A Study of Experimental Medication BMS-986036 in Adults With Nonalcoholic Steatohepatitis (NASH) and Stage 3 Liver Fibrosis (FALCON 1)

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

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).

Study Overview

• Status: Completed
• Conditions: Nonalcoholic Steatohepatitis; Liver Fibrosis; Nonalcoholic Fatty Liver Disease (NAFLD)
• Intervention / Treatment: Drug: BMS-986036; Other: Placebo

• Study Type: Interventional
• Enrollment (Actual): 197
• Phase: Phase 2

Contacts and Locations

Study Locations

• Japan
  • Fukushima, Japan, 960-1295
    • Fukushima Medical University Hospital
  • Fukuoka
    • Kurume, Fukuoka, Japan, 8300011
      • Kurume University Hospital
  • Kanagawa
    • Yokohama, Kanagawa, Japan, 236-0004
      • Local Institution - 0056
  • Nara
    • Kashihara, Nara, Japan, 6348522
      • Local Institution - 0072
  • Tokyo
    • Minato, Tokyo, Japan, 105-8470
      • Toranomon Hospital
    • Shinjuku-ku, Tokyo, Japan, 1600016
      • Keio University Hospital
• United States
  • Alabama
    • Madison, Alabama, United States, 35758
      • Local Institution - 0087
  • Arizona
    • Chandler, Arizona, United States, 85224
      • Local Institution - 0005
    • Phoenix, Arizona, United States, 85013
      • Local Institution - 0088
    • Phoenix, Arizona, United States, 85054
      • Local Institution - 0001
    • Tucson, Arizona, United States, 85712
      • The Institute for Liver Health - Tucson
  • California
    • Corona, California, United States, 92879
      • Kindred Medical Institute for Clinical Trials
    • Coronado, California, United States, 92118
      • Local Institution - 0092
    • La Jolla, California, United States, 92037
      • University of California San Diego
    • Los Angeles, California, United States, 90048
      • Cedars-Sinai Medical Center
    • Los Angeles, California, United States, 90036
      • Local Institution - 0017
    • Los Angeles, California, United States, 90067-2015
      • GastroIntestinal BioSciences
    • Montclair, California, United States, 91763
      • Catalina Research Institute
    • Oakland, California, United States, 94611
      • Local Institution - 0008
    • Oxnard, California, United States, 93030
      • Local Institution - 0044
    • Pasadena, California, United States, 91105
      • Huntington Medical Research Institutes - HMRI Liver Center
    • Pasadena, California, United States, 91105
      • Local Institution - 0019
    • Redwood City, California, United States, 94063
      • Local Institution - 0074
    • Rialto, California, United States, 92377
      • Local Institution - 0013
    • San Clemente, California, United States, 92673
      • Local Institution - 0089
    • San Diego, California, United States, 92123
      • Medical Associates Research Group
    • San Francisco, California, United States, 94115
      • Local Institution - 0068
  • Connecticut
    • Bridgeport, Connecticut, United States, 06610
      • Bridgeport Hospital
  • District of Columbia
    • Washington, District of Columbia, United States, 20007
      • MedStar Georgetown University Hospital
  • Florida
    • Coral Gables, Florida, United States, 33134
      • Local Institution - 0079
    • Cutler Bay, Florida, United States, 33189
      • Top Medical Research
    • Gainesville, Florida, United States, 32610
      • Local Institution - 0100
    • Homestead, Florida, United States, 33030
      • Clinical Research of Homestead
    • Jacksonville, Florida, United States, 32224
      • Local Institution - 0082
    • Lakewood Ranch, Florida, United States, 34211
      • Local Institution - 0003
    • Miami, Florida, United States, 33136
      • Local Institution - 0002
    • Miami, Florida, United States, 33144
      • A+ Research
    • Miami, Florida, United States, 33157
      • IMIC Research
    • Ocoee, Florida, United States, 34761
      • Sensible Healthcare
    • Orlando, Florida, United States, 32806
      • Local Institution - 0081
    • Tampa, Florida, United States, 33606
      • Tampa General Hospital
  • Georgia
    • Marietta, Georgia, United States, 30060
      • Local Institution - 0105
  • Louisiana
    • Marrero, Louisiana, United States, 70072
      • Tandem Clinical Research
    • New Orleans, Louisiana, United States, 70112
      • Tulane University Health Sciences Center
    • New Orleans, Louisiana, United States, 70121
      • Local Institution - 0027
  • Maryland
    • Baltimore, Maryland, United States, 21202
      • Local Institution - 0007
    • Catonsville, Maryland, United States, 21228
      • Local Institution - 0057
  • Massachusetts
    • Boston, Massachusetts, United States, 02118
      • Boston Medical Center
    • Fall River, Massachusetts, United States, 02721
      • NECCR PrimaCare Research
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan
  • Missouri
    • Chesterfield, Missouri, United States, 63005
      • Local Institution - 0063
    • Kansas City, Missouri, United States, 64111
      • Saint Lukes Hospital of Kansas City
    • Saint Louis, Missouri, United States, 63110
      • Saint Louis University
  • New York
    • Buffalo, New York, United States, 14203
      • University at Buffalo
    • Manhasset, New York, United States, 11030
      • Local Institution - 0078
    • New York, New York, United States, 10029
      • Icahn School of Medicine at Mount Sinai
    • New York, New York, United States, 10003
      • Local Institution - 0083
    • New York, New York, United States, 10016
      • Local Institution - 0038
  • North Carolina
    • Butner, North Carolina, United States, 27509-1626
      • Local Institution - 0067
    • Charlotte, North Carolina, United States, 28204
      • Local Institution - 0064
    • Concord, North Carolina, United States, 28027
      • Local Institution - 0096
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Local Institution - 0009
    • Pittsburgh, Pennsylvania, United States, 15213
      • Local Institution - 0006
  • Tennessee
    • Germantown, Tennessee, United States, 38138
      • Local Institution - 0047
    • Hermitage, Tennessee, United States, 37076
      • Local Institution - 0041
    • Nashville, Tennessee, United States, 37232-5280
      • Vanderbilt University Medical Center
  • Texas
    • Arlington, Texas, United States, 76012
      • Texas Clinical Research Institute
    • Austin, Texas, United States, 78757
      • Local Institution - 0066
    • Dallas, Texas, United States, 75390-88520
      • University of Texas Southwestern Medical Center
    • Dallas, Texas, United States, 75203
      • Local Institution - 0053
    • Dallas, Texas, United States, 75234
      • Local Institution - 0052
    • Dallas, Texas, United States, 75246
      • Texas Digestive Disease Consultants - Dallas
    • Fort Worth, Texas, United States, 76104
      • Texas Digestive Disease Consultants - Southlake
    • Houston, Texas, United States, 77002
      • Local Institution - 0004
    • Houston, Texas, United States, 77030
      • Local Institution - 0059
    • Houston, Texas, United States, 77030
      • Local Institution - 0062
    • San Antonio, Texas, United States, 78215
      • Local Institution - 0029
    • San Antonio, Texas, United States, 78229
      • Local Institution - 0012
    • San Antonio, Texas, United States, 78229
      • Local Institution - 0101
  • Vermont
    • Burlington, Vermont, United States, 05401
      • University of Vermont Medical Center
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • University of Virginia Health System
    • Falls Church, Virginia, United States, 22042
      • Inova Fairfax Hospital
    • Manassas, Virginia, United States, 20110
      • Gastroenterology Associates, PC
    • Norfolk, Virginia, United States, 23502
      • Local Institution - 0069
    • Reston, Virginia, United States, 20191
      • The Gastroenterology Group
    • Richmond, Virginia, United States, 23226
      • Bon Secours Liver Institute of Richmond
    • Richmond, Virginia, United States, 23249
      • Local Institution - 0077
    • Richmond, Virginia, United States, 23298
      • Local Institution - 0049

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 73 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: BMS-986036 Dose Level 1; Administered by subcutaneous injection.	Drug: BMS-986036; Specified dose on specified days.; Other Names: Pegbelfermin
Experimental: BMS-986036 Dose Level 2; Administered by subcutaneous injection.	Drug: BMS-986036; Specified dose on specified days.; Other Names: Pegbelfermin
Experimental: BMS-986036 Dose Level 3; Administered by subcutaneous injection.	Drug: BMS-986036; Specified dose on specified days.; Other Names: Pegbelfermin
Placebo Comparator: Placebo; Administered by subcutaneous injection.	Other: Placebo; Specified dose on specified days.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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
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
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
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
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
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

Collaborators and Investigators

• Sponsor: Bristol-Myers Squibb

Publications and helpful links

General Publications

• 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.

Helpful Links

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting
• Investigator Inquiry Form
• FDA Safety Alerts and Recalls

Study record dates

Study Major Dates

• Study Start (Actual): June 19, 2018
• Primary Completion (Actual): September 14, 2020
• Study Completion (Actual): August 17, 2021

Study Registration Dates

• First Submitted: March 30, 2018
• First Submitted That Met QC Criteria: March 30, 2018
• First Posted (Actual): April 3, 2018

Study Record Updates

• Last Update Posted (Actual): September 9, 2022
• Last Update Submitted That Met QC Criteria: August 16, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Liver Diseases; Fibrosis; Fatty Liver; Liver Cirrhosis; Non-alcoholic Fatty Liver Disease
• Other Study ID Numbers: MB130-068

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No