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

Study Overview
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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.

Official Title
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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

Conditions
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Non-Alcoholic Steatohepatitis (NASH)

Intervention / Treatment
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* Drug: SEL
* Biological: SIM


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SEL 6 mg<br>Selonsertib (SEL) 6 mg for 24 weeks. | Drug: SEL<br>* SEL tablet administered orally once daily<br>* Other names: GS-4997;|
| Experimental: SEL 18 mg<br>SEL 18 mg for 24 weeks. | Drug: SEL<br>* SEL tablet administered orally once daily<br>* Other names: GS-4997;|
| Experimental: SEL 6 mg+SIM 125 mg<br>SEL 6 mg plus SIM 125 mg for 24 weeks. | Drug: SEL<br>* SEL tablet administered orally once daily<br>* Other names: GS-4997;Biological: SIM<br>* Simtuzumab (SIM) 125 mg/mL single-dose vials administered subcutaneously once weekly<br>* Other names: GS-6624;|
| Experimental: SEL 18 mg+SIM 125 mg<br>SEL 18 mg plus SIM 125 mg for 24 weeks. | Drug: SEL<br>* SEL tablet administered orally once daily<br>* Other names: GS-4997;Biological: SIM<br>* Simtuzumab (SIM) 125 mg/mL single-dose vials administered subcutaneously once weekly<br>* Other names: GS-6624;|
| Experimental: SIM 125 mg<br>SIM 125 mg for 24 weeks. | Biological: SIM<br>* Simtuzumab (SIM) 125 mg/mL single-dose vials administered subcutaneously once weekly<br>* Other names: GS-6624;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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GS-4997, Non-alcoholic fatty liver disease (NAFLD), Fibrosis, Simtuzumab (SIM), Apoptosis signal-regulating kinase 1, ASK1 inhibitor