Evaluating the Safety, Tolerability, and Efficacy of GS-9674 in Participants With Nonalcoholic Steatohepatitis (NASH)

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-9674 in participants with nonalcoholic steatohepatitis (NASH).

Official Title
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A Phase 2, Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Safety, Tolerability, and Efficacy of GS-9674 in Subjects With Nonalcoholic Steatohepatitis (NASH)

Conditions
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Nonalcoholic Steatohepatitis (NASH)

Intervention / Treatment
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* Drug: GS-9674
* Drug: Placebo to match GS-9674


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Meets the following conditions: A clinical diagnosis of nonalcoholic fatty liver disease (NAFLD) Screening magnetic resonance imaging - proton density fat fraction (MRI-PDFF) with ≥ 8% steatosis Screening magnetic resonance elastography (MRE) with liver stiffness ≥ 2.5 kilopascal (kPa) OR A historical liver biopsy within 12 months of screening consistent with NASH with fibrosis, but not cirrhosis, and No documented weight loss > 5% between the date of the liver biopsy and screening. Platelet count ≥ 150,000/mm^3 Albumin ≥ 3.3 g/dL Serum creatinine ≤ upper limit of normal (ULN) Key Exclusion Criteria: Pregnant or lactating females Alanine aminotransferase (ALT) > 5x upper limit of the normal range (ULN) Other causes of liver disease including autoimmune, viral, and alcoholic liver disease Cirrhosis of the liver Prior history of decompensated liver disease, including ascites, hepatic encephalopathy, or variceal bleeding Body mass index (BMI) < 18 kg/m^2 Uncontrolled diabetes mellitus (hemoglobin A1c > 9% at screening) International normalized ratio (INR) > 1.2 unless on anticoagulant therapy Total bilirubin > 1 x ULN, except with diagnosis of Gilbert's syndrome Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GS-9674 30 mg<br>GS-9674 30 mg + placebo to match GS-9674 100 mg for 24 weeks | Drug: GS-9674<br>* Tablet administered orally once daily<br>Drug: Placebo to match GS-9674<br>* Tablet(s) administered orally once daily<br>|
| Experimental: GS-9674 100 mg<br>GS-9674 100 mg + placebo to match GS-9674 30 mg for 24 weeks | Drug: GS-9674<br>* Tablet administered orally once daily<br>Drug: Placebo to match GS-9674<br>* Tablet(s) administered orally once daily<br>|
| Placebo Comparator: Placebo<br>Placebo to match GS-9674 30 mg + placebo to match GS-9674 100 mg for 24 weeks | Drug: Placebo to match GS-9674<br>* Tablet(s) administered orally once daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Safety of GS-9674 as Assessed By Percentage of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs) | TEAEs were defined as 1 or both of the following: 1) Any adverse events (AE) with an onset date on or after the study drug start date and no later than 30 days after permanent discontinuation of study drug, 2) Any AEs leading to premature discontinuation of study drug. | Up to 24 weeks plus 30 days | 
| Overall Safety of GS-9674 as Assessed By Percentage of Participants With Treatment-Emergent Laboratory Abnormalities | Treatment-emergent laboratory abnormalities are defined as values that increase at least 1 toxicity grade from baseline at any post-baseline time point, up to and including the date of last dose of study drug plus 30 days for participants who permanently discontinued study. | Up to 24 weeks plus 30 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Non-alcoholic fatty liver disease (NAFLD), Fibrosis, GS-9674