Safety and Efficacy of Selonsertib in Adults With Nonalcoholic Steatohepatitis (NASH) and Bridging (F3) Fibrosis (STELLAR-3)

Gilead Sciences

Status and phase: Terminated; Phase 3

Conditions: Nonalcoholic Steatohepatitis

Treatments: Drug: Placebo to match SEL 6 mg; Drug: SEL; Drug: Placebo to match SEL 18 mg

Study type: Interventional

Funder types: Industry

Identifiers

NCT03053050

2016-004374-18 (EudraCT Number)

GS-US-384-1943

Details and patient eligibility

About

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.

Enrollment: 808 patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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808 participants in 3 patient groups, including a placebo group

SEL 18 mg

Experimental group

Description:

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.

Treatment:

Drug: Placebo to match SEL 6 mg

Drug: SEL

SEL 6 mg

Experimental group

Description:

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.

Treatment:

Drug: SEL

Drug: Placebo to match SEL 18 mg

Placebo

Placebo Comparator group

Description:

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.

Treatment:

Drug: Placebo to match SEL 6 mg

Drug: Placebo to match SEL 18 mg