Nonalcoholic Steatohepatitis (NASH)Phase 2NCT02781584
Safety, Tolerability, and Efficacy of Selonsertib, Firsocostat, and Cilofexor in Adults With Nonalcoholic Steatohepatitis (NASH)
A Phase 2 study testing SEL, FIR and CILO in people with Nonalcoholic Steatohepatitis (NASH) and Nonalcoholic Fatty Liver Disease (NAFLD), run by Gilead Sciences at 13 sites in 2 countries.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Nonalcoholic Steatohepatitis (NASH), Nonalcoholic Fatty Liver Disease (NAFLD)
- What is being tested?
- SEL, FIR and CILO
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 220 participants
- Where
- 13 sitesin 2 countries
- Study dates
- 13 Jun 2016to 17 Dec 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
- For Cohorts 1 through 6 and 9, individuals must meet the following conditions:
- Clinical diagnosis of nonalcoholic fatty liver disease (NAFLD)
- Screening FibroTest® < 0.75, unless a historical liver biopsy within 12 months of Screening does not reveal cirrhosis. In individuals with Gilbert's syndrome or hemolysis, FibroTest® will be calculated using direct bilirubin instead of total bilirubin,
- Screening magnetic resonance imaging - proton density fat fraction (MRI-PDFF) with ≥ 10% steatosis,
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- Screening magnetic resonance elastography (MRE) with liver stiffness ≥ 2.88 kPa, OR
- A historical liver biopsy within 12 months of Screening consistent with NASH (defined as the presence of steatosis, inflammation, and ballooning) with stage 2-3 fibrosis according to the NASH Clinical Research Network (CRN) classification (or equivalent), AND
- No documented weight loss > 5% between the date of the liver biopsy and Screening;
- For Cohorts 7 and 8, individuals must have a clinical diagnosis of NAFLD and have at least one of the following criteria:
- Screening MRE with liver stiffness ≥ 4.67 kPa,
- A historical FibroScan® ≥ 14 kPa within 6 months of Screening,
- Screening FibroTest® ≥ 0.75,
- A historical liver biopsy consistent with stage 4 fibrosis according to the NASH CRN classification (or equivalent);
- For Cohorts 10 and 11, individuals must have a clinical diagnosis of NAFLD and meet at least two criteria for metabolic syndrome modified from the NCEP ATP III Guidelines and one of the following criteria at Screening:
- 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,
- Screening liver stiffness by MRE ≥ 3.64 kPa;
- Screening liver stiffness by FibroScan® ≥ 9.9 kPa;
- For Cohorts 12 and 13, individuals must have a clinical diagnosis of NAFLD/NASH and at least two criteria for metabolic syndrome as modified from the NCEPT ATP III Guidelines, OR one of the following criteria:
- A historical liver biopsy within 6 months of Screening consistent with NASH for individuals without compensated cirrhosis (F4); or within 12 months of Screening consistent with NASH for individuals with compensated cirrhosis (F4) in the opinion of the investigator,
- A historical MRE with liver stiffness ≥ 2.88 kPa within 6 months of Screening,
- A historical FibroScan® with liver stiffness ≥ 9.9 kPa within 6 months of Screening, AND
- No documented weight loss > 5% between the date of the historical liver biopsy, historical MRE, or historical FibroScan® and Screening;
- Platelet count ≥ 100,000/µL;
- Serum creatinine < 2 mg/dL (Cohorts 1-9) at Screening;
- Estimated glomerular filtration rate (eGFR) ≥ 80 mL/min (Cohorts 10-11) or ≥ 60 mL/min (Cohorts 12-13), as calculated by the Cockcroft-Gault equation at Screening;
- For Cohorts 10-13, serum triglyceride level ≥ 150 mg/dL at Screening.
Who cannot join
- 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
- History of hepatocellular carcinoma;
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- Weight reduction surgery in the past 2 years or planned during the study;
- Documented weight loss > 5% between the date of the historical liver biopsy and Screening, if applicable;
- Body Mass Index (BMI) < 18 kg/m2;
- ALT > 5 x ULN at Screening;
- For Cohorts 10-13, HbA1c ≥ 9.5% (or serum fructosamine ≥ 381 µmol if HbA1c is unable to be resulted) at Screening;
- For Cohorts 10-13, hemoglobin ≤ 10.6 g/dL at Screening;
- INR > 1.2 (Cohorts 1-9) or INR > 1.4 (Cohorts 10-13) at Screening, unless on anticoagulation therapy;
- Total bilirubin > 1x ULN (Cohorts 1 through 6 and 9), >1.5 x ULN (Cohorts 7 and 8), or >1.3 x ULN (Cohorts 10-13) except in confirmed cases of Gilbert's syndrome;
- Triglycerides ≥ 500 mg/dL (Cohorts 5-8 and 10-13) or ≥ 250 mg/dL (Cohort 9) at Screening;
- Model for End-Stage Liver Disease (MELD) score > 12 at Screening (Cohorts 10 -13), unless due to an alternate etiology such as therapeutic anticoagulation;
- Chronic hepatitis B (HBsAg positive);
- Chronic hepatitis C (HCV RNA positive). individuals cured of HCV infection less than 2 years prior to the Screening visit are not eligible (Cohorts 10-13);
- HIV Ab positive;
- Presence of gallstones within 6 months of Screening (Cohorts 10-13);
- Alcohol consumption greater than 21 oz/week for males or 14 oz/week for females (1oz/30 mL of alcohol is present in 1 12oz/360 mL beer, 1 4oz/120 mL glass of wine, and a 1 oz/30 mL measure of 40% proof alcohol);
- Positive urine screen for amphetamines, cocaine or opiates (i.e., heroin, morphine) at Screening. Individuals on stable methadone or buprenorphine maintenance treatment for at least 6 months prior to Screening may be included in the study. Individuals with a positive urine drug screen due to prescription opioid-based medication are eligible if the prescription and diagnosis are reviewed and approved by the investigator;
- Unstable cardiovascular disease;
- History of intestinal resection of the extent that would result in malabsorption;
- Use of any prohibited concomitant medications as described in the protocol;
- History of a malignancy within 5 years of Screening with the following exceptions:
- Adequately treated carcinoma in situ of the cervix,
- Adequately treated basal or squamous cell cancer or other localized non-melanoma skin cancer.
- Note: Other protocol defined Inclusion/Exclusion criteria may apply.
Trial locations and contacts
13 sites in 2 countries.
13 sites in 2 countries
United States12 sites
Delta Research Partners, LLC
Bastrop, Louisiana, 71220
Arizona Liver Health
Chandler, Arizona, 85224
Gastro One
Germantown, Tennessee, 38138
Altman Clinical and Translational Research Clinic
La Jolla, California, 92093
Florida Research Institute
Lakewood Rch, Florida, 34211
Pinnacle Clinical Research, PLLC
Live Oak, Texas, 78233
Ruane Clinical Research Group Inc.
Los Angeles, California, 90036
Cedars-Sinai Medical Center
Los Angeles, California, 90048
Quality Medical Research
Nashville, Tennessee, 37211
American Research Corporation at the Texas Liver Institute
San Antonio, Texas, 78215
Pinnacle Clinical Research, PLLC
San Antonio, Texas, 78229
Stanford Hospital and Clinics (SHC)
Stanford, California, 94305
About this study
Official title: A Proof of Concept, Open-Label Study Evaluating the Safety, Tolerability, and Efficacy of Regimens in Subjects With Nonalcoholic Steatohepatitis (NASH)
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).
- Being tested
- SEL, FIR, CILO, FENO, VAS
- 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.
SELDrug
Also called GS-4997
Administered orally once daily
FIRDrug
Also called GS-0976
Administered orally once daily
CILODrug
Also called GS-9674
Administered orally once daily
FENODrug
Administered orally once daily
VASDrug
Administered orally two times daily
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1: SEL 18 mg (Non-cirrhotic) | Experimental | Non-cirrhotic participants will receive selonsertib (SEL) 18 mg tablet orally once daily for 12 weeks. Receives: Drug: SEL |
| Cohort 2: FIR 20 mg (Non-cirrhotic) | Experimental | Non-cirrhotic participants will receive firsocostat (FIR) 20 mg tablet orally once daily for 12 weeks. Receives: Drug: FIR |
| Cohort 3: CILO 30 mg (Non-cirrhotic) | Experimental | Non-cirrhotic participants will receive cilofexor (CILO) 30 mg tablet once daily for 12 weeks. Receives: Drug: CILO |
| Cohort 4: SEL 18 mg + CILO 30 mg (Non-cirrhotic) | Experimental | Non-cirrhotic participants will receive SEL 18 mg tablet + CILO 30 mg tablet once daily for 12 weeks. Receives: Drug: SEL; Drug: CILO |
| Cohort 5: SEL 18 mg + FIR 20 mg (Non-cirrhotic) | Experimental | Non-cirrhotic participants will receive SEL 18 mg tablet + FIR 20 mg tablet once daily for 12 weeks. Receives: Drug: SEL; Drug: FIR |
| Cohort 6: CILO 30 mg + FIR 20 mg (Non-cirrhotic) | Experimental | Non-cirrhotic participants will receive CILO 30 mg tablet + FIR 20 mg tablet once daily for 12 weeks. Receives: Drug: FIR; Drug: CILO |
| Cohort 7: CILO 20 mg (Cirrhotic) | Experimental | Participants with Child-Pugh-Turcotte Class A cirrhosis will receive FIR 20 mg tablet once daily for 12 weeks. Receives: Drug: FIR |
| Cohort 8: CILO 30 mg (Cirrhotic) | Experimental | Participants with Child-Pugh-Turcotte Class A cirrhosis will receive CILO 30 mg tablet once daily for 12 weeks. Receives: Drug: CILO |
| Cohort 9: SEL 18 mg + FIR 20 mg + CILO 30 mg (Non-cirrhotic) | Experimental | Non-cirrhotic participants will receive SEL 18 mg tablet + FIR 20 mg tablet + CILO 30 mg tablet once daily for 12 weeks. Receives: Drug: SEL; Drug: FIR; Drug: CILO |
| Cohort 10: FIR 20 mg + FENO 48 mg | Experimental | Participants will receive fenofibrate (FENO) 48 mg tablet orally once daily for 2 weeks in the pretreatment phase, then FIR 20 mg tablet + FENO 48 mg tablet orally once daily for 24 weeks in the treatment phase. Participants with compensated cirrhosis due to NASH will be accepted to participate in this cohort. Receives: Drug: FIR; Drug: FENO |
| Cohort 11: FIR 20 mg + FENO 145 mg | Experimental | Participants will receive FENO 145 mg tablet orally once daily for 2 weeks in the pretreatment phase, then FIR 20 mg tablet + FENO 145 mg tablet orally once daily for 24 weeks in the treatment phase. Participants with compensated cirrhosis due to NASH will be accepted to participate in this cohort. Receives: Drug: FIR; Drug: FENO |
| Cohort 12: FIR 20 mg + CILO 30 mg + VAS 2g | Experimental | Participants will receive Vascepa® (VAS) 2 g capsule orally twice daily for 2 weeks in the pretreatment phase, then FIR 20 mg tablet once daily + CILO 30 mg tablet once daily + VAS 2 g capsule twice daily for 6 weeks in the treatment phase. Participants with compensated cirrhosis due to NASH will be accepted to participate in this cohort. Receives: Drug: FIR; Drug: CILO; Drug: VAS |
| Cohort 13: FIR 20 mg + CILO 30 mg + FENO 145 mg | Experimental | Participants will receive FENO 145 mg tablet orally once daily for 2 weeks in the pretreatment phase, then FIR 20 mg tablet once daily + CILO 30 mg tablet once daily + FENO 145 mg tablet orally once daily for 6 weeks in the treatment phase. Participants with compensated cirrhosis due to NASH will be accepted to participate in this cohort. Receives: Drug: FIR; Drug: CILO; Drug: FENO |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants Who Experienced Treatment-Emergent Adverse Events
Treatment-emergent AEs were defined as events that met 1 or both of the following criteria:
- Any AEs with onset dates on or after the study drug start date and no later than 30 days after permanent discontinuation of study drug
- Any AEs leading to premature discontinuation of study drug
Measured: Cohorts 1-9: First dose date up to 12 weeks plus 30 days; Cohorts 10-11: First dose date up to 26 weeks plus 30 days; Cohorts 12-13: First dose date up to 8 weeks plus 30 days. For Cohorts 10-13, the first dose date included the Pre-treatment Phase.
Percentage of Participants Who Experienced Treatment Emergent Serious Adverse Events
A treatment emergent serious adverse event (SAE) was defined as an event that, at any dose, results in the following:
- Death
- Life-threatening
- In-patient hospitalization or prolongation of existing hospitalization
- Persistent or significant disability/incapacity
- A congenital anomaly/birth defect
- A medically important event or reaction
Measured: Cohorts 1-9: First dose date up to 12 weeks plus 30 days; Cohorts 10-11: First dose date up to 26 weeks plus 30 days; Cohorts 12-13: First dose date up to 8 weeks plus 30 days. For Cohorts 10-13, the first dose date included the Pre-treatment Phase.
Percentage of Participants Who Experienced Grade 3 or Higher Laboratory Abnormalities
Treatment-emergent laboratory abnormalities were defined as values that increased at least 1 toxicity grade from baseline at any postbaseline time point, up to and including the date of last dose of study drug plus 30 days for subjects who permanently discontinued study drug. If baseline laboratory data were missing, then any abnormality of at least Grade 1 was considered treatment emergent. Graded laboratory abnormalities were defined using the grading scheme in the Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03 for Cohorts 1-9 and CTCAE Version 5.0 for Cohorts 10-13.
Measured: Cohorts 1-9: First dose date up to 12 weeks plus 30 days; Cohorts 10-11: First dose date up to 26 weeks plus 30 days; Cohorts 12-13: First dose date up to 8 weeks plus 30 days. For Cohorts 10-13, the first dose date included the Pre-treatment Phase.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 May 2016 (estimated)
- Study start13 Jun 2016
- Primary completion17 Dec 2020
- Study completion17 Dec 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 (7)Papers the sponsor has linked to this study.
- Other trials for Nonalcoholic Steatohepatitis (NASH)Studies 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
- Non-randomised
- Intervention model
- Parallel groups
- 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. Cohorts 12 and 13 will be randomized in parallel.
- Masking
- None (open label)
- Enrolment
- 220 participants (actual)
Sponsor and investigators
- Lead sponsor
- Gilead Sciences
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Gilead Study Director, Study director, Gilead Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02781584
- Sponsor's protocol ID
- GS-US-384-3914
- Status last verified
- Mar 2022
- First submitted
- 20 May 2016
- Last updated
- 16 Mar 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Lawitz E, Neff G, Ruane P, Ziad Y, Jia C, Chuang J, et al. Fenofibrate Mitigates Increases in Serum Triglycerides Due to the ACC Inhibitor Firsocostat in Patients with Advanced Fibrosis Due to NASH. Poster presented at: The American Association for the Study of Liver Diseases (AASLD): The Liver Meeting; November 8-12, 2019; Boston, MA.
Lawitz EJ, Coste A, Poordad F, Alkhouri N, Loo N, McColgan BJ, Tarrant JM, Nguyen T, Han L, Chung C, Ray AS, McHutchison JG, Subramanian GM, Myers RP, Middleton MS, Sirlin C, Loomba R, Nyangau E, Fitch M, Li K, Hellerstein M. Acetyl-CoA Carboxylase Inhibitor GS-0976 for 12 Weeks Reduces Hepatic De Novo Lipogenesis and Steatosis in Patients With Nonalcoholic Steatohepatitis. Clin Gastroenterol Hepatol. 2018 Dec;16(12):1983-1991.e3. doi: 10.1016/j.cgh.2018.04.042. Epub 2018 Apr 26.
PubMed 29705265Lawitz E, Herring R, Younes ZH, Gane E, Ruane P, Schall RA, et al. Proof of Concept Study of an Apoptosis-Signal Regulating Kinase (ASK1) Inhibitor (Selonsertib) in Combination With An Acetyl-CoA Carboxylase Inhibitor (GS-0976) or a Farnesoid X Receptor Agonist (GS-9674) in Nash [Abstract PS-105]. European Association for the Study of the Liver (EASL); 2018 11-15 April; Paris, France.
Lawitz E, Li K, Tarrant JM, Vimal M, Xu R, Song Q, et al. Hepatic de Novo Lipogenesis is Elevated in Patients with NASH Independent of Disease Severity [Abstract 2217]. American Association for the Study of Liver Diseases (AASLD); 2017 20-24 October Washington, DC.
Lawitz EJ, Poordad F, Coste A, Loo N, Djedjos CS, McColgan B, et al. Acetyl-CoA carboxylase (ACC) inhibitor GS-0976 leads to suppression of hepatic de novo lipogenesis and significant improvements in MRI-PDFF, MRE, and markers of fibrosis after 12 weeks of therapy in patients with NASH [Abstract GS-009]. The International Liver Congress™ 2017: European Association for the Study of the Liver (EASL); 2017 19-23 April; Amsterdam, the Netherlands.
Lawitz E, Bhandari BR, Ruane P, Kohli A, Harting E, Jia C, et al. Fenofibrate is Safe and Mitigates Increases in Serum Triglycerides in NASH Patients Treated with the Combination of the ACC Inhibitor Firsocostat and the FXR Agonist Cilofexor: A Randomized Trial. Poster presented at: The European Association for the Study of the Liver (EASL): International Liver Congress; June 23-26, 2021; Virtual Meeting.
Lawitz EJ, Bhandari BR, Ruane PJ, Kohli A, Harting E, Ding D, Chuang JC, Huss RS, Chung C, Myers RP, Loomba R. Fenofibrate Mitigates Hypertriglyceridemia in Nonalcoholic Steatohepatitis Patients Treated With Cilofexor/Firsocostat. Clin Gastroenterol Hepatol. 2023 Jan;21(1):143-152.e3. doi: 10.1016/j.cgh.2021.12.044. Epub 2022 Jan 6.
PubMed 34999207
Study at a glance
From the registry record, last updated by the sponsor on 16 Mar 2022. 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 Regimens in Subjects With Nonalcoholic Steatohepatitis (NASH)
- ClinicalTrials.gov ID
- NCT02781584
- Acronym / sponsor ID
- GS-US-384-3914
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 220 participants (actual)
- Lead sponsor
- Gilead SciencesIndustry (pharma, biotech, devices)
- Study start
- 13 Jun 2016 (actual)
- Primary completion
- 17 Dec 2020 (actual)
- Study completion
- 17 Dec 2020 (actual)
- First posted
- 24 May 2016 (estimated)
- Results
- Posted 2 Feb 2022
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 selonsertib, firsocostat, cilofexor, fenofibrate and/or Vascepa® in adults with nonalcoholic fatty liver disease (NAFLD) or nonalcoholic steatohepatitis (NASH).
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 13
- 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. Cohorts 12 and 13 will be randomized in parallel.
| Arm | Type | Receives |
|---|---|---|
| Cohort 1: SEL 18 mg (Non-cirrhotic) | Experimental | Drug: SELNon-cirrhotic participants will receive selonsertib (SEL) 18 mg tablet orally once daily for 12 weeks. |
| Cohort 2: FIR 20 mg (Non-cirrhotic) | Experimental | Drug: FIRNon-cirrhotic participants will receive firsocostat (FIR) 20 mg tablet orally once daily for 12 weeks. |
| Cohort 3: CILO 30 mg (Non-cirrhotic) | Experimental | Drug: CILONon-cirrhotic participants will receive cilofexor (CILO) 30 mg tablet once daily for 12 weeks. |
| Cohort 4: SEL 18 mg + CILO 30 mg (Non-cirrhotic) | Experimental | Drug: SEL, Drug: CILONon-cirrhotic participants will receive SEL 18 mg tablet + CILO 30 mg tablet once daily for 12 weeks. |
| Cohort 5: SEL 18 mg + FIR 20 mg (Non-cirrhotic) | Experimental | Drug: SEL, Drug: FIRNon-cirrhotic participants will receive SEL 18 mg tablet + FIR 20 mg tablet once daily for 12 weeks. |
| Cohort 6: CILO 30 mg + FIR 20 mg (Non-cirrhotic) | Experimental | Drug: FIR, Drug: CILONon-cirrhotic participants will receive CILO 30 mg tablet + FIR 20 mg tablet once daily for 12 weeks. |
| Cohort 7: CILO 20 mg (Cirrhotic) | Experimental | Drug: FIRParticipants with Child-Pugh-Turcotte Class A cirrhosis will receive FIR 20 mg tablet once daily for 12 weeks. |
| Cohort 8: CILO 30 mg (Cirrhotic) | Experimental | Drug: CILOParticipants with Child-Pugh-Turcotte Class A cirrhosis will receive CILO 30 mg tablet once daily for 12 weeks. |
| Cohort 9: SEL 18 mg + FIR 20 mg + CILO 30 mg (Non-cirrhotic) | Experimental | Drug: SEL, Drug: FIR, Drug: CILONon-cirrhotic participants will receive SEL 18 mg tablet + FIR 20 mg tablet + CILO 30 mg tablet once daily for 12 weeks. |
| Cohort 10: FIR 20 mg + FENO 48 mg | Experimental | Drug: FIR, Drug: FENOParticipants will receive fenofibrate (FENO) 48 mg tablet orally once daily for 2 weeks in the pretreatment phase, then FIR 20 mg tablet + FENO 48 mg tablet orally once daily for 24 weeks in the treatment phase. Participants with compensated cirrhosis due to NASH will be accepted to participate in this cohort. |
| Cohort 11: FIR 20 mg + FENO 145 mg | Experimental | Drug: FIR, Drug: FENOParticipants will receive FENO 145 mg tablet orally once daily for 2 weeks in the pretreatment phase, then FIR 20 mg tablet + FENO 145 mg tablet orally once daily for 24 weeks in the treatment phase. Participants with compensated cirrhosis due to NASH will be accepted to participate in this cohort. |
| Cohort 12: FIR 20 mg + CILO 30 mg + VAS 2g | Experimental | Drug: FIR, Drug: CILO, Drug: VASParticipants will receive Vascepa® (VAS) 2 g capsule orally twice daily for 2 weeks in the pretreatment phase, then FIR 20 mg tablet once daily + CILO 30 mg tablet once daily + VAS 2 g capsule twice daily for 6 weeks in the treatment phase. Participants with compensated cirrhosis due to NASH will be accepted to participate in this cohort. |
| Cohort 13: FIR 20 mg + CILO 30 mg + FENO 145 mg | Experimental | Drug: FIR, Drug: CILO, Drug: FENOParticipants will receive FENO 145 mg tablet orally once daily for 2 weeks in the pretreatment phase, then FIR 20 mg tablet once daily + CILO 30 mg tablet once daily + FENO 145 mg tablet orally once daily for 6 weeks in the treatment phase. Participants with compensated cirrhosis due to NASH will be accepted to participate in this cohort. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (27 listed)
- 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
- For Cohorts 1 through 6 and 9, individuals must meet the following conditions:
- For Cohorts 7 and 8, individuals must have a clinical diagnosis of NAFLD and have at least one of the following criteria:
- For Cohorts 10 and 11, individuals must have a clinical diagnosis of NAFLD and meet at least two criteria for metabolic syndrome modified from the NCEP ATP III Guidelines and one of the following criteria at Screening:
Key exclusion criteria (29 listed)
- 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
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 |
|---|---|---|
| SELAlso: GS-4997Administered orally once daily | Drug | Cohort 1: SEL 18 mg (Non-cirrhotic), Cohort 4: SEL 18 mg + CILO 30 mg (Non-cirrhotic), Cohort 5: SEL 18 mg + FIR 20 mg (Non-cirrhotic), Cohort 9: SEL 18 mg + FIR 20 mg + CILO 30 mg (Non-cirrhotic) |
| FIRAlso: GS-0976Administered orally once daily | Drug | Cohort 10: FIR 20 mg + FENO 48 mg, Cohort 11: FIR 20 mg + FENO 145 mg, Cohort 12: FIR 20 mg + CILO 30 mg + VAS 2g, Cohort 13: FIR 20 mg + CILO 30 mg + FENO 145 mg, Cohort 2: FIR 20 mg (Non-cirrhotic), Cohort 5: SEL 18 mg + FIR 20 mg (Non-cirrhotic), Cohort 6: CILO 30 mg + FIR 20 mg (Non-cirrhotic), Cohort 7: CILO 20 mg (Cirrhotic), Cohort 9: SEL 18 mg + FIR 20 mg + CILO 30 mg (Non-cirrhotic) |
| CILOAlso: GS-9674Administered orally once daily | Drug | Cohort 12: FIR 20 mg + CILO 30 mg + VAS 2g, Cohort 13: FIR 20 mg + CILO 30 mg + FENO 145 mg, Cohort 3: CILO 30 mg (Non-cirrhotic), Cohort 4: SEL 18 mg + CILO 30 mg (Non-cirrhotic), Cohort 6: CILO 30 mg + FIR 20 mg (Non-cirrhotic), Cohort 8: CILO 30 mg (Cirrhotic), Cohort 9: SEL 18 mg + FIR 20 mg + CILO 30 mg (Non-cirrhotic) |
| FENOAdministered orally once daily | Drug | Cohort 10: FIR 20 mg + FENO 48 mg, Cohort 11: FIR 20 mg + FENO 145 mg, Cohort 13: FIR 20 mg + CILO 30 mg + FENO 145 mg |
| VASAdministered orally two times daily | Drug | Cohort 12: FIR 20 mg + CILO 30 mg + VAS 2g |
Primary outcome
Percentage of Participants Who Experienced Treatment-Emergent Adverse Events
Time frame: Cohorts 1-9: First dose date up to 12 weeks plus 30 days; Cohorts 10-11: First dose date up to 26 weeks plus 30 days; Cohorts 12-13: First dose date up to 8 weeks plus 30 days. For Cohorts 10-13, the first dose date included the Pre-treatment Phase.
Treatment-emergent AEs were defined as events that met 1 or both of the following criteria: * Any AEs with onset dates on or after the study drug start date and no later than 30 days after permanent discontinuation of study drug * Any AEs leading to premature discontinuation of study drug
Percentage of Participants Who Experienced Treatment Emergent Serious Adverse Events
Time frame: Cohorts 1-9: First dose date up to 12 weeks plus 30 days; Cohorts 10-11: First dose date up to 26 weeks plus 30 days; Cohorts 12-13: First dose date up to 8 weeks plus 30 days. For Cohorts 10-13, the first dose date included the Pre-treatment Phase.
A treatment emergent serious adverse event (SAE) was defined as an event that, at any dose, results in the following: * Death * Life-threatening * In-patient hospitalization or prolongation of existing hospitalization * Persistent or significant disability/incapacity * A congenital anomaly/birth defect * A medically important event or reaction
Percentage of Participants Who Experienced Grade 3 or Higher Laboratory Abnormalities
Time frame: Cohorts 1-9: First dose date up to 12 weeks plus 30 days; Cohorts 10-11: First dose date up to 26 weeks plus 30 days; Cohorts 12-13: First dose date up to 8 weeks plus 30 days. For Cohorts 10-13, the first dose date included the Pre-treatment Phase.
Treatment-emergent laboratory abnormalities were defined as values that increased at least 1 toxicity grade from baseline at any postbaseline time point, up to and including the date of last dose of study drug plus 30 days for subjects who permanently discontinued study drug. If baseline laboratory data were missing, then any abnormality of at least Grade 1 was considered treatment emergent. Graded laboratory abnormalities were defined using the grading scheme in the Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03 for Cohorts 1-9 and CTCAE Version 5.0 for Cohorts 10-13.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Mar 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- BackgroundLawitz E, Neff G, Ruane P, Ziad Y, Jia C, Chuang J, et al. Fenofibrate Mitigates Increases in Serum Triglycerides Due to the ACC Inhibitor Firsocostat in Patients with Advanced Fibrosis Due to NASH. Poster presented at: The American Association for the Study of Liver Diseases (AASLD): The Liver Meeting; November 8-12, 2019; Boston, MA.
- Background: PubMed 29705265Lawitz EJ, Coste A, Poordad F, Alkhouri N, Loo N, McColgan BJ, Tarrant JM, Nguyen T, Han L, Chung C, Ray AS, McHutchison JG, Subramanian GM, Myers RP, Middleton MS, Sirlin C, Loomba R, Nyangau E, Fitch M, Li K, Hellerstein M. Acetyl-CoA Carboxylase Inhibitor GS-0976 for 12 Weeks Reduces Hepatic De Novo Lipogenesis and Steatosis in Patients With Nonalcoholic Steatohepatitis. Clin Gastroenterol Hepatol. 2018 Dec;16(12):1983-1991.e3. doi: 10.1016/j.cgh.2018.04.042. Epub 2018 Apr 26.
- BackgroundLawitz E, Herring R, Younes ZH, Gane E, Ruane P, Schall RA, et al. Proof of Concept Study of an Apoptosis-Signal Regulating Kinase (ASK1) Inhibitor (Selonsertib) in Combination With An Acetyl-CoA Carboxylase Inhibitor (GS-0976) or a Farnesoid X Receptor Agonist (GS-9674) in Nash [Abstract PS-105]. European Association for the Study of the Liver (EASL); 2018 11-15 April; Paris, France.
- BackgroundLawitz E, Li K, Tarrant JM, Vimal M, Xu R, Song Q, et al. Hepatic de Novo Lipogenesis is Elevated in Patients with NASH Independent of Disease Severity [Abstract 2217]. American Association for the Study of Liver Diseases (AASLD); 2017 20-24 October Washington, DC.
- BackgroundLawitz EJ, Poordad F, Coste A, Loo N, Djedjos CS, McColgan B, et al. Acetyl-CoA carboxylase (ACC) inhibitor GS-0976 leads to suppression of hepatic de novo lipogenesis and significant improvements in MRI-PDFF, MRE, and markers of fibrosis after 12 weeks of therapy in patients with NASH [Abstract GS-009]. The International Liver Congress™ 2017: European Association for the Study of the Liver (EASL); 2017 19-23 April; Amsterdam, the Netherlands.
- Results publicationLawitz E, Bhandari BR, Ruane P, Kohli A, Harting E, Jia C, et al. Fenofibrate is Safe and Mitigates Increases in Serum Triglycerides in NASH Patients Treated with the Combination of the ACC Inhibitor Firsocostat and the FXR Agonist Cilofexor: A Randomized Trial. Poster presented at: The European Association for the Study of the Liver (EASL): International Liver Congress; June 23-26, 2021; Virtual Meeting.
- Derived from this study: PubMed 34999207Lawitz EJ, Bhandari BR, Ruane PJ, Kohli A, Harting E, Ding D, Chuang JC, Huss RS, Chung C, Myers RP, Loomba R. Fenofibrate Mitigates Hypertriglyceridemia in Nonalcoholic Steatohepatitis Patients Treated With Cilofexor/Firsocostat. Clin Gastroenterol Hepatol. 2023 Jan;21(1):143-152.e3. doi: 10.1016/j.cgh.2021.12.044. Epub 2022 Jan 6.
- 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
13 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing SEL, FIR and CILO in people with Nonalcoholic Steatohepatitis (NASH) and Nonalcoholic Fatty Liver Disease (NAFLD), run by Gilead Sciences at 13 sites in 2 countries.
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 27 inclusion and 29 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 16 Mar 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 13 sites in United States, New Zealand. 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 2 Feb 2022). 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 Who Experienced Treatment-Emergent Adverse Events (time frame: Cohorts 1-9: First dose date up to 12 weeks plus 30 days; Cohorts 10-11: First dose date up to 26 weeks plus 30 days; Cohorts 12-13: First dose date up to 8 weeks plus 30 days. For Cohorts 10-13, the first dose date included the Pre-treatment Phase.). The study lists 3 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 NCT02781584, which also lists 7 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 16 Mar 2022.