A Study of Experimental Medication BMS-986036 in Adults With Nonalcoholic Steatohepatitis (NASH) and Stage 3 Liver Fibrosis

Phase 2

Completed

• Conditions: Liver Fibrosis; Nonalcoholic Fatty Liver Disease (NAFLD); Nonalcoholic Steatohepatitis
• Interventions: Drug: BMS-986036; Other: Placebo

• Registration Number: NCT03486899
• Lead Sponsor: Bristol-Myers Squibb

Brief Summary

This is a study of experimental medication BMS-986036 given to adults with Nonalcoholic Steatohepatitis (NASH; the buildup of fat and inflammation in the liver that is not caused by alcohol) and stage 3 liver fibrosis (severe fibrosis).

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: 2018-03-30
• Study First Submitted QC: 2018-03-30
• Study First Posted: 2018-04-03
• Study Start: 2018-06-19
• Primary Completion: 2020-09-14
• Disposition First Submitted: 2021-07-09
• Disposition First Submitted QC: 2021-07-09
• Disposition First Posted: 2021-07-13
• Study Completion: 2021-08-17
• Status Verified: 2022-08
• Results First Submitted: 2022-08-16
• Results First Submitted QC: 2022-08-16
• Last Update Submitted: 2022-08-16
• Results First Posted: 2022-09-09
• Last Update Posted: 2022-09-09

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 197

Inclusion Criteria

• Liver biopsy performed within 6 months (26 weeks) prior to the screening period. If historical biopsy is not available, a liver biopsy will be performed during the screening period. Biopsy must be consistent with NASH, with: a) a score of at least 1 for each NAS component (steatosis, lobular inflammation, and ballooning), as assessed by the central reader, and b) stage 3 liver fibrosis according to the NASH CRN classification, as assessed by the central reader
• Participants taking anti-diabetic, anti-obesity, or anti-dyslipidemic medications must have been on stable regimens for at least 3 months (12 weeks) (6 weeks for statins) prior to and during the screening period
• Participants taking vitamin E at doses greater than or equal to (>=) 800 IU/day must have been on stable doses for at least 6 months (26 weeks) prior to and during the Screening Period. Vitamin E treatment (>=800 IU/day) must not have been initiated after the qualifying liver biopsy was performed.

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Exclusion Criteria

• Other causes of liver disease (e.g., alcoholic liver disease, hepatitis B virus infection, chronic hepatitis C virus [HCV] infection, autoimmune hepatitis, drug-induced hepatotoxicity, Wilson disease, α-1-antitrypsin deficiency, iron overload, and hemochromatosis); participants with HCV sustained viral response (undetectable HCV RNA) for at least 2 years prior to biopsy confirming study eligibility may be eligible
• Current or past history of hepatocellular carcinoma (HCC)
• Past or current evidence of hepatic decompensation (e.g., ascites, variceal bleeding, hepatic encephalopathy and/or spontaneous bacterial peritonitis) or liver transplantation

Other protocol defined inclusion/exclusion criteria could apply

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
BMS-986036 Dose Level 1	BMS-986036	Administered by subcutaneous injection.
BMS-986036 Dose Level 2	BMS-986036	Administered by subcutaneous injection.
BMS-986036 Dose Level 3	BMS-986036	Administered by subcutaneous injection.
Placebo	Placebo	Administered by subcutaneous injection.

Primary Outcome Measures

Name	Time	Method
The Percentage of Participants With Improvement in Fibrosis or Nonalcoholic Steatohepatitis (NASH) at Week 24	From first dose to 24 weeks after first dose	The percentage of participants who achieved a ≥1-stage improvement in fibrosis without worsening of NASH or NASH improvement with no worsening of fibrosis at week 24 in liver biopsy. Improvement in fibrosis is defined by the NASH Clinical Research Network (CRN) Fibrosis Score. Improvement in NASH is defined by a ≥2-stage decrease in the nonalcoholic fatty liver disease activity score (NAS). Worsening of NASH is defined as an increase of the nonalcoholic fatty liver disease (NAFLD) Activity Score (NAS) by ≥1 point. Worsening of fibrosis is defined as an increase of fibrosis by ≥1 point as determined by the NASH CRN Fibrosis Score. NASH CRN Fibrosis is staged on a 0-4 scale: 0 (none); 1 (perisinusoidal or periportal fibrosis); 2 (perisinusoidal and portal/periportal fibrosis); 3 (bridging fibrosis); 4 (cirrhosis).

Secondary Outcome Measures

Name	Time	Method
The Percentage of Participants Who Achieved an Improvement in Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN) Fibrosis Score at Week 24	From first dose to 24 weeks after first dose	An improvement in fibrosis is defined as a decrease of ≥ 1-stage in the NASH CRN Fibrosis Score at week 24 in liver biopsy. NASH CRN Fibrosis is staged on a 0-4 scale: 0 (none); 1 (perisinusoidal or periportal fibrosis); 2 (perisinusoidal and portal/periportal fibrosis); 3 (bridging fibrosis); 4 (cirrhosis).
The Percentage of Participants Who Achieve a ≥ 1-Stage Improvement in Ishak Fibrosis Score at Week 24	From first dose to 24 weeks after first dose	An improvement in Ishak fibrosis is defined as a decrease of fibrosis by ≥ 1-stage in the Ishak fibrosis score at week 24 in liver biopsy. ISHAKs uses a 0-6 scale: 1: centrilobular pericellular fibrosis, 2: centrilobular and periportal fibrosis, 3: bridging fibrosis (few bridges), 4: bridging fibrosis (many bridges), 5: early or incomplete cirrhosis, 6: established or advanced cirrhosis.
The Percentage of Participants With Any Improvement in Collagen Proportionate Area (CPA) at Week 24	From first dose to 24 weeks after first dose	An improvement in CPA is defined as any decrease in CPA at week 24 in liver biopsy.
The Percentage of Participants With Nonalcoholic Steatohepatitis (NASH) Resolution Without Worsening of Fibrosis at Week 24	From first dose to 24 weeks after first dose	The percentage of participants with NASH resolution without worsening of fibrosis at week 24 in liver biopsy. NASH resolution defined by the nonalcoholic fatty liver disease activity score (NAS) component of ballooning = 0 and inflammation = 0-1. Worsening of fibrosis is defined as an increase of fibrosis by ≥ 1-stage in the NASH Clinical Research Network (CRN) Fibrosis Score.; Ballooning = 0 (none) inflammation = 0 (none) - 1 (Grade \<2). NASH CRN Fibrosis is staged on a 0-4 scale: 0 (none); 1 (perisinusoidal or periportal fibrosis); 2 (perisinusoidal and portal/periportal fibrosis); 3 (bridging fibrosis); 4 (cirrhosis).
The Percentage of Participants With Nonalcoholic Steatohepatitis (NASH) Resolution at Week 24	From first dose to 24 weeks after first dose	NASH resolution defined by the nonalcoholic fatty liver disease activity score (NAS) component of ballooning = 0 and inflammation = 0-1 at week 24 in liver biopsy. Ballooning = 0 (none) inflammation = 0 (none) - 1 (Grade \<2).
The Percentage of Participants With Nonalcoholic Steatohepatitis (NASH) Improvement Without Worsening of Fibrosis at Week 24	From first dose to 24 weeks after first dose	The percentage of participants with NASH improvement without worsening of fibrosis at week 24 in liver biopsy. NASH improvement defined as a reduction of nonalcoholic fatty liver disease activity score (NAS) by ≥2 points with contribution from \>1 NAS component. Worsening of fibrosis is defined as an increase of ≥1-point in the NASH Clinical Research Network (CRN) Fibrosis Score. NASH CRN Fibrosis is staged on a 0-4 scale: 0 (none); 1 (perisinusoidal or periportal fibrosis); 2 (perisinusoidal and portal/periportal fibrosis); 3 (bridging fibrosis); 4 (cirrhosis).
The Percentage of Participants Who Achieve a ≥ 1-Stage Improvement in Fibrosis Without Worsening of Nonalcoholic Steatohepatitis (NASH) at Week 24	From first dose to 24 weeks after first dose	An improvement in fibrosis is defined as a decrease of fibrosis by ≥1-stage in the NASH Clinical Research Network (CRN) Fibrosis Score at week 24 in liver biopsy. Worsening of NASH is defined as an increase of the nonalcoholic fatty liver disease activity score (NAS) by ≥ 1-stage. NASH CRN Fibrosis is staged on a 0-4 scale: 0 (none); 1 (perisinusoidal or periportal fibrosis); 2 (perisinusoidal and portal/periportal fibrosis); 3 (bridging fibrosis); 4 (cirrhosis).
The Percentage of Participants With Nonalcoholic Steatohepatitis (NASH) Improvement at Week 24	From first dose to 24 weeks after first dose	The percentage of participants with NASH improvement at week 24 in liver biopsy. NASH improvement is defined as a reduction of nonalcoholic fatty liver disease activity score (NAS) by ≥ 2 points with contribution from \> 1 NAS component. The NASH CRN system assesses liver biopsies for degree of steatosis (0-3), lobular inflammation (0-3), hepatocellular ballooning (0-2), and fibrosis (0-4). The 3 categories are added together in an unweighted fashion to determine the NAS, which ranges from 0 to 8.
The Percentage of Participants With Progression to Cirrhosis at Week 24	From first dose to 24 weeks after first dose	Progression to cirrhosis is defined by the nonalcoholic steatohepatitis clinical research network (NASH CRN) Fibrosis Stage 4 at Week 24 in liver biopsy. NASH CRN Fibrosis is staged on a 0-4 scale: 0 (none); 1 (perisinusoidal or periportal fibrosis); 2 (perisinusoidal and portal/periportal fibrosis); 3 (bridging fibrosis); 4 (cirrhosis).

Trial Locations

Locations (89)

Local Institution - 0101; 🇺🇸 San Antonio, Texas, United States

Local Institution - 0079; 🇺🇸 Coral Gables, Florida, United States

Saint Lukes Hospital of Kansas City; 🇺🇸 Kansas City, Missouri, United States

Local Institution - 0066; 🇺🇸 Austin, Texas, United States

Tandem Clinical Research; 🇺🇸 Marrero, Louisiana, United States

Sensible Healthcare; 🇺🇸 Ocoee, Florida, United States

Local Institution - 0088; 🇺🇸 Phoenix, Arizona, United States

Tampa General Hospital; 🇺🇸 Tampa, Florida, United States

MedStar Georgetown University Hospital; 🇺🇸 Washington, District of Columbia, United States

Tulane University Health Sciences Center; 🇺🇸 New Orleans, Louisiana, United States

Inova Fairfax Hospital; 🇺🇸 Falls Church, Virginia, United States

Saint Louis University; 🇺🇸 Saint Louis, Missouri, United States

Texas Digestive Disease Consultants - Southlake; 🇺🇸 Fort Worth, Texas, United States

Local Institution - 0038; 🇺🇸 New York, New York, United States

Local Institution - 0027; 🇺🇸 New Orleans, Louisiana, United States

Local Institution - 0083; 🇺🇸 New York, New York, United States

Clinical Research of Homestead; 🇺🇸 Homestead, Florida, United States

Fukushima Medical University Hospital; 🇯🇵 Fukushima, Japan

Local Institution - 0077; 🇺🇸 Richmond, Virginia, United States

Local Institution - 0029; 🇺🇸 San Antonio, Texas, United States

Local Institution - 0049; 🇺🇸 Richmond, Virginia, United States

Local Institution - 0003; 🇺🇸 Lakewood Ranch, Florida, United States

The Gastroenterology Group; 🇺🇸 Reston, Virginia, United States

Local Institution - 0068; 🇺🇸 San Francisco, California, United States

University of Michigan; 🇺🇸 Ann Arbor, Michigan, United States

Local Institution - 0100; 🇺🇸 Gainesville, Florida, United States

Local Institution - 0082; 🇺🇸 Jacksonville, Florida, United States

Local Institution - 0012; 🇺🇸 San Antonio, Texas, United States

Kurume University Hospital; 🇯🇵 Kurume, Fukuoka, Japan

Local Institution - 0067; 🇺🇸 Butner, North Carolina, United States

Local Institution - 0047; 🇺🇸 Germantown, Tennessee, United States

Local Institution - 0041; 🇺🇸 Hermitage, Tennessee, United States

Gastroenterology Associates, PC; 🇺🇸 Manassas, Virginia, United States

Local Institution - 0069; 🇺🇸 Norfolk, Virginia, United States

Local Institution - 0057; 🇺🇸 Catonsville, Maryland, United States

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

Local Institution - 0002; 🇺🇸 Miami, Florida, United States

A+ Research; 🇺🇸 Miami, Florida, United States

Local Institution - 0105; 🇺🇸 Marietta, Georgia, United States

Local Institution - 0078; 🇺🇸 Manhasset, New York, United States

Local Institution - 0007; 🇺🇸 Baltimore, Maryland, United States

University of Texas Southwestern Medical Center; 🇺🇸 Dallas, Texas, United States

Local Institution - 0063; 🇺🇸 Chesterfield, Missouri, United States

Local Institution - 0009; 🇺🇸 Philadelphia, Pennsylvania, United States

University of Pennsylvania; 🇺🇸 Philadelphia, Pennsylvania, United States

Local Institution - 0006; 🇺🇸 Pittsburgh, Pennsylvania, United States

Texas Clinical Research Institute; 🇺🇸 Arlington, Texas, United States

University of Vermont Medical Center; 🇺🇸 Burlington, Vermont, United States

Local Institution - 0053; 🇺🇸 Dallas, Texas, United States

Local Institution - 0004; 🇺🇸 Houston, Texas, United States

Local Institution - 0052; 🇺🇸 Dallas, Texas, United States

Local Institution - 0059; 🇺🇸 Houston, Texas, United States

Boston Medical Center; 🇺🇸 Boston, Massachusetts, United States

Icahn School of Medicine at Mount Sinai; 🇺🇸 New York, New York, United States

Toranomon Hospital; 🇯🇵 Minato, Tokyo, Japan

Local Institution - 0056; 🇯🇵 Yokohama, Kanagawa, Japan

Local Institution - 0087; 🇺🇸 Madison, Alabama, United States

Local Institution - 0005; 🇺🇸 Chandler, Arizona, United States

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

Local Institution - 0001; 🇺🇸 Phoenix, Arizona, United States

Local Institution - 0092; 🇺🇸 Coronado, California, United States

University of California San Diego; 🇺🇸 La Jolla, California, United States

Kindred Medical Institute for Clinical Trials; 🇺🇸 Corona, California, United States

Cedars-Sinai Medical Center; 🇺🇸 Los Angeles, California, United States

Catalina Research Institute; 🇺🇸 Montclair, California, United States

Local Institution - 0044; 🇺🇸 Oxnard, California, United States

Local Institution - 0019; 🇺🇸 Pasadena, California, United States

Local Institution - 0074; 🇺🇸 Redwood City, California, United States

Local Institution - 0013; 🇺🇸 Rialto, California, United States

Local Institution - 0089; 🇺🇸 San Clemente, California, United States

Bridgeport Hospital; 🇺🇸 Bridgeport, Connecticut, United States

IMIC Research; 🇺🇸 Miami, Florida, United States

Top Medical Research; 🇺🇸 Cutler Bay, Florida, United States

Local Institution - 0081; 🇺🇸 Orlando, Florida, United States

NECCR PrimaCare Research; 🇺🇸 Fall River, Massachusetts, United States

University at Buffalo; 🇺🇸 Buffalo, New York, United States

Local Institution - 0064; 🇺🇸 Charlotte, North Carolina, United States

Local Institution - 0096; 🇺🇸 Concord, North Carolina, United States

Texas Digestive Disease Consultants - Dallas; 🇺🇸 Dallas, Texas, United States

Local Institution - 0062; 🇺🇸 Houston, Texas, United States

Bon Secours Liver Institute of Richmond; 🇺🇸 Richmond, Virginia, United States

Local Institution - 0072; 🇯🇵 Kashihara, Nara, Japan

Keio University Hospital; 🇯🇵 Shinjuku-ku, Tokyo, Japan

Local Institution - 0017; 🇺🇸 Los Angeles, California, United States

Huntington Medical Research Institutes - HMRI Liver Center; 🇺🇸 Pasadena, California, United States

Medical Associates Research Group; 🇺🇸 San Diego, California, United States

Local Institution - 0008; 🇺🇸 Oakland, California, United States

University of Virginia Health System; 🇺🇸 Charlottesville, Virginia, United States

Vanderbilt University Medical Center; 🇺🇸 Nashville, Tennessee, United States