Brief Summary
The primary objective of this study is to evaluate whether selonsertib (SEL; GS-4997) can cause fibrosis regression and reduce progression to cirrhosis and associated complications in adults with NASH and bridging (F3) fibrosis.
Brief Title
Safety and Efficacy of Selonsertib in Adults With Nonalcoholic Steatohepatitis (NASH) and Bridging (F3) Fibrosis
Completion Date
Completion Date Type
Actual
Conditions
Nonalcoholic Steatohepatitis
Eligibility Criteria
Key Inclusion Criteria:
* Liver biopsy consistent with NASH and bridging (F3 fibrosis) according to the NASH Clinical Research Network (CRN) classification in the opinion of the central reader
* Has the following laboratory parameters at the screening visit:
* Alanine aminotransferase (ALT) ≤ 8 x upper limit of normal (ULN)
* Creatinine Clearance (CLcr) ≥ 30 milliliter/minute (mL/min), as calculated by the Cockcroft-Gault equation
* Hemoglobin A1c (HbA1c) ≤ 9.5% (or serum fructosamine ≤ 381 μmol if HbA1c is unable to be resulted)
* Total bilirubin ≤ 1.3 x ULN (unless an alternate etiology such as Gilbert's syndrome or hemolytic anemia is present)
Key Exclusion Criteria:
* Prior history of decompensated liver disease including clinical ascites, hepatic encephalopathy (HE), or variceal bleeding
* Child-Pugh (CP) score \> 6, as determined at screening, unless due to therapeutic anti-coagulation
* Model for End-stage Liver Disease (MELD) score \> 12, as determined at screening, unless due to therapeutic anti-coagulation
* Other causes of liver disease including, but not limited to, alcoholic liver disease, hepatitis B, hepatitis C, autoimmune disorders, drug-induced hepatotoxicity, Wilson disease, iron overload, and alpha-1-antitryspin deficiency, based on medical history and/ or centralized review of liver histology.
* History of liver transplantation
* Current or history of hepatocellular carcinoma (HCC)
Note: Other protocol defined Inclusion/Exclusion criteria may apply.
* Liver biopsy consistent with NASH and bridging (F3 fibrosis) according to the NASH Clinical Research Network (CRN) classification in the opinion of the central reader
* Has the following laboratory parameters at the screening visit:
* Alanine aminotransferase (ALT) ≤ 8 x upper limit of normal (ULN)
* Creatinine Clearance (CLcr) ≥ 30 milliliter/minute (mL/min), as calculated by the Cockcroft-Gault equation
* Hemoglobin A1c (HbA1c) ≤ 9.5% (or serum fructosamine ≤ 381 μmol if HbA1c is unable to be resulted)
* Total bilirubin ≤ 1.3 x ULN (unless an alternate etiology such as Gilbert's syndrome or hemolytic anemia is present)
Key Exclusion Criteria:
* Prior history of decompensated liver disease including clinical ascites, hepatic encephalopathy (HE), or variceal bleeding
* Child-Pugh (CP) score \> 6, as determined at screening, unless due to therapeutic anti-coagulation
* Model for End-stage Liver Disease (MELD) score \> 12, as determined at screening, unless due to therapeutic anti-coagulation
* Other causes of liver disease including, but not limited to, alcoholic liver disease, hepatitis B, hepatitis C, autoimmune disorders, drug-induced hepatotoxicity, Wilson disease, iron overload, and alpha-1-antitryspin deficiency, based on medical history and/ or centralized review of liver histology.
* History of liver transplantation
* Current or history of hepatocellular carcinoma (HCC)
Note: Other protocol defined Inclusion/Exclusion criteria may apply.
Inclusion Criteria
Inclusion Criteria:
* Liver biopsy consistent with NASH and bridging (F3 fibrosis) according to the NASH Clinical Research Network (CRN) classification in the opinion of the central reader
* Has the following laboratory parameters at the screening visit:
* Alanine aminotransferase (ALT) ≤ 8 x upper limit of normal (ULN)
* Creatinine Clearance (CLcr) ≥ 30 milliliter/minute (mL/min), as calculated by the Cockcroft-Gault equation
* Hemoglobin A1c (HbA1c) ≤ 9.5% (or serum fructosamine ≤ 381 μmol if HbA1c is unable to be resulted)
* Total bilirubin ≤ 1.3 x ULN (unless an alternate etiology such as Gilbert's syndrome or hemolytic anemia is present)
Inclusion/
* Liver biopsy consistent with NASH and bridging (F3 fibrosis) according to the NASH Clinical Research Network (CRN) classification in the opinion of the central reader
* Has the following laboratory parameters at the screening visit:
* Alanine aminotransferase (ALT) ≤ 8 x upper limit of normal (ULN)
* Creatinine Clearance (CLcr) ≥ 30 milliliter/minute (mL/min), as calculated by the Cockcroft-Gault equation
* Hemoglobin A1c (HbA1c) ≤ 9.5% (or serum fructosamine ≤ 381 μmol if HbA1c is unable to be resulted)
* Total bilirubin ≤ 1.3 x ULN (unless an alternate etiology such as Gilbert's syndrome or hemolytic anemia is present)
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
70 Years
Minimum Age
18 Years
NCT Id
NCT03053050
Org Class
Industry
Org Full Name
Gilead Sciences
Org Study Id
GS-US-384-1943
Overall Status
Terminated
Phases
Phase 3
Primary Completion Date
Primary Completion Date Type
Actual
Official Title
A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Safety and Efficacy of Selonsertib in Subjects With Nonalcoholic Steatohepatitis (NASH) and Bridging (F3) Fibrosis
Primary Outcomes
Outcome Description
Fibrosis improvement was defined as ≥ 1-stage decrease from baseline in fibrosis according to the NASH CRN classification. NASH CRN fibrosis stages range from 0 to 4, with higher scores indicating greater fibrosis (0=None, 4=Cirrhosis). Worsening of NASH was defined as ≥ 1 point increase from baseline in hepatocellular ballooning or lobular inflammation according to the Non-Alcoholic Fatty Liver Disease (NAFLD) Activity Score (NAS) criteria. As defined by NAS, hepatocellular ballooning ranges from 0-2 and lobular inflammation ranges from 0-3, with higher scores indicating more severe hepatocellular ballooning or lobular inflammation.
Outcome Measure
Percentage of Participants Who Achieved a ≥ 1-Stage Improvement in Fibrosis According to the Nonalcoholic Steatohepatitis (NASH) Clinical Research Network (CRN) Classification Without Worsening of NASH at Week 48
Outcome Time Frame
Week 48
Outcome Description
EFS was assessed by the time to the first clinical event, including progression to cirrhosis on liver biopsy, liver decompensation events, liver transplantation, and all-cause mortality.
Outcome Measure
Event-Free Survival (EFS) at Week 240 as Assessed by Time to First Clinical Event
Outcome Time Frame
Week 240
Secondary Ids
Secondary Id
2016-004374-18
Secondary Outcomes
Outcome Description
Progression to cirrhosis was defined as a change in NASH CRN fibrosis stage from \< 4 at baseline to 4 at Week 48.
Outcome Time Frame
Week 48
Outcome Measure
Percentage of Participants Who Had Progression to Cirrhosis at Week 48
Outcome Description
Fibrosis improvement was defined as ≥ 1-stage decrease from baseline in fibrosis according to the NASH CRN classification. NASH CRN fibrosis stages range from 0 to 4, with higher scores indicating greater fibrosis (0=None, 4=Cirrhosis). Worsening of NASH was defined as ≥ 1 point increase from baseline in hepatocellular ballooning or lobular inflammation according to the NAS criteria. As defined by NAS, hepatocellular ballooning ranges from 0-2 and lobular inflammation ranges from 0-3, with higher scores indicating more severe hepatocellular ballooning or lobular inflammation.
Outcome Time Frame
Week 240
Outcome Measure
Percentage of Participants Who Had a ≥ 1-Stage Improvement in Fibrosis Without Worsening of NASH at Week 240
Outcome Description
Fibrosis improvement was defined as ≥ 1-stage decrease from baseline in fibrosis according to the NASH CRN classification. NASH CRN fibrosis stages range from 0 to 4, with higher scores indicating greater fibrosis (0=None, 4=Cirrhosis).
Outcome Time Frame
Week 48
Outcome Measure
Percentage of Participants Who Had a ≥ 1-Stage Improvement in Fibrosis at Week 48
Outcome Description
Fibrosis improvement was defined as ≥ 1-stage decrease from baseline in fibrosis according to the NASH CRN classification. NASH CRN fibrosis stages range from 0 to 4, with higher scores indicating greater fibrosis (0=None, 4=Cirrhosis).
Outcome Time Frame
Week 240
Outcome Measure
Percentage of Participants Who Had a ≥ 1-Stage Improvement in Fibrosis at Week 240
Outcome Description
NASH resolution was defined as lobular inflammation of 0 or 1 from ≥ 1 at baseline and hepatocellular ballooning of 1 from a value ≥ 1 at baseline; both criteria were necessary conditions. Evaluable participants had baseline lobular inflammation and hepatocellular ballooning ≥ 1. Worsening of Fibrosis was defined by an increase in Fibrosis stage from 3 to 4 as defined by NASH CRN.
Outcome Time Frame
Week 48
Outcome Measure
Percentage of Participants Who Had NASH Resolution Without Worsening of Fibrosis at Week 48
Outcome Description
NASH resolution was defined as lobular inflammation of 0 or 1 from ≥ 1 at baseline and hepatocellular ballooning of 1 from a value ≥ 1 at baseline; both criteria were necessary conditions. Evaluable participants had baseline lobular inflammation and hepatocellular ballooning ≥ 1. Worsening of Fibrosis was defined by an increase in Fibrosis stage from 3 to 4 as defined by NASH CRN.
Outcome Time Frame
Week 240
Outcome Measure
Percentage of Participants Who Had NASH Resolution Without Worsening of Fibrosis at Week 240
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)
70
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