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

Nonalcoholic Steatohepatitis Clinical Trial

Official title:

A Proof of Concept, Open-Label Study Evaluating the Safety, Tolerability, and Efficacy of Monotherapy and Combination Regimens in Subjects With Nonalcoholic Steatohepatitis (NASH)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03987074
• Other study ID #: GS-US-454-5533
• Status: Completed
• Phase: Phase 2
• Start date: July 29, 2019
• Est. completion date: July 13, 2020

Study information

• Verified date: June 2021
• Source: Gilead Sciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 109
• Est. completion date: July 13, 2020
• Est. primary completion date: July 13, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Fatty Liver
• Non-alcoholic Fatty Liver Disease
• Nonalcoholic Steatohepatitis

Intervention

Drug:
• Semaglutide
Solution administered subcutaneously with pre-filled PDS290 pen-injector once weekly
• Firsocostat
Tablets administered orally once daily
• Cilofexor
Tablets administered orally once daily

Locations

Country	Name	City	State
United States	Texas Clinical Research Institute	Arlington	Texas
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Institute for Liver Health - Arizona Liver Health	Chandler	Arizona
United States	Southern California Research Centers	Coronado	California
United States	The Liver Institute at Methodist Dallas Medical Center	Dallas	Texas
United States	Gastro One	Germantown	Tennessee
United States	Gastro One	Huntersville	North Carolina
United States	University of California San Diego (UCSD)	La Jolla	California
United States	Jubilee Clinical Research, Inc.	Las Vegas	Nevada
United States	Cedars Sinai Medical Center	Los Angeles	California
United States	Ruane Clinical Research Group, Inc	Los Angeles	California
United States	Northwell Health	Manhasset	New York
United States	Gastrointestinal Specialists of Georgia	Marietta	Georgia
United States	Quality Medical Research, PLLC	Nashville	Tennessee
United States	University Gastroenterology	Providence	Rhode Island
United States	Inland Empire Clinical Trials, LLC	Rialto	California
United States	American Research Corporation	San Antonio	Texas
United States	Medical Associates Research Group	San Diego	California

Sponsors (2)

Lead Sponsor	Collaborator
Gilead Sciences	Novo Nordisk A/S

Country where clinical trial is conducted

United States, 

References & Publications (1)

Alkhouri N et al. Safety and Efficacy of Combination Therapies Including Semaglutide, Cilofexor, and Firsocostat in Patients with NASH [accepted for oral presentation]. American Association for the Study of Liver Diseases (AASLD); 2020; Virtual.

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs)	Treatment-emergent adverse events (TEAEs) were defined as, any AEs with an onset date on or after the study drug start date and no later than 30 days after permanent discontinuation of study drug or any AEs leading to premature discontinuation of study drug. Participants were assessed for AEs according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.	First dose date up to Week 24 plus 30 days
Primary	Percentage of Participants Experiencing Treatment-Emergent Laboratory Abnormalities	Treatment-emergent laboratory abnormalities, defined as values that increase at least one toxicity grade from baseline at any time post-baseline up to and including the date of last dose of study drug plus 30 days, were summarized by treatment group. Graded laboratory abnormalities were defined using the grading scheme in the CTCAE 5.0.	First dose date up to 24 weeks plus 30 days