Date: 2017-08-14
Type of
information: Completion of patient enrollment
phase: 2b
Announcement: completion of patient enrollment
Company: Conatus Pharmaceuticals (USA - CA)
Product: emricasan
Action
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)
Therapeutic
area: Hepatic diseases - Liver diseases
Country: Germany, Spain, USA
Trial
details:
- The ENCORE-NF clinical trial is expected to be conducted at approximately 100 U.S. and EU clinical sites. Patients were randomized 1:1:1 to receive 5 mg of emricasan, 50 mg of emricasan, or placebo twice daily for 72 weeks. The 5 mg and 50 mg doses have previously been shown to be equally effective in reducing ALT, AST and mechanism-specific biomarkers in patients with liver fibrosis, while the 50 mg dose may provide additional benefit in patients with liver cirrhosis. The primary endpoint is a biopsy-based improvement in fibrosis by at least one stage vs. placebo using NASH CRN without worsening of steatohepatitis. Secondary endpoints include resolution of steatohepatitis without worsening of fibrosis, nonalcoholic fatty liver disease (NAFLD) activity score (NAS) and its components (steatosis, lobular inflammation, and ballooning), collagen and fat content by biopsy, key serum biomarkers, and health-related quality of life, as well as safety and tolerability of emricasan. (NCT02686762)
- In collaboration with Novartis, Conatus is conducting four randomized, double-blind, placebo-controlled Phase 2b clinical trials designed to evaluate emricasan treatment in various patient populations, including three in the EmricasaN, a Caspase inhibitOR, for Evaluation (ENCORE) series in patients with fibrosis or cirrhosis caused by NASH, and a fourth in POLT-HCV-SVR patients:ENCORE-NF (for NASH Fibrosis), initiated in the first quarter of 2016, in approximately 330 patients with NASH fibrosis, with top-line results expected in the first half of 2019;
ENCORE-PH (for Portal Hypertension), initiated in the fourth quarter of 2016, in approximately 240 patients with compensated or early decompensated NASH cirrhosis and severe portal hypertension, with top-line results expected in 2018 followed by an integrated 6-month treatment extension period for clinical outcomes;
ENCORE-LF (for Liver Function), initiated in the second quarter of 2017, in approximately 210 patients with decompensated NASH cirrhosis, with top-line results expected in 2019; and
POLT-HCV-SVR, initiated in the second quarter of 2014, 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, with top-line results 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.
Latest
news:
- • On August 14, 2017, Conatus Pharmaceuticals announced the completion of enrollment in ENCORE-NF, a randomized, double-blind, placebo-controlled, Phase 2b clinical trial evaluating emricasan, the company’s first-in-class, orally-active pan-caspase inhibitor, in approximately 330 patients with biopsy-confirmed nonalcoholic steatohepatitis (NASH) and stage 1 to 3 fibrosis using the NASH Clinical Research Network (CRN) Histologic Scoring System. This trial is designed to evaluate the long-term safety and efficacy of emricasan in patients with NASH fibrosis as well as support the initial registration focus in liver cirrhosis.
- • On January 11, 2016, Conatus Pharmaceuticals announced the initiation of active patient recruitment in ENCORE-NF, a randomized, double-blind, placebo-controlled, Phase 2b clinical trial evaluating emricasan, the company's first-in-class, orally-active pan-caspase inhibitor, in approximately 330 patients with biopsy-confirmed nonalcoholic steatohepatitis (NASH) and stage 1 to 3 fibrosis using the NASH Clinical Research Network (CRN) Histologic Scoring System. This trial is designed to evaluate differentiated dosing and establish efficacy of emricasan in the large and growing NASH fibrosis market as well as add long-term safety data in support of the company's initial registration focus in liver cirrhosis. Top-line results from the ENCORE-NF clinical trial are expected in 2018.
- The ENCORE-NF clinical trial is the first of multiple parallel EmricasaN, a Caspase inhibitOR, for Evaluation (ENCORE) Phase 2b clinical trials designed to evaluate multiple doses of emricasan over various treatment durations in chronic liver disease of different etiologies and disease stages. The ENCORE trials are designed to provide clinically relevant efficacy, dosing, and safety data to support the initial registration of emricasan for chronic administration in patients with liver cirrhosis. Results from the combined ENCORE clinical trials are expected to support the design of Phase 3 efficacy and safety trials, but could warrant earlier discussions with regulatory agencies regarding potential accelerated approval. Conatus expects to initiate the remainder of these trials on a staggered basis through early 2017 and expects top-line results from the ENCORE clinical trials to be available periodically beginning in the first half of 2018.
Is
general: Yes
