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Safety, Tolerability, and Efficacy of Monotherapy and Combination Regimens in Participants With Nonalcoholic Steatohepatitis (NASH)

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ClinicalTrials.gov Identifier: NCT03987074
Recruitment Status : Completed
First Posted : June 14, 2019
Results First Posted : July 15, 2021
Last Update Posted : July 15, 2021
Sponsor:
Collaborator:
Novo Nordisk A/S
Information provided by (Responsible Party):
Gilead Sciences

Brief Summary:
The primary objective of this study is to evaluate the safety and tolerability of study drug(s) in participants with nonalcoholic steatohepatitis (NASH).

Condition or disease Intervention/treatment Phase
Nonalcoholic Steatohepatitis Drug: Semaglutide Drug: Firsocostat Drug: Cilofexor Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 109 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Proof of Concept, Open-Label Study Evaluating the Safety, Tolerability, and Efficacy of Monotherapy and Combination Regimens in Subjects With Nonalcoholic Steatohepatitis (NASH)
Actual Study Start Date : July 29, 2019
Actual Primary Completion Date : July 13, 2020
Actual Study Completion Date : July 13, 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Semaglutide
Semaglutide 0.24 mg - 2.4 mg (dose escalated over 16 weeks) for 24 weeks
Drug: Semaglutide
Solution administered subcutaneously with pre-filled PDS290 pen-injector once weekly

Experimental: Semaglutide + Firsocostat 20 mg
Semaglutide 0.24 mg - 2.4 mg (dose escalated over 16 weeks) + firsocostat 20 mg for 24 weeks
Drug: Semaglutide
Solution administered subcutaneously with pre-filled PDS290 pen-injector once weekly

Drug: Firsocostat
Tablets administered orally once daily
Other Name: GS-0976

Experimental: Semaglutide + Cilofexor 30 mg
Semaglutide 0.24 mg - 2.4 mg (dose escalated over 16 weeks) + cilofexor 30 mg for 24 weeks
Drug: Semaglutide
Solution administered subcutaneously with pre-filled PDS290 pen-injector once weekly

Drug: Cilofexor
Tablets administered orally once daily
Other Name: GS-9674

Experimental: Semaglutide + Cilofexor 100 mg
Semaglutide 0.24 mg - 2.4 mg (dose escalated over 16 weeks) + cilofexor 100 mg for 24 weeks
Drug: Semaglutide
Solution administered subcutaneously with pre-filled PDS290 pen-injector once weekly

Drug: Cilofexor
Tablets administered orally once daily
Other Name: GS-9674

Experimental: Semaglutide + Firsocostat 20 mg + Cilofexor 30 mg
Semaglutide 0.24 mg - 2.4 mg (dose escalated over 16 weeks) + firsocostat 20 mg + cilofexor 30 mg for 24 weeks
Drug: Semaglutide
Solution administered subcutaneously with pre-filled PDS290 pen-injector once weekly

Drug: Firsocostat
Tablets administered orally once daily
Other Name: GS-0976

Drug: Cilofexor
Tablets administered orally once daily
Other Name: GS-9674




Primary Outcome Measures :
  1. Percentage of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs) [ Time Frame: First dose date up to Week 24 plus 30 days ]
    Treatment-emergent adverse events (TEAEs) were defined as, any AEs with an onset date on or after the study drug start date and no later than 30 days after permanent discontinuation of study drug or any AEs leading to premature discontinuation of study drug. Participants were assessed for AEs according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.

  2. Percentage of Participants Experiencing Treatment-Emergent Laboratory Abnormalities [ Time Frame: First dose date up to 24 weeks plus 30 days ]
    Treatment-emergent laboratory abnormalities, defined as values that increase at least one toxicity grade from baseline at any time post-baseline up to and including the date of last dose of study drug plus 30 days, were summarized by treatment group. Graded laboratory abnormalities were defined using the grading scheme in the CTCAE 5.0.



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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Key Inclusion Criteria:

  • Historical liver biopsy consistent with NASH with stage 2-3 fibrosis according to NASH Clinical Research Network (CRN) classification OR clinical diagnosis of nonalcoholic fatty liver disease and screening FibroTest, magnetic resonance imaging - proton density fat fraction (MRI-PDFF), and FibroScan
  • Screening laboratory parameters, as determined by central laboratory:

    • Alanine aminotransferase (ALT) ≤ 5 x upper limit of the normal range (ULN)
    • Estimated glomerular filtration rate (eGFR) ≥ 30 milliliter/minute (mL/min), as calculated by the Modification of Diet in Renal Disease (MDRD) study equation
    • HbA1c ≤ 9.5%
    • International normalized ratio (INR) ≤ 1.2, unless due to therapeutic anti-coagulation therapy
    • Platelet count ≥ 100,000/μL
    • Total bilirubin < 1.3 x ULN unless alternate etiology such as Gilbert's syndrome present
    • Calcitonin ≤ 100 ng/L
  • Body Mass Index (BMI) > 23 kg/m^2 and body weight of > 60 kg

Key Exclusion Criteria:

  • Any historical liver biopsy consistent with cirrhosis
  • Any history of decompensated liver disease, including ascites, hepatic encephalopathy, or variceal bleeding
  • Other causes of liver disease, including but not limited to: alcoholic liver disease, hepatitis B, hepatitis C, autoimmune disorders (eg, primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC), autoimmune hepatitis), drug-induced hepatotoxicity, Wilson disease, clinically significant iron overload, or alpha-1-antitrypsin deficiency requiring treatment
  • History of liver transplantation
  • History of hepatocellular carcinoma
  • History of pancreatitis (acute or chronic)
  • Personal or first degree relative(s) history of multiple endocrine neoplasia type 2 or medullary thyroid carcinoma
  • Treatment with glucagon-like peptide-1 receptor agonists (GLP-1 RA) in the period from 90 days prior to the date of the Screening Visit
  • Individuals on antidiabetic medications must be on a stable dose for at least 90 days prior to the date of the Screening Visit and in the period between the date of the Screening Visit and Enrollment (Day -14)

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): NCT03987074


Locations
Show Show 18 study locations
Sponsors and Collaborators
Gilead Sciences
Novo Nordisk A/S
Investigators
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Study Director: Gilead Study Director Gilead Sciences
  Study Documents (Full-Text)

Documents provided by Gilead Sciences:
Study Protocol  [PDF] October 22, 2019
Statistical Analysis Plan  [PDF] August 6, 2020

Publications of Results:
Alkhouri N et al. Safety and Efficacy of Combination Therapies Including Semaglutide, Cilofexor, and Firsocostat in Patients with NASH [accepted for oral presentation]. American Association for the Study of Liver Diseases (AASLD); 2020; Virtual.

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Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT03987074    
Other Study ID Numbers: GS-US-454-5533
First Posted: June 14, 2019    Key Record Dates
Results First Posted: July 15, 2021
Last Update Posted: July 15, 2021
Last Verified: June 2021
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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Fatty Liver
Non-alcoholic Fatty Liver Disease
Liver Diseases
Digestive System Diseases
Firsocostat
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action