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

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

The primary objective of this study is to evaluate the safety and tolerability of GS-9674 in participants with nonalcoholic steatohepatitis (NASH).

Study Overview

• Status: Completed
• Conditions: Nonalcoholic Steatohepatitis (NASH)
• Intervention / Treatment: Drug: GS-9674; Drug: Placebo to match GS-9674

• Study Type: Interventional
• Enrollment (Actual): 140
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 4Z6
      • University of Calgary
  • Ontario
    • Toronto, Ontario, Canada, M5G 2C4
      • Toronto General Hospital
    • Toronto, Ontario, Canada, M6H 3M1
      • Toronto Liver Center
    • Toronto, Ontario, Canada, M4G 3E8
      • LMC Clinical Research Inc (Bayview)
    • Vaughan, Ontario, Canada, L4L 4Y7
      • Toronto Digestive Disease Associates, Inc.
• Hong Kong
  • Kowloon, Hong Kong
    • Princess Margaret Hospital
  • Sha Tin, Hong Kong
    • The Chinese University of Hong Kong
• New Zealand
  • Auckland, New Zealand, 1010
    • Auckland Clinical Studies
• Switzerland
  • Bern, Switzerland, 3010
    • Universitatsspital Bern, Inselspital, Universitatsklinik fur Viszerale Chirurgie und Medizin, Hepatologie
  • Zurich, Switzerland, CH-8091
    • UniversitätsSpital Zürich
• United Kingdom
  • Cambridge, United Kingdom, CB2 0QQ
    • Addenbrooke's Hospital
• United States
  • California
    • Los Angeles, California, United States, 90048
      • Cedars Sinai Medical Center
    • Los Angeles, California, United States, 90036
      • Ruane Clinical Research Group Inc.
    • Rialto, California, United States, 92377
      • Inland Empire Liver Foundation
  • Florida
    • Coral Gables, Florida, United States, 33134
      • Clinical Research of South Florida
  • Georgia
    • Atlanta, Georgia, United States, 30308
      • Atlanta Gastroenterology Associates
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern Memorial Hospital, Clinical Research Unit
  • Louisiana
    • Metairie, Louisiana, United States, 70006
      • Crescent Clinical Research Center, LLC
    • New Orleans, Louisiana, United States, 70112
      • Tulane University Health Sciences Center
  • Missouri
    • Kansas City, Missouri, United States, 64131
      • Kansas City Research Institute
  • New York
    • New York, New York, United States, 10016
      • Concorde Medical Group, PLLC
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center, Duke South Clinics
    • Durham, North Carolina, United States, 28078
      • Carolinas Center for Liver Disease/Carolinas HealthCare System
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University
  • Tennessee
    • Germantown, Tennessee, United States, 38138
      • Gastro One
    • Nashville, Tennessee, United States, 37211
      • Quality Medical Research, PC
  • Texas
    • Arlington, Texas, United States, 76012
      • Texas Clinical Research Institute
    • Dallas, Texas, United States, 75203
      • The Liver Institute at Methodist Dallas Medical Center
    • Dallas, Texas, United States, 75246
      • Texas Digestive Disease Consultants
    • Houston, Texas, United States, 77030
      • Houston Methodist Hospital
    • Live Oak, Texas, United States, 78233
      • Pinnacle Clinical Research
    • San Antonio, Texas, United States, 78215
      • American Research Corporation at the Texas Liver Institute
  • Utah
    • Murray, Utah, United States, 84107
      • Intermountain Liver Disease and Transplant Center
  • Virginia
    • Newport News, Virginia, United States, 23602
      • Bon Secours St. Mary's Hospital of Richmond, Inc d/b/a Bon Secours Liver Institute of Virginia
    • Richmond, Virginia, United States, 23249
      • McGuire VA Medical Center
    • Richmond, Virginia, United States, 23226
      • Bon Secours St. Mary's Hospital of Richmond, Inc. d/b/a Bon Secours Liver Institute of Virginia
  • Washington
    • Seattle, Washington, United States, 98104
      • Swedish Organ Transplant and Liver Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Gilead Sciences

Publications and helpful links

General Publications

• Patel K, Harrison SA, Elkhashab M, Trotter JF, Herring R, Rojter SE, Kayali Z, Wong VW, Greenbloom S, Jayakumar S, Shiffman ML, Freilich B, Lawitz EJ, Gane EJ, Harting E, Xu J, Billin AN, Chung C, Djedjos CS, Subramanian GM, Myers RP, Middleton MS, Rinella M, Noureddin M. Cilofexor, a Nonsteroidal FXR Agonist, in Patients With Noncirrhotic NASH: A Phase 2 Randomized Controlled Trial. Hepatology. 2020 Jul;72(1):58-71. doi: 10.1002/hep.31205.

Study record dates

Study Major Dates

• Study Start (Actual): October 26, 2016
• Primary Completion (Actual): January 9, 2018
• Study Completion (Actual): January 9, 2018

Study Registration Dates

• First Submitted: July 29, 2016
• First Submitted That Met QC Criteria: July 29, 2016
• First Posted (Estimate): August 3, 2016

Study Record Updates

• Last Update Posted (Actual): January 29, 2019
• Last Update Submitted That Met QC Criteria: January 7, 2019
• Last Verified: January 1, 2019

More Information

Terms related to this study

• Keywords: Fibrosis; Non-alcoholic fatty liver disease (NAFLD); GS-9674
• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease
• Other Study ID Numbers: GS-US-402-1852; 2016-002496-10 (EudraCT Number)

Drug and device information, study documents

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