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

Liver Fibrosis Clinical Trial

— FALCON 2  

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 Compensated Liver Cirrhosis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03486912
• Other study ID #: MB130-069
• Status: Completed
• Phase: Phase 2
• Start date: June 12, 2018
• Est. completion date: September 14, 2021

Study information

• Verified date: October 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 liver cirrhosis (liver damage characterized by normal liver tissue being replaced by scar tissue).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 155
• Est. completion date: September 14, 2021
• Est. primary completion date: October 8, 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 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, 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
• 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

Related Conditions & MeSH terms

• Fatty Liver
• Fibrosis
• Hepatic Cirrhosis
• 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 - 0055	Yokohama	Kanagawa
United States	University of Michigan	Ann Arbor	Michigan
United States	Texas Clinical Research Institute	Arlington	Texas
United States	Local Institution	Atlanta	Georgia
United States	Local Institution - 0066	Austin	Texas
United States	Local Institution - 0010	Baltimore	Maryland
United States	Boston Medical Center	Boston	Massachusetts
United States	Local Institution - 0042	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 - 0058	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	Chattanooga	Tennessee
United States	Clinical Research Professionals	Chesterfield	Missouri
United States	Northeast GI Research Division	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 - 0051	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	Local Institution - 0084	Fort Worth	Texas
United States	Local Institution - 0046	Germantown	Tennessee
United States	Local Institution - 0041	Hermitage	Tennessee
United States	Clinical Research of Homestead	Homestead	Florida
United States	Local Institution - 0002	Houston	Texas
United States	Local Institution - 0057	Houston	Texas
United States	Local Institution - 0063	Houston	Texas
United States	Mayo Clinic - Jacksonville	Jacksonville	Florida
United States	Local Institution - 0031	Kansas City	Missouri
United States	Local Institution - 0038	La Jolla	California
United States	Local Institution - 0001	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	North Alabama Health Research, LLC	Madison	Alabama
United States	Gastroenterology Associates, PC	Manassas	Virginia
United States	Northwell Health	Manhasset	New York
United States	Local Institution - 0108	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 - 0003	Miami	Florida
United States	Catalina Research Institute	Montclair	California
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	Local Institution - 0026	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 - 0036	New York	New York
United States	Mount Sinai Hospital	New York	New York
United States	Local Institution - 0069	Norfolk	Virginia
United States	Kaiser Permanente	Oakland	California
United States	Sensible Healthcare	Ocoee	Florida
United States	Local Institution - 0081	Orlando	Florida
United States	Diverse Research Solutions	Oxnard	California
United States	Huntington Medical Research Institutes - HMRI Liver Center	Pasadena	California
United States	Local Institution - 0020	Pasadena	California
United States	Local Institution - 0009	Philadelphia	Pennsylvania
United States	University of Pennsylvania	Philadelphia	Pennsylvania
United States	Local Institution - 0006	Phoenix	Arizona
United States	Local Institution - 0088	Phoenix	Arizona
United States	Local Institution - 0004	Pittsburgh	Pennsylvania
United States	Local Institution - 0073	Redwood City	California
United States	The Gastroenterology Group	Reston	Virginia
United States	Local Institution - 0012	Rialto	California
United States	Bon Secours Liver Institute of Richmond	Richmond	Virginia
United States	Local Institution - 0050	Richmond	Virginia
United States	Local Institution - 0077	Richmond	Virginia
United States	Saint Louis University	Saint Louis	Missouri
United States	Local Institution - 0011	San Antonio	Texas
United States	Local Institution - 0028	San Antonio	Texas
United States	Local Institution - 0102	San Antonio	Texas
United States	Local Institution - 0089	San Clemente	California
United States	Local Institution	San Diego	California
United States	Local Institution - 0014	San Diego	California
United States	Local Institution - 0068	San Francisco	California
United States	Local Institution	Tampa	Florida
United States	Local Institution - 0090	Tucson	Arizona
United States	Local Institution	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 Who Achieve a = 1-Stage Improvement in Fibrosis Without Worsening of Nonalcoholic Steatohepatitis (NASH) at Week 48	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.	From first dose to 48 weeks after first dose
Secondary	The Percentage of Participants Who Achieve a = 1-Stage Improvement in Ishak Fibrosis Score at Week 48	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.	From first dose to 48 weeks after first dose
Secondary	The Percentage of Participants With Improvement in Fibrosis Without Worsening of Nonalcoholic Steatohepatitis (NASH) or NASH Improvement at Week 48	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).	From first dose to 48 weeks after first dose
Secondary	The Percentage of Participants Who Achieved >=1 Point Improvement in Fibrosis at Week 48	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).	From first dose to 48 weeks after first dose
Secondary	The Percentage of Participants With Any Improvement in Collagen Proportionate Area (CPA) at Week 48	An improvement in CPA is defined as any decrease in CPA at week 48 in liver biopsy.	From first dose to 48 weeks after first dose
Secondary	The Percentage of Participants With Nonalcoholic Steatohepatitis (NASH) Resolution at Week 48	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).	From first dose to 48 weeks after first dose
Secondary	The Percentage of Participants With Nonalcoholic Steatohepatitis (NASH) Improvement at Week 48	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.	From first dose to 48 weeks after first dose

External Links

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