Safety, Tolerability, and Efficacy of Monotherapy and Combination Regimens in Participants With Nonalcoholic Steatohepatitis (NASH)
A Proof of Concept, Open-Label Study Evaluating the Safety, Tolerability, and Efficacy of Monotherapy and Combination Regimens in Subjects With Nonalcoholic Steatohepatitis (NASH)
1 other identifier
interventional
109
1 country
18
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).
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_2
Started Jul 2019
Shorter than P25 for phase_2
18 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
June 12, 2019
CompletedFirst Posted
Study publicly available on registry
June 14, 2019
CompletedStudy Start
First participant enrolled
July 29, 2019
CompletedPrimary Completion
Last participant's last visit for primary outcome
July 13, 2020
CompletedStudy Completion
Last participant's last visit for all outcomes
July 13, 2020
CompletedResults Posted
Study results publicly available
July 15, 2021
CompletedJuly 15, 2021
June 1, 2021
12 months
June 12, 2019
June 25, 2021
June 25, 2021
Conditions
Outcome Measures
Primary Outcomes (2)
Percentage of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs)
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.
First dose date up to Week 24 plus 30 days
Percentage of Participants Experiencing Treatment-Emergent Laboratory Abnormalities
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.
First dose date up to 24 weeks plus 30 days
Study Arms (5)
Semaglutide
EXPERIMENTALSemaglutide 0.24 mg - 2.4 mg (dose escalated over 16 weeks) for 24 weeks
Semaglutide + Firsocostat 20 mg
EXPERIMENTALSemaglutide 0.24 mg - 2.4 mg (dose escalated over 16 weeks) + firsocostat 20 mg for 24 weeks
Semaglutide + Cilofexor 30 mg
EXPERIMENTALSemaglutide 0.24 mg - 2.4 mg (dose escalated over 16 weeks) + cilofexor 30 mg for 24 weeks
Semaglutide + Cilofexor 100 mg
EXPERIMENTALSemaglutide 0.24 mg - 2.4 mg (dose escalated over 16 weeks) + cilofexor 100 mg for 24 weeks
Semaglutide + Firsocostat 20 mg + Cilofexor 30 mg
EXPERIMENTALSemaglutide 0.24 mg - 2.4 mg (dose escalated over 16 weeks) + firsocostat 20 mg + cilofexor 30 mg for 24 weeks
Interventions
Solution administered subcutaneously with pre-filled PDS290 pen-injector once weekly
Tablets administered orally once daily
Tablets administered orally once daily
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- 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)
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Gilead Scienceslead
- Novo Nordisk A/Scollaborator
Study Sites (18)
Institute for Liver Health - Arizona Liver Health
Chandler, Arizona, 85224, United States
Southern California Research Centers
Coronado, California, 92118, United States
University of California San Diego (UCSD)
La Jolla, California, 92093, United States
Ruane Clinical Research Group, Inc
Los Angeles, California, 90036, United States
Cedars Sinai Medical Center
Los Angeles, California, 90048, United States
Inland Empire Clinical Trials, LLC
Rialto, California, 92377, United States
Medical Associates Research Group
San Diego, California, 92123, United States
Gastrointestinal Specialists of Georgia
Marietta, Georgia, 30060, United States
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02215, United States
Jubilee Clinical Research, Inc.
Las Vegas, Nevada, 89109, United States
Northwell Health
Manhasset, New York, 11030, United States
Gastro One
Huntersville, North Carolina, 28078, United States
University Gastroenterology
Providence, Rhode Island, 02905, United States
Gastro One
Germantown, Tennessee, 38138, United States
Quality Medical Research, PLLC
Nashville, Tennessee, 37211, United States
Texas Clinical Research Institute
Arlington, Texas, 76012, United States
The Liver Institute at Methodist Dallas Medical Center
Dallas, Texas, 75203, United States
American Research Corporation
San Antonio, Texas, 78215, United States
Related Publications (2)
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.
RESULTAlkhouri N, Herring R, Kabler H, Kayali Z, Hassanein T, Kohli A, Huss RS, Zhu Y, Billin AN, Damgaard LH, Buchholtz K, Kjaer MS, Balendran C, Myers RP, Loomba R, Noureddin M. Safety and efficacy of combination therapy with semaglutide, cilofexor and firsocostat in patients with non-alcoholic steatohepatitis: A randomised, open-label phase II trial. J Hepatol. 2022 Sep;77(3):607-618. doi: 10.1016/j.jhep.2022.04.003. Epub 2022 Apr 16.
PMID: 35439567DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Results Point of Contact
- Title
- Gilead Clinical Study Information Center
- Organization
- Gilead Sciences
Study Officials
- STUDY DIRECTOR
Gilead Study Director
Gilead Sciences
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
June 12, 2019
First Posted
June 14, 2019
Study Start
July 29, 2019
Primary Completion
July 13, 2020
Study Completion
July 13, 2020
Last Updated
July 15, 2021
Results First Posted
July 15, 2021
Record last verified: 2021-06
Data Sharing
- IPD Sharing
- Will not share