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
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
1 other identifier
interventional
72
2 countries
28
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_2
Started Jun 2015
Shorter than P25 for phase_2
28 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
June 5, 2015
CompletedStudy Start
First participant enrolled
June 8, 2015
CompletedFirst Posted
Study publicly available on registry
June 9, 2015
CompletedPrimary Completion
Last participant's last visit for primary outcome
October 11, 2016
CompletedStudy Completion
Last participant's last visit for all outcomes
October 11, 2016
CompletedResults Posted
Study results publicly available
June 26, 2019
CompletedJune 26, 2019
May 1, 2019
1.3 years
June 5, 2015
May 31, 2019
May 31, 2019
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
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)
Number of Participants Who Prematurely Discontinued Study Drug or Study Due to Adverse Events
Baseline up to follow up visit (Week 28)
Study Arms (5)
SEL 6 mg
EXPERIMENTALSelonsertib (SEL) 6 mg for 24 weeks.
SEL 18 mg
EXPERIMENTALSEL 18 mg for 24 weeks.
SEL 6 mg+SIM 125 mg
EXPERIMENTALSEL 6 mg plus SIM 125 mg for 24 weeks.
SEL 18 mg+SIM 125 mg
EXPERIMENTALSEL 18 mg plus SIM 125 mg for 24 weeks.
SIM 125 mg
EXPERIMENTALSIM 125 mg for 24 weeks.
Interventions
Eligibility Criteria
You may qualify if:
- Males and non-pregnant, non-lactating females
- Evidence of NASH with fibrosis on biopsy
You may not qualify if:
- 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)
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Gilead Scienceslead
Study Sites (28)
Stanford University Medical Center
Palo Alto, California, 94304, United States
University of California San Diego
San Diego, California, 92103, United States
University of California San Francisco
San Francisco, California, 94143, United States
University of Colorado Denver
Aurora, Colorado, 80045, United States
Northwestern University
Chicago, Illinois, 60611, United States
Indiana University School of Medicine
Indianapolis, Indiana, 46202, United States
Mercy Medical Center
Baltimore, Maryland, 21202, United States
Walter Reed National Military Medical Center
Bethesda, Maryland, 20889, United States
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02215, United States
Kansas City Research Institute
Kansas City, Missouri, 64131, United States
Duke University Medical Center
Durham, North Carolina, 03125, United States
Hospital of the University of Pennsylvania
Philadelphia, Pennsylvania, 19104, United States
University of Pittsburg Medical Center
Pittsburgh, Pennsylvania, 15143, United States
Texas Clinical Research Institute
Arlington, Texas, 76012, United States
Methodist Dallas Medical Center
Dallas, Texas, 75203, United States
CHI St. Luke's Health Baylor College of Medicine
Houston, Texas, 77030, United States
Brooke Army Medical Center Ft. Sam
Houston, Texas, 78234, United States
Digestive Research Center
Live Oak, Texas, 78233, United States
American Research Corporation at Texas Liver Institute
San Antonio, Texas, 78215, United States
Intermountain Medical Center
Murray, Utah, 84107, United States
University of Virginia
Charlottesville, Virginia, 22908, United States
Inova Fairfax Hospital
Falls Church, Virginia, 22042, United States
Mary Immaculate Hospital
Newport News, Virginia, 23602, United States
St. Mary's Hospital
Richmond, Virginia, 23226, United States
Virginia Commonwealth University Health System
Richmond, Virginia, 23298, United States
Swedish Medical Center
Seattle, Washington, 98104, United States
University of Calgary
Calgary, Alberta, T2N4Z6, Canada
Toronto Liver Centre
Toronto, Ontario, M6H 3M1, Canada
Related Publications (4)
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.
RESULTDiehl 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.
RESULTMiddleton 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.
RESULTLoomba 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.
RESULT
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Results Point of Contact
- Title
- Gilead Clinical Study Information Center
- Organization
- Gilead Sciences
Study Officials
- STUDY DIRECTOR
Gilead Study Director
Gilead Sciences
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
June 5, 2015
First Posted
June 9, 2015
Study Start
June 8, 2015
Primary Completion
October 11, 2016
Study Completion
October 11, 2016
Last Updated
June 26, 2019
Results First Posted
June 26, 2019
Record last verified: 2019-05