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

Phase 2

Terminated

• Conditions: Nonalcoholic Steatohepatitis (NASH)
• Interventions: Drug: BMS-986263; Other: Placebo

• Registration Number: NCT04267393
• Lead Sponsor: Bristol-Myers Squibb

Brief Summary

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).

Detailed Description

Not available

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2020-02-11
• Study First Submitted QC: 2020-02-11
• Study First Posted: 2020-02-12
• Study Start: 2021-03-17
• Primary Completion: 2023-08-16
• Status Verified: 2024-02
• Study Completion: 2024-02-09
• Last Update Submitted: 2024-02-13
• Last Update Posted: 2024-02-14

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 124

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Dose A BMS-986263	BMS-986263	-
Dose B BMS-986263	BMS-986263	-
Placebo	Placebo	-

Primary Outcome Measures

Name	Time	Method
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.	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).

Secondary Outcome Measures

Name	Time	Method
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.	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).
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.	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).
Percentage of Participants Who Achieve ≥ 1 Stage Improvement in Liver Fibrosis (Modified Ishak Score) After 12 Weeks of Treatment.	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
Percentage of Participants Who Achieve ≥ 2 Stage Improvement in Liver Fibrosis (Modified Ishak Score) After 12 Weeks of Treatment.	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
Mean Change From Baseline in CPA After 12 Weeks of Treatment	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.
Number of Participants With Treatment Emergent Adverse Events (TEAE) and Treatment Emergent Serious Adverse Events (TESAE)	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.
Number of Participants With Clinically Significant Changes in Clinical Laboratory Values.	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.
Number of Participants With Clinically Significant Changes in Vitals Signs.	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.
Number of Participants With Clinically Significant Changes in Physical Examination Findings.	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).
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 electrocardiogram readings.
Number of Participants With Clinically Significant Changes in BMD.	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.
Plasma Concentration of BMS-986263 Components at the End of 12 Weeks or ETT.	12 Weeks	Plasma concentrations of BMS-986263 components: siRNA, DPD, HEDC, and S104.

Trial Locations

Locations (102)

Local Institution - 0150; 🇺🇸 Baltimore, Maryland, United States

Local Institution - 0171; 🇺🇸 Dallas, Texas, United States

Local Institution - 0143; 🇺🇸 Redwood City, California, United States

GastroIntestinal BioSciences; 🇺🇸 Los Angeles, California, United States

Local Institution - 0061; 🇺🇸 Miami, Florida, United States

Local Institution - 0025; 🇺🇸 Winter Park, Florida, United States

Local Institution - 0177; 🇺🇸 Philadelphia, Pennsylvania, United States

Local Institution - 0017; 🇺🇸 Philadelphia, Pennsylvania, United States

University Diabetes & Endocrine Consultants; 🇺🇸 Chattanooga, Tennessee, United States

Local Institution - 0128; 🇨🇦 Victoria, British Columbia, Canada

Local Institution - 0097; 🇨🇦 Toronto, Ontario, Canada

Local Institution - 0051; 🇮🇹 Pisa, Italy

Local Institution - 0094; 🇫🇷 Lyon, France

Arizona Clinical Trials - Tucson; 🇺🇸 Chandler, Arizona, United States

Local Institution - 0124; 🇬🇧 Liverpool, United Kingdom

Local Institution - 0196; 🇧🇷 Sao Bernardo do Campo, SAO Paulo, Brazil

Local Institution - 0099; 🇩🇪 Essen, Germany

Local Institution - 0115; 🇮🇹 Palermo, Italy

Local Institution - 0173; 🇺🇸 Chandler, Arizona, United States

Local Institution - 0140; 🇺🇸 La Jolla, California, United States

Local Institution; 🇬🇧 Southampton, United Kingdom

Local Institution - 0205; 🇺🇸 Lancaster, California, United States

Local Institution - 0024; 🇺🇸 Leesburg, Florida, United States

The Institute for Liver Health-The Institute for Liver Health; 🇺🇸 Chandler, Arizona, United States

Florida Research Institute; 🇺🇸 Lakewood Ranch, Florida, United States

Research Foundation of SUNY - University of Buffalo; 🇺🇸 Buffalo, New York, United States

NYU Langone Health-Department of Medicine; 🇺🇸 New York, New York, United States

Local Institution - 0121; 🇺🇸 Iowa City, Iowa, United States

Local Institution - 0206; 🇺🇸 Morehead City, North Carolina, United States

Local Institution - 0109; 🇺🇸 Houston, Texas, United States

Local Institution - 0013; 🇺🇸 San Antonio, Texas, United States

Local Institution - 0089; 🇦🇷 Ciudad de Buenos Aires, Buenos Aires, Argentina

Local Institution - 0126; 🇦🇷 Florencio Varela, Buenos Aires, Argentina

Local Institution - 0209; 🇦🇷 Quilmes, Ciudad Autónoma De Buenos Aires, Argentina

Local Institution - 0059; 🇦🇷 Buenos Aires, Argentina

Local Institution - 0009; 🇧🇪 Edegem, Belgium

Local Institution - 0006; 🇧🇪 Gent, Belgium

Local Institution - 0083; 🇧🇷 Salvador, Bahia, Brazil

Local Institution - 0133; 🇧🇪 Leuven, Belgium

Local Institution - 0182; 🇧🇷 Bento Goncalves, RIO Grande DO SUL, Brazil

Local Institution - 0187; 🇧🇷 Barretos, SAO Paulo, Brazil

Local Institution - 0188; 🇧🇷 Botucatu, SAO Paulo, Brazil

Local Institution - 0120; 🇧🇷 Sao Paulo, Brazil

Local Institution - 0031; 🇫🇷 Nice, France

Local Institution - 0101; 🇫🇷 Paris, France

Local Institution - 0105; 🇫🇷 Paris, France

Local Institution - 0202; 🇫🇷 Créteil, Île-de-France, France

Local Institution - 0137; 🇫🇷 Strasbourg, France

Local Institution - 0029; 🇫🇷 Vandoeuvre les Nancy, France

Local Institution - 0091; 🇩🇪 Berlin, Germany

Local Institution - 0082; 🇩🇪 Frankfurt, Hessen, Germany

Local Institution - 0076; 🇮🇱 Petah Tikva, Israel

Local Institution - 0096; 🇩🇪 Hannover, Germany

Local Institution - 0073; 🇩🇪 Kiel, Germany

Local Institution - 0194; 🇩🇪 Lübeck, Germany

Local Institution - 0071; 🇩🇪 Mainz, Germany

Local Institution - 0054; 🇮🇹 Bologna, Italy

Local Institution - 0060; 🇩🇪 Munich, Germany

Local Institution - 0204; 🇩🇪 Trier, Germany

Local Institution - 0056; 🇮🇱 Haifa, Israel

Local Institution - 0058; 🇮🇱 Ramat Gan, Israel

Local Institution - 0057; 🇮🇱 Tel Aviv, Israel

Azienda Ospedaliera Universitaria Di Messina G. Martino-D.A.I. Medicina Interna; 🇮🇹 Messina, Italy

Local Institution - 0200; 🇯🇵 Toon, Ehime, Japan

Local Institution - 0138; 🇯🇵 Minato-ku, Tokyo, Japan

Local Institution - 0074; 🇨🇭 Berne, Switzerland

Local Institution - 0155; 🇯🇵 Matsumoto, Nagano, Japan

Local Institution - 0111; 🇯🇵 Kashihara, Nara, Japan

Local Institution - 0048; 🇯🇵 Kurume, Fukuoka, Japan

Local Institution - 0049; 🇯🇵 Sapporo, Hokkaido, Japan

Local Institution - 0127; 🇯🇵 Shiwagun Yahabatyo, Iwate, Japan

Local Institution - 0075; 🇯🇵 Yokohama, Kanagawa, Japan

Local Institution - 0163; 🇯🇵 Sakai, Osaka, Japan

Local Institution - 0125; 🇯🇵 Bunkyō, Tokyo, Japan

Local Institution - 0199; 🇯🇵 Aomori, Japan

Local Institution - 0193; 🇯🇵 Gifu, Japan

Local Institution - 0026; 🇯🇵 Hiroshima, Japan

Local Institution - 0135; 🇯🇵 Kagoshima, Japan

Local Institution - 0131; 🇯🇵 Kyoto, Japan

Local Institution - 0132; 🇯🇵 Yamagata, Japan

Local Institution - 0093; 🇰🇷 Incheon, Incheon-gwangyeoksi [Incheon], Korea, Republic of

Local Institution - 0040; 🇪🇸 Barcelona, Spain

Local Institution - 0066; 🇰🇷 Seodaemun-gu, Korea, Republic of

Local Institution - 0012; 🇵🇷 San Juan, Puerto Rico

Local Institution - 0080; 🇪🇸 Madrid, Spain

Local Institution - 0039; 🇪🇸 Madrid, Spain

Local Institution - 0038; 🇪🇸 Madrid, Spain

Local Institution - 0090; 🇰🇷 Seoul, Korea, Republic of

Local Institution - 0035; 🇪🇸 Valencia, Spain

Local Institution - 0041; 🇪🇸 Sevilla, Spain

Local Institution - 0036; 🇪🇸 Malaga, Spain

Local Institution - 0037; 🇪🇸 Santander, Spain

Local Institution - 0043; 🇪🇸 València, Spain

Local Institution - 0102; 🇨🇭 Lugano, Ticino, Switzerland

Local Institution - 0001; 🇨🇳 Kaohsiung, Taiwan

Local Institution - 0005; 🇬🇧 London, United Kingdom

Local Institution - 0004; 🇨🇳 Taoyuan, Taiwan

Local Institution - 0011; 🇬🇧 Nottingham, Nottinghamshire, United Kingdom

Local Institution - 0034; 🇬🇧 Hull, United Kingdom

Local Institution - 0077; 🇺🇸 Kansas City, Missouri, United States

Local Institution - 0186; 🇺🇸 Omaha, Nebraska, United States

Local Institution - 0122; 🇺🇸 Richmond, Virginia, United States