Clinical trial NCT02854605: Evaluating the Safety, Tolerability, and Efficacy of GS-9674 in Participants With Nonalcoholic Steatohepatitis (NASH)
Official title: A Phase 2, Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Safety, Tolerability, and Efficacy of GS-9674 in Subjects With Nonalcoholic Steatohepatitis (NASH)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Nonalcoholic Steatohepatitis (NASH)
Keywords: Non-alcoholic fatty liver disease (NAFLD)
Fibrosis
GS-9674
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2016-08-03
Enrollment: 140
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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


Eligibility criteria: 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.

Primary outcomes:
measure: Overall Safety of GS-9674 as Assessed By Percentage of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs)
timeFrame: Up to 24 weeks plus 30 days
measure: Overall Safety of GS-9674 as Assessed By Percentage of Participants With Treatment-Emergent Laboratory Abnormalities
timeFrame: Up to 24 weeks plus 30 days
Secondary outcomes:
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Ruane Clinical Research Group Inc.
state: California
city: Los Angeles
country: United States
facility: Cedars Sinai Medical Center
state: California
city: Rialto
country: United States
facility: Inland Empire Liver Foundation
state: California
city: Coral Gables
country: United States
facility: Clinical Research of South Florida
state: Florida
city: Atlanta
country: United States
facility: Atlanta Gastroenterology Associates
state: Georgia
city: Chicago
country: United States
facility: Northwestern Memorial Hospital, Clinical Research Unit
state: Illinois
city: Metairie
country: United States
facility: Crescent Clinical Research Center, LLC
state: Louisiana
city: New Orleans
country: United States
facility: Tulane University Health Sciences Center
state: Louisiana
city: Kansas City
country: United States
facility: Kansas City Research Institute
state: Missouri
city: New York
country: United States
facility: Concorde Medical Group, PLLC
state: New York
city: Durham
country: United States
facility: Duke University Medical Center, Duke South Clinics
state: North Carolina
city: Durham
country: United States
facility: Carolinas Center for Liver Disease/Carolinas HealthCare System
state: North Carolina
city: Philadelphia
country: United States
facility: Thomas Jefferson University
state: Pennsylvania
city: Germantown
country: United States
facility: Gastro One
state: Tennessee
city: Nashville
country: United States
facility: Quality Medical Research, PC
state: Tennessee
city: Arlington
country: United States
facility: Texas Clinical Research Institute
state: Texas
city: Dallas
country: United States
facility: The Liver Institute at Methodist Dallas Medical Center
state: Texas
city: Dallas
country: United States
facility: Texas Digestive Disease Consultants
state: Texas
city: Houston
country: United States
facility: Houston Methodist Hospital
state: Texas
city: Live Oak
country: United States
facility: Pinnacle Clinical Research
state: Texas
city: San Antonio
country: United States
facility: American Research Corporation at the Texas Liver Institute
state: Texas
city: Murray
country: United States
facility: Intermountain Liver Disease and Transplant Center
state: Utah
city: Newport News
country: United States
facility: Bon Secours St. Mary's Hospital of Richmond, Inc d/b/a Bon Secours Liver Institute of Virginia
state: Virginia
city: Richmond
country: United States
facility: Bon Secours St. Mary's Hospital of Richmond, Inc. d/b/a Bon Secours Liver Institute of Virginia
state: Virginia
city: Richmond
country: United States
facility: McGuire VA Medical Center
state: Virginia
city: Seattle
country: United States
facility: Swedish Organ Transplant and Liver Center
state: Washington
city: Calgary
country: Canada
facility: University of Calgary
state: Alberta
city: Toronto
country: Canada
facility: LMC Clinical Research Inc (Bayview)
state: Ontario
city: Toronto
country: Canada
facility: Toronto General Hospital
state: Ontario
city: Toronto
country: Canada
facility: Toronto Liver Center
state: Ontario
city: Vaughan
country: Canada
facility: Toronto Digestive Disease Associates, Inc.
state: Ontario
city: Kowloon
country: Hong Kong
facility: Princess Margaret Hospital
city: Sha Tin
country: Hong Kong
facility: The Chinese University of Hong Kong
city: Auckland
country: New Zealand
facility: Auckland Clinical Studies
city: Bern
country: Switzerland
facility: Universitatsspital Bern, Inselspital, Universitatsklinik fur Viszerale Chirurgie und Medizin, Hepatologie
city: Zurich
country: Switzerland
facility: Universitatsspital Zurich
city: Cambridge
country: United Kingdom
facility: Addenbrooke's Hospital
Study officials:
affiliation: Gilead Sciences
name: Gilead Study Director
role: STUDY_DIRECTOR
References:
citation: 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.