Safety and Efficacy of Selonsertib in Adults With Compensated Cirrhosis Due to Nonalcoholic Steatohepatitis (NASH) (STELLAR-4)

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

NCT03053063

2016-004148-13 (EudraCT Number)

GS-US-384-1944

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 associated complications in adults with cirrhosis due to NASH.

Enrollment: 883 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 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

Key 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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883 participants in 3 patient groups, including a placebo group

SEL 6 mg

Experimental group

Description:

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.

Treatment:

Drug: Placebo to match SEL 18 mg

Drug: SEL

SEL 18 mg

Experimental group

Description:

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.

Treatment:

Drug: Placebo to match SEL 6 mg

Drug: SEL

Placebo

Placebo Comparator group

Description:

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.

Treatment:

Drug: Placebo to match SEL 18 mg

Drug: Placebo to match SEL 6 mg