information: Initiation of the trial
Announcement: initiation of the trial
Company: Conatus Pharmaceuticals (USA - CA)
mechanism: caspase converting enzyme inhibitor. Emricasan is a first-in-class, orally active caspase protease inhibitor designed to reduce the activity of enzymes that mediate inflammation and cell death, or apoptosis. In February 2016, the FDA granted Fast Track designation to the emricasan development program for the treatment of liver cirrhosis caused by NASH.
Disease: NASH (non-alcoholic steatohepatitis)
area: Hepatic diseases - Liver diseases
details: The ENCORE-LF clinical trial is designed to evaluate dosing, efficacy and safety of emricasan in approximately 210 patients with decompensated NASH cirrhosis. Patients will be randomized 1:1:1 to receive 5 mg of emricasan, 25 mg of emricasan, or placebo twice daily for at least 48 weeks. The primary endpoint is event-free survival for each treatment group compared with the placebo group. For the purposes of the trial, events are defined as all-cause mortality, new decompensation events, or a progression of ?4 points in the Model for End-stage Liver Disease (MELD) score. Key secondary endpoints include safety and tolerability, MELD and Child-Pugh scores, liver transplantation rates, liver metabolic function using the BreathID® Methacetin Breath Test, and health-related quality of life.
- • On May 4, 2017, Conatus Pharmaceuticals announced that Novartis has exercised its option to an exclusive license for the global development and commercialization of emricasan under terms of the agreement signed in December 2016. The option exercise followed notification by Conatus of the initiation of the Phase 2b ENCORE-LF (for Liver Function) randomized, double-blind, placebo-controlled clinical trial evaluating emricasan in patients with decompensated liver cirrhosis caused by nonalcoholic steatohepatitis (NASH).
- The ENCORE-LF clinical trial is expected to be conducted at approximately 90 clinical sites, and is designed to evaluate dosing, efficacy and safety of emricasan in approximately 210 patients with decompensated NASH cirrhosis.
- Conatus is conducting three ongoing EmricasaN, a Caspase inhibitOR, for Evaluation (ENCORE) clinical trials designed to evaluate emricasan treatment in various NASH patient populations: ENCORE-LF, in decompensated NASH cirrhosis, with top-line results expected in 2019;
- ENCORE-NF (for NASH Fibrosis), a randomized, double-blind, placebo-controlled Phase 2b clinical trial, initiated in the first quarter of 2016, evaluating potential improvements in fibrosis and steatohepatitis in approximately 330 patients with NASH fibrosis. Based on anticipated completion of enrollment, top-line results after 18 months of twice-daily treatment with emricasan or placebo are now expected in the first half of 2019; and
- ENCORE-PH (for Portal Hypertension), a randomized, double-blind, placebo-controlled Phase 2b clinical trial, initiated in the fourth quarter of 2016, evaluating dosing, efficacy and safety of emricasan in approximately 240 patients with compensated or early decompensated NASH cirrhosis and severe portal hypertension. Conatus has amended the ENCORE-PH clinical trial protocol to integrate a six-month treatment extension period for clinical outcomes, rather than conduct a separate extension trial. Top-line results for the primary endpoint after the first six months of twice-daily treatment with emricasan or placebo are expected in 2018.
- Conatus Pharmaceuticals is also conducting a fourth ongoing clinical trial in hepatitis C virus (HCV) patients. POLT-HCV-SVR is a randomized, double-blind, placebo-controlled Phase 2b clinical trial, initiated in the second quarter of 2014. The trial is evaluating potential improvements in fibrosis in approximately 60 post-orthotopic liver transplant (POLT) recipients with liver fibrosis or cirrhosis post-transplant as a result of recurrent HCV infection who have successfully achieved a sustained viral response (SVR) following HCV antiviral therapy. Top-line results after two years of twice-daily treatment with emricasan or placebo are expected in the first half of 2018.
- Results from the four ongoing emricasan clinical trials are expected to support the design of Phase 3 clinical efficacy and safety trials.