Clinical trial NCT03486899: A Study of Experimental Medication BMS-986036 in Adults With Nonalcoholic Steatohepatitis (NASH) and Stage 3 Liver Fibrosis
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Liver Fibrosis
Nonalcoholic Fatty Liver Disease (NAFLD)
Nonalcoholic Steatohepatitis
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
First posted: 2018-04-03
Enrollment: 197
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


Eligibility criteria: 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, 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

Primary outcomes:
measure: The Percentage of Participants With Improvement in Fibrosis or Nonalcoholic Steatohepatitis (NASH) at Week 24
timeFrame: From first dose to 24 weeks after first dose
Secondary outcomes:
measure: The Percentage of Participants Who Achieved an Improvement in Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN) Fibrosis Score at Week 24
timeFrame: From first dose to 24 weeks after first dose
measure: The Percentage of Participants Who Achieve a ≥ 1-Stage Improvement in Ishak Fibrosis Score at Week 24
timeFrame: From first dose to 24 weeks after first dose
measure: The Percentage of Participants With Any Improvement in Collagen Proportionate Area (CPA) at Week 24
timeFrame: From first dose to 24 weeks after first dose
measure: The Percentage of Participants With Nonalcoholic Steatohepatitis (NASH) Resolution Without Worsening of Fibrosis at Week 24
timeFrame: From first dose to 24 weeks after first dose
measure: The Percentage of Participants With Nonalcoholic Steatohepatitis (NASH) Resolution at Week 24
timeFrame: From first dose to 24 weeks after first dose
measure: The Percentage of Participants With Nonalcoholic Steatohepatitis (NASH) Improvement Without Worsening of Fibrosis at Week 24
timeFrame: From first dose to 24 weeks after first dose
measure: The Percentage of Participants Who Achieve a ≥ 1-Stage Improvement in Fibrosis Without Worsening of Nonalcoholic Steatohepatitis (NASH) at Week 24
timeFrame: From first dose to 24 weeks after first dose
measure: The Percentage of Participants With Nonalcoholic Steatohepatitis (NASH) Improvement at Week 24
timeFrame: From first dose to 24 weeks after first dose
measure: The Percentage of Participants With Progression to Cirrhosis at Week 24
timeFrame: From first dose to 24 weeks after first dose
Other outcomes:
Locations:
city: Madison
country: United States
facility: Local Institution - 0087
state: Alabama
city: Chandler
country: United States
facility: Local Institution - 0005
state: Arizona
city: Phoenix
country: United States
facility: Local Institution - 0088
state: Arizona
city: Phoenix
country: United States
facility: Local Institution - 0001
state: Arizona
city: Tucson
country: United States
facility: The Institute for Liver Health - Tucson
state: Arizona
city: Coronado
country: United States
facility: Local Institution - 0092
state: California
city: Corona
country: United States
facility: Kindred Medical Institute for Clinical Trials
state: California
city: La Jolla
country: United States
facility: University of California San Diego
state: California
city: Los Angeles
country: United States
facility: Local Institution - 0017
state: California
city: Los Angeles
country: United States
facility: Cedars-Sinai Medical Center
state: California
city: Los Angeles
country: United States
facility: GastroIntestinal Biosciences
state: California
city: Montclair
country: United States
facility: Catalina Research Institute
state: California
city: Oakland
country: United States
facility: Local Institution - 0008
state: California
city: Oxnard
country: United States
facility: Local Institution - 0044
state: California
city: Pasadena
country: United States
facility: Huntington Medical Research Institutes - HMRI Liver Center
state: California
city: Pasadena
country: United States
facility: Local Institution - 0019
state: California
city: Redwood City
country: United States
facility: Local Institution - 0074
state: California
city: Rialto
country: United States
facility: Local Institution - 0013
state: California
city: San Clemente
country: United States
facility: Local Institution - 0089
state: California
city: San Diego
country: United States
facility: Medical Associates Research Group
state: California
city: San Francisco
country: United States
facility: Local Institution - 0068
state: California
city: Bridgeport
country: United States
facility: Bridgeport Hospital
state: Connecticut
city: Washington
country: United States
facility: MedStar Georgetown University Hospital
state: District of Columbia
city: Coral Gables
country: United States
facility: Local Institution - 0079
state: Florida
city: Cutler Bay
country: United States
facility: Top Medical Research
state: Florida
city: Gainesville
country: United States
facility: Local Institution - 0100
state: Florida
city: Homestead
country: United States
facility: Clinical Research of Homestead
state: Florida
city: Jacksonville
country: United States
facility: Local Institution - 0082
state: Florida
city: Lakewood Ranch
country: United States
facility: Local Institution - 0003
state: Florida
city: Miami
country: United States
facility: Local Institution - 0002
state: Florida
city: Miami
country: United States
facility: A+ Research
state: Florida
city: Miami
country: United States
facility: IMIC Research
state: Florida
city: Ocoee
country: United States
facility: Sensible Healthcare
state: Florida
city: Orlando
country: United States
facility: Local Institution - 0081
state: Florida
city: Tampa
country: United States
facility: Tampa General Hospital
state: Florida
city: Marietta
country: United States
facility: Local Institution - 0105
state: Georgia
city: Marrero
country: United States
facility: Tandem Clinical Research
state: Louisiana
city: New Orleans
country: United States
facility: Tulane University Health Sciences Center
state: Louisiana
city: New Orleans
country: United States
facility: Local Institution - 0027
state: Louisiana
city: Baltimore
country: United States
facility: Local Institution - 0007
state: Maryland
city: Catonsville
country: United States
facility: Local Institution - 0057
state: Maryland
city: Boston
country: United States
facility: Boston Medical Center
state: Massachusetts
city: Fall River
country: United States
facility: NECCR PrimaCare Research
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Chesterfield
country: United States
facility: Local Institution - 0063
state: Missouri
city: Kansas City
country: United States
facility: Saint Lukes Hospital of Kansas City
state: Missouri
city: Saint Louis
country: United States
facility: Saint Louis University
state: Missouri
city: Buffalo
country: United States
facility: University at Buffalo
state: New York
city: Manhasset
country: United States
facility: Local Institution - 0078
state: New York
city: New York
country: United States
facility: Local Institution - 0083
state: New York
city: New York
country: United States
facility: Local Institution - 0038
state: New York
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai
state: New York
city: Butner
country: United States
facility: Local Institution - 0067
state: North Carolina
city: Charlotte
country: United States
facility: Local Institution - 0064
state: North Carolina
city: Concord
country: United States
facility: Local Institution - 0096
state: North Carolina
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Philadelphia
country: United States
facility: Local Institution - 0009
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Local Institution - 0006
state: Pennsylvania
city: Germantown
country: United States
facility: Local Institution - 0047
state: Tennessee
city: Hermitage
country: United States
facility: Local Institution - 0041
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Arlington
country: United States
facility: Texas Clinical Research Institute
state: Texas
city: Austin
country: United States
facility: Local Institution - 0066
state: Texas
city: Dallas
country: United States
facility: Local Institution - 0053
state: Texas
city: Dallas
country: United States
facility: Local Institution - 0052
state: Texas
city: Dallas
country: United States
facility: Texas Digestive Disease Consultants - Dallas
state: Texas
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
city: Fort Worth
country: United States
facility: Texas Digestive Disease Consultants - Southlake
state: Texas
city: Houston
country: United States
facility: Local Institution - 0004
state: Texas
city: Houston
country: United States
facility: Local Institution - 0059
state: Texas
city: Houston
country: United States
facility: Local Institution - 0062
state: Texas
city: San Antonio
country: United States
facility: Local Institution - 0029
state: Texas
city: San Antonio
country: United States
facility: Local Institution - 0012
state: Texas
city: San Antonio
country: United States
facility: Local Institution - 0101
state: Texas
city: Burlington
country: United States
facility: University of Vermont Medical Center
state: Vermont
city: Charlottesville
country: United States
facility: University of Virginia Health System
state: Virginia
city: Falls Church
country: United States
facility: Inova Fairfax Hospital
state: Virginia
city: Manassas
country: United States
facility: Gastroenterology Associates, PC
state: Virginia
city: Norfolk
country: United States
facility: Local Institution - 0069
state: Virginia
city: Reston
country: United States
facility: The Gastroenterology Group
state: Virginia
city: Richmond
country: United States
facility: Bon Secours Liver Institute of Richmond
state: Virginia
city: Richmond
country: United States
facility: Local Institution - 0077
state: Virginia
city: Richmond
country: United States
facility: Local Institution - 0049
state: Virginia
city: Kurume
country: Japan
facility: Kurume University Hospital
state: Fukuoka
city: Yokohama
country: Japan
facility: Local Institution - 0056
state: Kanagawa
city: Kashihara
country: Japan
facility: Local Institution - 0072
state: Nara
city: Minato
country: Japan
facility: Toranomon Hospital
state: Tokyo
city: Shinjuku-ku
country: Japan
facility: Keio University Hospital
state: Tokyo
city: Fukushima
country: Japan
facility: Fukushima Medical University Hospital
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References:
citation: Abdelmalek MF, Charles ED, Sanyal AJ, Harrison SA, Neuschwander-Tetri BA, Goodman Z, Ehman RA, Karsdal M, Nakajima A, Du S, Tirucherai GS, Klinger GH, Mora J, Yamaguchi M, Shevell DE, Loomba R. The FALCON program: Two phase 2b randomized, double-blind, placebo-controlled studies to assess the efficacy and safety of pegbelfermin in the treatment of patients with nonalcoholic steatohepatitis and bridging fibrosis or compensated cirrhosis. Contemp Clin Trials. 2021 May;104:106335. doi: 10.1016/j.cct.2021.106335. Epub 2021 Feb 28.