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Trial · Interventional

CompletedPhase 2Results postedRegistry data

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

Overview

Status
Completed
Phase
Phase 2
Enrollment
109 participants (actual)
Sponsor
Gilead Sciences · Industry
Design
Randomized · Open label (no masking)
Countries
1 country

United States

Start
29 Jul 2019
Primary completion
13 Jul 2020
Completion
13 Jul 2020
First posted
14 Jun 2019
Last update posted
15 Jul 2021
Conditions
Nonalcoholic Steatohepatitis

Timeline

1 trial · 1 completed · 1 with posted results

  • Completed
  • Ongoing
  • Not yet recruiting
  • Stopped
  • Estimated dates (est.)
  • Results posted
201920202021
  1. Ph 2

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

    NCT03987074

    29 Jul 2019 to 13 Jul 2020

Registry summary

Text and fields below are the sponsor's entries at ClinicalTrials.gov, shown as posted.

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

Interventions

  • SemaglutideDrug
  • FirsocostatDrug
  • CilofexorDrug

Arms5

  • Experimental

    Semaglutide

    Semaglutide 0.24 mg - 2.4 mg (dose escalated over 16 weeks) for 24 weeks

  • Experimental

    Semaglutide + Firsocostat 20 mg

    Semaglutide 0.24 mg - 2.4 mg (dose escalated over 16 weeks) + firsocostat 20 mg for 24 weeks

  • Experimental

    Semaglutide + Cilofexor 30 mg

    Semaglutide 0.24 mg - 2.4 mg (dose escalated over 16 weeks) + cilofexor 30 mg for 24 weeks

  • Experimental

    Semaglutide + Cilofexor 100 mg

    Semaglutide 0.24 mg - 2.4 mg (dose escalated over 16 weeks) + cilofexor 100 mg for 24 weeks

  • 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

Primary outcomes2

Outcomes the sponsor listed as primary.

  1. Percentage of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs)

    Time frame · First dose date up to Week 24 plus 30 days

    Registry description

    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

    Registry description

    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.

Posted results

Values are shown as posted at ClinicalTrials.gov, with their units. PepBank has not converted, pooled or compared them.

Primary outcome results

Primary outcomeNumber· First dose date up to Week 24 plus 30 days

Percentage of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs)

GroupValue (percentage of participants)
Semaglutide81.0
Semaglutide + Firsocostat 20 mg86.4
Semaglutide + Cilofexor 30 mg81.8
Semaglutide + Cilofexor 100 mg72.7
Semaglutide + Firsocostat 20 mg + Cilofexor 30 mg90.5
Primary outcomeNumber· First dose date up to 24 weeks plus 30 days

Percentage of Participants Experiencing Treatment-Emergent Laboratory Abnormalities

GroupValue (percentage of participants)
Semaglutide61.9
Semaglutide + Firsocostat 20 mg63.6
Semaglutide + Cilofexor 30 mg36.4
Semaglutide + Cilofexor 100 mg50.0
Semaglutide + Firsocostat 20 mg + Cilofexor 30 mg66.7

Adverse events, as posted

Adverse events as posted: participants affected out of participants at risk, by group
GroupDeathsSerious eventsOther events
SemaglutideParticipants received semaglutide 0.24 mg - 2.4 mg (dose escalated over 16 weeks) subcutaneously with prefilled PDS290 pen-injector once weekly for 24 weeks.0 / 211 / 2116 / 21
Semaglutide + Firsocostat 20 mgParticipants received semaglutide 0.24 mg - 2.4 mg (dose escalated over 16 weeks) subcutaneously with prefilled PDS290 pen-injector once weekly for 24 weeks + firsocostat 20 mg tablet orally once daily with or without food for 24 weeks.0 / 220 / 2217 / 22
Semaglutide + Cilofexor 30 mgParticipants received semaglutide 0.24 mg - 2.4 mg (dose escalated over 16 weeks) subcutaneously with prefilled PDS290 pen-injector once weekly for 24 weeks + cilofexor 30 mg tablet orally once daily with or without food for 24 weeks.0 / 220 / 2218 / 22
Semaglutide + Cilofexor 100 mgSemaglutide + Cilofexor 100 mg Participants received semaglutide 0.24 mg - 2.4 mg (dose escalated over 16 weeks) subcutaneously with prefilled PDS290 pen-injector once weekly for 24 weeks + cilofexor 100 mg tablet orally once daily with or without food for 24 weeks.0 / 221 / 2213 / 22
Semaglutide + Firsocostat 20 mg + Cilofexor 30 mgParticipants received semaglutide 0.24 mg - 2.4 mg (dose escalated over 16 weeks) subcutaneously with prefilled PDS290 pen-injector once weekly for 24 weeks + firsocostat 20 mg tablet orally once daily + cilofexor 30 mg tablet orally once daily with or without food for 24 weeks.0 / 210 / 2117 / 21

Each cell reads participants affected / participants at risk, as the registry posted them.

Registry data comes from ClinicalTrials.gov. Study results come from studies, not from the registry. How PepBank works

Studies1

Studies that cite this trial.

Studies with results

1 study on this page

Indexing hint: Randomized controlled trial · 2022

6 results

Safety and efficacy of combination therapy with semaglutide, cilofexor and firsocostat in patients with non-alcoholic steatohepatitis: A randomised, open-label phase II trial.

Alkhouri et al. 2022Journal of hepatologycited by 195

PMID 35439567DOI 10.1016/j.jhep.2022.04.003PUB-35439567

Full text at the publisher6 results

Other registry references

References listed at the registry that are not in PepBank. They link to PubMed.

  • ResultAlkhouri 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.

Eligibility

Who could join, as posted.

Sex
All
Age
from 18 Years up to 75 Years
Healthy volunteers
Not accepted
Inclusion and exclusion criteria, as posted
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.

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