A Multicenter, Randomized, Double-Blind, Placebo-controlled Trial of Emricasan (IDN-6556-12), an Oral Caspase Inhibitor, in Subjects With Non-alcoholic Steatohepatitis (NASH) Fibrosis
Overview
- Phase
- Phase 2
- Intervention
- Emricasan (5 mg)
- Conditions
- Non-alcoholic Steatohepatitis
- Sponsor
- Conatus Pharmaceuticals Inc.
- Enrollment
- 318
- Locations
- 103
- Primary Endpoint
- Fibrosis improvement by at least one stage without worsening of steatohepatitis
- Status
- Completed
- Last Updated
- 6 years ago
Overview
Brief Summary
This is a multicenter, double-blind, randomized, placebo-controlled trial involving subjects with a diagnosis of "definite NASH" with fibrosis (excluding cirrhosis) as determined by the central histopathologist. Upon successful screening, subjects will be randomized to receive either emricasan 50 mg BID or emricasan 5 mg BID or matching placebo BID.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Male or female subjects 18 years or older, able to provide written informed consent, and able to understand and willing to comply with the requirements of the study
- •Histological evidence of definite NASH based on NASH CLinical Research Network (CRN) criteria, as confirmed by the central histopathologist, on a liver biopsy obtained no more than 6 months prior to Day 1
- •NAFLD Activity Score (NAS) of 4 or greater with a score of at least 1 in each component of the NAS (steatosis scored 0-3, lobular inflammation scored 0-3, ballooning scored 0-2)
- •Fibrosis stage 1 (limited to 20% of subjects), stage 2, or stage 3 using the NASH CRN Histologic Scoring System
- •a. Subjects with fibrosis stage 1 must also have diabetes mellitus or metabolic syndrome
- •Willingness to utilize effective contraception (for both males and females of childbearing potential) from Screening to 4 weeks after the last dose of study drug
- •If on vitamin E or pioglitazone, subjects must have been on a stable dose for at least 3 months prior to the biopsy (whether historical or qualifying biopsy)
Exclusion Criteria
- •Current or history of significant alcohol consumption, defined as more than 20 g/day for females and more than 30 g/day in males on average, or inability to reliably quantify alcohol consumption based on investigator's judgement
- •Use of the following drugs (which may have potential hepatotoxic effects) within 6 months prior to Day 1: amiodarone, methotrexate, tamoxifen, valproic acid, estrogens at doses greater than those used for hormone replacement or contraception, anabolic steroids, or systemic glucocorticoids for more than 4 weeks at doses greater than replacement doses
- •Uncontrolled diabetes (HbA1c ≥9%) within 60 days prior to Day 1
- •Presence of cirrhosis on liver biopsy (fibrosis stage 4 based on the central histopathologist reading)
- •Hepatitis and fibrosis more likely related to etiologies other than NASH such as:
- •alcoholic steatohepatitis
- •autoimmune hepatitis
- •hepatitis B virus (HBV) infection
- •hepatitis C virus (HCV) infection
- •primary biliary cirrhosis
Arms & Interventions
Emricasan (5 mg)
Subjects with Non-alcoholic Steatohepatitis (NASH) Fibrosis will be administered orally with emricasan (5 mg) twice a day.
Intervention: Emricasan (5 mg)
Emricasan (50 mg)
Subjects with Non-alcoholic Steatohepatitis (NASH) Fibrosis will be administered orally with emricasan (50 mg) twice a day.
Intervention: Emricasan (50 mg)
Matching Placebo
Subjects with Non-alcoholic Steatohepatitis (NASH) Fibrosis will be administered orally with a matching placebo twice a day.
Intervention: Placebo
Outcomes
Primary Outcomes
Fibrosis improvement by at least one stage without worsening of steatohepatitis
Time Frame: Week 72
Proportion of subjects who improve fibrosis on liver biopsy by at least one stage without worsening of steatohepatitis in the emricasan group compared to placebo
Secondary Outcomes
- Improvement in the Non-alcoholic fatty liver disease (NAFLD) Activity Score(Baseline & Week 72)
- Steatohepatitis resolution (based on liver biopsy)(Baseline & Week 72)
- Caspase 3/7 Relative Light Units and Alanine aminotransferase (ALT)(Day 1, week 4, 24, 48, and 72)