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

NCT ID: NCT02856555

Last Updated: 2020-07-24

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

127 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-08-08

Study Completion Date

2017-07-18

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).

Detailed Description

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Conditions

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Nonalcoholic Steatohepatitis (NASH)

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

SEQUENTIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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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.

Group Type EXPERIMENTAL

Firsocostat

Intervention Type DRUG

Capsules orally once daily.

Placebo

Intervention Type DRUG

Placebo matched to firsocostat orally once daily.

Firsocostat 20 mg

Participants will receive firsocostat 2 X 10 mg + 2 x placebo matched to firsocostat 5 mg for 12 weeks.

Group Type EXPERIMENTAL

Firsocostat

Intervention Type DRUG

Capsules orally once daily.

Placebo

Intervention Type DRUG

Placebo matched to firsocostat orally once daily.

Placebo

Participants will receive 2 x placebo matched to firsocostat 5 mg + 2 x placebo matched to firsocostat 10 mg for 12 weeks.

Group Type EXPERIMENTAL

Placebo

Intervention Type DRUG

Placebo matched to firsocostat orally once daily.

Interventions

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Firsocostat

Capsules orally once daily.

Intervention Type DRUG

Placebo

Placebo matched to firsocostat orally once daily.

Intervention Type DRUG

Other Intervention Names

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GS-0976

Eligibility Criteria

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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

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
Minimum Eligible Age

18 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Gilead Sciences

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Gilead Study Director

Role: STUDY_DIRECTOR

Gilead Sciences

Locations

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Coronado, California, United States

Site Status

Foster City, California, United States

Site Status

Los Angeles, California, United States

Site Status

Los Angeles, California, United States

Site Status

Rialto, California, United States

Site Status

San Diego, California, United States

Site Status

San Diego, California, United States

Site Status

San Francisco, California, United States

Site Status

San Francisco, California, United States

Site Status

Miami, Florida, United States

Site Status

Miami, Florida, United States

Site Status

Atlanta, Georgia, United States

Site Status

Chicago, Illinois, United States

Site Status

Indianapolis, Indiana, United States

Site Status

New Orleans, Louisiana, United States

Site Status

Boston, Massachusetts, United States

Site Status

Rochester, Minnesota, United States

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Kansas City, Missouri, United States

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New York, New York, United States

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Durham, North Carolina, United States

Site Status

Statesville, North Carolina, United States

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Philadelphia, Pennsylvania, United States

Site Status

Pittsburgh, Pennsylvania, United States

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Germantown, Tennessee, United States

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Memphis, Tennessee, United States

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Nashville, Tennessee, United States

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Arlington, Texas, United States

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Live Oak, Texas, United States

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San Antonio, Texas, United States

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Murray, Utah, United States

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Falls Church, Virginia, United States

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Richmond, Virginia, United States

Site Status

Richmond, Virginia, United States

Site Status

Richmond, Virginia, United States

Site Status

Richland, Washington, United States

Site Status

Seattle, Washington, United States

Site Status

Countries

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United States

References

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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.

Reference Type RESULT

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.

Reference Type DERIVED
PMID: 30059671 (View on PubMed)

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.

Reference Type DERIVED
PMID: 29705265 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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GS-US-426-3989

Identifier Type: -

Identifier Source: org_study_id

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