Phase 3 study RESOLVE-IT
In November 2015, GENFIT announced the design of the global Phase 3 trial RESOLVE-IT to evaluate the benefits of Elafibranor treatment on NASH patients.
RESOLVE-IT is a randomized pivotal trial, double-blind, placebo-controlled (2:1), conducted in approximately 2 000 patients, at 250 centers worldwide. The study population is NASH patients (NAS=4) with F2 or F3 fibrosis. Elafibranor 120 mg or placebo are administered once daily.
An interim analysis, for initial market approval under Subpart H, will be performed after 72 weeks of treatment in order to evaluate the beneficial effect of Elafibranor on the liver histology of the first 1 000 patients. To support full approval, the trial will continue in order to demonstrate the impact of Elafibranor on the prevention of cirrhosis and other liver related outcomes on the full study population. A group of patients with F1 fibrosis and concomitant cardiometabolic comorbidities, which are associated with rapid progression of the disease, will also be enrolled.
Initial approval will be based on the interim analysis (72 weeks / 1 000 patients) of the following surrogate histological primary endpoint: NASH resolution without worsening of fibrosis, corresponding to ballooning=0, inflammation=0-1. This criteria defining disease activity, based on a centralized histological reading, is considered by the regulatory authorities as well as NASH experts as a surrogate endpoint for approval.
In order to confirm the long-term clinical benefits of NASH resolution induced by Elafibranor 120mg, the trial will continue post-marketing and remain blinded after the interim analysis. All patients will be followed until the occurrence of a pre-defined number of progressions to cirrhosis and other liver related events.
The trial will also evaluate key secondary histological endpoints, including an improvement on fibrosis, and non-invasive markers of steatohepatitis. In addition, the trial will assess the improvement of cardiometabolic profile, including plasma lipids, glucose homeostasis and inflammatory markers.