Conditions: Hepatic Cirrhosis Liver Fibrosis
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 61
Healthy volunteers: no

Brief summary:
This is a study of experimental medication BMS-986263 in adult patients with advanced hepatic fibrosis (scar tissue in the liver caused by inflammation that is far on in progress) after the patient is cured of hepatitis C (an infection caused by a virus that attacks the liver and leads to inflammation).

Detailed description:

Arms:
arm 1: None arm 2: None arm 3: None arm 4: None arm 5: None arm 6: None arm 7: None

Interventions: intervention 1: BMS-986263 intervention 2: Placebo
Intervention descriptions: intervention 1: Administered by intravenous (IV) infusion intervention 2: Administered by intravenous (IV) infusion

Protocol document:
Prot_004.pdf: 
 
BMS CONFIDENTIAL 
 
 
Page: 1 
Protocol Number: IM025006 
IND Number: 136523 
 
EUDRACT Number: Not applicable 
Date: 21-Feb-2019 
 
Version: Final Approved v7.0 
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   
Test Drug: BMS-986263 
Study Director 
Medical Monitor 
 
 
24-hour Emergency Telephone Number 
 
Bristol-Myers Squibb Research and Development 
Route 206 & Province Line Road 
Lawrenceville, NJ 08543 
    
 
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) (IECs). Any other use, 
copying, disclosure or dissemination of this information is strictly prohibited unless expressly 
authorized in writing by BMS. Any supplemental information (eg, amendments) 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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DOCUMENT HISTORY 
Document 
Date of Issue 
Summary of Changes 
Approvers 
Original Protocol 
01-Nov-2017 
Not Applicable 
Amendment 01 
05-Jan-2018 
Incorporates changes to multiple 
sections of the protocol in response 
to Health Authority interactions. 
Provides clarifications of 
interpretation of the protocol and 
increases consistency within the 
protocol. 
Revised Protocol 01 
(Final Approved v2.0) 
05-Jan-2018 
Incorporates Amendment 01 
Amendment 02 
22-Mar-2018 
Incorporates changes to multiple 
sections of the protocol based on 
regulatory interactions. Addition of 
dose arm in Part 1 and changes to 
study drug administration. Increases 
consistency within the protocol. 
Incorporates minor grammatical and 
editorial corrections.  
Revised Protocol 02 
(Final Approved v3.0) 
22-Mar-2018 
Incorporates Amendment 02 
Amendment 03 
19-Jun-2018 
Incorporates changes to various 
sections of the protocol based on 
feedback received from the 
Investigator and recent submission 
to Health Authority. Includes 
clarification for study treatment 
administration 
 
 
Revised Protocol 03 
(Final Approved v4.0) 
19-Jun-2018 
Incorporates Amendment 03 
Amendment 04 
17-Aug-2018 
 
 Additionally, 
incorporates updates in the 
eligibility criteria and clarifications 
in study treatment discontinuation 
criteria. 
Revised Protocol 04 
17-Aug-2018 
Incorporated Amendment 04 
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Document 
Date of Issue 
Summary of Changes 
Approvers 
(Final Approved v5.0) 
Amendment 05 
13-Nov-2018 
Appendix 2 revised to remove text 
that incorrectly suggested that 
disease-related events do not meet 
the AE definition and, therefore, 
should not be reported as AEs. All 
such events must be reported as 
AEs. 
Revised Protocol 05 
(Final Approved v6.0) 
13-Nov-2018 
Incorporated Amendment 05 
Amendment 06 
21-Feb-2019 
 
 Additional 
clarifications for select 
endpoints/objectives related to 
MRE, collection of concomitant 
medication data, and for SAE 
reporting (to designee of Sponsor) 
included. 
Revised Protocol 06 
(Final Approved v7.0) 
21-Feb-2019 
Incorporated Amendment 06 
 
 
 
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1. PROTOCOL SUMMARY  
1.1 Synopsis 
NAME OF SPONSOR: Bristol-Myers Squibb (BMS) 
PROTOCOL No.: IM025006 
NAME OF STUDY TREATMENT: BMS-986263 
TITLE OF STUDY: 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 
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STUDY CENTERS: Approximately 41 centers in the United States 
STUDY PERIOD: Up to 35 days screening followed by 12 weeks or 24 weeks 
of treatment in Part 1 or Part 2, respectively, and 24 weeks or 12 weeks follow-up 
period in Part 1 or Part 2, respectively, for a total study period of approximately 
10 months. 
PHASE OF 
DEVELOPMENT: Phase 2 
PLANNED STUDY DATES: January 2018 – December 2020 
OBJECTIVES:  
Primary Objective: 
• 
Part 1: To assess the effect of treatment with 90 mg QW BMS-986263 on the proportion of participants 
with ≥ 1 stage improvement in liver fibrosis (METAVIR score), as compared to placebo after 12 weeks of 
treatment 
• 
Part 2: To assess the effect of treatment with 45 mg Q2W, 90 mg Q2W, and 90 mg Q4W BMS-986263 on 
the proportion of participants with ≥ 1 stage improvement in liver fibrosis (METAVIR score), as compared 
to placebo after 24 weeks of treatment  
Secondary Objectives: 
• 
Part 1  
o 
To assess the effect of treatment with 90 mg QW BMS-986263 on the change in collagen 
proportionate area (CPA), as compared to placebo after 12 weeks of treatment 
o 
To assess the effect of treatment with 90 mg QW BMS-986263 on the proportion of participants 
with ≥ 1 stage improvement in liver fibrosis (Ishak score), as compared to placebo after 12 weeks 
of treatment 
o 
To assess the effect of treatment with 90 mg QW BMS-986263 on the proportion of participants 
with ≥ 2 stage improvement in liver fibrosis (METAVIR score), as compared to placebo after 
12 weeks of treatment 
o 
To assess the effect of treatment with 90 mg QW BMS-986263 on the proportion of participants 
with ≥ 2 stage improvement in liver fibrosis (Ishak score), as compared to placebo after 12 weeks 
of treatment 
o 
To assess the effect of treatment with 90 mg QW BMS-986263 on the proportion of participants 
with a ≥ 15% reduction in liver stiffness as measured by MRE compared to placebo at Week 12 
o 
To assess the effect of treatment with 90 mg QW BMS-986263 on the change in liver stiffness 
from baseline as measured by MRE compared to placebo at Week 12 
o 
To assess the safety and tolerability of 45 mg QW and 90 mg QW BMS-986263 throughout 
36 weeks of treatment and follow-up 
o 
To assess the PK of 45 mg QW and 90 mg QW BMS-986263 
o 
To describe the effect of treatment with 45 mg QW BMS-986263 on liver fibrosis after 12 weeks 
of treatment 
 
 
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• 
Part 2  
o 
To assess the effect of treatment with several doses of BMS-986263 on the change in CPA, as 
compared to placebo after 24 weeks of treatment 
o 
To assess the effect of treatment with several doses of BMS-986263 on the proportion of 
participants with ≥ 1 stage improvement in liver fibrosis (Ishak score), as compared to placebo 
after 24 weeks of treatment 
o 
 To assess the effect of treatment with several doses of BMS-986263 on the proportion of 
participants with ≥ 2 stage improvement in liver fibrosis (METAVIR score), as compared to 
placebo after 24 weeks of treatment 
o 
To assess the effect of treatment with several doses of BMS-986263 on the proportion of 
participants with ≥ 2 stage improvement in liver fibrosis (Ishak score), as compared to placebo 
after 24 weeks of treatment 
o 
To assess the effect of treatment with several doses of BMS-986263 on the proportion of 
participants with a ≥ 15% reduction in liver stiffness as measured by MRE compared to placebo 
at Week 24 
o 
To assess the effect of treatment with several doses of BMS-986263 on the change in liver stiffness 
from baseline as measured by MRE compared to placebo at Week 24 
o 
To assess the safety and tolerability of several doses BMS-986263 throughout 36 weeks of 
treatment and follow-up 
o 
To assess the PK of BMS-986263 
STUDY DESIGN AND METHODOLOGY:  
This is a randomized, double-blind, placebo-controlled, parallel group study to evaluate the efficacy and safety of 
BMS-986263 in adults with advanced hepatic fibrosis due to HCV who have achieved SVR for at least 1 year. This 
study will enroll approximately 60 participants in Part 1, randomized in a 1:2:1 ratio to treatment with 45 mg 
BMS-986263 QW, 90 mg BMS-986263 QW, or placebo QW for 12 weeks; and approximately 120 participants in 
Part 2, randomized in a 1:1:1:1 ratio to receive 45 mg BMS-986263 Q2W, 90 mg BMS-986263 Q2W, 90 mg 
BMS-986263 Q4W, or placebo Q2W for 24 weeks. The primary study endpoint is the proportion of participants that 
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Visit details are provided in the Screening and Day 1 (Randomization) Procedural Outline for Part 1 and Part 2 in 
Table 1. 
Part 1 Treatment Period and Follow-up 
Approximately 60 participants meeting eligibility criteria during the screening period will be randomized into the 
Part 1 treatment period. These participants will be randomized via interactive response technology (IRT) in a 
1:2:1 ratio to receive 45 mg BMS-986263 QW, 90 mg BMS-986263 QW, or placebo QW in a double-blind manner. 
The randomization of participants will be stratified by fibrosis stage (METAVIR Stage 3 or Stage 4). Participants 
will receive study treatment via IV administration for a total of 12 weeks. 
Fibrosis stage will be assessed by liver biopsy during the screening period and on Day 85. Liver stiffness will be 
assessed by MRE at baseline, Day 43, Day 85 (primary efficacy endpoint), Day 169, and Day 253.  
After 12 weeks (Day 85) of treatment, participants in Part 1 will enter the 24-week follow-up period. During this 
time, they will not receive infusions of either active drug or placebo.  
See the Schedule of Activities for Part 1 in Table 2 and Table 3 (Section 1.2).  
 
Part 2 Treatment Period and Follow-up 
Participants meeting eligibility criteria during the screening period will enter the Part 2 treatment period. 
Approximately 120 participants will be randomized via IRT in a 1:1:1:1 ratio to receive 45 mg BMS-986263 Q2W, 
90 mg BMS-986263 Q2W, 90 mg BMS-986263 Q4W, or placebo Q2W in a double-blind manner. Randomization 
of the participants will be stratified by fibrosis stage (METAVIR Stage 3 or Stage 4). Participants will receive study 
treatment via IV administration for a total of 24 weeks. Liver biopsy will be performed during the screening period 
and on Day 169. MRE will be collected at Day 43, Day 85, Day 169, and Day 253 in Part 2.  
After 24 weeks (Day 169) of treatment, participants in Part 2 will enter the follow-up period for 12 weeks. During 
this time, they will not receive infusions of either active drug or placebo.  
See the Schedule of Activities for Part 2 in Table 4 and Table 6 (Section 1.2).  
STUDY POPULATION AND MAIN ELIGIBILITY CRITERIA:  
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. 
Participants must be willing to participate in the study and sign the informed consent form (ICF). 
b. Participants must be willing and able to complete all study-specific procedures and visits. 
2. Participants must provide documentation showing an SVR for at least 1 year prior to the date of screening. 
SVR is defined as a negative HCV RNA at least 12 weeks from the end of antiviral therapy. Thus, the 
minimum duration is 12 weeks of negative HCV RNA (to establish SVR) plus 1 year of sustained SVR (ie, 
52 weeks + at least 12 weeks).  
3. The participant must have METAVIR Stage 3 or Stage 4 fibrosis (or equivalent if using other classification; 
eg, Ishak) assessed by liver biopsy.  
4. Participants must have a mean score of ≥ 5.0 kPa by FibroScan (Section 8.6.1.4). If a participant has not 
had a liver biopsy within 8 weeks of screening, the biopsy will be carried out during the screening period 
following determination of eligibility by FibroScan assessment (ie, has mean FibroScan score of ≥ 5.0 kPa). 
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5. The participant must have an adequate MRE and DXA performed during screening confirmed by the central 
imaging facility prior to randomization.   
6. Age and reproductive status 
a. 
Males or females ≥ 21 and ≤ 75 years of age at the time of screening 
b. Women of childbearing potential (WOCBP) must have a negative urine pregnancy test (minimum 
sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin) within 24 hours prior to the 
start of study and prior to each dose of study treatment.  
c. 
To confirm menopause, females must have a serum follicle stimulating hormone (FSH) level 
> 40 mIU/mL.  
d. Women must not be breastfeeding 
e. 
WOCBP must agree to follow instructions for method(s) of highly effective contraception, as defined 
in Appendix 3, for the duration of treatment (BMS-986263 or placebo) plus 5 half-lives of study 
treatment (5 days) plus 30 days (duration of ovulatory cycle) for a total of 35 days post-treatment. 
f. 
Males who are sexually active with WOCBP must agree to have their female partners follow 
instructions for method(s) of highly effective contraception, as defined in Appendix 3, for the 
duration of treatment with study treatment (BMS-986263 or placebo) plus 5 half-lives of the study 
treatment plus 90 days (duration of sperm turnover) for a total of 95 days after treatment completion. 
In addition, male participants must be willing to refrain from sperm donation during this time. 
g. Azoospermic males are exempt from contraceptive requirements for the purposes of prevention of 
pregnancy (ie, male study participants with partners who are WOCBP). However, in addition to the 
use of highly effective methods of contraception, males in the study who are sexually active with 
WOCBP must use barrier methods (eg. male condom, female condom) to prevent transmission of 
seminal fluid that may contain traces of study drug. Barrier methods must be used for the duration of 
exposure with study treatment (BMS-986263 or placebo) plus 5 half-lives of the study treatment plus 
90 days (duration of sperm turnover) for a total of 95 days after treatment completion. 
h. WOCBP who are continuously not heterosexually active are also exempt from contraceptive 
requirements, and still must undergo pregnancy testing as described in this section.  
Investigators shall counsel WOCBP and male participants (and/or their caregivers, as applicable) who are sexually 
active with WOCBP, on the importance of using highly effective pregnancy in light of the potential for teratogenicity 
(Appendix 3). Investigators shall advise on the use of highly effective methods of contraception (ie, those that have 
a failure rate of < 1% when used consistently and correctly). 
Exclusion Criteria 
1. Target disease exclusions  
a. 
Other causes of liver disease including but not limited to alcoholic liver disease, hepatitis B virus 
(HBV; serologically-positive as determined using United States Centers for Disease Control and 
Prevention guidance for interpretation of hepatitis B serologic test results), autoimmune hepatitis, 
drug-induced hepatotoxicity, Wilson disease, iron overload, -1-antitrypsin deficiency, NASH, 
hemochromatosis); participants having liver diseases associated with infection with any other 
hepatitis virus are to be excluded. It is up to the investigator to be sure the participants do not have 
any of the above mentioned pathologies.  
b. 
Detectable HCV RNA at screening 
c. 
Child-Pugh score > 6 at screening (Appendix 7) 
d. 
MELD score > 12 based on screening laboratories (Appendix 8) 
e. 
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 or 
ultrasound; based on local assessment):  
i. 
AFP > 100 ng/mL (> 82.6 IU/mL) OR 
ii. 
AFP ≥ 50 and ≤ 100 ng/mL (≥ 41.3 IU/mL and ≤ 82.6 IU/mL) with liver imaging showing 
evidence of HCC 
2. Medical conditions 
a. 
Blood transfusion in the last 6 months prior to screening due to the risk of reinfection with HCV, 
HBV, human immunodeficiency virus (HIV), etc 
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b. The participant has any disease or condition which, in the opinion of the investigator, might 
compromise patient safety (eg, hematologic, cardiovascular, pulmonary, renal, gastrointestinal, 
hepatic, skeletal, central nervous system, or complement-mediated disease). 
c. 
Hepatitis B surface antigen (HBsAg)-positive participants or hepatitis B core antibody 
(HbcAb)-positive participants with detectable hepatitis B viral DNA. Where required by local 
regulations or standard practice, hepatitis B surface antibody (HBsAb)-positive participants must 
also have HBV DNA testing performed.  
d. Known immunocompromised status, including but not limited to individuals who have undergone 
organ transplantation or who are positive for HIV or have acquired immunodeficiency 
syndrome-related illness, as reported by the participant and/or documentation.  
e. 
History of liver transplantation or planned liver transplant 
f. 
Any history of hepatic decompensation, including ascites, variceal bleeding, hepatic encephalopathy 
or spontaneous bacterial peritonitis. 
g. The participant has a 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. 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 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.  
i. 
History of alcohol consumption 21 units/week (males) or 14 units/week (females) 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. Participants should limit 
alcohol during their participation in the study (Section 8.4.4).  
j. 
History, within the last 2 years, of alcohol or frequent marijuana abuse (in the opinion of the 
Investigator), significant mental illness, or physical dependence on any opioid. 
k. Positive urine test during screening for illegal drugs of abuse (with the exception of marijuana), 
unless these drugs are prescribed by the treating physician (prescription must be documented by the 
investigator or the designee in source documents).  
l. 
History of intravenous drug use within the 3 years prior to screening. 
m. History of bariatric surgery within the 5 years prior to screening or planned during the conduct of the 
study. 
n. History of major surgery within 3 months of screening; this includes surgery that involves a risk to 
the life of the patient, specifically, within the cranium, chest, abdomen, or pelvic cavity.  
o. History of weight gain/loss ≥ 10% of body weight in the 6 months prior to screening.  
p. Inability to tolerate IV medication or other study procedures  
q. Presence of pacemaker and or other metal objects in the body  
3. Prior and concomitant therapy 
a. 
Participants who take any medications that, in the opinion of the investigator, increase the risk for 
complications during liver biopsy (eg, chronic or high-dose nonsteroidal inflammatory drugs, 
anticoagulants, or fish oil supplements) 
b. Participants taking anti-obesity agents (eg, ORLISTAT®) within 4 weeks of the first dose of study 
treatment.  
c. 
Participants receiving interferon therapy for any disease, or received interferon therapy for any 
disease within 52 weeks prior to administration of study treatment. 
d. The participant takes any vitamin A containing supplements or multivitamins, or vitamin A 
containing medications after signing the ICF. 
e. 
Participants taking anti-diabetic or anti-dyslipidemic medication receiving stable doses for less than 
30 days prior to the first dose of study medication. 
f. 
Participants unable to comply with restrictions and prohibited treatments. 
g. Participants who have not discontinued other investigational agents must be discontinued at least 
12 weeks or 5 half-lives before the first dose of study treatment, whichever is longer.  
h. Prior exposure to BMS-986263 
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i.
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).
4.
Physical and laboratory test findings
a.
Evidence of organ dysfunction or any clinically significant deviation from normal in physical
examination, vital signs, electrocardiogram (ECG), or clinical laboratory determinations beyond
what is consistent with the target population
b.
Body mass index (BMI) > 34 kg/m2. Participants with a BMI of 30-34 kg/m2 must have an
ALT ≤ upper limit of the normal range (ULN).
c.
The participant’s baseline laboratory test results include abnormal values considered to be clinically
significant by the investigator.
d.
The participant’s laboratory test results at screening include any of the following:
•
albumin < 3.5 g/dL
•
INR > ULN
•
ALT value ≥ 2× the ULN
•
hemoglobin A1c ≥ 9.0%
•
total bilirubin > ULN
•
hemoglobin < lower limit of normal (LLN)
•
platelet count < 100,000/µL
•
white blood cell count ≤ 3000/µL
e.
Glomerular filtration rate < 30 mL/min/1.73 m2 according to the Modification of Diet in Renal
Disease equation.
f.
The participant’s vitamin A levels at screening are > ULN.
g.
Alpha-fetoprotein (AFP; see Exclusion 1e, above):
i.
AFP > 100 ng/mL (> 82.6 IU/mL) OR
ii.
AFP ≥ 50 and ≤ 100 ng/mL (≥ 41.3 IU/mL and ≤ 82.6 IU/mL) with liver ultrasound showing
findings suspicious for HCC.
5.
Not applicable
6.
Allergies and adverse drug reaction
a.
History of allergy to BMS-986263 or related compounds
7.
Other exclusion criteria
a.
Prisoners or participants who are involuntarily incarcerated. Note: Under certain specific
circumstances, 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.
Participants who participated in an interventional study with the last intervention occurring within
24 weeks prior to administration of study treatment.
d.
Any factor, which in the opinion of the investigator would jeopardize the evaluation or safety or be
associated with poor adherence to the protocol.
MRI Contraindications 
The imaging specialist at the site’s imaging facility will be responsible for determining whether a participant is 
contraindicated from undergoing these procedures. Common conditions that may preclude the participant from scans 
include, but are not limited to: 
a.
History of claustrophobia
b.
Physical limitations related to fitting into the bore of the magnet or weight greater than that allowable
by the imaging instrument (i.e., body weight in excess of 250 pounds or 113.4 kg)
c.
Participants with a pacemaker, epicardial pacemaker wires, MRI-incompatible cardiac valve
prostheses, MRI-incompatible vascular clips less than 2 months old, or MRI-incompatible aneurysm
clips of any age
d.
Participants with MRI-incompatible cochlear implants
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e.
Participants with spinal nerve stimulators
f.
Participants with an infusion pump
g.
Participants with known metallic fragments in the body
h.
Employment history that involves exposure to welding
The above list should not be used as a substitute for local clinical standards of care. The ultimate decision to perform 
any scan should rest with the site radiologist, the investigator, and the standard set by the IEC. 
Lifestyle Restrictions: 
Participants should not consume ≥ 7 units/week of alcohol during the study. One drink “unit” or one standard drink 
is equivalent to 12 ounces of beer, 4 ounces of wine, or 1 ounce of hard liquor.  
NUMBER OF PARTICIPANTS: 
It is planned that approximately 180 male and female participants will be evaluable for analysis. In Part 1, 
approximately 60 participants will be randomized in a 1:2:1 ratio to receive 45 mg BMS-986263 QW, 90 mg 
BMS-986263 QW, or placebo QW. In Part 2, approximately 120 participants will be randomized in a 1:1:1:1 ratio 
to 45 mg BMS-986263 Q2W, 90 mg BMS-986263 Q2W, 90 mg BMS-986263 Q4W, or placebo Q2W. If a higher 
than expected proportion of study participants discontinue from the study prior to the evaluation of the primary 
endpoint, the sponsor may choose to enroll additional participants to ensure an adequate number of participants are 
available for evaluation of the primary endpoint. 
STUDY TREATMENT(S): 
Test Product and Reference Therapy, Dose and Mode of Administration: 
BMS-986263 (45 mg or 90 mg) or placebo will be administered as an IV infusion according to the treatment schedule 
outlined in the Schedule of Activities (Section 1.2).  
BMS-986263 has the potential to treat liver fibrosis as it combines an HSP47 siRNA with a formulation designed to 
target the HSP47 siRNA to HSCs. 
Please refer to the Pharmacy Manual for complete information on BMS-986263 and placebo storage, handling and 
infusion, and exact volumes and instructions on the preparation of study treatment infusion. 
Study Treatment Infusion Rate 
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The study medication should not be infused at a duration lesser than 60 minutes. The infusion rate may be 
modified by the investigator based on clinical discretion and/or the participant’s previous tolerance of the infusion, 
including any infusion reactions that may have occurred in the past. In addition, the investigator may choose to 
pause the infusion depending on the participant’s clinical condition and history.  
Of note, while the rate of infusion can be modified as described above; no reductions or modifications of the total 
dose to be administered are allowed. 
If a participant experiences an infusion-related reaction, temporary interruption of the infusion and/or reduction of 
the infusion rate (for example, but not limited to, modification of infusion rate and/or a pause in the infusion) may 
lead to improvement of signs and symptoms. Medications, emergency equipment, and trained personnel able to treat 
immediate or delayed infusion-related reactions should be available for immediate access at the clinical site(s).  
Premedication 
To reduce the potential for possible infusion reactions, based on the discretion of the investigator, the 20 participants 
in Part 1 may be pretreated 15 to 30 minutes before the start of the study treatment infusion. The investigator may 
choose to administer any or all of the following premedications: 50 mg diphenhydramine hydrochloride IV, 20 mg 
famotidine IV, and/or hydrocortisone 100 mg IV. Hydrocortisone IV may be replaced with methylprednisolone 
sodium succinate 125 mg IV based on the discretion of the investigator. Additionally, the investigator may choose 
not to administer any premedication. If IV diphenhydramine is not available, an oral dose of 5 mg levocetirizine 
dihydrochloride or an oral dose of 50 mg diphenhydramine hydrochloride may be substituted and administered 2 
hours ± 15 minutes before the start of study treatment infusion.  
Participants who receive antihistamine premedication should be advised that these medications may be sedating and 
cautioned against driving or operating heavy machinery for at least 3 hours after administration, although a longer 
observation period may be necessary for an individual participant. The decision to observe a study participant beyond 
the required 3 hours will be at the discretion of the attending investigator.  
DURATION OF TREATMENT: In Part 1, each participant will undergo 12 weeks of treatment. In Part 2, each 
participant will undergo 24 weeks of treatment. All treatment groups will be followed for a total of 36 weeks, 
consisting of 24 weeks follow-up for Part 1, and 12 weeks follow-up for Part 2 (see schematic, above). 
STUDY EVALUATIONS: 
Primary Efficacy Endpoint: 
The primary efficacy endpoint is the proportion of participants who achieve ≥ 1 stage improvement in liver fibrosis 
(METAVIR score) as determined by liver biopsy after 12 weeks of treatment in Part 1 and after 24 weeks in Part 2. 
Secondary Efficacy Endpoints: 
•
Change in CPA, as compared to placebo after 12 weeks of treatment in Part 1 and after 24 weeks of
treatment in Part 2
•
Proportion of participants with ≥ 1 stage improvement in liver fibrosis (Ishak score), as compared to placebo
after 12 weeks of treatment in Part 1 and after 24 weeks of treatment in Part 2
•
Proportion of participants with ≥ 2 stage improvement in liver fibrosis (METAVIR score), as compared to
placebo after 12 weeks of treatment in Part 1 and after 24 weeks of treatment in Part 2
•
Proportion of participants with ≥ 2 stage improvement in liver fibrosis (Ishak score), as compared to placebo
after 12 weeks of treatment in Part 1 and after 24 weeks of treatment in Part 2
•
Proportion of participants with ≥ 15% decrease from baseline in liver stiffness as measured by MRE at
Day 85 in Part 1 and Day 169 in Part 2
•
Change from baseline in liver stiffness as measured by MRE Day 85 in Part 1 and Day 169 in Part 2
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Other analyses: 
•
Safety endpoints include incidence of adverse events (AEs), serious adverse events (SAEs), 
 AEs leading to discontinuation, and death, as well as marked abnormalities in clinical
laboratory tests, vital sign measurements, ECGs, physical examinations 
•
Pharmacokinetics, PD, 
 of BMS-986263 will be analyzed based on the time points
indicated in the Schedule of Activities (Section 1.2).
STATISTICAL METHODS: 
Primary Endpoint Part 1: 
To evaluate the effect of BMS-986263 (90 mg QW) on METAVIR fibrosis Stage at Week 12, a 95.0% confidence 
interval (CI) of response rate for treatment vs placebo will be used to estimate the difference between the proportion 
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of participants with ≥ 1 stage improvement in fibrosis as determined by liver biopsy. Additionally, the odds ratio 
will be used to estimate improvement of treatment as compared to placebo for the proportion of participants with > 
1 stage improvement in fibrosis on liver biopsy at Week 12. 
Primary Endpoint Part 2:  
To evaluate the effect of BMS-986263 (45 mg Q2W, 90 mg Q2W, and 90 mg Q4W), on METAVIR Fibrosis Stage 
vs placebo, a stratified Cochran Armitage Trend Test controlling for hepatic fibrosis stage (Stage 3 or Stage 4) will 
be used to analyze the proportion of participants with ≥ 1 stage improvement in fibrosis on liver biopsy at Week 24. 
After the assessment of trend, comparisons of each treatment group with placebo will be performed utilizing a 
stratified (fibrosis stage) Cochran Mantel-Haenszel test (CMH). All of these analyses will be performed at 1-sided 
0.05 level of significance. In addition, 95% CIs for the response rates and odds-ratios will be calculated. A sensitivity 
analysis using an extended CMH correlation test will be used to assess the trend among the proportions for treatment 
groups with an adjustment to strata (fibrosis stage). Two- sided 0.1 level of significance will be used. 
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. 
Continuous endpoints may be analyzed by analysis of covariance methods. 
Categorical endpoints will be summarized using counts and percentages and when appropriate may be analyzed 
using categorical analysis methods. 
Subgroup analyses will be performed including hepatic fibrosis stage. 
Safety Analysis:  
Safety assessments 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.  
DATE AND VERSION: 21-Feb-2019, Final Approved v7.0 
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1.2 Schedule of Activities 
Visit details are provided for the Screening and Day 1 (Randomization) Procedural Outline for 
Part 1 and Part 2 in Table 1. Visit details are provided for Part 1 treatment and follow-up periods 
in Table 2 and Table 3, respectively, Part 2 treatment Period in Table 4 and Table 5, and Part 2 
follow-up period in Table 6. 
In the event that multiple procedures are required at a single timepoint, the electrocardiogram 
(ECG) may be obtained up to 15 minutes earlier; vital signs may be obtained up to 10 minutes 
earlier; and, clinical laboratory sample may be obtained up to 5 minutes earlier than the nominal 
time point, ensuring the pharmacokinetic (PK) samples can be collected on time. These study 
procedures must be performed prior to infusion. 
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Table 1 
Screening and Day 1 (Randomization) Procedural Outline IM025006: Part 1 and Part 2 
Procedure 
Screeninga 
Day -35 to -1 
Day 1 
(Randomization) 
Notes 
Eligibility Assessments 
Informed consent 
X 
 
The approved informed consent form (ICF) must be signed before completing 
any protocol-specific procedures. A participant will be considered enrolled 
only when the informed consent is signed. 
Inclusion/exclusion criteria 
X 
 
 
Medical history 
X 
X 
 
Prior medications 
X 
X 
Prior medications are medications taken within 4 weeks before the first dose 
of study medication and discontinued before the first dose of study 
medication. 
Call via IRT to register 
participant 
X 
 
See Section 8.5.2 for additional information. 
Safety Assessments  
Concomitant medication use 
X 
X 
 
Monitor for AEs 
 
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 
will occur at every study visit. 
Monitor for SAEs 
X 
X 
All SAEs must be collected from the date of participant’s written consent 
until 30 days after the final dose of the study treatment or the participant’s 
participation in the study if the last scheduled visit occurs at a later time. 
Monitoring for SAEs will occur at every study visit. 
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Table 1 
Screening and Day 1 (Randomization) Procedural Outline IM025006: Part 1 and Part 2 
Procedure 
Screeninga 
Day -35 to -1 
Day 1 
(Randomization) 
Notes 
Physical and Metabolic 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) evaluation. 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, 
extremities, height, and body weight.  
Abbreviated physical 
assessment 
 
X 
Abbreviated examinations will include vital signs, weight, an abdominal 
exam, assessments of ascites and hepatic encephalopathy, and symptom-
focused assessments. 
Collect height and weight 
X 
X 
 
Body mass index calculation 
X 
X 
Appendix 8 
Vital Signs 
X 
X 
Includes body temperature, respiratory rate, and seated 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 electrocardiogram 
X 
X* 
* On Day 1 (Randomization), ECGs should be recorded prior to infusion but 
after the participant has been supine for at least 5 minutes.  
Liver biopsy 
X 
 
Refer to Section 8.6.1.1 for eligibility criteria.  
Key eligibility criteria should be evaluated prior to biopsy, MRE, and DXA.  
For participants with prior biopsies, hepatic tissue must be made available for 
central analysis.  
For participants undergoing biopsy, eligibility must be confirmed as described 
in Section 8.1.1.  
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Table 1 
Screening and Day 1 (Randomization) Procedural Outline IM025006: Part 1 and Part 2 
Procedure 
Screeninga 
Day -35 to -1 
Day 1 
(Randomization) 
Notes 
DXA 
X 
DXA must be conducted at least 5 days ahead of Day 1 (Randomization) to 
allow adequate time for results to be provided. Adequacy of DXA should be 
confirmed by the imaging vendor prior to randomization. See Section 8.6.2.8. 
Key eligibility criteria should be evaluated prior to biopsy, MRE, and DXA.  
MRE 
X 
MRE must be conducted at least 5 days ahead of Day 1 (Randomization) to 
allow adequate time for results to be provided. Participants must fast for 4 
hours prior to MRE. Adequacy of MRE should be confirmed by the imaging 
vendor prior to randomization. See Section 8.1.1 and Section 8.6.1.2. Key 
eligibility criteria should be evaluated prior to biopsy, MRE, and DXA.  
FibroScan® 
X 
Use of FibroScan to determine eligibility is described in Section 8.1.1. 
Participants must fast for 4 hours prior to FibroScan assessments and must 
have a mean score of ≥ 5.0 kPa by FibroScan at baseline. 
See Section 8.6.1.4. 
Ultrasound 
X 
 
Ultrasound must be conducted at screening for potential evidence of HCC, as 
described in Section 8.4.2.  
Laboratory Assessments 
Hematology 
X 
X 
Pre-infusion when on a dosing day. To assess stability of liver function, 
Screening and Day 1 (Randomization) hematology assessments must be 
performed at least 2 weeks apart (Section 8.1.1).  
See Section 8.6.2.7 and Table 11.  
Chemistry  
X 
X 
Pre-infusion when on a dosing day. To assess stability of liver function, 
Screening and Day 1 (Randomization) chemistry assessments must be 
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Table 1 
Screening and Day 1 (Randomization) Procedural Outline IM025006: Part 1 and Part 2 
Procedure 
Screeninga 
Day -35 to -1 
Day 1 
(Randomization) 
Notes 
performed at least 2 weeks apart (Section 8.1.1). 
See Section 8.6.2.7 and Table 11. 
HbA1C 
X 
 
See Section 8.6.2.7 and Table 11. 
Urinalysis 
X 
X 
See Section 8.6.2.7 and Table 11.  
Serology/viral load 
X 
 
HBsAg-positive participants or HbcAb-positive participants will be tested for 
HBV DNA. Where required by local regulations or standard practice, 
HBsAb-positive participants must also have HBV DNA testing performed. 
HCV genotype 
 
X 
Provided by historical documentation of testing only.  
Drug test 
X 
 
To test for drugs of abuse (amphetamines, barbiturates, benzodiazepines, 
marijuana, cocaine, opiates, and phencyclidine [PCP]).  
Serum AFP 
X 
 
See Section 8.4.2. 
Urine pregnancy test 
X 
X 
For WOCBP only. Urine pregnancy test must be completed to confirm 
participant is not pregnant prior to each infusion. 
See Section 8.6.2.7.  
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Table 1 
Screening and Day 1 (Randomization) Procedural Outline IM025006: Part 1 and Part 2 
Procedure 
Screeninga 
Day -35 to -1 
Day 1 
(Randomization) 
Notes 
FSH 
X 
  
See Appendix 3. 
Pharmacokinetic 
 Sampling 
Blood PK sampling 
 
X 
On Day 1 (Randomization), blood PK samples should be obtained  
• 
Pre-infusion: Time is relative to the start of infusion. Samples may 
be collected up to 120 minutes prior to the start of the infusion.  
• 
Mid-infusion: Time is relative to the start of infusion. Samples 
should be collected ± 3 minutes within specified timeframe. If 
infusion is administered at a modified rate, the timing of collection of 
this sample should correspond to the middle of the modified infusion 
duration of the total administered dose. 
• 
End-of-infusion: Samples should be collected 2 minutes within 
specified timeframe. This sample should be taken immediately prior 
to stopping the infusion. If the end-of-infusion is delayed to beyond 
the nominal infusion duration, the collection of this sample should 
also be delayed accordingly.  
• 
Postinfusion: Time is relative to the end-of-infusion. Samples should 
be collected ± 3 minutes within specified timeframe. See Table 12 
and Table 13.   
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Table 1 
Screening and Day 1 (Randomization) Procedural Outline IM025006: Part 1 and Part 2 
Procedure 
Screeninga 
Day -35 to -1 
Day 1 
(Randomization) 
Notes 
Randomization and Study Treatment/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 8.5.2).  
Administer study treatment 
 
X 
See Section 8.5.1 and Section 8.5.4.  
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AE = adverse event; AFP = alpha-fetoprotein; 
 
 
 
 
 
 
 
 
 
 
 DXA = dual-energy X-ray absorptiometry; 
 ECG = electrocardiogram; FSH = follicle-stimulating hormone; 
HBsAg = hepatitis B surface antigen; HbcAb = hepatitis B core antibody; HBsAb = hepatitis B surface antibody; HBV = hepatitis B virus; HCC = hepatocellular carcinoma; 
HCV = hepatitis C virus; IRT = interactive response technology; 
 MRE = magnetic resonance elastography; 
 
 PK = pharmacokinetics; 
 SAE = serious adverse event; WOCBP = women of child bearing 
potential 
a Participants who experience an acute infection or require additional time for scheduling screening procedures may extend the screening period beyond 35 days after consultation 
with the medical monitor, but not beyond a total of 56 days (8 weeks) from the signing of the informed consent. The screening visit window may also be extended up to 5 additional 
days to accommodate unanticipated delays in obtaining required screening results. An extension beyond 5 days will require approval by the Medical Monitor. Also, as the hematology 
and chemistry laboratory screening and Day 1 (Randomization) assessments must be at least 2 weeks apart, the screening duration is Day -35 to -14 days. 
 
 
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Table 2 
On-Treatment Procedural Outline IM025006: Part 1, Treatment Period (Day 4 through Day 85) 
Procedure/Vi
sit Day  
(± 3 days for 
all visits 
unless 
otherwise 
noted) 
12-week, Double-Blind, Treatment Period 
Notes 
D  
4a 
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 
 
 
W 
1 
W 
2 
W
3 
W 
4 
W 
5 
W  
6 
 
W 
7 
W  
8 
W 
9 
W 
10 
W 
11 
W 
12 
 
Safety Assessments 
Concomitant 
medication use 
 
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. 
Monitor for 
AEs  
 
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 drug through the date of the 
follow-up or last visit. Monitoring for AEs will occur at 
every study visit. 
Monitor for 
SAEs 
 
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 after the final 
dose of the study drug or their participation in the study 
if the last scheduled visit occurs at a later time. 
Monitoring for SAEs will occur at every study visit. 
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Table 2 
On-Treatment Procedural Outline IM025006: Part 1, Treatment Period (Day 4 through Day 85) 
Procedure/Vi
sit Day  
(± 3 days for 
all visits 
unless 
otherwise 
noted) 
12-week, Double-Blind, Treatment Period 
Notes 
D  
4a 
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 
 
 
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 and Metabolic Assessments 
Full physical 
examination 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
A full examination will include general appearance, 
skin, head, eyes, ears, nose, throat, neck, thyroid, 
chest/lungs, heart, abdomen, lymph nodes, extremities, 
height, and body weight. 
Abbreviated 
physical 
assessment 
 
 
X 
 
X 
 
X 
 
 
X 
 
 
 
 
Abbreviated examinations will include vital signs, 
weight, an abdominal exam, assessments of ascites and 
hepatic encephalopathy, and symptom-focused 
assessments. 
12-lead 
electrocardiogr
am  
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
ECGs should be after the participant has been supine for 
at least 5 minutes.  
Liver biopsy  
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
See Section 8.6.1.1. 
MRE 
 
 
 
 
 
 
X 
 
 
 
 
 
 
X 
MRE to be performed ± 7 days of this day to allow sites 
scheduling flexibility. Participants must fast for 4 hours 
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Table 2 
On-Treatment Procedural Outline IM025006: Part 1, Treatment Period (Day 4 through Day 85) 
Procedure/Vi
sit Day  
(± 3 days for 
all visits 
unless 
otherwise 
noted) 
12-week, Double-Blind, Treatment Period 
Notes 
D  
4a 
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 
 
 
W 
1 
W 
2 
W
3 
W 
4 
W 
5 
W  
6 
 
W 
7 
W  
8 
W 
9 
W 
10 
W 
11 
W 
12 
 
prior to MRE. 
See Section 8.6.1.2. 
Laboratory Assessments 
Hematology  
 
 
X 
 
X 
 
X 
 
 
X 
 
X 
 
X 
Pre-infusion when on a dosing day  
See Section 8.6.2.7 and Table 11. 
Chemistry  
 
X 
X 
X 
X 
X 
X 
 
X 
X 
X 
X 
X 
X 
Pre-infusion when on a dosing day  
See Section 8.6.2.7 and Table 11. 
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Table 2 
On-Treatment Procedural Outline IM025006: Part 1, Treatment Period (Day 4 through Day 85) 
Procedure/Vi
sit Day  
(± 3 days for 
all visits 
unless 
otherwise 
noted) 
12-week, Double-Blind, Treatment Period 
Notes 
D  
4a 
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 
 
 
W 
1 
W 
2 
W
3 
W 
4 
W 
5 
W  
6 
 
W 
7 
W  
8 
W 
9 
W 
10 
W 
11 
W 
12 
 
HbA1C 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
See Section 8.6.2.7 and Table 11. 
Urinalysis 
 
 
X 
 
X 
 
X 
 
 
X 
 
 
 
X 
See Section 8.6.2.7 and Table 11. 
Serum AFP 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
See Section 8.6.2.7 and Table 11. 
Urine 
Pregnancy 
 
X 
X 
X 
X 
X 
X 
 
X 
X 
X 
X 
X 
 
For WOCBP only. Urine pregnancy test must be 
completed to confirm participant is not pregnant prior to 
each infusion.  
See Section 8.6.2.1.5. 
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Table 2 
On-Treatment Procedural Outline IM025006: Part 1, Treatment Period (Day 4 through Day 85) 
Procedure/Vi
sit Day  
(± 3 days for 
all visits 
unless 
otherwise 
noted) 
12-week, Double-Blind, Treatment Period 
Notes 
D  
4a 
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 
 
 
W 
1 
W 
2 
W
3 
W 
4 
W 
5 
W  
6 
 
W 
7 
W  
8 
W 
9 
W 
10 
W 
11 
W 
12 
 
Pharmacokinetic 
 Sampling 
Blood PK 
sampling 
X 
X 
X 
 
X 
X 
X 
X 
X 
X 
 
 
X 
X 
See Section 8.6.3 and Table 12. 
*Day 4 and Day 46: Postinfusion: Sample may be 
collected ± 1 day at the PK visit. 
Day 15, Day 36, Day 50, and Day 57: Pre-infusion: 
Samples may be collected up to 120 minutes prior to the 
start of the infusion.  
Day 85: Collect sample 1 week after last administration. 
Day 8, Day 29, Day 43, and Day 78: Samples should be 
collected at:  
• 
Pre-infusion: Samples may be collected up to 
120 minutes prior to the start of the infusion. 
• 
Mid-infusion: Samples should be collected ± 
3 minutes within specified timeframe. If 
infusion is administered at a modified rate, the 
timing of collection of this sample should 
correspond to the middle of the modified 
infusion duration of the total administered dose. 
• 
End-of-infusion: Samples should be collected 
2 minutes within specified timeframe. This 
sample should be taken immediately prior to 
stopping the infusion. If the end of infusion is 
delayed to beyond the nominal infusion 
duration, the collection of this sample should 
also be delayed accordingly. 
• 
Postinfusion: Samples should be collected 1 
hour ± 3 minutes postinfusion. 
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Table 2 
On-Treatment Procedural Outline IM025006: Part 1, Treatment Period (Day 4 through Day 85) 
Procedure/Vi
sit Day  
(± 3 days for 
all visits 
unless 
otherwise 
noted) 
12-week, Double-Blind, Treatment Period 
Notes 
D  
4a 
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 
 
 
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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Table 2 
On-Treatment Procedural Outline IM025006: Part 1, Treatment Period (Day 4 through Day 85) 
Procedure/Vi
sit Day  
(± 3 days for 
all visits 
unless 
otherwise 
noted) 
12-week, Double-Blind, Treatment Period 
Notes 
D  
4a 
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 
 
 
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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Table 2 
On-Treatment Procedural Outline IM025006: Part 1, Treatment Period (Day 4 through Day 85) 
Procedure/Vi
sit Day  
(± 3 days for 
all visits 
unless 
otherwise 
noted) 
12-week, Double-Blind, Treatment Period 
Notes 
D  
4a 
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 
 
 
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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Table 2 
On-Treatment Procedural Outline IM025006: Part 1, Treatment Period (Day 4 through Day 85) 
Procedure/Vi
sit Day  
(± 3 days for 
all visits 
unless 
otherwise 
noted) 
12-week, Double-Blind, Treatment Period 
Notes 
D  
4a 
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 
 
 
W 
1 
W 
2 
W
3 
W 
4 
W 
5 
W  
6 
 
W 
7 
W  
8 
W 
9 
W 
10 
W 
11 
W 
12 
 
Study Treatment/Placebo Administration (X = BMS-986263; O = placebo) 
45 mg 
BMS-986263 
QW  
 
X 
X 
X 
X 
X 
X 
 
X 
X 
X 
X 
X 
 
See Section 8.5.1 and Section 8.5.4.  
90 mg 
BMS-986263 
QW  
 
X 
X 
X 
X 
X 
X 
 
X 
X 
X 
X 
X 
 
See Section 8.5.1 and Section 8.5.4.  
Placebo QW  
 
O 
O 
O 
O 
O 
O 
 
O 
O 
O 
O 
O 
 
See Section 8.5.1 and Section 8.5.4.  
AE = adverse event; AFP = alpha-fetoprotein; 
 D = Day; 
 ECG = electrocardiogram; 
 MRE = magnetic resonance elastography; 
O = placebo; 
 PK = pharmacokinetics; 
 QW = every week; 
 
 SAE = serious adverse event; W = Week; WOCBP = women of childbearing potential 
a Days 4 and 46: PK-only collection visits; see Table 12. 
 
 
 
 
Approved
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v


Clinical Protocol  
 
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BMS-986263 
 
HSP47 siRNA 
21-Feb-2019, Final Approved v7.0 
BMS CONFIDENTIAL 
34 
Table 3 
On-Treatment Procedural Outline IM025006: Part 1, Follow-up Period (Day 99 through Day 253) 
Procedure/Visit 
Day  
(± 3 days for all 
visits unless 
otherwise noted) 
24-week, Follow-up Period  
Notes 
D 
99 
D 
113 
D 
127 
D 
141 
D 
155 
D 
169 
D 
197  
(± 7) 
D 
225 
D 
253 
(± 7) 
EOS 
ET 
 
W 
14 
W 
16 
W 
18 
W 
20 
W 
22 
W 
24 
W  
28 
W 
32 
W  
36 
 
 
Safety Assessments 
Concomitant 
medication use 
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. 
Monitor for AEs  
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 will occur at every study visit. 
Monitor for SAEs 
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 after the final dose of the study treatment or 
participant’s participation in the study if the last scheduled visit 
occurs at a later time. Monitoring for SAEs will occur at every 
study visit. 
Physical and Metabolic Assessments 
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, extremities, height, and body weight. 
Abbreviated 
physical 
assessment 
 
X 
 
X 
 
X 
X 
X 
 
 
Abbreviated examinations will include vital signs, weight, an 
abdominal exam, assessments of ascites and hepatic 
encephalopathy, and symptom-focused assessments. 
Approved
1.0
v


Clinical Protocol  
 
IM025006 
BMS-986263 
 
HSP47 siRNA 
21-Feb-2019, Final Approved v7.0 
BMS CONFIDENTIAL 
35 
Table 3 
On-Treatment Procedural Outline IM025006: Part 1, Follow-up Period (Day 99 through Day 253) 
Procedure/Visit 
Day  
(± 3 days for all 
visits unless 
otherwise noted) 
24-week, Follow-up Period  
Notes 
D 
99 
D 
113 
D 
127 
D 
141 
D 
155 
D 
169 
D 
197  
(± 7) 
D 
225 
D 
253 
(± 7) 
EOS 
ET 
 
W 
14 
W 
16 
W 
18 
W 
20 
W 
22 
W 
24 
W  
28 
W 
32 
W  
36 
 
 
12-lead ECG 
 
 
 
 
 
 
 
 
X 
X 
ECGs should be after the participant has been supine for at least 
5 minutes. 
Liver biopsy  
 
 
 
 
 
 
 
 
 
X 
Liver biopsy must be carried out at the early termination visit 
only if the participant’s prior liver biopsy occurred > 8 weeks 
prior to termination.  
See Section 8.6.1.1. 
Approved
1.0
v


Clinical Protocol  
 
IM025006 
BMS-986263 
 
HSP47 siRNA 
21-Feb-2019, Final Approved v7.0 
BMS CONFIDENTIAL 
36 
Table 3 
On-Treatment Procedural Outline IM025006: Part 1, Follow-up Period (Day 99 through Day 253) 
Procedure/Visit 
Day  
(± 3 days for all 
visits unless 
otherwise noted) 
24-week, Follow-up Period  
Notes 
D 
99 
D 
113 
D 
127 
D 
141 
D 
155 
D 
169 
D 
197  
(± 7) 
D 
225 
D 
253 
(± 7) 
EOS 
ET 
 
W 
14 
W 
16 
W 
18 
W 
20 
W 
22 
W 
24 
W  
28 
W 
32 
W  
36 
 
 
MRE 
 
 
 
 
 
X 
 
 
X 
X* 
MRE is to be performed ± 7 days of this day to allow sites 
scheduling flexibility. Participants must fast for 4 hours prior to 
MRE. 
* MRE must be conducted at the early termination visit only if 
the participant’s prior MRE occurred > 4 weeks prior to 
termination. 
See Section 8.6.1.2. 
Laboratory Assessments 
Hematology  
X 
 
X 
 
X 
 
 
X 
X 
X 
See Section 8.6.2.7 and Table 11. 
Chemistry 
X 
X 
X 
 
X 
 
X 
X 
X 
X 
See Section 8.6.2.7 and Table 11. 
Approved
1.0
v


Clinical Protocol  
 
IM025006 
BMS-986263 
 
HSP47 siRNA 
21-Feb-2019, Final Approved v7.0 
BMS CONFIDENTIAL 
37 
Table 3 
On-Treatment Procedural Outline IM025006: Part 1, Follow-up Period (Day 99 through Day 253) 
Procedure/Visit 
Day  
(± 3 days for all 
visits unless 
otherwise noted) 
24-week, Follow-up Period  
Notes 
D 
99 
D 
113 
D 
127 
D 
141 
D 
155 
D 
169 
D 
197  
(± 7) 
D 
225 
D 
253 
(± 7) 
EOS 
ET 
 
W 
14 
W 
16 
W 
18 
W 
20 
W 
22 
W 
24 
W  
28 
W 
32 
W  
36 
 
 
HbA1C 
 
 
 
 
 
 
 
 
X 
X 
See Section 8.6.2.7 and Table 11. 
Urinalysis 
X 
 
X 
 
X 
 
 
X 
X 
 
See Section 8.6.2.7 and Table 11. 
Serum AFP 
 
 
 
 
X 
 
 
X 
X 
 
See Section 8.6.2.7 and Table 11. 
Urine Pregnancy  
 
X 
 
 
 
 
 
  
 
 
For WOCBP only. See Section 8.6.2.1.5.  
Pharmacokinetic 
 Sampling 
Blood PK sampling 
X 
 
 
 
 
 
 
 
 
X 
Day 99: To be taken 3 weeks after last administration.  
See Section 8.6.3 and Table 12. 
Approved
1.0
v


Clinical Protocol  
 
IM025006 
BMS-986263 
 
HSP47 siRNA 
21-Feb-2019, Final Approved v7.0 
BMS CONFIDENTIAL 
38 
Table 3 
On-Treatment Procedural Outline IM025006: Part 1, Follow-up Period (Day 99 through Day 253) 
Procedure/Visit 
Day  
(± 3 days for all 
visits unless 
otherwise noted) 
24-week, Follow-up Period  
Notes 
D 
99 
D 
113 
D 
127 
D 
141 
D 
155 
D 
169 
D 
197  
(± 7) 
D 
225 
D 
253 
(± 7) 
EOS 
ET 
 
W 
14 
W 
16 
W 
18 
W 
20 
W 
22 
W 
24 
W  
28 
W 
32 
W  
36 
 
 
Study Treatment/Placebo Administration (X = BMS-986263; O = placebo) 
45 mg   
BMS-986263 QW 
 
 
 
 
 
 
 
 
 
 
 
Approved
1.0
v


Clinical Protocol  
 
IM025006 
BMS-986263 
 
HSP47 siRNA 
21-Feb-2019, Final Approved v7.0 
BMS CONFIDENTIAL 
39 
Table 3 
On-Treatment Procedural Outline IM025006: Part 1, Follow-up Period (Day 99 through Day 253) 
Procedure/Visit 
Day  
(± 3 days for all 
visits unless 
otherwise noted) 
24-week, Follow-up Period  
Notes 
D 
99 
D 
113 
D 
127 
D 
141 
D 
155 
D 
169 
D 
197  
(± 7) 
D 
225 
D 
253 
(± 7) 
EOS 
ET 
 
W 
14 
W 
16 
W 
18 
W 
20 
W 
22 
W 
24 
W  
28 
W 
32 
W  
36 
 
 
90 mg   
BMS-986263 QW  
 
 
 
 
 
 
 
 
 
 
 
Placebo QW 
 
 
 
 
 
 
 
 
 
 
 
AE = adverse event; AFP = alpha-fetoprotein; 
 D = Day; 
 ECG = electrocardiogram; EOS = end of study; 
 ET = early termination; 
 
 MRE = magnetic resonance elastography; 
 PK = pharmacokinetics; 
 
 QW = every week; 
 SAE = serious adverse event; W = Week; WOCBP = women of childbearing potential 
 
Approved
1.0
v


Clinical Protocol  
 
IM025006 
BMS-986263 
 
HSP47 siRNA 
21-Feb-2019, Final Approved v7.0 
BMS CONFIDENTIAL 
40 
Table 4 
On-Treatment Procedural Outline IM025006: Part 2, Treatment Period (Day 4 through Day 85) 
 
24-week, Double-Blind, Treatment Period 
Notes 
Procedure/ 
Visit Day  
(± 3 days for all 
visits unless 
otherwise noted) 
D 
4a 
D 
8 
D 
15 
D 
2
2 
D 
29 
D 
36 
D  
4
3 
D  
46 
a 
D 
50 
D 
57 
D 
64 
D 
71 
D 
78 
D 
85 
 
 
W
1 
W
2 
W
3 
W
4 
W 
5 
W  
6 
 
W 
7 
W 
8 
W 
9 
W 
10 
W 
11 
W 
12 
 
Safety Assessments 
Concomitant 
medication use 
 
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. 
Monitor AEs 
 
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 will occur at every study 
visit. 
Monitor SAEs 
 
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 after the final dose of the study 
treatment or participant’s participation in the study if the last 
scheduled visit occurs at a later time. Monitoring for SAEs 
will occur at every study visit. 
Physical and Metabolic Assessments 
Full physical 
examination 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
A full examination will include general appearance, skin, 
head, eyes, ears, nose, throat, neck, thyroid, chest/lungs, heart, 
abdomen, lymph nodes, extremities, height, and body weight. 
Abbreviated 
physical 
assessment 
 
 
X 
 
X 
 
 
 
 
X 
 
 
 
 
Abbreviated examinations will include vital signs, weight, an 
abdominal exam, assessments of ascites and hepatic 
encephalopathy, and symptom-focused assessments. 
Approved
1.0
v


Clinical Protocol  
 
IM025006 
BMS-986263 
 
HSP47 siRNA 
21-Feb-2019, Final Approved v7.0 
BMS CONFIDENTIAL 
41 
Table 4 
On-Treatment Procedural Outline IM025006: Part 2, Treatment Period (Day 4 through Day 85) 
 
24-week, Double-Blind, Treatment Period 
Notes 
Procedure/ 
Visit Day  
(± 3 days for all 
visits unless 
otherwise noted) 
D 
4a 
D 
8 
D 
15 
D 
2
2 
D 
29 
D 
36 
D  
4
3 
D  
46 
a 
D 
50 
D 
57 
D 
64 
D 
71 
D 
78 
D 
85 
 
 
W
1 
W
2 
W
3 
W
4 
W 
5 
W  
6 
 
W 
7 
W 
8 
W 
9 
W 
10 
W 
11 
W 
12 
 
12-lead ECG  
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
ECGs should be recorded after the participant has been supine 
for at least 5 minutes.  
Liver biopsy  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Section 8.6.1.1. 
MRE 
 
 
 
 
 
 
X 
 
 
 
 
 
 
X 
MRE is to be performed ± 7 days of this day to allow sites 
scheduling flexibility. Participants must fast for 4 hours prior 
to MRE. 
A Week 6 (Day 43) MRE in Part 2 will be carried out only if 
deemed necessary based on the Week 6 analysis in Part 1 
(Section 9.3.4). 
See Section 8.6.1.2.  
Laboratory Assessments 
Approved
1.0
v


Clinical Protocol  
 
IM025006 
BMS-986263 
 
HSP47 siRNA 
21-Feb-2019, Final Approved v7.0 
BMS CONFIDENTIAL 
42 
Table 4 
On-Treatment Procedural Outline IM025006: Part 2, Treatment Period (Day 4 through Day 85) 
 
24-week, Double-Blind, Treatment Period 
Notes 
Procedure/ 
Visit Day  
(± 3 days for all 
visits unless 
otherwise noted) 
D 
4a 
D 
8 
D 
15 
D 
2
2 
D 
29 
D 
36 
D  
4
3 
D  
46 
a 
D 
50 
D 
57 
D 
64 
D 
71 
D 
78 
D 
85 
 
 
W
1 
W
2 
W
3 
W
4 
W 
5 
W  
6 
 
W 
7 
W 
8 
W 
9 
W 
10 
W 
11 
W 
12 
 
Hematology  
 
 
X 
 
X 
 
X 
 
 
X 
 
 
 
X 
Pre-infusion when on a dosing day. 
See Section 8.6.2.7 and Table 11. 
Chemistry 
 
X 
X 
X 
X 
X 
X 
 
X 
X 
X 
X 
X 
X 
Pre-infusion when on a dosing day.  
See Section 8.6.2.7 and Table 11. 
HbA1C 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
See Section 8.6.2.7 and Table 11 
Urinalysis 
 
 
X 
 
X 
 
X 
 
 
X 
 
X 
 
X 
See Section 8.6.2.7 and Table 11. 
Serum AFP 
 
 
 
 
 
 
X 
 
 
 
 
 
 
X 
See Section 8.6.2.7 and Table 11. 
Urine Pregnancy 
 
 
X 
 
X 
 
X 
 
 
X 
 
X 
 
X 
For WOCBP only. Urine pregnancy test must be completed to 
confirm the participant is not pregnant prior to each infusion. 
See Section 8.6.2.1.5. 
Approved
1.0
v


Clinical Protocol  
 
IM025006 
BMS-986263 
 
HSP47 siRNA 
21-Feb-2019, Final Approved v7.0 
BMS CONFIDENTIAL 
43 
Table 4 
On-Treatment Procedural Outline IM025006: Part 2, Treatment Period (Day 4 through Day 85) 
 
24-week, Double-Blind, Treatment Period 
Notes 
Procedure/ 
Visit Day  
(± 3 days for all 
visits unless 
otherwise noted) 
D 
4a 
D 
8 
D 
15 
D 
2
2 
D 
29 
D 
36 
D  
4
3 
D  
46 
a 
D 
50 
D 
57 
D 
64 
D 
71 
D 
78 
D 
85 
 
 
W
1 
W
2 
W
3 
W
4 
W 
5 
W  
6 
 
W 
7 
W 
8 
W 
9 
W 
10 
W 
11 
W 
12 
 
Pharmacokinetic 
 Sampling 
Blood PK sampling 
X 
 
X 
 
X 
 
X 
X 
 
X 
 
X 
 
X 
Days 4 and 46: Postinfusion: Sample may be collected ± 1 
day at the PK visit on these days. 
Days 15, 57, 71, 99, 113, 127, and 155: Pre-infusion: may be 
collected up to 120 minutes prior to start of infusion.  
Days 29, 43, 85, and 141: Collect samples:  
• 
Pre-infusion: up to 120 minutes prior to infusion. 
• 
Mid-infusion: ± 3 minutes within specified 
timeframe. If infusion is administered at a modified 
rate, the timing of collection of this sample should 
correspond to the middle of the modified infusion 
duration of the total administered dose. 
• 
End-of-infusion: 2 minutes within specified 
timeframe; taken immediately prior to stopping the 
infusion. If end of infusion is delayed to beyond the 
nominal infusion duration, the collection of this 
sample should also be delayed accordingly. 
• 
Postinfusion: 1 hour ± 3 minutes postinfusion 
Day 169: Postinfusion: Samples are to be collected 14 days 
postinfusion. 
See Section 8.6.3 and Table 12. 
Approved
1.0
v


Clinical Protocol  
 
IM025006 
BMS-986263 
 
HSP47 siRNA 
21-Feb-2019, Final Approved v7.0 
BMS CONFIDENTIAL 
44 
Table 4 
On-Treatment Procedural Outline IM025006: Part 2, Treatment Period (Day 4 through Day 85) 
 
24-week, Double-Blind, Treatment Period 
Notes 
Procedure/ 
Visit Day  
(± 3 days for all 
visits unless 
otherwise noted) 
D 
4a 
D 
8 
D 
15 
D 
2
2 
D 
29 
D 
36 
D  
4
3 
D  
46 
a 
D 
50 
D 
57 
D 
64 
D 
71 
D 
78 
D 
85 
 
 
W
1 
W
2 
W
3 
W
4 
W 
5 
W  
6 
 
W 
7 
W 
8 
W 
9 
W 
10 
W 
11 
W 
12 
 
Approved
1.0
v


Clinical Protocol  
 
IM025006 
BMS-986263 
 
HSP47 siRNA 
21-Feb-2019, Final Approved v7.0 
BMS CONFIDENTIAL 
45 
Table 4 
On-Treatment Procedural Outline IM025006: Part 2, Treatment Period (Day 4 through Day 85) 
 
24-week, Double-Blind, Treatment Period 
Notes 
Procedure/ 
Visit Day  
(± 3 days for all 
visits unless 
otherwise noted) 
D 
4a 
D 
8 
D 
15 
D 
2
2 
D 
29 
D 
36 
D  
4
3 
D  
46 
a 
D 
50 
D 
57 
D 
64 
D 
71 
D 
78 
D 
85 
 
 
W
1 
W
2 
W
3 
W
4 
W 
5 
W  
6 
 
W 
7 
W 
8 
W 
9 
W 
10 
W 
11 
W 
12 
 
Study Drug/Placebo Administration (X = BMS-986263; O = placebo) 
45 mg 
BMS-986263 Q2W 
 
 
X 
 
X 
 
X 
 
 
X 
 
X 
 
X 
See Section 8.5.1 and Section 8.5.4.  
90 mg 
BMS-986263 Q2W 
 
 
X 
 
X 
 
X 
 
 
X 
 
X 
 
X 
See Section 8.5.1 and Section 8.5.4.  
90 mg 
BMS-986263 Q4W 
 
 
O 
 
X 
 
O 
 
 
X 
 
O 
 
X 
See Section 8.5.1 and Section 8.5.4.  
Placebo Q2W 
 
 
O 
 
O 
 
O 
 
 
O 
 
O 
 
O 
See Section 8.5.1 and Section 8.5.4.  
AE = adverse event; AFP = alpha-fetoprotein; 
 D = day; 
; ECG = electrocardiogram; 
MRE = magnetic resonance 
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Clinical Protocol  
 
IM025006 
BMS-986263 
 
HSP47 siRNA 
21-Feb-2019, Final Approved v7.0 
BMS CONFIDENTIAL 
46 
elastography; O = placebo; 
 PK = pharmacokinetics; 
 Q2W = once every 2 
weeks; Q4W = once every 4 weeks; 
 SAE = serious adverse event; W = week; WOCBP = women of childbearing potential 
a Days 4 and 46: PK-only collection visits; see Table 12. 
Approved
1.0
v


Clinical Protocol  
 
IM025006 
BMS-986263 
 
HSP47 siRNA 
21-Feb-2019, Final Approved v7.0 
BMS CONFIDENTIAL 
47 
Table 5 
On-Treatment Procedural Outline IM025006: Part 2, Treatment Period (Day 99 through Day 169) 
 
24-week, Double-Blind,  
Treatment Period 
Notes 
Procedure/ 
Visit Day 
(± 3 days for all visits unless 
otherwise noted) 
D 
99 
D 
113 
D 
127 
D 
141 
D 
155 
D 
169 
 
W 
14 
W 
16 
W 
18 
W 
20 
W 
22 
W 
24 
 
Safety Assessments 
Concomitant medication use 
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. 
Monitor AEs 
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 will 
occur at every study visit. 
Monitor SAEs 
X 
X 
X 
X 
X 
X 
All SAEs must be collected from the date of participant’s written consent until 30 
days after the final dose of the study treatment or participant’s participation in the 
study if the last scheduled visit occurs at a later time. Monitoring for SAEs will 
occur at every study visit. 
Physical and Metabolic Assessments 
Full physical examination 
 
 
 
 
 
X 
A full examination will include general appearance, skin, head, eyes, ears, nose, 
throat, neck, thyroid, chest/lungs, heart, abdomen, lymph nodes, extremities, height, 
and body weight. 
Abbreviated physical 
assessment 
 
X 
 
X 
 
X 
Abbreviated examinations will include vital signs, weight, an abdominal exam, 
assessments of ascites and hepatic encephalopathy, and symptom-focused 
assessments. 
12-lead ECG  
 
 
 
 
 
 
ECG is not performed during this study period. 
Liver biopsy  
 
 
 
 
 
X 
See Section 8.6.1.1. 
Approved
1.0
v


Clinical Protocol  
 
IM025006 
BMS-986263 
 
HSP47 siRNA 
21-Feb-2019, Final Approved v7.0 
BMS CONFIDENTIAL 
48 
Table 5 
On-Treatment Procedural Outline IM025006: Part 2, Treatment Period (Day 99 through Day 169) 
 
24-week, Double-Blind,  
Treatment Period 
Notes 
Procedure/ 
Visit Day 
(± 3 days for all visits unless 
otherwise noted) 
D 
99 
D 
113 
D 
127 
D 
141 
D 
155 
D 
169 
 
W 
14 
W 
16 
W 
18 
W 
20 
W 
22 
W 
24 
 
MRE 
 
 
 
 
 
X 
MRE to be performed ± 7 days of this day to allow sites scheduling flexibility. 
Participants must fast for 4 hours prior to MRE. 
See Section 8.6.1.2. 
Laboratory Assessments 
Hematology  
 
X 
 
X 
 
X 
Pre-infusion when on a dosing day 
See Section 8.6.2.7 and Table 11. 
Chemistry 
X 
X 
X 
X 
X 
X 
Pre-infusion when on a dosing day  
See Section 8.6.2.7 and Table 11. 
Approved
1.0
v


Clinical Protocol  
 
IM025006 
BMS-986263 
 
HSP47 siRNA 
21-Feb-2019, Final Approved v7.0 
BMS CONFIDENTIAL 
49 
Table 5 
On-Treatment Procedural Outline IM025006: Part 2, Treatment Period (Day 99 through Day 169) 
 
24-week, Double-Blind,  
Treatment Period 
Notes 
Procedure/ 
Visit Day 
(± 3 days for all visits unless 
otherwise noted) 
D 
99 
D 
113 
D 
127 
D 
141 
D 
155 
D 
169 
 
W 
14 
W 
16 
W 
18 
W 
20 
W 
22 
W 
24 
 
HbA1C 
 
 
 
 
 
X 
See Section 8.6.2.7 and Table 11. 
Urinalysis 
 
X 
 
X 
 
X 
See Section 8.6.2.7 and Table 11. 
Serum AFP 
 
 
 
 
 
X 
See Section 8.6.2.7 and Table 11. 
Urine Pregnancy  
X 
X 
X 
X 
X 
X 
For WOCBP only. Urine pregnancy test must be completed to confirm participant is 
not pregnant prior to each infusion. 
See Section 8.6.2.1.5. 
Approved
1.0
v


Clinical Protocol  
 
IM025006 
BMS-986263 
 
HSP47 siRNA 
21-Feb-2019, Final Approved v7.0 
BMS CONFIDENTIAL 
50 
Table 5 
On-Treatment Procedural Outline IM025006: Part 2, Treatment Period (Day 99 through Day 169) 
 
24-week, Double-Blind,  
Treatment Period 
Notes 
Procedure/ 
Visit Day 
(± 3 days for all visits unless 
otherwise noted) 
D 
99 
D 
113 
D 
127 
D 
141 
D 
155 
D 
169 
 
W 
14 
W 
16 
W 
18 
W 
20 
W 
22 
W 
24 
 
Pharmacokinetic 
 Sampling 
Blood PK sampling 
X 
X 
X 
X 
X 
X 
Days 4 and 46: Postinfusion: Sample may be collected ± 1 day at the PK visit on. 
Days 15, 43, 57, 71, 99, 113, 127, and 155: Pre-infusion: may be collected up to 
120 minutes prior to start of infusion.  
Days 29, 85, and 141: Collect samples:  
• 
Pre-infusion: up to 120 minutes prior to infusion. 
• 
Mid-infusion: ± 3 minutes within specified timeframe. If infusion is 
administered at a modified rate, the timing of collection of this sample 
should correspond to the middle of the modified infusion duration of the 
total administered dose. 
• 
End-of-infusion: 2 minutes within specified timeframe; taken immediately 
prior to stopping the infusion. If end of infusion is delayed to beyond the 
nominal infusion duration, the collection of this sample should also be 
delayed accordingly. 
• 
Postinfusion: 1 hour ± 3 minutes postinfusion 
Day 169: Postinfusion: Samples are to be collected 14 days postinfusion. 
See Section 8.6.3 and Table 13. 
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Table 5 
On-Treatment Procedural Outline IM025006: Part 2, Treatment Period (Day 99 through Day 169) 
 
24-week, Double-Blind,  
Treatment Period 
Notes 
Procedure/ 
Visit Day 
(± 3 days for all visits unless 
otherwise noted) 
D 
99 
D 
113 
D 
127 
D 
141 
D 
155 
D 
169 
 
W 
14 
W 
16 
W 
18 
W 
20 
W 
22 
W 
24 
 
Study Treatment/Placebo Administration (X = BMS-986263; O = placebo) 
45 mg BMS986263 Q2W 
X 
X 
X 
X 
X 
 
See Section 8.5.1 and Section 8.5.4.  
90 mg BMS-986263 Q2W 
X 
X 
X 
X 
X 
 
See Section 8.5.1 and Section 8.5.4.  
90 mg BMS-986263 Q4W 
O 
X 
O 
X 
O 
 
See Section 8.5.1 and Section 8.5.4.  
Placebo Q2W 
O 
O 
O 
O 
O 
 
See Section 8.5.1 and Section 8.5.4.  
AE = adverse event; AFP = alpha-fetoprotein; 
 D = day; 
 ECG = electrocardiogram; 
 MRE = magnetic resonance 
elastography; O = placebo; 
 PK = pharmacokinetics; 
 Q2W = once every 2 
weeks; Q4W = once every 4 weeks; 
 SAE = serious adverse event; W = week; WOCBP = women of childbearing potential 
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Table 6 
On-Treatment Procedural Outline IM025006: Part 2, Follow-up Period (Day 197 through Day 253) 
 
12-week, Follow-up Period 
 
Notes 
Procedure/Visit Day  
(± 3 days for all visits unless 
otherwise noted) 
D 197 
±7 days 
D 225 
D 253 
±7 days 
EOS  
ET 
W 28 
W 32 
W 36 
 
 
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. 
Monitor AEs 
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 will 
occur at every study visit. 
Monitor SAEs 
X 
X 
X 
X 
All SAEs must be collected from the date of participant’s written consent until 
30 days after the final dose of the study treatment or participant’s participation in 
the study if the last scheduled visit occurs at a later time. Monitoring for SAEs will 
occur at every study visit. 
Physical and Metabolic Assessments 
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, extremities, 
height, and body weight. 
Abbreviated physical 
assessment 
X 
X 
 
 
Abbreviated examinations will include vital signs, weight, an abdominal exam, 
assessments of ascites and hepatic encephalopathy, and symptom-focused 
assessments. 
12-lead ECG  
 
 
X 
X 
ECGs should be after the participant has been supine for at least 5 minutes. 
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Table 6 
On-Treatment Procedural Outline IM025006: Part 2, Follow-up Period (Day 197 through Day 253) 
 
12-week, Follow-up Period 
 
Notes 
Procedure/Visit Day  
(± 3 days for all visits unless 
otherwise noted) 
D 197 
±7 days 
D 225 
D 253 
±7 days 
EOS  
ET 
W 28 
W 32 
W 36 
 
 
Liver biopsy  
 
 
 
X 
Liver biopsy must be carried out at the early termination visit only if the 
participant’s prior liver biopsy occurred > 8weeks prior to termination. 
See Section 8.6.1.1. 
MRE 
 
 
X 
X 
MRE is to be performed ± 7 days of this day to allow sites scheduling flexibility. 
Participants must fast for 4 hours prior to MRE. 
MRE must be conducted at the early termination visit only if the participant’s prior 
MRE occurred > 4 weeks prior to termination. 
See Section 8.6.1.2. 
Laboratory Assessments 
Hematology  
X 
 
X 
X 
See Section 8.6.2.7 and Table 11. 
Chemistry 
X 
X 
X 
X 
See Section 8.6.2.7 and Table 11. 
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Table 6 
On-Treatment Procedural Outline IM025006: Part 2, Follow-up Period (Day 197 through Day 253) 
 
12-week, Follow-up Period 
 
Notes 
Procedure/Visit Day  
(± 3 days for all visits unless 
otherwise noted) 
D 197 
±7 days 
D 225 
D 253 
±7 days 
EOS  
ET 
W 28 
W 32 
W 36 
 
 
HbA1C 
 
 
X 
X 
See Section 8.6.2.7 and Table 11. 
Urinalysis 
 
 
X 
X 
See Section 8.6.2.7 and Table 11. 
Serum AFP 
 
 
X 
X 
See Section 8.6.2.7 and Table 11. 
Urine Pregnancy  
X 
 
 
 
For WOCBP only. See Section 8.6.2.1.5.  
Pharmacokinetic 
 Sampling 
Blood PK sampling 
X 
 
 
X 
See Section 8.6.3 and Table 12. 
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Table 6 
On-Treatment Procedural Outline IM025006: Part 2, Follow-up Period (Day 197 through Day 253) 
 
12-week, Follow-up Period 
 
Notes 
Procedure/Visit Day  
(± 3 days for all visits unless 
otherwise noted) 
D 197 
±7 days 
D 225 
D 253 
±7 days 
EOS  
ET 
W 28 
W 32 
W 36 
 
 
Study Treatment/ Placebo Administration (X = BMS-986263; O = placebo) 
45 mg BMS-986263 Q2W 
 
 
 
 
 
90 mg BMS-986263 Q2W 
 
 
 
 
 
90 mg BMS-986263 Q4W 
 
 
 
 
 
Placebo Q2W 
 
 
 
 
 
AE = adverse event; AFP = alpha-fetoprotein; 
 
 
 
 D = day; 
 ECG = electrocardiogram; EOS = 
end of study; 
 ET = early termination; MOA = mechanism of action; MRE = magnetic resonance elastography; 
 
 
 
 Q2W = once 
every 2 weeks; Q4W = once every 4 weeks; 
 SAE = serious adverse event; W = week; WOCBP = women of childbearing potential 
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2. TABLE OF CONTENTS 
DOCUMENT HISTORY ..................................................................................................................... 2 
1. 
PROTOCOL SUMMARY ......................................................................................... 4 
1.1 
Synopsis ........................................................................................................................ 4 
1.2 
Schedule of Activities ................................................................................................. 17 
2. 
TABLE OF CONTENTS ......................................................................................... 56 
3. 
LIST OF ABBREVIATIONS AND DEFINITION OF TERMS .......................... 60 
4. 
ETHICS ..................................................................................................................... 63 
4.1 
Ethics Committee ........................................................................................................ 63 
4.2 
Ethical Conduct of the Study ...................................................................................... 63 
4.3 
Participant Information and Consent .......................................................................... 63 
5. 
STUDY ADMINISTRATION AND CONTACTS ................................................. 64 
7. 
STUDY OBJECTIVES ............................................................................................. 78 
7.1 
Primary Study Objectives ........................................................................................... 78 
7.2 
Secondary Study Objectives ....................................................................................... 78 
8. 
INVESTIGATIONAL PLAN .................................................................................. 80 
8.1 
Overall Study Design .................................................................................................. 80 
8.1.1 
Screening for Part 1 and Part 2 ................................................................................... 81 
8.1.2 
Part 1 Treatment Period and Follow-up ...................................................................... 83 
8.1.4 
Part 2 Treatment Period and Follow-up ...................................................................... 83 
8.2 
Data Monitoring Committee and Other Committees .................................................. 84 
8.3 
End of Study Definition .............................................................................................. 84 
8.4 
Study Population ......................................................................................................... 84 
8.4.1 
Inclusion Criteria ........................................................................................................ 84 
8.4.2 
Exclusion Criteria ....................................................................................................... 86 
8.4.3 
MRI Contraindications ............................................................................................... 88 
8.4.4 
Lifestyle Restrictions .................................................................................................. 89 
8.4.5 
Screen Failures, Retesting, and Rescreening .............................................................. 89 
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8.4.6 
Withdrawal and Replacement of Participants ............................................................. 90 
8.4.6.1 
Discontinuation of Treatment ..................................................................................... 90 
8.4.6.2 
Discontinuation from the Study .................................................................................. 92 
8.4.6.3 
Lost to Follow-up ........................................................................................................ 93 
8.4.6.4 
Replacement of Participants ....................................................................................... 93 
8.5 
Study Treatment .......................................................................................................... 93 
8.5.1 
Treatments Administered ............................................................................................ 94 
8.5.1.1 
Study Treatment Infusion Rate ................................................................................... 95 
8.5.1.2 
Premedication ............................................................................................................. 95 
8.5.2 
Method of Treatment Assignment .............................................................................. 96 
8.5.3 
Blinding of Study Medication ..................................................................................... 97 
8.5.3.1 
Maintaining the Blind ................................................................................................. 97 
8.5.3.2 
Circumstances for Unblinding .................................................................................... 97 
8.5.4 
Study Treatment Preparation, Handling, Storage, and Accountability ....................... 98 
 
8.5.5 
Dose Modification ...................................................................................................... 98 
8.5.6 
Treatment Compliance ................................................................................................ 98 
8.5.7 
Prior and Concomitant Therapy .................................................................................. 99 
8.5.8 
Treatment After the End of the Study ......................................................................... 99 
8.6 
Efficacy and Safety Assessments ................................................................................ 99 
8.6.1 
Efficacy Assessments ............................................................................................... 100 
8.6.1.1 
Liver Biopsy ............................................................................................................. 100 
8.6.1.1.1 
Histological Assessment and METAVIR scoring ...................................................... 102 
8.6.1.1.2 
Histological Assessment and Ishak scoring .............................................................. 102 
8.6.1.1.3 
Morphometric Analysis of Collagen Proportionate Area in Stained Tissue ............. 102 
8.6.1.2 
MRE Imaging Assessment ........................................................................................ 102 
8.6.1.3 
Pharmacokinetic 
 Sampling .............................................................. 103 
8.6.1.4 
FibroScan .................................................................................................................. 103 
8.6.2 
Safety Assessments ................................................................................................... 105 
8.6.2.1 
Adverse Events ......................................................................................................... 105 
8.6.2.1.1 
Time Period and Frequency for Collecting AE and SAE Information...................... 106 
8.6.2.1.2 
Method of Detecting AEs and SAEs .......................................................................... 106 
8.6.2.1.3 
Follow-up of AEs and SAEs ...................................................................................... 106 
8.6.2.1.4 
Regulatory Reporting Requirements for SAEs .......................................................... 107 
8.6.2.1.5 
Pregnancy ................................................................................................................. 107 
8.6.2.1.6 
Laboratory Test Result Abnormalities ...................................................................... 108 
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8.6.2.1.7 
Potential Liver Injury ................................................................................................ 108 
8.6.2.1.8 
Other Safety Considerations ..................................................................................... 108 
8.6.2.2 
Overdose ................................................................................................................... 109 
8.6.2.3 
Physical Examinations .............................................................................................. 109 
8.6.2.7 
Clinical Safety Laboratory Assessments .................................................................. 114 
8.6.2.8 
Imaging Safety Assessments – DXA ........................................................................ 115 
8.6.3 
Pharmacokinetics ...................................................................................................... 116 
9. 
STATISTICAL CONSIDERATIONS .................................................................. 122 
9.1 
Sample Size Determination....................................................................................... 122 
9.2 
Populations for Analyses .......................................................................................... 123 
9.3 
Statistical Analyses ................................................................................................... 123 
9.3.1 
Efficacy ..................................................................................................................... 123 
9.3.1.1 
Efficacy Endpoints .................................................................................................... 123 
9.3.1.2 
Analysis Methodology .............................................................................................. 125 
9.3.2 
Safety ........................................................................................................................ 126 
9.3.3 
Other Analyses .......................................................................................................... 126 
9.3.3.1 
Pharmacokinetics ...................................................................................................... 126 
11. 
APPENDICES ......................................................................................................... 130 
APPENDIX 1 STUDY GOVERNANCE CONSIDERATIONS .................................................. 130 
APPENDIX 2 ADVERSE EVENTS AND SERIOUS ADVERSE EVENTS: DEFINITIONS 
AND PROCEDURES FOR RECORDING, EVALUATING, FOLLOW-UP 
AND REPORTING ................................................................................................. 138 
APPENDIX 3 WOMEN OF CHILDBEARING POTENTIAL DEFINITIONS AND 
METHODS OF CONTRACEPTION ................................................................... 143 
APPENDIX 7 CHILD-PUGH SCORING ..................................................................................... 157 
APPENDIX 8 FORMULAE FOR MEASUREMENTS ............................................................... 158 
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LIST OF TABLES 
Table 1 
Screening and Day 1 (Randomization) Procedural Outline IM025006: Part 1 and 
Part 2 ........................................................................................................................... 18 
Table 2 
On-Treatment Procedural Outline IM025006: Part 1, Treatment Period (Day 4 
through Day 85) .......................................................................................................... 25 
Table 3 
On-Treatment Procedural Outline IM025006: Part 1, Follow-up Period (Day 99 
through Day 253) ........................................................................................................ 34 
Table 4 
On-Treatment Procedural Outline IM025006: Part 2, Treatment Period (Day 4 
through Day 85) .......................................................................................................... 40 
Table 5 
On-Treatment Procedural Outline IM025006: Part 2, Treatment Period (Day 99 
through Day 169) ........................................................................................................ 47 
Table 6 
On-Treatment Procedural Outline IM025006: Part 2, Follow-up Period (Day 197 
through Day 253) ........................................................................................................ 52 
Table 7 
Study Treatments for IM025006 ................................................................................. 94 
Table 8 
Selection and Timing of Dose ..................................................................................... 96 
Table 11 
Hematology, Chemistry, Urinalysis, 
 Assessments........................... 114 
Table 12 
Pharmacokinetic
 Sampling 
Schedule for BMS-986263 in Part 1 ......................................................................... 117 
Table 13 
Pharmacokinetic 
 Sampling 
Schedule for BMS-986263 in Part 2 ......................................................................... 119 
 
 
LIST OF FIGURES 
Figure 1 
Study Design Schematic ............................................................................................. 81 
 
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3. LIST OF ABBREVIATIONS AND DEFINITION OF TERMS 
Term 
Definition 
AE 
adverse event 
AFP  
alpha-fetoprotein 
Anti-HB 
hepatitis B surface antibody 
Anti-HBc 
hepatitis B core antibody 
anti-HCV 
hepatitis C virus antibody 
ALP 
alkaline phosphatase 
ALT 
alanine aminotransferase 
AST 
aspartate aminotransferase 
BMD 
bone mineral density 
BMI 
body mass index  
BMS 
Bristol-Myers Squibb 
BUN  
blood urea nitrogen 
CFR 
Code of Federal Regulations 
CI 
confidence interval 
CMH 
Cochran Mantel-Haenszel  
CPA 
Collagen Proportionate Area 
Ctrough 
trough observed plasma concentration  
CYP 
cytochrome P 450 
CSR 
Clinical Study Report 
DDI 
drug-drug interaction 
DILI 
drug-induced liver injury 
DMC 
data monitoring committee 
DNA 
deoxyribonucleic acid 
dsDNA 
double-stranded deoxyribonucleic acid 
DXA  
dual-energy X-ray absorptiometry 
ECG 
electrocardiogram 
eCRF 
electronic case report form 
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EOS 
end of study 
FDA 
Food and Drug Administration 
FSH  
follicle stimulating hormone 
GGT  
gamma-glutamyl transferase 
HbcAb  
hepatitis B core antibody 
HBsAb  
hepatitis B surface antibody 
HBsAg 
hepatitis B surface antigen 
HBV 
hepatitis B virus  
HBV core IgM 
hepatitis B virus core-specific immunoglobulin mu antibody 
HCC 
hepatocellular carcinoma  
HCV 
hepatitis C virus 
HIV 
human immunodeficiency virus 
HSC 
hepatic stellate cell 
IB 
Investigator’s Brochure 
ICF 
informed consent form 
IEC 
Independent Ethics Committee 
Ig 
immunoglobulin 
IMP 
investigational medicinal product  
INR 
international normalized ratio 
IP 
investigational product 
IRT 
interactive response technology 
IV 
intravenous 
LDH 
lactate dehydrogenase 
LLN 
lower limit of normal 
MCH 
mean corpuscular hemoglobin; 
MELD 
Model End Stage Liver Disease 
mITT 
modified intent-to-treat 
MRE  
magnetic resonance elastography 
MRI 
magnetic resonance imaging  
NASH 
nonalcoholic steatohepatitis 
NOAEL 
no observed adverse effect level 
PCP 
phencyclidine  
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PID 
participant identification number 
PK 
Pharmacokinetics 
PT  
prothrombin time 
PTT  
partial thromboplastin time 
QW 
once every week  
Q2W 
once every 2 weeks  
Q4W 
once every 4 weeks 
RBC 
red blood cell 
RNA  
ribonucleic acid 
RNASEQ 
RNA sequencing 
SAE 
serious adverse event 
SAP 
statistical analysis plan 
SLE 
systemic lupus erythematosus 
SVR 
sustained virologic response 
ULN 
upper limit of normal 
WOCBP 
women of childbearing potential 
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4. ETHICS 
4.1 Ethics Committee 
This study will be conducted in compliance with institutional review board (IRB)/IEC and 
International Council for Harmonisation (ICH) Good Clinical Practice (GCP) guidelines and 
in accordance with applicable regulations regarding clinical safety data management (E2A, 
E2B[R3]) and scientific integrity (E4, E8, E9 and E10). In addition, this study will adhere to 
all local regulatory requirements and requirements for data protection. 
Before initiating a study, the investigator must obtain written and dated approval from the 
IRB/IEC for the study protocol (and any amendments), written ICF, any consent form updates, 
participant recruitment procedures (eg, advertisements) and any written information to be 
provided to participants, and a statement from the IRB/IEC that these materials comply with 
GCP requirements. The approval must identify the protocol version as well as the documents 
reviewed. 
4.2 Ethical Conduct of the Study 
This study will be conducted in accordance with the Note for Guidance on GCP (ICH 
Harmonised Tripartite Guideline E6 (R1); FDA CFR [21 CFR § 50, 56, 312]), Declaration of 
Helsinki and all applicable regulatory requirements. 
4.3 Participant Information and Consent 
The investigator will explain the benefits and risks of participation in the study to each 
participant/legally acceptable representative in language readily understood by the participant. 
Written informed consent must be obtained before the participant enters the study and before 
any study-specific procedures are performed. If important new information becomes available 
requiring revisions to the ICF, the IRB/IEC-approved revised form will be used for reconsent 
of all participants.  
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5. STUDY ADMINISTRATION AND CONTACTS 
Contact Type / Role 
Contact 
Serious adverse event (SAE) and pregnancy reporting 
Medical Monitor 
(advice on protocol and study treatment) 
Study Director  
(overall responsibility for study conduct) 
 
 
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STUDY ACKNOWLEDGMENT/DISCLOSURE 
I understand that this protocol contains information that is confidential and proprietary to Bristol-Myers Squibb Company 
(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 protocol. 
I have read the original protocol/revised protocol and agree that it contains all necessary details for carrying out the study as 
described. I will conduct this protocol as outlined therein and will make a reasonable effort to complete the study within the 
time designated. 
I will provide copies of the protocol and access to all information furnished by BMS to study personnel under my supervision. 
I will discuss this material with them to ensure that they are fully informed about the investigational product and the study.  
I will provide protocol information to my Institutional Review Board(s) [IRB(s)] or Independent Ethics Committee(s) [IEC(s]. 
I understand that original protocol/revised protocols must be reviewed by the Institutional Review Board or Independent Ethics 
Committee overseeing the conduct of the study and approved or given favorable opinion by all necessary Health Authorities 
before implementation unless to eliminate an immediate hazard to subjects. 
I agree that the contents of the protocol may not be disclosed to any other person or entity or used for any other purpose 
without the prior written consent of BMS. The foregoing shall not apply to disclosure required by governmental regulations 
or laws; however, I will give prompt notice to BMS of any such disclosure. 
I agree that the study data derived from this protocol may only be used and disclosed in furtherance of the protocol, for the 
medical treatment of a study participant or for publication of study results in accordance with the terms of the clinical trial 
agreement or as otherwise permitted by the terms of the clinical trial agreement. 
I agree not to collect or use samples (e.g., tissue, blood, serum, urine) or collect data (other than for diagnostic or treatment 
purposes) from the study participants while enrolled in the study, except as expressly permitted by the protocol or the terms 
of the clinical trial agreement. 
I understand that I may terminate or suspend enrollment of the study at any time if it becomes necessary to protect the best 
interests of the study participants. Unless otherwise provided in the clinical trial agreement, the study may be terminated at 
any time by BMS, with or without cause. 
Original Protocol: 
 
 
Revised Protocol: 
 
Protocol Number: IM025006 
 
Site Number:  
Date of Protocol or Revised Protocol:   
 
 
IND Number: 136,523 
 
EUDRACT Number: Not applicable  
 
 
 
Investigator:  
 
Date:  
(signature) 
 
 
(printed name) 
 
 
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7. STUDY OBJECTIVES
Associated endpoints are described in Section 9.3. The study population is restricted to 
patients with advanced liver fibrosis due to HCV who have achieved SVR for a minimum of 
1 year. See Section 8.4 for detailed inclusion and exclusion criteria.
7.1 Primary Study Objectives 
•
Part 1: To assess the effect of treatment with 90 mg QW BMS-986263 on the
proportion of participants with ≥ 1 stage improvement in liver fibrosis (METAVIR
score), as compared to placebo after 12 weeks of treatment
•
Part 2: To assess the effect of treatment with 45 mg Q2W, 90 mg Q2W, and 90 mg
Q4W BMS-986263 on the proportion of participants with ≥ 1 stage improvement in
liver fibrosis (METAVIR score), as compared to placebo after 24 weeks of treatment
7.2 Secondary Study Objectives 
•
Part 1
o
To assess the effect of treatment with 90 mg QW BMS-986263 on the change
in collagen proportionate area (CPA), as compared to placebo after 12 weeks
of treatment
o
To assess the effect of treatment with 90 mg QW BMS-986263 on the
proportion of participants with ≥ 1 stage improvement in liver fibrosis (Ishak
score), as compared to placebo after 12 weeks of treatment
o
To assess the effect of treatment with 90 mg QW BMS-986263 on the
proportion of participants with ≥ 2 stage improvement in liver fibrosis
(METAVIR score), as compared to placebo after 12 weeks of treatment
o
To assess the effect of treatment with 90 mg QW BMS-986263 on the
proportion of participants with ≥ 2 stage improvement in liver fibrosis (Ishak
score), as compared to placebo after 12 weeks of treatment
o
To assess the effect of treatment with 90 mg QW BMS-986263 on the
proportion of participants with a ≥ 15% reduction in liver stiffness as measured
by MRE compared to placebo at Week 12
o
To assess the effect of treatment with 90 mg QW BMS-986263 on the change
in liver stiffness from baseline as measured by MRE compared to placebo at
Week 12
o
To assess the safety and tolerability of 45 mg QW and 90 mg QW BMS-986263
throughout 36 weeks of treatment and follow-up
o
To assess the PK of 45 mg QW and 90 mg QW BMS-986263
o
To describe the effect of treatment with 45 mg QW BMS-986263 on liver
fibrosis after 12 weeks of treatment
•
Part 2
o
To assess the effect of treatment with several doses of BMS-986263 on the
change in CPA, as compared to placebo after 24 weeks of treatment
o
To assess the effect of treatment with several doses of BMS-986263 on the
proportion of participants with ≥ 1 stage improvement in liver fibrosis (Ishak
score), as compared to placebo after 24 weeks of treatment
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o  To assess the effect of treatment with several doses of BMS-986263 on the 
proportion of participants with ≥ 2 stage improvement in liver fibrosis 
(METAVIR score), as compared to placebo after 24 weeks of treatment 
o To assess the effect of treatment with several doses of BMS-986263 on the 
proportion of participants with ≥ 2 stage improvement in liver fibrosis (Ishak 
score), as compared to placebo after 24 weeks of treatment 
o To assess the effect of treatment with several doses of BMS-986263 on the 
proportion of participants with a ≥ 15% reduction in liver stiffness as measured 
by MRE compared to placebo at Week 24 
o To assess the effect of treatment with several doses of BMS-986263 on the 
change in liver stiffness from baseline as measured by MRE compared to 
placebo at Week 24 
o To assess the safety and tolerability of several doses of BMS-986263 
throughout 36 weeks of treatment and follow-up 
o To assess the PK of BMS-986263 
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8. INVESTIGATIONAL PLAN 
8.1 Overall Study Design 
This is a randomized, double-blind, placebo-controlled, parallel group study to evaluate the 
efficacy and safety of BMS-986263 in adults with advanced hepatic fibrosis due to HCV who 
have achieved SVR for at least 1 year. This study will enroll approximately 60 participants in 
Part 1, randomized in a 1:2:1 ratio to receive 45 mg BMS-986263 QW, 90 mg BMS-986263 
QW, or placebo QW for 12 weeks; and approximately 120 participants in Part 2, randomized 
in a 1:1:1:1 ratio to receive 45 mg BMS-986263 Q2W, 90 mg BMS-986263 Q2W, 90 mg 
BMS-986263 Q4W, or placebo Q2W for 24 weeks. The primary study endpoint is the 
proportion of participants who achieve ≥ 1 stage improvement in liver fibrosis (METAVIR 
score) on biopsy after 12 weeks of treatment in Part 1 and after 24 weeks in Part 2.  
Part 1: The primary objective of Part 1 is to assess the effect of treatment with 90 mg QW 
BMS-986263 on the proportion participants with ≥ 1 stage improvement in liver fibrosis 
(METAVIR score) on biopsy, as compared to placebo after 12 weeks of treatment. This part of 
the study includes:  
• A screening period 
• A 12-week, double-blind treatment period, during which participants will receive 1 of 
the 3 following treatments: 45 mg BMS-986263 QW, 90 mg BMS-986263 QW, or 
placebo QW  
• A 24-week follow-up period 
Part 2: The primary objective of Part 2 is to assess the effect of treatment with 45 mg 
BMS-986263 Q2W, 90 mg BMS-986263 Q2W, and 90 mg BMS-986263 Q4W on the 
proportion of participants with ≥ 1 stage improvement in liver fibrosis (METAVIR score) as 
compared to placebo after 24 weeks of treatment. This part of the study includes:  
• A screening period 
• A 24-week, double-blind treatment period, during which participants will receive 1 of 
the 4 following treatments: 45 mg BMS-986263 Q2W, 90 mg BMS-986263 Q2W, 
90 mg BMS-986263 Q4W, or placebo Q2W 
• A 12-week follow-up period 
A schematic of the study design is provided in Figure 1.  
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Visit details are provided in the Screening and Day 1 (Randomization) Procedural Outline for 
Part 1 and Part 2 in Table 1.  
8.1.2 Part 1 Treatment Period and Follow-up 
Approximately 60 participants meeting eligibility criteria during the screening period will be 
randomized into the Part 1 treatment period. These participants will be randomized via 
interactive response technology (IRT) in a 1:2:1 ratio to receive 45 mg BMS-986263 QW, 
90 mg BMS-986263 QW, or placebo QW in a double-blind manner. The randomization of 
participants will be stratified by fibrosis stage (METAVIR Stage 3 or Stage 4). Participants 
will receive study treatment via IV administration for a total of 12 weeks. 
Fibrosis stage will be assessed by liver biopsy during the screening period and on Day 85. 
Liver stiffness will be assessed by MRE at baseline, Day 43, Day 85 (primary efficacy 
endpoint), Day 169, and Day 253.  
After 12 weeks (Day 85) of treatment, participants in Part 1 will enter the 24-week 
off- treatment follow-up period. During this time, they will not receive infusions of either 
active drug or placebo.  
See the Schedule of Activities for Part 1 in Table 2 and Table 3 (Section 1.2).  
8.1.4 Part 2 Treatment Period and Follow-up 
Participants meeting eligibility criteria during the screening period will enter the Part 2 
treatment period. Approximately 120 participants will be randomized via IRT in a 1:1:1:1 ratio 
to receive 45 mg BMS-986263 Q2W, 90 mg BMS-986263 Q2W, 90 mg BMS-986263 Q4W, 
or placebo Q2W in a double-blind manner. Randomization of the participants will be stratified 
by fibrosis stage (METAVIR Stage 3 or Stage 4). Participants will receive study treatment via 
IV administration for a total of 24 weeks. Liver biopsy will be performed during the screening 
period and on Day 169. MRE will be collected at Day 43, Day 85, Day 169, and Day 253 in 
Part 2.  
After 24 weeks (Day 169) of treatment, participants in Part 2 will enter the follow-up period 
for 12 weeks. During this time, they will not receive infusions of either active drug or placebo.  
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See the Schedule of Activities for Part 2 in Table 4 and Table 6 (Section 1.2).  
8.2 Data Monitoring Committee and Other Committees 
An external DMC will be used in this study to perform safety monitoring throughout 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 
 
 focusing on early signal detection. Further details on the 
frequency, content, and methods of data reports to the DMC will be outlined in the DMC 
charter along with the processes and procedures the committee will follow. 
8.3 End of Study Definition 
The start of the study is defined as the visit for first participant screening. The end of the study 
is defined as 2 years after the final Clinical Study Report (CSR) (including any addendums) is 
completed. A final summary report will be issued per regulations and local health authority 
requirements.  
The last participant visit is defined as the last visit or scheduled procedure shown in the 
Schedule of Activities (Section 1.2) for the last participant.  
The last day of the study will occur when the last participant has completed his/her Day 253 
visit or discontinues early. Study completion is defined as the final date on which data for the 
primary endpoint in Part 2 of the study was or is expected to be collected, if this is not the 
same. If Part 2 is not initiated, study completion is defined as the final date on which data for 
the primary endpoint in Part 1 of the study was or is expected to be collected, if this is not the 
same. 
Participants will be considered to have completed the study if they complete 253 days of 
evaluation, including all follow-up periods. 
8.4 Study Population 
8.4.1 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) Participants must be willing to participate in the study and sign the ICF. 
b) Participants must be willing and able to complete all study-specific procedures and 
visits. 
2. Participants must provide documentation showing an SVR for at least 1 year prior to the 
date of screening. SVR is defined as a negative HCV RNA at least 12 weeks from the end 
of antiviral therapy. Thus, the minimum duration is 12 weeks of negative HCV RNA (to 
establish SVR) plus 1 year of sustained SVR (ie, 52 weeks + at least 12 weeks).  
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3. The participant must have METAVIR Stage 3 or Stage 4 fibrosis (or equivalent if using 
other classification; eg, Ishak) assessed by liver biopsy.  
4. Participants must have a mean score of ≥ 5.0 kPa by FibroScan (Section 8.6.1.4). If a 
participant has not had a liver biopsy within 8 weeks of screening, the biopsy will be carried 
out during the screening period following determination of eligibility by FibroScan 
assessment (ie, has mean FibroScan score of ≥ 5.0 kPa). 
5. The participant must have an adequate MRE and DXA performed during screening 
confirmed by the central imaging facility prior to randomization.  
6. Age and reproductive status 
a) Males or females ≥ 21 and ≤ 75 years of age at the time of screening 
b) Women of childbearing potential (WOCBP) must have a negative urine pregnancy test 
(minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin) 
within 24 hours prior to the start of study and prior to each dose of study treatment. 
c) To confirm menopause, women must have a serum follicle stimulating hormone 
(FSH) level > 40 mIU/mL.  
d) Women must not be breastfeeding 
e) WOCBP must agree to follow instructions for method(s) of highly effective 
contraception, as defined in Appendix 3, for the duration of treatment (BMS-986263 
or placebo) plus 5 half-lives of study treatment (5 days) plus 30 days (duration of 
ovulatory cycle) for a total of 35 days post-treatment. 
f) Males who are sexually active with WOCBP must agree to have their female partners 
follow instructions for method(s) of highly effective contraception, as defined in 
Appendix 3, for the duration of treatment with study treatment (BMS-986263 or 
placebo) plus 5 half-lives of the study treatment plus 90 days (duration of sperm 
turnover) for a total of 95 days after treatment completion. In addition, male 
participants must be willing to refrain from sperm donation during this time. 
g) Azoospermic males are exempt from contraceptive requirements for the purposes of 
prevention of pregnancy (ie, male study participants with partners who are WOCBP). 
However, in addition to the use of highly effective methods of contraception, males in 
the study who are sexually active with WOCBP must use barrier methods (eg, male 
condom, female condom) to prevent transmission of seminal fluid that may contain 
traces of study drug. Barrier methods must be used for the duration of exposure with 
study treatment (BMS-986263 or placebo) plus 5 half-lives of the study treatment plus 
90 days (duration of sperm turnover) for a total of 95 days after treatment completion. 
h) WOCBP who are continuously not heterosexually active are also exempt from 
contraceptive requirements, and still must undergo pregnancy testing as described in 
this section. 
Investigators shall counsel WOCBP and male participants (and/or their caregivers, as 
applicable) who are sexually active with WOCBP, on the importance of using highly effective 
pregnancy prevention and the implications of an unexpected pregnancy in light of the potential 
for teratogenicity (Appendix 3). Investigators shall advise on the use of highly effective 
methods of contraception (ie, those that have a failure rate of < 1% when used consistently and 
correctly).  
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8.4.2 Exclusion Criteria 
1. Target disease exclusions  
a) Other causes of liver disease, including but not limited to alcoholic liver disease, HBV 
(serologically-positive as determined using United States Centers for Disease Control 
and Prevention guidance for interpretation of hepatitis B serologic test results), 
autoimmune hepatitis, drug-induced hepatotoxicity, Wilson disease, iron overload, 
- 1-antitrypsin deficiency, NASH, hemochromatosis); participants having liver 
diseases associated with infection with any other hepatitis virus are to be excluded. It 
is up to the investigator to be sure the participants do not have any of the above 
mentioned pathologies.  
b) Detectable HCV RNA at screening  
c) Child-Pugh score > 6 at screening (Appendix 7) 
d) MELD score > 12 based on screening laboratories (Appendix 8) 
e) 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 or ultrasound; based on local assessment):  
i. 
AFP > 100 ng/mL (> 82.6 IU/mL) OR 
ii. 
AFP ≥ 50 and ≤ 100 ng/mL (≥ 41.3 IU/mL and ≤ 82.6 IU/mL) with liver 
imaging showing evidence of HCC 
2. Medical conditions 
a) Blood transfusion in the last 6 months prior to screening due to the risk of reinfection 
with HCV, HBV, HIV, etc. 
b) The participant has any disease or condition which, in the opinion of the investigator, 
might compromise patient safety (eg, hematologic, cardiovascular, pulmonary, renal, 
gastrointestinal, hepatic, skeletal, central nervous system, or complement-mediated 
disease). 
c) Hepatitis B surface antigen (HBsAg)-positive participants or hepatitis B core antibody 
(HbcAb)-positive participants with detectable hepatitis B viral DNA. Where required 
by local regulations or standard practice, hepatitis B surface antibody 
(HBsAb)-positive participants must also have HBV DNA testing performed. 
d) Known immunocompromised status, including but not limited to, individuals who have 
undergone organ transplantation or who are positive for HIV or have acquired 
immunodeficiency syndrome (AIDS)-related illness, as reported by the participant 
and/or documentation.  
e) History of liver transplantation or planned liver transplant  
f) Any history of hepatic decompensation, including ascites, variceal bleeding, hepatic 
encephalopathy or spontaneous bacterial peritonitis. 
g) The participant has a 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) 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 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.  
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i) History of alcohol consumption 21 units/week (males) or 14 units/week (females) 
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 8.4.4).  
j) History, within the last 2 years, of alcohol or frequent marijuana abuse (in the opinion 
of the investigator), significant mental illness, or physical dependence on any opioid. 
k) Positive urine test during screening for illegal drugs of abuse (with the exception of 
marijuana), unless these drugs are prescribed by the treating physician (prescription 
must be documented by the investigator or the designee in source documents).  
l) History of intravenous drug use within the 3 years prior to screening. 
m) History of bariatric surgery within the 5 years prior to screening or planned during the 
conduct of the study. 
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 patient, specifically, within the cranium, 
chest, abdomen, or pelvic cavity.  
o) History of weight gain/loss ≥ 10% of body weight in the 6 months prior to screening.  
p) Inability to tolerate IV medication or other study procedures  
q) Presence of pacemaker and or other metal objects in the body  
3. Prior and concomitant therapy 
a) Participants who take any medications that, in the opinion of the investigator, increase 
the risk for complications during liver biopsy (eg, chronic or high-dose nonsteroidal 
inflammatory drugs, anticoagulants, or fish oil supplements) 
b) Participants taking anti-obesity agents (eg, ORLISTAT®) within 4 weeks of the first 
dose of study treatment.  
c) Participants receiving interferon therapy for any disease, or received interferon therapy 
for any disease within 52 weeks prior to administration of study treatment. 
d) The participant takes any vitamin A containing supplements or multivitamins, or 
vitamin A containing medications after signing the ICF. 
e) Participants taking anti-diabetic or anti-dyslipidemic medication receiving stable doses 
for less than 30 days prior to the first dose of study medication. 
f) Participants unable to comply with restrictions and prohibited treatments. 
g) Participants who have not discontinued other investigational agents must be 
discontinued at least 12 weeks or 5 half-lives before the first dose of study treatment, 
whichever is longer.  
h) Prior exposure to BMS-986263 
i) 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). 
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) Body mass index (BMI) > 34 kg/m2. Participants with a BMI of 30-34 kg/m2 must have 
an ALT ≤ upper limit of the normal range (ULN).  
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c) The participant’s baseline laboratory test results include abnormal values considered to 
be clinically significant by the investigator. 
d) The participant’s laboratory test results at screening include any of the following:  
• albumin < 3.5 g/dL 
• INR > ULN 
• ALT value ≥ 2× the ULN 
• hemoglobin A1c ≥ 9.0% 
• total bilirubin > ULN   
• hemoglobin < lower limit of normal (LLN) 
• platelet count < 100,000/µL 
• white blood cell count ≤ 3000/µL 
e) Glomerular filtration rate < 30 mL/min/1.73 m2 according to the Modification of Diet 
in Renal Disease equation. 
f) The participant’s vitamin A levels at screening are > ULN 
g) Alpha-fetoprotein (AFP; see Exclusion 1e, above):  
i. 
AFP > 100 ng/mL (> 82.6 IU/mL) OR 
ii. 
AFP ≥ 50 and ≤ 100 ng/mL (≥ 41.3 IU/mL and ≤ 82.6 IU/mL) with liver 
ultrasound showing findings suspicious for HCC. 
5. Not applicable. 
6. Allergies and adverse drug reaction 
a) History of allergy to BMS-986263 or related compounds 
7. Other exclusion criteria 
a) Prisoners or participants who are involuntarily incarcerated. Note: Under certain 
specific circumstances, 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) Participants who participated in an interventional study with the last intervention 
occurring within 24 weeks prior to administration of study treatment. 
d) Any factor, which in the opinion of the investigator would jeopardize the evaluation or 
safety or be associated with poor adherence to the protocol. 
8.4.3 MRI Contraindications  
The imaging specialist at the site’s imaging facility will be responsible for determining whether 
a participant is contraindicated from undergoing these procedures. Common conditions that 
may preclude the participant from scans include, but are not limited to: 
a) History of claustrophobia 
b) Physical limitations related to fitting into the bore of the magnet or weight greater than 
that allowable by the imaging instrument (i.e., body weight in excess of 250 pounds or 
113.4 kg) 
c) Participants with a pacemaker, epicardial pacemaker wires, MRI-incompatible cardiac 
valve prostheses, MRI-incompatible vascular clips less than 2 months old, or 
MRI--incompatible aneurysm clips of any age 
d) Participants with MRI-incompatible cochlear implants 
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e) Participants with spinal nerve stimulators
f)
Participants with an infusion pump
g) Participants with known metallic fragments in the body
h) Employment history that involves exposure to welding
The above list should not be used as a substitute for local clinical standards of care. The 
ultimate decision to perform any scan should rest with the site radiologist, the investigator, and 
the standard set by the IEC. 
8.4.4 Lifestyle Restrictions 
Participants should not consume ≥ 7 units/week of alcohol during the study. One drink “unit” 
or one standard drink is equivalent to 12 ounces of beer, 4 ounces of wine, or 1 ounce of hard 
liquor.  
8.4.5 Screen Failures, Retesting, and Rescreening 
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. 
Study assessments and/or laboratory parameters ( Table 11) may be repeated (retesting) 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. Other than exceptional circumstances, retesting is allowed only once. 
Rescreening is allowed but the participant must wait 4 weeks after the date of screen failure to 
re-enroll. For participants who are rescreened, biopsy, MRE and/or DXA assessments do not 
need to be repeated if obtained within 8 weeks of randomization. Other than exceptional 
circumstances, rescreening is allowed only once. 
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8.4.6 Withdrawal and Replacement of Participants 
8.4.6.1 Discontinuation of Treatment  
Participants MUST discontinue IP (and nonIP 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 
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• For participants with normal Day 1 (Randomization) liver enzymes and total bilirubin, 
if there is new elevation of ALT or AST > 3 × ULN, repeat testing should be performed 
within 48 to 72 hours. If elevation persists, then standard drug-induced liver injury 
(DILI) discontinuation criteria will be applied and study treatment will be discontinued 
if any of the following occur: 
o ALT or AST > 8 × ULN 
o ALT or AST > 5 × ULN for more than 2 weeks 
o ALT or AST > 3 × ULN and (total bilirubin > 2 × ULN or INR > 1.5) 
o 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 participant lives in a remote location, a local laboratory may be used for repeat 
testing, and results should be promptly communicated to the site. Participants meeting 
the criteria above may have potential DILI, see Section 8.6.2.1.7 for reporting 
requirements 
• For participants with elevated AST, ALT, or total bilirubin at Day 1 (Randomization), 
if there is new elevation of ALT or AST > 2 × ULN or total bilirubin 1.5 × Day 1 
bilirubin, repeat testing should be performed within 48 to 72 hours. If elevation persists, 
then study treatment will be discontinued if any of the following occur: 
o ALT or AST levels increase to > 5 × Day 1 (Randomization) measurement 
o 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 
o Appearance of fatigue, nausea, vomiting, right upper quadrant pain or 
tenderness, fever, rash, and/or eosinophilia (> 5%) 
Note: If participant lives in a remote location, a local laboratory may be used for repeat 
testing, and results should be promptly communicated to the site. Participants meeting 
the criteria above may have potential DILI, see Section 8.6.2.1.7 for reporting 
requirements 
• Termination of the study by BMS 
• Loss of ability to freely provide consent through imprisonment or involuntary 
incarceration for treatment of either a psychiatric or physical (eg, infectious disease) 
illness 
• Abnormal liver tests suggestive of liver injury, as defined in Section 8.6.2.1.7, or 
hepatic decompensation 
• 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 investigator feels that it is no longer in the participant’s best interest to continue 
study treatment. 
• The participant becomes pregnant (study treatment must be discontinued immediately): 
In the case of pregnancy (Section 8.6.2.1.5), the investigator must immediately notify 
the medical monitor or designee of this event. In the event a female participant becomes 
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pregnant during a clinical trial, the study treatment must be discontinued immediately. 
In most cases, the study treatment will be permanently discontinued in an appropriate 
manner (eg, dose tapering if necessary for participant safety). Please contact the 
medical monitor or designee within 24 hours of awareness of the pregnancy. 
See the Schedule of Activities (Section 1.2) 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. 
All participants who discontinue study treatment should comply with protocol-specified 
follow-up procedures as outlined in Section 1.2. The only exception to this requirement is when 
a participant withdraws consent for all study procedures including post-treatment 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). 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 electronic case report form (eCRF) page. As indicated, appropriate 
follow-up and/or alternate medical care must be arranged for the participant. 
Participants who discontinue study treatment will remain in the study for continued follow-up. 
8.4.6.2 Discontinuation from the Study 
Participants who request to discontinue study treatment will remain in the study and will 
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. Expectations are 
as follows:  
• 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, as to whether the withdrawal is from further treatment with study 
treatment only or also from study procedures and/or post treatment study follow-up, 
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/end of study 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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8.4.6.3 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. 
8.4.6.4 Replacement of Participants 
If a higher than expected proportion of participants discontinue from the study prior to the 
evaluation of the primary endpoint, the sponsor may choose to enroll additional participants to 
ensure an adequate number of participants are available for evaluation of the primary endpoint.  
Rescreening is discussed in Section 8.4.5.  
8.5 Study 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 
noninvestigational [medicinal] product (nonIP/nonIMP) and is described in Table 7. 
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.  
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Table 7 
Study Treatments for IM025006 
Product Description 
/ Class and Dosage 
Form 
Potency 
IP/ 
NonIP 
Blinded 
or Open 
Label 
Packaging / 
Appearance 
Storage 
Conditions 
(per label) 
BMS-986263 / 
siRNA / intravenous 
Placebo / intravenous 
NA 
IP 
Blinded  
On-site compounded 
solutiona 
Refer to 
pharmacy 
manual  
Diphenhydramine / 
antihistamine / 
intravenousb 
50 mg/mL; 
1 mL prefilled 
syringe 
NonIP 
Open 
Label 
Clear and colorless 
solution available as 
50 mg/mL in a 1 mL 
prefilled single-use 
syringe 
Stored at 20° to 
25°C; protected 
from freezing 
and light 
Famotidine / 
antihistamine / 
intravenousb 
20 mg/50 mL; 
50 mL single 
dose container  
NonIP 
Open 
Label 
Clear and colorless 
solution available as 
20 mg/50 mL in a 
50 mL container 
Stored at 20° to 
25°C; protected 
from light 
Levocetirizine 
dihydrochloride / 
diphenhydramine 
hydrochloride 
(antihistamine) / oralb 
5 mg 
NonIP 
Open 
Label 
White, oval, biconvex, 
film-coated functional 
scored tablets 
Stored at 68° to 
77°F, away from 
excess heat and 
moisture 
Hydrocortisone 
Sodium Succinate / 
intravenousb 
100 mg 
 
NonIP 
Open 
Label 
White, powder for 
solution for injection 
100 mg/2 mL 
Stored at 68° to 
77°F, protected 
from light 
IP = investigational product; NA = not applicable; siRNA = small interfering ribonucleic acid 
a The composition of the placebo solution is 100 mL D5W containing 0.3 – 0.6 mL of Intralipid® 20%.  
b To be administered at the discretion of the investigator. Methylprednisolone sodium succinate 125 mg IV may be used 
instead of hydrocortisone See Section 8.5.1.2 for more details.  
8.5.1 Treatments Administered 
The investigator must ensure that the IP will be used only in accordance with the protocol. The 
selection and timing of dose for each participant is shown in Table 8.  
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.  
The study treatment will be infused using an IV pump, as described in the Pharmacy Manual. 
The IV will be kept open before and after the infusion with sufficient quantities of 0.9% saline 
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to assure it remains patent. The time the infusion is initiated/adjusted/concluded, including any 
interruptions, will be documented in the eCRF.  
8.5.1.1 Study Treatment Infusion Rate 
The study medication should not be infused at a duration lesser than 60 minutes. The infusion 
rate may be modified by the investigator based on clinical discretion and/or the participant’s 
previous tolerance of the infusion, including any infusion reactions that may have occurred in 
the past. In addition, the investigator may choose to pause the infusion depending on the 
participant’s clinical condition and history.  
Of note, while the rate of infusion can be modified as described above; no reductions or 
modifications of the total dose to be administered are allowed.  
If a participant experiences an infusion-related reaction, temporary interruption of the infusion 
and/or reduction of the infusion rate (for example, but not limited to, modification of infusion 
rate and/or a pause in the infusion) may lead to improvement of signs and symptoms. 
Medications, emergency equipment, and trained personnel able to treat immediate or delayed 
infusion-related reactions should be available for immediate access at the clinical site(s).  
8.5.1.2 Premedication  
To reduce the potential for possible infusion reactions, based on the discretion of the 
investigator, the participants in Part 1 may be pretreated 15 to 30 minutes before the start of 
the study treatment infusion. The investigator may choose to administer any or all of the 
following premedications: 50 mg diphenhydramine hydrochloride IV, 20 mg famotidine IV, 
and/or hydrocortisone 100 mg IV. Hydrocortisone IV may be replaced with 
methylprednisolone sodium succinate 125 mg IV based on the discretion of the investigator. 
Additionally, the investigator may choose not to administer any premedication. If IV 
diphenhydramine is not available, an oral dose of 5 mg levocetirizine dihydrochloride or an 
oral dose of 50 mg diphenhydramine hydrochloride may be substituted and administered 
2 hours ± 15 minutes before the start of study treatment infusion.  
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, although a longer observation period may be necessary for an 
individual participant. The decision to observe a study participant beyond the required 3 hours 
will be at the discretion of the attending investigator. 
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Table 8 
Selection and Timing of Dose 
Study Treatment 
Unit dose 
strength(s)/Dosage 
level(s) 
Dosage formulation 
Frequency of 
Administration 
Route of 
Administration 
Part 1 
 
 
 
BMS-986263 
3 mg/mL  
total dose of 45 mg 
QW 
Intravenous 
BMS-986263 
3 mg/mL  
total dose of 90 mg 
QW 
Intravenous 
Placebo (Part 1) 
NA 
QW 
Intravenous 
Part 2 
 
 
 
BMS-986263 
3 mg/mL  
total dose of 45 mg 
Q2W 
Intravenous 
BMS-986263 
3 mg/mL  
total dose of 90 mg 
Q2W 
Intravenous 
BMS-986263 
3 mg/mL  
total dose of 90 mg 
Q4Wa 
Intravenous 
Placebo (Part 2) 
NA 
Q2W 
Intravenous 
NA = not applicable; QW = once every week; Q2W = once every 2 weeks; Q4W = once every 4 weeks 
a Alternating doses of active drug (90 mg Q4W) and placebo (Q2W) will be carried out with active drug dosing on Days 29, 
57, 85, 113, and 141 and placebo dosing on Days 15, 43, 71, 99, 127, and 155, as indicated in the Part 2 Schedule of Activities 
Table 4 and Table 6 (Section 1.2) 
Restrictions related to food and fluid intake are described in Section 8.4.4. 
8.5.2 Method of Treatment Assignment 
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 at the study visits 
as listed in Schedule of Activities (Section 1.2). 
At the time of the screening visit, immediately after informed consent is obtained and before 
any study-related procedures are performed, the investigative site will access the enrollment 
option using the IRT for assignment of the participant number, including participants not 
subsequently randomized or treated. This number will be unique across all sites. All enrolled 
participants will be assigned sequential participant numbers. The participant number may not 
be used for any other participant. If a potential participant is rescreened, they will be given a 
new identification number. 
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.  
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8.5.3 Blinding of Study Medication 
8.5.3.1 Maintaining the Blind 
Blinded treatment assignments will be managed using IRT. All vials (BMS-986263 and 
placebo) are identical in appearance, and they will be supplied as shown in Table 8. 
Investigative site staff, sponsor and designee personnel, and participants and their families will 
remain blinded to treatment assignments. 
The investigative site staff will include 2 individuals with well-defined roles, as follows:  
• An unblinded study drug administrator, who will be responsible for administering the 
infusion and/or adjusting the infusion rate and will ensure that the infusion set is 
concealed with adequate line-cover and bag-cover. This individual will not conduct any 
patient-facing assessments. 
• An assessor, who will be responsible for performing any study-related assessments on 
study participants including, but not limited to, those pertaining to safety, tolerability, 
or efficacy.   
At all times, every attempt will be made to ensure that the 2 roles are able to function separately 
to ensure blinding of study treatment. 
8.5.3.2 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 principal investigator or designee should only call in for 
emergency unblinding AFTER the decision to discontinue the participant has been made. 
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 IRT 
Manual. Participant and unblinded treatment information and the reason for the blind being 
broken must be recorded on the appropriate study status page of the eCRF. After unblinding 
via IRT, the investigator shall notify the medical monitor. 
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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. 
8.5.4 Study Treatment Preparation, Handling, Storage, and 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. 
Please refer to the study Pharmacy Manual for IP and nonIP preparation.  
Study treatment not supplied by BMS will be stored in accordance with the package insert.  
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).  
Further guidance and information for final disposition of unused study treatment are provided 
in Appendix 1.  
8.5.5 Dose Modification 
No reductions or modifications of the total dose are allowed. If a participant interrupts 
treatment due to an AE, study treatment can be restarted.   
8.5.6 Treatment Compliance 
As all study medication will be administered by site staff, treatment compliance will not be 
formally assessed.  
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8.5.7 Prior and Concomitant Therapy 
All medications taken from within 4 weeks before the first dose of study treatment until the 
last study visit must be recorded on the eCRF. Prior medications are defined as medications 
taken within 4 weeks of the first dose of study treatment and discontinued before the first dose 
of study treatment. Concomitant medications are defined as any medication taken after the first 
dose of study medication until the last study visit. Concomitant medications (prescription, 
over-the-counter, or herbal) should be administered during the study only if they are prescribed 
for treatment of specific clinical events. 
Restrictions and prohibitions on prior and concomitant medications are as follows: 
1. Anti-obesity agents (eg, ORLISTAT). 
2. Ongoing therapy for HCV or received therapy for HCV within 52 weeks prior to 
administration of study treatment. 
3. Interferon therapy for any disease, or received interferon therapy for any disease within 
52 weeks prior to administration of study treatment. 
5. Prior exposure to BMS-986263 is prohibited. 
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. 
7. Other investigational agents. Any other investigational agent must be discontinued at 
least 12 weeks or 5 half-lives before the first dose of study treatment, whichever is 
longer.  
8.5.8 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 other reasons, 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. 
8.6 Efficacy and Safety Assessments 
Study procedures and timing are summarized in the Schedule of Activities (Section 1.2). 
Waivers or exemptions from protocol-required evaluations are not allowed.  
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8.6.1 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 
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.  
The following procedures or tools will be used to assess participants’ fibrotic disease activity 
during the study (see Schedule of Activities in Section 1.2):  
• Liver biopsy assessments (Section 8.6.1.1) 
• Other noninvasive measures:  
o Liver stiffness as measured by MRE (Section 8.6.1.2) 
o Liver fibrosis scoring:  
▪ FibroScan (Section 8.6.1.4) 
8.6.1.1 Liver Biopsy 
Biopsies performed during screening for purposes of determining eligibility will be assessed 
by a local pathologist. Participants must have METAVIR Stage 3 or Stage 4 liver fibrosis to 
be eligible. If pathologic evidence suggesting a cause of liver fibrosis other than 
HVC-associated fibrosis is observed (eg, NASH), the participant is not eligible. If there is any 
question about the eligibility of a participant based on locally assessed biopsy results, the 
investigator should contact the medical monitor prior to randomizing the participant. 
Tissue from biopsies performed during the study (or tissue submitted from prior biopsies when 
appropriate, see Section 8.1.1) will be collected for analysis. All histological assessments 
related to efficacy of BMS-986263 will be performed by a central reader. Details on the 
acquisition, quality requirements, histological preparation, and shipping of histological 
samples are in the Central Laboratory Manual. Due to the delay in assessing tissue samples for 
study endpoints, a report from the central pathologist will not be provided to the study sites. If 
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a clinical assessment of the biopsy is required a portion of the sample should be submitted to 
a local pathologist following the standard procedure utilized by the study site. 
No more than 2 study associated biopsies will be conducted within a 48-week period. (Note: 
In some occasions the first pass for liver biopsy may not result in an adequate quantity of liver 
tissue, thus demanding for a second pass in order to obtain sufficient amount of liver tissue for 
analysis. The second pass should not be considered a second biopsy.)  
To assess potential HSC suppression, the following assessments will be performed:  
• Histology, including changes in hepatic architecture  
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8.6.1.1.1 Histological Assessment and METAVIR scoring 
The METAVIR system is used to assess the extent of inflammation and fibrosis by 
histopathological evaluation in a liver biopsy of patients with HCV. It assesses liver biopsies 
for activity grade (A0-A3: A0 = no activity, A1 = mild activity, A2 = moderate activity, 
A3 = severe activity) and fibrosis stage (Stage 1 – 4: 1 = portal fibrosis without septa; 
2 = portal fibrosis with few septa; 3 = numerous septa without cirrhosis; or 4 = cirrhosis). 
8.6.1.1.2 Histological Assessment and Ishak scoring 
The Ishak scoring system will also be used to grade fibrosis in the histology samples. The Ishak 
system (0 through 6 scale) was developed to grade portal-based liver fibrosis associated with 
viral hepatitis: 
• 0: No fibrosis 
• 1: Fibrous expansion of some portal areas, with or without short fibrous septa 
• 2: Fibrous expansion of most portal areas, with or without short fibrous septa 
• 3: Fibrous expansion of most portal areas with occasional portal to portal bridging 
• 4: Fibrous expansion of portal areas with marked bridging (portal to portal as well as 
portal to central) 
• 5: Marked bridging (portal–portal and/or portal–central) with occasional nodules 
(incomplete cirrhosis) 
• 6: Cirrhosis, probable or definite 
8.6.1.1.3 Morphometric Analysis of Collagen Proportionate Area in Stained Tissue  
There can be considerable intra- and inter-individual variation in the assessment of liver biopsy 
to determine fibrosis stage. Assessment of CPA is a method by which the amount (percentage) 
of collagen in stained tissue sections is analyzed using morphometric image analysis. This 
technique allows for a quantitative assessment of fibrosis. This morphometric assessment will 
be performed by a blinded central pathologist. 
8.6.1.2 MRE Imaging Assessment 
MRE is a noninvasive medical imaging technique approved by FDA in 2009. It quantitatively 
measures the stiffness of soft tissues by introducing shear waves and imaging their propagation 
using MRI. MRE has been demonstrated to be accurate and reproducible, and highly 
concordant compared to histopathology for staging liver fibrosis.23 
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In this study, MRE will be used to quantitate liver stiffness as a surrogate biomarker of liver 
fibrosis.  
MRE assessments should be performed at time points indicated in Schedule of Activities 
(Section 1.2). MRE should be conducted at the early termination visit only if the participant’s 
prior MRE occurred > 4 weeks prior to termination. The central imaging facility will perform 
all MRE imaging analyses. 
Adequacy of the MRE should be confirmed by the central imaging facility prior to 
randomization. Image acquisition guidelines and submission processes will be outlined in the 
IM025006 Imaging Manual, to be provided by the central imaging facility. The clinical sites 
will be trained in imaging procedures prior to scanning the first study participant. Images will 
be submitted to the central imaging facility for central review. The site will be informed of 
quality issues or the need to repeat scanning from the central imaging facility.  
Any incidental findings of potential clinical relevance that are not directly associated with the 
objectives of the protocol should be evaluated and handled by the investigator in collaboration 
with a local radiologist, as per standard medical/clinical judgement.  
8.6.1.3 Pharmacokinetic 
 Sampling 
Blood sampling will be carried out for the analysis of PK 
 
 
 
 
 
 
 
 
 
   
8.6.1.4 FibroScan  
FibroScan is an ultrasound-based medical device dedicated to the noninvasive measurement 
of liver stiffness, approved by FDA in 2013. The procedure is painless for the patient, 
noninvasive, rapid (5-10 minutes), and repeatable. Presently, there are more than 2,000 
FibroScan devices available in more than 70 countries in the world. It is widely utilized in 
hepatologists’ offices for the initial evaluation of patients with liver disease before or 
potentially to forgo liver biopsy.  
Multiple studies and meta-analyses have demonstrated that liver stiffness values measured by 
FibroScan correlate highly with advanced fibrosis in chronic liver diseases.24-27 Liver stiffness 
values above 9.6 kPa and 12.5 kPa are indicative of advanced fibrosis (Stage 3) and cirrhosis 
(Stage 4), respectively. 
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 During screening, FibroScan should demonstrate a mean liver 
stiffness measurement > 5.0 kPa for eligibility. 
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8.6.2 Safety Assessments 
Planned time points for all safety assessments are listed in the Schedule of Activities 
(Section 1.2). 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 of BMS-986263 will be assessed by evaluation of the incidence of all AEs and 
SAEs leading to withdrawal of study medication, 
 
 laboratory data, 
electrocardiogram (ECG) monitoring, physical examinations, vital signs, 
 
 
The participants must not have documented bone abnormalities at baseline as defined in the 
Exclusion Criteria (Section 8.4.2). 
 
 Since DXA is required at baseline, the 
investigator should consider the results of the assessment in determining the eligibility of a 
potential participant. 
8.6.2.1 Adverse Events 
The definitions of an AE or SAE can be found in Appendix 2. 
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.  
The event (term), along with its start and stop dates, maximum intensity (mild, moderate, or 
severe), seriousness (yes/no), relationship to the IP (yes/no), action taken with regard to the IP, 
and outcome will be recorded in the eCRF.  
Contacts for SAE reporting specified in Appendix 2. 
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8.6.2.1.1 Time Period and Frequency for Collecting AE and SAE Information 
Nonserious AEs will be collected from the time of the first dose of IP through the date of the 
follow-up or last visit, and at the time points specified in the Schedule of Activities 
(Section 1.2). 
The Reference Safety Information in Sections 5.6.1 and 5.6.2 of the IB should be used to 
determine the expectedness of SAEs for expedited reporting. Following the participant’s 
written consent to participate in the study, all SAEs, whether related or not related to study 
drug, must be collected, including those thought to be associated with protocol-specified 
procedures. 
All SAEs that occur from the time ICF is signed to 30 days after the final dose of the study 
drug must be reported to PRA Drug Safety. After that time, only SAEs deemed by the 
investigator to be related to the study drug or a study procedure should be reported. 
If applicable, SAEs must be collected that relate to any later protocol-specified procedure. 
• 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. 
• 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 sponsor or designee within 24 hours, as 
indicated in Appendix 2.  
• The investigator will submit any updated SAE data to the sponsor or designee within 
24 hours of this being available. 
Investigators are not obligated to actively seek AEs or SAEs in 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. 
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 2. 
8.6.2.1.2 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. 
8.6.2.1.3 Follow-up of AEs and SAEs 
Nonserious AEs should be followed to resolution, or stabilization, or reported as SAEs if they 
become serious (Appendix 2). 
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Follow-up is also required for nonserious AEs that cause interruption or discontinuation of 
study treatment and for those present at the end of study 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 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 8.4.6.3). 
Further information on follow-up procedures is given in Appendix 2. 
8.6.2.1.4 Regulatory Reporting Requirements for SAEs 
Prompt notification by the investigator to the sponsor of SAEs is essential so that legal 
obligations and ethical responsibilities towards 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/EC, if appropriate according to local requirements. 
The sponsor or designee will report AEs to regulatory authorities and IECs according to local 
applicable laws including European Directive 2001/20/EC and FDA CFR 21 CFR Parts 312 
and 320. A SUSAR (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. 
8.6.2.1.5 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 after product administration, the investigator must immediately notify the medical 
monitor/designee of this event and complete and forward a Pregnancy Surveillance Form to 
BMS Designee within 24 hours of awareness of the event and in accordance with SAE 
reporting procedures described in Appendix 2. 
If the participant becomes pregnant study treatment must be discontinued immediately. Please 
contact the medical monitor or designee 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. 
Any pregnancy that occurs in a female partner of a male study participant should be reported 
to sponsor or designee. In order for sponsor or designee to collect any pregnancy surveillance 
information from the female partner, the female partner must sign an ICF for disclosure of this 
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information. Information on this pregnancy will be collected on the Pregnancy Surveillance 
Form. 
8.6.2.1.6 Laboratory Test Result Abnormalities 
The following laboratory test result abnormalities should be captured on the nonserious AE 
eCRF page or SAE Report Form electronic, as appropriate. Paper forms are only intended as a 
back-up option when the electronic system is not functioning. 
• Any laboratory test result that is clinically significant or meets the definition of an 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 
It is expected that wherever possible, the clinical rather than laboratory term would be used by 
the reporting investigator (eg, anemia vs low hemoglobin value). 
8.6.2.1.7 Potential Liver Injury 
Wherever possible, timely confirmation of initial liver-related laboratory abnormalities should 
occur prior to the reporting of a potential DILI event. The study treatment discontinuation 
criteria are provided in Section 8.4.6.1. All occurrences of potential DILIs, meeting the defined 
criteria, must be reported as SAEs (Appendix 2 for reporting details).  
Participants who meet criteria for DILI should have relevant laboratory testing (eg, ALT, AST, 
and INR levels) repeated at least weekly until abnormalities have resolved. Tests should be 
repeated within 3 days; then, every 3 days until reversal is noted; and then, every week until 
normalization. The investigator should make every effort to determine if any other cause for 
the liver test abnormalities is present. 
8.6.2.1.8 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 AEs, as appropriate, and reported accordingly. 
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8.6.2.2 Overdose 
An overdose is defined as the accidental or intentional administration of any dose of a product 
that is considered both excessive and medically important. All occurrences of overdose must 
be reported as SAEs (Appendix 2). 
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. 
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 (determined 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. 
Decisions regarding dose interruptions or modifications will be made by the investigator in 
consultation with the medical monitor based on the clinical evaluation of the participant. 
8.6.2.3 Physical Examinations 
Schedules for physical examinations are provided in Schedule of Activities (Section 1.2). 
Complete and/or abbreviated physical examinations may be performed by a Doctor of 
Medicine (MD) or equivalent, or someone who is authorized to perform the examinations by 
training and has been delegated this task by the principal investigator.  
Full physical examinations will be performed at screening and Days 85 and 253 in Part 1 and 
screening and Days 85, 169, and 253 in Part 2. A full examination will include general 
appearance, skin, head, eyes, ears, nose, throat, neck, thyroid, chest/lungs, heart, abdomen, 
lymph nodes, extremities, height, and body weight.  
Abbreviated physical examinations will be performed at the other time points (Schedule of 
Activities; Section 1.2), which 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. 
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8.6.2.7 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. Results of clinical 
laboratory tests performed on Day -1 must be available prior to dosing.  
Hematology, serum chemistry and urinalysis assessments are listed below: 
 Table 11 
Hematology, Chemistry, Urinalysis, 
 Assessments 
Hematology 
• 
CBC 
• 
PT 
• 
PTT 
• 
INR  
• WBC (absolute)  
• Hemoglobin 
• Hematocrit 
• MCV 
• 
MCH concentration 
• 
Red cell distribution width  
• 
Platelet count 
Blood Chemistry 
• 
AST 
• 
ALT 
• 
Total bilirubin 
• 
Direct bilirubin 
• 
ALP 
• 
LDH 
• 
GGT  
• 
Creatinine  
• 
Creatinine clearance 
• 
Creatine kinase 
• 
BUN 
• 
Uric acid 
• 
Glucose 
• 
PTH  
• 
Total protein  
• 
Albumin sodium 
• 
Potassium 
• 
Chloride 
• 
Carbon dioxide 
• 
Calcium 
• 
Phosphorus 
• 
Glomerular filtration rate 
Urinalysis 
• 
pH 
• 
Specific gravity 
• 
Protein 
• 
Glucose 
• 
Ketones  
• 
Leukocyte esterase 
• 
Nitrite 
• 
Creatinine 
• 
Microscopic examination (only to 
follow-up abnormal findings) 
HbA1C 
Serology/viral load 
• 
HCV viral load 
(RNA) 
• 
HBsAg 
• 
HbcAb and HBV viral DNA if 
HbcAb-positive. 
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Other Analyses 
• 
FSH 
• 
AFP  
• 
Illegal drugs of abuse (urine or serum; 
amphetamine, barbiturate, 
benzodiazepines, marijuana, cocaine, 
opiate, or PCP) 
• 
pregnancy test (WOCBP only). 
AFP = alpha-fetoprotein; ALP = alkaline phosphatase; 
 ALT = alanine 
aminotransferase, AST = aspartate aminotransferase; 
 
 BUN = blood urea nitrogen; 
 
 CBC = complete blood count; 
 
 CVD = cardiovascular disease; DNA = deoxyribonucleic acid; 
 
 GGT = gamma-glutamyl transferase; 
 
 FSH = follicle stimulating hormone; HbA1c = hemoglobin A1c; HBsAg = hepatitis B surface antigen; 
HbcAb = hepatitis B core antibody; HBsAb = hepatitis B surface antibody; HDL = high-density lipoprotein; 
INR = international normalized ratio; LDH = lactate dehydrogenase; 
 MCH = mean 
corpuscular hemoglobin; MCV = mean corpuscular volume; MOA = mechanism of action; 
 
 PCP = phencyclidine; PT = prothrombin time; PTH = 
parathyroid hormone; PTT = partial thromboplastin time; 
 WBC = white blood cell; 
WOCBP = women of childbearing potential 
   
8.6.2.8 Imaging Safety Assessments – DXA 
DXA (femur, hip, and lumbar spine) will be performed at the time points indicated in Schedule 
of Activities (Section 1.2). DXA is to be scheduled at least 5 days ahead of Day 1 
(Randomization) to allow adequate time for results to be analyzed. 
 
 
  
Image acquisition guidelines and submission processes will be outlined in the IM025006 
Imaging Manual, to be provided by the central imaging facility. The clinical sites will be 
trained in imaging procedures prior to scanning the first study participant. All images will be 
submitted to the central imaging facility for assessment of the BMD.   
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Adequacy of DXA should be confirmed by the central imaging facility prior to randomization. 
The site will be informed of quality issues or the need to repeat scanning from the central 
imaging facility. 
Any incidental findings of potential clinical relevance that are not directly associated with the 
objectives of the protocol should be evaluated and handled by the investigator as per standard 
medical/clinical judgement.  
8.6.3 Pharmacokinetics 
Blood for PK samples for Part 1 will be drawn according to the sampling schedule shown in 
Table 12. For Part 2, blood for PK samples will be drawn according to the sampling schedule 
shown in Table 13.  
Samples from participants randomized to placebo will not be analyzed.  
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Table 12 
Pharmacokinetic 
 
Sampling Schedule for BMS-986263 in Part 1 
Daya 
Event 
Timeh 
(Relative to BMS-986263 Dose) 
Hour: Min 
BMS-986263 
Blood Sample for 
plasma PK 
1 
pre-infusion 
00:00b,    
X 
1 
mid-infusion 
00:30c 
X 
1 
end-of-infusion 
00:00d 
X 
1 
postinfusion 
01:00e,    
X 
4 (± 1 day) 
postinfusion 
72:00f 
X 
8 
pre-infusion 
00:00b,    
X 
8 
mid-infusion 
00:30c 
X 
8 
end-of-infusion 
00:00d 
X 
8 
postinfusion 
01:00e,    
X 
15 
pre-infusion 
00:00b,    
X 
29 
pre-infusion 
00:00b,    
X 
29 
mid-infusion 
00:30c 
X 
29 
end-of-infusion 
00:00d 
X 
29 
postinfusion 
01:00e,    
X 
36  
pre-infusion 
00:00b 
X 
43 
pre-infusion 
00:00b,    
X 
43 
mid-infusion 
00:30c 
X 
43 
end-of-infusion 
00:00d 
X 
43 
postinfusion 
01:00e,    
X 
46 (± 1 day) 
postinfusion  
72:00f 
X 
50 
pre-infusion 
00:00b 
X 
57 
pre-infusion 
00:00b,    
X 
78 
pre-infusion 
00:10b,    
X 
78 
mid-infusion 
00:30c 
X 
78 
end-of infusion 
00:00d 
X 
78 
postinfusion 
01:00e,    
X 
85 
postinfusion 
168:00 (7 days) f,    
X 
99 
postinfusion 
504:00 (21 days) f 
X 
PK = pharmacokinetics 
a The days for PK sampling are indicated in the Schedule of Activities (Section 1.2).  
b Time is relative to the start of infusion. Samples may be collected up to 120 minutes prior to the start of the infusion. 
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c Time is relative to the start of infusion. Samples should be collected ± 3 minutes within specified timeframe. If infusion is 
administered at a modified rate, the timing of collection of this sample should correspond to the middle of the modified 
infusion duration of the total administered dose. 
d Time is relative to the end-of-infusion. Samples should be collected -2 minutes within specified timeframe. This sample 
should be taken immediately prior to stopping the infusion. If the end-of-infusion is delayed to beyond the nominal infusion 
duration, the collection of this sample should also be delayed accordingly. 
e Time is relative to the end-of-infusion. Samples should be collected ± 3 minutes within specified timeframe. 
f Time is relative to the end-of-infusion of the previous dosing day. Sample may be collected ± 1 day at the PK visit on Day 4 
and Day 46. 
 
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Table 13 
Pharmacokinetic
 
Sampling Schedule for BMS-986263 in Part 2 
Daya 
Event 
Time 
(Relative to BMS-986263 
Dose) Hour: Min 
BMS-986263 
Blood Sample for 
plasma PK 
1 
pre-infusion 
00:00b,    
X 
1 
mid-infusion 
00:30c  
X 
1 
end-of-infusion 
 00:00d 
X 
1 
postinfusion 
01:00e,    
X 
4 (± 1 day) 
postinfusion 
72 :00f 
X 
15 
pre-infusion 
00:00b 
X 
29 
pre-infusion 
00:00b,    
X 
29 
mid-infusion 
00:30c 
X 
29 
end-of-infusion 
00:00d 
X 
29 
postinfusion 
01:00e,    
X 
43 
pre-infusion 
00:00b,    
X 
43 
mid-infusion 
00:30c 
X 
43 
end-of-infusion 
00:00d 
X 
43 
postinfusion 
01:00e,    
X 
46 (± 1 day) 
postinfusion 
72 :00f 
X 
57 
pre-infusion 
00:00b 
X 
71 
pre-infusion 
00:00b 
X 
85 
pre-infusion 
00:00b,    
X 
85 
mid-infusion 
00:30c 
X 
85 
end-of-infusion 
00:00d  
X 
85 
postinfusion 
01:00e,    
X 
99 
pre-infusion 
00:00b 
X 
113 
pre-infusion 
00:00b 
X 
127 
pre-infusion 
00:00b 
X 
141 
pre-infusion 
00:00b 
X 
141 
mid-infusion 
00:30c 
X 
141 
end-of-infusion 
00:00d  
X 
141 
postinfusion 
01:00e  
X 
155 
pre-infusion 
00:00b 
X 
169 
postinfusion 
336:00 (14 days) 
X 
PK = pharmacokinetics 
a The days for PK sampling are indicated in the Schedule of Activities (Section 1.2).  
b Time is relative to the start of infusion. Samples may be collected up to 120 minutes prior to the start of the infusion. 
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c Time is relative to the start of infusion. Samples should be collected ± 3 minutes within specified timeframe. If infusion is 
administered at a modified rate, the timing of collection of this sample should correspond to the middle of the modified 
infusion duration of the total administered dose. 
d Time is relative to the end-of-infusion. Samples should be collected -2 minutes within specified timeframe. This sample 
should be taken immediately prior to stopping the infusion. If the end-of-infusion is delayed to beyond the nominal infusion 
duration, the collection of this sample should also be delayed accordingly. 
e Time is relative to the end-of-infusion. Samples should be collected ± 3 minutes within specified timeframe. 
f Time is relative to the end-of-infusion. Sample may be collected ± 1 day at the PK visit on Day 4 and Day 46. 
 
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9. STATISTICAL CONSIDERATIONS 
9.1 Sample Size Determination 
This study will enroll a total of 60 participants in Part 1 of the study, randomized via IRT in a 
1:2:1 ratio to receive 45 mg BMS-986263 QW, 90 mg BMS-986263 QW, and placebo QW. 
The sample size for Part1 is not based on formal statistical justification. Part 1 of the study is 
designed for estimation purposes; no statistical testing will be performed. A 95% confidence 
interval (CI) for the primary endpoint of proportion of participants with ≥ 1 stage improvement 
in fibrosis on biopsy after 12 weeks of treatment and odds-ratios between treatment groups 
will be utilized for this purpose. 
In Part 2, approximately 120 participants will be randomized via IRT in a 1:1:1:1 ratio to 
receive 45 mg BMS-986263 Q2W, 90 mg BMS-986263 Q2W, 90 mg BMS-986263 Q4W, or 
placebo Q2W in a double-blind manner. The primary endpoint for Part 2 is the proportion of 
participants with ≥ 1 stage improvement in fibrosis on biopsy after 24 weeks of treatment. For 
this portion (Part 2) of the study, it is anticipated that approximately 10% of the participants 
will discontinue (dropout) early from study treatment. Participants who discontinue early 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. 
The response rates for the primary liver biopsy endpoint for the 4 treatment groups in Part 2 
are assumed to be as follows: placebo Q2W – 20%, 90 mg BMS-986263 Q4W – 30%, 45 mg 
BMS-986263 Q2W – 35%, and 90 mg BMS-986263 Q2W – 50%. With these assumptions, 
using a 1-sided 0.05 level of significance, there will be 80% power to detect a trend using a 
Cochran Armitage trend test in the primary endpoint among the 4 treatment groups with n = 30 
in each group.  
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9.2 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.  
Pharmacokinetic 
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.  
9.3 Statistical Analyses 
The statistical analysis plan (SAP) will be developed and finalized before database lock for the 
primary efficacy analysis and will provide detailed specifications of the analysis of all efficacy 
endpoints and safety and will also describe the selection of participants to be included in the 
analyses and procedures for accounting for missing, unused, and spurious data.  
This section provides a summary of planned statistical analyses of the primary and secondary 
endpoints.  
9.3.1 Efficacy 
9.3.1.1 Efficacy Endpoints 
The primary efficacy endpoint is the proportion of participants who achieve ≥ 1 stage 
improvement in liver fibrosis (METAVIR score) as determined by liver biopsy after 12 weeks 
of treatment in Part 1 and after 24 weeks in Part 2.  
Secondary efficacy endpoints are as follows:  
• Change in CPA, as compared to placebo after 12 weeks of treatment in Part 1 and after 
24 weeks of treatment in Part 2 
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• Proportion of participants with ≥ 1 stage improvement in liver fibrosis (Ishak score), as 
compared to placebo after 12 weeks of treatment in Part 1 and after 24 weeks of 
treatment in Part 2 
• Proportion of participants with ≥ 2 stage improvement in liver fibrosis (METAVIR 
score), as compared to placebo after 12 weeks of treatment in Part 1 and after 24 weeks 
of treatment in Part 2 
• Proportion of participants with ≥ 2 stage improvement in liver fibrosis (Ishak score), as 
compared to placebo after 12 weeks of treatment in Part 1 and after 24 weeks of 
treatment in Part 2 
• Proportion of participants with ≥ 15% decrease from baseline in liver stiffness as 
measured by MRE at Day 85 in Part 1 and Day 169 in Part 2 
• Change from baseline in liver stiffness as measured by MRE Day 85 in Part 1 and 
Day 169 in Part 2   
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9.3.1.2 Analysis Methodology 
Efficacy analyses will be performed using the modified intent-to-treat (mITT) population. The 
handling of missing values will be defined in the SAP.  
Primary Endpoint Part 1: To evaluate the effect of BMS-986263 (90 mg QW) on METAVIR 
Fibrosis Stage at Week 12, a 95.0% CI of response rate for treatment vs placebo will be used 
to estimate the difference between the proportion of participants with ≥ 1 stage improvement 
in fibrosis on liver biopsy. Additionally, the odds ratio of each treatment will be used to 
estimate improvement of treatment as compared to placebo for the proportion of participants 
with > 1 stage improvement in fibrosis on biopsy at Week 12. 
Primary Endpoint Part 2: To evaluate the effect of BMS-986263 (45 mg Q2W, 90 mg Q2W, 
90 mg Q4W) on METAVIR Fibrosis Stage vs placebo, a stratified Cochran Armitage Trend 
Test controlling for hepatic fibrosis stage (Stage 3 or Stage 4) will be used to analyze the 
proportion of participants with ≥ 1 stage improvement in fibrosis on biopsy at Week 24. After 
the assessment of trend, comparisons of each treatment group with placebo will be performed 
utilizing a stratified (fibrosis stage) Cochran Mantel-Haenszel test (CMH). All of these 
analyses will be performed at 1-sided 0.05 level of significance. In addition, 95% CI for the 
response rates and odds-ratios will be calculated.  
A sensitivity analysis using an extended CMH correlation test will be used to assess the trend 
among the proportions for treatment groups with an adjustment to strata (fibrosis stage).31 
Two-sided 0.10 level of significance will be used. 
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.  
Continuous endpoints may be analyzed by analysis of covariance methods. 
Categorical endpoints will be summarized using counts and percentages and when appropriate 
may be analyzed using categorical analysis methods. 
Subgroup analyses will be performed including hepatic fibrosis stage. 
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9.3.2 Safety 
Safety assessments 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 incidence of AEs, serious AEs, 
 
 
AEs leading to discontinuation, and death, as well as marked abnormalities in clinical 
laboratory tests, vital sign measurements, ECGs, physical examinations 
 
  
9.3.3 Other Analyses 
9.3.3.1 Pharmacokinetics 
Pharmacokinetics, pharmacodynamics, 
 of BMS-986263 will be analyzed 
based on the time points indicated in the Schedule of Activities (Section 1.2). 
 
 
  
PK evaluation is a secondary endpoint. 
BMS-986263, 
 plasma concentrations will be listed and 
summarized descriptively by dose, day and time.  
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11. APPENDICES 
APPENDIX 1 
STUDY GOVERNANCE CONSIDERATIONS 
The term ‘participant’ is intended to refer to a person 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: 
• GCP guidelines as defined by ICH guidance 
• In accordance with the ethical principles underlying European Union 
Directive 2001/20/EC 
• United States (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 
IIRB/EC, and regulatory authorities according to applicable local regulations prior to 
initiation of the study. 
All potential serious breaches must be reported to sponsor or designee immediately. A 
serious breach is a breach of the conditions and principles of GCP in connection with the 
study or the protocol, which is likely to affect, to a significant degree, the safety or physical 
or mental integrity of the participants of the study or the scientific value of the study. 
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/EC for the protocol, consent form, participant recruitment materials 
(eg, advertisements), and any other written information to be provided to 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 participants and any updates.  
The investigator, sponsor or designee should provide the IRB/EC 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/EC (and 
if applicable, also by local health authority) except where necessary to eliminate an 
immediate hazard(s) to study 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 or 
• 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 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 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 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 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 ICF which will include all elements required by ICH, GCP, and applicable regulatory 
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requirements. The sample ICF will adhere to the ethical principles that have their origin in 
the Declaration of Helsinki. 
Investigators must: 
• Provide a copy of the ICF 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 ICF 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 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 ICF 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 participants must be protected, respecting 
the privacy and confidentiality rules applicable to regulatory requirements, the participants’ 
signed ICF and, in the US, the 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.  
Participants unable to give their written consent (eg, those with stroke or severe dementia) 
may only be enrolled in the study with the consent of a legally acceptable representative. The 
participant must also be informed about the nature of the study to the extent compatible with 
his or her understanding, and should this participant become capable, he or she should 
personally sign and date the consent form as soon as possible. The explicit wish of a 
participant who is unable to give his or her written consent, but who is capable of forming an 
opinion and assessing information to refuse participation in, or to be withdrawn from, the 
clinical study at any time should be considered by the investigator. 
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The rights, safety, and well-being of the study 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), AE tracking/reporting, protocol-required assessments, 
and/or drug accountability records). 
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 
The study personnel will account for all study treatments dispensed to and returned from the 
participant. Study site personnel will account for all unused study treatments at the site, and 
unused study medication will be destroyed at the site or returned to the sponsor or designee 
for appropriate destruction, depending on circumstances. Records for study treatments 
(whether supplied by BMS, its vendors, or the site) must substantiate study treatment 
integrity and traceability from receipt, preparation, administration, and through destruction or 
return. Records will be reconciled with existing study medication by a study monitor prior to 
destruction of the product. Certificates of destruction should be signed and will be included 
in the Trial Master File. Records must be made available for review at the request of 
BMS/designee or a health authority. 
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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 (eg, lost, wasted)  
• amount returned to BMS or designee 
• 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. 
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 eCRF 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. Electronic case report 
forms 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, eCRFs 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 Pregnancy Surveillance Form, respectively. If an 
electronic SAE form is not available, a paper SAE form can be used. Spaces may be left 
blank only in those circumstances permitted by study-specific eCRF completion guidelines 
provided by sponsor or designee. 
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The confidentiality of records that could identify 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 eCRFs.  
The completed eCRF and SAE/pregnancy eCRFs, 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. For eCRFs, review and approval/signature is 
completed electronically through the BMS electronic data capture tool. The investigator must 
retain a copy of the eCRFs including records of the changes and corrections. 
Each individual electronically signing electronic eCRFs must meet sponsor or designee 
training requirements and must only access the BMS electronic data capture tool using the 
unique user account provided by sponsor or designee. User accounts are not to be shared or 
reassigned to other individuals. 
Monitoring 
BMS 
 representatives will review data on-site to identify potential 
issues to determine a schedule of on-site visits for 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 BMS 
 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 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 must contact BMS prior 
to destroying any records associated with the study. 
BMS or designee will notify the investigator 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.  
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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 (as applicable; some sites will return unused study treatments depending on 
circumstances).  
If … 
Then 
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) (eg, study 
treatments sourced from the site’s 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 standard operating procedures and a copy provided to BMS upon 
request. 
• Records are maintained that allow for traceability of each container, including the date 
disposed, quantity disposed, and identification of the person disposing the containers. The 
method of disposal (eg, 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 study 
monitor to review throughout the clinical trial period. 
 
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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. 
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 and Publications 
A Signatory Investigator must be selected to sign the clinical study report.  
For this protocol, the Signatory Investigator will be selected as appropriate based on one or 
more of the following criteria: 
• External Principal Investigator designated at protocol development 
• National Coordinating Investigator  
• Study Steering Committee chair or their designee 
• Participant recruitment (eg, among the top quartile of enrollers) 
• Involvement in trial design 
• Regional representation (eg, among top quartile of enrollers from a specified 
region or country) 
• Other criteria (as determined by the study team) 
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. 
 
 
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APPENDIX 2 
ADVERSE EVENTS AND SERIOUS ADVERSE EVENTS: 
DEFINITIONS AND PROCEDURES FOR RECORDING, 
EVALUATING, FOLLOW-UP AND REPORTING 
ADVERSE EVENTS 
Adverse Event Definition: 
An adverse event (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, ECG, radiological scans, vital signs 
measurements), including those that worsen from baseline, considered clinically 
significant in the medical and scientific judgement 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 pre-existing 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 
Serious Adverse Event Definition: 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 
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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 8.4.6.1 for the definition of potential 
DILI).  
 
Pregnancy and potential DILI must follow the same transmission timing and processes to 
BMS as used for SAEs (see Section 8.6.2.1.5 for reporting pregnancies). 
 
 
 
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EVALUATING AES AND SAES 
Assessment of Intensity 
The intensity of AEs is determined by a physician and will use the following levels: 
• Mild: An event that is easily tolerated by the 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. 
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 (IB) 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 to 
PRA Drug Safety within 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: 
 
SAE Fax Number:  
 
Americas:
 
 
Europe/East Asia Pacific: 
  
SAE Telephone Contact - For questions on SAE/pregnancy reporting, please call:  
 
Americas: 
 
 
Europe/East Asia Pacific: 
 
 
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APPENDIX 3 
WOMEN OF CHILDBEARING POTENTIAL DEFINITIONS AND 
METHODS OF CONTRACEPTION 
Definitions 
Woman of Childbearing Potential 
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: 
o Documented hysterectomy 
o Documented bilateral salpingectomy 
o 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 
o 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, females must have a serum FSH level > 40 mIU/mL to confirm 
menopause. 
 
Note: Females 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 periods below are suggested guidelines and the 
investigators should use their judgement 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. 
 
Contraception Guidance for Female Participants of Child Bearing Potential 
One of the contraception methods listed below as “Highly Effective” is required to be used 
during this study and until the end of relevant systemic exposure, defined as 5 days after the 
end of study treatment, plus 30 days. Hormonal contraception and methods listed as not 
highly effective or ineffective below are not permitted.  
 
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Contraceptive Methods Classified as Highly Effective 
User Independent Methods 
• Intrauterine device (IUD)c  
• Bilateral tubal occlusion 
• Vasectomized partner  
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.  
• 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. 
• 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.  
• Acceptable alternate methods of highly effective contraception must be discussed in 
the event that the WOCBP participants chooses to forgo complete abstinence  
 
Contraceptive Methods Not Classified as Highly Effective 
User Dependent Methods 
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 
Unacceptable Methods of Contraception 
• Periodic abstinence (calendar, symptothermal, postovulation methods) 
• Withdrawal (coitus interruptus) 
• Spermicide only 
• Lactation amenorrhea method  
Collection of Pregnancy Information 
Guidance for collection of Pregnancy Information and outcome of pregnancy on the 
Pregnancy Surveillance Form is provided in Section 8.6.2.1.5 and the Appendix for AEs 
and SAEs Definitions and Procedures for Evaluating, Follow-up, and Reporting 
(Appendix 2).  
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150 
 
Approved
1.0
v


Clinical Protocol  
 
IM025006 
BMS-986263 
 
HSP47 siRNA 
21-Feb-2019, Final Approved v7.0 
BMS CONFIDENTIAL 
151 
 
Approved
1.0
v


Clinical Protocol  
 
IM025006 
BMS-986263 
 
HSP47 siRNA 
21-Feb-2019, Final Approved v7.0 
BMS CONFIDENTIAL 
152 
 
Approved
1.0
v


Clinical Protocol  
 
IM025006 
BMS-986263 
 
HSP47 siRNA 
21-Feb-2019, Final Approved v7.0 
BMS CONFIDENTIAL 
153 
 
Approved
1.0
v


Clinical Protocol  
 
IM025006 
BMS-986263 
 
HSP47 siRNA 
21-Feb-2019, Final Approved v7.0 
BMS CONFIDENTIAL 
154 
 
Approved
1.0
v


Clinical Protocol  
 
IM025006 
BMS-986263 
 
HSP47 siRNA 
21-Feb-2019, Final Approved v7.0 
BMS CONFIDENTIAL 
155 
 
 
 
Approved
1.0
v


Clinical Protocol  
 
IM025006 
BMS-986263 
 
HSP47 siRNA 
21-Feb-2019, Final Approved v7.0 
BMS CONFIDENTIAL 
156 
  
Approved
1.0
v


Clinical Protocol  
 
IM025006 
BMS-986263 
 
HSP47 siRNA 
21-Feb-2019, Final Approved v7.0 
BMS CONFIDENTIAL 
157 
APPENDIX 7 
CHILD-PUGH SCORING  
Parameter 
Classification 
Score 
Bilirubin (Total) 
< 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 
Albumin 
> 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 Ratio 
< 1.7 
+1 
1.7-2.2 
+2 
> 2.2 
+3 
Ascites 
Absent 
+1 
Slight 
+2 
Moderate 
+3 
Encephalopathy 
No encephalopathy 
+1 
Grade 1-2 
+2 
Grade 3-4 
+3 
 
 
 
Approved
1.0
v


Clinical Protocol  
 
IM025006 
BMS-986263 
 
HSP47 siRNA 
21-Feb-2019, Final Approved v7.0 
BMS CONFIDENTIAL 
158 
APPENDIX 8 
FORMULAE FOR MEASUREMENTS  
• MELD Score = (9.57*ln[creatinine]) + (3.78 * ln[Bilirubin]) + 
(11.20* ln[INR]) + 6.43 
 
Method of BMI Calculation:  
• Use actual height and weight collected on the same day. Whenever possible, body 
weight should be measured using the same scale throughout the study. 
• To calculate BMI:  
o Convert weight pounds to kg (kg = pounds / 2.2) 
o Convert height inches to centimeters (cm = inches × 2.54) 
o BMI = (weight in kg) / (height in cm/100)2 
o Round to 1 decimal place (if 0.05 or greater, round up) 
Approved
1.0
v

SAP_005.pdf: 
 
 
 
Sponsor: Bristol-Myers Squibb  
Statistical Analysis Plan 
Protocol no: IM025006  
Version Date: 19-Feb-2019  
 
 
 
Page 1 of 30 
Strictly Confidential.  © 2004-2015, 
.  All rights reserved. 
 
Statistical Analysis Plan 
 
Sponsor: 
Bristol-Myers Squibb 
Protocol No./ 
Version 
IM025006/Amendment 6 v7.0  
Title: 
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 Viral Remission 
 
SAP Version 
No./Date: 
V1.1/19-Feb-2019 
 
 


 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
  
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 



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Approvals .................................................................................................................................................................................... 2 
Table of Contents ..................................................................................................................................................................... 3 
 Study Objectives ............................................................................................................................................................... 5 
2.1 Primary Study Objectives......................................................................................................................................... 5 
2.2 Secondary Study Objectives .................................................................................................................................... 5 
 
 Study Design ....................................................................................................................................................................... 6 
3.1 Overall Study Design .................................................................................................................................................. 6 
3.2 Sample Size Considerations .................................................................................................................................... 7 
3.3 Randomization ............................................................................................................................................................. 7 
 Study Variables and Covariates .................................................................................................................................. 7 
4.1 Primary Efficacy Variable ........................................................................................................................................ 7 
4.2 Secondary Efficacy Variables .................................................................................................................................. 8 
4.2.1 Collagen Proportionate Area .......................................................................................................................... 8 
4.2.2 Ishak Liver Fibrosis Score ............................................................................................................................... 8 
4.2.3 Liver Stiffness by MRE ...................................................................................................................................... 8 
4.5 Safety Variables .......................................................................................................................................................... 10 
4.5.1 Adverse Events .................................................................................................................................................. 11 
4.5.2 Laboratory Data................................................................................................................................................. 11 
4.5.3 Electrocardiograms .......................................................................................................................................... 12 
4.5.4 Physical Examinations .................................................................................................................................... 12 
4.5.5 Vital Signs ............................................................................................................................................................. 13 
4.5.6 Bone Density Testing....................................................................................................................................... 13 
4.6 Other Variables........................................................................................................................................................... 13 
4.7 Pharmacokinetics 
 Variables ............................................................................... 13 
4.9 Predetermined Covariates and Prognostic Factors .................................................................................... 14 
 Definitions ......................................................................................................................................................................... 14 
5.1 Screen Failures, Retesting, and Rescreening ................................................................................................. 14 
5.2 Baseline ......................................................................................................................................................................... 14 
5.3 Actual Treatment ....................................................................................................................................................... 15 
5.4 Change and Percentage from Baseline ............................................................................................................. 15 
5.5 Adverse Event, Serious Adverse Event ............................................................................................................. 15 
5.6 Treatment-Emergent Adverse Event (TEAE) ................................................................................................ 16 


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5.8 Study Treatment ........................................................................................................................................................ 16 
5.9 Treatment Duration (weeks)................................................................................................................................ 16 
5.10 Study Day ................................................................................................................................................................... 16 
5.11 Prior and Concomitant Medications ............................................................................................................... 16 
5.14 Other Calculations .................................................................................................................................................. 18 
 Analysis Sets ..................................................................................................................................................................... 18 
 
 Data Review ...................................................................................................................................................................... 19 
8.1 Data Handling and Transfer .................................................................................................................................. 19 
8.2 Data Screening ............................................................................................................................................................ 20 
 Statistical Methods ........................................................................................................................................................ 20 
9.1 Participant Disposition ........................................................................................................................................... 20 
9.2 Demographic and Baseline Characteristics .................................................................................................... 21 
9.3 Important Protocol Deviations ............................................................................................................................ 21 
9.4 Prior and Concomitant Medications .................................................................................................................. 21 
9.5 Efficacy Analyses ....................................................................................................................................................... 21 
9.5.1 Primary Efficacy Analysis .............................................................................................................................. 21 
9.5.2 Secondary Efficacy Analyses ........................................................................................................................ 22 
9.6 Safety Analyses ........................................................................................................................................................... 24 
9.6.1 Extent of Study Treatment Exposure ....................................................................................................... 24 
9.6.2 Adverse Events .................................................................................................................................................. 24 
9.6.4 Deaths and Serious Adverse Events .......................................................................................................... 25 
9.6.5 Laboratory Data................................................................................................................................................. 25 
9.6.6 Vital Signs, ECGs, Physical Examination, and Weight ........................................................................ 26 
9.6.7 Pharmacokinetics, 
 ...................................................... 26 
9.7 Methods for Handling Dropouts and Missing Data ..................................................................................... 26 
9.8 Multiplicity ................................................................................................................................................................... 26 
9.9 Pooling of Sites and Regional Analyses ............................................................................................................ 26 
 Validation ........................................................................................................................................................................ 27 
Appendix 1 Glossary of Abbreviations ......................................................................................................................... 28 
Appendix 2 Tables, Figures, Listings ............................................................................................................................. 30 
Appendix 3 Statistical Appendices ................................................................................................................................. 30 
 


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Sponsor: Bristol-Myers Squibb  
Statistical Analysis Plan 
Protocol no: IM025006  
Version Date: 19-Feb-2019  
 
 
 
Page 8 of 30 
Strictly Confidential.  © 2004-2015, 
.  All rights reserved. 
 
The METAVIR system is used to assess the extent of inflammation and fibrosis by histopathological 
evaluation in a liver biopsy of patients with HCV. It assesses liver biopsies for activity grade (A0-A3: A0 = no 
activity, A1 = mild activity, A2 = moderate activity, A3 = severe activity) and fibrosis stage (Stage 1 – 4: 
1 = portal fibrosis without septa; 2 = portal fibrosis with few septa; 3 = numerous septa without cirrhosis; or 
4 = cirrhosis). 
The METAVIR fibrosis score will also be used as a secondary efficacy variable for some endpoints.  
4.2 Secondary Efficacy Variables 
4.2.1 Collagen Proportionate Area 
There can be considerable intra- and inter-individual variation in the assessment of liver biopsy to determine 
fibrosis stage. Assessment of CPA is a method by which the amount (percentage) of collagen in stained 
tissue sections is analyzed using morphometric image analysis. This technique allows for a quantitative 
assessment of fibrosis. This morphometric assessment will be performed by a blinded central pathologist. 
The percentage of collagen proportionate area will be provided.  
4.2.2 Ishak Liver Fibrosis Score 
Ishak liver fibrosis scores will be done by the central pathologist using the liver biopsies. The Ishak system 
(0 through 6 scale) was developed to grade portal-based liver fibrosis associated with viral hepatitis: 
• 
0: No fibrosis 
• 
1: Fibrous expansion of some portal areas, with or without short fibrous septa 
• 
2: Fibrous expansion of most portal areas, with or without short fibrous septa 
• 
3: Fibrous expansion of most portal areas with occasional portal to portal bridging 
• 
4: Fibrous expansion of portal areas with marked bridging (portal to portal as well as portal to 
central) 
• 
5: Marked bridging (portal–portal and/or portal–central) with occasional nodules (incomplete 
cirrhosis) 
• 
6: Cirrhosis, probable or definite 
  
4.2.3 Liver Stiffness by MRE 
MRE is a noninvasive medical imaging technique approved by FDA in 2009. It quantitatively measures in 
kilopascal (kPA) the stiffness of soft tissues by introducing shear waves and imaging their propagation 
using magnetic resonance imaging (MRI). In this study, MRE will be used to quantitate liver stiffness as a 
surrogate biomarker of liver fibrosis. The central imaging facility will perform all MRE imaging analyses. 


 
 
 
Sponsor: Bristol-Myers Squibb  
Statistical Analysis Plan 
Protocol no: IM025006  
Version Date: 19-Feb-2019  
 
 
 
Page 9 of 30 
Strictly Confidential.  © 2004-2015, 
.  All rights reserved. 
 


 
 
 
Sponsor: Bristol-Myers Squibb  
Statistical Analysis Plan 
Protocol no: IM025006  
Version Date: 19-Feb-2019  
 
 
 
Page 10 of 30 
Strictly Confidential.  © 2004-2015, 
.  All rights reserved. 
 
4.5  Safety Variables  
The safety of BMS-986263 will be assessed by evaluation of the incidence of all adverse events (AEs) and 
serious adverse events (SAEs), 
 electrocardiogram (ECG) 
monitoring, physical examinations, vital signs, 
 
. 


 
 
 
Sponsor: Bristol-Myers Squibb  
Statistical Analysis Plan 
Protocol no: IM025006  
Version Date: 19-Feb-2019  
 
 
 
Page 11 of 30 
Strictly Confidential.  © 2004-2015, 
.  All rights reserved. 
 
4.5.1 Adverse Events 
The definition of adverse events and serious adverse events as well as their time periods for collection can 
be found in the protocol Section 8.6.2 and Protocol Appendix 2. The event (term), along with its start and 
stop dates, maximum intensity (mild, moderate, or severe), seriousness (yes/no), relationship to the IP 
(yes/no), action taken with regard to the IP, and outcome will be recorded in the electronic case report form 
(eCRF).  
Additional details for infusion related reactions will be collected including clinical signs and symptoms as 
well as the location, characteristics and severity of those signs or symptoms, and start and end time of the 
reaction.  
4.5.2 Laboratory Data 
Hematology, serum chemistry, urinalysis, and other assessments are listed below. A central laboratory will 
perform the analyses and will provide reference ranges for these tests.  
Hematology 
• 
CBC 
• 
PT 
• 
PTT 
• 
INR  
• WBC (absolute)  
• Hemoglobin 
• Hematocrit 
• MCV 
• 
MCH concentration 
• 
Red cell distribution width  
• 
Platelet count 
Blood Chemistry 
• 
AST 
• 
ALT 
• 
Total bilirubin 
• 
Direct bilirubin 
• 
ALP 
• 
LDH 
• 
GGT  
• 
Creatinine  
• 
Creatinine clearance 
• 
Creatine kinase 
• 
BUN 
• 
Uric acid 
• 
Glucose 
• 
PTH  
• 
Total protein  
• 
Albumin sodium 
• 
Potassium 
• 
Chloride 
• 
Carbon dioxide 
• 
Calcium 
• 
Phosphorus 
• 
Glomerular filtration rate 
Urinalysis 
• 
pH 
• 
Specific gravity 
• 
Protein 
• 
Glucose 
• 
Ketones  
• 
Leukocyte esterase 
• 
Nitrite 
• 
Creatinine 
• 
Microscopic examination (only to follow-up 
abnormal findings) 
HbA1C 
Serology/viral load 
• 
HCV viral load (RNA) 
• 
HBsAg 
• 
HbcAb and HBV viral DNA if HbcAb-positive. 


 
 
 
Sponsor: Bristol-Myers Squibb  
Statistical Analysis Plan 
Protocol no: IM025006  
Version Date: 19-Feb-2019  
 
 
 
Page 12 of 30 
Strictly Confidential.  © 2004-2015, 
.  All rights reserved. 
 
Other Analyses 
• 
FSH 
• 
AFP  
• 
Illegal drugs of abuse (urine or serum; 
amphetamine, barbiturate, benzodiazepines, 
marijuana, cocaine, opiate, or PCP) 
• 
pregnancy test (WOCBP only). 
AFP = alpha-fetoprotein; ALP = alkaline phosphatase; 
 ALT = alanine aminotransferase, 
AST = aspartate aminotransferase; 
 BUN = blood 
urea nitrogen; 
 
CBC = complete blood count; 
 CVD = cardiovascular disease; 
DNA = deoxyribonucleic acid; 
 GGT = gamma-glutamyl transferase; 
 FSH = follicle stimulating hormone; HbA1c = hemoglobin A1c; 
HBsAg = hepatitis B surface antigen; HbcAb = hepatitis B core antibody; HBsAb = hepatitis B surface antibody; 
 
 INR = international normalized ratio; LDH = lactate dehydrogenase; 
 MCH = mean 
corpuscular hemoglobin; MCV = mean corpuscular volume; MOA = mechanism of action; 
 
 PCP = phencyclidine; PT = prothrombin time; PTH = parathyroid hormone; 
PTT = partial thromboplastin time; 
 WBC = white blood cell; WOCBP = women of childbearing potential 
  
 
4.5.3 Electrocardiograms 
Variables collected from a central vendor for electrocardiograms include mean heart rate, RR interval, PR 
interval, QRS duration, QT interval, QTcB interval, QTcF interval, interpretation, atrioventricular conduction, 
axis and voltage, chamber hypertrophy or enlargement, intraventricular-intra atrial conduction, myocardial 
infarction (if applicable), pacemaker status, sinus node rhythms and arrhythmias (if applicable), 
supraventricular arrhythmias and tachyarrhythmias, ST segment, T and U waves, technical quality, and 
ventricular arrhythmias and tachyarrhythmias. 
4.5.4 Physical Examinations 
A full examination will include general appearance, skin, head, eyes, ears, nose, throat, neck, thyroid, 
chest/lungs, heart, abdomen, lymph nodes, extremities, height, and body weight. Abbreviated physical 
examinations will be performed at the other time points, which will include an abdominal exam, 
assessments for ascites and hepatic encephalopathy, as well as 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. 
Physical exam variables include exam date and time
 body system, 
result, whether abnormal and if abnormal the result, and whether this is clinically significant.  


 
 
 
Sponsor: Bristol-Myers Squibb  
Statistical Analysis Plan 
Protocol no: IM025006  
Version Date: 19-Feb-2019  
 
 
 
Page 13 of 30 
Strictly Confidential.  © 2004-2015, 
.  All rights reserved. 
 
4.5.5 Vital Signs 
Vital signs variables include height, weight, body mass index (BMI), temperature, systolic blood pressure, 
diastolic blood pressure, heart rate, respiratory rate, and clinical significance.  
4.5.6 Bone Density Testing 
DXA will be performed to assess bone density. The clinical sites will be trained in imaging procedures prior 
to scanning the first study participant. The baseline Z-score to determine participant’s eligibility will be based 
on local radiologist read at the clinical site. 
 
  Variables include the date and time of assessment, and total 
BMD and T- and Z-scores for hip, lumbar spine, and femoral neck. In addition, the number of lumbar spine 
segments and the segments included in the assessment (L1, L2, L3, L4) will be collected.  
4.6 Other Variables 
Other variables that will be collected include participant demographics (birth date, age, sex, ethnicity, race), 
general medical history, prior and concomitant medications, hospitalizations, and diagnostic and/or medical 
procedures that occur.  
In addition, variables will be collected for informed consent and re-consent if applicable, eligibility including 
pregnancy testing and childbearing potential, randomization or reason for non-randomization, ultrasound 
for detection of hepatocellular carcinoma (HCC) at screening, and previous enrollment and dates enrolled 
in a previous BMS study. Details of the regimen used to treat and cure Hepatitis C (date of sustained 
virologic response, treatment, start and end date, dose and unit per administration, frequency, and route) 
as well as disease diagnosis and specific disease history (date of diagnosis, and history of impaired fasting 
glucose and diabetes) will also be recorded. 
Treatment exposure variables will include start and end dates and times, total volume prepared (mL), actual 
volume and whether different from total volume prepared and reason (Adverse Event or Other), infusion 
rate (mL/hour), whether administration was interrupted and reason (Adverse Event or Other), and whether 
administration was resumed. Pre-treatment antihistamine and corticosteroid variables will include the 
medication name, date and start and end times, dose and unit, and route.  
End of treatment and end of study dates and reasons will be collected. When applicable, date of death, 
primary cause of death, and whether autopsy was performed will be recorded.  
4.7 Pharmacokinetics 
 Variables  
Blood for PK samples will be drawn at several time points according to the sampling schedules shown in 
the protocol Section 8.6.3. Samples from participants randomized to placebo will not be analyzed.  Plasma 
concentrations of BMS-986-263,  
 
 will be measured. 


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Sponsor: Bristol-Myers Squibb  
Statistical Analysis Plan 
Protocol no: IM025006  
Version Date: 19-Feb-2019  
 
 
 
Page 15 of 30 
Strictly Confidential.  © 2004-2015, 
.  All rights reserved. 
 
Many pre-infusion measures are collected per-protocol on study day 1 (randomization). For variables 
specified in the schedule of events to be collected prior to infusion the analysis will assume they were 
collected per-protocol and as such they will qualify as baseline measures. 
5.3 Actual Treatment 
All analyses conducted on the Safety Analysis Set will be performed using the Actual Treatment. Actual 
treatment is defined as the highest dose and frequency of active study treatment (BMS-986263) that a 
participant receives at any time during their participation in the study. Participants who only receive Placebo 
will be analyzed as such. 
5.4 Change and Percentage from Baseline 
Change from baseline (CFB) will be calculated as (post-baseline value – baseline value). CFB will be 
calculated for participants with both a baseline and post-baseline value as applicable.  Percent CFB will be 
calculated as (CFB/baseline)*100, where applicable. If a baseline value has not been recorded for a 
parameter, then CFB will not be calculated for that parameter. Participants with missing CFB values will be 
excluded from analyses in which CFB is the endpoint. In cases where baseline is zero and the post-baseline 
value is also zero percent CFB will be considered zero percent. 
5.5 Adverse Event, Serious Adverse Event 
The definitions of AE and SAE can be found in the Protocol Appendix 2.  If an adverse event causality or 
severity is missing, the causality or severity will not be imputed.  
 
 
The following imputation rules will be used for AE:  
Imputation Rules for Partial Dates (D = day, M = month, Y = year) 
Parameter 
Missing 
Additional Conditions 
Imputation 
Start date for 
AEs 
D 
M and Y same as M and Y of first 
dose of study treatment 
Date of first dose of study 
treatment 
M and/or Y not same as date of first 
dose of study treatment drug 
First day of month 
D and M 
Y same as Y of first dose of study 
treatment 
Date of first dose of study 
treatment 
Y prior to Y of first dose of study 
treatment but same as Y of 
screening date 
Date of screening date 
D, M, Y 
None – date completely missing 
Date of first dose of study 
treatment 
Stop date for 
AEs 
D 
M and Y same as M and Y of the 
Follow-up visit 
Date of the Follow-up visit 
M and/or Y not same as date of the 
Follow-up visit 
Use last day of month 
D and M 
Y same as Y of the Follow-up visit 
Date of the Follow-up visit 
Y not same as Y of the Follow-up 
visit 
Use Dec 31 
D, M, Y 
None – date completely missing 
No imputation, but assume 
ongoing 
Note: In all cases, if an estimated start date is after a complete stop date, use the first day of the stop date month. Similarly, if the 
estimated stop date is before a complete or imputed start date, use the last day of the start date month. 
 


 
 
 
Sponsor: Bristol-Myers Squibb  
Statistical Analysis Plan 
Protocol no: IM025006  
Version Date: 19-Feb-2019  
 
 
 
Page 16 of 30 
Strictly Confidential.  © 2004-2015, 
.  All rights reserved. 
 
For example for AE start date imputation, if a participant is dosed on 15MAY2018 and has an AE start date 
reported as MAY2018 the imputation would be 15MAY2018, but if the AE start date was reported as 
JUN2018 the imputation would be 01JUN2018. 
For example for AE stop date imputation, if a participant follow-up visit or cutoff date is 15MAY2018 and 
has an AE stop date reported as MAY2018 the imputation would be 15MAY2018, but if the AE stop date 
was reported as MAR2018 the imputation would be 31MAR2018. 
 
5.6 Treatment-Emergent Adverse Event (TEAE) 
Treatment-emergent adverse events (TEAEs) are those which first occur or increase in severity or 
relationship to study treatment after the first dose of study treatment and not more than 30 days after the 
last dose of study treatment. All Adverse Events (AEs) which change in severity or relationship to study 
treatment are assigned a new start date and captured as a new record. 
5.8 Study Treatment  
For the purposes of the calculations included in this SAP, study treatment will include only doses of BMS-
986263 or placebo.  
5.9 Treatment Duration (weeks) 
Treatment duration (weeks) will be calculated as: 
 
Part 1: (date of last dose of study treatment* during Part 1 – date of first dose of study treatment during 
Part 1 + 7)/7. The additional 7 days are added to account for the last week of treatment.  
 
*for the purposes of these calculations, study treatment refers to BMS-986263 or placebo.  
 
5.10 Study Day 
Study day is defined relative to the date of the first dose of study treatment. For assessments that occur on 
or after this visit date, study day is calculated as (assessment date – first dose date + 1). For assessments 
that occur prior to first dose date, study day will be calculated as (assessment date – first dose date); there 
is no Study Day 0. Study Day 1 is the day of first study treatment received. 
5.11 Prior and Concomitant Medications 
All medications taken from within 4 weeks before the first dose of study treatment until last visit must be 
recorded on the eCRF. Prior medications are defined as medications taken within 4 weeks of the first dose 
of study treatment and discontinued before the first dose of study treatment. Concomitant medications are 
defined as any medication taken after the first dose of study treatment until last visit  
 
Imputation Rules for Partial Dates (D = day, M = month, Y = year) 
Parameter 
Missing 
Additional Conditions 
Imputation 
Start date  
D only 
M and Y same as M and Y of first dose 
of study treatment 
Date of first dose of study 
treatment 


 
 
 
Sponsor: Bristol-Myers Squibb  
Statistical Analysis Plan 
Protocol no: IM025006  
Version Date: 19-Feb-2019  
 
 
 
Page 17 of 30 
Strictly Confidential.  © 2004-2015, 
.  All rights reserved. 
 
Imputation Rules for Partial Dates (D = day, M = month, Y = year) 
Parameter 
Missing 
Additional Conditions 
Imputation 
M and/or Y not same as date of first 
dose of study treatment 
First day of month 
M and D 
Y same as Y of first dose of study 
treatment 
Date of first dose of study 
treatment 
Y not same as Y of first dose of study 
treatment 
Use Jan 01 of Y 
M, D, and Y 
None – date completely missing 
Day prior to date of first dose of 
study treatment 
Stop date  
D only 
M and Y same as M and Y of the 
Follow-up visit 
Date of the Follow-up visit 
M and/or Y not same as date of the 
Follow-up visit 
Last day of month 
M and D 
Y same as Y of the Follow-up visit 
Date of the Follow-up visit 
Y not same as Y of the Follow-up visit 
Use Dec 31 of Y 
M, D, and Y 
None – date completely missing and 
NOT ongoing 
Date of the Follow-up visit 
Note:  In all cases, if an estimated start date is after a complete stop date, use the first day of the stop date month. Similarly, if the 
estimated stop date is before a complete or imputed start date, use the last day of the start day month. 
 
For example for a concomitant medication start date imputation, if a participant is dosed on 15MAY2018 
and has a concomitant medication start date reported as MAY2018 the imputation would be 15MAY2018, 
but if the concomitant medication start date was reported as JUN2018 the imputation would be 01JUN2018. 
For example for a concomitant medication stop date imputation, if a participant follow-up visit or cutoff 
date is 15MAY2018 and has a concomitant medication stop date reported as MAY2018 the imputation 
would be 15MAY2018, but if the concomitant medication stop date was reported as MAR2018 the 
imputation would be 31MAR2018. 
 
Note, if a medication is missing an end date and is recorded as ongoing, it will be classified as 
concomitant. Partial dates should be imputed before the classification of prior or concomitant.  


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Sponsor: Bristol-Myers Squibb 
Statistical Analysis Plan 
Protocol no: IM025006  
Version Date: 19-Feb-2019 
 
Page 21 of 30 
Strictly Confidential.  © 2004-2015, 
.  All rights reserved. 
The number of participants enrolled/randomized will be presented by study part, total within part and by 
treatment group, along with the number and percentage of participants who completed, discontinued, and 
are ongoing at the time of the data cut in total within part and by treatment group. The number and 
percentage of participants who completed the treatment period, withdrew from study treatment prematurely 
and a breakdown of the corresponding reasons for withdrawal from study treatment will be presented. The 
number and percentage of participants who completed the study, were ongoing at the time of the data 
snapshot (for the interim analysis report only), withdrew from the study prematurely, and a breakdown of 
the corresponding reasons for withdrawal will be presented. The summary will be presented by study part, 
treatment group, and total within part for the Randomized (RAS) Analysis Set. Also, by-participant listings 
will be generated. 
9.2 Demographic and Baseline Characteristics 
The following baseline demographic characteristics will be summarized by study part, treatment group and 
in total within part based on the RAS: sex, race, ethnicity, age, age group (<65 years, 65-<75 years, and 
>=75 years, as well as Adults [18-64 years], From 65-84 years, and 85 years and over), weight, height, 
body mass index (BMI).  
The following baseline disease characteristics will be summarized by part, treatment group and in total 
within part based on the RAS: METAVIR liver fibrosis stage used for randomization as well as via central 
reader, history of impaired fasting glucose or diabetes, months from Hepatitis C sustained virologic 
response to randomization, 
 baseline AST, ALT 
and INR, baseline MRE,FibroScan, and CPA values, and baseline Pro-C3.  
General medical history will be summarized for the Safety Analysis Set by part, treatment group, and in 
total within part. The number and percentage of participants with each event will be presented by SOC and 
PT. Note that counting will be by participant not event and participants are only counted once within each 
SOC and PT. 
Prior medications summaries will be presented for the Safety Analysis Set by part, treatment group, and in 
total within part. The number and percentage of participants with each prior medication will be presented 
by ATC and PT. Note that counting will be by participant and participants are only counted once within each 
ATC and PT. 
9.3 Important Protocol Deviations 
Important protocol deviations will be summarized by number and percentage of participants experiencing 
each deviation category. All protocol deviations will be listed.  
9.4 Prior and Concomitant Medications 
Based on the Safety Analysis Set, prior and concomitant medications will be summarized by part, treatment 
group, and in total within part. The number and percentage of participants using each medication will be 
displayed together with the number and percentage of participants using at least one medication for each 
ATC and PT. A by-participant listing will also be presented.  
9.5 Efficacy Analyses 
All efficacy analyses, both primary and secondary, will be performed on the Modified-Intent-to-Treat (mITT) 
analysis set. 
9.5.1 Primary Efficacy Analysis 
The primary efficacy endpoint is the proportion of participants who achieve ≥ 1 stage improvement in fibrosis 
(METAVIR score) on biopsy after 12 weeks of treatment in Part 1.  A “response” indicates the participant 


 
 
 
Sponsor: Bristol-Myers Squibb  
Statistical Analysis Plan 
Protocol no: IM025006  
Version Date: 19-Feb-2019  
 
 
 
Page 22 of 30 
Strictly Confidential.  © 2004-2015, 
.  All rights reserved. 
 
did achieve a ≥ 1 stage improvement in fibrosis. Summary tables will be provided for overall response and 
response by baseline METAVIR fibrosis stage via central reader (Stage less than 4, Stage 4), and shift 
tables will also be provided. Participants without an efficacy measurement at Week 12 will be considered 
as “non-responders”.  Spaghetti plots will also be provided for each treatment group. 
9.5.1.1 Part 1 
To evaluate the effect of BMS-986263 (90 mg QW) on METAVIR Fibrosis Stage at Week 12, a 95% exact 
CI of response rate for treatment versus placebo will be used to estimate the difference between the 
proportion of participants with ≥ 1 stage improvement in fibrosis on liver biopsy. Additionally, the odds ratio 
of each treatment will be used to estimate improvement of treatment as compared to placebo for the 
proportion of participants with ≥ 1 stage improvement in fibrosis on biopsy at Week 12.  
9.5.2 Secondary Efficacy Analyses 
Secondary efficacy endpoints are as follows:  
• 
Change in CPA, as compared to placebo after 12 weeks of treatment in Part 1  
• 
Proportion of participants with ≥ 1 stage improvement in liver fibrosis (Ishak score), as compared 
to placebo after 12 weeks of treatment in Part 1  
• 
Proportion of participants with ≥ 2 stage improvement in liver fibrosis (METAVIR score), as 
compared to placebo after 12 weeks of treatment in Part 1  
• 
Proportion of participants with ≥ 2 stage improvement in liver fibrosis (Ishak score), as compared 
to placebo after 12 weeks of treatment in Part 1  
• 
Proportion of participants with ≥ 15% decrease from baseline in liver stiffness as measured by MRE 
at Day 85 in Part 1  
• 
Change from baseline in liver stiffness as measured by MRE Day 85 in Part 1  
 
 
9.5.2.1 Collagen Proportionate Area  
The change from baseline in collagen proportionate area will be analyzed using an Analysis of Covariance 
(ANCOVA) at Week 12 for Part 1.  The model will include a fixed factor for treatment group and a covariate 
for baseline CPA. Contrasts will be used to compare the adjusted mean change from baseline between 
each treatment group and placebo and CIs will be presented for each comparison. In addition to actual, 
change from baseline, and percent change from baseline summaries by time point, box plots by treatment 
group and spaghetti plots by participant by treatment group will be provided.  
9.5.2.2 METAVIR and Ishak Fibrosis Scores 
An analysis similar to that used for the primary efficacy variable will be conducted for secondary efficacy 
analyses of the proportion of patients with ≥1 or ≥2 stage improvement in liver fibrosis according to Ishak 
and METAVIR scores. 
9.5.2.3 MRE Liver Stiffness  
An analysis similar to that used for the primary efficacy variable will be conducted for the proportion of 
participants with >15% decrease in MRE liver stiffness. An analysis similar to that used for the secondary 
endpoint of CPA will be conducted for continuous MRE liver stiffness.  


 
 
 
Sponsor: Bristol-Myers Squibb  
Statistical Analysis Plan 
Protocol no: IM025006  
Version Date: 19-Feb-2019  
 
 
Page 23 of 30 
Strictly Confidential.  © 2004-2015, 
.  All rights reserved. 
 


 
 
 
Sponsor: Bristol-Myers Squibb  
Statistical Analysis Plan 
Protocol no: IM025006  
Version Date: 19-Feb-2019  
 
 
 
Page 24 of 30 
Strictly Confidential.  © 2004-2015, 
.  All rights reserved. 
 
9.6 Safety Analyses 
9.6.1 Extent of Study Treatment Exposure 
Treatment duration will be summarized based on the Safety Analysis Set by treatment group.  The following 
summaries will be included: 
• 
Number of participants receiving at least 1 dose 
•       
Number of participants receiving at least 1 dose of pre-treatment antihistamine 
•       
Number of participants receiving at least 1 dose of pre-treatment corticosteroid 
• 
Summary of number of doses administered 
• 
Summary of total dose administered (mg) 
• 
Summary of participants with an interrupted infusion 
• 
Summary of weeks of exposure 
A by-participant listing will be presented. Data on pre-treatment antihistamine and/or steroids will be listed.  
9.6.2 Adverse Events 
All TEAE summaries will be generated based on the Safety Analysis Set by treatment group and total. A 
summary of TEAEs will be generated and will include the number of events reported and the number and 
percentage of participants reporting: 
• 
at least one AE 
• 
any severe AE 
• 
any treatment-related AE 
• 
any severe treatment-related AE 
• 
any AE with outcome of death 
• 
any SAE  
• 
any treatment-related SAE 
• 
any AE leading to the discontinuation of study treatment 
• 
any treatment-related AE leading to discontinuation of study treatment 
• 
any AE leading to discontinuation from the study 
• 
any treatment-related AE leading to discontinuation from the study. 
 
A summary of AEs will be presented by MedDRA SOC and PT. A breakdown of the number and percentage 
of participants reporting each TEAE, categorized by SOC, PT, and maximum severity, will be presented. 
Note that counting will be by participant not event and participants are only counted once within each SOC 
or PT. An additional summary of treatment-related TEAEs by SOC, PT, and maximum severity will be 
presented. 
Summaries of severe TEAE, treatment-related TEAE, severe treatment-related TEAE, TEAE with outcome 
of death, serious TEAE, treatment-related serious TEAE, TEAE leading to study treatment discontinuation, 
treatment-related TEAE leading to study treatment discontinuation, TEAE leading to study discontinuation, 
and treatment-related TEAE leading to study discontinuation will also be provided, grouped by SOC and 
PT.  


 
 
 
Sponsor: Bristol-Myers Squibb  
Statistical Analysis Plan 
Protocol no: IM025006  
Version Date: 19-Feb-2019  
 
 
 
Page 25 of 30 
Strictly Confidential.  © 2004-2015, 
.  All rights reserved. 
 
The first row on every treatment-emergent AEs summary will be the number and percentage of participants 
reporting at least one TEAE. Subsequent rows will be presented in descending order of participant counts 
in total with the most common SOC first, followed within each SOC by the PTs in descending participant 
count order.  
A by-participant listing of all AEs will be provided.  Details such as clinical signs and symptoms will be listed 
for infusion related reactions. 
9.6.4 Deaths and Serious Adverse Events 
A summary of SAEs, categorized by SOC and PT and coded according to the MedDRA dictionary, will be 
presented by treatment group and total in the Safety Analysis Set. Note that counting will be by participant 
not event and participants are only counted once within each SOC or PT. All SAEs will be listed by 
participant. An additional summary of treatment-related SAEs will be presented by SOC and PT. 
AEs with an outcome of death will be summarized by SOC and PT. All AEs with an outcome of death will 
be listed. 
9.6.5 Laboratory Data 
Based on the Safety Analysis Set, continuous laboratory results will be summarized using International 
System (SI) of units by visit, treatment group, and pooled BMS-986263. Categorical results such as those 
for urinalysis will be summarized by number and percentage of participants in each category.  These 
summaries will be based on central laboratory results.  Summaries will present both actual and change-
from-baseline results for continuous values. Not all clinical lab values will be summarized. Refer to the TFL 
shells for the specific parameters that will be summarized. Baseline to maximum postbaseline shift tables 
during the treatment period will be presented for hematology, blood chemistry, metabolic panel, and Hba1c 
and these summaries will not be pooled by treatment group.  
Elevated postbaseline values will be descriptively summarized by counts and percentages of participants 
ever experiencing specified elevated values per the TFL shells at any postbaseline time point for ALT, AST, 
Total Bilirubin, alpha-fetoprotein, 
.  
Laboratory values below the lower limit or above the upper limit of quantification will be set equal to the 
lower or upper limit, respectively, for summary tables. These actual values will be displayed in the listings. 
In rare circumstances where the number of evaluable lumbar spine segments changes over time for bone 
mineral density results, only participants with the same number and same segments as their baseline 
assessment will be included in change from baseline summaries of lumbar spine values. In addition, only 
participants with at least 2 evaluable lumbar spine segments at baseline will be included in the summary of 
the baseline time point. 
  
Where specified in the TFL shells, figures will be provided for mean change from baseline by timepoint by 
treatment group, with error bars for standard deviation of the mean change from baseline.  
All laboratory data specified in the summary tables will be present in listings. 


 
 
 
Sponsor: Bristol-Myers Squibb  
Statistical Analysis Plan 
Protocol no: IM025006  
Version Date: 19-Feb-2019  
 
 
 
Page 26 of 30 
Strictly Confidential.  © 2004-2015, 
.  All rights reserved. 
 
9.6.6 Vital Signs, ECGs, Physical Examination, and Weight 
Based on the Safety Analysis Set, vital sign and 12-lead ECG parameters will be summarized by Part, visit, 
treatment group, and pooled BMS-986263. All vital signs and ECG results will be listed. 
ECG results will be summarized for continuous variables and will be presented for the absolute result and 
CFB. QTc values will be presented with the implementation of corrections (i.e., Bazett’s and Fridericia’s) 
as defined in ICH Guidelines E14 by the following categories:   
Absolute QTc interval prolongation: 
o 
QTc interval > 450ms 
o 
QTc interval > 480ms  
o 
QTc interval > 500ms 
 
Change from baseline in QTc interval: 
o 
QTc interval increases from baseline >30ms  
o 
QTc interval increases from baseline >60ms. 
Total ECG impression as assessed by central reader and findings will be listed. 
Physical examination results and other safety data will be listed. 
9.6.7 Pharmacokinetics, 
 
BMS-986263, 
 
 
 plasma concentrations will be listed and summarized 
descriptively by dose, day and time among the PK Analysis Set.   
 
 
 
  
 
9.7 Methods for Handling Dropouts and Missing Data 
Imputation for missing dates for AEs and concomitant medications have been addressed in previous 
sections (5.6 and 5.12 respectively). 
 
 Assumptions for laboratory values below or above the limits 
of quantification have been specified in Section 9.6.5. Participants without an efficacy measurement at 
Week 12 will be considered as “non-responders”. No other imputations or missing data analyses are 
planned.  
9.8 Multiplicity 
There will be no adjustment for multiplicity. Many analyses will be considered descriptive in nature. 
9.9 Pooling of Sites and Regional Analyses 
There will be no pooling of sites in these analyses. 


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Sponsor: Bristol-Myers Squibb  
Statistical Analysis Plan 
Protocol no: IM025006  
Version Date: 19-Feb-2019  
 
 
 
Page 28 of 30 
Strictly Confidential.  © 2004-2015, 
.  All rights reserved. 
 
Appendix 1 Glossary of Abbreviations 
Term 
Definition 
AE 
adverse event 
AFP 
alpha-fetoprotein 
ALP 
alkaline phosphatase 
ALT 
alanine aminotransferase 
ANCOVA 
Analysis of Covariance 
AST 
aspartate aminotransferase 
ATC 
Anatomical Therapeutic Classification 
BMD 
bone mineral density 
BMI 
body mass index 
BMS 
Bristol-Myers Squibb 
BUN 
blood urea nitrogen 
CDISC 
Clinical Data interchange Standards Consortium 
CFB 
change from baseline 
CI 
confidence interval 
CMH 
Cochran Mantel-Haenszel 
CPA 
collagen proportionate area 
CRF 
case report form 
eCRF 
electronic case report form 
CSR 
clinical study report 
DMC 
  Data Monitoring Committee 
DMC 
data monitoring committee 
DXA 
dual-energy X-ray absorptiometry 
ECG 
electrocardiogram 
ET 
End of Treatment 
FDA 
U.S. Food and Drug Administration 
FSH 
follicle stimulating hormone 
GGT 
gamma-glutamyl transferase 
HbcAb 
hepatitis B core antibody 
HbsAg 
hepatitis B surface antigen 
HbsAb 
hepatitis B surface antibody 
HCC 
hepatocellular carcinoma 
HCV 
hepatitis C virus 


 
 
 
Sponsor: Bristol-Myers Squibb  
Statistical Analysis Plan 
Protocol no: IM025006  
Version Date: 19-Feb-2019  
 
 
 
Page 29 of 30 
Strictly Confidential.  © 2004-2015, 
.  All rights reserved. 
 
ICF 
informed consent form 
ICH 
International Council on Harmonization 
INR 
international normalized ratio 
IP 
investigational product 
IRT 
interactive response technology 
LDH 
lactate dehydrogenase 
MedDRA 
Medical Dictionary for Regulatory Activities 
mITT 
modified intent-to-treat 
MRE 
magnetic resonance elastography 
MRI 
magnetic resonance imaging 
OR 
odds ratio 
PCP 
phencyclidine 
PI 
principal investigator 
PK 
Pharmacokinetics 
PT 
Preferred term 
PTT 
partial thromboplastin time 
QW 
once every week 
Q2W 
once every 2 weeks 
Q4W 
once every 4 weeks 
RAS 
Randomized analysis set  
RNA 
ribonucleic acid 
SAE 
serious adverse event 
SAP 
statistical analysis plan 
SD 
standard deviation 
SOC 
system organ class 
SVR 
sustained virologic response 
TA 
Therapeutic Area 
TEAE 
treatment-emergent adverse event 
TFL 
tables, figures, and listings 
WOCBP 
women of childbearing potential 
 
 


 
 
 
Sponsor: Bristol-Myers Squibb  
Statistical Analysis Plan 
Protocol no: IM025006  
Version Date: 19-Feb-2019  
 
 
 
Page 30 of 30 
Strictly Confidential.  © 2004-2015, 
.  All rights reserved. 
 
Appendix 2 Tables, Figures, Listings 
Refer to the study TFL shell document. 
Appendix 3 Statistical Appendices  
 
Statistical appendices will be provided for primary endpoints containing raw SAS output. For ANCOVA 
analyses of secondary endpoints, appendices will be produced including plots to assess residuals and 
model fit.