Brief Summary
The primary objectives of this study are:
* To assess the safety and tolerability of selonsertib (SEL), firsocostat (FIR) and cilofexor (CILO), administered alone or in combination, in participants with bridging fibrosis or compensated cirrhosis due to NASH
* To evaluate changes in liver fibrosis, without worsening of NASH
* To assess the safety and tolerability of selonsertib (SEL), firsocostat (FIR) and cilofexor (CILO), administered alone or in combination, in participants with bridging fibrosis or compensated cirrhosis due to NASH
* To evaluate changes in liver fibrosis, without worsening of NASH
Brief Title
Study to Evaluate the Safety and Efficacy of Selonsertib, Firsocostat, Cilofexor, and Combinations in Participants With Bridging Fibrosis or Compensated Cirrhosis Due to Nonalcoholic Steatohepatitis (NASH)
Completion Date
Completion Date Type
Actual
Conditions
Nonalcoholic Steatohepatitis
Eligibility Criteria
Key Inclusion Criteria:
* Liver biopsy consistent with NASH and F3 or F4 in the opinion of the central reader
* In participants who have never had a liver biopsy, liver stiffness by FibroScan® ≥ 14.0 kPa and Enhanced Liver Fibrosis (ELF™) Test score ≥ 9.8 at Screening
* Screening laboratory parameters, as determined by the central laboratory:
* Estimated glomerular filtration rate (eGFR) ≥ 60 mL/min, as calculated by the Cockcroft-Gault equation
* Hemoglobin A1c (HbA1c) ≤ 9.5%
* Alanine aminotransferase (ALT) \< 5 x Upper Limits of Normal (ULN)
* Platelet count ≥ 125,000/μL
Key Exclusion Criteria:
* Prior history of decompensated liver disease including ascites, hepatic encephalopathy, or variceal bleeding
* Child-Pugh (CP) score \> 6 at Screening, unless due to an alternative etiology such as Gilbert's syndrome or therapeutic anticoagulation
* Model for End-Stage Liver Disease (MELD) score \> 12 at Screening, unless due to an alternate etiology such as therapeutic anticoagulation
* Other causes of liver disease based on medical history and/or centralized review of liver histology, including but not limited to: alcoholic liver disease, hepatitis B, hepatitis C, autoimmune disorders (eg, primary biliary cholangitis, primary sclerosing cholangitis, autoimmune hepatitis), drug-induced hepatotoxicity, Wilson disease, clinically significant iron overload, or alpha-1-antitrypsin deficiency requiring treatment
* History of liver transplantation
* Current or prior history of hepatocellular carcinoma
Note: Other protocol defined Inclusion/ Exclusion criteria may apply
* Liver biopsy consistent with NASH and F3 or F4 in the opinion of the central reader
* In participants who have never had a liver biopsy, liver stiffness by FibroScan® ≥ 14.0 kPa and Enhanced Liver Fibrosis (ELF™) Test score ≥ 9.8 at Screening
* Screening laboratory parameters, as determined by the central laboratory:
* Estimated glomerular filtration rate (eGFR) ≥ 60 mL/min, as calculated by the Cockcroft-Gault equation
* Hemoglobin A1c (HbA1c) ≤ 9.5%
* Alanine aminotransferase (ALT) \< 5 x Upper Limits of Normal (ULN)
* Platelet count ≥ 125,000/μL
Key Exclusion Criteria:
* Prior history of decompensated liver disease including ascites, hepatic encephalopathy, or variceal bleeding
* Child-Pugh (CP) score \> 6 at Screening, unless due to an alternative etiology such as Gilbert's syndrome or therapeutic anticoagulation
* Model for End-Stage Liver Disease (MELD) score \> 12 at Screening, unless due to an alternate etiology such as therapeutic anticoagulation
* Other causes of liver disease based on medical history and/or centralized review of liver histology, including but not limited to: alcoholic liver disease, hepatitis B, hepatitis C, autoimmune disorders (eg, primary biliary cholangitis, primary sclerosing cholangitis, autoimmune hepatitis), drug-induced hepatotoxicity, Wilson disease, clinically significant iron overload, or alpha-1-antitrypsin deficiency requiring treatment
* History of liver transplantation
* Current or prior history of hepatocellular carcinoma
Note: Other protocol defined Inclusion/ Exclusion criteria may apply
Inclusion Criteria
Inclusion Criteria:
* Liver biopsy consistent with NASH and F3 or F4 in the opinion of the central reader
* In participants who have never had a liver biopsy, liver stiffness by FibroScan® ≥ 14.0 kPa and Enhanced Liver Fibrosis (ELF™) Test score ≥ 9.8 at Screening
* Screening laboratory parameters, as determined by the central laboratory:
* Estimated glomerular filtration rate (eGFR) ≥ 60 mL/min, as calculated by the Cockcroft-Gault equation
* Hemoglobin A1c (HbA1c) ≤ 9.5%
* Alanine aminotransferase (ALT) \< 5 x Upper Limits of Normal (ULN)
* Platelet count ≥ 125,000/μL
Inclusion/
* Liver biopsy consistent with NASH and F3 or F4 in the opinion of the central reader
* In participants who have never had a liver biopsy, liver stiffness by FibroScan® ≥ 14.0 kPa and Enhanced Liver Fibrosis (ELF™) Test score ≥ 9.8 at Screening
* Screening laboratory parameters, as determined by the central laboratory:
* Estimated glomerular filtration rate (eGFR) ≥ 60 mL/min, as calculated by the Cockcroft-Gault equation
* Hemoglobin A1c (HbA1c) ≤ 9.5%
* Alanine aminotransferase (ALT) \< 5 x Upper Limits of Normal (ULN)
* Platelet count ≥ 125,000/μL
Inclusion/
Gender
All
Gender Based
false
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Maximum Age
80 Years
Minimum Age
18 Years
NCT Id
NCT03449446
Org Class
Industry
Org Full Name
Gilead Sciences
Org Study Id
GS-US-454-4378
Overall Status
Completed
Phases
Phase 2
Primary Completion Date
Primary Completion Date Type
Actual
Official Title
A Phase 2, Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Safety and Efficacy of Selonsertib, GS-0976, GS-9674, and Combinations in Subjects With Bridging (F3) Fibrosis or Compensated Cirrhosis (F4) Due to Nonalcoholic Steatohepatitis (NASH)
Primary Outcomes
Outcome Measure
Percentage of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs)
Outcome Time Frame
First dose date up to 48 weeks plus 30 days
Outcome Description
Treatment-emergent laboratory abnormalities were defined as values that increase at least one toxicity grade from baseline. Participants with any laboratory abnormality were reported.
Outcome Measure
Percentage of Participants Experiencing Treatment-Emergent Laboratory Abnormalities
Outcome Time Frame
First dose date up to 48 weeks plus 30 days
Outcome Description
Fibrosis improvement was defined as ≥ 1-stage decrease from baseline in fibrosis according to the NASH clinical research network classification (CRN) classification. Worsening of NASH was defined as ≥ 1-point increase from baseline in hepatocellular ballooning or lobular inflammation. The 95% CI was based on the Clopper-Pearson method.
Outcome Measure
Percentage of Participants Who Achieved a ≥ 1-Stage Improvement in Fibrosis Without Worsening of NASH at Week 48
Outcome Time Frame
Week 48
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Actual
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
80
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Samuel Sigal
Investigator Email
ssigal@montefiore.org
Investigator Phone
718-920-6240