A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Multiple-Dose Phase 2 Study to Evaluate the Efficacy and Safety of BMS-986263 in Adults With Compensated Cirrhosis From Nonalcoholic Steatohepatitis (NASH)
Phase: PHASE2
Conditions: Nonalcoholic Steatohepatitis (NASH)
Sponsor: Bristol-Myers Squibb

Official Title of Study: 
A Randomized, Double-blind, Placebo-controlled, Parallel-group, Multiple-dose Phase 2 Study 
to Evaluate the Efficacy and Safety of BMS-986263 in Adults With Compensated Cirrhosis From 
Nonalcoholic Steatohepatitis (NASH) 
 
NCT Number: NCT04267393 
Document Date (Date in which document was last revised): 13 October 2022 
 
 
 

Page:
1
Protocol Number:
IM025017
IND Number:
114,517
EUDRACT Number:
2019-003932-22
UTN Number:
U1111-1241-4762
Date, Version:
13-Oct-2022
CLINICAL PROTOCOL IM025017
A Randomized, Double-blind, Placebo-controlled, Parallel-group, Multiple-dose Phase 2 Study 
to Evaluate the Efficacy and Safety of BMS-986263 in Adults with Compensated Cirrhosis from 
Nonalcoholic Steatohepatitis (NASH)
Protocol Amendment Number 03
Study Director
Bristol-Myers Squibb Company
3401 Princeton Pike
Lawrenceville, NJ 08648
USA
Telephone: 
24-hr Emergency Telephone Number
USA: 
International: 
Bristol-Myers Squibb Research and Development
3401 Princeton Pike
Lawrenceville, NJ 08648
USA
1-2-1 Otemachi, Chiyoda-ku,
Tokyo 100-0004, Japan
This document is the confidential and proprietary information of Bristol-Myers Squibb Company (BMS) and 
its global affiliates. By reviewing this document, you agree to keep it confidential and to use and disclose it 
solely for the purpose of assessing whether your organization will participate in and/or the performance of the 
proposed BMS sponsored study. Any permitted disclosures will be made only on a confidential "need to know" 
basis within your organization or to your independent ethics committee(s). Any other use, copying, disclosure, 
or dissemination of this information is strictly prohibited unless expressly authorized in writing by BMS. Any 
supplemental information that may be added to this document is also confidential and proprietary to BMS and 
must be kept in confidence in the same manner as the contents of this document. Any person who receives this 
document without due authorization from BMS is requested to return it to BMS or promptly destroy it. All 
other rights reserved. References to BMS in this protocol may apply to partners to which BMS has transferred 
obligations, eg, a Contract Research Organization.
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Study IM025017
BMS-986263
HSP47 siRNA
Protocol Amendment No.: 03
Date: 13-Oct-2022
2
DOCUMENT HISTORY
Document
Date of Issue
Approvers
Summary of Changes
Protocol Amendment 03
im025017-protamend03
13-Oct-2022
 
 
Bristol-Myers Squibb
Updates include: change of study 
director; clarifications of when 
certain study procedures are 
required: DXA, liver biopsy, FSH, 
; Stable dose of 
treatment requirements; study 
procedures; addition of HbA1c 
measurement; addition of IM025015 
study information; timepoints for 
endpoints 
 
 
 updated; 
removal of Medical Monitor 
approval for screening extension; 
updates to inclusion/exclusion 
criteria (liver biopsy timing, MELD 
and Child-Pugh scoring criteria, 
COVID history, AFP and CT/MRI 
clarification, weight loss timing, 
vaccines, and HbA1c);
 
 
requirement to seek sponsor’s
approval for use of alternative 
brands of fat emulsions for placebo 
preparation; clarification to 
premedication administration 
timing; definition of infusion-related 
reactions (IRR) added, update to the 
most common symptoms of IRRs; 
updates to number and timing of PK 
sampling; reclassifications to types 
of 
 samples taken and 
correction of the matrix of 
 collected; removal of 
adiponectin and cluster of 
differentiation 163 
 
addition of a second interim 
analysis; updates to literature 
references; update to the serology 
criteria for diagnosis of hepatitis B 
infection (HBV) requiring
confirmation by HBV DNA testing; 
and update to countries of country-
specific requirements. 
Revised Protocol 2 Global
im025017-revprot02
25-Nov-2020
 
Bristol-Myers Squibb
Updates include: adjustment of 
Child-Pugh exclusion criteria, 
including laboratory exclusion 
criteria; adding data from Study 
IM025015; adjustment of step-wise 
infusion rates/number of steps;
addition of an HEDC assay; 
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BMS-986263
HSP47 siRNA
Protocol Amendment No.: 03
Date: 13-Oct-2022
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Document
Date of Issue
Approvers
Summary of Changes
addition of guidance 
 
 related to 
the COVID-19 pandemic; changing 
statistical sample size calculation, 
study stratification factors, and 
statistical analysis methodology for 
primary endpoint; excluding 
participants from the study who are 
taking anticoagulants; replacing 
liver ultrasound as screening 
procedure with liver CT/MRI for 
detection of HCC; updating 
exclusion criterion related to history 
of weight gain/loss and related to 
history of illegal IV drug use; and 
adding optionality for treatment of 
prolonged INR and/or low platelet 
counts prior to liver biopsy.
Revised Protocol 01 
Global
im025017-revprot01
27-May-2020
 
Bristol-Myers Squibb
Updates include: clarification of 
liver disease/biopsy requirements 
for study inclusion; addition of 
nintedanib as a concomitant 
medication restriction; 
 
 
 
 
addition/clarification of statistical 
methods for efficacy endpoints; 
updating of interim analysis; 
alignment with United 
States-specific Revised 
Protocol 00a, Japan-specific 
Protocol Amendment 01, and 
Global Original Protocol 
Administrative Letter 01; alignment 
with most current protocol template; 
updating of background clinical 
study data; addition of
recommended stepped infusion rates 
for study treatment; addition of
required pregnancy test prior to
DXA scan; referencing Independent 
Pathology Review Committee; and 
addition of appendix related to 
country-specific HIV exclusions.
Protocol Amendment 01 
Japan-Specific
im025017-amend01-jp-
specific
18-Mar-2020
 
Bristol-Myers Squibb
Updates to one of the components 
of the placebo formula for 
BMS-986263 and updated to align 
with Global Original Protocol 
Administrative Letter 01 and United 
States-specific Revised Protocol 
00a.
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BMS-986263
HSP47 siRNA
Protocol Amendment No.: 03
Date: 13-Oct-2022
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Document
Date of Issue
Approvers
Summary of Changes
Revised Protocol 00a 
US-Specific
im025017-revprot00a-us-
specific
21-Feb-2020
 
Bristol-Myers Squibb
 
Bristol-Myers Squibb
Updates related to the conduct of 
the 
 to 
be conducted at select sites in the 
US, including the addition of 
actions to be taken in the event of 
allergic reaction to albumin and 
criteria for stopping 
 
testing in the overall study. 
The Study Director/Medical 
Monitor contact was also changed, 
and the Study Acknowledgment/
Disclosure page was removed.
Original Protocol
19-Nov-2019
 
Bristol-Myers Squibb
 
Bristol-Myers Squibb
Not Applicable
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HSP47 siRNA
OVERALL RATIONALE FOR PROTOCOL AMENDMENT 03:
The primary purpose of this Revised Global Protocol is to add, clarify, or update study 
assessments, inclusion/exclusion criteria and endpoints, and to implement an additional interim 
analysis. Key secondary revisions include the following:

Updating the Study Director

Addition of study information for the IM025015 study, which is now complete

Clarifications pertaining to COVID-19 vaccination and interactions with BMS-986263

Addition of alternative emulsion solutions for placebo preparation

Updates to timing for administration of premedications 

Addition of definition of infusion-related reactions (IRRs) and updated the most common 
symptoms of IRRs according to the IB 16.0
All changes applied to the body were applied to the synopsis, as necessary; synopsis changes are 
not included in the list below.
Only major additions and deletions are provided in this summary; all minor grammatical, 
formatting, rephrasing, stylistic changes, or clarifications are not included.
The rationale(s) for changes to this Revised Protocol are provided in the summary of key changes 
table, as shown below:
SUMMARY OF KEY CHANGES TO THE REVISED PROTOCOL 03
Section Number & Title
Description of Change
Brief Rationale
Title Page 
Study Director was updated from 
 to 
. 
Contact info was updated 
accordingly. Address for BMS 
Belgium was removed and BMS 
Japan was updated. 
Updated with current contact 
information
Section 1.1: Synopsis
Added the potential for 4 week 
extension of screening for 
unavoidable circumstances 
Update made to align synopsis with 
study design in the body. 
Table 1: Screening Procedural 
Outline
It was previously stated that key 
eligibility criteria had to be evaluated
prior to liver biopsy at screening. 
This was changed to state that it was 
recommended. 
Updated to give the sites more 
flexibility.
Table 1: Screening Procedural 
Outline
Clarification that FSH assessment is 
only required to confirm menopause 
in women <55 years old. 
FSH requirement was listed in 
Appendix 4. Added in Table 1 to 
make it convenient for the sites 
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HSP47 siRNA
SUMMARY OF KEY CHANGES TO THE REVISED PROTOCOL 03
Section Number & Title
Description of Change
Brief Rationale
Table 1: Screening Procedural 
Outline
HbA1c was added to screening 
procedures.
HbA1c at Screening is one of the 
exclusionary laboratory assessments 
described in Section 9.4.1, Table 8. It 
has been added to Table 1 (Screening 
Procedures Outline) for consistency.
Table 2: Treatment Period 
Procedural Outline
Added that liver biopsy should be 
performed within ±3 days of the visit 
window for Wk12 and ETT visits, 
and that 4 additional days are 
allowed with Medical Monitor 
approval.
Updated for clarification.
Table 3: Follow-up Period 
Procedural Outline
 
 
Updated for clarification.
Section 3.2.2: Clinical Studies
Added study results from IM025015 
which has been completed.
Updated based on new data available.
Section 3.3.2: Coronavirus 
Disease 2019-Related and 
Section 7.7: Concomitant 
Therapy
Non-live COVID-19 vaccinations are 
allowed during the study, and should 
follow local standard practices. 
Benefit-risk section updated to 
include the sentence that the efficacy 
and safety of COVID-19 virus 
vaccines in patients using 
BMS-986263 is unknown at the 
moment.
Updated to align with BMS COVID-
19 guidance.
Section 5.1.1: Screening Period
Medical Monitor approval is no
longer required for the extension of 
screening period.
To decrease the sites burden. the 
Medical Monitor approval 
requirement was removed; allowing
the sites to extend the screening 
period up to 4 weeks if necessary,
without needing to contact the 
Medical Monitor.
Section 6.1: Inclusion Criteria
and Section 9.1.2: Liver Biopsy 
Assessments
Liver biopsy performed prior to 
screening was extended from 6 to 12 
months. Additionally NASH criteria 
could be fulfilled using biopsies of 
12 months instead of 6 months.
Updated to allow patients with 
historical biopsy 6 to 12 months prior 
to screening to enroll to the study. 
The study population patients with 
cirrhosis (Stage 4 fibrosis) have slow 
disease progression.  
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SUMMARY OF KEY CHANGES TO THE REVISED PROTOCOL 03
Section Number & Title
Description of Change
Brief Rationale
Section 6.1: Inclusion Criteria
Language clarified.
Updated to clarify who and how the 
DXA assessment will be analyzed. 
Section 6.1: Inclusion Criteria
Stable dose of treatment 
requirements was updated to 3 
months prior to screening.
Updated due to extension of 
historical biopsy to 12 months and 
requirement for stable dose to 15 
months prior to screening will be 
very difficult.
Section 6.2: Exclusion Criteria
and Section 8.1: Discontinuation 
from Study Treatment
Planned liver transplantation changed 
to planned during the study.
Updated to clarify timeframes of 
unacceptable liver transplantation. 
Section 6.2: Exclusion Criteria
Removed required discussion with 
Medical Monitor related to MELD 
and Child-Pugh Score criteria.
Updated to align with local UK 
amendment, and to provide more 
objective guidance for investigators 
to make the eligibility determination 
of participants with Gilbert syndrome 
whose MELD and Child-Pugh Scores 
are elevated due to a benign cause of 
unconjugated hyperbilirubinemia 
without requiring consultation with 
the Medical Monitor.
Section 6.2: Exclusion Criteria
Clarification added that both serum 
AFP and historical CT/MRI will be 
required for Screening. and if either 
of the results meets the criteria the 
participant will be excluded from 
study.
Updated for clarification.
Section 6.2: Exclusion Criteria
Updated history of SARS-CoV-2 
infection to history of severe 
COVID-19 disease and added 
timeframe for screening after mild 
and moderate infection.
Updated criteria to clarify specific 
timeframes for screening after 
COVID depending on the severity of 
the previous infection.
Section 6.2: Exclusion Criteria
History of significant weight 
gain/loss relative to the timing of the 
liver biopsy was removed, and any 
significant weight changes was 
updated to within 3 months of 
screening.
Removed due to extension of 
historical biopsy to 12 months and 
requirement for stable weight up to 
15 months prior to screening will be 
very difficult.
Section 6.2: Exclusion Criteria
Exclusion criteria updates so that 
vaccines approved by regulatory 
agencies other than the United States
Food and Drug Administration may 
also be considered for inclusion.
Updated to allow vaccines approved 
by other regulatory agencies.
Section 6.2: Exclusion Criteria
Exclusion criteria for laboratory 
results were updated that HbA1c 
could not be ≥ 9.5% instead of 9.0%.
Revised to expand the study 
population.
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SUMMARY OF KEY CHANGES TO THE REVISED PROTOCOL 03
Section Number & Title
Description of Change
Brief Rationale
Section 6.6.1: Retesting During 
Screening Period
Language clarified.
Updated to clarify timing of 
 
 DXA scan assessments.
Section 7: Treatment
Section 7.1.2: Premedication
Timing for administration of 
premedication before study start was 
clarified.
Added instruction for the sites.
Section 9.2.9: Infusion-related 
Reactions
Definition of IRRs was added. 
Details of IRRs seen with 
BMS-986263 administration in other 
studies were added. Clinical 
symptoms of IRRs aligned with the 
last IB (v16.0).
Added IRRs definition for the sites to 
assess the IRRs.
Section 9.5: PK 
 
 
Schedule for BMS-986263

The 
 PK sampling 
on 
 was removed, and the 
+1 day window for the Day 85 
sampling was removed.

Timing and timing windows 
relative to start or end of infusion 
were updated in footnote C, E, 
and F.

 was removed from 
footnote G.
Updated for the clarification to PK 
sampling timepoints and to increase 
window for some timepoints.
Section 10.4.5: Interim Analysis
Additional interim analysis added for
when 30% participants have either 
completed the Follow-up Week 4 or 
discontinued prior to the Follow-up 
Week 4.
Added the additional interim analysis 
to assess futility.
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SUMMARY OF KEY CHANGES TO THE REVISED PROTOCOL 03
Section Number & Title
Description of Change
Brief Rationale
Section 11: References
IB version number updated. List of 
reference updated.
Updated based on new IB. Updated
to include new references. 
Appendix 3: Adverse events and 
serious adverse events: 
definitions and procedures for 
recording, evaluating, follow-up, 
and reporting
Text modified or added using current 
template text.
Updated to align with current 
template language.
Appendix 7: Criteria for 
diagnosis and exclusion of 
Participants with hepatitis b 
virus and chronic Hepatitis c 
virus infection
Exclusion instructions added based 
on hepatitis B assessments.
Updated to include the HBV DNA 
test for HBV natural infection
Appendix 8: Country-specific 
requirements
Countries listed in country-specific 
requirements updated.
Updated to align with current country 
regulation 
 
.  
AFP = serum 
alpha-fetoprotein; 
BMS = Bristol-Myers 
Squibb; 
COVID-19 = coronavirus 
disease 
2019; 
CT = computed tomography; DNA = deoxyribonucleic acid; DXA = dual-energy X-ray absorptiometry; ETT = Early 
Treatment Termination; FSH = follicle-stimulating hormone; HbA1c = hemoglobin A1c; HBV = hepatitis B virus; 
IB = investigator’s brochure; IRR = infusion-related reaction; MELD = Model for End-stage Liver Disease; 
NASH = nonalcoholic steatohepatitis; 
PK = pharmacokinetic; 
 SARS-CoV-2 = severe acute respiratory 
syndrome coronavirus 2
Please provide a copy to your Investigational Review Board/Ethics Committee, unless 
agreed otherwise with BMS.
Protocol Amendment No.: 03
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TABLE OF CONTENTS 
 
 
TITLE PAGE ................................................................................................................ 
 
DOCUMENT HISTORY .............................................................................................. 
 
OVERALL RATIONALE FOR PROTOCOL AMENDMENT 03: ............................ 
 
SUMMARY OF KEY CHANGES TO THE REVISED PROTOCOL 03 ................... 
 
TABLE OF CONTENTS .............................................................................................. 
 
1 PROTOCOL SUMMARY ......................................................................................... 
 
1.1 Synopsis ............................................................................................................ 
 
1.2 Schema .............................................................................................................. 
 
2 SCHEDULE OF ACTIVITIES.................................................................................. 
 
3 INTRODUCTION ..................................................................................................... 
 
3.1 Study Rationale ................................................................................................. 
 
3.2 Background ....................................................................................................... 
 
3.2.1 Nonclinical Studies .................................................................................. 
 
3.2.2 Clinical Studies ........................................................................................ 
 
3.3 Benefit/Risk Assessment .................................................................................. 
 
3.3.1 Overall Benefit/Risk Assessment .............................................................. 
 
3.3.2 Coronavirus Disease 2019-Related ......................................................... 
 
4 OBJECTIVES AND ENDPOINTS ........................................................................... 
 
5 STUDY DESIGN....................................................................................................... 
 
5.1 Overall Design .................................................................................................. 
 
5.1.1 Screening Period ...................................................................................... 
 
5.1.2 Treatment Period and Follow-up............................................................. 
 
5.1.3 DMC and Other External Committees ..................................................... 
 
5.2 Number of Participants ..................................................................................... 
 
5.3 End of Study Definition .................................................................................... 
 
5.4 Scientific Rationale for Study Design............................................................... 
 
5.5 Justification for Dose ........................................................................................ 
 
6 STUDY POPULATION ............................................................................................ 
 
6.1 Inclusion Criteria .............................................................................................. 
 
6.2 Exclusion Criteria ............................................................................................. 
 
 
 
 
 
 
 
 
 
 
 
 
 
6.4 Lifestyle Restrictions ........................................................................................ 
 
6.5 Dietary and Lifestyle Counseling ..................................................................... 
 
6.6 Screen Failures .................................................................................................. 
 
6.6.1 Retesting During Screening Period ......................................................... 
 
7 TREATMENT ........................................................................................................... 
 
7.1 Treatments Administered .................................................................................. 
 
7.1.1 Study Treatment Infusion Rate ................................................................. 
 
7.1.2 Premedication .......................................................................................... 
 
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7.2 Method of Treatment Assignment .................................................................... 
 
7.3 Blinding............................................................................................................. 
 
7.3.1 Maintaining the Blind .............................................................................. 
 
7.3.2 Circumstances for Unblinding ................................................................. 
 
7.4 Dosage Modification ......................................................................................... 
 
7.5 Preparation/Handling/Storage/Accountability .................................................. 
 
7.5.1 Retained Samples for Bioavailability/Bioequivalence/Biocomparability 
 
7.6 Treatment Compliance ...................................................................................... 
 
7.7 Concomitant Therapy........................................................................................ 
 
7.7.1 Prohibited and/or Restricted Treatments................................................. 
 
 
 
 
7.8 Treatment After the End of the Study ............................................................... 
 
8 DISCONTINUATION CRITERIA ........................................................................... 
 
8.1 Discontinuation from Study Treatment ............................................................ 
 
8.1.1 Poststudy Treatment Study Follow-up ..................................................... 
 
8.2 Discontinuation from the Study ........................................................................ 
 
 
 
8.3 Lost to Follow-up .............................................................................................. 
 
9 STUDY ASSESSMENTS AND PROCEDURES ..................................................... 
 
9.1 Efficacy Assessments ........................................................................................ 
 
 
 
9.1.2 Liver Biopsy Assessments ........................................................................ 
 
9.1.2.1 Histological Scoring ....................................................................... 
 
9.1.2.2 Morphometric Analysis of CPA 
 in Stained 
Tissue .................................................................................................... 
 
 
 
 
 
 
 
 
 
 
 
 
 
9.2 Adverse Events ................................................................................................. 
 
9.2.1 Time Period and Frequency for Collecting AE and SAE Information .... 
 
9.2.2 Method of Detecting AEs and SAEs ......................................................... 
 
9.2.3 Follow-up of AEs and SAEs ..................................................................... 
 
9.2.4 Regulatory Reporting Requirements for SAEs ......................................... 
 
9.2.5 Pregnancy ................................................................................................ 
 
9.2.6 Laboratory Test Result Abnormalities ..................................................... 
 
9.2.7 Potential DILI .......................................................................................... 
 
9.2.8 Adverse Events of Special Interest ........................................................... 
 
9.2.9 Infusion-related Reactions ....................................................................... 
 
9.2.10 Other Safety Considerations .................................................................. 
 
9.3 Overdose ........................................................................................................... 
 
9.4 Safety ................................................................................................................ 
 
9.4.1 Clinical Safety Laboratory Assessments .................................................. 
 
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9.4.2 Vital Signs ................................................................................................ 
 
9.4.3 Physical Examinations ............................................................................. 
 
9.4.4 Electrocardiograms ................................................................................. 
 
9.4.5 Imaging Safety Assessment – DXA Scan .................................................. 
 
 
 
9.5 PK 
 Sampling Schedule for BMS-986263 ....................... 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
10 STATISTICAL CONSIDERATIONS .................................................................... 
 
10.1 Sample Size Determination ............................................................................. 
 
10.2 Populations for Analyses ................................................................................ 
 
10.3 Endpoints ........................................................................................................ 
 
10.3.1 Primary Endpoint................................................................................... 
 
10.3.2 Secondary Endpoints ............................................................................. 
 
 
 
10.4 Statistical Analyses ......................................................................................... 
 
10.4.1 Efficacy Analyses ................................................................................... 
 
10.4.2 Safety Analyses....................................................................................... 
 
 
 
10.4.3.1 PK 
 ................................................................ 
 
 
 
10.4.4 Week 12 Analyses ................................................................................... 
 
10.4.5 Interim Analysis ..................................................................................... 
 
11 REFERENCES ........................................................................................................ 
 
12 APPENDICES ......................................................................................................... 
 
APPENDIX 1 ABBREVIATIONS AND TRADEMARKS ........................................ 
 
APPENDIX 2 STUDY GOVERNANCE CONSIDERATIONS ................................. 
 
APPENDIX 3 ADVERSE EVENTS AND SERIOUS ADVERSE EVENTS: 
DEFINITIONS AND PROCEDURES FOR RECORDING, EVALUATING, 
FOLLOW-UP, AND REPORTING ....................................................................... 
 
APPENDIX 4 WOMEN OF CHILDBEARING POTENTIAL DEFINITIONS AND 
METHODS OF CONTRACEPTION ..................................................................... 
 
APPENDIX 5 CHILD-PUGH SCORING .................................................................... 
 
APPENDIX 6 FORMULAS FOR MEASUREMENTS .............................................. 
 
APPENDIX 7 CRITERIA FOR DIAGNOSIS AND EXCLUSION OF 
PARTICIPANTS WITH HEPATITIS B VIRUS AND CHRONIC HEPATITIS C 
VIRUS INFECTION .............................................................................................. 
 
APPENDIX 8 COUNTRY-SPECIFIC REQUIREMENTS ......................................... 
 
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APPENDIX 9 PROTOCOL AMENDMENT SUMMARY OF CHANGE HISTORY
................................................................................................................................. 
 
 
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1
PROTOCOL SUMMARY
1.1
Synopsis
Protocol Title: A Randomized, Double-blind, Placebo-controlled, Parallel-group, Multiple-dose 
Phase 2 Study to Evaluate the Efficacy and Safety of BMS-986263 in Adults with Compensated 
Cirrhosis from Nonalcoholic Steatohepatitis (NASH)
Short Title: Efficacy and Safety of BMS-986263 in Adults with Compensated Cirrhosis from 
NASH
Study Phase: 2
Rationale: Study IM025017 aims to demonstrate the antifibrotic efficacy of BMS-986263, using 
a liver fibrosis histological endpoint, and the safety and tolerability of BMS-986263, as assessed 
by adverse events (AEs), serious adverse events (SAEs), laboratory results (including assessment 
of potential drug-induced liver injury), vital signs, physical examinations, electrocardiograms 
(ECGs),
 infusion-related reaction monitoring, and bone mineral 
density (BMD) monitoring, in participants with nonalcoholic steatohepatitis (NASH) and 
compensated cirrhosis.
Nonalcoholic fatty liver disease (NAFLD) is one of the most common causes of chronic liver 
disease in the world today. NASH, which is the more advanced form of NAFLD, is defined as the 
presence of hepatic steatosis and inflammation with hepatocyte injury (ballooning), with or 
without fibrosis. NASH is associated with increased mortality rates due to cardiovascular-, liver-, 
and cancer-related deaths. Currently, there are no approved drugs for the treatment of NASH. With 
the increasing prevalence of obesity and obesity-related diseases, NASH could soon become the 
leading indication for liver transplantation and the leading cause of hepatocellular carcinoma 
(HCC) globally.
NASH patients with cirrhosis have a particularly high unmet medical need for effective therapies. 
Among NASH patients, the stage of fibrosis is the strongest predictor of disease-specific mortality, 
and patients with cirrhosis are at the greatest risk for disease-related morbidity and mortality.
Patients with cirrhosis are particularly at increased risk for poor clinical outcomes, including 
hepatic decompensation events and the need for liver transplant. It is reasonable to assume that an 
improvement in fibrosis would be predictive of clinical benefit, and a reduction of fibrosis in
patients with compensated cirrhosis, if substantial, could lead to improvements in liver function 
and long-term clinical outcomes.
Study Population: Study IM025017 will be conducted in adults who have compensated cirrhosis 
due to NASH. Participants must fully meet all eligibility criteria defined in Section 6 of the 
protocol; key inclusion and exclusion criteria are summarized as follows:
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BMS-986263
HSP47 siRNA
Key inclusion criteria

Male and female participants, ages ≥21 years to ≤75 years of age, inclusive, at the time of 
screening

Liver biopsy performed within 12 months prior to the screening visit or performed during the
screening period. A liver biopsy performed prior to informed consent form, if utilized for 
eligibility, must be available for central pathology reading prior to Randomization.
i)
Liver biopsy consistent with NASH Clinical Research Network (CRN) Fibrosis Score 
Stage 4, as assessed by central pathology reading.
ii) Liver biopsy must either be consistent with steatohepatitis, as assessed by central 
pathology reading, OR, for liver biopsies without definite steatohepatitis, there should 
be some evidence of steatosis and/or ballooning and the following definition of NASH 
cirrhosis must be fulfilled:
1) Absence of other causes of liver disease AND either of the following:
a) At least 2 of the 3 following criteria:
(i) History of body mass index [BMI] ≥30 kg/m2
(ii) History of type 2 diabetes mellitus
(iii)History of hypertension AND/OR history of dyslipidemia
OR
b) Previous histologic readings of steatohepatitis (in a past biopsy prior to the one
utilized for eligibility) AND either history of BMI ≥30 kg/m2 OR history of 
type 2 diabetes mellitus.
NOTE: At least 80% of participants will be required to have definite steatohepatitis on 
the biopsy used to confirm eligibility.
Key exclusion criteria

Other active causes of liver disease (eg, alcoholic liver disease, hepatitis B virus infection, 
chronic hepatitis C virus infection, autoimmune hepatitis, primary biliary cholangitis, primary 
sclerosing cholangitis, drug-induced hepatotoxicity, Wilson disease, homozygous -1-
antitrypsin deficiency, iron overload [with blood iron saturation > 50%], or hemochromatosis)

Past or current evidence of hepatic decompensation (eg, ascites, variceal bleeding, hepatic 
encephalopathy, or spontaneous bacterial peritonitis)

Liver transplantation (past or planned during the study)

Child-Pugh Score > 6 at screening (APPENDIX 5). Exception: Participants with Gilbert 
Syndrome who have a Child-Pugh Score > 6 with elevated total bilirubin and direct bilirubin 
≤ the upper limit of normal (ULN) may be included, provided that total bilirubin is < 4.0 mg/dL

Model for End-stage Liver Disease (MELD) score > 14 at screening (APPENDIX 6). 
Exception:  Participants with Gilbert Syndrome who have a MELD Score > 14 with elevated
total bilirubin, and direct bilirubin ≤ the ULN may be included, provided that total bilirubin 
is < 4.0 mg/dL
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Study IM025017
BMS-986263
HSP47 siRNA

Evidence of HCC at screening based on (i) serum alpha-fetoprotein (AFP) > 20 ng/mL 
(> 16.5 IU/mL) or (ii) Liver Reporting & Data System 3, 4, or 5 as determined by historical 
computed tomography (CT)/magnetic resonance imaging (MRI) with contrast within 3 months 
prior to screening or from multiphasic CT/MRI of liver during screening. Both AFP and 
CT/MRI assessments will be required from all participants to determine eligibility. 

The participant’s laboratory test results at screening include any of the following:

Albumin < 2.8 g/dL

INR > 2.2

Alanine aminotransferase value ≥5× the ULN

Aspartate aminotransferase value ≥5× the ULN

Total bilirubin > 3.0 mg/dL, unless participant has a documented diagnosis of Gilbert 
Syndrome, provided that total bilirubin is < 4.0 mg/dL and direct bilirubin is ≤ULN

Platelet count < 85,000/µL

Hemoglobin A1c ≥9.5%

Serum vitamin A (retinol) > ULN

Inability to safely undergo a liver biopsy in the opinion of the investigator.
 
 
 
 
Objectives and Endpoints:
The following table summarizes the primary and secondary objectives and endpoints:
Objective
Endpoint
Primary

To evaluate the efficacy of BMS-986263 
compared with placebo to improve liver 
fibrosis in participants with compensated 
cirrhosis due to NASH

Proportion of participants who achieve 
≥1 stage improvement in liver fibrosis (NASH 
CRN Fibrosis Score), as determined by liver 
biopsy after 12 weeks of treatment
Secondary

To further assess the efficacy of BMS-986263 
compared with placebo to improve liver 
fibrosis, as determined by liver biopsy, in 
participants with compensated cirrhosis due to 
NASH

Proportion of participants with ≥1 stage 
improvement in liver fibrosis (NASH CRN 
Fibrosis Score), with no worsening of NASH 
after 12 weeks of treatment (worsening defined 
as an increase of the NAS by ≥1 point)
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BMS-986263
HSP47 siRNA
Objective
Endpoint

Proportion of participants with ≥2 stage 
improvement in liver fibrosis (NASH CRN 
Fibrosis Score) after 12 weeks of treatment

Proportion of participants with ≥1 stage 
improvement in liver fibrosis (modified Ishak 
score) after 12 weeks of treatment

Proportion of participants with ≥2 stage 
improvement in liver fibrosis (modified Ishak 
score) after 12 weeks of treatment

Change from baseline in CPA after 12 weeks 
of treatment

To assess the safety and tolerability of 
BMS-986263 in participants with compensated 
cirrhosis due to NASH

Incidences of SAEs, AEs, clinical laboratory 
values, vital signs, physical examination 
findings, and ECGs

Change from baseline in BMD, as measured by 
DXA scan, at Follow-up Week 24

To assess the PK of BMS-986263 in 
participants with compensated cirrhosis due to 
NASH

Plasma concentrations of siRNA, DPD, 
HEDC, 
and 
S104 
(components 
of 
BMS-986263 for injection)
AE = adverse event; BMD = bone mineral density; CPA = collagen proportionate area; CRN = Clinical Research 
Network; 
DPD = di-retinamide-PEG-di-retinamide; 
DXA 
= 
dual-energy 
X-ray 
absorptiometry; 
ECG = electrocardiogram; 
HEDC = (Bis[2-(tetradecanoyloxy)ethyl] 
carbamoylmethyl)-(2-
hydroxyethyl)dimethylazanium bromide; NAFLD = nonalcoholic fatty liver disease; NAS = NAFLD Activity Score; 
NASH = nonalcoholic steatohepatitis; PK = pharmacokinetics; SAE = serious adverse event; SiRNA = small 
interfering ribonucleic acid
Overall Design: This is a randomized, double-blind, placebo-controlled, parallel-group, 
multiple-dose Phase 2 study to evaluate the efficacy, safety, and tolerability of BMS-986263 in 
adults with compensated cirrhosis due to NASH. The primary study endpoint is the proportion of 
participants who achieve ≥1 stage improvement in liver fibrosis (NASH CRN Fibrosis Score) on 
biopsy after 12 weeks of treatment.
The study includes:

A screening period of up to 8 weeks; may be extended (up to an additional 4 weeks) to 
accommodate unanticipated delays in obtaining required screening results.

A 12-week, double-blind treatment period, during which participants will receive 1 of the 
following 3 treatments by intravenous (IV) infusion: 45 mg BMS-986263 once every week 
(QW), 90 mg BMS-986263 QW, or placebo QW

A follow-up period of 24 weeks, during which participants will not receive investigational 
treatment
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Study IM025017
BMS-986263
HSP47 siRNA
Participants meeting eligibility criteria during the screening period will enter the treatment period 
and be randomized to receive 45 mg BMS-986263 QW, 90 mg BMS-986263 QW, or placebo QW 
by IV infusion in a double-blind manner for 12 weeks. Participants will be stratified at 
Randomization by the presence of definite steatohepatitis on biopsy (yes versus no). At least 80% 
of participants will be required to have definite steatohepatitis on the biopsy used to confirm 
eligibility. Participants will receive study treatment via IV administration for a total of 12 weeks. 
Liver biopsy will be performed at Week 12.
This study will utilize an external Data Monitoring Committee for the duration of the study to 
assess safety data, and an external Independent Pathology Review Committee to assess liver 
biopsies for eligibility and efficacy.
Number of Participants: In this study, approximately 270 participants will be randomized via 
interactive response technology (IRT) in a 1:1:1 ratio to receive 45 mg BMS-986263 QW, 90 mg 
BMS-986263 QW, or placebo QW in a double-blind manner. The primary endpoint is the 
proportion of participants with ≥1 stage improvement in liver fibrosis (NASH CRN Fibrosis 
Score) as determined by liver biopsy after 12 weeks of treatment.
Assuming a Chi-Square test with an α = 0.05 and expected response rates for BMS-986263 90 mg, 
BMS-986263 45 mg, and placebo of 45%, 40%, and 20%, respectively, this study will have at 
least 80% power to detect superiority over placebo versus each dose, assuming a minimum 
difference of 20% from placebo. Accounting for a 6% dropout rate, approximately 90 participants 
will be randomized per treatment group.
Treatment Arms and Duration: Participants meeting eligibility criteria during the screening 
period will enter the treatment period. Approximately 270 participants will be randomized via IRT 
in a 1:1:1 ratio to receive 45 mg BMS-986263 QW, 90 mg BMS-986263 QW, or placebo QW by 
IV infusion in a double-blind manner for 12 weeks.
After 12 weeks of treatment or after early treatment discontinuation, participants will enter the 
24-week follow-up period. After all participants complete the Follow-up Week 4 visit, the study 
will be unblinded and analyses of the available Week 12 data will be conducted.
Study Treatment:
Study Drug for IM025017
Medication 
Potency 
IP/Non-IP 
BMS-986263 for injection
10 mg per vial; 3 mg/mL after reconstitution
IP
Placeboa for BMS-986263 for 
injection/on-site compounded 
sterile dosage form
NA
IP
IP = investigational product; IV = intravenous; NA = not applicable
a 
 
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Study IM025017
BMS-986263
HSP47 siRNA
Statistical Methods: Efficacy analyses will be performed using the modified intent-to-treat 
population. Participants who discontinue early and do not have an Early Treatment Termination 
liver biopsy or otherwise have the result from the liver biopsy missing will be considered a 
“nonresponder” for the evaluation of the primary endpoint and other binary endpoints based on 
liver biopsy.
Primary Endpoint Analysis: To evaluate the effect of BMS-986263 (90 mg QW and 45 mg QW) 
on NASH CRN Fibrosis Stage at Week 12, a 95.0% confidence interval of response rate for active 
treatment versus placebo will be used to estimate the difference between the proportions of 
participants with ≥1 stage improvement in fibrosis on liver biopsy. Additionally, the odds ratio 
will be used to estimate improvement of treatment as compared with placebo for the proportion of 
participants with > 1 stage improvement in fibrosis on biopsy at Week 12. A logistic regression 
will be performed with platelet count as independent covariate and stratified by the Randomization 
strata with a Z-test statistic at a two-sided significance level of α◦=◦0.05 to assess the difference of 
response rate separately between each BMS-986263 treatment group and placebo. To control for 
the family-wise (two-sided) Type◦1◦error rate of α◦=◦0.05, the statistical tests will be performed 
in the following hierarchical order: 1) BMS-986263 90◦mg versus placebo, and 2) BMS-986263 
45◦mg versus placebo. If the first comparison is not statistically significant, then the second 
comparison will be treated as descriptive in nature.
Secondary 
 Endpoint Analyses: No adjustment will be made for multiplicity for 
secondary 
 endpoints. Secondary 
 endpoints will be analyzed in a 
similar method as the primary endpoint unless otherwise specified in the statistical analysis plan 
(SAP).
Selected continuous endpoints will be characterized using descriptive statistics and may be 
analyzed by analysis of covariance methods and/or by a mixed model for repeated measurements. 
Treatment differences at prespecified time points will be estimated using least squares means. Full 
details regarding this model and covariance structure will be provided in the SAP.
Categorical endpoints will be summarized using counts and percentages and when appropriate,
may be analyzed using categorical analysis methods.
The stratified log-rank test and Kaplan-Meier estimate may be used to analyze time-to-event 
endpoints and will be specified in the SAP.
Subgroup analyses may be performed as specified in the SAP.
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Study IM025017
BMS-986263
HSP47 siRNA
1.2
Schema
D = Day; W = Week
The total duration of the study will be up to 48 weeks, including a screening period (up to 
12 weeks), a 12-week treatment period, and a 24-week follow-up period. Participants will be 
randomized to receive 1 of the following 3 treatments by IV infusion during the treatment period: 
45 mg BMS-986263 QW, 90 mg BMS-986263 QW, or placebo QW for 12 weeks. No reductions 
or modifications of the assigned dose are allowed. If the infusion is interrupted for any reason, the 
infusion may be restarted at the discretion of the investigator. If an incomplete dose is administered 
at any visit, the participant will resume the assigned dose/administration schedule at the next visit. 
Rules for discontinuation from study treatment and from the study are provided in Section 8.1 and 
Section 8.2, respectively. The study will utilize an external Data Monitoring Committee for the 
duration of the study.
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Study IM025017
BMS-986263
HSP47 siRNA
2
SCHEDULE OF ACTIVITIES
Visit details are provided for the Screening Procedural Outline in Table 1. Visit details are provided 
for the treatment and follow-up periods in Table 2 and Table 3, respectively.
Pharmacokinetic (PK) samples must be collected on time per the collection table 
 All 
study procedures 
 for 
 assessments must be performed prior to 
infusion on the infusion days (with the exception of PK samples taken during and after the 
infusion). All electronic patient-reported outcome evaluations must be completed before any other 
study procedures are started.
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BMS-986263
HSP47 siRNA
Table 1:
Screening Procedural Outline
Procedure
Screeninga
Day -56 to -1
Notes
Screening and History Assessments
Informed consent
X
Inclusion/exclusion criteria
X
Assess study eligibility criteria prior to 
Randomization.
Medical history
X
Prior medications
X
Prior medications are medications taken within 
4 weeks prior to screening.
Lifestyle restrictions
X
See Section 6.4.
Dietary and lifestyle counseling
X
See Section 6.5 for additional information.
Screening via IRT to register 
participant
X
See Section 7.2 for additional information.
Clinical Safety Assessments 
Full physical examination
X
If the screening physical examination is performed 
within 24 hours prior to dosing on Day 1 
(Randomization), then a single exam may count as 
both the screening and Day 1 (Randomization) 
abbreviated physical examination. Screening 
examination will be a full physical examination,
including general appearance, skin, head, eyes, ears, 
nose, throat, neck, thyroid, chest/lungs, heart, 
abdomen, lymph nodes, and extremities. (See 
Section 9.4.3).
Physical measurements
X
Includes body weight, height, and BMI (height and 
BMI calculation at screening only).
Vital signs
X
Includes body temperature, respiratory rate, blood 
pressure, and heart rate. Blood pressure and heart rate 
should be measured after the participant has been 
resting quietly for at least 5 minutes.
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Study IM025017
BMS-986263
HSP47 siRNA
Table 1:
Screening Procedural Outline
Procedure
Screeninga
Day -56 to -1
Notes
Multiphasic liver CT/MRI
X
A historical liver CT/MRI conducted within 3 months 
prior to screening may replace the screening 
CT/MRI, provided that the images and report are 
available. An MRI scan is preferred to a CT scan, and 
it is preferred that the MRI be conducted at the time 
of the screening 
, if an 
 is conducted. See 
Section 6.2 for liver-related exclusion criteria.
12-lead ECG
X
ECG should be performed after the participant has 
been supine for at least 5 minutes.
DXA scan
X
Adequacy of DXA scan must be determined by the 
imaging vendor prior to Randomization. See 
Section 9.4.5.
Urine pregnancy test should be 
performed in WOCBP prior to DXA scan.
Serious adverse events
X
All SAEs must be collected from the date of 
participant’s written consent until 30 days post
discontinuation of dosing or participant’s 
participation in the study if the last scheduled visit 
occurs at a later time (last visit for participation). 
See Section 9.2.
Clinical Efficacy Assessments
Liver biopsy
X
See Section 9.1.2. It is recommended that key 
eligibility criteria should be evaluated prior to 
biopsy. Refer to Section 6.1 for eligibility criteria.
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Study IM025017
BMS-986263
HSP47 siRNA
Table 1:
Screening Procedural Outline
Procedure
Screeninga
Day -56 to -1
Notes
Laboratory Assessments
Pregnancy test
X
For WOCBP only. Serum or urine pregnancy test 
must be completed to confirm participant is not 
pregnant at screening. See Section 9.2.5. Urine
pregnancy test should be performed in WOCBP 
prior to DXA scan.
FSH
X
In women < 55 years to confirm menopause. See
Section 9.4.1 and APPENDIX 4.
Hematology
X
See Section 9.4.1 and Table 8.
Chemistry
X
See Section 9.4.1 and Table 8.
Serum vitamin A (retinol)
X
Collected after fasting ≥10 hours. Note: Once 
collected, the sample must be protected from light.
Urinalysis
X
See Section 9.4.1 and Table 8.
Serology/viral load
X
Refer to APPENDIX 7.
HIV test (only where mandated 
locally)
X
Refer to APPENDIX 8.
Serum AFP
X
See Section 6.2 and Section 9.4.1.
HbA1c
X
See Section 9.4.1 and Table 8.
AFP = alpha-fetoprotein; BMI = body mass index; CT = computed tomography; DXA = dual-energy X-ray absorptiometry; ECG = electrocardiogram; 
FSH = follicle-stimulating hormone; HbA1c = hemoglobin A1c; HIV = human immunodeficiency virus; IRT = interactive response technology; 
 
MRI = magnetic resonance imaging; SAE = serious adverse event; WOCBP = women of 
childbearing potential
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Clinical Protocol
Study IM025017
BMS-986263
HSP47 siRNA
a The screening period may be extended up to an additional 4 weeks to accommodate unanticipated delays in obtaining required screening results.
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Study IM025017
BMS-986263
HSP47 siRNA
Table 2:
Treatment Period Procedural Outline
Procedure/
Visit Day
(± 3 days for all visits 
unless otherwise noted)
D
1
D
4
D
8
D 
15
D 
22
D 
29
D 
36
D 
43
D 
46a
D 
50
D 
57
D 
64
D 
71
D 
78
D 
85
ETT
Notes
R
W
1
W
2
W
3
W
4
W 
5
W 
6
W 
7
W 
8
W 
9
W 
10
W 
11
W 
12
Inclusion/Exclusion and History Assessments
Inclusion/exclusion 
criteria
X
Recheck prior to Day 1 dosing.
Medical history
X
Prior medications
X
Prior medications are 
medications taken within 4 
weeks prior to screening. Check 
prior to Day 1 dosing.
Lifestyle restrictions
X
X
X
X
X
X
X
X
X
X
X
X
X
See Section 6.4.
Clinical Safety Assessments
Concomitant medication 
use
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Concomitant medications are 
medications taken any time after 
the first dose of study medication 
until the last study visit.
Full physical 
examination
X
X
A full examination will include 
general appearance, skin, head, 
eyes, ears, nose, throat, neck, 
thyroid, chest/lungs, heart, 
abdomen, lymph nodes, and 
extremities (See Section 9.4.3).
Abbreviated physical 
assessment
X
X
X
X
Abbreviated examinations will 
include an abdominal exam, 
assessments of ascites and 
hepatic encephalopathy, and 
symptom-focused assessments
(See Section 9.4.3).
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Clinical Protocol
Study IM025017
BMS-986263
HSP47 siRNA
Table 2:
Treatment Period Procedural Outline
Procedure/
Visit Day
(± 3 days for all visits 
unless otherwise noted)
D
1
D
4
D
8
D 
15
D 
22
D 
29
D 
36
D 
43
D 
46a
D 
50
D 
57
D 
64
D 
71
D 
78
D 
85
ETT
Notes
R
W
1
W
2
W
3
W
4
W 
5
W 
6
W 
7
W 
8
W 
9
W 
10
W 
11
W 
12
Physical measurements
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Includes body weight only.
Vital signs
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Includes body temperature, 
respiratory rate, blood pressure, 
and heart rate. Blood pressure 
and heart rate should be 
measured after the participant has 
been resting quietly for at least 
5 minutes. 
12-lead ECG
X
X
ECG should be performed after 
the participant has been supine 
for at least 5 minutes.
Adverse events
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Nonserious AEs must be 
collected from the time of the 
first dose of the study treatment 
through the date of the follow-up 
or last visit. Monitoring for AEs 
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Clinical Protocol
Study IM025017
BMS-986263
HSP47 siRNA
Table 2:
Treatment Period Procedural Outline
Procedure/
Visit Day
(± 3 days for all visits 
unless otherwise noted)
D
1
D
4
D
8
D 
15
D 
22
D 
29
D 
36
D 
43
D 
46a
D 
50
D 
57
D 
64
D 
71
D 
78
D 
85
ETT
Notes
R
W
1
W
2
W
3
W
4
W 
5
W 
6
W 
7
W 
8
W 
9
W 
10
W 
11
W 
12
will occur at every study visit.
(See Section 9.2).
Serious adverse events
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
All SAEs must be collected from 
the date of participant’s written 
consent until 30 days post
discontinuation of dosing or 
participant’s participation in the 
study if the last scheduled visit 
occurs at a later time (last visit 
for participation). See 
Section 9.2.
Clinical Efficacy Assessments
Liver biopsy
X
X
Liver biopsy should be 
performed within ± 3 days of 
visit window. Four additional 
days are allowed under 
extenuating circumstances with 
Medical Monitor approval. In 
case of early termination of 
treatment, to be obtained at ETT
visit only if the participant has 
completed at least the Week 6 
visit. See Section 9.1.2.
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Clinical Protocol
Study IM025017
BMS-986263
HSP47 siRNA
Table 2:
Treatment Period Procedural Outline
Procedure/
Visit Day
(± 3 days for all visits 
unless otherwise noted)
D
1
D
4
D
8
D 
15
D 
22
D 
29
D 
36
D 
43
D 
46a
D 
50
D 
57
D 
64
D 
71
D 
78
D 
85
ETT
Notes
R
W
1
W
2
W
3
W
4
W 
5
W 
6
W 
7
W 
8
W 
9
W 
10
W 
11
W 
12
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Clinical Protocol
Study IM025017
BMS-986263
HSP47 siRNA
Table 2:
Treatment Period Procedural Outline
Procedure/
Visit Day
(± 3 days for all visits 
unless otherwise noted)
D
1
D
4
D
8
D 
15
D 
22
D 
29
D 
36
D 
43
D 
46a
D 
50
D 
57
D 
64
D 
71
D 
78
D 
85
ETT
Notes
R
W
1
W
2
W
3
W
4
W 
5
W 
6
W 
7
W 
8
W 
9
W 
10
W 
11
W 
12
Laboratory Assessments
Pregnancy testc
X
X
X
X
X
X
X
X
X
X
X
X
X
X
For WOCBP only. Serum or 
urine pregnancy test must be 
completed within 24 hours prior 
to each infusion to confirm the 
participant is not pregnant. See 
Section 9.2.5.
Hematology 
X
X
X
X
X
X
X
X
Preinfusion when on a dosing 
day. See Section 9.4.1 and Table 
8.
Chemistry
X
X
X
X
X
X
X
X
Preinfusion when on a dosing 
day. See Section 9.4.1 and Table 
8.
Serum vitamin A 
(retinol)
X
X
X
Collected after fasting 
≥10 hours. Note: Once collected, 
the sample must be protected 
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Table 2:
Treatment Period Procedural Outline
Procedure/
Visit Day
(± 3 days for all visits 
unless otherwise noted)
D
1
D
4
D
8
D 
15
D 
22
D 
29
D 
36
D 
43
D 
46a
D 
50
D 
57
D 
64
D 
71
D 
78
D 
85
ETT
Notes
R
W
1
W
2
W
3
W
4
W 
5
W 
6
W 
7
W 
8
W 
9
W 
10
W 
11
W 
12
from light. See 
Section 9.4.3.
Metabolic panel 
X
X
X
Collected after fasting 
≥10 hours. See Section 9.4.1 and 
Table 8.
HbA1c
X
X
X
See Section 9.4.1 and Table 8.
Insulin
X
X
X
Collected after fasting ≥10 hours 
and prior to infusion when on a 
dosing day. See Section 9.4.1 and 
Table 8.
Urinalysis
X
X
X
X
X
X
X
X
See Section 9.4.1 and Table 8.
Serum AFP
X
X
X
X
See Section 6.2 and 
Section 9.4.1.
PK
 Sampling
Blood PK sampling
See Notes
Refer to
for sampling 
schedule
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Table 2:
Treatment Period Procedural Outline
Procedure/
Visit Day
(± 3 days for all visits 
unless otherwise noted)
D
1
D
4
D
8
D 
15
D 
22
D 
29
D 
36
D 
43
D 
46a
D 
50
D 
57
D 
64
D 
71
D 
78
D 
85
ETT
Notes
R
W
1
W
2
W
3
W
4
W 
5
W 
6
W 
7
W 
8
W 
9
W 
10
W 
11
W 
12
Randomization and Study Drug/Placebo Administration 
Randomization via IRT
X
Study eligibility should be 
confirmed before contacting IRT 
to randomize. Eligible 
participants will be centrally 
randomized using IRT. 
Randomization to a treatment 
group will be assigned prior to 
dosing (Section 7.2).
Study Drug or Placebo
X
X
X
X
X
X
X
X
X
X
X
X
See Section 7.1 and Section 7.5. 
AE = adverse 
event; 
AFP = alpha-fetoprotein; 
 
 
 
 
 
D = Day; 
ECG = electrocardiogram; 
 ETT = Early Treatment Termination; HbA1c = hemoglobin A1c; 
IRT = interactive response technology; 
 
 
PK = pharmacokinetics; 
 
R = Randomization; SAE = serious adverse event; 
 W = Week; WOCBP = women of 
childbearing potential
a Day 46 is an optional visit.
 
c Serum or urine pregnancy test should be performed in WOCBP prior to 
 to confirm that participant is not pregnant.
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Table 3:
Follow-up Period Procedural Outline
Procedure/Visit Day
(visit window)
Follow-up 
Visit 1
(Week 4)
(±3 days)
Follow-up 
Visit 2
(Week 12)
(±7 days)
Follow-up
Visit 3 
(Week 24/EOS)
(±7 days)
EST
Notes
Clinical Safety Assessments
Concomitant medication use
X
X
X
X
Concomitant medications are medications taken any time after the 
first dose of study medication until the last study visit.
Full physical examination
X
X
A full examination will include general appearance, skin, head, 
eyes, ears, nose, throat, neck, thyroid, chest/lungs, heart, abdomen, 
lymph nodes, and extremities. (See Section 9.4.3).
Abbreviated physical 
assessment
X
X
Abbreviated examinations will include an abdominal exam, 
assessments of ascites and hepatic encephalopathy, and 
symptom-focused assessments. (See Section 9.4.3).
Physical measurements
X
X
X
X
Includes body weight only.
Vital signs
X
X
X
X
Includes body temperature, respiratory rate, blood pressure, heart 
rate. Blood pressure and heart rate should be measured after the 
participant has been resting quietly for at least 5 minutes.
DXA scan
X
X
The EST DXA scan assessment should be performed only if the 
participant has received at least 1 dose of study drug. The EST 
DXA scan should be performed within 7 days of the EST visit. 
Urine pregnancy test should be performed in WOCBP prior to 
DXA scan.
Adverse events
X
X
X
X
Nonserious AEs must be collected from the time of the first dose 
of the study drug through the date of the follow-up or last visit. 
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Table 3:
Follow-up Period Procedural Outline
Procedure/Visit Day
(visit window)
Follow-up 
Visit 1
(Week 4)
(±3 days)
Follow-up 
Visit 2
(Week 12)
(±7 days)
Follow-up
Visit 3 
(Week 24/EOS)
(±7 days)
EST
Notes
Monitoring for AEs will occur at every study visit. See 
Section 9.2.
Serious adverse events
X
X
X
X
All SAEs must be collected from the date of participant’s written 
consent until 30 days post discontinuation of dosing or 
participant’s participation in the study if the last scheduled visit 
occurs at a later time (last visit for participation). See Section 9.2.
Clinical Efficacy Assessments
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HSP47 siRNA
Table 3:
Follow-up Period Procedural Outline
Procedure/Visit Day
(visit window)
Follow-up 
Visit 1
(Week 4)
(±3 days)
Follow-up 
Visit 2
(Week 12)
(±7 days)
Follow-up
Visit 3 
(Week 24/EOS)
(±7 days)
EST
Notes
Laboratory Assessments
Hematology 
X
X
X
X
See Section 9.4.1 and Table 8.
Chemistry
X
X
X
X
See Section 9.4.1 and Table 8.
Metabolic panel 
X
X
Collected after fasting ≥10 hours. See Section 9.4.1 and Table 8.
HbA1c
X
X
See Section 9.4.1 and Table 8.
Urinalysis
X
X
X
X
See Section 9.4.1 and Table 8.
Serum AFP
X
X
X
X
See Section 6.2 and Section 9.4.1.
Pregnancy test
X
Xa
Xa,b
For WOCBP only. See Section 9.2.5. Urine pregnancy test should 
be performed in WOCBP prior to DXA scan.
PK 
 Sampling
Blood PK sampling
See Notes
Refer to
for sampling schedule
AE = adverse event; AFP = alpha-fetoprotein; 
 DXA = dual-energy X-ray 
absorptiometry; EOS = end of study; 
 EST = Early Study Termination; HbA1c = hemoglobin 
A1c; 
 
 
PK = pharmacokinetic; 
 SAE = serious adverse event; 
WOCBP = women of childbearing potential
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a Serum or urine pregnancy test should be performed in WOCBP prior to 
 to confirm that participant is not pregnant.
b If site is not participating in the
, pregnancy testing is required only if Follow-up Visit 1 (Week 4) pregnancy testing is not completed.
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3
INTRODUCTION
BMS-986263 is a lipid nanoparticle (LNP) formulation that incorporates 6 lipid components and 
a 
-conjugated targeting agent (di-retinamide-PEG-di-retinamide [DPD]). The DPD moiety 
is present on the external surface of the nanoparticle and enables targeting and uptake by hepatic 
stellate cells (HSCs, the cells responsible for hepatic collagen synthesis) via receptors for retinol 
binding protein.
The LNPs contain a small interfering ribonucleic acid (siRNA) active ingredient which is a 
nuclease-resistant, synthetic, double-stranded ribonucleic acid (RNA) designed to temporarily 
inhibit the expression of heat shock protein 47 (HSP47) via RNA interference. Briefly, RNA 
interference (RNAi) involves a process of degrading target messenger ribonucleic acid (mRNA)
transcripts, which prevents the translation of target protein. In this case, the siRNA component of 
BMS-986263, which is a nuclease-resistant, synthetic double-stranded siRNA, pairs with the 
mRNA of HSP47, thereby blocking the translation process and preventing the formation of HSP47 
protein. The resultant decreased intracellular level of HSP47 leads to a decrease in the formation 
of stable collagen, and it is hypothesized to result in decreased liver fibrosis.
3.1
Study Rationale
This study aims to demonstrate the antifibrotic efficacy of BMS-986263, using a liver fibrosis 
histological endpoint, and the safety and tolerability of BMS-986263, as assessed by adverse 
events (AEs), serious adverse events (SAEs), laboratory results (including assessment of potential 
drug-induced liver injury [DILI]), vital signs, physical examinations, electrocardiograms (ECGs), 
 infusion-related reaction (IRR) monitoring, and bone mineral density 
(BMD) monitoring, in participants with nonalcoholic steatohepatitis (NASH) and compensated 
cirrhosis.
Nonalcoholic fatty liver disease (NAFLD) is one of the most common causes of chronic liver 
disease in the world today. NASH, which is the more advanced form of NAFLD, is defined as the 
presence of hepatic steatosis and inflammation with hepatocyte injury (ballooning), with or 
without fibrosis.1 NASH is associated with increased mortality rates due to cardiovascular-, liver-, 
and cancer-related deaths. Currently, there are no approved drugs for the treatment of NASH. With 
the increasing prevalence of obesity and obesity-related diseases, NASH could soon become the 
leading indication for liver transplantation and the leading cause of hepatocellular carcinoma 
(HCC) globally.2
NASH patients with cirrhosis have a particularly high unmet medical need for effective therapies. 
Among NASH patients, the stage of fibrosis is the strongest predictor of disease-specific mortality, 
and patients with cirrhosis are at the greatest risk for disease-related morbidity and mortality.3,4,5,6
Patients with cirrhosis are particularly at increased risk for poor clinical outcomes, including 
hepatic decompensation events and the need for liver transplant.
It is reasonable to assume that an improvement in fibrosis would be predictive of clinical benefit, 
and a reduction of fibrosis in patients with compensated cirrhosis, if substantial, could lead to 
improvements in liver function and long-term clinical outcomes.
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3.2
Background
A detailed description of the chemistry, pharmacology, efficacy, and safety of BMS-986263 is 
provided in the Investigator’s Brochure (IB).7
Liver Fibrosis
Deposition of collagen is a tightly regulated process that is vital to normal organ structure and 
function. Cytokines associated with acute or chronic inflammation induce the production of 
collagen to provide a fibrotic band for healing. Regulation of fibrosis mechanisms ensures both 
production of sufficient quantities of specific collagen types at the appropriate time and in the 
appropriate location, and removal and remodeling to prevent accumulation of unneeded collagen 
that could impair organ and tissue function.
In some circumstances, such as when inflammatory processes and/or collagen deposition are 
prolonged, collagen removal and remodeling can become dysregulated, causing excessive amounts 
of collagen to accumulate. Hepatic fibrosis may result from a wide range of causes, including 
NASH, chronic hepatitis C virus (HCV) or hepatitis B virus (HBV) infection, and alcoholic 
hepatitis. All of these chronic diseases have a necroinflammatory component and frequently result 
in excessive collagen deposition and scarring of the liver parenchyma. This damage often leads to 
progression to cirrhosis, necrosis of hepatocytes, and end-stage liver disease.
Role of HSP47 in Liver Fibrosis
The principal cell type responsible for collagen deposition in the liver is the HSC, a resident 
perisinusoidal cell. When stimulated by reactive oxygen intermediates or inflammatory mediators 
(eg, transforming growth factor-β, tumor necrosis factor-α, and platelet-derived growth factor), 
HSCs become activated. Upon activation, HSCs are transformed into proliferative, fibrogenic, and 
contractile myofibroblasts that synthesize and secrete procollagen.8 Procollagen is enzymatically 
cleaved to form insoluble collagen that accumulates in tissue, resulting in fibrosis.
HSP47 is a necessary component of the collagen deposition mechanism in myofibroblasts. By 
acting as an intracellular chaperone of early collagen precursors for Type I to Type V collagens, 
HSP47 facilitates collagen formation, prevents collagen degradation, and ensures proper 
triple-helix formation of procollagen in the endoplasmic reticulum.9,10 While HSP47 is not the 
initiating factor in the pathologic accumulation of extracellular collagen matrix, a number of 
experimental models have shown that HSP47 is required to produce high quality collagen.11,12,13,14
Intracellular HSP47 levels increase with increased demand for collagen synthesis.10 The 
demonstration that liver fibrosis in animals15 and humans16 can regress when collagen synthesis is 
inhibited suggests that fibrosis can be reversed. This reversal most likely involves the activity of 
tissue enzymes such as matrix metalloproteinases (MMPs). Various therapeutic approaches, either 
to inhibit collagen synthesis or to activate collagen removal mechanisms, have been investigated 
in animal models.17,18 However, none have yet been applied clinically, often because of side effects 
resulting from an inability to specifically target particular molecules and/or cells.
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3.2.1
Nonclinical Studies
Initial bioinformatic analysis predicted that BMS-986263 would be a highly selective siRNA with 
low probability of off-target activity. In vitro cellular studies performed with BMS-986263 
confirmed specificity of the RNAi activity. Additional in vitro cellular studies demonstrated potent 
RNAi activity elicited by BMS-986263 against both human and rat versions of HSP47. 
BMS-986263 elicited knockdown of HSP47 mRNA in rat primary HSCs. The presence of DPD in 
the formulation was shown to be essential for achieving RNAi activity, validating the targeting 
strategy of this formulation for effective delivery to the HSCs.
In vivo, BMS-986263 resulted in effective knockdown of HSP47 mRNA levels in rat liver after a 
single dose in the dimethylnitrosamine (DMN) quick model. Significant efficacy was also 
observed in the rat DMN chronic model of liver fibrosis as demonstrated by reduced collagen 
deposition (based on hydroxyproline level); improved histopathology, fibrosis scores with 
trichrome stain; and improved overall health based on increased total body and relative liver 
weights; compared with the Vehicle group. Refer to the BMS-986263 IB7 for further details.
The most salient toxicology findings were bone changes resulting in fractures in rats, increases in 
complement levels in monkeys, and fetal malformations in rabbits.
Gross and histological evidence of fractures were observed at doses ≥ 10 mg/kg/dose twice per 
week (BIW) in the 5-week and 8 mg/kg/dose BIW in the 13-week studies in rats.19,20 In the 
26-week rat study, there was no BMS-986263-related bone findings at any dose 
(no-observed-adverse-effect level [NOAEL] = 8 mg/kg/week, the highest dose administered, with 
steady state area under the curve (AUC) exposures of approximately 6× higher than the observed 
human exposure at a clinical dose of 
In monkeys, there were no adverse bone 
effects noted at any dose after repeated dosing for up to 39 weeks.22 The NOAEL in this study was 
15 mg/kg/week (AUC multiple: 82). Although drug product-related changes in bone size, mineral 
content, and mineral density were observed in female monkeys at all doses (2.5 mg/kg/week) 
and male monkeys at the high dose of 15 mg/kg/week, these changes were considered nonadverse
based on their small magnitude, and had no associated negative impacts on bone strength.
The underlying mechanism of the fractures in the rat is an increase in osteoclast activity in the 
subperiosteal regions of the diaphysis of long bones, a decrease in osteoclast numbers, and reduced 
osteoid in the trabecular regions of the bones, which translates into reduced bone formation. The 
literature suggests that rats are sensitive to bone fractures related to hypervitaminosis A.23,24
However, the majority of the protein in bone is collagen, and there is literature suggesting that 
HSP47 is involved in bone formation.25,26 Given the observation of fractures in animals that 
received empty-LNP formulation (ie, without siRNA inhibition of HSP47) it is hypothesized that 
LNP played a role in the observed findings.
In the 39-week repeat-dose study in monkeys, modest and transient elevations of complement 
components were reported; onset of these occurred as soon as 10 minutes postinfusion and were 
resolved by 24 hours.27 BMS-986263-related findings were limited to nonadverse changes in the 
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skin and vaginal epithelium at all doses, likely related to the 
 component of the formulation, 
and minimal decreases in red cell mass parameters at the high dose.
In a 13-day expanded range-finding study in pregnant rabbits (1 and 3 mg/kg intravenous [IV]
every other day), malformations of the thoracic or lumbar vertebrae and/or ribs was observed at 
3 mg/kg but not at 1 mg/kg (weekly AUC = 0.2× human AUC 
These included 
hemivertebrae, small or enlarged vertebral arches and centra, and misaligned vertebrae, fused ribs, 
and fused costal cartilages (rib precursors). The observed teratogenicity is not unexpected given 
the LNP formulation contains a 
 Because these malformations occurred in the absence of 
any detectable maternal toxicity, ND-L02-s0201/BMS-986263 is considered to be a selective 
developmental toxicant in rabbits.
Additional details on the nonclinical program and the potential risks associated with the use of 
BMS-986263 are available in the IB.7
3.2.2
Clinical Studies
The clinical development program of BMS-986263 consists of 7 completed studies: 3 studies in 
healthy participants (ND-L02-s0201-001, ND-L02-s0201-004, and IM025001),29,30,31 3 studies in 
participants with liver fibrosis (ND-L02-s0201-002, ND-L02-s0201-003, and IM025006),32,33,34
and 1 study in participants with hepatic impairment (HI) (Study IM025015). For further details on 
the completed studies, refer to the BMS-986263 IB.7
Clinical Efficacy
The efficacy of BMS-986263 has been investigated in 3 clinical studies:

Study ND-L02-s0201-00232 (N = 25) was a Phase 1b/2, open-label, randomized, multicenter, 
repeat-dose, dose-escalation study at doses of 0.2, 0.4, and 0.6 mg/kg/week administered once 
every week (QW) or BIW for 5 weeks in participants with moderate to extensive progressive 
hepatic fibrosis (METAVIR F3 to F4) due to either NASH or chronic HCV. In this study, 
evidence indicative of biological activity was observed with improvements noted in 
METAVIR, Ishak, and Knodell fibrosis scores, as well as decreased stiffness was observed 
with Fibroscan® at Week 5, all of which are measures of hepatic fibrosis.

Study ND-L02-s0201-00333 (N = 10) was a Phase 1b/2, open-label, randomized, multicenter, 
repeat-dose, dose-escalation study at doses of 0.2, 0.4, and 0.6 mg/kg/week QW for 5 weeks 
in participants with moderate to extensive progressive hepatic fibrosis (METAVIR F3 to F4) 
due to NASH, chronic HCV, or alcoholic liver disease. In this study, evidence indicative of 
biological activity was observed with improvements noted in METAVIR, Ishak, and Knodell 
fibrosis scores, as well as decreased stiffness was observed with Fibroscan® at Week 5, all of 
which are measures of hepatic fibrosis.

Study IM02500634 was a Phase 2, randomized, double-blind, placebo-controlled study of 
45 mg BMS-986263 versus 90 mg BMS-986263 versus placebo (randomized 1:2:1) dosed 
weekly for 12 weeks in 61 participants with advanced fibrosis due to chronic HCV who had 
achieved sustained virologic response (SVR) at least 1 year prior to screening. The primary 
endpoint was the proportion of participants that achieved ≥1 stage improvement in liver 
fibrosis (METAVIR) on liver biopsy after 12 weeks of treatment. One patient who received 
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90 mg BMS-986263 had a nonevaluable biopsy at the end of study; for the primary endpoint, 
a missing biopsy was considered not to be improvement (failure). All results should be 
interpreted with caution given the small sample size.

All participants were required to have HCV-SVR for at least 52 weeks and METAVIR 
Fibrosis Stage 3 or Stage 4 to be eligible to participate. The participants were enrolled on 
the basis of results of liver biopsy as read by the local pathologist. 
 
 
 
 
baseline liver stiffness assessed by magnetic resonance elastography (MRE)
 
 were comparable across treatment groups.

A ≥1 stage improvement in METAVIR score was observed for 6 of 28 (21%), 3 of 
18 (17%), and 2 of 15 (13%) participants in the 90 mg BMS-986263, 45 mg BMS-986263, 
and placebo groups, respectively.
In participants with a baseline METAVIR score of 4 (equivalent to cirrhosis), a 
≥1 stage improvement in METAVIR score was observed for 3 of 6 (50%), 1 of 
2 (50%), and 0 of 2 participants in the 90 mg BMS-986263, 45 mg BMS-986263, and 
placebo groups, respectively.

The secondary endpoints included improvements in Ishak score. A ≥2 stage improvement 
in Ishak score was observed in 5 of 28 (18%), 0 of 18 (0%), and 0 of 15 participants in the 
90 mg BMS-986263, 45 mg BMS-986263, and placebo groups, respectively.
Clinical Safety in Participants with Advanced Liver Fibrosis
In the 3 clinical studies in participants with advanced liver fibrosis, BMS-986263 was generally 
well tolerated and demonstrated an acceptable safety profile.

In studies ND-L02-s0201-002 and ND-L02-s0201-003, the most frequent AEs experienced by 
participants were temporally related to the infusion of the drug product and were mainly 
associated with IRRs. These reactions were mild to moderate in severity. The signs and 
symptoms of IRRs included, but were not limited to, back pain, fever, chills, hot or warm 
sensation, flushing, throat constriction, shortness of breath, chest tightness, tachypnea, 
tachycardia, hypotension, urticaria, pruritus, erythema, and/or edema. In general, back pain 
was the most common symptom reported for these IRRs. Refer to the BMS-986263 IB for 
more details on these studies.

In Study IM025006, IRRs were the most frequently experienced AEs. All infusion-related 
AEs were mild or moderate in intensity. The AEs associated with IRRs included back pain 
(most commonly reported), hypertension, hives/urticaria, flushing, shortness of breath, dry 
mouth, and hypoxia. In the 45 mg BMS‑986263 group, of the 6 participants who had IRRs, 
3 participants had at least 1 infusion interrupted due to an AE. In the 90 mg BMS-986263 
group, of the 15 participants who had IRRs, 13 participants had at least 1 infusion interrupted 
due to an AE. All subjects who had IRRs completed the treatment period.
In this study, BMS-986263 was not associated with evidence of 
 based 
on monitoring of signs and symptoms of vitamin A toxicity and liver biopsy. None of the 
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HSP47 siRNA
participants had serum or plasma vitamin A (retinol) levels above the upper limit of normal 
(ULN) (defined as 3.42 µmol/L) during the course of treatment.
Clinical Safety and Pharmacokinetic (PK) in Participants with HI

Study IM025015 - This was a Phase 1, open-label, single-dose study to evaluate the PK, 
safety, and tolerability of BMS-986263 90 mg IV in participants with varying degrees of HI. 
Study IM025015 consisted of 2 parts. A total of 52 participants were screened, and 40 
participants were enrolled in the study: 24 of these were enrolled in Part 1 (8 participants in 
normal matched Group D, 8 participants in mild HI [Group A], and 8 participants in moderate 
HI [Group B]) and 16 participants were enrolled in Part 2 (8 participants in normal matched 
Group E and 8 participants in severe HI [Group C]). Overall, 39 participants completed the 
study, and 1 participant in the moderate HI group withdrew consent during the study. 
In this study, single doses of BMS-986263 were generally safe and well tolerated in 
participants with normal hepatic function and several degrees of HI. Most of treatment 
emergent AEs (TEAEs) were mild or moderate in severity. The most frequent two TEAEs 
were flu-like illness and IRRs. There were no TEAEs that led to death or treatment 
discontinuation. One treatment emergent SAE of hematemesis was reported in a participant 
with moderate HI and was considered not related to BMS-986263. 
Compared to the respective matching normal group, exposure estimates of BMS-986263 
siRNA exposures [geometric mean AUC(0-T) and AUC(INF)] were similar in the HI mild 
group, and 1.34- and 1.33-fold higher, respectively, in the moderate HI group and 2.63-fold 
higher for both in the severe HI group. For DPD, exposure estimates were modestly lower in 
both the mild HI and moderate HI groups, compared with the matching normal groups, whereas 
AUC(0-T), and AUC(INF) were 1.31, and 1.33 higher for the severe HI, respectively. For 
S104, higher exposure trends related to HI severity were noted in Cmax, AUC(0-T), and 
AUC(INF), with the highest exposure observed in HI severe group with a geometric mean 
AUC(0-T) 5.5-fold higher than the matching normal group. S104 is a component with a short 
half-life (~36 hours) and, based on modeling studies, it does not accumulate with weekly 
dosing. Additionally, S104 is an excipient with no known biological activity.
Based on the PK of siRNA, DPD, and S104 components of BMS-986263 and safety 
observations from this study, no dose adjustment is recommended for BMS-986263 in patients 
with mild or moderate HI. Results from this and other studies will guide the dose selection for 
patients with severe HI.
Based on the clinical studies to date, there were no safety trends observed in the laboratory 
assessments, physical examinations, vital signs, and ECG assessments. There were no changes in 
BMD as assessed by dual-energy X-ray absorptiometry (DXA) scan and there were no cases of 
potential DILI in the clinical studies.
3.3
Benefit/Risk Assessment
3.3.1
Overall Benefit/Risk Assessment
In the completed clinical studies BMS-986263 has been generally well tolerated, with an
acceptable safety profile in patients with mild or moderate HI. More detailed information about 
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the known and expected benefits and risks and reasonably anticipated AEs of BMS-986263 may 
be found in the IB.7
In Phase 1b and Phase 2 studies involving participants with advanced liver fibrosis, including 
compensated cirrhosis, a proportion of participants administered BMS-986263 have had an 
improvement of fibrosis. As previously mentioned, there is no approved therapy for patients with 
advanced liver fibrosis. A reduction in fibrosis in NASH patients with compensated cirrhosis may 
lead to a reduced risk liver decompensation, need for liver transplant, HCC, and mortality.
In nonclinical and Phase 1 and 2 clinical studies to date, potential risks associated with 
BMS-986263 have been identified. One is the risk of IRRs observed in the Phase 1 and 2 studies. 
In all cases, infusion reactions were mild to moderate in severity and self-limited. There was no 
evidence of anaphylaxis, and participants were not discontinued from the studies due to these 
reactions. In an attempt to reduce the risk of these IRRs, the total dose is administered in step-wise
fashion as described in the Pharmacy Manual (see Section 7.1.1). If clinical signs and/or symptoms 
indicate an IRR, the infusion may be interrupted. In addition, to potentially decrease the frequency 
or severity of infusion reactions, premedication (antihistamines and/or corticosteroids) may be 
used, at the discretion of the investigator. The premedication may be administered (at the discretion 
of the investigator) to ensure safety of the participants, as mentioned in Section 7.1.2.
Other identified risks include the impact of exposure to DPD 
 associated with 
administration of BMS-986263. These include possible impact on bone, liver, and fetal 
development.
Bone Risk
Although HSP47 and generation of collagen are important for bone formation, it is hypothesized 
that the DPD component of BMS-986263 is responsible for bone abnormalities identified in the 
nonclinical rat studies. However, no significant bone abnormalities were observed in cynomolgus 
monkeys. In this study, participants will be assessed for changes in BMD by DXA scan; 
.
Reproductive Risk
In nonclinical studies, BMS-986263 had effects on fetal development, including fetal 
teratogenicity and skeletal malformations in nonclinical rabbit studies. In this study, women of 
childbearing potential (WOCBP) and male participants who are sexually active with WOCBP must 
agree to follow instructions for method(s) of highly effective contraception, as defined in 
APPENDIX 4.
Other DPD-Risks, Including Liver Risk
The theoretical risk of DPD-related liver toxicity is mitigated by the short treatment duration of 
this study (12 weeks). In the previous Phase 2 study in HCV-SVR participants, no participants had 
a constellation of clinical signs and symptoms that was suggestive of 
. 
Furthermore, there was no laboratory evidence of potential DILI or new histologic changes 
suggestive of 
 to HSCs. In this study, all participants will be monitored closely for 
signs and/or symptoms of 
. Moreover, liver safety will be monitored by 
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serial history, abdominal physical exams, and laboratory assessments. 
 
 
In this study, participants will be queried for symptoms suggestive of 
 including 
but not limited to dry skin, vaginal dryness, cheilosis, gingivitis, muscle and joint pains, fatigue, 
mental dullness, and depression. Physical examinations during 
 evaluation will be 
performed that include signs of 
 including skin and oral mucosa changes and 
hepatomegaly.
Additional safety monitoring will include laboratory assessments to rule out development of 
anemia, leucopenia, thrombocytopenia, liver enzyme (aspartate aminotransferase [AST], alanine 
aminotransferase [ALT], alkaline phosphatase [ALP]) and total bilirubin elevations. Use of 
over-the-counter (OTC) herbal supplements and multivitamins containing vitamin A (including 
Cod liver oil), or other medications that may contain vitamin A, are prohibited while participating 
in the study (Section 7.7.1). Prior to starting study treatment and throughout the study, participants 
will be educated about vitamin A-containing foods, medications, and herbal supplements, as well 
as the signs and symptoms of vitamin A toxicity. In addition, liver biopsy specimens will also be 
assessed for histologic evidence suggestive of 
 (Section 9.4.6).
In order to minimize the overall risk to participants, this protocol has eligibility criteria appropriate 
to the population and proposed treatments, exclusionary screening tests, and specific follow-up 
safety assessments. In addition, the AEs and SAEs will be reviewed on an ongoing basis by the 
Medical Monitors and the pharmacovigilance group to look for trends and any emergent or 
unexpected safety issues. An independent Data Monitoring Committee (DMC) will also review 
safety data on a regular basis.
3.3.2
Coronavirus Disease 2019-Related
The ongoing global coronavirus disease 2019 (COVID-19) pandemic has been identified as a 
potential risk to trial participants in general and it may particularly affect individuals with 
underlying chronic diseases. The individual benefit-risk considerations regarding COVID-19 
infection remains the responsibility of the investigator. Vaccination as well as testing to exclude
infection prior to enrollment and to inform decisions about participant care during the study
should follow local standard practice and requirements. Non-live COVID-19 vaccination is 
allowed during the study, will be documented as a concomitant medication, and should follow 
local standard practices during administration. The efficacy and safety of COVID-19 vaccines in 
subjects receiving BMS-986263 are unknown. BMS-986263 is not immunomodulatory. It is not 
known whether taking BMS-986263 changes the risk of SARS-CoV-2 infection, or the duration 
or severity of COVID-19 disease. 
 
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4
OBJECTIVES AND ENDPOINTS
Table 4:
Objectives and Endpoints
Objectives
Endpoints
Primary

To evaluate the efficacy of BMS-986263 
compared with placebo to improve liver 
fibrosis in participants with compensated 
cirrhosis due to NASH

Proportion of participants who achieve ≥1 stage 
improvement in liver fibrosis (NASH CRN 
Fibrosis Score), as determined by liver biopsy 
after 12 weeks of treatment

Secondary

To further assess the efficacy of 
BMS-986263 compared with placebo to 
improve liver fibrosis, as determined by 
liver biopsy, in participants with 
compensated cirrhosis due to NASH

Proportion of participants with ≥1 stage 
improvement in liver fibrosis (NASH CRN 
Fibrosis Score), with no worsening of NASH after 
12 weeks of treatment (worsening defined as an 
increase of the NAS by ≥1 point)

Proportion of participants with ≥2 stage 
improvement in liver fibrosis (NASH CRN 
Fibrosis Score) after 12 weeks of treatment

Proportion of participants with ≥1 stage 
improvement in liver fibrosis (modified Ishak 
score) after 12 weeks of treatment

Proportion of participants with ≥2 stage 
improvement in liver fibrosis (modified Ishak 
score) after 12 weeks of treatment

Change from baseline in CPA after 12 weeks of 
treatment

To assess the safety and tolerability of 
BMS-986263 
in 
participants 
with 
compensated cirrhosis due to NASH

Incidences of SAEs, AEs, clinical laboratory 
values, vital signs, physical examination findings, 
and ECGs

Change from baseline in BMD, as measured by 
DXA scan, at Follow-up Week 24

To assess the PK of BMS-986263 in 
participants with compensated cirrhosis due 
to NASH

Plasma concentrations of siRNA, DPD, HEDC, 
and S104 (components of BMS-986263 for 
injection)
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Table 4:
Objectives and Endpoints
Objectives
Endpoints

Exploratory

Exploratory
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Table 4:
Objectives and Endpoints
Objectives
Endpoints

Exploratory
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Table 4:
Objectives and Endpoints
Objectives
Endpoints
 AE = adverse event; ALT = alanine aminotransferase; 
 
 AST = aspartate aminotransferase; BMD = bone mineral density; 
 
 CPA = collagen proportionate 
area; CRN = Clinical Research Network; 
 
DPD = di-retinamide-PEG-di-retinamide; 
; DXA = dual-energy X-ray absorptiometry; 
ECG = electrocardiogram; 
 
 
 HEDC = (Bis[2-(tetradecanoyloxy)ethyl] 
carbamoylmethyl)-(2-hydroxyethyl)dimethylazanium bromide; 
 
 INR = international normalized ratio; 
 
 
 
 
 
 NASH = nonalcoholic steatohepatitis; 
 
 
PK = pharmacokinetics; 
 
 SAE = serious adverse event; 
 
SiRNA = small interfering ribonucleic acid; 
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5
STUDY DESIGN
5.1
Overall Design
This is a randomized, double-blind, placebo-controlled, parallel-group, multiple-dose Phase 2
study to evaluate the efficacy, safety, and tolerability of BMS-986263 in adults with compensated 
cirrhosis due to NASH. The primary study endpoint is the proportion of participants who achieve 
≥1 stage improvement in liver fibrosis (NASH [Clinical Research Network (CRN)] Fibrosis Score) 
on biopsy after 12 weeks of treatment.
The study includes:

A screening period

A 12-week, double-blind treatment period, during which participants will receive 1 of the 
following 3 treatments by IV infusion: 45 mg BMS-986263 QW, 90 mg BMS-986263 QW, or 
placebo QW

A follow-up period of 24 weeks during which participants will not receive investigational 
treatment
The study design schematic is presented in Figure 1.
Figure 1:
Study Design Schematic
D = Day; W = Week
5.1.1
Screening Period
Eligibility will be based on specified inclusion and exclusion criteria (Section 6.1 and Section 6.2, 
respectively), including medical history, disease activity, and safety assessments. Eligibility
criteria for this study have been carefully considered to ensure the safety of the participants and 
that the results of the study can be analyzed properly. It is imperative that participants fully meet 
all eligibility criteria. Participants will have a diagnosis of NASH with compensated cirrhosis
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(requirements in Section 6.1); ≥80% of subjects will be required to have definite steatohepatitis
on the biopsy used to confirm eligibility. In addition to the main study, additional eligibility criteria 
for participation 
 are provided in 
. Participation in the 
 is required if 
available at the site, unless it is contraindicated for a participant to have an 
.
The investigator will maintain a screening log to record details of all participants screened and to 
confirm eligibility or record reasons for screening failure, as applicable. Certain procedures 
conducted as part of the participant’s routine clinical management and obtained before signing of 
informed consent may be utilized for screening purposes provided the procedure meets the 
protocol-defined criteria and has been performed within the timeframe defined in the Schedule of 
Activities (SOA) (Section 2).
Randomization should occur within 56 days (8 weeks) of signing the informed consent. The 
screening period may be extended (up to an additional 4 weeks) to accommodate unanticipated 
delays in obtaining required screening results.
Visit details are provided in the Screening Procedural Outline in the SOA (Section 2).
5.1.2
Treatment Period and Follow-up
Participants meeting eligibility criteria during the screening period will enter the treatment period. 
Approximately 270 participants will be randomized via interactive response technology (IRT) in 
a 1:1:1 ratio to receive 45 mg BMS-986263 QW, 90 mg BMS-986263 QW, or placebo QW by IV 
infusion in a double-blind manner.
Participants will be stratified at Randomization by the presence of definite steatohepatitis on 
biopsy (yes versus no). At least 80% of participants will be required to have definite steatohepatitis
on the biopsy used to confirm eligibility. Participants will receive study treatment via IV infusion 
for a total of 12 weeks. Liver biopsy will be performed at Week 12.
After 12 weeks (Day 85) of treatment or after early treatment discontinuation, participants will 
enter the 24-week follow-up period, during which participants will not receive investigational 
treatment. After all participants complete the Follow-up Week 4 visit, the study will be unblinded 
and analyses of the available Week 12 data will be conducted (Section 10.4.4). Participants who 
discontinue study treatment before the Week 11 Visit will have an Early Treatment Termination 
(ETT) visit and will continue into the 24-week follow-up period.
See the SOA in Table 2 and Table 3 (Section 2).
5.1.3
DMC and Other External Committees
This study will utilize an external DMC for the duration of the study. Data summaries and listings 
will be provided to the DMC to facilitate their assessments at the regularly scheduled times and on 
an ad hoc basis if needed. The safety review includes SAEs and events of special interest (eg, bone 
fractures, IRRs, and anaphylaxis), focusing on early signal detection. This study will also utilize 
an Independent Pathology Review Committee (IPRC) to perform central pathology assessments 
of the liver biopsy samples to support study eligibility and histological efficacy endpoints analyses.
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The DMC and IPRC responsibilities, authorities, and procedures will be documented and followed 
according to their respective charters.
5.2
Number of Participants
Approximately 270 participants are planned to be randomized in a 1:1:1 ratio to receive 45 mg 
BMS-986263 QW, 90 mg BMS-986263 QW, or placebo QW by IV infusion for 12 weeks.
5.3
End of Study Definition
The start of the study is defined as the first visit for first participant screened. End of study (EOS) 
is defined as the last visit or scheduled procedure shown in the SOA (Section 2) for the last 
participant. Study completion is defined as the final date on which data for the primary endpoint 
was or is expected to be collected, if this is not the same. The end of the study for analysis of 
 samples is included in 
.
5.4
Scientific Rationale for Study Design
Phase 1b and Phase 2 studies of BMS-986263 enrolled participants with advanced liver fibrosis 
caused by NASH or HCV. Review of safety data from these studies demonstrated that 
BMS-986263 was generally safe and well tolerated. Based on efficacy data from the small number 
of participants in these studies who had advanced liver fibrosis, Study IM025017 will investigate 
the effects of BMS-986263 in a larger population of participants with compensated cirrhosis due 
to NASH.
The focus of this placebo-controlled, Phase 2 study is to demonstrate the efficacy, safety, 
tolerability, PK, 
 effects of BMS-986263 in participants with 
compensated cirrhosis due to NASH. The study schematic is provided in Figure 1.
The study will seek to confirm the findings of prior clinical studies demonstrating improvement in 
fibrosis in participants with advanced liver fibrosis. In this study, BMS-986263 at doses of 45 mg 
or 90 mg QW for 12 weeks, compared with placebo, will be utilized to assess proof-of-concept of 
the efficacy (as measured by the improvement of liver fibrosis), safety, and tolerability of 
BMS-986263 in the study population. The 45 mg and 90 mg doses were chosen because these 
doses were studied in the prior Phase 2 study of HCV-SVR patients; these doses appeared to be 
efficacious and were generally safe and well tolerated. A treatment duration of 12 weeks was 
chosen because an antifibrotic effect was observed after 12 weeks of therapy in that study. The 
follow-up period will allow assessment (utilizing noninvasive assessments of fibrosis) of the 
off-treatment durability of efficacy through Follow-up Week 24 (or up to 36 weeks total duration).
Efficacy, safety, PK, 
 effects will be compared with results from placebo-treated 
participants and across treatment arms to identify the optimal doses and dosing regimen for future 
development.
Complete details of the study design are provided in Section 5.
5.5
Justification for Dose
In a Phase 1 single-ascending dose study (ND-L02-s0201-001) in healthy, normal, male 
participants, dosing was weight-based 
 BMS-986263 was generally safe and 
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well tolerated at all dose levels. After IV infusion administration at the dose ranges given above, 
plasma concentrations of the siRNA component, NDT-05-0038, were consistent over time with an 
open, 
IV infusion model.
The model-predicted values for the primary PK parameters total plasma clearance (CL) and 
volume of the central compartment were consistent among participants and among doses and a 
log-log plot of the model-predicted area under the concentration vs time curve extrapolated to 
infinity vs dose was linear 
 
. The mean elimination half-life across 
 with no apparent 
dose-related trends. 
 
 
In the present study, the doses of 45 mg QW and 90 mg QW BMS-986263 will be investigated in 
participants with compensated cirrhosis due to NASH. Selection of the doses is based on 
nonclinical safety data and the clinical studies conducted to date. 
 
 
6
STUDY POPULATION
6.1
Inclusion Criteria
In order to be eligible to participate in this study, an individual must meet all of the following 
criteria:
1) Signed written informed consent
a) Not applicable per Revised Global Protocol v01.
b) Willing and able to complete all study-specific procedures and visits.
c) Willing to participate in the study and sign the informed consent form (ICF) by participants 
(or legally acceptable representative).
2) Type of Participant and Target Disease Characteristics
a) Not applicable per Revised Global Protocol v01.
b) Not applicable per Protocol Amendment 03 - Participants taking sodium glucose 
cotransporter 2 (SGLT2) inhibitors, glucagon-like peptide-1 (GLP-1) receptor agonists, 
anti-obesity agents, or approved NASH treatment must have been on stable doses for at least 
3 months prior to the liver biopsy used to confirm eligibility.
c) Participants taking vitamin E at doses ≥800 IU/day must have been on stable doses for at 
least 6 months prior to the screening visit. If used, vitamin E must have been initiated prior 
to the liver biopsy used to determine eligibility.
d) Not applicable per Protocol Amendment 03 - Adequate DXA scan performed during 
screening confirmed by the central imaging facility prior to Randomization (see Section 
6.2).
e) Not applicable per Protocol Amendment 03 - Liver biopsy performed within 6 months 
prior to the screening visit or performed during the screening period. A liver biopsy 
performed prior to ICF, if utilized for eligibility, must be available for central pathology 
reading prior to Randomization.
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i)
Liver biopsy consistent with NASH CRN Fibrosis Score Stage 4, as assessed by central 
pathology reading.
ii) Liver biopsy must either be consistent with steatohepatitis, as assessed by central 
pathology reading, OR, for liver biopsies without definite steatohepatitis, there should 
be some evidence of steatosis and/or ballooning and the following definition of NASH 
cirrhosis must be fulfilled:
(1) Absence of other causes of liver disease AND either of the following:
(a) At least 2 of the 3 following criteria:
(i) History of body mass index (BMI) ≥30 kg/m2
(ii) History of type 2 diabetes mellitus
(iii)History of hypertension AND/OR history of dyslipidemia
OR
(b) Previous histologic readings of steatohepatitis (for biopsies > 6 months prior to 
screening visit) AND either history of BMI ≥30 kg/m2 OR history of 
type 2 diabetes mellitus.
NOTE: At least 80% of participants will be required to have definite steatohepatitis 
on the biopsy used to confirm eligibility.
f)
Adequate DXA scan performed during screening and determined by the central imaging 
vendor prior to Randomization (see Section 6.2).
g) Liver biopsy performed within 12 months prior to the screening visit or performed during 
the screening period. A liver biopsy performed prior to ICF, if utilized for eligibility, must 
be available for central pathology reading prior to Randomization.
i)
Liver biopsy consistent with NASH CRN Fibrosis Score Stage 4, as assessed by central 
pathology reading.
ii) Liver biopsy must either be consistent with steatohepatitis, as assessed by central 
pathology reading, OR, for liver biopsies without definite steatohepatitis, there should 
be some evidence of steatosis and/or ballooning and the following definition of NASH 
cirrhosis must be fulfilled:
(1) Absence of other causes of liver disease AND either of the following:
(a) At least 2 of the 3 following criteria:
(i) History of body mass index (BMI) ≥30 kg/m2
(ii) History of type 2 diabetes mellitus
(iii)History of hypertension AND/OR history of dyslipidemia
OR
(b) Previous histologic readings of steatohepatitis (in a past biopsy prior to the one 
utilized for eligibility) AND either history of BMI ≥30 kg/m2 OR history of 
type 2 diabetes mellitus.
NOTE: At least 80% of participants will be required to have definite steatohepatitis
on the biopsy used to confirm eligibility.
h) Participants taking sodium glucose cotransporter 2 (SGLT2) inhibitors, glucagon-like 
peptide-1 (GLP-1) receptor agonists, anti-obesity agents, or approved NASH treatment 
must have been on stable doses for at least 3 months prior to screening.
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3) Age and reproductive status
Investigators shall counsel WOCBP, and male participants who are sexually active with WOCBP, 
on the importance of pregnancy prevention, the implications of an unexpected pregnancy, and the 
potential of fetal toxicity occurring due to transmission of study drug, present in seminal fluid, to 
a developing fetus, even if the participant has undergone a successful vasectomy or if the partner 
is pregnant.

The investigator shall evaluate the effectiveness of the contraceptive method in relationship to 
the first dose of study intervention.

Local laws and regulations may require the use of alternative and/or additional contraception 
methods.
a) Female Participants
i)
Female participants ages ≥21 years to ≤75 years of age, inclusive, at the time of 
screening.
ii) Not applicable per Revised Global Protocol v01.
iii) WOCBP must have a negative highly sensitive serum or urine pregnancy test 
(minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin) 
within 24 hours prior to the following: start of study treatment and each dose of study 
treatment.
(1) If a urine test cannot be confirmed as negative (eg, an ambiguous result), a serum 
pregnancy test is required. In such cases, the participant must be excluded from 
participation if the serum pregnancy result is positive.
(2) Additional requirements for pregnancy testing during and after study intervention 
are located in Section 2, SOA.
(3) The investigator is responsible for review of medical history, menstrual history, and 
recent sexual activity to decrease the risk for inclusion of a woman with an early 
undetected pregnancy.
iv) Not applicable per Revised Global Protocol v01.
v) A female participant is eligible to participate if she is not pregnant or breastfeeding, 
and at least one of the following conditions applies:
(1) Is not a WOCBP (female participants must have documented proof that they are 
not of childbearing potential)
OR
(2) Is a WOCBP and is using a contraceptive method that is highly effective (with a 
failure rate of < 1% per year), as described in APPENDIX 4, during the intervention 
period and for at least 20 days after the last dose of study intervention and agrees 
not to donate eggs (ova, oocytes) for the purpose of reproduction for the same time 
period.
vi) WOCBP must agree to follow instructions for highly effective method(s) of 
contraception, as defined in APPENDIX 4 and as described below and included in the 
ICF.
(1) WOCBP are permitted to use hormonal contraception methods (as described in 
APPENDIX 4)
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(2) Women who are not of childbearing potential are exempt from contraceptive 
requirements
b) Male Participants
i)
Male participants ages ≥21 years to ≤75 years of age, inclusive, at the time of 
screening.
ii) Male participants who are sexually active with WOCBP must agree to follow 
instructions for method(s) of contraception, as defined in APPENDIX 4 and as 
described below.
iii) Not applicable per Revised Global Protocol v01.
iv) Not applicable per Revised Global Protocol v01.
v) Not applicable per Revised Global Protocol v01.
vi) Not applicable per Revised Global Protocol v01.
vii)Not applicable per Revised Global Protocol v01.
viii)
Breastfeeding partners should be advised to consult their healthcare providers about 
using appropriate highly effective contraception during the time the participant is 
required to use condoms.
ix) Azoospermic male participants are not exempt from contraceptive requirements and 
will be required to always use a latex or other synthetic condom during any sexual 
activity (eg, vaginal, anal, oral) with WOCBP, even if the participant has undergone a 
successful vasectomy or if the partner is pregnant.
x) Male participants must be willing to and will be required to always use a latex or other 
synthetic condom during any sexual activity (eg, vaginal, anal, oral) with WOCBP; 
even if the participants have undergone a successful vasectomy or if their partner is 
already pregnant or breastfeeding. Male participants should continue to use a condom 
during the intervention period and for at least 20 days after the last dose of study 
intervention.
xi) Male participants with a pregnant or breastfeeding partner must agree to remain 
abstinent from sexual activity or use a male condom during any sexual activity (eg, 
vaginal, anal, oral) even if the participants have undergone a successful vasectomy, 
during the intervention period and for at least 20 days after the last dose of study 
intervention.
xii)Male participants must refrain from donating sperm during the intervention period and 
for at least 20 days after the last dose of study intervention.
xiii)
Female partners of male participants participating in the study should be advised to 
use highly effective methods of contraception during the intervention period and for at 
least 20 days after the last dose of study intervention in the male participant.
6.2
Exclusion Criteria
An individual who meets any of the following criteria will be excluded from participation in this 
study:
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1) Target disease exclusions
a) Other active causes of liver disease (eg, alcoholic liver disease, HBV infection [see 
APPENDIX 7)], chronic HCV infection [see APPENDIX 7], autoimmune hepatitis,
primary biliary cholangitis, primary sclerosing cholangitis, drug-induced hepatotoxicity,
Wilson disease, homozygous -1-antitrypsin deficiency, iron overload [with blood iron 
saturation > 50%], or hemochromatosis).
b) Past or current evidence of hepatic decompensation (eg, ascites, variceal bleeding, hepatic 
encephalopathy, or spontaneous bacterial peritonitis).
c) Not applicable per Protocol Amendment 03 - Liver transplantation (past or planned).
d) Not applicable per Revised Global Protocol v01.
e) Not applicable per Revised Global Protocol v02 - Model for End-stage Liver Disease
(MELD) Score > 14 at screening (APPENDIX 6). Participants who have a MELD 
Score > 14 due to an isolated elevated INR and who are taking an anticoagulant known to 
prolong INR or who have Gilbert Syndrome and direct bilirubin ≤ULN may be included 
after discussion with the Medical Monitor.
f)
Not applicable per Revised Global Protocol v02 - Evidence of HCC at screening based 
on serum alpha-fetoprotein (AFP) levels, as indicated below, or any imaging technique (eg, 
magnetic resonance imaging [MRI], computed tomography [CT], or ultrasound; based on 
local assessment):
i)
AFP > 20 ng/mL (> 16.5 IU/mL) OR
ii) LI-RADS35 3, 4, or 5 noted on the last historical CT or MRI, regardless of the AFP at 
screening. If screening ultrasound has a hepatic lesion > 10 mm in size, the participant 
must have the last historical CT or MRI performed within 3 months prior to screening 
or a new CT or MRI can be performed.
g) Not applicable per Revised Global Protocol v02 - Child-Pugh Score > 5 at screening 
(APPENDIX 5). Participants who have a Child-Pugh Score > 5 due to an isolated elevated 
INR and who are taking an anticoagulant known to prolong INR, or who have Gilbert 
Syndrome and direct bilirubin ≤the ULN, may be included after discussion with the 
Medical Monitor.
h) Not applicable per Protocol Amendment 03 - MELD Score > 14 at screening 
(APPENDIX 6). Participants with a MELD Score > 14 with elevated total bilirubin and 
who have Gilbert Syndrome and direct bilirubin ≤ULN may be included after discussion 
with the Medical Monitor.
i)
Not applicable per Protocol Amendment 03 - Evidence of HCC at screening based on 
(i) serum alpha-fetoprotein (AFP) > 20 ng/mL (> 16.5 IU/mL) or (ii) Liver Reporting & 
Data System35 3, 4, or 5 as determined by historical CT/ MRI within 3 months prior to 
screening or from multiphasic CT/MRI of liver during screening.
j)
Not applicable per Protocol Amendment 03 - Child-Pugh Score > 6 at screening 
(APPENDIX 5). Participants with a Child-Pugh Score > 6 with elevated total bilirubin and 
who have Gilbert Syndrome and direct bilirubin ≤the ULN, may be included after 
discussion with the Medical Monitor.
k) Liver transplantation (past or planned during the study).
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l)
MELD Score > 14 at screening (APPENDIX 6). Exception: Participants with Gilbert
Syndrome who have a MELD Score > 14 with elevated total bilirubin, and direct bilirubin
≤ ULN may be included provided that total bilirubin is < 4.0 mg/dL.
m) Evidence of HCC at screening based on (i) serum alpha-fetoprotein (AFP) > 20 ng/mL 
(> 16.5 IU/mL) or (ii) Liver Reporting & Data System35 3, 4, or 5 as determined by 
historical computed tomography (CT)/magnetic resonance imaging (MRI)within 3 months 
prior to screening or from multiphasic CT/MRI of liver during screening. Both AFP and 
CT/MRI assessments will be required from all participants to determine eligibility.
n) Child-Pugh Score > 6 at screening (APPENDIX 5). Exception: Participants with Gilbert
Syndrome who have a Child-Pugh Score > 6 with elevated total bilirubin, and direct
bilirubin  ≤ the ULN may be included, provided that total bilirubin is < 4.0 mg/dL.
2) Medical conditions
a) Evidence of worsening liver disease or hepatic decompensation, in the opinion of the 
investigator or Medical Monitor, during the screening period.
b) Medical history of gastroesophageal varices, except if esophagogastroduodenoscopy 
performed within 12 months prior to the screening period has shown ≤Grade 1 varices and 
without red wale signs, as assessed by the investigator.36
c) Not applicable per Revised Global Protocol v02 - History of alcohol consumption 21 
units/week (male participants) or 14 units/week (female participants) within the 2 years 
prior to the biopsy used to determine eligibility. One drink “unit” or one standard drink is 
equivalent to 12 ounces of beer, 4 ounces of wine, or 1 ounce of hard liquor. Note: 
Participants should limit alcohol during their participation in the study (Section 6.4).
d) History of bariatric surgery or intestinal bypass surgery within the 5 years prior to informed
consent or planned during the conduct of the study.
e) History of hepatocellular carcinoma.
f)
Participants who have: 1) current malignancy or 2) a previous malignancy up to 5 years 
prior to screening are excluded except for those with a documented history of cured 
nonmetastatic squamous cell skin carcinoma, basal cell skin carcinoma, or cervical 
carcinoma in situ. Participants who have a liver biopsy that is suspicious for malignancy, 
and in whom the possibility of malignancy cannot be reasonably excluded following 
additional clinical, laboratory, or other diagnostic evaluations, are also excluded.
g) History of bone disease, including osteoporosis and osteomalacia, Paget’s disease of bone, 
or a history of unexplained fractures or fractures after minimal trauma as assessed by the 
investigator.
h) Any disease or condition which, in the opinion of the investigator, might compromise 
participant safety (eg, hematologic, cardiovascular, pulmonary, renal, gastrointestinal, 
hepatic, skeletal, central nervous system, or complement-mediated disease).
i)
Any acute or chronic cardiovascular condition (eg, ischemic heart disease, congestive heart 
failure) considered clinically significant by the investigator.
j)
Uncontrolled hypertension, as defined by systolic blood pressure > 160 mmHg and/or 
diastolic blood pressure > 100 mmHg at screening, unless discussed with Medical Monitor. 
Blood pressure may be rechecked as clinically indicated.
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k) Known immunocompromised status, including but not limited to, individuals who have 
undergone organ transplantation or who are positive for human immunodeficiency virus 
(HIV) or have acquired immunodeficiency syndrome-related illness, as reported by the 
participant and/or documentation. NOTE: Testing for HIV must be performed at sites 
where mandated locally (see APPENDIX 8).
l)
History, within the last 2 years, of alcohol or drug abuse (in the opinion of the investigator), 
significant mental illness, or physical dependence on any opioid as per clinical discretion 
of the investigator.
m) Not applicable per Revised Global Protocol v02 - History of illegal IV drug use within 
the 3 years prior to screening.
n) History of major surgery within 3 months of screening; this includes but is not limited to 
surgery that involves a risk to the life of the participant, specifically, within the cranium, 
chest, abdomen, or pelvic cavity.
o) Not applicable per Revised Global Protocol v02 - History of weight gain/loss ≥10% of 
body weight in the 6 months prior to the eligibility liver biopsy.
p) Inability to tolerate IV medication or other study procedures, eg, lack of venous access.
q) Inability to safely undergo a liver biopsy, in the opinion of the investigator.
r)
Not applicable per Protocol Amendment 03 - History of severe acute respiratory 
syndrome coronavirus 2 (SARS-CoV-2) infection (either suspected or confirmed) within
4 weeks prior to signing consent. Additionally, in the case of prior SARS-CoV-2 infection, 
symptoms must have completely resolved and, based on investigator assessment in 
consultation with the Sponsor’s Medical Monitor, there are no sequelae that would place 
the participant at a higher risk when receiving investigational treatment.
NOTE: COVID reverse transcription - polymerase chain reaction (RT-PCR) viral testing 
may be required prior to Randomization based on specific country/local guidelines, and the 
results of this testing may impact study participation. Testing results should be discussed 
with the Medical Monitor to confirm eligibility.
s) History of alcohol consumption 21 units/week (male participants) or 14 units/week 
(female participants) within the 2 years prior to the biopsy used to determine eligibility. 
One drink “unit” or one standard drink is equivalent to 12 ounces (360 mL) of beer, 
4 ounces (120 mL) of wine, or 1 ounce (30 mL) of hard liquor. Note: Participants should 
limit alcohol during their participation in the study (Section 6.4).
t)
History of illegal IV drug use within the 2 years prior to screening.
u) Not applicable per Protocol Amendment 03 - History of weight gain/loss ≥10% of body 
weight in the 3 months prior to the eligibility liver biopsy and any significant weight 
changes (± 10% of body weight) during screening.
v) History of severe COVID-19 infection (either suspected or confirmed) within 4 weeks prior 
to signing consent or a previous mild or moderate COVID-19 infection within 10 days 
prior screening. Additionally, for any COVID-19 infection prior to enrollment, symptoms 
must have completely resolved and, based on investigator assessment in consultation with 
the Sponsor’s Medical Monitor, there are no sequelae that would place the participant at a 
higher risk when receiving investigational treatment.
NOTE: COVID reverse transcription - polymerase chain reaction (RT-PCR) viral testing 
may be required prior to Randomization based on specific country/local guidelines, and the 
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results of this testing may impact study participation. Testing results should be discussed 
with the Medical Monitor to confirm eligibility.
w) Any significant weight changes (± 10% of body weight) in the 3 months prior and during 
screening.
3) Prior and concomitant therapy
a) Participants taking any OTC vitamin A-containing supplements or multivitamins, or 
vitamin A-containing medications after signing the ICF.
b) Participants unable to comply with restrictions and prohibited treatments.
c) Not applicable per Revised Global Protocol v02 - Participants who have taken other 
investigational agents within 3 months prior to the liver biopsy used to confirm eligibility 
or within 12 weeks or 5 half-lives prior to the first dose of study treatment, whichever is 
longer.
d) Prior exposure to BMS-986263.
e) The participant has received recent treatment with alternative therapies, which, in the 
opinion of the investigator, could potentially confound clinical or laboratory assessments 
(eg, herbal supplements).
f)
Concomitant use of nintedanib is prohibited. Prior use of nintedanib is permitted but must 
be discontinued at least 3 days before the first dose of study treatment.
g) Not applicable per Protocol Amendment 03 - Participants who have received live 
attenuated vaccine or investigational SARS-CoV-2 vaccine within 3 months prior to the 
first dose of study treatment. Participants who have received a vaccine approved for 
Emergency Use Authorization by the United States (US) Food and Drug Administration 
(FDA) may be considered for inclusion, after discussion with the Medical Monitor.
h) Participants who have taken other investigational agents except for investigational SARS-
CoV-2 vaccine within 3 months prior to the liver biopsy used to confirm eligibility or 
within 12 weeks or 5 half-lives prior to the first dose of study treatment, whichever is 
longer.
i)
Participants taking any anticoagulants after signing the ICF.
j)
Participants who have received live attenuated vaccine or investigational SARS-CoV-2
vaccine within 3 months prior to the first dose of study treatment. Participants who have
received a vaccine approved for Emergency Use Authorization by the United States (US)
Food and Drug Administration (FDA) or other applicable country-specific regulatory 
agencies may be considered for inclusion.
4) Physical and laboratory test findings
a) Evidence of organ dysfunction or any clinically significant deviation from normal in 
physical examination, vital signs, ECG, or clinical laboratory determinations beyond what 
is consistent with the target population.
b) The participant’s baseline laboratory test results include abnormal values considered to be 
clinically significant by the investigator.
c) Not applicable per Revised Global Protocol v02 - The participant’s laboratory test results 
at screening include any of the following:

Albumin < 3.5 g/dL
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
INR > 1.4 (participants who have an INR > 1.4 and who are taking an anticoagulant 
known to prolong INR may be included after discussion with the Medical Monitor)

ALT value ≥5× the ULN

AST value ≥5× the ULN

Total bilirubin > 1.5 mg/dL, unless participant has a diagnosis of Gilbert Syndrome 
and direct bilirubin ≤ULN

Platelet count < 140,000/µL

Hemoglobin A1c ≥9.0%

Serum vitamin A (retinol) > ULN
d) Glomerular filtration rate < 30 mL/min/1.73 m2 according to the Modification of Diet in 
Renal Disease equation at screening.
e) Centrally-read DXA scan BMD T-Score of -2.5 or less at the femoral neck, total hip, or 
lumbar spine during screening (in participants 40 years of age or older).
f)
Not applicable per Protocol Amendment 03 - The participant’s laboratory test results at 
screening include any of the following:

Albumin < 2.8 g/dL

INR > 2.2

ALT value ≥5× the ULN

AST value ≥5× the ULN

Total bilirubin > 3.0 mg/dL, unless participant has a diagnosis of Gilbert Syndrome 
and direct bilirubin ≤ULN

Platelet count < 85,000/µL

Hemoglobin A1c ≥9.0%

Serum vitamin A (retinol) > ULN
g) The participant’s laboratory test results at screening include any of the following:

Albumin < 2.8 g/dL

International normalized ratio (INR) > 2.2

ALT value ≥ 5× the ULN

AST value ≥ 5× the ULN

Total bilirubin > 3.0 mg/dL, unless participant has a documented diagnosis of 
Gilbert Syndrome, provided that total bilirubin is < 4.0 mg/dL and direct bilirubin 
is ≤ ULN

Platelet count < 85,000/µL

Hemoglobin A1c ≥ 9.5%

Serum vitamin A (retinol) > ULN
5) Allergies and adverse drug reaction
a) Not applicable per Revised Global Protocol v01.
b) History of allergies to soybeans or eggs.
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c) History of allergy 
 
6) Other exclusion criteria
a) Prisoners or participants who are involuntarily incarcerated. (Note: Under certain specific 
circumstances and only in countries where local regulations permit, a person who has been 
imprisoned may be included or permitted to continue as a participant. Strict conditions 
apply and BMS approval is required.)
b) Participants who are compulsorily detained for treatment of either a psychiatric or physical 
(eg, infectious disease) illness.
c) Any factor, which in the opinion of the investigator would jeopardize the evaluation or 
safety or be associated with poor adherence to the protocol.
Eligibility criteria for this study have been carefully considered to ensure the safety of the study 
participants and that the results of the study can be used. It is imperative that participants fully 
meet all eligibility criteria.
 
 
 
 
 
 
 
 
 
 
 
 
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6.4
Lifestyle Restrictions
Participants should not consume ≥7 units/week of alcohol during the study. One drink “unit” or 
1 standard drink is equivalent to 12 ounces (360 mL) of beer, 4 ounces (120 mL) of wine, or 
1 ounce (30 mL) of hard liquor.
During the study, OTC herbal supplements or multivitamins containing vitamin A (including Cod 
liver oil), or other medications that may contain vitamin A are prohibited (Section 7.7.1). Prior to 
starting study treatment and throughout the study, the investigator will educate participants about 
vitamin 
A-containing 
foods, 
medications, 
and 
herbal 
supplements
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(https://ods.od.nih.gov/factsheets/VitaminA-Consumer, or equivalent country-specific national 
dietary recommendations), as well as the signs and symptoms of 
. Consultation 
with a nutritionist should be considered if necessary.
6.5
Dietary and Lifestyle Counseling
At the screening visit, after receiving the signed ICF, sites will provide all participants with the 
following dietary and lifestyle counseling:

Reduce body weight (if obese or overweight) through diet and exercise

Follow a balanced diet

Increase physical activity

Avoid alcohol as much as possible
6.6
Screen Failures
Screen failures are defined as participants who consent to participate in the clinical study 
(ie, enroll) but are not subsequently randomized into the study. A minimal set of screen failure 
information is required to ensure transparent reporting of screen failure participants, to meet the 
Consolidated Standards of Reporting Trials publishing requirements, and to respond to queries 
from regulatory authorities. Minimal information includes date of consent, demography, screen 
failure details, eligibility criteria, and any serious AEs. 
 
6.6.1
Retesting During Screening Period
Participant Re-enrollment: This study permits the re-enrollment of a participant that has 
discontinued the study as a pretreatment failure (ie, participant has not been randomized/has not 
been treated). If re-enrolled, the participant must be re-consented.
Retesting of laboratory parameters and/or other assessments within any single screening or lead-in 
period will be permitted (in addition to any parameters that require a confirmatory value). The 
most current result prior to Randomization is the value by which study inclusion will be assessed, 
as it represents the participant’s most current, clinical state. Laboratory parameters and/or 
assessments that are included in Table 1, Screening Procedural Outline may be repeated in an 
effort to find all possible well-qualified participants. Consultation with the Medical Monitor may 
be needed to identify whether repeat testing of any particular parameter is clinically relevant.
Participants who are screen failures may be rescreened only once; additional rescreening may be 
allowed after consultation with the Medical Monitor. An additional rescreening is permitted for 
study participants who have failed screening due to SARS-CoV-2 infection. All participants who 
are re-enrolled will be assigned a new participant identification. For participants who are 
rescreened, 
 DXA scan assessments can be reused without repeating if 
performed 3 months prior to rescreening visit (Section 2).
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7
TREATMENT
Study treatment is defined as any investigational treatment(s), marketed product(s), placebo, or 
medical device intended to be administered to a study participant according to the study 
randomization or treatment allocation.
Study 
treatment 
includes 
both 
investigational 
[medicinal] 
product 
(IP/IMP) 
and 
non-investigational [medicinal] product (nonIP/nonIMP) as shown in Table 5.
An IP, also known as IMP in some regions, is defined a pharmaceutical form of an active substance 
or placebo being tested or used as a reference in a clinical study, including products already with 
a marketing authorization but used or assembled (formulated or packaged) differently than the 
authorized form, or used for an unauthorized indication, or when used to gain further information 
about the authorized form.
Other medications used as support or escape medication for preventative, diagnostic, or therapeutic 
reasons, as components of the standard of care for a given diagnosis, may be considered as nonIP.
Table 5:
Study Treatments
Product 
Description/Cla
ss and Dosage 
Form
Potency
IP/
NonI
P
Blinded 
or Open-
Label
Packaging/
Appearanc
e
Storage Conditions
(Per Label)
BMS-986263 for 
injection
10 mg per 
vial; 
3 mg/mL 
after 
reconstitutio
n
IP
Blindeda
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Placebob for 
BMS-986263 for 
injection/
 
 
 
NA
IP
Blindeda
 
 
 
 
 
IP = investigational product; IV = intravenous; NA = not applicable
a The medication is provided to the pharmacy open-label, and an unblinded pharmacist (or another appropriately 
delegated qualified individual) will prepare the blinded solutions for IV infusion.
b
 
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7.1
Treatments Administered
The investigator must ensure that the IP will be used only in accordance with the protocol and 
Pharmacy Manual. The selection and timing of dose for each participant is shown in Table 6.
Table 6:
Study Treatment Doses, Dosing Frequency, and Route of 
Administration
Study Treatment
Unit Dose 
Strength(s)/Dosage 
Level(s)
Frequency of 
Administration
Route of Administration
45 mg BMS-986263 
QW
IV infusion
90 mg BMS-986263 
QW
IV infusion
Placebo 
QW
IV infusion
IV = intravenous; QW = once every week
Treatment Preparation
An unblinded pharmacist (or another appropriately delegated qualified individual) will prepare 
matching IV infusion solutions 
 
 according to the participant’s treatment assignment (Section 7.2). 
 
 
 
Please refer to the Pharmacy Manual for complete information on BMS-986263 and placebo 
storage, handling, and exact volumes, and instructions on the preparation of study treatment 
infusion.
Treatment Administration
The study treatment will be infused using an IV pump, as described in the Pharmacy Manual. The 
IV access will be kept open before and after the infusion with sufficient quantities of 0.9%◦saline 
or 5% dextrose in water to assure it remains patent. The time the infusion is 
initiated/adjusted/concluded, including any interruptions, will be documented in the electronic 
case report form (eCRF).
Study treatment infusions should be administered on the same day of each week to the extent that 
this is possible with a window of ± 3 days. Infusions must be separated by at least 3 days. At the 
study treatment infusion visits, all study procedures and assessments must be completed prior to 
initiation of the study treatment infusion (with the exception of PK samples collected during and 
postinfusion). When fasting is required for the preinfusion study procedures, participants may eat 
once all of the preinfusion testing and assessments are performed.
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7.1.1
Study Treatment Infusion Rate
The study medication is suggested to be infused in a step-wise approach as described below, as 
used in the IM025006 final clinical study report (CSR)34. The total dose of the study medication 
should not be infused in less than 60 minutes. The initial rate of the administration should not be 
any greater than the initial rate specified below.
Recommended blinded treatment stepped titration infusion rates:
The infusion rates may be decreased by the investigator based on the participant’s previous 
tolerance of the infusion, including any IRRs that may have occurred in the past. Consultation with 
the Medical Monitor is recommended if any other modification of these recommended infusion 
rates is being considered. In addition, the investigator may choose to pause the infusion depending 
on the participant’s clinical condition and history. If clinical signs and/or symptoms indicate an 
IRR, the infusion may be interrupted. If the infusion is interrupted for any reason, the infusion may 
be restarted at the discretion of the investigator.
Additional details on IRRs, including the management of IRRs, are provided in Section 9.2.9.
7.1.2
Premedication
Based on the discretion of the investigator, the participants may be administered IV or oral 
premedication approximately 
, respectively, before the start of the study 
treatment infusion. The investigator may choose to administer IV antihistamines 
(eg, diphenhydramine 
hydrochloride 50 mg, 
famotidine 20 mg) or oral antihistamines 
(eg, levocetirizine 
5 mg) 
and/or 
IV corticosteroids 
(eg, hydrocortisone 100 mg 
or 
methylprednisolone sodium succinate 125 mg).
Participants who receive antihistamine premedication should be advised that the premedication 
may be sedating and cautioned against driving or operating heavy machinery for at least 3 hours 
after administration. For sites participating in the 
, the pretreatment 
 
activities must be completed prior to the start of any premedication.
7.2
Method of Treatment Assignment
At the time of the screening visit, before any study-related procedures are performed, the 
investigative site will access the enrollment option of the IRT system for assignment of a subject
number. This number is assigned sequentially by the system and will be unique across all sites. If 
a potential participant is rescreened, a new identification number will be used.
Before the study is initiated, each user (at investigative sites) will receive log-in information and 
directions on how to access the IRT. Study treatment will be dispensed and administered at the 
study visits as listed in SOA (Section 2).
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Eligible participants will be centrally randomized using IRT to receive BMS-986263 or placebo 
according to a computer-generated block randomization scheme and in accordance with 
stratification criteria. Randomization to a treatment group will be assigned prior to dosing.
7.3
Blinding
7.3.1
Maintaining the Blind
Blinded treatment assignments will be managed using IRT. All infusion solutions (prepared by an 
unblinded pharmacist (or another appropriately delegated qualified individual) at the investigative 
site per the Pharmacy Manual) are matching in appearance, and will be supplied as shown in Table 
6. Investigative site staff, Sponsor and designee personnel, and participants and their families will 
remain blinded to treatment assignments.
The investigative site staff will include the following:

An unblinded pharmacist (or another appropriately delegated qualified individual), who will 
be responsible for preparing the infusion solutions and providing in a blinded manner to the 
study team, ensuring that the infusion solutions are protected from light as described in the 
Pharmacy Manual. The unblinded pharmacist (or another appropriately delegated qualified 
individual) must not reveal potentially unblinding information to the study team.
7.3.2
Circumstances for Unblinding
Blinding of treatment assignment is critical to the integrity of this clinical study. However, in the 
event of a medical emergency or pregnancy in an individual participant in which knowledge of the 
IP is critical to the participant’s management, the blind for that participant may be broken by the 
investigator. The participant’s safety takes priority over any other considerations in determining if 
a treatment assignment should be unblinded.
Before breaking the blind of an individual participant’s treatment, the investigator should 
determine that the unblinded information is necessary (ie, that it will alter the participant’s 
immediate medical management). In many cases, particularly when the emergency is clearly not 
related to the IP, the problem may be properly managed by assuming that the participant is 
receiving active product. It is highly desirable that the decision to unblind treatment assignment 
be discussed with the Medical Monitor, but the investigator always has ultimate authority for the 
decision to unblind. The actual TASK of unblinding can be delegated by the investigator to a 
designee assigned the task on the Delegation of Authority. The principal investigator or appointed 
designee should only call in for emergency unblinding AFTER the decision to unblind the 
participant has been documented.
In case of an emergency, the investigator has unrestricted access to randomization information via 
IRT and is capable of breaking the blind through the IRT system without prior approval from the 
Sponsor. After the unblinding, the investigator shall notify the Medical Monitor and/or Study 
Director. The method of unblinding for emergency purposes is described in the reference 
manual(s).
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In cases of accidental unblinding, contact the Medical Monitor and ensure every attempt is made 
to preserve the blind. Any request to unblind a participant for nonemergency purposes should be 
discussed with the Medical Monitor.
Designated staff of BMS Research & Development may be unblinded (obtain the randomization 
codes) prior to database lock to facilitate the bioanalytical analysis of PK samples 
 
. A bioanalytical scientist in the Bioanalytical Sciences department of BMS 
Research & Development (or a designee in the external central bioanalytical laboratory) will be 
unblinded to (may obtain) the randomized treatment assignments in order to minimize unnecessary 
bioanalytical analysis of samples.
The study will be unblinded once all participants have completed the Follow-up Week 4 visit and 
all data have been collected through that time point to facilitate analyses (Section 10.4.4).
7.4
Dosage Modification
No reductions or modifications of the assigned dose are allowed. If the infusion is interrupted for 
any reason, the infusion may be restarted at the discretion of the investigator. If an incomplete dose 
is administered at any visit, the participant will resume the assigned dose/administration schedule 
at the next visit. See Section 9.2.9 for management of IRRs.
7.5
Preparation/Handling/Storage/Accountability
The IP should be stored in a secure area according to local regulations. It is the responsibility of 
the investigator to ensure that IP is only dispensed to study participants. The IP must be dispensed 
only from official study sites by authorized personnel according to local regulations.
 
 
 
 
 
 
The product storage manager should ensure that the study treatment is stored in accordance with 
the environmental conditions (temperature, light, and humidity) as determined by BMS. If 
concerns regarding the quality or appearance of the study treatment arise, the study treatment 
should not be dispensed and BMS contacted immediately.
Please refer to the Pharmacy Manual for IP preparation.
Study treatment not supplied by BMS will be stored in accordance with the package insert.
The IP documentation (whether supplied by BMS or not) must be maintained that includes all 
processes required to ensure drug is accurately administered. This includes documentation of drug 
storage, administration, and, as applicable, storage temperatures, reconstitution, and use of 
required processes (eg, required diluents, administration sets).
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Further guidance and information for final disposition of unused study treatment are provided in
APPENDIX 2.
7.5.1
Retained Samples for Bioavailability/Bioequivalence/Biocomparability
Not applicable.
7.6
Treatment Compliance
Not applicable.
7.7
Concomitant Therapy
All medications taken from 4 weeks prior to the screening visit until the last study visit must be 
recorded on the eCRF. Prior medications are defined as medications taken within 4 weeks of the 
screening visit. Concomitant medications are defined as any medication taken after the first dose 
of study medication until the last study visit. Concomitant medications (prescription, OTC, or 
herbal) should be administered during the study only if they are prescribed for treatment of specific 
clinical events.
Participants taking vitamin E, SGLT2 inhibitors, GLP-1 receptor agonists, anti-obesity agents, or 
an approved NASH treatment at stable doses prior to screening (as specified in Section 6.1) should
maintain stable dosing throughout the entire study. In certain circumstances, dose modifications 
of concomitant medications may be made based upon the investigator’s clinical judgement, after 
consultation with the Medical Monitor.
SARS-CoV-2 vaccines approved for Emergency Use Authorization by local regulatory agency
that are not live attenuated are allowed during the study and should be handled in the same manner 
as other vaccines.
7.7.1
Prohibited and/or Restricted Treatments
Restrictions and prohibitions on prior and concomitant medications and/or treatments are as 
follows:
1) Prior exposure to BMS-986263 is prohibited.
2) NASH therapies with only accelerated approval from the US FDA or conditional approval 
from the European Medicines Agency are prohibited from the time of the liver biopsy to 
confirm eligibility until Week 12 or early termination.
3) OTC herbal supplements or multivitamins containing vitamin A (including Cod liver oil), or 
other medications that may contain vitamin A are prohibited after signing the ICF and 
throughout the study.
4) Other investigational agents. Any other investigational agent must be discontinued at least 
3 months prior to the liver biopsy used to confirm eligibility or within 12 weeks or 5 half-lives 
prior to the first dose of study treatment, whichever is longer.
5) Medical or surgical treatments for obesity should not be initiated while the participant is 
participating in the study.
6) Concomitant use of nintedanib is prohibited. Prior use of nintedanib is permitted but must be 
discontinued at least 3 days before the first dose of study treatment.
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7) Participation in other interventional clinical trials.
8) Use of anticoagulants is prohibited after signing the ICF and throughout the study, unless 
needed in the opinion of the investigator for safety reasons after Randomization.
 
 
 
 
7.8
Treatment After the End of the Study
At the end of the study, BMS will not continue to provide BMS-supplied study treatment to 
participants/investigators unless BMS chooses to extend the study. The investigator should ensure 
that each participant receives appropriate standard of care to treat the condition under study.
BMS reserves the right to terminate access to BMS-supplied study treatment if any of the following 
occur: a) the study is terminated due to safety concerns or other reasons; b) the development of 
BMS-986263 is terminated for any reason, including but not limited to lack of efficacy and/or not 
meeting the study objectives; c) the participant can obtain medication from a 
government-sponsored or private health program. In all cases BMS will follow local regulations.
8
DISCONTINUATION CRITERIA
8.1
Discontinuation from Study Treatment
Participants MUST discontinue IP (and non-IP at the discretion of the investigator) for any of the 
following reasons:

Participant’s request to stop study treatment. Participants who request to discontinue study 
treatment will remain in the study and must continue to be followed for protocol-specified 
follow-up procedures. The only exception to this is when a participant specifically withdraws 
consent for any further contact with him/her or persons previously authorized by participant to 
provide this information.

Any clinical AE, laboratory abnormality, or intercurrent illness which, in the opinion of the 
investigator, indicates that continued participation in the study is not in the best interest of the 
participant.

Termination of the study and/or program by BMS.

Loss of ability to freely provide consent through imprisonment or involuntarily incarceration 
for treatment of either a psychiatric or physical (eg, infectious disease) illness.

Symptoms, physical exam findings, or laboratory abnormalities consistent with 
 that, at the discretion of the investigator, cannot be explained by 
another cause.
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
For participants with normal Day 1 (Randomization) liver enzymes, total bilirubin, and INR, 
if there is new elevation of ALT or AST > 3 × ULN, repeat testing should be performed within 
48 hours to 72 hours. If elevation persists, then DILI discontinuation criteria will be applied 
and study treatment will be discontinued if any of the following occur:

ALT or AST > 8 × ULN

ALT or AST > 5 × ULN for more than 2 weeks

ALT or AST > 3 × ULN and (total bilirubin > 2 × ULN or INR > 1.5)

ALT or AST > 3 × ULN with the appearance of fatigue, nausea, vomiting, right upper 
quadrant pain or tenderness, fever, rash, and/or eosinophilia (> 5%)
Note: If necessary, a local laboratory may be used for repeat testing, and results should be 
promptly communicated to the site. The site should also promptly communicate results to 
BMS. Participants meeting the criteria above may have potential DILI, see Section 9.2.7
for reporting requirements.

For participants with elevated AST, ALT, or total bilirubin at Day 1 (Randomization), if there 
is a new elevation of ALT or AST > 2 × baseline, or total bilirubin > 1.5 × Day 1 total bilirubin 
(and to > ULN), repeat testing should be performed within 48 hours to 72 hours. If elevation 
persists, then study treatment will be discontinued if any of the following occur:

ALT or AST levels increase to > 5 × Day 1 (Randomization) measurement

ALT or AST levels increase > 2 × Day 1 (Randomization) measurements AND the 
increase is accompanied by a concomitant increase in total bilirubin to > 2 × Day 1 
bilirubin or the INR concomitantly increases by > 0.3

Appearance of fatigue, nausea, vomiting, right upper quadrant pain or tenderness, fever, 
rash, and/or eosinophilia (> 5%)
Note: If necessary, a local laboratory may be used for repeat testing, and results should be 
promptly communicated to the site. The site should also promptly communicate results to 
BMS. Participants meeting the criteria above may have potential DILI, see Section 9.2.7
for reporting requirements.

Clinical signs of hepatic decompensation, including ascites, variceal bleeding, hepatic 
encephalopathy, or spontaneous bacterial peritonitis.

Liver transplantation or planned liver transplant during the study.

HCC.

Any significant protocol violation (eg, demonstrated lack of treatment compliance). The 
violation should be discussed with the Medical Monitor prior to discontinuing the participant. 
Waivers for protocol violations will not be provided by the Sponsor or the Medical Monitor.

The participant becomes pregnant (study treatment must be discontinued immediately). In the 
case of pregnancy (Section 9.2.5), the investigator must notify the Medical Monitor/designee
of this event within 24 hours of awareness of the pregnancy. Follow-up information regarding 
the course of the pregnancy, including perinatal and neonatal outcome and, where applicable, 
offspring information must be reported on the Pregnancy Surveillance Form.

Emergency unblinding performed by principal investigator.
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See the SOA (Section 2) for details on the data to be collected at the time of treatment 
discontinuation and follow-up and any further evaluations that need to be completed.
Participants are not to be replaced. If study treatment is discontinued prior to the participant’s 
completion of the study, the reason for the discontinuation must be documented in the participant’s 
medical records and entered on the appropriate eCRF page. As indicated, appropriate follow-up 
and/or alternate medical care must be arranged for the participant.
Participants who discontinue study treatment before the Week 11 visit will have an ETT visit and 
will continue into the 24-week follow-up period. AEs and SAEs will be followed-up in line with 
Section 9.2.3 and APPENDIX 3.
8.1.1
Poststudy Treatment Study Follow-up
Participants who discontinue study treatment prior to last dose will have an ETT visit and will 
continue into the 24-week follow-up period. All participants who discontinue study treatment 
should comply with protocol-specified follow-up procedures as outlined in Table 2 and Table 3 of 
the SOA (Section 2). The only exception to these requirements is when a participant withdraws 
consent for all study procedures, including posttreatment study follow-up, or loses the ability to 
consent freely (ie, is imprisoned or involuntarily incarcerated for the treatment of either a 
psychiatric or physical illness).
8.2
Discontinuation from the Study
Participants who request to discontinue study treatment will remain in the study and must continue 
to be followed for protocol-specified follow-up procedures. See the SOA (Section 2, Table 2 and 
Table 3) for details on the data to be collected at the time of treatment discontinuation and follow-
up and any further evaluations that need to be completed. The only exception to this is when a 
participant specifically withdraws consent for any further contact with him/her or persons 
previously authorized by participant to provide this information.

Participants should notify the investigator of the decision to withdraw consent from future 
follow-up in writing, whenever possible.

The withdrawal of consent should be explained in detail in the medical records by the 
investigator and entered on the appropriate eCRF page.

In the event that vital status (whether the participant is alive or dead) is being measured, 
publicly available information should be used to determine vital status only as appropriately 
directed in accordance with local law.

If the participant withdraws consent for disclosure of future information, the Sponsor may 
retain and continue to use any data collected before such a withdrawal of consent.

Assessments for the end of treatment/EOS visit must be performed, provided that the 
participant has not withdrawn consent for these activities.

All required eCRF pages must be completed, including the date of, and explanation for, the 
withdrawal.

As indicated, appropriate follow-up and/or alternate medical care must be arranged for the 
participant.
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8.3
Lost to Follow-up

All reasonable efforts must be made to locate participants to determine and report their ongoing 
status. This includes follow-up with persons authorized by the participant.

Lost to follow-up is defined by the inability to reach the participant after a minimum of 
3 documented phone calls, faxes, or emails as well as lack of response by participant to 
one registered mail letter. All attempts should be documented in the participant’s medical 
records.

If it is determined that the participant has died, the site will use permissible local methods to 
obtain date and cause of death.

If investigator’s use of third-party representative to assist in the follow-up portion of the study 
has been included in the participant’s informed consent, then the investigator may use a 
Sponsor retained third-party representative to assist site staff with obtaining participant’s 
contact information or other public vital status data necessary to complete the follow-up 
portion of the study.

The site staff and representative will consult publicly available sources, such as public health 
registries and databases, in order to obtain updated contact information.

If after all attempts, the participant remains lost to follow-up, then the last known alive date as 
determined by the investigator should be reported and documented in the participant’s medical 
records.
9
STUDY ASSESSMENTS AND PROCEDURES

Study procedures and timing are summarized in the SOA (Section 2).

Protocol waivers or exemptions are not allowed.
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
All immediate safety concerns must be discussed with the Medical Monitor immediately upon 
occurrence or awareness, to determine if the participant should continue or discontinue 
treatment.

Adherence to the study design requirements, including those specified in the SOA, is essential 
and required for study conduct.

All screening evaluations must be completed and reviewed to confirm that potential 
participants meet all eligibility criteria before Randomization. The investigator will maintain 
a screening log to record details of all participants screened and to confirm eligibility or record 
reasons for screening failure, as applicable.

Procedures conducted as part of the participant’s routine clinical management (eg, blood count) 
and obtained before signing of informed consent may be utilized for screening or baseline 
purposes provided the procedure meets the protocol-defined criteria and has been performed 
within the timeframe defined in the SOA (Section 2).
9.1
Efficacy Assessments
Every effort must be made to ensure that the same evaluator(s) completes the assessment for each 
participant. If the evaluator(s) is unable to complete the evaluation, then a qualified individual with 
overlapping experience may perform the assessment. Documentation of who performed the 
assessment is to be recorded in source documents. Assessments should be performed at 
approximately the same time of day throughout the duration of the study. Day 1 (Randomization) 
assessments must be performed per protocol (standard of care assessments may not be used for 
baseline). Procedures not specified in the protocol that are part of standard of care may be 
performed if they do not interfere with study procedures; any data arising from such procedures 
are not to be reported in the eCRF.
 
 
 
9.1.2
Liver Biopsy Assessments
Efficacy endpoints will be assessed from liver biopsy samples. The following will be used as 
primary and secondary efficacy endpoint assessments:

Histological Assessments (Section 9.1.2.1)

NASH CRN Fibrosis Score

NAFLD Activity Score (NAS)

Modified Ishak Score

Morphometric Analysis of collagen proportionate area (CPA) (Section 9.1.2.2)
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Liver biopsy assessments (performed by central pathology) are used to screen for study eligibility 
and to evaluate efficacy. A historical biopsy may be acceptable to determine eligibility, if (1) the 
liver biopsy was performed within 12 months prior to screening, as defined in Section 6.1, and 
(2) adequate sample is available for assessment by central pathology. If a historical biopsy is 
unavailable, a liver biopsy will be performed during screening and will be assessed by central 
pathology reading to determine eligibility. A percutaneous liver biopsy is preferred to a 
transjugular biopsy. The investigator must consult with the Medical Monitor prior to performing 
a transjugular biopsy. Participants must have a liver biopsy demonstrating NASH CRN Fibrosis 
Score Stage 4 liver fibrosis (as determined by central pathology) and meeting all other liver 
biopsy-related inclusion and exclusion criteria as defined in Section 6.1 and Section 6.2, 
respectively, to be eligible. Liver biopsy assessments at screening may be shared with the sites. 
Any local incidental findings of potential clinical relevance identified at screening that are not 
directly associated with the objectives of the protocol should be evaluated and handled by the study 
investigator as per standard medical/clinical judgment. Participants who have a prolonged INR 
and/or lower platelet count may receive treatments to correct coagulation abnormalities and/or low 
platelet counts prior to liver biopsy based on investigator’s clinical judgment in order to reduce 
the risk of bleeding. It is the investigator’s responsibility to assess any potential risks that may be 
associated with the use of these agents (eg, transfusion of fresh/frozen plasma or platelets).37
Additional details on liver biopsy sample collection, preparation, and submission, as well as central 
pathology procedures are described in the Laboratory Manual.
Tissue from biopsies performed during the study will be collected for analysis. Histological 
assessments related to efficacy of BMS-986263 will be performed by central pathology reading. 
The on-treatment liver biopsy results will remain blinded to site personnel until at least 
post-database lock. If local pathology assessment is necessary, a portion of the sample should be 
submitted to a local pathologist following the standard procedure utilized by the study site. Any 
local incidental findings of potential clinical relevance identified at this post-baseline assessment 
that are not directly associated with the objectives of the protocol should be evaluated and handled 
by the study investigator as per standard medical/clinical judgment.
Liver tissue should be collected using a 16-gauge (or larger lumen) cutting needle (eg, Bard,
Microvasive, or TruCut) whenever possible. Use of suction needles (eg, Menghini, Jamshedi, or 
Klatskin) should be avoided because they may cause fragmentation of fibrotic specimens and 
impede the evaluation of fibrosis.38 Use of suction needles should be discussed with the Medical 
Monitor. At least 2 cm length of tissue should be obtained. Additional details on the acquisition, 
quality requirements, histological preparation, and shipping of histological samples are in the 
Laboratory Manual.
9.1.2.1
Histological Scoring
For associated endpoints, the NASH CRN system39 will be used to score the histologic samples by 
the central pathologist and results are reported as the NASH CRN Fibrosis Score and the NAS. The 
NASH CRN system is based on the concept that stage of fibrosis and necroinflammatory lesions 
should be evaluated separately; it assesses liver biopsies for degree of fibrosis (0 to 4), steatosis 
(0 to 3), lobular inflammation (0 to 3), and hepatocellular ballooning (0 to 2).
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NASH CRN Fibrosis
For the NASH CRN Fibrosis Score, fibrosis is staged on a 0 to 4 scale: 0 (none); 1 (perisinusoidal 
or periportal fibrosis); 2 (perisinusoidal and portal/periportal fibrosis); 3 (bridging fibrosis); 
4 (cirrhosis).
NAS
Steatosis, lobular inflammation, and ballooning scores are added together in an unweighted fashion 
to determine the NAS, which ranges from 0 to 8 (Table 7).
The NAS should not be considered a replacement for the diagnosis of NASH.
Table 7:
NAS Scoring System
Histology Variable
Grade
Score
Steatosis
< 5%
0
5 – 33%
1
> 33 – 66%
2
> 66%
3
Lobular Inflammationa
None
0
< 2
1
2 – 4
2
> 4
3
Ballooning
None
0
Few
1
Many
2
NAS = NAFLD Activity Score
a Foci per x 200 field
Modified Ishak Score
A modified Ishak scoring system40 will be used as a secondary endpoint to grade fibrosis in the
histologic samples. The Ishak system (0 to 6 scale) was originally developed to grade portal-based
liver fibrosis associated with viral hepatitis. The modified Ishak system has been adapted to grade 
central-based liver fibrosis associated with NASH, and it also uses a 0 to 6 scale:

0: No fibrosis

1: perisinusoidal or periportal fibrosis

2: perisinusoidal and portal/periportal fibrosis

3: bridging fibrosis with linkage of < 50% of vascular structures (portal and centrilobular)

4: bridging fibrosis with linkage of > 50% of vascular structures (portal and centrilobular)

5: early or incomplete cirrhosis
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
6: established or advanced cirrhosis
9.1.2.2
Morphometric Analysis of CPA 
 in Stained Tissue
Assessment of CPA is a method by which the amount (percentage) of collagen in stained tissue 
sections is analyzed using morphometric image analysis. This allows for a quantitative assessment 
of fibrosis. 
 in stained tissue sections is also analyzed using morphometric image 
analysis.
Analysis of CPA is included as a secondary endpoint 
 
.
 
 
 
 
 
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9.2
Adverse Events
The definitions of an AE or SAE can be found in APPENDIX 3.
AEs will be reported by the participant (or, when appropriate, by a caregiver, surrogate, or the 
participant’s legally authorized representative).
The investigator and any designees are responsible for detecting, documenting, and reporting 
events that meet the definition of an AE or SAE and remain responsible for following up AEs that 
are serious, considered related to the study treatment or the study, or that caused the participant to 
discontinue before completing the study.
Contacts for SAE reporting specified in APPENDIX 3.
9.2.1
Time Period and Frequency for Collecting AE and SAE Information
The collection of nonserious AE information should begin at initiation of study treatment until 
discharge, at the time points specified in the SOA (Section 2). Nonserious AE information should 
also be collected from the start of a placebo lead-in period or other observational period intended 
to establish a baseline status for the participants. The Reference Safety Information in 
Sections 5.6.1 and 5.6.2 of the IB7 should be used to determine the expectedness of SAEs for 
expedited reporting.
All SAEs must be collected from the time of signing the consent, including those thought to be 
associated with protocol-specified procedures and within 30 days of discontinuation of dosing (or 
participant’s participation in the study if the last scheduled visit occurs at a later time).

The investigator must report any SAE that occurs after this time period and that is believed to 
be related to study treatment or protocol-specified procedure (eg, a follow-up skin biopsy).

Medical occurrences that begin before the start of study treatment but after obtaining informed 
consent will be recorded on the appropriate section of the eCRF.

All SAEs will be recorded and reported to the Sponsor or designee within 24 hours, as 
indicated in APPENDIX 3.

The investigator will submit any updated SAE data to the Sponsor or designee within 24 hours 
of updated information being available.
Investigators are not obligated to actively seek AEs or SAEs from former study participants. 
However, if the investigator learns of any SAE, including a death, at any time after a participant 
has been discharged from the study, and he/she considers the event reasonably related to the study 
treatment or study participation, the investigator must promptly notify the Sponsor or designee.
The method of evaluating intensity and assessing causality of AEs and SAEs and the procedures 
for completing and reporting/transmitting SAE reports are provided in APPENDIX 3.
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9.2.2
Method of Detecting AEs and SAEs
AEs can be spontaneously reported or elicited during open-ended questioning, examination, or 
evaluation of a participant. (In order to prevent reporting bias, participants should not be 
questioned regarding the specific occurrence of one or more AEs.)
Participants will be queried for symptoms suggestive of vitamin A toxicity including but not 
limited to dry skin, vaginal dryness, cheilosis, gingivitis, muscle and joint pains, fatigue, mental 
dullness, and depression.
9.2.3
Follow-up of AEs and SAEs

Nonserious AEs should be followed to resolution, or stabilization, or reported as SAEs if they 
become serious (APPENDIX 3).

Follow-up is also required for nonserious AEs that cause interruption or discontinuation of 
study treatment and for those present at the EOS treatment as appropriate.

All identified nonserious AEs must be recorded and described on the nonserious AE page of 
the eCRF. Completion of supplemental eCRFs may be requested for AEs and/or laboratory 
abnormalities that are reported/identified during the course of the study.
After the initial AE/SAE report, the investigator is required to proactively follow each participant 
at subsequent visits/contacts. All SAEs and nonserious AEs of special interest (AESI) (defined in 
Section 9.2.8) will be followed until resolution, until the condition stabilizes, until the event is 
otherwise explained, or until the participant is lost to follow-up (as defined in Section 8.3).
Further information on follow-up procedures is given in APPENDIX 3.
9.2.4
Regulatory Reporting Requirements for SAEs

Prompt notification by the investigator to the Sponsor of SAEs is essential so that legal 
obligations and ethical responsibilities toward the safety of participants and the safety of a 
product under clinical investigation are met.

An investigator who receives an investigator safety report describing SAEs or other specific 
safety information (eg, summary or listing of SAEs) from the Sponsor will file it along with 
the IB and will notify the IRB/IEC, if appropriate according to local requirements.
Sponsor or designee will report AEs to regulatory authorities and IECs according to local 
applicable laws including European Directive 2001/20/EC and the following FDA CFRs:
21 CFR Part 312 and Part 320. A Suspected Unexpected Serious Adverse Reaction is a subset of 
SAEs and will be reported to the appropriate regulatory authorities and investigators following 
local and global guidelines and requirements.
9.2.5
Pregnancy
If, following initiation of the study treatment, it is subsequently discovered that a participant is 
pregnant or may have been pregnant at the time of study exposure, including during at least 
5 half-lives (20 days) after study product administration, the study treatment must be discontinued 
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immediately and the investigator must immediately notify the Sponsor or designee of this event 
and complete and forward a Pregnancy Surveillance Form to the Sponsor or designee within 
24 hours of awareness of the event and in accordance with SAE reporting procedures described in 
APPENDIX 3.
The investigator must also notify the Medical Monitor or designee of this event within 24 hours 
of awareness of the pregnancy.
Protocol-required procedures for study discontinuation and follow-up must be performed on the 
participant.
Follow-up information regarding the course of the pregnancy, including perinatal and neonatal 
outcome and, where applicable, offspring information must be reported on the Pregnancy 
Surveillance Form.
Any pregnancy that occurs in a female partner of a male study participant should be reported to 
the Sponsor or designee. In order for Sponsor or designee to collect any pregnancy surveillance 
information from the female partner, the female partner(s) must sign an ICF for disclosure of this 
information. Information on this pregnancy will be collected on the Pregnancy Surveillance Form.
9.2.6
Laboratory Test Result Abnormalities
The following laboratory test result abnormalities should be captured on the AE eCRF page:

Any laboratory test result that is clinically significant or meets the definition of an AE or SAE

Any laboratory test result abnormality that required the participant to have study treatment 
discontinued or interrupted

Any laboratory test result abnormality that required the participant to receive specific 
corrective therapy
If a laboratory test result meets the definition of an AE or SAE, the laboratory test result should be 
reported as an AE or SAE and submitted to the Sponsor or designee, as specified in APPENDIX 3.
It is expected that wherever possible, the clinical rather than laboratory term would be used by the 
reporting investigator (eg, anemia versus low hemoglobin value).
9.2.7
Potential DILI
Wherever possible, timely confirmation of initial liver-related laboratory abnormalities should 
occur prior to the reporting of a potential DILI event. The definition of potential DILI, as well as 
study treatment discontinuation criteria, are provided in Section 8. All occurrences of potential 
DILIs, meeting the defined criteria, must be reported as SAEs (see APPENDIX 3 for reporting 
details). Participants who meet criteria for potential DILI should have relevant laboratory testing 
(eg, ALT, AST, total bilirubin, and INR) repeated at least weekly until abnormalities have resolved 
or returned to baseline. Tests should be repeated within 3 days; then within every 3 days thereafter 
until reversal is noted; and thereafter, every week until normalization (or return to baseline). The 
investigator should make every effort to determine if any other cause for the liver test abnormalities 
is present.
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9.2.8
Adverse Events of Special Interest
All AEs and SAEs that arise in the study will be reported and investigated. However, because of 
the characteristics of the disease under study and BMS-986263 in particular, some AEs are 
considered AESI. AESI may be serious or nonserious. Such events may require further 
investigation to better characterize and understand them. In the BMS-986263 clinical development 
program, bone fractures, IRRs, and anaphylaxis have been identified as potential AESI; however, 
there has been no definitive assessment of the causal relationship between these events and 
treatment with BMS-986263.
9.2.9
Infusion-related Reactions
An IRR is defined as: Any AE that occurs after the start and within 24 hours after the start of 
infusion of the IP and meets at least 1 of the following criteria:

Considered to be at least possibly related to the IP.

Resulted in interruption of infusion.

Resulted in change of the infusion rate.

Was considered by the investigator to be an IRR.
Note: Local reactions related to the infusion site are not considered IRRs.
In previous clinical studies of BMS-986263, in participants who experienced IRRs, back pain was 
the most common symptom reported for these IRRs. Other signs and symptoms less commonly 
associated with IRRs included, but were not limited to the following: hot or warm sensation, 
flushing, throat constriction, shortness of breath, chest tightness, tachypnea, tachycardia, 
hypertension, urticaria, pruritus, and/or erythema. These reactions routinely had a rapid onset 
within 
 after start of the infusion and were generally short lasting with most 
resolving within 
 of their occurrence.
The details of IP administration and infusion rate for this study are provided in Section 7.1.
If a participant experiences an IRR, temporary interruption of the infusion and/or reduction of the 
infusion rate may lead to improvement of signs and symptoms. The infusion may be restarted, at 
the discretion of the investigator, after signs and symptoms of IRRs have abated.
Medications, emergency equipment, and trained personnel able to treat immediate or delayed IRRs 
should be available for immediate access at the clinical site(s).
9.2.10
Other Safety Considerations
Any significant worsening noted during interim or final physical examinations, ECG, x-ray 
filming, or any other potential safety assessment required or not required by protocol should also 
be recorded as a nonserious or serious AE, as appropriate, and reported accordingly.
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9.3
Overdose
For this study, any dose of BMS-986263 for injection > 10% above the assigned dose (eg, 
of study drug infusion) within a 24-hour time period will be considered an overdose. 
See APPENDIX 3 for AE/SAE reporting requirements for overdose.
In the event of an overdose, the investigator should do the following:
1) Contact the Medical Monitor immediately.
2) Closely monitor the participant for AEs/SAEs and laboratory abnormalities until BMS-986263 
can no longer be detected systemically (at least 20 days).
3) Obtain a plasma sample for PK analysis within 2 days from the date of the last dose of study 
treatment if requested by the Medical Monitor (on a case-by-case basis).
4) Document the quantity of the excess dose as well as the duration of the overdosing in the eCRF.
9.4
Safety
Planned time points for all safety assessments are listed in the SOA (Section 2). All urgent safety 
concerns must be discussed with the Sponsor immediately upon occurrence or awareness to 
determine if the participant should continue or discontinue treatment.
The safety and tolerability of BMS-986263 will be assessed by evaluation of the incidence of all 
AEs (including AESI) and SAEs, laboratory results (including assessment of potential DILI), vital 
signs, physical examinations, ECG monitoring, 
 IRR monitoring, and 
change in BMD.
The participants must not have documented bone abnormalities at baseline as defined in the 
exclusion criteria (Section 6.2). DXA scan will be used to assess BMD.
9.4.1
Clinical Safety Laboratory Assessments
Investigators must document their review of each laboratory safety report. A central laboratory 
will perform the analyses and will provide reference ranges for these tests, except as noted below.
Hematology, serum chemistry, and urinalysis assessments are listed in Table 8.
Table 8:
Hematology, Chemistry, and Urinalysis Assessments
Hematology

CBC with differential

PT

PTT

INR 

RBC

WBC (absolute)

Hemoglobin

Hematocrit

MCV

MCH concentration

Red cell distribution width

Platelet count
Blood Chemistry

AST

ALT

Total bilirubin

Creatine kinase

BUN

Uric acid

Sodium

Potassium

Chloride
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Table 8:
Hematology, Chemistry, and Urinalysis Assessments

Direct bilirubin

ALP

LDH

GGT

Creatinine

Glucose

PTH

Total protein

Albumin 

Carbon dioxide

Calcium

Phosphorus

GFRa
Urinalysis

pH

Specific gravity

Protein (quantitative)

Albumin (quantitative)

Glucose

Ketones

Leukocyte esterase

Nitrite

Creatinine

Microscopic examination (only 
to follow-up abnormal findings)

Urine 
protein, 
total 
(quantitative) for urine protein 
to creatinine ratio

Urinary albumin
to urinary 
creatinine ratio
Metabolic Panel (≥10 hours fast)

Lipid panel (triglycerides, total 
cholesterol, LDL, HDL)
Other Analyses

FSHb

AFP 

HbA1c

Insulin 

Pregnancy test (WOCBP only; 
can be performed locally)

Serology/viral 
load
(APPENDIX 7)

HIV testing must be performed 
where mandated by local 
requirements
(APPENDIX 8),
and 
the 
test will be performed at a local 
lab
AFP = alpha-fetoprotein; 
ALP = alkaline 
phosphatase; 
ALT = alanine 
aminotransferase; 
AST = aspartate 
aminotransferase; BUN = blood urea nitrogen; CBC = complete blood count; FSH = follicle-stimulating hormone; 
GFR = glomerular 
filtration 
rate;
GGT = gamma-glutamyl 
transferase; 
HbA1c = hemoglobina A1c; 
HDL = high-density lipoprotein; HIV = human immunodeficiency virus; INR = international normalized ratio; 
LDH = lactate dehydrogenase; LDL = low-density lipoprotein; MCH = mean corpuscular hemoglobin; MCV = mean 
corpuscular volume; PT = prothrombin time; PTH = parathyroid hormone; PTT = partial thromboplastin time; RBC 
= red blood cell; WBC = white blood cell; WOCBP = women of childbearing potential
a Estimated GFR, as calculated by the Modification of Diet in Renal Disease equation 56
b FSH performed only in female participants < 55 years to confirm menopause (APPENDIX 4)
9.4.2
Vital Signs
Refer to SOA in Section 2 for timing of vital signs assessments.
9.4.3
Physical Examinations
Schedules for physical examinations are provided in the SOA (Section 2). Complete and/or 
abbreviated physical examinations may be performed by a Doctor of Medicine (MD) or equivalent, 
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or someone who is authorized to perform the examinations by training and has been delegated this 
task by the principal investigator.
A physical exam for signs of 
, including skin and oral mucosa changes and 
hepatomegaly, will be performed at visits listed in the SOA (Section 2).
A full examination will include general appearance, skin, head, eyes, ears, nose, throat, neck, 
thyroid, chest/lungs, heart, abdomen, lymph nodes, and extremities. If the screening full physical 
examination is performed within 24 hours prior to dosing on Day 1, then a single exam may count 
as both the screening and Day 1 (abbreviated) physical examination.
Abbreviated physical exams will include an abdominal exam, assessments of ascites and hepatic 
encephalopathy, and symptom-focused assessments. An abbreviated examination may note any 
changes in the participant’s condition (body systems) since the last assessment and does not 
preclude examination of any of the other body systems as clinically indicated. Every effort should 
be made to ensure the same evaluator will complete the examination for each participant at all 
visits throughout the study. Documentation of who performed the examination is to be recorded in 
source notes.
9.4.4
Electrocardiograms
Refer to SOA in Section 2 for timing of ECGs.
9.4.5
Imaging Safety Assessment – DXA Scan
DXA scan (hip [including femoral neck] and lumbar spine) will be performed at the time points 
indicated in the SOA (Section 2).
Image acquisition guidelines and submission processes will be outlined in the site imaging manual, 
to be provided by the central imaging vendor. The sites will be trained and qualified in imaging 
procedures prior to scanning the first study participant. All images will be submitted to the central 
imaging vendor for assessment of the BMD.
Adequacy of DXA scan must be determined by the central imaging vendor prior to Randomization. 
The site will be informed of quality issues or the need to repeat scanning from the central imaging 
vendor. Note that at least 1 of the requested anatomic sites (hip [including femoral neck] or lumbar 
spine) must be evaluable for participants to be eligible for the study (See Section 6.2).
Any local incidental imaging findings of potential clinical relevance that are not directly associated 
with the objectives of the protocol should be evaluated and handled by the study investigator as 
per standard medical/clinical judgment.
 
 
 
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9.5
PK 
Sampling Schedule for BMS-986263
Blood for PK samples will be drawn according to the sampling schedule shown in 
 Blood 
for PK samples drawn on dosing days is strongly recommended to be taken from the contralateral 
arm to the IV drug administration. Information on the collecting, processing, and submission of 
samples to the central laboratory are in the reference manual(s).
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10
STATISTICAL CONSIDERATIONS
10.1
Sample Size Determination
In this study, approximately 270 participants will be randomized via IRT in a 1:1:1 ratio to receive 
45 mg BMS-986263 QW, 90 mg BMS-986263 QW, or placebo QW by IV infusion in a 
double-blind manner. The primary endpoint is the proportion of participants with ≥1 stage 
improvement in liver fibrosis (NASH CRN Fibrosis Score) as determined by liver biopsy after 
12 weeks of treatment.
Assuming a Chi-Square test with an α = 0.05 and expected response rates for BMS-986263 90 mg,
BMS-986263 45 mg, and placebo of 45%, 40%, and 20%, respectively, approximately 
85 evaluable participants per treatment group in this study will have at least 80% power to detect 
superiority over placebo versus each dose, assuming a minimum difference of 20% from placebo. 
Accounting for a 6% dropout rate, approximately 90 participants will be randomized per treatment 
group.
10.2
Populations for Analyses
The following populations are defined for analysis purposes:
Population
Description
Enrolled 
All participants who sign informed consent.
Randomized
All participants who are randomized to a treatment, analyzed as 
per randomized treatment. 
Modified intent-to-treat 
(mITT)
All participants who are randomized to a treatment and receive at 
least 1 dose of study medication analyzed as per randomized 
treatment. All primary efficacy analyses will be conducted using 
this population. 
PK
All participants who receive at least 1 dose of BMS-986263 and 
have any available concentration-time data.
Safety (As-treated) 
All randomized participants who receive at least 1 dose of study 
treatment, analyzed according to the treatment actually received. 
All safety analyses will be conducted using this population. 
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10.3
Endpoints
10.3.1
Primary Endpoint

Proportion of participants who achieve ≥ 1 stage improvement in liver fibrosis (NASH CRN
Fibrosis Score), as determined by liver biopsy after 12 weeks of treatment
10.3.2
Secondary Endpoints

Proportion of participants with ≥1 stage improvement in liver fibrosis (NASH CRN Fibrosis 
Score), with no worsening of NASH after 12 weeks of treatment (worsening of NASH is 
defined as an increase of the NAS by ≥ 1 point)

Proportion of participants with ≥2 stage improvement in liver fibrosis (NASH CRN Fibrosis 
Score) after 12 weeks of treatment

Proportion of participants with ≥1 stage improvement in liver fibrosis (modified Ishak score) 
after 12 weeks of treatment

Proportion of participants with ≥2 stage improvement in liver fibrosis (modified Ishak score) 
after 12 weeks of treatment

Change from baseline in CPA after 12 weeks of treatment

Incidences of SAEs, AEs, clinical laboratory values, vital signs, physical examination findings, 
and ECGs

Change from baseline in BMD, as measured by DXA scan, at Follow-up Week 24

Plasma concentrations of siRNA, DPD, HEDC, and S104 (components of BMS-986263 for 
injection)
 
 
 
 
 
 
 
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10.4
Statistical Analyses
The statistical analysis plan (SAP) will be finalized prior to the first unblinding event of the study 
and will provide detailed specifications of the analysis of all efficacy endpoints and safety and will 
also describe the populations used for analyses and procedures for accounting for missing, unused, 
and spurious data.
This section provides a summary of planned statistical analyses.
10.4.1
Efficacy Analyses
Efficacy analyses will be performed using the mITT population. Participants who discontinue early 
and do not have an ETT liver biopsy or otherwise have the result from the liver biopsy missing 
will be considered a “nonresponder” for the evaluation of the primary endpoint and other binary 
endpoints based on liver biopsy.
Primary Endpoint: To evaluate the effect of BMS-986263 (90 mg QW and 45 mg QW) on NASH 
CRN Fibrosis Stage at Week 12, a 95.0% confidence interval (CI) of response rate for treatment 
versus placebo will be used to estimate the difference between the proportions of participants with 
≥1 stage improvement in fibrosis on liver biopsy. Additionally, the odds ratio will be used to 
estimate improvement of treatment as compared with placebo for the proportion of participants 
with > 1 stage improvement in fibrosis on biopsy at Week 12. A logistic regression will be 
performed with platelet count as continuous independent covariate and stratified by the 
Randomization strata with a Z-test statistic at a two-sided significance level of α◦=◦0.05 to assess 
the difference in distribution of response rate separately between each BMS-986263 treatment 
group and placebo. To control for the family-wise (two-sided) Type◦1◦error rate of α◦=◦0.05, the 
statistical tests will be performed in the following hierarchical order: 1) BMS-986263 90◦mg 
versus placebo, and 2) BMS-986263 45◦mg versus placebo. If the first comparison is not 
statistically significant, then the second comparison will be treated as descriptive in nature.
Secondary 
Endpoints: No adjustment will be made for multiplicity for 
secondary 
 endpoints. Secondary 
 endpoints will be analyzed in a 
similar method as the primary endpoint unless otherwise specified in the SAP.
Selected continuous endpoints will be characterized using descriptive statistics and may be 
analyzed by analysis of covariance methods and/or by a mixed model for repeated measurements. 
Treatment differences at prespecified time points will be estimated using least squares means. Full 
details regarding this model and covariance structure will be provided in the SAP.
Categorical endpoints will be summarized using counts and percentages and when appropriate,
may be analyzed using categorical analysis methods.
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The stratified log-rank test and Kaplan-Meier estimate may be used to analyze time-to-event 
endpoints and will be specified in the SAP.
Subgroup analyses may be performed as specified in the SAP.
10.4.2
Safety Analyses
Safety analyses will be performed using the safety population. For analysis, all treatment-emergent 
AEs recorded that occur during the conduct of the study will be listed and summarized by system 
organ class, preferred term, and treatment. Vital signs and clinical laboratory test results will be 
listed and summarized by treatment. ECG readings will be evaluated by the investigator and 
abnormalities, if present, will be summarized and listed.
Safety assessments include incidences of AEs, SAEs, and AESI (Section 9.2), AEs leading to 
discontinuation, and death, as well as marked abnormalities in clinical laboratory tests, vital sign 
measurements, ECGs, physical examinations, and change in BMD collected by DXA scan from 
baseline to Follow-up Week 24. Furthermore, the occurrence of IRRs will be analyzed as a 
function of the infusion rates and compared between treatment groups.
 
 
 
10.4.3.1
PK
PK
 of BMS-986263 will be analyzed based on the time points indicated in
 Plasma concentrations of the components of the LNP, such as DPD, S104, and HEDC
will also be measured.
PK evaluation is a secondary endpoint. Plasma concentrations of siRNA, DPD, HEDC, and S104 
(components of BMS-986263 for injection) will be listed and summarized descriptively by dose, 
day, and time.
Analysis of PK and exposure-response relationships of BMS-986263 will be conducted using a 
population approach as appropriate and reported separately from the CSR.
 
 
 
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10.4.4
Week 12 Analyses
After all participants have either completed the Follow-up Week 4 visit or have discontinued the 
study prior to the Follow-up Week 4 visit, the study will be unblinded and the primary analysis for 
the study will be conducted.
10.4.5
Interim Analysis
Two interim analyses may be performed after approximately 30% and 50% of participants have 
either completed the Follow-up Week 4 visit or have discontinued the study prior to the Follow-
up Week 4 visit. 
The purpose of the 30% interim analyses will be to assess futility. The DMC will review the 
available data to make recommendation on the following options: 

Continue the study as planned

Terminate the study for futility
The futility decision criteria and the review process by the DMC will be specified in the DMC 
Charter and the DMC SAP.
The purpose of the 50% interim analysis will be to help in early planning for accelerating further 
clinical development of the compound. No formal test of statistical significance is planned. Results 
will be descriptive and based on the estimation of effect size and associated CIs. Thus, no 
adjustments to overall Type I error will be made.
The interim analysis results on both occasions will be reviewed by the independent DMC; and the 
Sponsor’s Internal Review Committee (IRC) if needed. The blinding to investigators and the study 
team will be maintained until the end of the study.
Within the DMC Charter, for each interim analysis, the Sponsor will specify:

Conditions under which interim results could be shared with select individuals within BMS to 
help in early planning of clinical development of the compound

Steps taken to ensure the blinding of the other BMS personnel (that are not unblinded) and 
investigators to interim results

Statistical summaries that will be prepared for review
Details of the interim analyses will be described in the DMC SAP and DMC Charter, which will 
be revised and finalized prior to the DMC meeting.
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11
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16
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26
Marini JC, Reich A, Smith SM. Osteogenesis imperfecta due to mutations in non-collagenous 
genes: lessons in the biology of bone formation. Curr Opin Pediatr 2014;26(4):500-7.
27
A 39-week (40 doses) intravenous toxicity study of ND-L02-s0201 in cynomolgus monkeys, 
with a 6-week recovery period (Insymbiosis Study No. 2500/Test Facility Study No. 5001795) 
(Study 5001795). Insymbiosis; 2018. Document Control No. 930125400.
 
29
A phase 1, randomized, double-blind, placebo-controlled, escalating single dose study to 
evaluate the safety, tolerability and pharmacokinetics of ND-L02-s0201 injection, a vitamin 
A-coupled lipid nanoparticle containing siRNA against HSP47, in healthy normal subjects 
(Study ND-L02-s0201-001); Clinical Study Report. Nitto Denko Corporation; 2017. 
Document Control No. 930113265.
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Phase 1, open-label, randomized-sequence, single-crossover, bridging study to evaluate the 
single-dose pharmacokinetics, safety, and tolerability of two ND-L02-s0201 formulations, 
frozen versus lyophilized, administered by intravenous infusion to healthy male and female 
subjects (Study ND-L02-s0201-004); Clinical Study Report. Nitto Denko Corporation; 2017. 
Document Control No. 930115313.
31
A randomized, placebo-controlled, double-blind, multiple dose study to evaluate the safety, 
tolerability, pharmacokinetics and pharmacodynamics of BMS-986263 in healthy participants 
(Study IM025001); Clinical Study Report. Bristol-Myers Squibb Company; 2018. Document 
Control No. 930132863.
32
A phase 1b/2, open label, randomized, repeat-dose, dose-escalation study to evaluate the 
safety, tolerability, biological activity, and pharmacokinetics of ND-L02-s0201 injection, a 
vitamin A-coupled lipid nanoparticle containing siRNA against HSP47, in subjects with 
moderate to extensive hepatic fibrosis (METAVIR F3-4) (Study ND-L02-s0201-002); Clinical 
Study Report. Nitto Denko Corporation; 2017. Document Control No. 930113585.
33
A phase 1, repeat dose study to evaluate the safety, tolerability, biological activity, and 
pharmacokinetics of ND-L02-s0201 injection in Japanese subjects with advanced hepatic 
fibrosis (METAVIR F3-4) (Study ND-L02-s0201-003); Clinical Study Report. Nitto Denko 
Corporation; 2017. Document Control No. Pending.
34
A randomized, double-blind, placebo-controlled, 2-part, parallel group, multiple dose Phase 2 
study to evaluate the efficacy and safety of BMS-986263 in adults with advanced hepatic 
fibrosis from hepatitis C who have achieved sustained virologic response (Study IM025006). 
Bristol-Myers Squibb Company; 2020. Document Control No. 930152959.
35
American College of Radiology. CT/MRI LI-RADS® v2018 CORE. 2018. Accessed 05 
September 2019.
36
Garcia-Tsao G, Sanyal AJ, Grace ND, et al. Prevention and management of gastroesophageal 
varices and variceal hemorrhage in cirrhosis. Hepatology 2007;46(3):922-38.
37
Laubham M, Kallwitz E. Coagulation in chronic liver disease and the use of prothrombin 
complex concentrate for an emergent procedure: a case report and review of literature. J 
Community Hosp Intern Med Perspect 2018;8(3):138-41.
38
Bedossa P. Diagnosis of non-alcoholic fatty liver disease/non-alcoholic steatohepatitis: Why 
liver biopsy is essential. Liver Int 2018;38 Suppl 1:64-6.
39
Kleiner DE, Brunt EM, Van Natta M, et al. Design and validation of a histological scoring 
system for nonalcoholic fatty liver disease. Hepatology 2005;41(6):1313-21.
40
Anstee QM, Neuschwander-Tetri BA, Wong VW, et al. Cenicriviroc for the treatment of liver 
fibrosis in adults with nonalcoholic steatohepatitis: AURORA Phase 3 study design. Contemp 
Clin Trials 2020;89:105922.
 
 
 
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Levey AS, Coresh J, Greene T, et al. Using standardized serum creatinine values in the 
modification of diet in renal disease study equation for estimating glomerular filtration rate. 
Ann Intern Med 2006;145(4):247-54.
 
 
 
 
 
 
 
 
 
 
 
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APPENDICES
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APPENDIX 1
ABBREVIATIONS AND TRADEMARKS
Term
Definition
AE
adverse event
AESI
adverse events of special interest
AFP 
alpha-fetoprotein
ALP
alkaline phosphatase
ALT
alanine aminotransferase
APRI
AST-to-platelet ratio index
AST
aspartate aminotransferase
AUC
area under the plasma drug concentration-time curve
AUC(INF)
area under the concentration-time curves from zero to infinity
AUC(0-T)
area under the concentration-time curves from time zero to the time of 
the last quantifiable concentration
BIW
twice per week
BMD
bone mineral density
BMI
body mass index 
BMS
Bristol-Myers Squibb
BUN 
blood urea nitrogen
C3M
matrix metalloproteinase-derived collagen Type III-specific 
neoepitope peptide
CBC
complete blood count
CFR
Code of Federal Regulations
CI
confidence interval
CL
total plasma clearance 
Cmax
maximum observed plasma concentration
CMH
Cochran-Mantel-Haenszel
COVID-19
coronavirus disease 2019
CPA
collagen proportionate area
CRN
Clinical Research Network
CSR
clinical study report
CT
computed tomography
DILI
drug-induced liver injury
DMC
Data Monitoring Committee
DMN
dimethylnitrosamine 
DNA
deoxyribonucleic acid
DPD
di-retinamide-PEG-di-retinamide
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DXA 
dual-energy X-ray absorptiometry
ECG
electrocardiogram
eCRF
electronic case report form
ELF
enhanced liver fibrosis
ePRO
electronic patient-reported outcomes
EOS
End of Study
EST
Early Study Termination
ETT
Early Treatment Termination
FDA
Food and Drug Administration
FIB-4
Fibrosis-4
FSH
follicle-stimulating hormone
GFR
glomerular filtration rate
GGT 
gamma-glutamyl transferase
GLP-1
glucagon-like peptide-1
HbA1c
hemoglobin A1c
HbcAb 
hepatitis B core antibody
HbsAb 
hepatitis B surface antibody
HbsAg
hepatitis B surface antigen
HBV
hepatitis B virus
HCC
hepatocellular carcinoma 
HCV
hepatitis C virus
HDL 
high-density lipoprotein
HEDC
(Bis[2-(tetradecanoyloxy)ethyl] carbamoylmethyl)-(2-
hydroxyethyl)dimethylazanium bromide
HI
hepatic impairment
HIV
human immunodeficiency virus
HSC
hepatic stellate cell
HSP47
heat shock protein 47
IB
Investigator’s Brochure
ICF
informed consent form
IEC
Independent Ethics Committee
IMP
investigational medicinal product 
INR
international normalized ratio
IP
investigational product
IPRC
Independent Pathology Review Committee
IRB
Institutional Review Board
IRR
infusion-related reaction
IRT
interactive response technology
IV
intravenous
LAM
lactational amenorrhea method
LDH
lactate dehydrogenase
LDL 
low-density lipoprotein
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LNP
lipid nanoparticle
MCH
mean corpuscular hemoglobin;
MCV
mean corpuscular volume
MELD
Model for End-stage Liver Disease
mITT
modified intent-to-treat
MRE 
magnetic resonance elastography
MRI
magnetic resonance imaging 
mRNA
messenger ribonucleic acid
NAFLD
nonalcoholic fatty liver disease
NAS
NAFLD Activity Score
NASH
nonalcoholic steatohepatitis
NOAEL
no-observed-adverse-effect level
OTC
over-the-counter
PK
pharmacokinetics
PRO-C3
N-terminal Type III collagen propeptide
PT 
prothrombin time
PTH
parathyroid hormone
PTT 
partial thromboplastin time
QW
once every week 
RBC
red blood cell
RNA
ribonucleic acid
RNAi
ribonucleic acid interference
RT-PCR
reverse transcription - polymerase chain reaction
SAE
serious adverse event
SAP
statistical analysis plan
SARS-CoV-2
severe acute respiratory syndrome coronavirus 2
SGLT2
sodium glucose cotransporter 2
siRNA
small interfering ribonucleic acid
SOA
Schedule of Activities
SVR
sustained virologic response
TEAE
treatment emergent adverse event
ULN
upper limit of normal
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WBC
white blood cell
WOCBP
women of childbearing potential
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APPENDIX 2
STUDY GOVERNANCE CONSIDERATIONS
The term ‘Participant’ is used in the protocol to refer to a person who has consented to participate 
in the clinical research study. The term ‘Subject’ used in the electronic case report form (eCRF) is 
intended to refer to a person (Participant) who has consented to participate in the clinical research 
study.
REGULATORY AND ETHICAL CONSIDERATIONS
GOOD CLINICAL PRACTICE
This study will be conducted in accordance with:

Good Clinical Practice (GCP),

As defined by the International Council for Harmonisation (ICH)

In accordance with the ethical principles underlying European Union Directive 2001/20/EC

US Code of Federal Regulations, Title 21, Part 50 (21CFR50)

Applicable local requirements.
The study will be conducted in compliance with the protocol. The protocol and any amendments 
and the participant informed consent will receive approval/favorable opinion by Institutional 
Review Board/Independent Ethics Committee (IRB/IEC), and regulatory authorities according to 
applicable local regulations prior to initiation of the study.
All potential serious breaches must be reported to the Sponsor or designee immediately. A 
potential serious breach is defined as a Quality Issue (eg, protocol deviation, etc) that is likely to 
affect, to a significant degree one or more of the following: (1) the physical, safety or mental 
integrity of one or more subjects/participants; (2) the scientific value of the trial (eg, reliability and 
robustness of generated data). Items (1) or (2) can be associated with either GCP Regulation(s) or 
Trial protocol(s).
Personnel involved in conducting this study will be qualified by education, training, and 
experience to perform their respective tasks.
This study will not use the services of study personnel where sanctions have been invoked or where 
there has been scientific misconduct or fraud (eg, loss of medical licensure, debarment).
INSTITUTIONAL REVIEW BOARD/INDEPENDENT ETHICS COMMITTEE
Before study initiation, the investigator must have written and dated approval/favorable opinion 
from the IRB/IEC for the protocol, consent form, participant recruitment materials 
(eg, advertisements), and any other written information to be provided to subjects/participants. The 
investigator or BMS should also provide the IRB/IEC with a copy of the IB or product labeling 
information to be provided to subjects/participants and any updates.
The investigator, Sponsor or designee should provide the IRB/IEC with reports, updates and other 
information (eg, expedited safety reports, amendments, and administrative letters) according to 
regulatory requirements or institution procedures.
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COMPLIANCE WITH THE PROTOCOL AND PROTOCOL REVISIONS
The investigator should not implement any deviation or change to the protocol without prior 
review and documented approval/favorable opinion of an amendment from the IRB/IEC (and if 
applicable, also by local Health Authority) except where necessary to eliminate an immediate 
hazard(s) to study subjects/participants.
If a deviation or change to a protocol is implemented to eliminate an immediate hazard(s) prior to 
obtaining relevant approval/favorable opinion(s) the deviation or change will be submitted, as soon 
as possible to:

IRB/IEC for

Regulatory Authority(ies), if applicable by local regulations (per national requirements)
Documentation of approval/favorable opinion signed by the chairperson or designee of the 
IRB(s)/IEC(s) and if applicable, also by local Health Authority must be sent to BMS.
If an amendment substantially alters the study design or increases the potential risk to the 
participant: (1) the consent form must be revised and submitted to the IRB(s)/IEC(s) for review 
and approval/favorable opinion; (2) the revised form must be used to obtain consent from 
subjects/participants currently enrolled in the study if they are affected by the amendment; and 
(3) the new form must be used to obtain consent from new subjects/participants prior to 
enrollment.
If the revision is done via an administrative letter, investigators must inform their IRB(s)/IEC(s).
FINANCIAL DISCLOSURE
Investigators and subinvestigators will provide the Sponsor with sufficient, accurate financial 
information in accordance with local regulations to allow the Sponsor to submit complete and 
accurate financial certification or disclosure statements to the appropriate Health Authorities. 
Investigators are responsible for providing information on financial interests during the course of 
the study and for 1 year after completion of the study.
INFORMED CONSENT PROCESS
Investigators must ensure that subjects/participants are clearly and fully informed about the 
purpose, potential risks, and other critical issues regarding clinical studies in which they volunteer 
to participate.
In situations where consent cannot be given to subjects/participants, their legally acceptable 
representatives (as per country guidelines) are clearly and fully informed about the purpose, 
potential risks, and other critical issues regarding clinical studies in which the participant 
volunteers to participate.
Sponsor or designee will provide the investigator with an appropriate (ie, Global or Local) sample 
informed consent form (ICF) which will include all elements required by ICH, GCP, and 
applicable regulatory requirements. The sample ICF will adhere to the ethical principles that have 
their origin in the Declaration of Helsinki.
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Investigators must:

Provide a copy of the consent form and written information about the study in the language in 
which the participant is most proficient prior to clinical study participation. The language must 
be nontechnical and easily understood.

Allow time necessary for participant or participant's legally acceptable representative to 
inquire about the details of the study.

Obtain an informed consent signed and personally dated by the participant or the participant's 
legally acceptable representative and by the person who conducted the informed consent 
discussion.

Obtain the IRB/IEC’s written approval/favorable opinion of the written ICF and any other 
information to be provided to the subjects/participants, prior to the beginning of the study, and 
after any revisions are completed for new information.
If informed consent is initially given by a participant’s legally acceptable representative or legal 
guardian, and the participant subsequently becomes capable of making and communicating his or 
her informed consent during the study, consent must additionally be obtained from the participant.
Revise the informed consent whenever important new information becomes available that is 
relevant to the participant's consent. The investigator, or a person designated by the investigator, 
should fully inform the participant or the participant's legally acceptable representative or legal 
guardian, of all pertinent aspects of the study and of any new information relevant to the 
participant's willingness to continue participation in the study. This communication should be 
documented.
The confidentiality of records that could identify subjects/participants must be protected, 
respecting the privacy and confidentiality rules applicable to regulatory requirements, the 
subjects'/participants’ signed ICF and, in the US, the subjects’/participants’ signed Health 
Insurance Portability and Accountability Act Authorization.
The consent form must also include a statement that BMS and regulatory authorities have direct 
access to participant records.
The rights, safety, and well-being of the study subjects/participants are the most important 
considerations and should prevail over interests of science and society.
SOURCE DOCUMENTS
The investigator is responsible for ensuring that the source data are accurate, legible, 
contemporaneous, original, and attributable, whether the data are hand-written on paper or entered 
electronically. If source data are created (first entered), modified, maintained, archived, retrieved, 
or transmitted electronically via computerized systems (and/or any other kind of electronic 
devices) as part of regulated clinical trial activities, such systems must be compliant with all 
applicable laws and regulations governing use of electronic records and/or electronic signatures. 
Such systems may include, but are not limited to, electronic medical/health records (EMRs/EHRs), 
adverse event (AE) tracking/reporting, protocol-required assessments, and/or drug accountability 
records).
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When paper records from such systems are used in place of electronic format to perform regulated 
activities, such paper records should be certified copies. A certified copy consists of a copy of 
original information that has been verified, as indicated by a dated signature, as an exact copy 
having all of the same attributes and information as the original.
STUDY TREATMENT RECORDS
Records for study treatments (whether supplied by Bristol-Myers Squibb [BMS], its vendors, or 
the site) must substantiate study treatment integrity and traceability from receipt, preparation, 
administration, and through destruction or return. Records must be made available for review at 
the request of BMS/designee or a Health Authority.
If..
Then
Supplied by BMS (or its vendors):
Records or logs must comply with applicable 
regulations and guidelines and should include:

Amount received and placed in storage 
area

Amount currently in storage area

Label identification number or batch
number

Amount dispensed to and returned by 
each participant, including unique 
participant identifiers

Amount transferred to another area/site 
for dispensing or storage

Nonstudy disposition (e.g., lost, wasted)

Amount destroyed at study site, if 
applicable

Amount returned to BMS

Retain samples for 
bioavailability/bioequivalence, if 
applicable

Dates and initials of person responsible 
for investigational product 
dispensing/accountability, as per the 
Delegation of Authority Form.
Sourced by site, and not supplied by BMS or 
its vendors (examples include investigational
product sourced from the sites stock or 
commercial supply, or a specialty pharmacy)
The investigator or designee accepts 
responsibility for documenting traceability 
and study treatment integrity in accordance 
with requirements applicable under law and 
the standard operating procedures 
(SOPs)/standards of the sourcing pharmacy.
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These records should include:

Label identification number or batch 
number

Amount dispensed to and returned by 
each participant, including unique 
participant identifiers

Dates and initials of person responsible 
for investigational product 
dispensing/accountability, as per the 
Delegation of Authority Form.
BMS or designee will provide forms to facilitate inventory control if the investigational site does 
not have an established system that meets these requirements.
CASE REPORT FORMS
An investigator is required to prepare and maintain adequate and accurate case histories designed 
to record all observations and other data pertinent to the investigation on each individual treated 
or entered as a control in the investigation. Data that are derived from source documents and 
reported on the case report form (CRF) must be consistent with the source documents or the 
discrepancies must be explained. Additional clinical information may be collected and analyzed 
in an effort to enhance understanding of product safety. CRFs may be requested for AEs and/or 
laboratory abnormalities that are reported or identified during the course of the study.
For sites using the Sponsor or designee electronic data capture tool, electronic CRFs will be 
prepared for all data collection fields except for fields specific to SAEs and pregnancy, which will 
be reported on the electronic SAE form and paper Pregnancy Surveillance Form, respectively. If 
electronic SAE form is not available, a paper SAE form can be used.
The confidentiality of records that could identify subjects/participants must be protected, 
respecting the privacy and confidentiality rules in accordance with the applicable regulatory 
requirement(s).
The investigator will maintain a signature sheet to document signatures and initials of all persons 
authorized to make entries and/or corrections on CRFs.
The completed CRF, SAE/pregnancy CRFs, must be promptly reviewed, signed, and dated by the 
investigator or qualified physician who is a subinvestigator and who is delegated this task on the 
Delegation of Authority Form. Subinvestigators in Japan may not be delegated the CRF approval 
task. For electronic CRFs, review and approval/signature is completed electronically through the 
electronic data capture tool. The investigator must retain a copy of the CRFs including records of 
the changes and corrections.
Each individual electronically signing electronic CRFs must meet Sponsor or designee training 
requirements and must only access the electronic data capture tool using the unique user account 
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provided by Sponsor or designee. User accounts are not to be shared or reassigned to other 
individuals.
MONITORING
Sponsor or designee representatives will review data centrally to identify potential issues to 
determine a schedule of on-site visits for targeted review of study records.
Representatives of BMS must be allowed to visit all study site locations periodically to assess the 
data quality and study integrity. On site they will review study records and directly compare them 
with source documents, discuss the conduct of the study with the investigator, and verify that the 
facilities remain acceptable. Certain eCRF pages and/or electronic files may serve as the source 
documents:
In addition, the study may be evaluated by Sponsor or designee internal auditors and government 
inspectors who must be allowed access to eCRFs, source documents, other study files, and study 
facilities. BMS audit reports will be kept confidential.
The investigator must notify BMS promptly of any inspections scheduled by regulatory authorities, 
and promptly forward copies of inspection reports to Sponsor or designee.
RECORDS RETENTION
The investigator (or head of the study site in Japan) must retain all study records and source 
documents for the maximum period required by applicable regulations and guidelines, or 
institution procedures, or for the period specified by BMS or designee, whichever is longer. The 
investigator (or head of the study site in Japan) must contact BMS prior to destroying any records 
associated with the study.
BMS or designee will notify the investigator (or head of the study site in Japan) when the study 
records are no longer needed.
If the investigator withdraws from the study (eg, relocation, retirement), the records shall be 
transferred to a mutually agreed upon designee (eg, another investigator, study site, IRB). Notice 
of such transfer will be given in writing to BMS or designee.
RETURN OF STUDY TREATMENT
For this study, study treatments (those supplied by BMS, a vendor or sourced by the investigator) 
such as partially used study treatment containers, vials, and syringes may be destroyed on-site.
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Study treatments supplied by BMS (including 
its vendors)
Any unused study treatments supplied by BMS 
can only be destroyed after being inspected and 
reconciled by the responsible study monitor 
unless study treatments containers must be 
immediately destroyed as required for safety, 
or to meet local regulations (eg, cytotoxics or 
biologics).
If study treatments will be returned, the return 
will be arranged by the responsible study 
monitor.
Study treatments sourced by site, not supplied 
by BMS (or its vendors) (examples include 
study treatments sourced from the sites stock 
or 
commercial 
supply, 
or 
a 
specialty 
pharmacy)
It 
is 
the 
investigator’s 
or 
designee’s 
responsibility to dispose of all containers 
according to the institutional guidelines and 
procedures.
It is the investigator’s or designee’s responsibility to arrange for disposal, provided that procedures 
for proper disposal have been established according to applicable federal, state, local, and 
institutional guidelines and procedures, and provided that appropriate records of disposal are kept. 
The following minimal standards must be met:

On-site disposal practices must not expose humans to risks from the drug.

On-site disposal practices and procedures are in agreement with applicable laws and 
regulations, including any special requirements for controlled or hazardous substances.

Written procedures for on-site disposal are available and followed. The procedures must be 
filed with the site’s SOPs and a copy provided to BMS upon request.

Records are maintained that allow for traceability of each container, including the date 
disposed of, quantity disposed, and identification of the person disposing the containers. The 
method of disposal, ie, incinerator, licensed sanitary landfill, or licensed waste disposal vendor 
must be documented.

Accountability and disposal records are complete, up-to-date, and available for the Monitor to 
review throughout the clinical trial period.
It is the investigator’s or designee’s responsibility to arrange for disposal of all empty containers.
If conditions for destruction cannot be met, the responsible study monitor will make arrangements 
for return of study treatments provided by BMS (or its vendors). Destruction of nonstudy 
treatments sourced by the site, not supplied by BMS, is solely the responsibility of the investigator 
or designee.
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For sites that will not destroy study treatment on-site, it is the investigator’s or designee’s 
responsibility to arrange for disposal of all empty study treatment containers, provided that 
procedures for proper disposal have been established according to applicable federal, state, local, 
and institutional guidelines and procedures, and provided that appropriate records of disposal are 
kept. The return of full or partially used study treatments supplied by BMS or its vendors will be 
arranged by the responsible study monitor.
CLINICAL STUDY REPORT
A signatory investigator must be selected to sign the clinical study report (CSR).
For each CSR related to this protocol, the following criteria will be used to select the signatory 
investigator:

Participant recruitment (eg, among the top quartile of enrollers)

Regional representation (eg, among top quartile of enrollers from a specified region or country)

Scientific expertise or contribution to data interpretation and review
SCIENTIFIC PUBLICATIONS
The data collected during this study are confidential and proprietary to Sponsor or designee. Any 
publications or abstracts arising from this study must adhere to the publication requirements set 
forth in the clinical trial agreement (CTA) governing study site or investigator participation in the 
study. These requirements include, but are not limited to, submitting proposed publications to 
Sponsor or designee at the earliest practicable time prior to submission or presentation and 
otherwise within the time period set forth in the CTA.
Scientific Publications (such as abstracts, congress podium presentations and posters, and 
manuscripts) of the study results will be a collaborative effort between the study Sponsor and the 
external authors. No public presentation or publication of any interim results may be made by any 
principal investigator, subinvestigator, or any other member of the study staff without the prior 
written consent of the Sponsor.
Authorship of publications at BMS is aligned with the criteria of the International Committee of 
Medical Journal Editors (ICMJE; www.icmje.org). Authorship selection is based upon significant 
contributions to the study (ie, ICMJE criterion #1). Authors must meet all 4 ICMJE criteria for 
authorship:
1) Substantial intellectual contribution to the conception or design of the work; or the acquisition 
of data (ie, evaluable subjects with quality data), analysis, or interpretation of data for the work 
(eg, problem solving, advice, evaluation, insights, and conclusion); AND
2) Drafting the work or revising it critically for important intellectual content; AND
3) Final approval of the version to be published; AND
4) Agreement to be accountable for all aspects of the work in ensuring that questions related to 
the accuracy or integrity of any part of the work are appropriately investigated and resolved.
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Those who make the most significant contributions, as defined above, will be considered by BMS 
for authorship of the primary publication. Subinvestigators will generally not be considered for 
authorship in the primary publication. Geographic representation will also be considered.
Authors will be listed by order of significant contributions (highest to lowest), with the exception 
of the last author. Authors in first and last position have provided the most significant contributions 
to the work.
For secondary analyses and related publications, author list and author order may vary from 
primary to reflect additional contributions.
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APPENDIX 3
ADVERSE EVENTS AND SERIOUS ADVERSE EVENTS: 
DEFINITIONS AND PROCEDURES FOR RECORDING, 
EVALUATING, FOLLOW-UP, AND REPORTING
ADVERSE EVENTS
AE Definition
An AE is defined as any new untoward medical occurrence or worsening of a preexisting 
medical condition in a clinical investigation participant administered study drug and that does 
not necessarily have a causal relationship with this treatment. 
An AE can therefore be any unfavorable and unintended sign (such as an abnormal laboratory 
finding), symptom, or disease temporally associated with the use of study drug, whether or not 
considered related to the study drug.
Events Meeting the AE Definition

Any abnormal laboratory test results (hematology, clinical chemistry, or urinalysis) or 
results from other safety assessments (eg, electrocardiogram [ECG], radiological scans, 
vital signs measurements), including those that worsen from baseline, considered clinically 
significant in the medical and scientific judgment of the investigator. Note that abnormal 
lab tests or other safety assessments should only be reported as AEs if the final diagnosis is 
not available. Once the final diagnosis is known, the reported term should be updated to be 
the diagnosis.

Exacerbation of a chronic or intermittent preexisting condition including either an increase 
in frequency and/or intensity of the condition.

New conditions detected or diagnosed after study intervention administration even though 
it may have been present before the start of the study.

Signs, symptoms, or the clinical sequelae of a suspected drug-drug interaction.

Signs, symptoms, or the clinical sequelae of a suspected overdose of either study 
intervention or a concomitant medication. Overdose, as a verbatim term (as reported by the 
investigator), should not be reported as an AE/SAE unless it is an intentional overdose 
taken with possible suicidal/self-harming intent. Such overdoses should be reported 
regardless of sequelae and should specify “intentional overdose” as the verbatim term.
Events NOT Meeting the AE Definition

Medical or surgical procedure (eg, endoscopy, appendectomy): the condition that leads to 
the procedure is the AE.

Situations in which an untoward medical occurrence did not occur (social and/or 
convenience admission to a hospital).
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DEFINITION OF SAE
If an event is not an AE per definition above, then it cannot be an SAE even if serious conditions 
are met.
SERIOUS ADVERSE EVENTS
SAE Definition is defined as any untoward medical occurrence that, at any dose:
Results in death
Is life-threatening (defined as an event in which the participant was at risk of death at the time 
of the event; it does not refer to an event which hypothetically might have caused death if it 
were more severe)
Requires inpatient hospitalization or causes prolongation of existing hospitalization (see note 
below)
NOTE: The following hospitalizations are not considered SAEs in BMS clinical studies:

a visit to the emergency room or other hospital department < 24 hours, that does not result 
in admission (unless considered an important medical or life-threatening event)

elective surgery, planned prior to signing consent

admissions as per protocol for a planned medical/surgical procedure

routine health assessment requiring admission for baseline/trending of health status (eg, 
routine colonoscopy)

medical/surgical admission other than to remedy ill health and planned prior to entry into 
the study. Appropriate documentation is required in these cases

admission encountered for another life circumstance that carries no bearing on health status 
and requires no medical/surgical intervention (eg, lack of housing, economic inadequacy, 
caregiver respite, family circumstances, administrative reason)

admission for administration of anticancer therapy in the absence of any other SAEs 
(applies to oncology protocols)
Results in persistent or significant disability or permanent damage
Is a congenital anomaly/birth defect
Is an important medical event (defined as a medical event(s) that may not be immediately 
life-threatening or result in death or hospitalization but, based upon appropriate medical and 
scientific judgment, may jeopardize the participant or may require intervention [eg, medical, 
surgical] to prevent one of the other serious outcomes listed in the definition above). Examples 
of such events include, but are not limited to, intensive treatment in an emergency room or at 
home for allergic bronchospasm; blood dyscrasias, or convulsions that do not result in 
hospitalization. Potential drug-induced liver injury (DILI) is also considered an important 
medical event (see Section 9.2.7 for the definition of potential DILI).
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Pregnancy and potential DILI must follow the same transmission timing and processes to BMS 
as used for SAEs (see Section 9.2.5 for reporting pregnancies).
EVALUATING AES AND SAES
Assessment of Intensity
The investigator will make an assessment of intensity for each AE and SAE reported 
during the study and assign it to 1 of the following categories: 

Mild: An event that is easily tolerated by the subject/participant, causing minimal 
discomfort, and not interfering with everyday activities.

Moderate: An event that causes sufficient discomfort and interferes with normal 
everyday activities.

Severe: An event that prevents normal everyday activities. An AE that is assessed as 
severe should not be confused with an SAE. Severe is a category utilized for rating 
the intensity of an event; and both AEs and SAEs can be assessed as severe.
An event is defined as “serious” when it meets at least 1 of the predefined outcomes as 
described in the definition of an SAE, NOT when it is rated as severe.
Assessment of Causality

The investigator is obligated to assess the relationship between study intervention and 
each occurrence of each AE/SAE. A “reasonable possibility of a relationship” 
conveys that there are facts, evidences, and/or arguments to suggest a causal 
relationship rather than a relationship cannot be ruled out.

The investigator will use clinical judgment to determine the relationship.

Alternative causes, such as underlying disease(s), concomitant therapy, and other risk 
factors, as well as the temporal relationship of the event to study intervention 
administration will be considered and investigated.

The investigator will also consult the Investigator’s Brochure and/or Product 
Information, for marketed products, in his/her assessment.

For each AE/SAE, the investigator must document in the medical notes that he/she 
has reviewed the AE/SAE and has provided an assessment of causality.

There may be situations in which an SAE has occurred and the investigator has 
minimal information to include in the initial report to Sponsor. However, it is very 
important that the investigator always make an assessment of causality for every event 
before the initial transmission of the SAE data to Sponsor.

The investigator may change his/her opinion of causality in light of follow-up 
information and send a SAE follow-up report with the updated causality assessment.

The causality assessment is one of the criteria used when determining regulatory 
reporting requirements.
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Follow-up of AEs and SAEs
If only limited information is initially available, follow-up reports are required. Note: 
Follow-up SAE reports must include the same investigator term(s) initially reported.
If an ongoing SAE changes in its intensity or relationship to study drug or if new 
information becomes available, the SAE report must be updated and submitted within
24 hours to BMS (or designee) using the same procedure used for transmitting the initial 
SAE report.
All SAEs must be followed to resolution or stabilization.
REPORTING OF SAES TO SPONSOR OR DESIGNEE
SAEs, whether related or not related to study drug, and pregnancies must be reported 
immediately to BMS (or designee) but no later than 24 hours of awareness of the event.
SAEs must be recorded on the SAE Report Form. For studies capturing SAEs through 
electronic data capture, electronic submission is the required method for reporting. In the 
event the electronic system is unavailable for transmission, paper forms must be used and 
submitted immediately. When paper forms are used, the original paper forms are to 
remain on-site.
Pregnancies must be recorded on a paper Pregnancy Surveillance Form and transmitted 
via email or confirmed facsimile (fax) transmission to:
SAE Email Address: Refer to Contact Information list.
SAE Fax Number: Refer to Contact Information list.
SAE Telephone Contact - For questions on SAE/pregnancy reporting: Refer to 
Contact Information list.
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APPENDIX 4
WOMEN OF CHILDBEARING POTENTIAL DEFINITIONS AND 
METHODS OF CONTRACEPTION
DEFINITIONS
Woman of Childbearing Potential (WOCBP)
A woman is considered fertile following menarche and until becoming postmenopausal unless 
permanently sterile. Permanent sterilization methods include hysterectomy, bilateral 
salpingectomy, and bilateral oophorectomy.
Women in the following categories are not considered WOCBP

Premenarchal

Premenopausal female with 1 of the following:

Documented hysterectomy

Documented bilateral salpingectomy

Documented bilateral oophorectomy
Note: Documentation can come from the site personnel’s review of the participant’s medical 
records, medical examination, or medical history interview.

Postmenopausal female

A postmenopausal state is defined as 12 months of amenorrhea in a woman over age 
45 years in the absence of other biological or physiological causes. In addition, female 
participants under the age of 55 years must have a serum follicle-stimulating hormone 
(FSH) level > 40 mIU/mL to confirm menopause.
Note: Female participants treated with hormone replacement therapy (HRT) are likely to have 
artificially suppressed FSH levels and may require a washout period in order to obtain a 
physiologic FSH level. The duration of the washout period is a function of the type of HRT used. 
The duration of the washout period below are suggested guidelines and the investigators should 
use their judgment in checking serum FSH levels.

1 week minimum for vaginal hormonal products (rings, creams, gels)

4 week minimum for transdermal products

8 week minimum for oral products
Other parenteral products may require washout periods as long as 6 months. If the serum FSH 
level is > 40 mIU/mL at any time during the washout period, the woman can be considered 
postmenopausal.
End of Relevant Systemic Exposure
End of relevant systemic exposure is the time point where the IMP or any active major metabolites 
has decreased to a concentration that is no longer considered to be relevant for human 
teratogenicity or fetotoxicity. This should be evaluated in context of safety margins from the 
no-observed-adverse-effect level or the time required for 5 half-lives of the IMP to pass.
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METHODS OF CONTRACEPTION
Local laws and regulations may require use of alternative and/or additional contraception methods.
Highly Effective Contraceptive Methods That Are User Dependent
Failure rate of < 1% per year when used consistently and correctly.a

Combined (estrogen- and progestogen-containing) hormonal contraception associated with 
inhibition of ovulation and/or implantation (This method of contraception can only be used 
by WOCBP participants in studies where hormonal contraception is permitted by the study 
protocol)b

oral (birth control pills)

intravaginal (vaginal birth control suppositories, rings, creams, gels)

transdermal

Combined (estrogen-and progestogen-containing) hormonal contraception must begin at 
least 30 days prior to initiation of study therapy

Progestogen-only hormonal contraception associated with inhibition of ovulation (This 
method of contraception can only be used by WOCBP participants in studies where 
hormonal contraception is permitted by the study protocol)b

oral

injectable

Progestogen-only hormonal contraception must begin at least 30 days prior to initiation of 
study therapy
Highly Effective Methods That Are User Independent

Implantable progestogen-only hormonal contraception associated with inhibition of 
ovulation and/or implantation (This method of contraception can only be used by WOCBP 
participants in studies where hormonal contraception is permitted by the study protocol)b

Intrauterine device (IUD)c

Intrauterine hormone-releasing system (This method of contraception can only be used by 
WOCBP participants in studies where hormonal contraception is permitted by the study 
protocol)b,c

Bilateral tubal occlusion

Vasectomized partner
Having a vasectomized partner is a highly effective contraception method provided that the 
partner is the sole male sexual partner of the WOCBP and the absence of sperm has been 
confirmed. If not, an additional highly effective method of contraception should be used.
Male participants will be required to always use a latex or other synthetic condom during 
any sexual activity (eg, vaginal, anal, oral) with WOCBP; even if the participants have 
undergone a successful vasectomy or if their partner is already pregnant or breastfeeding.
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
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 treatment. 
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.

Continuous abstinence must begin at least 30 days prior to initiation of study therapy.

It is not necessary to use any other method of contraception when complete abstinence is 
elected.

WOCBP participants who choose complete abstinence must continue to have pregnancy 
tests, as specified in the Schedule of Activities, Section 2.

Acceptable alternate methods of highly effective contraception must be discussed in the 
event that the WOCBP participants chooses to forego complete abstinence.

Periodic abstinence (including but not limited to calendar, symptothermal, postovulation 
methods), withdrawal (coitus interruptus), spermicides only, and lactational amenorrhoea 
method (LAM) are not acceptable methods of contraception for this study.
NOTES:
a Typical use failure rates may differ from those when used consistently and correctly. Use 
should be consistent with local regulations regarding the use of contraceptive methods for 
participants participating in clinical studies.
b Hormonal contraception may be susceptible to interaction with the study treatment, which 
may reduce the efficacy of the contraceptive method. Hormonal contraception is permissible 
only when there is sufficient evidence that the IMP and other study medications will not alter 
hormonal exposures such that contraception would be ineffective or result in increased 
exposures that could be potentially hazardous. In this case, alternative methods of 
contraception should be utilized.
c Intrauterine hormone-releasing systems are acceptable methods of contraception in the 
absence of definitive drug interaction studies when hormone exposures from intrauterine 
devices do not alter contraception effectiveness
Less Than Highly Effective Contraceptive Methods That are User Dependent
Failure rate of > 1% per year when used consistently and correctly.

Male or female condom with or without spermicide. Male and female condoms cannot be 
used simultaneously

Diaphragm with spermicide

Cervical cap with spermicide

Vaginal Sponge with spermicide

Progestogen-only oral hormonal contraception, where inhibition of ovulation is not the 
primary mechanism of action (This method of contraception cannot be used by WOCBP 
participants in studies where hormonal contraception is prohibited.)
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Unacceptable Methods of Contraception

Periodic abstinence (calendar, symptothermal, postovulation methods)

Withdrawal (coitus interruptus)

Spermicide only

LAM
COLLECTION OF PREGNANCY INFORMATION
Guidance for collection of Pregnancy Information and outcome of pregnancy on the Pregnancy 
Surveillance Form is provided in Section 9.2.5 and APPENDIX 3.
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APPENDIX 5
CHILD-PUGH SCORING
Parameter
Classification
Score
Bilirubin (Total)a
< 2 mg/dL (< 34.2 µmol/L)
+1
2-3 mg/dL (34.2-51.3 µmol/L)
+2
> 3 mg/dL (> 51.3 µmol/L)
+3
Albumina
> 3.5 g/dL (> 35 g/L)
+1
2.8-3.5 g/dL (28-35 g/L)
+2
< 2.8 g/dL (< 28 g/L)
+3
International Normalized Ratioa
< 1.7
+1
1.7-2.2
+2
> 2.2
+3
Ascites
Absent
+1
Slight
+2
Moderate
+3
Encephalopathy
No encephalopathy
+1
Mild to moderate (Grade 1-2)
+2
Severe (Grade 3-4)
+3
a All laboratory parameters must be taken from the same blood draw.
Note: in the event of retesting of Child-Pugh Score, all laboratory parameters should be retested to allow for accurate 
calculations.
For the calculation of the Child-Pugh Score1, 2 the sum of the scoring points from the 5 clinical 
parameters (total bilirubin, albumin, INR, ascites, and encephalopathy) corresponds to 1 of 
3 categories:
Child-Pugh A = 5 to 6 points
Child-Pugh B = 7 to 9 points
Child-Pugh C = ≥10 points.
REFERENCES:
1.
Cholongitas E, Papatheodoridis GV, Vangeli M, et al. Systematic review: The model for 
end-stage liver disease--should it replace Child-Pugh's classification for assessing prognosis in 
cirrhosis? Aliment Pharmacol Ther 2005;22(11-12):1079-89.
2.
Weissenborn K. Hepatic Encephalopathy: Definition, Clinical Grading and Diagnostic 
Principles. Drugs 2019;79(Suppl 1):5-9.
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APPENDIX 6
FORMULAS FOR MEASUREMENTS

Model for End-stage Liver Disease (MELD) 
Score = (9.57*ln[creatinine]) + (3.78 * ln[Bilirubin]) + (11.20* ln[INR]) + 6.43

Enhanced liver fibrosis (ELF)1 assessment combines hyaluronic acid, procollagen 3 amino 
terminal peptide, and tissue inhibitor of metalloproteinase 1. An algorithm is used to evaluate 
each of these markers by immunoassay to create an ELF Score

Fibrosis-4 
(FIB-4)2
Score = (age [years] × aspartate 
aminotransferase 
[AST] 
level 
[U/L])/(platelet count [x109/L] × square root of alanine aminotransferase [ALT] [U/L])

Nonalcoholic 
fatty 
liver 
disease
(NAFLD) 
Fibrosis 
Score3 = -1.675 + 0.037 × age 
(years) + 0.094 × body mass index (kg/m2) + 1.13 × impaired fasting glucose/diabetes 
(yes = 1, no = 0) + 0.99 × AST/ALT ratio – 0.013 × platelet count [× 109/L] – 0.66 × albumin 
(g/dL)

AST-to-platelet ratio index (APRI)4 Score = ([AST divided by AST Upper Limit of 
Normal]/platelet count [× 109/L]) × 100
Note: all laboratory parameters must be taken from the same blood draw. In the event of retesting, 
all laboratory parameters should be retested to allow for accurate calculations.
REFERENCES:
1.
Anstee QM, Lawitz EJ, Alkhouri N, et al. Noninvasive tests accurately identify advanced 
fibrosis due to NASH: Baseline data from the STELLAR trials. Hepatology 2019.
2.
Shah AG, Lydecker A, Murray K, et al. Comparison of noninvasive markers of fibrosis in 
patients with nonalcoholic fatty liver disease. Clin Gastroenterol Hepatol 
2009;7(10):1104-12.
3.
Angulo P, Hui JM, Marchesini G, et al. The NAFLD fibrosis score: a noninvasive system 
that identifies liver fibrosis in patients with NAFLD. Hepatology 2007;45(4):846-54.
4.
Adams LA, George J, Bugianesi E, et al. Complex non-invasive fibrosis models are more 
accurate than simple models in non-alcoholic fatty liver disease. J Gastroenterol Hepatol 
2011;26(10):1536-43.
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APPENDIX 7
CRITERIA FOR DIAGNOSIS AND EXCLUSION OF 
PARTICIPANTS WITH HEPATITIS B VIRUS AND CHRONIC 
HEPATITIS C VIRUS INFECTION
HBV Infection
HBsAg
HBsAb
HBcAb
HBV Infection
Excluded?
Positive
Negative
Positive
Yes
Yes
Negative
Negative
Positive
Maybe
See (a)
Negative
Positive
Positive
Maybe
See (a)
Positive
Positive
Negative
Maybe
See (b)
Negative
Negative
Negative
No
No
Negative
Positive
Negative
No
No
HBsAB = hepatitis B surface antibody; HBsAg = hepatitis B surface antigen; HBcAB = hepatitis B core antibody; 
HBV = hepatitis B virus
a) Perform hepatitis B virus (HBV) deoxyribonucleic acid (DNA):
If HBV DNA is detected, then participant must be excluded.
If HBV DNA is not detected, then the participant may be considered eligible for 
enrollment based on the investigator’s judgment and after discussion with the study 
Medical Monitor.
b) Participant must be excluded unless:
Participant was recently vaccinated for HBV (within 2 weeks of testing) AND repeat 
hepatitis B surface antigen (HBsAg) is negative (repeat HBsAg should occur 4 to 6 
weeks after vaccination).
Any positive HBV DNA result is exclusionary.
HCV Infection
A participant who is hepatitis C virus (HCV) antibody positive must be excluded unless:

The participant has a history of clearance of HCV infection for > 2 years prior to the screening
biopsy AND the HCV ribonucleic acid is undetectable at the screening visit.
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APPENDIX 8
COUNTRY-SPECIFIC REQUIREMENTS
Argentina, Germany,  and Any Other Countries in Which Exclusion of HIV-Positive 
Participants is Locally Mandated
Country-specific Language
Section 2 Schedule of Activities, Table 1 Screening 
Procedural Outline ‒ Laboratory Assessments
Add “HIV” to the list of laboratory tests
Section 6.2 Exclusion Criteria, Exclusion 
criterion 2) k)
Replace
“Known immunocompromised status, including but not 
limited to, individuals who have undergone organ 
transplantation or who are positive for human 
immunodeficiency virus (HIV) or have acquired 
immunodeficiency syndrome-related illness, as 
reported by the participant and/or documentation.”
with
“Known immunocompromised status, including but not 
limited to, individuals who have undergone organ 
transplantation or who have a positive human 
immunodeficiency virus (HIV) test.”
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APPENDIX 9
PROTOCOL AMENDMENT SUMMARY OF CHANGE HISTORY
Overall Rationale for the Revised Protocol 02, 25-Nov-2020
The primary purpose of this Global Revised Protocol is to expand the patient population from 
Child-Pugh A5 to Child-Pugh A6, including corresponding laboratory exclusion criteria, based on 
preliminary results from hepatic impairment (HI) study IM025015. Key secondary revisions 
include the following:

Adding results from Part 1 of HI study IM025015, which supports the changes in Child-
Pugh/laboratory exclusion criteria

Adjustment of step-wise infusion rates (decreased number of steps)

Adding guidance 
 related to the coronavirus disease 2019 
(COVID-19) pandemic

Changing statistical sample size calculation, study stratification factors, and statistical analysis 
methodology for primary endpoint

Excluding participants from the study who are taking anticoagulants

Replacing liver ultrasound as a screening procedure for detection of hepatocellular carcinoma 
(HCC) with multiphasic liver computed tomography (CT)/magnetic resonance imaging (MRI)

Updating exclusion criterion related to history of weight gain/loss

Updating exclusion criterion related to history of illegal intravenous (IV) drug use

Adding option for participants who have a prolonged international normalized ratio (INR) 
and/or lower platelet count to potentially receive treatments for coagulation abnormalities 
and/or low platelet counts prior to liver biopsy
All changes applied to the body were applied to the synopsis, as necessary; synopsis changes are 
not included in the list below.
Only major additions and deletions are provided in this summary; all minor grammatical, 
formatting, rephrasing, stylistic changes, or clarifications are not included.
The rationale(s) for changes to this Revised Protocol are provided in the summary of key changes 
table, as shown below:
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SUMMARY OF KEY CHANGES TO THE REVISED PROTOCOL 02
Section Number & Title
Description of Change
Brief Rationale
2 Schedule of Activities, 
Table 1
6.2 Exclusion Criteria
1) Target disease 
exclusions
Replaced as follows:
1)f) → 1)i)
Replaced liver ultrasound at 
screening with multiphasic 
liver CT/MRI because 
diagnostic performance of liver 
ultrasound for early detection 
of HCC can be reduced 
particularly in subjects with 
central obesity or marked 
parenchymal heterogeneity due 
to cirrhosis, justifying the 
adoption of a more sensitive 
method for detection of HCC 
prior to initiation of study 
treatment.
2 Schedule of Activities, 
Table 2
3.3.2 COVID-19-Related
4 Objectives and 
Endpoints, Table 4
5.4 Scientific Rationale for 
Study Design
6.2 Exclusion Criteria, 2) 
Medical Conditions and 3) 
Prior and concomitant 
therapy
6.6.1 Retesting During 
Screening Period
7.7.1 Prohibited and/or 
Restricted Treatments
 
Added guidance 
 
 
related to COVID-19 
pandemic, including addition 
of the following Exclusion 
Criteria:
2)r) and 3)g)
and replacement of the 
following Exclusion Criterion:
3)c) → 3)h)
Added to ensure 
participant/investigative site 
staff safety and reliability of 
results
3.2.2 Clinical Studies
3.3.1 Overall Benefit/Risk 
Assessment
Added study results from 
Part 1 of HI study IM025015
These study results from Part 1 
of Study IM025015 in 
participants with mild or 
moderate HI support the 
changes in Child-Pugh 
exclusion criteria, including 
corresponding laboratory 
exclusion criteria.
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HSP47 siRNA
SUMMARY OF KEY CHANGES TO THE REVISED PROTOCOL 02
Section Number & Title
Description of Change
Brief Rationale
4 Objectives and 
Endpoints, Table 4
10.3.2 Secondary 
Endpoints
10.4.3.1 PK 
 
 
To include the assessment of 
the plasma PK of this lipid 
component of BMS-986263.
5.1.2 Treatment Period and 
Follow-up
10.4.1 Efficacy Analyses
Platelet count removed as 
stratification factor at 
Randomization and added as 
independent covariate in the 
logistic regression
Removed because too many 
stratification factors may result
in reduced power in analyses 
and imbalance in 
randomization.
5.1.2 Treatment Period and 
Follow-up
Country (Non-Japan versus 
Japan) removed as 
stratification factor at 
Randomization 
Removed because too many 
stratification factors may result 
in reduced power in analyses 
and imbalance in 
randomization.
7.2 Exclusion Criteria
1) Target disease 
exclusions
3) Prior and 
concomitant therapy
7.7.1 Prohibited and/or 
Restricted Treatments
Replaced as follows:
1)e) → 1)h)
Added 3)i)
Added 8)
 to 
exclude participants who are 
taking anticoagulants in order 
to mitigate bleeding risks 
associated with the liver 
biopsy.
6.2 Exclusion Criteria
1) Target disease 
exclusions
Replaced as follows:
1)g) → 1)j)
Updated exclusion criterion to 
exclude participants with a 
Child-Pugh Score > 6, instead 
of > 5 based on results from 
Part 1 of Study IM025015.
6.2 Exclusion Criteria
2) Medical conditions
6.4 Lifestyle Restrictions
Replaced as follows:
2)c) → 2)s)
Updated exclusion criterion to 
specify alcohol consumption 
limits in mL, as well as in 
ounces.
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HSP47 siRNA
SUMMARY OF KEY CHANGES TO THE REVISED PROTOCOL 02
Section Number & Title
Description of Change
Brief Rationale
6.2 Exclusion Criteria
2) Medical conditions
Replaced as follows:
2)m) → 2)t)
Reduced the duration of 
exclusionary history of illegal 
IV drug use from 3 to 2 years 
since 2 years should be
sufficient to ensure study 
compliance related to illegal 
IV drug use.
6.2 Exclusion Criteria
2) Medical conditions
Replaced as follows:
2)o) → 2)u)
Updated the exclusion criterion 
related to history of weight 
gain/loss before and after the 
eligibility liver biopsy to 
ensure that the biopsy used for 
eligibility reflects the 
participant’s disease severity at 
baseline.
6.2 Exclusion Criteria
4) Physical and 
laboratory test findings
Replaced as follows:
4)c) → 4)f)
Updated exclusion criterion to 
exclude participants with 
albumin < 2.8 g/dL, INR > 2.2, 
total bilirubin > 3.0 mg/dL, 
and platelet count 
< 85,000/µL, instead of 
< 3.5 g/dL, > 1.4, > 1.5 mg/dL, 
and < 140,000/µL, 
respectively, allowing 
enrollment of subjects with a 
wider range of laboratory 
values, supported by safety 
results from Part 1 of Study 
IM025015 in subjects with 
mild and moderate HI.
7.1.1 Study Treatment 
Infusion Rate
9.5 PK 
 
 Sampling 
Schedule for BMS-986263, 
Adjusted step-wise infusion 
durations 
Adjusted to simplify the 
infusion process.
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HSP47 siRNA
SUMMARY OF KEY CHANGES TO THE REVISED PROTOCOL 02
Section Number & Title
Description of Change
Brief Rationale
9.1.2 Liver Biopsy 
Assessments
Added the following text:
Participants who have a 
prolonged INR and/or lower 
platelet count may receive 
treatments to correct 
coagulation abnormalities 
and/or low platelet counts prior 
to liver biopsy based on 
investigator’s clinical 
judgment in order to reduce the 
risk of bleeding. It is the 
investigator’s responsibility to 
assess any potential risks that 
may be associated with the use 
of these agents (eg, transfusion 
of fresh/frozen plasma or 
platelets).
Added to allow investigators to 
administer treatments to 
correct abnormal INR or 
platelets prior to liver biopsy, 
in order to reduce the risk of 
bleeding associated with the 
liver biopsy, based on 
investigator’s assessment of 
the benefits-risks of these 
treatments.
10.1 Sample Size 
Determination
Participant dropout rate 
changed from 10% to 6% and 
evaluable number of 
participants changed from 79 
to 85 participants
To adjust the estimated 
dropout rate and maintain 80% 
power with the study sample 
size of approximately 
270 participants.
10.1 Sample Size 
Determination
Replaced CMH test with 
Chi-Square test
The CMH test is no longer 
applicable to justify the sample 
size, as the final analysis was 
changed from CMH to logistic 
regression. Treatment group 
comparisons using the logistic 
regression model are 
Chi-square-based test statistics.
CMH = Cochran-Mantel-Haenszel; 
COVID-19 = coronavirus 
disease 
2019; 
CT = computed 
tomography; 
 
 
 
 
 
 
 
HCC = hepatocellular 
carcinoma; 
HI = hepatic 
impairment; 
INR = international normalized ratio; IV = intravenous; MRI = magnetic resonance imaging; PK = pharmacokinetics; 
US = United States
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BMS-986263
HSP47 siRNA
Overall Rationale for the Revised Protocol 01, 27-May-2020
The primary purpose of this Global Revised Protocol is to adjust an inclusion criterion for 
participants without steatohepatitis (to add a biopsy-based requirement). Key secondary revisions 
include the following:

Correcting an exclusion criterion-related equation for estimated glomerular filtration rate, now 
replaced by literature reference

Adding nintedanib as a concomitant medication restriction

Adding/clarifying statistical analysis methods for primary and secondary
 efficacy 
endpoints

Updating interim analyses to include a single analysis only

Incorporating changes previously provided in country-specific amendments and an 
administrative letter

Updating sections to align with current protocol template

Updating background clinical study data

Adding the recommended stepped infusion rates for study treatment

Adding required urine pregnancy test prior to visits in which dual-energy X-ray absorptiometry 
is conducted

Clarifying study exclusion exceptions related to Child-Pugh exclusion criterion

Specifically referencing an Independent Pathology Review Committee and respective charter 
to be utilized in the study

Adding an appendix for exclusion of human immunodeficiency virus positive participants 
where locally required
All changes applied to the body were applied to the synopsis, as necessary; synopsis changes are 
not included in the list below.
Only major additions and deletions are provided in this summary document; all minor 
grammatical, formatting, rephrasing, stylistic changes, or clarifications are not included.
The rationale(s) for changes to this Revised Protocol are provided in the summary of key changes 
table, as shown below:
SUMMARY OF KEY CHANGES TO THE REVISED PROTOCOL 01
Section Number & Title
Description of Change
Brief Rationale
Title Page
Updated Medical Monitor
Updated with current contact 
(initially updated with Protocol 
Administrative Letter 01, dated 
01-Feb-2020).
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BMS-986263
HSP47 siRNA
SUMMARY OF KEY CHANGES TO THE REVISED PROTOCOL 01
Section Number & Title
Description of Change
Brief Rationale
Study Acknowledgment/
Disclosure
Removed
Will be included as separate 
stand-alone document with 
added placeholder for Study 
Director/Medical Monitor 
signature (to align with 
US-specific Revised Protocol 
00a, dated 21-Feb-2020).
1.3 Schedule of Activities, 
Table 2 and Table 3
3 Objectives and Endpoints
4.1.1 Screening Period
 
 
5.4 Lifestyle Restrictions
6.7.2 Concomitant 
Medication Restrictions for 
the 13C MBT Assessment
 
 
 
 
Appendix 1 Abbreviations 
and Trademarks
Removed 
 
 
information/sections
Removed to reduce operational 
complexity and number of visit 
procedures.
1.3 Schedule of Activities, 
Table 1 and Table 3
Added required urine 
pregnancy test prior to visits in 
which a DXA scan is 
conducted
Added because pregnancy 
testing prior to DXA scan is 
standard practice.
2.2.2 Clinical Studies
Updated background clinical 
study data
Updated to align with data 
from the Study IM025006 final 
CSR and the current 
Investigator’s Brochure.
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BMS-986263
HSP47 siRNA
SUMMARY OF KEY CHANGES TO THE REVISED PROTOCOL 01
Section Number & Title
Description of Change
Brief Rationale
4.1.3 DMC and Other 
External Committees
Referenced the utilization of an 
IPRC and respective charter in 
the study
Original protocol referenced a 
central pathologist; this change 
is to reflect use of a pathology 
review committee.
5.1 Inclusion Criteria
2) Type of Participant 
and Target Disease 
Characteristics
Replaced as follows:
2)a) → 2)e)
Revised to clarify liver biopsy 
inclusion criteria for subjects 
without definite steatohepatitis.
5.1 Inclusion Criteria
3) Age and reproductive 
status
Replaced as follows:

3)a)b → 3)a)e

3)a)d → 3)a)f

3)b)c → 3)b)i

3)b)d → 3)b)j

3)b)e → 3)b)k

3)b)f → 3)b)l

3)b)g → 3)b)m
Revised to align with current 
protocol template.
5.2 Exclusion Criteria
1) Target disease
Replaced as follows:

1)d) → 1)g)
Revised to clarify study 
exclusion exceptions related to 
Child-Pugh exclusion criterion.
5.2 Exclusion Criteria
3) Prior and concomitant 
therapy
6.7.1 Prohibited and/or 
Restricted Treatments
Added nintedanib as a 
concomitant medication 
restriction [added as 3)f)]
Added due to a preclinical 
finding of enhancement of 
bone toxicity with nintedanib 
in combination with 
BMS-986263.
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HSP47 siRNA
SUMMARY OF KEY CHANGES TO THE REVISED PROTOCOL 01
Section Number & Title
Description of Change
Brief Rationale
5.2 Exclusion Criteria
5) Allergies and adverse 
drug reaction
6 Treatment
6.1 Treatments 
Administered
Updated exclusion criterion 
(and sections with 
corresponding text) to 
parenthetically include 
 as follows:

5)a) → 5)c)
 
 
6.1.1 Study Treatment 
Infusion Rate
Added recommended stepped 
infusion rates for study 
treatment and recommended 
course of action if infusion rate 
modifications are being 
considered
Added to provide guidance 
regarding the recommended 
rates for study treatment 
infusion.
8.4.1 Clinical Safety 
Laboratory Assessments
Replaced equation for the 
eGFR rate with up-to-date 
literature reference
Replaced because previously 
included equation was 
incomplete.
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HSP47 siRNA
SUMMARY OF KEY CHANGES TO THE REVISED PROTOCOL 01
Section Number & Title
Description of Change
Brief Rationale
9.4.1 Efficacy Analyses/
Primary Endpoint
Replaced Chi-square test with 
Cochran-Mantel-Haenszel test 
stratified by randomization 
strata to test the difference in 
distribution of response rate 
among 3 treatment groups, and 
specified test significance level 
prompting pairwise 
comparisons to placebo
The Chi-square test does not 
specifically allow for adjusting 
for randomized strata; the 
Cochran-Mantel-Haenszel test 
does allow for this adjustment.
9.4.1 Efficacy Analyses/
Secondary 
 
Endpoints
Added mixed model for 
repeated measurements
Added additional statistical 
analysis option for continuous 
secondary 
 
endpoints.
9.4.5 Interim Analysis
Removed first interim analysis 
(after approximately 30% of 
participants completed the 
Follow-up Week 4 
visit/discontinued prior to this 
visit) and specified contents of 
the DMC Charter related to 
interim analysis
To reduce the number of 
interim analyses performed in 
the study, this analysis will 
only be conducted one time, 
when 50% of participants have 
completed Follow-up Week 4.
Appendix 8 
Country-specific 
Requirements
Added appendix
Added to indicate changes to 
be made to appropriate 
protocol sections related to 
participants who are HIV 
positive in countries in which 
it is locally mandated that such 
patients be excluded.
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