Clinical trial NCT03987074: Safety, Tolerability, and Efficacy of Monotherapy and Combination Regimens in Participants With Nonalcoholic Steatohepatitis (NASH)
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Nonalcoholic Steatohepatitis
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
Collaborators: name: Novo Nordisk A/S
First posted: 2019-06-14
Enrollment: 109
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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


Eligibility 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.

Primary outcomes:
measure: Percentage of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs)
timeFrame: First dose date up to Week 24 plus 30 days
measure: Percentage of Participants Experiencing Treatment-Emergent Laboratory Abnormalities
timeFrame: First dose date up to 24 weeks plus 30 days
Secondary outcomes:
Other outcomes:
Locations:
city: Chandler
country: United States
facility: Institute for Liver Health - Arizona Liver Health
state: Arizona
city: Coronado
country: United States
facility: Southern California Research Centers
state: California
city: La Jolla
country: United States
facility: University of California San Diego (UCSD)
state: California
city: Los Angeles
country: United States
facility: Ruane Clinical Research Group, Inc
state: California
city: Los Angeles
country: United States
facility: Cedars Sinai Medical Center
state: California
city: Rialto
country: United States
facility: Inland Empire Clinical Trials, LLC
state: California
city: San Diego
country: United States
facility: Medical Associates Research Group
state: California
city: Marietta
country: United States
facility: Gastrointestinal Specialists of Georgia
state: Georgia
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Las Vegas
country: United States
facility: Jubilee Clinical Research, Inc.
state: Nevada
city: Manhasset
country: United States
facility: Northwell Health
state: New York
city: Huntersville
country: United States
facility: Gastro One
state: North Carolina
city: Providence
country: United States
facility: University Gastroenterology
state: Rhode Island
city: Germantown
country: United States
facility: Gastro One
state: Tennessee
city: Nashville
country: United States
facility: Quality Medical Research, PLLC
state: Tennessee
city: Arlington
country: United States
facility: Texas Clinical Research Institute
state: Texas
city: Dallas
country: United States
facility: The Liver Institute at Methodist Dallas Medical Center
state: Texas
city: San Antonio
country: United States
facility: American Research Corporation
state: Texas
Study officials:
affiliation: Gilead Sciences
name: Gilead Study Director
role: STUDY_DIRECTOR
References:
citation: 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.
citation: Alkhouri N, Herring R, Kabler H, Kayali Z, Hassanein T, Kohli A, Huss RS, Zhu Y, Billin AN, Damgaard LH, Buchholtz K, Kjaer MS, Balendran C, Myers RP, Loomba R, Noureddin M. Safety and efficacy of combination therapy with semaglutide, cilofexor and firsocostat in patients with non-alcoholic steatohepatitis: A randomised, open-label phase II trial. J Hepatol. 2022 Sep;77(3):607-618. doi: 10.1016/j.jhep.2022.04.003. Epub 2022 Apr 16.