Nonalcoholic SteatohepatitisPhase 2NCT03987074
Safety, Tolerability, and Efficacy of Monotherapy and Combination Regimens in Participants With Nonalcoholic Steatohepatitis (NASH)
A Phase 2 study testing Semaglutide, Firsocostat and Cilofexor in people with Nonalcoholic Steatohepatitis, run by Gilead Sciences at 18 sites in United States.
Trial summary
The primary objective of this study is to evaluate the safety and tolerability of study drug(s) in participants with nonalcoholic steatohepatitis (NASH). Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Nonalcoholic Steatohepatitis
- What is being tested?
- Semaglutide, Firsocostat and Cilofexor
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 109 participants
- Where
- 18 sitesUnited States
- Study dates
- 29 Jul 2019to 13 Jul 2020
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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)
Show all 10Show fewer
- 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.
Trial locations and contacts
18 sites in 1 country.
18 sites in 1 country
United States18 sites
Texas Clinical Research Institute
Arlington, Texas, 76012
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02215
Institute for Liver Health - Arizona Liver Health
Chandler, Arizona, 85224
Southern California Research Centers
Coronado, California, 92118
The Liver Institute at Methodist Dallas Medical Center
Dallas, Texas, 75203
Gastro One
Germantown, Tennessee, 38138
Gastro One
Huntersville, North Carolina, 28078
University of California San Diego (UCSD)
La Jolla, California, 92093
Jubilee Clinical Research, Inc.
Las Vegas, Nevada, 89109
Ruane Clinical Research Group, Inc
Los Angeles, California, 90036
Cedars Sinai Medical Center
Los Angeles, California, 90048
Northwell Health
Manhasset, New York, 11030
Gastrointestinal Specialists of Georgia
Marietta, Georgia, 30060
Quality Medical Research, PLLC
Nashville, Tennessee, 37211
University Gastroenterology
Providence, Rhode Island, 02905
Inland Empire Clinical Trials, LLC
Rialto, California, 92377
American Research Corporation
San Antonio, Texas, 78215
Medical Associates Research Group
San Diego, California, 92123
About this study
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)
The primary objective of this study is to evaluate the safety and tolerability of study drug(s) in participants with nonalcoholic steatohepatitis (NASH).
- Conditions
- Nonalcoholic Steatohepatitis
- Being tested
- Semaglutide, Firsocostat, Cilofexor
- Medical subject headings
- Non-alcoholic Fatty Liver Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SemaglutideDrug
Solution administered subcutaneously with pre-filled PDS290 pen-injector once weekly
FirsocostatDrug
Also called GS-0976
Tablets administered orally once daily
CilofexorDrug
Also called GS-9674
Tablets administered orally once daily
| Study group | Role | What they receive |
|---|---|---|
| Semaglutide | Experimental | Semaglutide 0.24 mg - 2.4 mg (dose escalated over 16 weeks) for 24 weeks Receives: Drug: Semaglutide |
| Semaglutide + Firsocostat 20 mg | Experimental | Semaglutide 0.24 mg - 2.4 mg (dose escalated over 16 weeks) + firsocostat 20 mg for 24 weeks Receives: Drug: Semaglutide; Drug: Firsocostat |
| Semaglutide + Cilofexor 30 mg | Experimental | Semaglutide 0.24 mg - 2.4 mg (dose escalated over 16 weeks) + cilofexor 30 mg for 24 weeks Receives: Drug: Semaglutide; Drug: Cilofexor |
| Semaglutide + Cilofexor 100 mg | Experimental | Semaglutide 0.24 mg - 2.4 mg (dose escalated over 16 weeks) + cilofexor 100 mg for 24 weeks Receives: Drug: Semaglutide; Drug: Cilofexor |
| Semaglutide + Firsocostat 20 mg + Cilofexor 30 mg | Experimental | Semaglutide 0.24 mg - 2.4 mg (dose escalated over 16 weeks) + firsocostat 20 mg + cilofexor 30 mg for 24 weeks Receives: Drug: Semaglutide; Drug: Firsocostat; Drug: Cilofexor |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: First dose date up to 24 weeks plus 30 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Jun 2019
- Study start29 Jul 2019
- Primary completion13 Jul 2020
- Study completion13 Jul 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Nonalcoholic SteatohepatitisStudies of the same condition, open and under way.
- More trials run by Gilead SciencesThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 109 participants (actual)
Sponsor and investigators
- Lead sponsor
- Gilead Sciences
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Novo Nordisk A/S
- Responsible party
- Sponsor
- Investigators
- Gilead Study Director, Study director, Gilead Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03987074
- Sponsor's protocol ID
- GS-US-454-5533
- Status last verified
- Jun 2021
- First submitted
- 12 Jun 2019
- Last updated
- 15 Jul 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
Alkhouri 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.
PubMed 35439567
Study at a glance
From the registry record, last updated by the sponsor on 15 Jul 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT03987074
- Acronym / sponsor ID
- GS-US-454-5533
- Conditions
- Nonalcoholic Steatohepatitis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 109 participants (actual)
- Lead sponsor
- Gilead SciencesIndustry (pharma, biotech, devices)
- Collaborators
- Novo Nordisk A/S
- Study start
- 29 Jul 2019 (actual)
- Primary completion
- 13 Jul 2020 (actual)
- Study completion
- 13 Jul 2020 (actual)
- First posted
- 14 Jun 2019 (actual)
- Results
- Posted 15 Jul 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The primary objective of this study is to evaluate the safety and tolerability of study drug(s) in participants with nonalcoholic steatohepatitis (NASH).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| Semaglutide | Experimental | Drug: SemaglutideSemaglutide 0.24 mg - 2.4 mg (dose escalated over 16 weeks) for 24 weeks |
| Semaglutide + Firsocostat 20 mg | Experimental | Drug: Semaglutide, Drug: FirsocostatSemaglutide 0.24 mg - 2.4 mg (dose escalated over 16 weeks) + firsocostat 20 mg for 24 weeks |
| Semaglutide + Cilofexor 30 mg | Experimental | Drug: Semaglutide, Drug: CilofexorSemaglutide 0.24 mg - 2.4 mg (dose escalated over 16 weeks) + cilofexor 30 mg for 24 weeks |
| Semaglutide + Cilofexor 100 mg | Experimental | Drug: Semaglutide, Drug: CilofexorSemaglutide 0.24 mg - 2.4 mg (dose escalated over 16 weeks) + cilofexor 100 mg for 24 weeks |
| Semaglutide + Firsocostat 20 mg + Cilofexor 30 mg | Experimental | Drug: Semaglutide, Drug: Firsocostat, Drug: CilofexorSemaglutide 0.24 mg - 2.4 mg (dose escalated over 16 weeks) + firsocostat 20 mg + cilofexor 30 mg for 24 weeks |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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:
- Body Mass Index (BMI) > 23 kg/m^2 and body weight of > 60 kg
Key exclusion criteria (10 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SemaglutideSolution administered subcutaneously with pre-filled PDS290 pen-injector once weekly | Drug | Semaglutide, Semaglutide + Cilofexor 100 mg, Semaglutide + Cilofexor 30 mg, Semaglutide + Firsocostat 20 mg, Semaglutide + Firsocostat 20 mg + Cilofexor 30 mg |
| FirsocostatAlso: GS-0976Tablets administered orally once daily | Drug | Semaglutide + Firsocostat 20 mg, Semaglutide + Firsocostat 20 mg + Cilofexor 30 mg |
| CilofexorAlso: GS-9674Tablets administered orally once daily | Drug | Semaglutide + Cilofexor 100 mg, Semaglutide + Cilofexor 30 mg, Semaglutide + Firsocostat 20 mg + Cilofexor 30 mg |
Primary outcome
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.
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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Jul 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publicationAlkhouri 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.
- Derived from this study: PubMed 35439567Alkhouri 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Gilead Study Director study director
Gilead Sciences
18 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Semaglutide, Firsocostat and Cilofexor in people with Nonalcoholic Steatohepatitis, run by Gilead Sciences at 18 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 15 Jul 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 18 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 15 Jul 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs) (time frame: First dose date up to Week 24 plus 30 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03987074, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Jul 2021.