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Safety, Tolerability, and Efficacy of Selonsertib, Firsocostat, and Cilofexor in Adults With Nonalcoholic Steatohepatitis (NASH)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02781584
Recruitment Status : Recruiting
First Posted : May 24, 2016
Last Update Posted : June 30, 2020
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences

Brief Summary:
The primary objective of this study is to evaluate the safety and tolerability of selonsertib, firsocostat, cilofexor, fenofibrate and/or Vascepa® in adults with nonalcoholic fatty liver disease (NAFLD) or nonalcoholic steatohepatitis (NASH).

Condition or disease Intervention/treatment Phase
Nonalcoholic Steatohepatitis (NASH) Nonalcoholic Fatty Liver Disease (NAFLD) Drug: SEL Drug: Firsocostat Drug: Cilofexor Drug: Fenofibrate Drug: Vascepa Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 214 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Cohorts 1-6 and 9 will be enrolled sequentially while Cohorts 7 and 8 will be randomized in parallel. Cohorts 10 and 11 will be randomized in parallel. New cohorts 12 and 13 will be randomized in parallel.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Proof of Concept, Open-Label Study Evaluating the Safety, Tolerability, and Efficacy of Regimens in Subjects With Nonalcoholic Steatohepatitis (NASH)
Actual Study Start Date : July 13, 2016
Estimated Primary Completion Date : November 2020
Estimated Study Completion Date : November 2020


Arm Intervention/treatment
Experimental: SEL (Cohort 1)
SEL (1 x 18 mg tablet) for 12 weeks
Drug: SEL
Administered orally once daily
Other Name: GS-4997

Experimental: Firsocostat (Cohort 2)

Firsocostat (2 x 10 mg capsules) for 12 weeks

Enrollment into Cohort 2 will begin upon completion of enrollment for Cohort 1.

Drug: Firsocostat
Administered orally once daily

Experimental: Cilofexor (Cohort 3)

Cilofexor (3 x 10 mg tablets) for 12 weeks

Enrollment into Cohort 3 will begin upon completion of enrollment for Cohort 2.

Drug: Cilofexor
Administered orally once daily
Other Name: GS-9674

Experimental: SEL+ Cilofexor(Cohort 4)

SEL (1 x 18 mg tablet) + Cilofexor (1 x 30 mg tablet) for 12 weeks

Enrollment into Cohort 4 will begin upon completion of enrollment for Cohort 3.

Drug: SEL
Administered orally once daily
Other Name: GS-4997

Drug: Cilofexor
Administered orally once daily
Other Name: GS-9674

Experimental: SEL + Firsocostat(Cohort 5)

SEL (1 x 18 mg tablet) + firsocostat (1 x 20 mg tablet) for 12 weeks

Enrollment into Cohort 5 will begin upon completion of enrollment for Cohort 4.

Drug: SEL
Administered orally once daily
Other Name: GS-4997

Drug: Firsocostat
Administered orally once daily

Experimental: Firsocostat + Cilofexor(Cohort 6)

Firsocostat (1 x 20 mg tablet) + Cilofexor (1 x 30 mg tablet) for 12 weeks

Enrollment into Cohort 6 will begin upon completion of enrollment for Cohort 5.

Drug: Firsocostat
Administered orally once daily

Drug: Cilofexor
Administered orally once daily
Other Name: GS-9674

Experimental: Firsocostat Cirrhotic (Cohort 7)

Firsocostat (1 x 20 mg tablet) for 12 weeks (participants with Child-Pugh-Turcotte Class A (CPT A) cirrhosis)

Enrollment into Cohorts 7 and 8 will be randomized in parallel.

Drug: Firsocostat
Administered orally once daily

Experimental: Cilofexor Cirrhotic (Cohort 8)

Cilofexor (1 x 30 mg tablet) for 12 weeks (participants with CPT A cirrhosis)

Enrollment into Cohorts 7 and 8 will be randomized in parallel.

Drug: Cilofexor
Administered orally once daily
Other Name: GS-9674

Experimental: SEL + Firsocostat + Cilofexor (Cohort 9)

SEL (1 x 18 mg tablet) + Firsocostat (1 x 20 mg tablet) + Cilofexor (1 x 30 mg tablet) for 12 weeks

Enrollment into Cohort 9 will begin upon completion of enrollment for Cohort 6.

Drug: SEL
Administered orally once daily
Other Name: GS-4997

Drug: Firsocostat
Administered orally once daily

Drug: Cilofexor
Administered orally once daily
Other Name: GS-9674

Experimental: Firsocostat + Fenofibrate 48 mg (Cohort 10)
Pre-treatment with fenofibrate 48 mg from Day -14 to Day -1 and will be treated with firsocostat (1 x 20 mg tablet) + fenofibrate (1 x 48 mg tablet) for 24 weeks
Drug: Firsocostat
Administered orally once daily

Drug: Fenofibrate
Administered orally once daily

Experimental: Firsocostat + Fenofibrate 145 mg (Cohort 11)
Pre-treatment with fenofibrate 145 mg from Day -14 to Day -1 and will be treated with firsocostat (1 x 20 mg tablet) + fenofibrate (1 x 145 mg tablet) for 24 weeks
Drug: Firsocostat
Administered orally once daily

Drug: Fenofibrate
Administered orally once daily

Experimental: Firsocostat + Cilofexor 30 mg + Vascepa® 4 g (Cohort 12)
Pre-treatment with Vascepa® (2 x 1 g tablet twice daily) from Day -14 to Day -1. Then, treatment with Firsocostat (1 x 20 mg tablet once daily) + Cilofexor (1 x 30 mg tablet once daily) + Vascepa® (2 x 1 g tablet twice daily) for 6 weeks
Drug: Firsocostat
Administered orally once daily

Drug: Cilofexor
Administered orally once daily
Other Name: GS-9674

Drug: Vascepa
Administered orally two times daily

Experimental: Firsocostat + Cilofexor 30 mg + fenofibrate 145 mg (Cohort 13)
Pre-treatment with fenofibrate (1 x 145 mg tablet once daily) from Day -14 to Day -1. Then, treatment with Firsocostat (1 x 20 mg tablet once daily) + Cilofexor (1 x 30 mg tablet once daily) + fenofibrate (1 x 145 mg tablet once daily) for 6 weeks
Drug: Firsocostat
Administered orally once daily

Drug: Cilofexor
Administered orally once daily
Other Name: GS-9674

Drug: Fenofibrate
Administered orally once daily




Primary Outcome Measures :
  1. Incidence of Treatment-Emergent Adverse Events [ Time Frame: Up to 24 weeks plus 30 days ]
  2. Incidence of Treatment-Emergent Serious Adverse Events [ Time Frame: Up to 24 weeks plus 30 days ]
  3. Incidence of Treatment-Emergent Laboratory Abnormalities [ Time Frame: Up to 24 weeks plus 30 days ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Key Inclusion Criteria:

  • Males and females between 18-75 years of age (Cohorts 1-9: 18-75 years and Cohorts 10-13: ≥ 18 years); inclusive based on the date of the screening visit
  • Willing and able to provide informed consent prior to any study specific procedures being performed
  • Meets the following conditions (Cohorts 1-6 and 9):

    • Clinical diagnosis of non-alcoholic fatty liver disease and evidence of F2-3 fibrosis
  • For Cohorts 7 and 8, participants must have a clinical diagnosis of NAFLD and cirrhosis
  • For Cohorts 10 and 11, individuals must have a clinical diagnosis of NAFLD and meet one of the following criteria :

    • a) A historical liver biopsy within 6 months of Screening consistent with NASH and bridging fibrosis (F3) or within 12 months of Screening consistent with NASH and compensated cirrhosis (F4) in the opinion of the investigator,
    • b) Screening liver stiffness by MRE ≥ 3.64 kPa;
    • c) Screening liver stiffness by FibroScan® ≥ 9.9 kPa;
  • For Cohorts 12 and 13, subjects must have a clinical diagnosis of NAFLD/NASH and one of the following criteria:

    • a) At least two criteria for metabolic syndrome
    • b) Historical liver biopsy consistent with NASH within 6-12 months of Screening
    • c) Historical MRE with liver stiffness ≥ 2.88 kPa within 6 months of Screening
    • d) Historical FibroScan® with liver stiffness ≥ 9.9 kPa within 6 months of Screening,

Key Exclusion Criteria:

  • Pregnant or lactating females
  • Other causes of liver disease including autoimmune, viral, and alcoholic liver disease
  • Any history of decompensated liver disease, including ascites, hepatic encephalopathy or variceal bleeding
  • For Cohorts 7-8, 10-13, Child-Pugh-Turcotte (CPT) score > 6
  • History of liver transplantation

Note: Other protocol defined Inclusion/Exclusion criteria may apply.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02781584


Contacts
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Contact: Gilead Study Team GileadClinicalTrials@gilead.com

Locations
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United States, Arizona
Arizona Liver Health Recruiting
Chandler, Arizona, United States, 85224
United States, California
Altman Clinical and Translational Research Clinic Recruiting
La Jolla, California, United States, 92037
Ruane Clinical Research Group Inc. Recruiting
Los Angeles, California, United States, 90036
Cedars-Sinai Medical Center Recruiting
Los Angeles, California, United States, 90048
Stanford Hospital and Clinics (SHC) Completed
Stanford, California, United States, 94305
United States, Florida
Florida Research Institute Completed
Lakewood Ranch, Florida, United States, 34211
United States, Louisiana
Delta Research Partners, LLC Recruiting
Bastrop, Louisiana, United States, 71220
United States, Tennessee
Gastro One Completed
Germantown, Tennessee, United States, 38138
Quality Medical Research Completed
Nashville, Tennessee, United States, 37211
United States, Texas
Pinnacle Clinical Research, PLLC Completed
Live Oak, Texas, United States, 78233
American Research Corporation at the Texas Liver Institute Recruiting
San Antonio, Texas, United States, 78215
New Zealand
Auckland Clinical Studies Ltd Completed
Auckland, New Zealand, 1010
Sponsors and Collaborators
Gilead Sciences
Investigators
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Study Director: Gilead Study Director Gilead Sciences
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Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT02781584    
Other Study ID Numbers: GS-US-384-3914
First Posted: May 24, 2016    Key Record Dates
Last Update Posted: June 30, 2020
Last Verified: June 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Liver Diseases
Fatty Liver
Non-alcoholic Fatty Liver Disease
Digestive System Diseases
Fenofibrate
Firsocostat
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Lipid Regulating Agents
Enzyme Inhibitors