REGENERATE: Design of a pivotal, randomised, phase 3 study evaluating the safety and efficacy of obeticholic acid in patients with fibrosis due to nonalcoholic steatohepatitis
Vlad Ratziu, Arun J Sanyal, Rohit Loomba, Mary Rinella, Stephen Harrison, Quentin M Anstee, Zachary Goodman, Pierre Bedossa, Leigh MacConell, Reshma Shringarpure, Amrik Shah, Zobair Younossi, Vlad Ratziu, Arun J Sanyal, Rohit Loomba, Mary Rinella, Stephen Harrison, Quentin M Anstee, Zachary Goodman, Pierre Bedossa, Leigh MacConell, Reshma Shringarpure, Amrik Shah, Zobair Younossi
Abstract
Background: Nonalcoholic steatohepatitis (NASH) is a chronic, progressive, and severe form of nonalcoholic fatty liver disease. In FLINT, obeticholic acid (OCA) treatment improved multiple histological NASH features. The design and endpoints of REGENERATE, an ongoing phase 3 study, further evaluate OCA treatment in patients with fibrosis due to NASH.
Aims: The Month 18 interim analysis assesses the effect of OCA on liver histology, defined as improvement of fibrosis by ≥1 stage with no worsening of NASH or resolution of NASH with no worsening of fibrosis. The end-of-study analyses evaluate the effect of OCA on mortality, liver-related clinical outcomes, and long-term safety.
Methods: REGENERATE is a pivotal, long-term study of ~2400 patients with NASH, including ~2100 patients with stage 2 or 3 liver fibrosis. Additionally, ~300 patients with stage 1 fibrosis and ≥1 accompanying comorbidity are included to gather information on the safety of OCA and liver disease progression. Patients are randomised 1:1:1 to receive placebo or OCA (10 or 25 mg). A liver biopsy evaluation occurs at screening, Months 18 and 48, and end of study. The duration of the study is dependent upon accrual of a predetermined number of clinical outcome events.
Conclusions: REGENERATE is designed in conjunction with regulatory authorities to support regulatory approvals in NASH. This robust phase 3 study assesses the effect of OCA on liver histology as a surrogate for transplant-free survival and liver-related outcomes, including progression to cirrhosis and mortality, and will ultimately assess clinical benefit through specific evaluation of these outcomes.
Clinical trial registration: ClinicalTrials.gov with the identifier NCT02548351.
Keywords: Farnesoid X receptor; NASH; Nonalcoholic fatty liver disease; Nonalcoholic steatohepatitis; Obeticholic acid.
Copyright © 2019 Intercept Pharmaceuticals, Inc. Published by Elsevier Inc. All rights reserved.
Source: PubMed