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

Liver Fibrosis Clinical Trial

— FALCON 1  

Official title:

A Phase 2B Randomized Double-Blind, Placebo-Controlled Study Evaluating the Safety and Efficacy of BMS-986036 (PEG-FGF21) in Adults With Nonalcoholic Steatohepatitis (NASH) and Stage 3 Liver Fibrosis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03486899
• Other study ID #: MB130-068
• Status: Completed
• Phase: Phase 2
• Start date: June 19, 2018
• Est. completion date: August 17, 2021

Study information

• Verified date: August 2022
• Source: Bristol-Myers Squibb
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 197
• Est. completion date: August 17, 2021
• Est. primary completion date: September 14, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

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, a-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

Related Conditions & MeSH terms

• Fatty Liver
• Fibrosis
• Liver Cirrhosis
• Liver Diseases
• Liver Fibrosis
• Non-alcoholic Fatty Liver Disease
• Nonalcoholic Fatty Liver Disease (NAFLD)
• Nonalcoholic Steatohepatitis

Intervention

Drug:
• BMS-986036
Specified dose on specified days.

Other:
• Placebo
Specified dose on specified days.

Locations

Country	Name	City	State
Japan	Fukushima Medical University Hospital	Fukushima
Japan	Local Institution - 0072	Kashihara	Nara
Japan	Kurume University Hospital	Kurume	Fukuoka
Japan	Toranomon Hospital	Minato	Tokyo
Japan	Keio University Hospital	Shinjuku-ku	Tokyo
Japan	Local Institution - 0056	Yokohama	Kanagawa
United States	University of Michigan	Ann Arbor	Michigan
United States	Texas Clinical Research Institute	Arlington	Texas
United States	Local Institution - 0066	Austin	Texas
United States	Local Institution - 0007	Baltimore	Maryland
United States	Boston Medical Center	Boston	Massachusetts
United States	Bridgeport Hospital	Bridgeport	Connecticut
United States	University at Buffalo	Buffalo	New York
United States	University of Vermont Medical Center	Burlington	Vermont
United States	Local Institution - 0067	Butner	North Carolina
United States	Local Institution - 0057	Catonsville	Maryland
United States	Local Institution - 0005	Chandler	Arizona
United States	Local Institution - 0064	Charlotte	North Carolina
United States	University of Virginia Health System	Charlottesville	Virginia
United States	Local Institution - 0063	Chesterfield	Missouri
United States	Local Institution - 0096	Concord	North Carolina
United States	Local Institution - 0079	Coral Gables	Florida
United States	Kindred Medical Institute for Clinical Trials	Corona	California
United States	Local Institution - 0092	Coronado	California
United States	Top Medical Research	Cutler Bay	Florida
United States	Local Institution - 0052	Dallas	Texas
United States	Local Institution - 0053	Dallas	Texas
United States	Texas Digestive Disease Consultants - Dallas	Dallas	Texas
United States	University of Texas Southwestern Medical Center	Dallas	Texas
United States	NECCR PrimaCare Research	Fall River	Massachusetts
United States	Inova Fairfax Hospital	Falls Church	Virginia
United States	Texas Digestive Disease Consultants - Southlake	Fort Worth	Texas
United States	Local Institution - 0100	Gainesville	Florida
United States	Local Institution - 0047	Germantown	Tennessee
United States	Local Institution - 0041	Hermitage	Tennessee
United States	Clinical Research of Homestead	Homestead	Florida
United States	Local Institution - 0004	Houston	Texas
United States	Local Institution - 0059	Houston	Texas
United States	Local Institution - 0062	Houston	Texas
United States	Local Institution - 0082	Jacksonville	Florida
United States	Saint Lukes Hospital of Kansas City	Kansas City	Missouri
United States	University of California San Diego	La Jolla	California
United States	Local Institution - 0003	Lakewood Ranch	Florida
United States	Cedars-Sinai Medical Center	Los Angeles	California
United States	GastroIntestinal Biosciences	Los Angeles	California
United States	Local Institution - 0017	Los Angeles	California
United States	Local Institution - 0087	Madison	Alabama
United States	Gastroenterology Associates, PC	Manassas	Virginia
United States	Local Institution - 0078	Manhasset	New York
United States	Local Institution - 0105	Marietta	Georgia
United States	Tandem Clinical Research	Marrero	Louisiana
United States	A+ Research	Miami	Florida
United States	IMIC Research	Miami	Florida
United States	Local Institution - 0002	Miami	Florida
United States	Catalina Research Institute	Montclair	California
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	Local Institution - 0027	New Orleans	Louisiana
United States	Tulane University Health Sciences Center	New Orleans	Louisiana
United States	Icahn School of Medicine at Mount Sinai	New York	New York
United States	Local Institution - 0038	New York	New York
United States	Local Institution - 0083	New York	New York
United States	Local Institution - 0069	Norfolk	Virginia
United States	Local Institution - 0008	Oakland	California
United States	Sensible Healthcare	Ocoee	Florida
United States	Local Institution - 0081	Orlando	Florida
United States	Local Institution - 0044	Oxnard	California
United States	Huntington Medical Research Institutes - HMRI Liver Center	Pasadena	California
United States	Local Institution - 0019	Pasadena	California
United States	Local Institution - 0009	Philadelphia	Pennsylvania
United States	University of Pennsylvania	Philadelphia	Pennsylvania
United States	Local Institution - 0001	Phoenix	Arizona
United States	Local Institution - 0088	Phoenix	Arizona
United States	Local Institution - 0006	Pittsburgh	Pennsylvania
United States	Local Institution - 0074	Redwood City	California
United States	The Gastroenterology Group	Reston	Virginia
United States	Local Institution - 0013	Rialto	California
United States	Bon Secours Liver Institute of Richmond	Richmond	Virginia
United States	Local Institution - 0049	Richmond	Virginia
United States	Local Institution - 0077	Richmond	Virginia
United States	Saint Louis University	Saint Louis	Missouri
United States	Local Institution - 0012	San Antonio	Texas
United States	Local Institution - 0029	San Antonio	Texas
United States	Local Institution - 0101	San Antonio	Texas
United States	Local Institution - 0089	San Clemente	California
United States	Medical Associates Research Group	San Diego	California
United States	Local Institution - 0068	San Francisco	California
United States	Tampa General Hospital	Tampa	Florida
United States	The Institute for Liver Health - Tucson	Tucson	Arizona
United States	MedStar Georgetown University Hospital	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Bristol-Myers Squibb

Countries where clinical trial is conducted

United States,  Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The Percentage of Participants With Improvement in Fibrosis or Nonalcoholic Steatohepatitis (NASH) at Week 24	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).	From first dose to 24 weeks after first dose
Secondary	The Percentage of Participants Who Achieved an Improvement in Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN) Fibrosis Score at Week 24	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).	From first dose to 24 weeks after first dose
Secondary	The Percentage of Participants Who Achieve a = 1-Stage Improvement in Ishak Fibrosis Score at Week 24	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.	From first dose to 24 weeks after first dose
Secondary	The Percentage of Participants With Any Improvement in Collagen Proportionate Area (CPA) at Week 24	An improvement in CPA is defined as any decrease in CPA at week 24 in liver biopsy.	From first dose to 24 weeks after first dose
Secondary	The Percentage of Participants With Nonalcoholic Steatohepatitis (NASH) Resolution Without Worsening of Fibrosis at Week 24	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).	From first dose to 24 weeks after first dose
Secondary	The Percentage of Participants With Nonalcoholic Steatohepatitis (NASH) Resolution at Week 24	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).	From first dose to 24 weeks after first dose
Secondary	The Percentage of Participants With Nonalcoholic Steatohepatitis (NASH) Improvement Without Worsening of Fibrosis at Week 24	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).	From first dose to 24 weeks after first dose
Secondary	The Percentage of Participants Who Achieve a = 1-Stage Improvement in Fibrosis Without Worsening of Nonalcoholic Steatohepatitis (NASH) at Week 24	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).	From first dose to 24 weeks after first dose
Secondary	The Percentage of Participants With Nonalcoholic Steatohepatitis (NASH) Improvement at Week 24	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.	From first dose to 24 weeks after first dose
Secondary	The Percentage of Participants With Progression to Cirrhosis at Week 24	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).	From first dose to 24 weeks after first dose

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