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

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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

Tracking Information
First Submitted Date  ICMJE May 20, 2016
First Posted Date  ICMJE May 24, 2016
Last Update Posted Date June 30, 2020
Actual Study Start Date  ICMJE July 13, 2016
Estimated Primary Completion Date November 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 28, 2018)
  • Incidence of Treatment-Emergent Adverse Events [ Time Frame: Up to 24 weeks plus 30 days ]
  • Incidence of Treatment-Emergent Serious Adverse Events [ Time Frame: Up to 24 weeks plus 30 days ]
  • Incidence of Treatment-Emergent Laboratory Abnormalities [ Time Frame: Up to 24 weeks plus 30 days ]
Original Primary Outcome Measures  ICMJE
 (submitted: May 20, 2016)
Incidence of adverse events [ Time Frame: Up to 12 weeks plus 30 days ]
Safety of GS-4997 in adults with hepatic steatosis and elevated liver stiffness will be measured by the incidence of adverse events.
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Safety, Tolerability, and Efficacy of Selonsertib, Firsocostat, and Cilofexor in Adults With Nonalcoholic Steatohepatitis (NASH)
Official Title  ICMJE A Proof of Concept, Open-Label Study Evaluating the Safety, Tolerability, and Efficacy of Regimens in Subjects With Nonalcoholic Steatohepatitis (NASH)
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).
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE 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
Condition  ICMJE
  • Nonalcoholic Steatohepatitis (NASH)
  • Nonalcoholic Fatty Liver Disease (NAFLD)
Intervention  ICMJE
  • 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
  • Drug: Fenofibrate
    Administered orally once daily
  • Drug: Vascepa
    Administered orally two times daily
Study Arms  ICMJE
  • Experimental: SEL (Cohort 1)
    SEL (1 x 18 mg tablet) for 12 weeks
    Intervention: Drug: SEL
  • 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.

    Intervention: Drug: Firsocostat
  • 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.

    Intervention: Drug: Cilofexor
  • 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.

    Interventions:
    • Drug: SEL
    • Drug: Cilofexor
  • 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.

    Interventions:
    • Drug: SEL
    • Drug: Firsocostat
  • 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.

    Interventions:
    • Drug: Firsocostat
    • Drug: Cilofexor
  • 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.

    Intervention: Drug: Firsocostat
  • 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.

    Intervention: Drug: Cilofexor
  • 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.

    Interventions:
    • Drug: SEL
    • Drug: Firsocostat
    • Drug: Cilofexor
  • 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
    Interventions:
    • Drug: Firsocostat
    • Drug: Fenofibrate
  • 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
    Interventions:
    • Drug: Firsocostat
    • Drug: Fenofibrate
  • 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
    Interventions:
    • Drug: Firsocostat
    • Drug: Cilofexor
    • Drug: Vascepa
  • 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
    Interventions:
    • Drug: Firsocostat
    • Drug: Cilofexor
    • Drug: Fenofibrate
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: February 25, 2020)
214
Original Estimated Enrollment  ICMJE
 (submitted: May 20, 2016)
10
Estimated Study Completion Date  ICMJE November 2020
Estimated Primary Completion Date November 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Gilead Study Team GileadClinicalTrials@gilead.com
Listed Location Countries  ICMJE New Zealand,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02781584
Other Study ID Numbers  ICMJE GS-US-384-3914
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Gilead Sciences
Study Sponsor  ICMJE Gilead Sciences
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Gilead Study Director Gilead Sciences
PRS Account Gilead Sciences
Verification Date June 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP