to remove certain procedures, to implement changes regarding
immune-related gastro-intestinal adverse event management based on Health Authority feedback and
clarifications of sampling collection.
Section number 
and Name
Description of Change 
Brief Rationale
1.1. Synopsis
1.3.1. Schedule of Activities
–Screening Phase and
Study Intervention Phase
4.1. Overall Design
5. STUDY POPULATION
Text added to indicate the screening duration extension to
6 weeks (42 days)
To take into account
the turnaround time
for certain screening
tests
1.3.1. Schedule of Activities
–Screening Phase and
Study Intervention Phase
1.3.2. Schedule of Activities
–Follow-up Phase
5.2. Exclusion Criteria
10.2. Appendix 2: Clinical
Laboratory Tests
Text was added to provide a full list of autoantibodies to
be tested and their respective exclusionary cut-off
To allow inclusion
of participants with
low titers of
autoantibodies.
Autoantibodies may
be found in
otherwise healthy
participants
1.1. Synopsis
1.3.1. Schedule of Activities
–Screening Phase and
Study Intervention Phase
1.3.2. Schedule of Activities
–Follow-up Phase
3. OBJECTIVES AND
ENDPOINTS
8.5. Pharmacodynamics
Functional receptor occupancy (RO) assay was removed
Time points for RO assay for Arm 1 and Arm 2,
previously provided in Table 14 (removed), were added to
the Schedule of Activities
Comparative
functional RO data
is not available for
nivolumab
For clarification
1.3.1. Schedule of Activities
–Screening Phase and
Study Intervention Phase
8.4.1. Evaluations
Text was added to clarify blood sampling for sparse PK  
For clarification

JNJ-73763989 
Clinical Protocol 73763989PAHPB2008 Amendment 3
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
135
Status: Approved, Date: 30 June 2023
Section number 
and Name
Description of Change 
Brief Rationale
1.3.2. Schedule of Activities 
–Follow-up Phase 
Text was added in the footnote of Schedule of Activities to 
clarify that participants who discontinued study
prematurely will have an early withdrawal visit
For clarification
1.3.1. Schedule of Activities 
–Screening Phase and 
Study Intervention Phase 
1.3.2. Schedule of Activities 
–Follow-up Phase 
8.7. Exploratory Host 
Biomarkers
Removal of the platelet aggregation test 
Platelet aggregation
test is not part of the
recommended pre
fine needle
aspiration (FNA)
work-up
5.2. Exclusion Criteria 
Text was added to exclude participants with absolute 
neutrophil count <1,500/mm3 (<1,000/mm3 for 
participants of African ancestry)
Nivolumab may
induce neutropenia
7.2.1. Withdrawal From the 
Use of Research Samples 
Text was added to align with guidance regarding 
management of optional research samples 
To not destroy
samples already
collected in case of
participant
withdrawal if the
participant agrees to
have his/her samples
further stored and
analyzed
8. STUDY 
ASSESSMENTS AND 
PROCEDURES  
Text was added to reflect adjustment of total blood, 
peripheral blood mononuclear cell (PBMC) and 
pharmacogenomic sample volumes 
Blood volumes were
adjusted to reflect
total volumes
collected during the
study
8.3.6.1. Intervention- 
emergent ALT/AST 
Elevations Including 
Immune-related Hepatic 
AEs 
Table 5 
Text was updated to clarify mandatory histologic 
assessment in case of potential immune-related hepatic AE 
The histologic
assessment as a
prerequisite to
initiate
corticosteroids and
stop nivolumab was
made not mandatory
to avoid delay in
potential irAE
management
8.3.6.2.1. Gastrointestinal 
Adverse Events 
Text was added to specify medical assessment for 
treatment-emergent colitis ≥Grade 2 
To align with
American society of
clinical oncology
(ASCO) guidelines
for the management
of immune-related
Adverse Events in
patients treated with
Immune Checkpoint
Inhibitor therapy
1.1. Synopsis 
9.5. Interim Analysis 
Text was added to indicate an additional interim analysis 
when all randomized participants have completed 
Week 24 or discontinued earlier 
Optimization of the
interim analysis
schedule
10.2. Appendix 2: Clinical 
Laboratory Tests
Table updated to add C-reactive protein (CRP) 
For clarification
10.9. Appendix 9: Study 
Conduct During a Natural 
Disaster 
Text was revised to clarify nucleos(t)ide analog (NA) 
background treatment and remove reference to 
direct-to-patients process. 
Clarification of NA
background
treatment

JNJ-73763989 
Clinical Protocol 73763989PAHPB2008 Amendment 3
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
136
Status: Approved, Date: 30 June 2023
Section number 
and Name
Description of Change 
Brief Rationale
7.1.2. Discontinuation of 
Nivolumab 
Text was added to include discontinuation of nivolumab 
by the investigator for safety reasons
For completeness
10.1. Appendix 1: 
Abbreviations and
Definitions
Abbreviation and definition list updated 
For completeness
Throughout the protocol 
Minor grammatical, spelling changes or formatting 
changes were made 
Minor errors were
noted

JNJ-73763989 
Clinical Protocol 73763989PAHPB2008 Amendment 3
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
137
Status: Approved, Date: 30 June 2023
11. 
REFERENCES
Clinical Protocol Amendment 2: 73763989HPB2001 (REEF-1). Janssen Research & Development (January 2020).
Clinical Protocol Amendment 2: 73763989PAHPB2002 (REEF-2). Intervention-specific Appendix 2 to Master
Protocol PLATFORMPAHPB2001. Janssen Research & Development (January 2020).
Clinical Protocol Amendment 2: 73763989PAHPB2006 (PENGUIN). Intervention-specific Appendix 4 to Master
Protocol PLATFORMPAHPB2001. Janssen Research & Development (May 2021).
Brahmer JR, Drake CG, Wollner I, et al. Phase I study of single-agent anti-programmed death-1 (MDX-1106) in
refractory solid tumors: safety, clinical activity, pharmacodynamics, and immunologic correlates. J Clin Oncol
2010;28(19):3167-3175.
Cattley RC and Cullen JM. Chapter 45: Liver and Gall Bladder. Haschek and Rousseaux’s. Handbook of
Toxicologic Pathology, Third Ed., 2013.
Ebeling M, Kung E, See A, et al. Genome-based analysis of the nonhuman primate Macaca fascicularis as a model
for drug safety assessment. Genome Res. 2011; 21:1746-1756.
El-Khoueiry AB, Sangro B, Yau T, et al. Nivolumab in patients with advanced hepatocellular carcinoma
(CheckMate 040): an open-label, non- comparative, phase 1/2 dose escalation and expansion trial. Lancet. 2017;
389(10088):2492-2502.
Fang Z, Li J, Yu X, et al. Polarization of monocytic myeloid-derived suppressor cells by hepatitis B surface antigen
is mediated via ERK/IL-6/STAT3 signaling feedback and restrains the activation of T cells in chronic hepatitis B
virus infection. J Immunol. 2015;195(10):4873-4483.
Gane E, Daniel JV, Anna EB, et al. Anti-PD-1 blockade with nivolumab with and without therapeutic vaccination
for virally suppressed chronic hepatitis B: A pilot study. J Hepatol 2019;71:900-907-
Givlaari (givosiran; NDA212194) NDA/BLA Multi-Disciplinary Review and Evaluation, Center for Drug
Evaluation and Research. 20 November 2019.
Greaves P. Chapter 2: Integumentary system- skin and subcutaneous tissue (pages 39-42). Histopathology of
preclinical toxicity studies: Interpretation and relevance in drug safety studies, Fourth editioned., 2012.
Henry SP, Johnson M, Zanardi TA, et al. Renal uptake and tolerability of a 2’-O-methoxyethyl modified antisense
oligonucleotide (ISIS 113715) in monkey. Toxicology. 2012;301(1-3):13-20.
Holsapple MP, Pitot HC, Cohen SM, et al. Mode of action in relevance of rodent liver tumors to human cancer risk.
Toxicol Sci, 2006; 89(1):51-56.
Investigator’s Brochure: JNJ-73763989 (IB JNJ-3989) Edition 6 Janssen Research & Development (8 April 2022).
Janas MM, Harbison CE, Perry VK, et al. The nonclinical safety profile of GalNac-conjugated RNAi therapeutics in
subacute studies. Toxicol Pathol. 2018a;46(7):735-745.
Janas MM, Schlegel MK, Harbison CE, et al. Selection of GalNAc-conjugated siRNAs with limited off-target-
driven rat hepatotoxicity. Nat Commun, 2018b;9(1):723.
Lautenschlager I, Höckerstedt K, Häyry P. Fine-needle aspiration biopsy in the monitoring of liver allografts.
Transpl Int. 1991;4(1):54-61.
Li H, Zhai N, Wang Z, et al. Regulatory NK cells mediated between immunosuppressive monocytes and
dysfunctional T cells in chronic HBV infection. Gut. 2018;67(11):2035-2044.
Memorandum to Advisory Committee Members and Guests from Entecavir Review Team. Briefing document for
NDA 21-797, entecavir 0.5 and 1 mg tablets and NDA 21-798, entecavir oral solution 0.05 mg/mL,
10 February 2005.
Memorandum to the file for BLA 125554 OPDIVO (nivolumab). Approvability of Pharmacology and Toxicology.
Bristol-Myers Squibb Company; 04 December 2014.
Nivolumab Summary of Product Characteristics (NSPC). Uxbridge, United Kingdom: Bristol-Myers Squibb Pharma
EEIG. https://www.ema.europa.eu/en/documents/product-information/nivolumab-bms-epar-product-
information_en.pdf. Accessed 23 March 2023.

JNJ-73763989 
Clinical Protocol 73763989PAHPB2008 Amendment 3
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
138
Status: Approved, Date: 30 June 2023
Nivolumab US Package Insert (NUSPI). Princeton, NJ: Bristol-Myers Squibb Company.
https://packageinserts.bms.com/pi/pi_opdivo.pdf. Accessed 23 March 2023.
Setten RL, Rossi JJ and Han S-P. The current state and future directions of RNAi-based therapeutics. Nat Rev Drug
Discov. 2019;18(6):421-446.
Shah NJ, Al-Shbool G, BlackburnM, et al. Safety and efficacy of immune checkpoint inhibitors (ICIs) in cancer
patients with HIV, hepatitis B, or hepatitis C viral infection. J Immunother Cancer. 2019;7(1):353.
Tang TJ, Janssen HLA, Kusters JG, et al. The intrahepatic immune response during chronic hepatitis B infection can
be monitored by the fine-needle aspiration biopsy technique. FEMS Immunol Med Microbiol. 2003;39(1):69-72.
Topalian SL, Hodi FS, Brahmer JR, et al. Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N
Engl J Med 2012;366(26):2443-2454.
Wang S, Chen Z, Hu C, et al. Hepatitis B virus surface antigen selectively inhibits TLR2 ligand-induced IL-12
production in monocytes/macrophages by interfering with JNK activation. J Immunol. 2013;190(10):5142-5151.
Wooddell CI, Yuen M-F, Chan HKL, et al. RNAi-Based Treatment of Chronically Infected Patients and
Chimpanzees Implicates Integrated Hepatitis B Virus DNA as a Source of HBsAg. Sci. Transl. Med. 2017; 9(409).
Yang S, Zeng W, Zhang J, et al. Restoration of a functional antiviral immune response to chronic HBV infection by
reducing viral antigen load: if not sufficient, is it necessary? Emerg Microbes Infect. 2021;10(1):1545-1554.
Yuen M-F, Gane JE, Kim DJ, et al. Antiviral Activity, Safety, and Pharmacokinetics of Capsid Assembly Modulator
NVR 3-778 in Patients with Chronic HBV Infection. Gastroenterology 2019; 156(5):1392-1403.e7.

JNJ-73763989 
Clinical Protocol 73763989PAHPB2008 Amendment 3
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
139
Status: Approved, Date: 30 June 2023
INVESTIGATOR AGREEMENT
I have read this protocol and agree that in conjunction with the accompanying Master Protocol, it contains
all necessary details for carrying out this study. I will conduct the study as outlined herein and will complete
the study within the time designated.
I will provide copies of the protocol and all pertinent information to all individuals responsible to me who
assist in the conduct of this study. I will discuss this material with them to ensure that they are fully informed
regarding the study intervention, the conduct of the study, and the obligations of confidentiality.
Coordinating Investigator (where required):
Name (typed or printed):
Institution and Address:
Signature: 
Date:
(Day Month Year)
Principal (Site) Investigator:
Name (typed or printed):
Institution and Address:
Telephone Number:
Signature: 
Date:
(Day Month Year)
Sponsor's Responsible Medical Officer:
Name (typed or printed): 
Institution: 
Janssen Research & Development
Signature: electronic signature appended at the end of the protocol 
Date:
(Day Month Year)
Note: If the address or telephone number of the investigator changes during the study, written notification will be
provided by the investigator to the sponsor, and a protocol amendment will not be required.
PPD

Signature
User 
Date 
Reason
30-Jun-2023
16:06:26
(GMT)
Document Approval
PPD