A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Safety and Efficacy of Selonsertib in Subjects With Compensated Cirrhosis Due to Nonalcoholic Steatohepatitis (NASH)
Trial Snapshot
- Phase
- Phase 3
- Status
- Terminated
- Sponsor
- Gilead Sciences
- Enrollment
- 883
- Locations
- 281
- Primary Endpoint
- Percentage of Participants Who Achieve a ≥ 1-Stage Improvement in Fibrosis According to the Nonalcoholic Steatohepatitis (NASH) Clinical Research Network (CRN) Classification Without Worsening of NASH
Study Overview
Brief Summary
The primary objective of this study is to evaluate whether selonsertib (SEL; GS-4997) can cause fibrosis regression and reduce associated complications in adults with cirrhosis due to NASH.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Double (Participant, Care Provider)
Eligibility Criteria
- Ages
- 18 Years to 70 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Liver biopsy consistent with NASH and cirrhosis (F4 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, as determined by the central laboratory:
- •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
- •HbA1c ≤ 9.5% (or serum fructosamine ≤ 381 micromole (μmol) if HbA1c is unable to be resulted)
- •International normalised ratio (INR) ≤ 1.4, unless due to therapeutic anti-coagulation
- •Platelet count ≥ 100,000/μL
Exclusion Criteria
- •Prior history of decompensated liver disease including clinical ascites, hepatic encephalopathy (HE), or variceal bleeding
- •Child-Pugh (CP) score > 7, 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-antitrypsin 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.
Arms & Interventions
SEL 6 mg
Randomized Phase: SEL 6 mg plus placebo to match SEL 18 mg for up to 240 weeks.
Open-Label (OL) Phase: Participants who experienced a hepatic clinical event during the randomized phase prior to completing the Week 240 visit, will be offered the option to receive OL SEL 18 mg daily for a total treatment duration of 240 weeks inclusive of the Randomized Phase.
Intervention: SEL (Drug)
SEL 6 mg
Randomized Phase: SEL 6 mg plus placebo to match SEL 18 mg for up to 240 weeks.
Open-Label (OL) Phase: Participants who experienced a hepatic clinical event during the randomized phase prior to completing the Week 240 visit, will be offered the option to receive OL SEL 18 mg daily for a total treatment duration of 240 weeks inclusive of the Randomized Phase.
Intervention: Placebo to match SEL 18 mg (Drug)
SEL 18 mg
Randomized Phase: SEL 18 mg plus placebo to match SEL 6 mg for up to 240 weeks.
Open-Label Phase: Participants who experienced a hepatic clinical event during the randomized phase prior to completing the Week 240 visit, will be offered the option to receive OL SEL 18 mg daily for a total treatment duration of 240 weeks inclusive of the Randomized Phase.
Intervention: SEL (Drug)
SEL 18 mg
Randomized Phase: SEL 18 mg plus placebo to match SEL 6 mg for up to 240 weeks.
Open-Label Phase: Participants who experienced a hepatic clinical event during the randomized phase prior to completing the Week 240 visit, will be offered the option to receive OL SEL 18 mg daily for a total treatment duration of 240 weeks inclusive of the Randomized Phase.
Intervention: Placebo to match SEL 6 mg (Drug)
Placebo
Randomized Phase: Placebo to match SEL 6 mg plus placebo to match SEL 18 mg for up to 240 weeks.
Open-Label Phase: Participants who experienced a hepatic clinical event during the randomized phase prior to completing the Week 240 visit, will be offered the option to receive OL SEL 18 mg daily for a total treatment duration of 240 weeks inclusive of the Randomized Phase.
Intervention: Placebo to match SEL 6 mg (Drug)
Placebo
Randomized Phase: Placebo to match SEL 6 mg plus placebo to match SEL 18 mg for up to 240 weeks.
Open-Label Phase: Participants who experienced a hepatic clinical event during the randomized phase prior to completing the Week 240 visit, will be offered the option to receive OL SEL 18 mg daily for a total treatment duration of 240 weeks inclusive of the Randomized Phase.
Intervention: Placebo to match SEL 18 mg (Drug)
Outcomes
Primary Outcomes
Percentage of Participants Who Achieve a ≥ 1-Stage Improvement in Fibrosis According to the Nonalcoholic Steatohepatitis (NASH) Clinical Research Network (CRN) Classification Without Worsening of NASH
Time Frame: Week 48
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.
Event-Free Survival (EFS) at Week 240 as Assessed by Time to First Clinical Event
Time Frame: Week 240
EFS was assessed by the time to the first clinical event, including liver decompensation events, liver transplantation and all-cause mortality.
Secondary Outcomes
- Percentage of Participants Who Had a ≥ 1-Stage Improvement in Fibrosis Without Worsening of NASH at Week 240(Week 240)
- Percentage of Participants Who Had a ≥ 1-Stage Improvement in Fibrosis at Week 240(Week 240)
- Percentage of Participants Who Had NASH Resolution at Week 240(Week 240)
- Percentage of Participants Who Had a ≥ 1-Stage Improvement in Fibrosis at Week 48(Week 48)
- Percentage of Participants Who Had NASH Resolution at Week 48(Week 48)