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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

Lookup NU author(s): Professor Arun Sanyal, Professor Quentin AnsteeORCiD, Professor Pierre Bedossa



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


© 2019 Intercept Pharmaceuticals, Inc. 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: with the identifier NCT02548351.

Publication metadata

Author(s): Ratziu V, Sanyal AJ, Loomba R, Rinella M, Harrison S, Anstee QM, Goodman Z, Bedossa P, MacConell L, Shringarpure R, Shah A, Younossi Z

Publication type: Article

Publication status: Published

Journal: Contemporary Clinical Trials

Year: 2019

Volume: 84

Print publication date: 01/09/2019

Online publication date: 29/06/2019

Acceptance date: 27/06/2019

Date deposited: 31/07/2019

ISSN (print): 1551-7144

ISSN (electronic): 1559-2030

Publisher: Elsevier Inc.


DOI: 10.1016/j.cct.2019.06.017


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