Safety, Tolerability, and Efficacy of Monotherapy and Combination Regimens in Participants With Nonalcoholic Steatohepatitis (NASH)

Gilead Sciences

Status and phase: Completed; Phase 2

Conditions: Nonalcoholic Steatohepatitis

Treatments: Drug: Firsocostat; Drug: Semaglutide; Drug: Cilofexor

Study type: Interventional

Funder types: Industry

Identifiers

NCT03987074

GS-US-454-5533

Details and patient eligibility

About

The primary objective of this study is to evaluate the safety and tolerability of study drug(s) in participants with nonalcoholic steatohepatitis (NASH).

Enrollment: 109 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Key Inclusion Criteria:

• Historical liver biopsy consistent with NASH with stage 2-3 fibrosis according to NASH Clinical Research Network (CRN) classification OR clinical diagnosis of nonalcoholic fatty liver disease and screening FibroTest, magnetic resonance imaging - proton density fat fraction (MRI-PDFF), and FibroScan

• Screening laboratory parameters, as determined by central laboratory:

  • Alanine aminotransferase (ALT) ≤ 5 x upper limit of the normal range (ULN)
  • Estimated glomerular filtration rate (eGFR) ≥ 30 milliliter/minute (mL/min), as calculated by the Modification of Diet in Renal Disease (MDRD) study equation
  • HbA1c ≤ 9.5%
  • International normalized ratio (INR) ≤ 1.2, unless due to therapeutic anti-coagulation therapy
  • Platelet count ≥ 100,000/μL
  • Total bilirubin < 1.3 x ULN unless alternate etiology such as Gilbert's syndrome present
  • Calcitonin ≤ 100 ng/L

• Body Mass Index (BMI) > 23 kg/m^2 and body weight of > 60 kg

Key Exclusion Criteria:

• Any historical liver biopsy consistent with cirrhosis
• Any history of decompensated liver disease, including ascites, hepatic encephalopathy, or variceal bleeding
• Other causes of liver disease, including but not limited to: alcoholic liver disease, hepatitis B, hepatitis C, autoimmune disorders (eg, primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC), autoimmune hepatitis), drug-induced hepatotoxicity, Wilson disease, clinically significant iron overload, or alpha-1-antitrypsin deficiency requiring treatment
• History of liver transplantation
• History of hepatocellular carcinoma
• History of pancreatitis (acute or chronic)
• Personal or first degree relative(s) history of multiple endocrine neoplasia type 2 or medullary thyroid carcinoma
• Treatment with glucagon-like peptide-1 receptor agonists (GLP-1 RA) in the period from 90 days prior to the date of the Screening Visit
• Individuals on antidiabetic medications must be on a stable dose for at least 90 days prior to the date of the Screening Visit and in the period between the date of the Screening Visit and Enrollment (Day -14)

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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109 participants in 5 patient groups

Semaglutide

Experimental group

Description:

Semaglutide 0.24 mg - 2.4 mg (dose escalated over 16 weeks) for 24 weeks

Treatment:

Drug: Semaglutide

Semaglutide + Firsocostat 20 mg

Experimental group

Description:

Semaglutide 0.24 mg - 2.4 mg (dose escalated over 16 weeks) + firsocostat 20 mg for 24 weeks

Treatment:

Drug: Semaglutide

Drug: Firsocostat

Semaglutide + Cilofexor 30 mg

Experimental group

Description:

Semaglutide 0.24 mg - 2.4 mg (dose escalated over 16 weeks) + cilofexor 30 mg for 24 weeks

Treatment:

Drug: Cilofexor

Drug: Semaglutide

Semaglutide + Cilofexor 100 mg

Experimental group

Description:

Semaglutide 0.24 mg - 2.4 mg (dose escalated over 16 weeks) + cilofexor 100 mg for 24 weeks

Treatment:

Drug: Cilofexor

Drug: Semaglutide

Semaglutide + Firsocostat 20 mg + Cilofexor 30 mg

Experimental group

Description:

Semaglutide 0.24 mg - 2.4 mg (dose escalated over 16 weeks) + firsocostat 20 mg + cilofexor 30 mg for 24 weeks

Treatment:

Drug: Cilofexor

Drug: Semaglutide

Drug: Firsocostat