MedDRA version: 18.1 Level: PT Classification code 10053219 Term: Non-alcoholic steatohepatitis System Organ Class: 10019805 - Hepatobiliary disorders
Conditions
Sponsors
Conatus Pharmaceuticals Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. 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 2. Histological evidence of definite NASH based on NASH CRN criteria, as confirmed by the central histopathologist, on a liver biopsy obtained no more than 6 months prior to Day 1 3. 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) 4. 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 5. 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 6. 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) Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 264 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 66
Exclusion criteria
Exclusion criteria: 1. 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 2. 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, systemic glucocorticoids for more than 4 weeks at doses greater than replacement doses 3. Uncontrolled diabetes (glycated hemoglobin [HbA1c] ?9%) within 60 days prior to Day 1 4. Presence of cirrhosis on liver biopsy (fibrosis stage 4 based on the central histopathologist reading) 5. Evidence of other forms of chronic liver disease such as: a. autoimmune hepatitis b. active infection with hepatitis B virus (HBV) c. hepatitis C virus (HCV) infection d. primary biliary cirrhosis e. primary sclerosing cholangitis f. Wilson?s disease g. alpha-1-antitrypsin deficiency h. hemochromatosis or iron overload i. drug-induced liver disease j. other biliary liver disease 6. ALT or AST >5 times upper limit of normal (ULN) or total bilirubin >1.5 times ULN during screening (unless subject has elevated total bilirubin due to Gilbert?s as documented in the medical records) 7. Alpha-fetoprotein >100 ng/mL 8. Hemoglobin 480 milliseconds (msec) 20. Prior or pla
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess whether treatment with emricasan compared to matching placebo in subjects with NASH fibrosis improves fibrosis on liver biopsy by at least one stage without worsening of steatohepatitis using the NASH Clinical Research Network (CRN) Histologic Scoring System.; Secondary Objective: - To assess the safety and tolerability of emricasan in subjects with NASH fibrosis, including any potential effects on metabolic parameters (insulin resistance, glycemic control, lipid levels) - To assess whether emricasan compared to placebo can resolve steatohepatitis without worsening of fibrosis in subjects with NASH fibrosis - To assess whether emricasan compared to placebo can improve NAFLD Activity Score (NAS), its components (steatosis, lobular inflammation, ballooning), and portal inflammation in subjects with NASH fibrosis - To assess whether emricasan compared to placebo can improve collagen and fat content based on liver biopsy morphometry in subjects with NASH fibrosis - To assess whether emricasan compared to placebo improves biomarkers (caspase 3/7, cCK18/M30, flCK18/M65, ALT, AST, serum fibrosis markers) in subjects with NASH fibrosis - To assess whether emricasan compared to placebo improves health-related quality of life in subjects with NASH fibrosis ;Timepoint(s) of evaluation of this end point: Week 72; Primary end point(s): Change from baseline in fibrosis stage at 72 weeks; All subjects who complete the study will have a liver biopsy at week 72. Subjects discontinuing the study early will be contacted and asked to sign a separate consent to return for a week 72 liver biopsy. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Resolution of steatohepatitis (no ballooning and no more than 1 point in inflammation) without worsening of fibrosis - Decrease in NAS of at least 2 points without worsening of fibrosis ;Timepoint(s) of evaluation of this end point: Week 72 | — |
Countries
Germany, Spain, United States
Contacts
Public ContactClinical Trial Information
Conatus Pharmaceuticals Inc.
Outcome results
None listed