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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

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ClinicalTrials.gov Identifier: NCT02466516
Recruitment Status : Completed
First Posted : June 9, 2015
Results First Posted : June 26, 2019
Last Update Posted : June 26, 2019
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences

Study Description
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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.

Condition or disease Intervention/treatment Phase
Non-Alcoholic Steatohepatitis (NASH) Drug: SEL Biological: SIM Phase 2

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 72 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : June 8, 2015
Actual Primary Completion Date : October 11, 2016
Actual Study Completion Date : October 11, 2016

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: SEL 6 mg
Selonsertib (SEL) 6 mg for 24 weeks.
 Drug: SEL
SEL tablet administered orally once daily
Other Name: GS-4997
Experimental: SEL 18 mg
SEL 18 mg for 24 weeks.
 Drug: SEL
SEL tablet administered orally once daily
Other Name: GS-4997
Experimental: SEL 6 mg+SIM 125 mg
SEL 6 mg plus SIM 125 mg for 24 weeks.
 Drug: SEL
SEL tablet administered orally once daily
Other Name: GS-4997

Biological: SIM
Simtuzumab (SIM) 125 mg/mL single-dose vials administered subcutaneously once weekly
Other Name: GS-6624
Experimental: SEL 18 mg+SIM 125 mg
SEL 18 mg plus SIM 125 mg for 24 weeks.
 Drug: SEL
SEL tablet administered orally once daily
Other Name: GS-4997

Biological: SIM
Simtuzumab (SIM) 125 mg/mL single-dose vials administered subcutaneously once weekly
Other Name: GS-6624
Experimental: SIM 125 mg
SIM 125 mg for 24 weeks.
 Biological: SIM
Simtuzumab (SIM) 125 mg/mL single-dose vials administered subcutaneously once weekly
Other Name: GS-6624


Outcome Measures
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Primary Outcome Measures :
  1. Number of Participants Who Experienced Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (SAEs), and Any Grade ≥ 1 Laboratory Abnormality [ Time Frame: 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.

  2. Number of Participants Who Prematurely Discontinued Study Drug or Study Due to Adverse Events [ Time Frame: Baseline up to follow up visit (Week 28) ]

Eligibility Criteria
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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02466516


Locations
Show Show 28 study locations
Sponsors and Collaborators
Gilead Sciences
Investigators
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Study Director: Gilead Study Director Gilead Sciences
More Information
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Publications of Results:
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.
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.
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.
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.

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Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT02466516    
Other Study ID Numbers: GS-US-384-1497
First Posted: June 9, 2015    Key Record Dates
Results First Posted: June 26, 2019
Last Update Posted: June 26, 2019
Last Verified: May 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Gilead Sciences:
GS-4997
Non-alcoholic fatty liver disease (NAFLD)
Fibrosis
 Simtuzumab (SIM)
Apoptosis signal-regulating kinase 1
ASK1 inhibitor
Additional relevant MeSH terms:
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Fatty Liver
Non-alcoholic Fatty Liver Disease
Fibrosis
 Pathologic Processes
Liver Diseases
Digestive System Diseases