Purpose

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.

Condition

Eligibility

Eligible Ages
Between 18 Years and 70 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

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)

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.

Study Design

Phase
Phase 3
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
Double (Participant, Care Provider)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
SEL 18 mg
Randomized Phase: Selonsertib (SEL) 18 mg tablet + placebo to match SEL 6 mg tablet for 240 weeks Open-Label (OL) Phase: Participants who experience a hepatic clinical event or have biopsy confirmed progression to cirrhosis during the randomized phase, prior to completing the Week 240 visit, will be offered the option to roll over into an OL phase to receive OL SEL 18 mg for a total treatment duration of 240 weeks inclusive of the randomized phase.
  • Drug: SEL
    Tablets administered orally once daily
    Other names:
    • selonsertib
    • GS-4997
  • Drug: Placebo to match SEL 6 mg
    Tablets administered orally once daily
Experimental
SEL 6 mg
Randomized Phase: SEL 6 mg tablet + placebo to match SEL 18 mg tablet for 240 weeks OL Phase: Participants who experience a hepatic clinical event or have biopsy confirmed progression to cirrhosis during the randomized phase, prior to completing the Week 240 visit, will be offered the option to roll over into an OL phase to receive OL SEL 18 mg for a total treatment duration of 240 weeks inclusive of the randomized phase.
  • Drug: SEL
    Tablets administered orally once daily
    Other names:
    • selonsertib
    • GS-4997
  • Drug: Placebo to match SEL 18 mg
    Tablets administered orally once daily
Placebo Comparator
Placebo
Randomized Phase: Placebo to match SEL 6 mg tablet + placebo to match SEL 18 mg tablet for 240 weeks OL Phase: Participants who experience a hepatic clinical event or have biopsy confirmed progression to cirrhosis during the randomized phase, prior to completing the Week 240 visit, will be offered the option to roll over into an OL phase to receive OL SEL 18 mg for a total treatment duration of 240 weeks inclusive of the randomized phase.
  • Drug: Placebo to match SEL 6 mg
    Tablets administered orally once daily
  • Drug: Placebo to match SEL 18 mg
    Tablets administered orally once daily

More Details

Status
Terminated
Sponsor
Gilead Sciences

Study Contact

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.