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

A Phase 2, Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Safety, Tolerability, and Efficacy of GS-0976 in Subjects With Nonalcoholic Steatohepatitis

The primary objective of this study is to evaluate the safety and tolerability of firsocostat in adults with nonalcoholic steatohepatitis (NASH).

Study Overview

• Status: Completed
• Conditions: Nonalcoholic Steatohepatitis (NASH)
• Intervention / Treatment: Drug: Firsocostat; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 127
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Coronado, California, United States, 92118
    • Foster City, California, United States, 94404
    • Los Angeles, California, United States, 90048
    • Los Angeles, California, United States, 90036
    • Rialto, California, United States, 92377
    • San Diego, California, United States, 92103
    • San Diego, California, United States, 92123
    • San Francisco, California, United States, 94115
    • San Francisco, California, United States, 94143
  • Florida
    • Miami, Florida, United States, 33136
    • Miami, Florida, United States, 33165
  • Georgia
    • Atlanta, Georgia, United States, 30308
  • Illinois
    • Chicago, Illinois, United States, 60611
  • Indiana
    • Indianapolis, Indiana, United States, 46202
  • Louisiana
    • New Orleans, Louisiana, United States, 70112
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
  • Minnesota
    • Rochester, Minnesota, United States, 55905
  • Missouri
    • Kansas City, Missouri, United States, 64131
  • New York
    • New York, New York, United States, 10016
  • North Carolina
    • Durham, North Carolina, United States, 27710
    • Statesville, North Carolina, United States, 28677
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19707
    • Pittsburgh, Pennsylvania, United States, 15213
  • Tennessee
    • Germantown, Tennessee, United States, 38138
    • Memphis, Tennessee, United States, 38104
    • Nashville, Tennessee, United States, 37211
  • Texas
    • Arlington, Texas, United States, 76012
    • Live Oak, Texas, United States, 78233
    • San Antonio, Texas, United States, 78215
  • Utah
    • Murray, Utah, United States, 84107
  • Virginia
    • Falls Church, Virginia, United States, 22042
    • Richmond, Virginia, United States, 23298
    • Richmond, Virginia, United States, 23249
    • Richmond, Virginia, United States, 23226
  • Washington
    • Richland, Washington, United States, 99352
    • Seattle, Washington, United States, 98104

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 73 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Gilead Sciences

Publications and helpful links

General Publications

• Loomba R, Kayali Z, Noureddin M, Ruane P, Lawitz EJ, Gitlin N, Bennett M, Harting EJ, McColgan BJ, Myers RP, Subramanian GM, McHutchison JG, Middleton MS, Sirlin C, Lai M, Charlton M, Harrison SA. Acetyl-CoA carboxylase (ACC) inhibitor GS-0976 leads to significant improvements in MRI-PDFF in a Phase 2, randomized, placebo-controlled trial of patients with NASH. American Association for the Study of Liver Diseases Meeting; 2017; Washington, DC, USA.
• Loomba R, Kayali Z, Noureddin M, Ruane P, Lawitz EJ, Bennett M, Wang L, Harting E, Tarrant JM, McColgan BJ, Chung C, Ray AS, Subramanian GM, Myers RP, Middleton MS, Lai M, Charlton M, Harrison SA. GS-0976 Reduces Hepatic Steatosis and Fibrosis Markers in Patients With Nonalcoholic Fatty Liver Disease. Gastroenterology. 2018 Nov;155(5):1463-1473.e6. doi: 10.1053/j.gastro.2018.07.027. Epub 2018 Jul 27.
• Lawitz EJ, Coste A, Poordad F, Alkhouri N, Loo N, McColgan BJ, Tarrant JM, Nguyen T, Han L, Chung C, Ray AS, McHutchison JG, Subramanian GM, Myers RP, Middleton MS, Sirlin C, Loomba R, Nyangau E, Fitch M, Li K, Hellerstein M. Acetyl-CoA Carboxylase Inhibitor GS-0976 for 12 Weeks Reduces Hepatic De Novo Lipogenesis and Steatosis in Patients With Nonalcoholic Steatohepatitis. Clin Gastroenterol Hepatol. 2018 Dec;16(12):1983-1991.e3. doi: 10.1016/j.cgh.2018.04.042. Epub 2018 Apr 26.

Study record dates

Study Major Dates

• Study Start (Actual): August 8, 2016
• Primary Completion (Actual): July 18, 2017
• Study Completion (Actual): July 18, 2017

Study Registration Dates

• First Submitted: August 2, 2016
• First Submitted That Met QC Criteria: August 4, 2016
• First Posted (Estimate): August 5, 2016

Study Record Updates

• Last Update Posted (Actual): July 24, 2020
• Last Update Submitted That Met QC Criteria: July 8, 2020
• Last Verified: July 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Firsocostat
• Other Study ID Numbers: GS-US-426-3989

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No