Clinical Trials

Date: 2017-02-10

Type of information: update on patient enrollment

phase: 3

Announcement: update

Company: Intercept Pharmaceuticals (USA - NY)

Product: Ocaliva® (obeticholic acid - OCA)

Action mechanism: farnesoid X receptor agonist. Obeticholic acid (OCA) is a bile acid analog and a first-in-class farnesoid X receptor (FXR) agonist being developed for primary biliary cirrhosis (PBC), NASH and other chronic liver indications. Intercept has initiated a rolling New Drug Application with the FDA for PBC, and expects to complete the NDA and MAA submission in 2Q 2015. The commercial launch of OCA in the U.S. and Europe is planned in 2016. OCA was also recently granted breakthrough therapy designation by FDA for the treatment of NASH with liver fibrosis.

Disease: NASH (non-alcoholic steatohepatitis)

Therapeutic area: Liver diseases - Hepatic diseases

Country: USA

Trial details:

• REGENERATE has been designed as a double-blind, placebo-controlled Phase 3 clinical trial expected to enroll approximately 2,000 NASH patients at up to 300 qualified centers worldwide and assess the potential benefits of OCA treatment on liver-related and other clinical outcomes. The trial will include a pre-planned interim histology analysis after 72 weeks of treatment in 1,400 patients, which is intended to serve as the basis for seeking initial U.S. and international marketing approvals of OCA for the treatment of NASH patients with fibrosis. Two co-primary endpoints will be assessed in the interim analysis:
• (i) fibrosis improvement with no worsening of NASH and
• (ii) NASH resolution with no worsening of fibrosis. (NCT02548351)

Latest news:

• • On February 10, 2017, Intercept Pharmaceuticals announced an update on the Phase 3 REGENERATE trial of obeticholic acid in NASH patients with liver fibrosis. The FDA has approved the redesign of the study. Intercept Pharmaceuticals now only needs to achieve one of the two co-primary endpoints of the trial. The two endpoints of REGENERATE include fibrosis improvement with no worsening of NASH and NASH resolution with no worsening of fibrosis. Intercept Pharmaceuticals and the FDA have also agreed with the definition of  NASH resolution in the trial and the company has adopted the international definition of the disease. These decisions enable Intercept Pharmaceuticals to reduce its recruitement target from 1 400 to 750.
• • On September 28, 2015, Intercept Pharmaceuticals announced the initiation of the REGENERATE trial, an international Phase 3 trial of obeticholic acid (OCA), the company's lead FXR agonist, in patients with non-cirrhotic nonalcoholic steatohepatitis (NASH) with advanced liver fibrosis. The study population will be primarily comprised of NASH patients with stage 2 or stage 3 liver fibrosis. Advanced liver fibrosis has been shown to be the best predictor of liver transplant and mortality in patients with NASH. In addition, the trial will include an exploratory cohort of NASH patients with early stage 1 liver fibrosis and concomitant diabetes, obesity or elevated alanine aminotransferase (ALT) who are at increased risk of progression to cirrhosis.
• • On May 19, 2015, Intercept Pharmaceuticals announced its plans for an international Phase 3 trial of obeticholic acid (OCA), the company's lead FXR agonist, in patients with non-cirrhotic nonalcoholic steatohepatitis (NASH) with liver fibrosis. OCA has received breakthrough therapy designation in this patient population from the FDA. In accordance with harmonized advice from the FDA and European Medicines Authority (EMA), the Randomized Global Phase 3 Trial to Evaluate the Impact on NASH with Fibrosis of Obeticholic Acid Treatment (REGENERATE) has been designed as a double-blind, placebo-controlled pivotal Phase 3 clinical trial expected to enroll up to approximately 2,500 patients and assess the potential benefit of OCA treatment on liver-related clinical outcomes. The trial will include a pre-planned interim histology analysis after 72 weeks of treatment in approximately 1,400 patients which is intended to serve as the basis for seeking U.S. and international marketing approvals of OCA for the treatment of NASH patients with liver fibrosis.
• The REGENERATE trial will be conducted at approximately 250 centers in North America , Europe and other regions and trial initiation is anticipated in 3Q 2015. Patients will be randomized 1:1:1 to one of placebo, 10 mg of OCA, or 25 mg of OCA, taken once daily. The study population will primarily be comprised of NASH patients with stage 2 or stage 3 advanced liver fibrosis who will be evaluated on the primary efficacy endpoints in the 72-week interim analysis and subsequently. In addition, a relatively small group of NASH patients with stage 1 early liver fibrosis with an increased risk of rapid progression due to concomitant diabetes, obesity or active liver inflammation indicated by elevated ALT will also be enrolled, but not included in the primary endpoint analyses.
• The interim analysis after 72 weeks of treatment in approximately 1,400 patients will be conducted on the following co-primary endpoints, which are intended to serve as the basis for seeking U.S. and international marketing approvals: (i) the proportion of OCA-treated patients relative to placebo achieving at least one stage of liver fibrosis improvement with no worsening NASH; and (ii) the proportion of OCA-treated patients relative to placebo achieving NASH resolution with no worsening of liver fibrosis. Additional supportive histologic endpoints and non-invasive markers of liver fibrosis and steatohepatitis will also be evaluated. The REGENERATE trial will remain blinded after the interim analysis and continue to follow patients until the occurrence of a pre-specified number of adverse liver-related clinical events, including progression to cirrhosis, to confirm clinical benefit on a post-marketing basis.

Is general: Yes