A Study of Experimental Medication BMS-986036 in Adults With Nonalcoholic Steatohepatitis (NASH) and Liver Cirrhosis
- Conditions
- Hepatic CirrhosisLiver FibrosisNonalcoholic SteatohepatitisNonalcoholic Fatty Liver Disease (NAFLD)
- Interventions
- Drug: BMS-986036Other: Placebo
- Registration Number
- NCT03486912
- 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 liver cirrhosis (liver damage characterized by normal liver tissue being replaced by scar tissue).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 155
- 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 and cirrhosis according to the NASH CRN classification, as assessed by the central reader
- Must be 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
- Other causes of liver disease (e.g., alcoholic liver disease, hepatitis B virus infection, chronic hepatitis C virus infection [HCV], 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
- Medical history of gastroesophageal varices, except if esophagogastroduodenoscopy [EGD] performed within 12 months prior to the Screening Period has shown <= Grade 1 varices
Other protocol-defined inclusion/exclusion criteria apply
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description BMS-986036 Dose Level 3 BMS-986036 - Placebo Placebo - BMS-986036 Dose Level 2 BMS-986036 - BMS-986036 Dose Level 1 BMS-986036 -
- Primary Outcome Measures
Name Time Method The Percentage of Participants Who Achieve a ≥ 1-Stage Improvement in Fibrosis Without Worsening of Nonalcoholic Steatohepatitis (NASH) at Week 48 From first dose to 48 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 48 in liver biopsy. Worsening of NASH is defined as an increase of the nonalcoholic fatty liver disease activity score (NAS) by ≥ 1-stage.
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.
- Secondary Outcome Measures
Name Time Method The Percentage of Participants Who Achieve a ≥ 1-Stage Improvement in Ishak Fibrosis Score at Week 48 From first dose to 48 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 48 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 Improvement in Fibrosis Without Worsening of Nonalcoholic Steatohepatitis (NASH) or NASH Improvement at Week 48 From first dose to 48 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 48 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). 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 Achieved >=1 Point Improvement in Fibrosis at Week 48 From first dose to 48 weeks after first dose An improvement in fibrosis is defined as a decrease of ≥ 1-stage in the non-alcoholic steatohepatitis clinical research network (NASH CRN) Fibrosis Score at week 48 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 With Any Improvement in Collagen Proportionate Area (CPA) at Week 48 From first dose to 48 weeks after first dose An improvement in CPA is defined as any decrease in CPA at week 48 in liver biopsy.
The Percentage of Participants With Nonalcoholic Steatohepatitis (NASH) Resolution at Week 48 From first dose to 48 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 48 in liver biopsy. Ballooning = 0 (none) inflammation = 0 (none) - 1 (Grade \<2).
The Percentage of Participants With Nonalcoholic Steatohepatitis (NASH) Improvement at Week 48 From first dose to 48 weeks after first dose The percentage of participants with NASH improvement at week 48 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.
Trial Locations
- Locations (87)
Local Institution - 0009
🇺🇸Philadelphia, Pennsylvania, United States
University of Texas Southwestern Medical Center
🇺🇸Dallas, Texas, United States
Local Institution - 0017
🇺🇸Los Angeles, California, United States
Local Institution - 0010
🇺🇸Baltimore, Maryland, United States
Local Institution - 0003
🇺🇸Miami, Florida, United States
Local Institution - 0002
🇺🇸Houston, Texas, United States
Local Institution - 0014
🇺🇸San Diego, California, United States
Local Institution - 0028
🇺🇸San Antonio, Texas, United States
Local Institution - 0068
🇺🇸San Francisco, California, United States
Vanderbilt University Medical Center
🇺🇸Nashville, Tennessee, United States
Clinical Research Professionals
🇺🇸Chesterfield, Missouri, United States
North Alabama Health Research, LLC
🇺🇸Madison, Alabama, United States
Local Institution - 0005
🇺🇸Chandler, Arizona, United States
Local Institution - 0092
🇺🇸Coronado, California, United States
Catalina Research Institute
🇺🇸Montclair, California, United States
Diverse Research Solutions
🇺🇸Oxnard, California, United States
Huntington Medical Research Institutes - HMRI Liver Center
🇺🇸Pasadena, California, United States
Local Institution - 0089
🇺🇸San Clemente, California, United States
Local Institution - 0020
🇺🇸Pasadena, California, United States
Local Institution - 0079
🇺🇸Coral Gables, Florida, United States
Local Institution - 0001
🇺🇸Lakewood Ranch, Florida, United States
Mayo Clinic - Jacksonville
🇺🇸Jacksonville, Florida, United States
Local Institution - 0108
🇺🇸Marietta, Georgia, United States
IMIC Research
🇺🇸Miami, Florida, United States
Tandem Clinical Research
🇺🇸Marrero, Louisiana, United States
Sensible Healthcare
🇺🇸Ocoee, Florida, United States
NECCR PrimaCare Research
🇺🇸Fall River, Massachusetts, United States
Icahn School of Medicine at Mount Sinai
🇺🇸New York, New York, United States
Saint Louis University
🇺🇸Saint Louis, Missouri, United States
Local Institution - 0064
🇺🇸Charlotte, North Carolina, United States
Local Institution - 0067
🇺🇸Butner, North Carolina, United States
Northeast GI Research Division
🇺🇸Concord, North Carolina, United States
University of Pennsylvania
🇺🇸Philadelphia, Pennsylvania, United States
Local Institution - 0004
🇺🇸Pittsburgh, Pennsylvania, United States
Texas Clinical Research Institute
🇺🇸Arlington, Texas, United States
Texas Digestive Disease Consultants - Dallas
🇺🇸Dallas, Texas, United States
Local Institution - 0084
🇺🇸Fort Worth, Texas, United States
Local Institution - 0057
🇺🇸Houston, Texas, United States
Local Institution - 0063
🇺🇸Houston, Texas, United States
Local Institution - 0102
🇺🇸San Antonio, Texas, United States
Local Institution - 0011
🇺🇸San Antonio, Texas, United States
Gastroenterology Associates, PC
🇺🇸Manassas, Virginia, United States
The Gastroenterology Group
🇺🇸Reston, Virginia, United States
Local Institution - 0069
🇺🇸Norfolk, Virginia, United States
Local Institution - 0055
🇯🇵Yokohama, Kanagawa, Japan
Local Institution - 0072
🇯🇵Kashihara, Nara, Japan
Fukushima Medical University Hospital
🇯🇵Fukushima, Japan
Local Institution - 0046
🇺🇸Germantown, Tennessee, United States
Local Institution - 0090
🇺🇸Tucson, Arizona, United States
Top Medical Research
🇺🇸Cutler Bay, Florida, United States
Local Institution - 0088
🇺🇸Phoenix, Arizona, United States
Local Institution - 0006
🇺🇸Phoenix, Arizona, United States
Local Institution - 0081
🇺🇸Orlando, Florida, United States
Local Institution - 0031
🇺🇸Kansas City, Missouri, United States
Local Institution - 0066
🇺🇸Austin, Texas, United States
Local Institution - 0077
🇺🇸Richmond, Virginia, United States
Local Institution - 0050
🇺🇸Richmond, Virginia, United States
Cedars-Sinai Medical Center
🇺🇸Los Angeles, California, United States
Kindred Medical Institute for Clinical Trials
🇺🇸Corona, California, United States
GastroIntestinal Biosciences
🇺🇸Los Angeles, California, United States
Kaiser Permanente
🇺🇸Oakland, California, United States
Local Institution - 0012
🇺🇸Rialto, California, United States
Local Institution
🇺🇸Chattanooga, Tennessee, United States
Local Institution - 0042
🇺🇸Bridgeport, Connecticut, United States
Clinical Research of Homestead
🇺🇸Homestead, Florida, United States
Local Institution - 0058
🇺🇸Catonsville, Maryland, United States
Boston Medical Center
🇺🇸Boston, Massachusetts, United States
University at Buffalo
🇺🇸Buffalo, New York, United States
Mount Sinai Hospital
🇺🇸New York, New York, United States
Local Institution - 0036
🇺🇸New York, New York, United States
Local Institution - 0041
🇺🇸Hermitage, Tennessee, United States
Local Institution - 0051
🇺🇸Dallas, Texas, United States
Local Institution - 0053
🇺🇸Dallas, Texas, United States
Inova Fairfax Hospital
🇺🇸Falls Church, Virginia, United States
University of Virginia Health System
🇺🇸Charlottesville, Virginia, United States
Kurume University Hospital
🇯🇵Kurume, Fukuoka, Japan
Local Institution - 0038
🇺🇸La Jolla, California, United States
Local Institution - 0073
🇺🇸Redwood City, California, United States
A+ Research
🇺🇸Miami, Florida, United States
Northwell Health
🇺🇸Manhasset, New York, United States
University of Vermont Medical Center
🇺🇸Burlington, Vermont, United States
Keio University Hospital
🇯🇵Shinjuku-ku, Tokyo, Japan
Toranomon Hospital
🇯🇵Minato, Tokyo, Japan
Tulane University Health Sciences Center
🇺🇸New Orleans, Louisiana, United States
Local Institution - 0026
🇺🇸New Orleans, Louisiana, United States
University of Michigan
🇺🇸Ann Arbor, Michigan, United States
Bon Secours Liver Institute of Richmond
🇺🇸Richmond, Virginia, United States