Study to Evaluate the Safety and Efficacy of Selonsertib, Firsocostat, Cilofexor, and Combinations in Participants With Bridging Fibrosis or Compensated Cirrhosis Due to Nonalcoholic Steatohepatitis (NASH) (ATLAS)

Gilead Sciences

Status and phase: Completed; Phase 2

Conditions: Nonalcoholic Steatohepatitis

Treatments: Drug: Placebo to match SEL; Drug: FIR; Drug: CILO; Drug: Placebo to match FIR; Drug: SEL; Drug: Placebo to match CILO

Study type: Interventional

Funder types: Industry

Identifiers

NCT03449446

GS-US-454-4378

Details and patient eligibility

About

The primary objectives of this study are:

• To assess the safety and tolerability of selonsertib (SEL), firsocostat (FIR) and cilofexor (CILO), administered alone or in combination, in participants with bridging fibrosis or compensated cirrhosis due to NASH
• To evaluate changes in liver fibrosis, without worsening of NASH

Enrollment: 395 patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Key Inclusion Criteria:

• Liver biopsy consistent with NASH and F3 or F4 in the opinion of the central reader

• In participants who have never had a liver biopsy, liver stiffness by FibroScan® ≥ 14.0 kPa and Enhanced Liver Fibrosis (ELF™) Test score ≥ 9.8 at Screening

• Screening laboratory parameters, as determined by the central laboratory:

  • Estimated glomerular filtration rate (eGFR) ≥ 60 mL/min, as calculated by the Cockcroft-Gault equation
  • Hemoglobin A1c (HbA1c) ≤ 9.5%
  • Alanine aminotransferase (ALT) < 5 x Upper Limits of Normal (ULN)
  • Platelet count ≥ 125,000/μL

Key Exclusion Criteria:

• Prior history of decompensated liver disease including ascites, hepatic encephalopathy, or variceal bleeding
• Child-Pugh (CP) score > 6 at Screening, unless due to an alternative etiology such as Gilbert's syndrome or therapeutic anticoagulation
• Model for End-Stage Liver Disease (MELD) score > 12 at Screening, unless due to an alternate etiology such as therapeutic anticoagulation
• Other causes of liver disease based on medical history and/or centralized review of liver histology, including but not limited to: alcoholic liver disease, hepatitis B, hepatitis C, autoimmune disorders (eg, primary biliary cholangitis, primary sclerosing cholangitis, autoimmune hepatitis), drug-induced hepatotoxicity, Wilson disease, clinically significant iron overload, or alpha-1-antitrypsin deficiency requiring treatment
• History of liver transplantation
• Current or prior history of hepatocellular carcinoma

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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395 participants in 7 patient groups

Selonsertib (SEL)

Experimental group

Description:

Participants will receive SEL + placebo to match firsocostat 20 mg tablet + placebo to match cilofexor 30 mg tablet orally once daily for 48 weeks.

Treatment:

Drug: Placebo to match FIR

Drug: Placebo to match CILO

Drug: SEL

Firsocostat (FIR)

Experimental group

Description:

Participants will receive placebo to match SEL 18 mg tablet + FIR + placebo to match CILO 30 mg tablet orally once daily for 48 weeks.

Treatment:

Drug: Placebo to match SEL

Drug: FIR

Drug: Placebo to match CILO

Cilofexor (CILO)

Experimental group

Description:

Participants will receive placebo to match SEL 18 mg tablet + placebo to match FIR 20 mg tablet + CILO orally once daily for 48 weeks.

Treatment:

Drug: Placebo to match SEL

Drug: CILO

Drug: Placebo to match FIR

Selonsertib (SEL) + Firsocostat (FIR)

Experimental group

Description:

Participants will receive SEL + FIR + placebo to match CILO 30 mg tablet orally once daily for 48 weeks.

Treatment:

Drug: FIR

Drug: Placebo to match CILO

Drug: SEL

Selonsertib (SEL) + Cilofexor (CILO)

Experimental group

Description:

Participants will receive SEL + placebo to match FIR 20 mg tablet + CILO orally once daily for 48 weeks.

Treatment:

Drug: CILO

Drug: Placebo to match FIR

Drug: SEL

Firsocostat (FIR) + Cilofexor (CILO)

Experimental group

Description:

Participants will receive placebo to match SEL 18 mg tablet + FIR + CILO orally once daily for 48 weeks.

Treatment:

Drug: Placebo to match SEL

Drug: CILO

Drug: FIR

Placebo

Experimental group

Description:

Participants will receive placebo to match SEL 18 mg + placebo to match FIR 20 mg tablet + placebo to match CILO 30 mg tablet orally once daily for 48 weeks.

Treatment:

Drug: Placebo to match SEL

Drug: Placebo to match FIR

Drug: Placebo to match CILO