Safety and Effectiveness of BMS-986263 in Adults With Compensated Cirrhosis (Liver Disease) From Nonalcoholic Steatohepatitis (NASH)

August 9, 2024 updated by: Bristol-Myers Squibb

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

The purpose of this randomized study is to assess safety and effectiveness of BMS-986263 in adults with compensated cirrhosis (chronic liver disease) from nonalcoholic steatohepatitis (fatty liver disease) (NASH).

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

124

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Argentina
      • Buenos Aires, Argentina, C1280AEB
        • Local Institution - 0059
    • Buenos Aires
      • Ciudad de Buenos Aires, Buenos Aires, Argentina, 1181
        • Local Institution - 0089
      • Florencio Varela, Buenos Aires, Argentina, 1888
        • Local Institution - 0126
    • Ciudad Autónoma De Buenos Aires
      • Quilmes, Ciudad Autónoma De Buenos Aires, Argentina, 1879
        • Local Institution - 0209
  • Belgium
      • Edegem, Belgium, 2650
        • Local Institution - 0009
      • Gent, Belgium, 9000
        • Local Institution - 0006
      • Leuven, Belgium, 3001
        • Local Institution - 0133
  • Brazil
      • Sao Paulo, Brazil, 01.308-050
        • Local Institution - 0120
      • Sao Paulo, Brazil, 05652000
        • Local Institution
    • Bahia
      • Salvador, Bahia, Brazil, 40110-060
        • Local Institution - 0083
    • RIO Grande DO SUL
      • Bento Goncalves, RIO Grande DO SUL, Brazil, 95700-084
        • Local Institution - 0182
      • Porto Alegre, RIO Grande DO SUL, Brazil, 90035004
        • Local Institution
    • SAO Paulo
      • Barretos, SAO Paulo, Brazil, 14780-320
        • Local Institution - 0187
      • Botucatu, SAO Paulo, Brazil, 18618.687
        • Local Institution - 0188
      • Ribeirão Preto, SAO Paulo, Brazil, 14049900
        • Local Institution
      • Sao Bernardo do Campo, SAO Paulo, Brazil, 09715-090
        • Local Institution - 0196
  • Canada
    • British Columbia
      • Victoria, British Columbia, Canada, V8V 3M9
        • Local Institution - 0128
    • Ontario
      • Toronto, Ontario, Canada, M6H 3M1
        • Local Institution - 0097
  • France
      • Lyon, France, 69004
        • Local Institution - 0094
      • Nice, France, 06200
        • Local Institution - 0031
      • Paris, France, 75013
        • Local Institution - 0101
      • Paris, France, 75014
        • Local Institution - 0105
      • Strasbourg, France, 67098
        • Local Institution - 0137
      • Vandoeuvre les Nancy, France, 54500
        • Local Institution - 0029
    • Île-de-France
      • Créteil, Île-de-France, France, 94000
        • Local Institution - 0202
  • Germany
      • Berlin, Germany, 13353
        • Local Institution - 0091
      • Essen, Germany, 45147
        • Local Institution - 0099
      • Hannover, Germany, 30625
        • Local Institution - 0096
      • Kiel, Germany, 24105
        • Local Institution - 0073
      • Lübeck, Germany, 23538
        • Local Institution - 0194
      • Mainz, Germany, 55131
        • Local Institution - 0071
      • Munich, Germany, 81377
        • Local Institution - 0060
      • Trier, Germany, 54292
        • Local Institution - 0204
    • Hessen
      • Frankfurt, Hessen, Germany, 60590
        • Local Institution - 0082
  • Israel
      • Haifa, Israel, 3436212
        • Local Institution - 0056
      • Petah Tikva, Israel, 4941492
        • Local Institution - 0076
      • Ramat Gan, Israel, 5262100
        • Local Institution - 0058
      • Tel Aviv, Israel, 6423906
        • Local Institution - 0057
  • Italy
      • Bologna, Italy, 40138
        • Local Institution - 0054
      • Messina, Italy
        • Azienda Ospedaliera Universitaria Di Messina G. Martino-D.A.I. Medicina Interna
      • Palermo, Italy, 90127
        • Local Institution - 0115
      • Pisa, Italy, 56124
        • Local Institution - 0051
      • Rome, Italy, 168
        • Local Institution
  • Japan
      • Aomori, Japan, 030-8553
        • Local Institution - 0199
      • Gifu, Japan, 5008513
        • Local Institution - 0193
      • Hiroshima, Japan, 7348551
        • Local Institution - 0026
      • Kagoshima, Japan, 8908520
        • Local Institution - 0135
      • Kyoto, Japan, 602-8566
        • Local Institution - 0131
      • Yamagata, Japan, 990-9585
        • Local Institution - 0132
    • Ehime
      • Toon, Ehime, Japan, 791-0295
        • Local Institution - 0200
    • Fukuoka
      • Kurume, Fukuoka, Japan, 830-0011
        • Local Institution - 0048
    • Hokkaido
      • Sapporo, Hokkaido, Japan, 0608648
        • Local Institution - 0049
    • Iwate
      • Shiwagun Yahabatyo, Iwate, Japan, 028-3695
        • Local Institution - 0127
    • Kanagawa
      • Yokohama, Kanagawa, Japan, 236-0004
        • Local Institution - 0075
    • Nagano
      • Matsumoto, Nagano, Japan, 390-8621
        • Local Institution - 0155
    • Nara
      • Kashihara, Nara, Japan, 634-0813
        • Local Institution - 0111
    • Osaka
      • Sakai, Osaka, Japan, 591-8025
        • Local Institution - 0163
    • Tokyo
      • Bunkyō, Tokyo, Japan, 113-8519
        • Local Institution - 0125
      • Minato-ku, Tokyo, Japan, 105-8470
        • Local Institution - 0138
  • Korea, Republic of
      • Seodaemun-gu, Korea, Republic of, 03722
        • Local Institution - 0066
      • Seoul, Korea, Republic of, 04401
        • Local Institution - 0090
    • Incheon-gwangyeoksi [Incheon]
      • Incheon, Incheon-gwangyeoksi [Incheon], Korea, Republic of, 22332
        • Local Institution - 0093
  • Puerto Rico
      • San Juan, Puerto Rico, 00927
        • Local Institution - 0012
  • Spain
      • Barcelona, Spain, 08035
        • Local Institution - 0040
      • Madrid, Spain, 28007
        • Local Institution - 0080
      • Madrid, Spain, 28222
        • Local Institution - 0038
      • Madrid, Spain, 28034
        • Local Institution - 0039
      • Malaga, Spain, 29010
        • Local Institution - 0036
      • Santander, Spain, 39008
        • Local Institution - 0037
      • Sevilla, Spain, 41013
        • Local Institution - 0041
      • Valencia, Spain, 46010
        • Local Institution - 0035
      • València, Spain, 46026
        • Local Institution - 0043
  • Switzerland
      • Berne, Switzerland, 3010
        • Local Institution - 0074
    • Ticino
      • Lugano, Ticino, Switzerland, 6900
        • Local Institution - 0102
  • Taiwan
      • Kaohsiung, Taiwan, 807
        • Local Institution - 0001
      • Taipei, Taiwan, 11217
        • Local Institution
      • Taipei, Taiwan, 10002
        • Local Institution
      • Taoyuan, Taiwan, 333
        • Local Institution - 0004
  • United Kingdom
      • Hull, United Kingdom, HU3 2JZ
        • Local Institution - 0034
      • Liverpool, United Kingdom, L9 7AL
        • Local Institution - 0124
      • London, United Kingdom, SE5 9RS
        • Local Institution - 0005
      • Southampton, United Kingdom, SO16 6YD
        • Local Institution
    • Nottinghamshire
      • Nottingham, Nottinghamshire, United Kingdom, NG7 2UH
        • Local Institution - 0011
  • United States
    • Arizona
      • Chandler, Arizona, United States, 85224
        • Arizona Clinical Trials - Tucson
      • Chandler, Arizona, United States, 85224
        • Local Institution - 0173
      • Chandler, Arizona, United States, 85224
        • The Institute for Liver Health-The Institute for Liver Health
      • Phoenix, Arizona, United States, 85013
        • Local Institution
    • California
      • La Jolla, California, United States, 92037
        • Local Institution - 0140
      • Lancaster, California, United States, 93534
        • Local Institution - 0205
      • Los Angeles, California, United States, 90067
        • GastroIntestinal BioSciences
      • Redwood City, California, United States, 94063
        • Local Institution - 0143
    • Florida
      • Lakewood Ranch, Florida, United States, 34211
        • Florida Research Institute
      • Leesburg, Florida, United States, 34748
        • Local Institution - 0024
      • Miami, Florida, United States, 33136
        • Local Institution - 0061
      • Winter Park, Florida, United States, 32789
        • Local Institution - 0025
    • Iowa
      • Iowa City, Iowa, United States, 52242
        • Local Institution - 0121
    • Maryland
      • Baltimore, Maryland, United States, 21202
        • Local Institution - 0150
    • Massachusetts
      • Fall River, Massachusetts, United States, 02721
        • Local Institution
    • Missouri
      • Kansas City, Missouri, United States, 64111
        • Local Institution - 0077
    • Nebraska
      • Omaha, Nebraska, United States, 68198
        • Local Institution - 0186
    • New York
      • Buffalo, New York, United States, 14203
        • Research Foundation of SUNY - University of Buffalo
      • New York, New York, United States, 10029
        • Local Institution
      • New York, New York, United States, 10016
        • NYU Langone Health-Department of Medicine
    • North Carolina
      • Morehead City, North Carolina, United States, 28557
        • Local Institution - 0206
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • Local Institution - 0177
      • Philadelphia, Pennsylvania, United States, 19107
        • Local Institution - 0017
    • Tennessee
      • Chattanooga, Tennessee, United States, 37411
        • University Diabetes & Endocrine Consultants
    • Texas
      • Dallas, Texas, United States, 75203
        • Local Institution - 0171
      • Houston, Texas, United States, 77030
        • Local Institution - 0109
      • McAllen, Texas, United States, 78504
        • Local Institution
      • San Antonio, Texas, United States, 78215
        • Local Institution - 0013
    • Virginia
      • Richmond, Virginia, United States, 232980341
        • Local Institution - 0122

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

21 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Participants with liver biopsy fibrosis score stage 4 (NASH CRN) performed within 12 months
  • Men and women must agree to follow methods of contraception

Exclusion Criteria:

  • Worsening liver disease or any disease might compromise participant safety in the opinion of the investigator
  • Known immunocompromised status or any disease or condition which might compromise participant safety
  • Prior exposure to BMS-986263
  • Clinically relevant abnormal physical examination, vital signs, ECG, or clinical laboratory tests
  • Hepatic decompensation

Other protocol-defined inclusion/exclusion criteria apply

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Placebo
Other: Placebo
Specified dose on specified days
Experimental: Dose A BMS-986263
Drug: BMS-986263
Specified dose on specified days
Experimental: Dose B BMS-986263
Drug: BMS-986263
Specified dose on specified days

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage of Participants Who Achieve ≥ 1 Stage Improvement in Liver Fibrosis (NASH CRN Fibrosis Score), as Determined by Liver Biopsy After 12 Weeks of Treatment.
Time Frame: 12 Weeks

Percentage of participants who achieve ≥ 1 stage improvement in liver fibrosis (NASH CRN Fibrosis Score), as determined by liver biopsy after 12 weeks of treatment.

For the NASH CRN Fibrosis Score, fibrosis is staged on a 0 to 4 scale: 0 (none); 1 (perisinusoidal or periportal fibrosis); 2 (perisinusoidal and portal/periportal fibrosis); 3 (bridging fibrosis); 4 (cirrhosis).

Responder is defined as achieved >=1 stage improvement in liver fibrosis (NASH CRN Fibrosis Score) as determined by liver biopsy from baseline to week 12/early treatment termination (ETT).
12 Weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage of Participants Who Achieve ≥ 1 Stage Improvement in Liver Fibrosis (NASH CRN Fibrosis Score) With no Worsening of NASH After 12 Weeks of Treatment.
Time Frame: 12 Weeks

Percentage of participants who achieve ≥ 1 stage improvement in liver fibrosis (NASH CRN Fibrosis Score) with no worsening of NASH after 12 weeks of treatment.

For the NASH CRN Fibrosis Score, fibrosis is staged on a 0 to 4 scale: 0 (none); 1 (perisinusoidal or periportal fibrosis); 2 (perisinusoidal and portal/periportal fibrosis); 3 (bridging fibrosis); 4 (cirrhosis).
12 Weeks
Percentage of Participants Who Achieve ≥ 2 Stage Improvement in Liver Fibrosis (NASH CRN Fibrosis Score) With no Worsening of NASH After 12 Weeks of Treatment.
Time Frame: 12 Weeks

Percentage of participants who achieve ≥ 2 stage improvement in liver fibrosis (NASH CRN Fibrosis Score) with no worsening of NASH after 12 weeks of treatment.

For the NASH CRN Fibrosis Score, fibrosis is staged on a 0 to 4 scale: 0 (none); 1 (perisinusoidal or periportal fibrosis); 2 (perisinusoidal and portal/periportal fibrosis); 3 (bridging fibrosis); 4 (cirrhosis).
12 Weeks
Percentage of Participants Who Achieve ≥ 1 Stage Improvement in Liver Fibrosis (Modified Ishak Score) After 12 Weeks of Treatment.
Time Frame: 12 Weeks

Percentage of participants who achieve ≥ 1 stage improvement in liver fibrosis (modified Ishak score) after 12 weeks of treatment.

A modified Ishak scoring system (0 to 6 scale) was originally developed to grade portal-based liver fibrosis associated with viral hepatitis. The modified Ishak system has been adapted to grade central-based liver fibrosis associated with NASH, and it also uses a 0 to 6 scale:

0: No fibrosis

  1. perisinusoidal or periportal fibrosis
  2. perisinusoidal and portal/periportal fibrosis
  3. bridging fibrosis with linkage of < 50% of vascular structures (portal and centrilobular)
  4. bridging fibrosis with linkage of > 50% of vascular structures (portal and centrilobular)
  5. early or incomplete cirrhosis
  6. established or advanced cirrhosis
12 Weeks
Percentage of Participants Who Achieve ≥ 2 Stage Improvement in Liver Fibrosis (Modified Ishak Score) After 12 Weeks of Treatment.
Time Frame: 12 Weeks

Percentage of participants who achieve ≥ 2 stage improvement in liver fibrosis (modified Ishak score) after 12 weeks of treatment.

A modified Ishak scoring system (0 to 6 scale) was originally developed to grade portal-based liver fibrosis associated with viral hepatitis. The modified Ishak system has been adapted to grade central-based liver fibrosis associated with NASH, and it also uses a 0 to 6 scale:

0: No fibrosis

  1. perisinusoidal or periportal fibrosis
  2. perisinusoidal and portal/periportal fibrosis
  3. bridging fibrosis with linkage of < 50% of vascular structures (portal and centrilobular)
  4. bridging fibrosis with linkage of > 50% of vascular structures (portal and centrilobular)
  5. early or incomplete cirrhosis
  6. established or advanced cirrhosis
12 Weeks
Mean Change From Baseline in CPA After 12 Weeks of Treatment
Time Frame: 12 Weeks

Change from baseline in CPA after 12 weeks of treatment.

Assessment of collagen proportionate area(CPA) is a method by which the amount (percentage) of collagen in stained tissue sections is analyzed using morphometric image analysis. This allows for a quantitative assessment of fibrosis. Percentage of fat in stained tissue sections is also analyzed using morphometric image analysis.
12 Weeks
Number of Participants With Treatment Emergent Adverse Events (TEAE) and Treatment Emergent Serious Adverse Events (TESAE)
Time Frame: From First Treatment to end of Follow up (36 weeks)
An AE is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study drug and that does have a causal relationship with this treatment.
From First Treatment to end of Follow up (36 weeks)
Number of Participants With Clinically Significant Changes in Clinical Laboratory Values.
Time Frame: From First Treatment to end of Follow up (36 weeks)

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.

clinical laboratory assessments analyzed: Hematology, Blood Chemistry, Urinalysis and a Metabolic Panel.
From First Treatment to end of Follow up (36 weeks)
Number of Participants With Clinically Significant Changes in Vitals Signs.
Time Frame: From First Treatment to end of Follow up (36 weeks)
Includes body temperature, respiratory rate, blood pressure, and heart rate. Blood pressure and heart rate should be measured after the participant has been resting quietly for at least 5 minutes.
From First Treatment to end of Follow up (36 weeks)
Number of Participants With Clinically Significant Changes in Physical Examination Findings.
Time Frame: From First Treatment to end of Follow up (36 weeks)
Physical examination includes body weight, height, and BMI (height and BMI calculation at screening only).
From First Treatment to end of Follow up (36 weeks)
Number of Participants With Clinically Significant Changes in Electrocardiogram Readings.
Time Frame: From First Treatment to end of Follow up (36 weeks)
Number of Participants with clinically significant changes in electrocardiogram readings.
From First Treatment to end of Follow up (36 weeks)
Number of Participants With Clinically Significant Changes in BMD.
Time Frame: From First Treatment to end of Follow up (36 weeks)
Bone Mineral Density(BMD) will be measured by a dual-energy X-ray absorptiometry (DXA) Scan.
From First Treatment to end of Follow up (36 weeks)
Plasma Concentration of BMS-986263 Components at the End of 12 Weeks or ETT.
Time Frame: 12 Weeks
Plasma concentrations of BMS-986263 components: siRNA, DPD, HEDC, and S104.
12 Weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Bristol-Myers Squibb

Investigators

  • Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 17, 2021

Primary Completion (Actual)

August 16, 2023

Study Completion (Actual)

February 9, 2024

Study Registration Dates

First Submitted

February 11, 2020

First Submitted That Met QC Criteria

February 11, 2020

First Posted (Actual)

February 12, 2020

Study Record Updates

Last Update Posted (Actual)

September 4, 2024

Last Update Submitted That Met QC Criteria

August 9, 2024

Last Verified

August 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IM025-017
  • 2019-003932-22 (EudraCT Number)
  • U1111-1241-4762 (Other Identifier: UTN Number)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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