Study to Evaluate Safety, Tolerability, and Efficacy of GS-0976 in Adults With Nonalcoholic Steatohepatitis

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 firsocostat in adults 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-0976 in Subjects With Nonalcoholic Steatohepatitis

Conditions
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Nonalcoholic Steatohepatitis (NASH)

Intervention / Treatment
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* Drug: Firsocostat
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Meets all of 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 kPa OR A historical liver biopsy consistent with NASH and non-cirrhotic fibrosis Platelet count ≥ 100,000/mm^3 Creatinine Clearance (CLcr ) as calculated by the Cockcroft-Gault equation ≥ 60 ml/min Key Exclusion Criteria: Pregnant or lactating females Alanine aminotransferase (ALT) > 5 x 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 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: Sequential Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Firsocostat 5 mg<br>Participants will receive firsocostat 1 x 5 mg + 1 x placebo matched to firsocostat 5 mg + 2 x placebo matched to firsocostat 10 mg for 12 weeks. | Drug: Firsocostat<br>* Capsules orally once daily.<br>* Other names: GS-0976;Drug: Placebo<br>* Placebo matched to firsocostat orally once daily.<br>|
| Experimental: Firsocostat 20 mg<br>Participants will receive firsocostat 2 X 10 mg + 2 x placebo matched to firsocostat 5 mg for 12 weeks. | Drug: Firsocostat<br>* Capsules orally once daily.<br>* Other names: GS-0976;Drug: Placebo<br>* Placebo matched to firsocostat orally once daily.<br>|
| Experimental: Placebo<br>Participants will receive 2 x placebo matched to firsocostat 5 mg + 2 x placebo matched to firsocostat 10 mg for 12 weeks. | Drug: Placebo<br>* Placebo matched to firsocostat orally once daily.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Experiencing Treatment-Emergent Adverse Events |  | First Dose date up to last dose (Week 12) plus 30 days |