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

Non-Alcoholic Steatohepatitis (NASH) Clinical Trial

Official title:

A Phase 2, Randomized, Open Label Study Evaluating the Safety, Tolerability, and Efficacy of GS-4997 Alone or in Combination With Simtuzumab (SIM) in Subjects With Nonalcoholic Steatohepatitis (NASH) and Fibrosis Stages F2-F3

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02466516
• Other study ID #: GS-US-384-1497
• Status: Completed
• Phase: Phase 2
• Start date: June 8, 2015
• Est. completion date: October 11, 2016

Study information

• Verified date: May 2019
• Source: Gilead Sciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 72
• Est. completion date: October 11, 2016
• Est. primary completion date: October 11, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

Key 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.

Related Conditions & MeSH terms

• Fatty Liver
• Fibrosis
• Non-alcoholic Fatty Liver Disease
• Non-Alcoholic Steatohepatitis (NASH)

Intervention

Drug:
• SEL
SEL tablet administered orally once daily

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

Locations

Country	Name	City	State
Canada	University of Calgary	Calgary	Alberta
Canada	Toronto Liver Centre	Toronto	Ontario
United States	Texas Clinical Research Institute	Arlington	Texas
United States	University of Colorado Denver	Aurora	Colorado
United States	Mercy Medical Center	Baltimore	Maryland
United States	Walter Reed National Military Medical Center	Bethesda	Maryland
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	University of Virginia	Charlottesville	Virginia
United States	Northwestern University	Chicago	Illinois
United States	Methodist Dallas Medical Center	Dallas	Texas
United States	Duke University Medical Center	Durham	North Carolina
United States	Inova Fairfax Hospital	Falls Church	Virginia
United States	Brooke Army Medical Center Ft. Sam	Houston	Texas
United States	CHI St. Luke's Health Baylor College of Medicine	Houston	Texas
United States	Indiana University School of Medicine	Indianapolis	Indiana
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	Mary Immaculate Hospital	Newport News	Virginia
United States	Stanford University Medical Center	Palo Alto	California
United States	Hospital of the University of Pennsylvania	Philadelphia	Pennsylvania
United States	University of Pittsburg Medical Center	Pittsburgh	Pennsylvania
United States	St. Mary's Hospital	Richmond	Virginia
United States	Virginia Commonwealth University Health System	Richmond	Virginia
United States	American Research Corporation at Texas Liver Institute	San Antonio	Texas
United States	University of California San Diego	San Diego	California
United States	University of California San Francisco	San Francisco	California
United States	Swedish Medical Center	Seattle	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Gilead Sciences

Countries where clinical trial is conducted

United States,  Canada, 

References & Publications (4)

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

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

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, p

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants Who Experienced Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (SAEs), and Any Grade = 1 Laboratory Abnormality	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.	Baseline up to last dose plus 30 days (up to Week 28)
Primary	Number of Participants Who Prematurely Discontinued Study Drug or Study Due to Adverse Events		Baseline up to follow up visit (Week 28)