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

Phase 2

Completed

• Conditions: Non-Alcoholic Steatohepatitis (NASH)
• Interventions: Drug: SEL; Biological: SIM

• Registration Number: NCT02466516
• Lead Sponsor: Gilead Sciences

Brief Summary

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

Not available

Study Timeline

• Study First Submitted: 2015-06-05
• Study First Submitted QC: 2015-06-05
• Study Start: 2015-06-08
• Study First Posted: 2015-06-09
• Primary Completion: 2016-10-11
• Study Completion: 2016-10-11
• Disposition First Submitted: 2017-02-23
• Disposition First Submitted QC: 2017-02-23
• Disposition First Posted: 2017-02-27
• Status Verified: 2019-05
• Results First Submitted: 2019-05-31
• Results First Submitted QC: 2019-05-31
• Last Update Submitted: 2019-05-31
• Results First Posted: 2019-06-26
• Last Update Posted: 2019-06-26

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 72

Inclusion Criteria

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

Key

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)

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
SEL 6 mg+SIM 125 mg	SEL	SEL 6 mg plus SIM 125 mg for 24 weeks.
SEL 18 mg	SEL	SEL 18 mg for 24 weeks.
SIM 125 mg	SIM	SIM 125 mg for 24 weeks.
SEL 6 mg	SEL	Selonsertib (SEL) 6 mg for 24 weeks.
SEL 6 mg+SIM 125 mg	SIM	SEL 6 mg plus SIM 125 mg for 24 weeks.
SEL 18 mg+SIM 125 mg	SEL	SEL 18 mg plus SIM 125 mg for 24 weeks.
SEL 18 mg+SIM 125 mg	SIM	SEL 18 mg plus SIM 125 mg for 24 weeks.

Primary Outcome Measures

Name	Time	Method
Number of Participants Who Experienced Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (SAEs), and Any Grade ≥ 1 Laboratory Abnormality	Baseline up to last dose plus 30 days (up to Week 28)	Treatment-emergent events began on or after the first dosing date up to 30 days after the last dosing date or led to premature discontinuation of study drug. The severity of laboratory abnormalities was assessed as Grade 0, 1 (mild), 2 (moderate), 3 (severe), or 4 (potentially life threatening) using the Common Terminology Criteria for Adverse Events (CTCAE), version 4.03.
Number of Participants Who Prematurely Discontinued Study Drug or Study Due to Adverse Events	Baseline up to follow up visit (Week 28)

Trial Locations

Locations (28)

University of California San Francisco; 🇺🇸 San Francisco, California, United States

University of Colorado Denver; 🇺🇸 Aurora, Colorado, United States

Stanford University Medical Center; 🇺🇸 Palo Alto, California, United States

Walter Reed National Military Medical Center; 🇺🇸 Bethesda, Maryland, United States

Kansas City Research Institute; 🇺🇸 Kansas City, Missouri, United States

Digestive Research Center; 🇺🇸 Live Oak, Texas, United States

Intermountain Medical Center; 🇺🇸 Murray, Utah, United States

Inova Fairfax Hospital; 🇺🇸 Falls Church, Virginia, United States

University of Virginia; 🇺🇸 Charlottesville, Virginia, United States

St. Mary's Hospital; 🇺🇸 Richmond, Virginia, United States

Mary Immaculate Hospital; 🇺🇸 Newport News, Virginia, United States

Virginia Commonwealth University Health System; 🇺🇸 Richmond, Virginia, United States

Toronto Liver Centre; 🇨🇦 Toronto, Ontario, Canada

University of California San Diego; 🇺🇸 San Diego, California, United States

Northwestern University; 🇺🇸 Chicago, Illinois, United States

Indiana University School of Medicine; 🇺🇸 Indianapolis, Indiana, United States

Mercy Medical Center; 🇺🇸 Baltimore, Maryland, United States

Beth Israel Deaconess Medical Center; 🇺🇸 Boston, Massachusetts, United States

Duke University Medical Center; 🇺🇸 Durham, North Carolina, United States

Hospital of the University of Pennsylvania; 🇺🇸 Philadelphia, Pennsylvania, United States

University of Pittsburg Medical Center; 🇺🇸 Pittsburgh, Pennsylvania, United States

Texas Clinical Research Institute; 🇺🇸 Arlington, Texas, United States

Methodist Dallas Medical Center; 🇺🇸 Dallas, Texas, United States

CHI St. Luke's Health Baylor College of Medicine; 🇺🇸 Houston, Texas, United States

Brooke Army Medical Center Ft. Sam; 🇺🇸 Houston, Texas, United States

American Research Corporation at Texas Liver Institute; 🇺🇸 San Antonio, Texas, United States

Swedish Medical Center; 🇺🇸 Seattle, Washington, United States

University of Calgary; 🇨🇦 Calgary, Alberta, Canada