Clinical trial NCT02856555: Study to Evaluate Safety, Tolerability, and Efficacy of GS-0976 in Adults With Nonalcoholic Steatohepatitis
Official title: A Phase 2, Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Safety, Tolerability, and Efficacy of GS-0976 in Subjects With Nonalcoholic Steatohepatitis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Nonalcoholic Steatohepatitis (NASH)
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2016-08-05
Enrollment: 127
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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


Eligibility criteria: 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.

Primary outcomes:
measure: Percentage of Participants Experiencing Treatment-Emergent Adverse Events
timeFrame: First Dose date up to last dose (Week 12) plus 30 days
Secondary outcomes:
Other outcomes:
Locations:
city: Coronado
country: United States
state: California
city: Foster City
country: United States
state: California
city: Los Angeles
country: United States
state: California
city: Los Angeles
country: United States
state: California
city: Rialto
country: United States
state: California
city: San Diego
country: United States
state: California
city: San Diego
country: United States
state: California
city: San Francisco
country: United States
state: California
city: San Francisco
country: United States
state: California
city: Miami
country: United States
state: Florida
city: Miami
country: United States
state: Florida
city: Atlanta
country: United States
state: Georgia
city: Chicago
country: United States
state: Illinois
city: Indianapolis
country: United States
state: Indiana
city: New Orleans
country: United States
state: Louisiana
city: Boston
country: United States
state: Massachusetts
city: Rochester
country: United States
state: Minnesota
city: Kansas City
country: United States
state: Missouri
city: New York
country: United States
state: New York
city: Durham
country: United States
state: North Carolina
city: Statesville
country: United States
state: North Carolina
city: Philadelphia
country: United States
state: Pennsylvania
city: Pittsburgh
country: United States
state: Pennsylvania
city: Germantown
country: United States
state: Tennessee
city: Memphis
country: United States
state: Tennessee
city: Nashville
country: United States
state: Tennessee
city: Arlington
country: United States
state: Texas
city: Live Oak
country: United States
state: Texas
city: San Antonio
country: United States
state: Texas
city: Murray
country: United States
state: Utah
city: Falls Church
country: United States
state: Virginia
city: Richmond
country: United States
state: Virginia
city: Richmond
country: United States
state: Virginia
city: Richmond
country: United States
state: Virginia
city: Richland
country: United States
state: Washington
city: Seattle
country: United States
state: Washington
Study officials:
affiliation: Gilead Sciences
name: Gilead Study Director
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.