Safety, Tolerability, and Efficacy of GS-4997 Alone or in Combination With Simtuzumab (SIM) in Adults With Nonalcoholic Steatohepatitis (NASH) and Fibrosis Stages F2-F3

NCT ID: NCT02466516

Last Updated: 2019-06-26

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

72 participants

Study Classification

INTERVENTIONAL

Study Start Date

2015-06-08

Study Completion Date

2016-10-11

Brief Summary

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The primary objective of this study is to evaluate the safety and tolerability of GS-4997 (selonsertib \[SEL\]) alone or in combination with simtuzumab (SIM) in adults with nonalcoholic steatohepatitis (NASH) and fibrosis stages F2-F3. Participants will be randomized in a 2:2:1:1:1 ratio to 1 of 5 study treatment arms.

Detailed Description

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Conditions

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Non-Alcoholic Steatohepatitis (NASH)

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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SEL 6 mg

Selonsertib (SEL) 6 mg for 24 weeks.

Group Type EXPERIMENTAL

SEL

Intervention Type DRUG

SEL tablet administered orally once daily

SEL 18 mg

SEL 18 mg for 24 weeks.

Group Type EXPERIMENTAL

SEL

Intervention Type DRUG

SEL tablet administered orally once daily

SEL 6 mg+SIM 125 mg

SEL 6 mg plus SIM 125 mg for 24 weeks.

Group Type EXPERIMENTAL

SEL

Intervention Type DRUG

SEL tablet administered orally once daily

SIM

Intervention Type BIOLOGICAL

Simtuzumab (SIM) 125 mg/mL single-dose vials administered subcutaneously once weekly

SEL 18 mg+SIM 125 mg

SEL 18 mg plus SIM 125 mg for 24 weeks.

Group Type EXPERIMENTAL

SEL

Intervention Type DRUG

SEL tablet administered orally once daily

SIM

Intervention Type BIOLOGICAL

Simtuzumab (SIM) 125 mg/mL single-dose vials administered subcutaneously once weekly

SIM 125 mg

SIM 125 mg for 24 weeks.

Group Type EXPERIMENTAL

SIM

Intervention Type BIOLOGICAL

Simtuzumab (SIM) 125 mg/mL single-dose vials administered subcutaneously once weekly

Interventions

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SEL

SEL tablet administered orally once daily

Intervention Type DRUG

SIM

Simtuzumab (SIM) 125 mg/mL single-dose vials administered subcutaneously once weekly

Intervention Type BIOLOGICAL

Other Intervention Names

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GS-4997 GS-6624

Eligibility Criteria

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Inclusion Criteria

* Males and non-pregnant, non-lactating females
* Evidence of NASH with fibrosis on biopsy

Exclusion Criteria

* Cirrhosis of the liver (e.g. Brunt/Kleiner score of F4)
* Other causes of liver disease including viral hepatitis and alcoholic liver disease
* Any history of decompensated liver disease, including ascites, hepatic encephalopathy or variceal bleeding
* History of liver transplantation
* Alcohol consumption greater than 21 oz/week for males or 14 oz/week for females (1 oz/30 mL of alcohol is present in 1 12 oz/360 mL beer, 1 4 oz/120 mL glass of wine, and a 1 oz/30 mL measure of 40% proof alcohol)
Minimum Eligible Age

18 Years

Maximum Eligible Age

70 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Gilead Sciences

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Gilead Study Director

Role: STUDY_DIRECTOR

Gilead Sciences

Locations

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Stanford University Medical Center

Palo Alto, California, United States

Site Status

University of California San Diego

San Diego, California, United States

Site Status

University of California San Francisco

San Francisco, California, United States

Site Status

University of Colorado Denver

Aurora, Colorado, United States

Site Status

Northwestern University

Chicago, Illinois, United States

Site Status

Indiana University School of Medicine

Indianapolis, Indiana, United States

Site Status

Mercy Medical Center

Baltimore, Maryland, United States

Site Status

Walter Reed National Military Medical Center

Bethesda, Maryland, United States

Site Status

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

Site Status

Kansas City Research Institute

Kansas City, Missouri, United States

Site Status

Duke University Medical Center

Durham, North Carolina, United States

Site Status

Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, United States

Site Status

University of Pittsburg Medical Center

Pittsburgh, Pennsylvania, United States

Site Status

Texas Clinical Research Institute

Arlington, Texas, United States

Site Status

Methodist Dallas Medical Center

Dallas, Texas, United States

Site Status

CHI St. Luke's Health Baylor College of Medicine

Houston, Texas, United States

Site Status

Brooke Army Medical Center Ft. Sam

Houston, Texas, United States

Site Status

Digestive Research Center

Live Oak, Texas, United States

Site Status

American Research Corporation at Texas Liver Institute

San Antonio, Texas, United States

Site Status

Intermountain Medical Center

Murray, Utah, United States

Site Status

University of Virginia

Charlottesville, Virginia, United States

Site Status

Inova Fairfax Hospital

Falls Church, Virginia, United States

Site Status

Mary Immaculate Hospital

Newport News, Virginia, United States

Site Status

St. Mary's Hospital

Richmond, Virginia, United States

Site Status

Virginia Commonwealth University Health System

Richmond, Virginia, United States

Site Status

Swedish Medical Center

Seattle, Washington, United States

Site Status

University of Calgary

Calgary, Alberta, Canada

Site Status

Toronto Liver Centre

Toronto, Ontario, Canada

Site Status

Countries

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United States Canada

References

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Loomba R, Lawitz E, Mantry PS, Jayakumar S, Caldwell SH, Arnold H, et al. GS-4997, an inhibitor of apoptosis signal-regulating kinase (ASK1), alone or in combination with simtuzumab for the treatment of nonalcoholic steatohepatitis (NASH): a randomized, phase 2 trial. Hepatol 2016; 64 (6S): 1119A-1120A.

Reference Type RESULT

Diehl AM, French D, Xu R, et al. Treatment with selonsertib, an inhibitor of apoptosis signal-regulating kinase 1, hepatic phospho-p38 expression and markers of hepatocellular apoptosis and necrosis in patients with nonalcoholic steatohepatitis. J Hepatol 2017;66:S51. PS-090.

Reference Type RESULT

Middleton MS, Lawitz E, Jayakumar S, et al. Hepatic proton density fat fraction correlates with histologic measures of steatosis and is responsive to change in those measures in a multi-center nonalcoholic steatohepatitis clinical trial. J Hepatol 2017;66:S668. SAT-483.

Reference Type RESULT

Loomba R, Lawitz E, Ghalib R, et al. Longitudinal changes in liver stiffness by magnetic resonance elastography (MRE), liver fibrosis, and serum markers of fibrosis in a multi-center clinical trial in nonalcoholic steatohepatitis (NASH). J Hepatol 2017;66:S671. SAT-489.

Reference Type RESULT

Other Identifiers

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GS-US-384-1497

Identifier Type: -

Identifier Source: org_study_id

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