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

Phase 2

Completed

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

Study Timeline

• Study First Submitted: 2018-03-30
• Study First Submitted QC: 2018-03-30
• Study First Posted: 2018-04-03
• Study Start: 2018-06-12
• Primary Completion: 2020-10-08
• Disposition First Submitted: 2021-07-09
• Study Completion: 2021-09-14
• Results First Submitted: 2022-08-22
• Status Verified: 2022-10
• Results First Submitted QC: 2022-10-11
• Disposition First Submitted QC: 2022-10-11
• Last Update Submitted: 2022-10-11
• Results First Posted: 2022-10-13
• Disposition First Posted: 2022-10-13
• Last Update Posted: 2022-10-13

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 155

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 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

Exclusion Criteria

• 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)

North Alabama Health Research, LLC; 🇺🇸 Madison, Alabama, United States

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

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

Local Institution - 0006; 🇺🇸 Phoenix, Arizona, United States

Local Institution - 0090; 🇺🇸 Tucson, Arizona, United States

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

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

Local Institution - 0038; 🇺🇸 La Jolla, California, United States

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

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

Scroll for more (77 remaining)