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

Primary Purpose

Liver Fibrosis, Nonalcoholic Fatty Liver Disease (NAFLD), Nonalcoholic Steatohepatitis

Status

Completed

Phase

Phase 2

Locations

International

Study Type

Interventional

Intervention

BMS-986036

Placebo

About this trial

This is an interventional treatment trial for Liver Fibrosis

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Placebo Comparator

Arm Label

BMS-986036 Dose Level 1

BMS-986036 Dose Level 2

BMS-986036 Dose Level 3

Placebo

Arm Description

Administered by subcutaneous injection.

Outcomes

Primary Outcome Measures

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).

Secondary Outcome Measures

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).

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.

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.

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).

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).

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).

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).

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.

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).

Full Information

NCT ID

NCT03486899

First Posted

March 30, 2018

Last Updated

August 16, 2022

Sponsor

Bristol-Myers Squibb

1. Study Identification

Unique Protocol Identification Number

NCT03486899

Brief Title

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

Acronym

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

Study Type

Interventional

2. Study Status

Record Verification Date

August 2022

Overall Recruitment Status

Completed

Study Start Date

June 19, 2018 (Actual)

Primary Completion Date

September 14, 2020 (Actual)

Study Completion Date

August 17, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Bristol-Myers Squibb

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Liver Fibrosis, Nonalcoholic Fatty Liver Disease (NAFLD), Nonalcoholic Steatohepatitis

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

197 (Actual)

8. Arms, Groups, and Interventions

Arm Title

BMS-986036 Dose Level 1

Arm Type

Experimental

Arm Description

Administered by subcutaneous injection.

Arm Title

BMS-986036 Dose Level 2

Arm Type

Experimental

Arm Description

Administered by subcutaneous injection.

Arm Title

BMS-986036 Dose Level 3

Arm Type

Experimental

Arm Description

Administered by subcutaneous injection.

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

Administered by subcutaneous injection.

Intervention Type

Drug

Intervention Name(s)

BMS-986036

Other Intervention Name(s)

Pegbelfermin

Intervention Description

Specified dose on specified days.

Intervention Type

Other

Intervention Name(s)

Placebo

Intervention Description

Specified dose on specified days.

Primary Outcome Measure Information:

Title

The Percentage of Participants With Improvement in Fibrosis or Nonalcoholic Steatohepatitis (NASH) at Week 24

Description

Time Frame