1 Sorbonne Université, Hôpital Pitié - Salpêtrière, 91-105 Boulevard de l'Hôpital, 75013 Paris, France. Electronic address: firstname.lastname@example.org.
2 Department of Internal Medicine, Virginia Commonwealth University, 1101 E Marshall St, Richmond, VA, USA.
3 University of California, San Diego, 9500 Gilman Dr, La Jolla, CA, USA.
4 Division of Gastroenterology and Hepatology, Feinberg School of Medicine, Northwestern University, 676 N Saint Clair St, Chicago, IL, USA.
5 Pinnacle Clinical Research Center, 5109 Medical Dr. Ste 200, San Antonio, TX 78229, United States.
6 Liver Research Group, Institute of Cellular Medicine, The Medical School, Newcastle University, Framlington Place, Newcastle-upon-Tyne, NE2 4HH, UK.
7 Betty and Guy Beatty Center for Integrated Research, Inova Health System, Claude Moore Health Education and Research Building, 3300 Gallows Rd, Falls Church, VA, USA.
8 Service d'Anatomie Pathologique, Hôpital Beaujon, Assistance Publique-Hôpitaux de Paris, INSERM UMR 1149-CRI, Université Denis Diderot Paris-7, 46 rue Henri Huchard, 75018 Clichy, France.
9 Intercept Pharmaceuticals, 4760 Eastgate Mall, San Diego, CA, USA.
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.