Emricasan, a Caspase Inhibitor, for Evaluation in Subjects With Non-Alcoholic Steatohepatitis (NASH) Fibrosis (ENCORE-NF)

C

Conatus Pharmaceuticals

Status and phase

Completed
Phase 2

Conditions

Non-alcoholic Steatohepatitis
Fibrosis
Liver Diseases

Treatments

Drug: Emricasan (50 mg)
Drug: Emricasan (5 mg)
Drug: Placebo

Study type

Interventional

Funder types

Industry

Identifiers

NCT02686762
IDN-6556-12

Details and patient eligibility

About

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.

Enrollment

318 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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 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

  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)

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, or systemic glucocorticoids for more than 4 weeks at doses greater than replacement doses

  3. Uncontrolled diabetes (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. Hepatitis and fibrosis more likely related to etiologies other than NASH such as:

    1. alcoholic steatohepatitis
    2. autoimmune hepatitis
    3. hepatitis B virus (HBV) infection
    4. hepatitis C virus (HCV) infection
    5. primary biliary cirrhosis
    6. primary sclerosing cholangitis
    7. Wilson's disease
    8. alpha-1-antitrypsin deficiency
    9. hemochromatosis or iron overload
    10. drug-induced liver disease
    11. 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 >200 ng/mL

  8. Hemoglobin <10 g/dL

  9. White blood cell count <2.0 x 10^3/mm3

  10. Estimated creatinine clearance <30 mL/min

  11. Current use of the following medications that are considered significant inhibitors of OATP1B1 and OATP1B3 transporters: atazanavir, cyclosporine, eltrombopag, gemfibrozil, indinavir, lopinavir, ritonavir, rifampin, saquinavir, simeprevir, telaprevir, tipranovir, or some combination of these medications

  12. Symptoms of biliary colic, e.g. due to symptomatic gallstones, within the last 6 months, unless resolved following cholecystectomy

  13. Inability to safely obtain a liver biopsy

  14. Known human immunodeficiency virus (HIV) infection

  15. Weight loss ≥ 10% within 6 months of Day 1

  16. Use of controlled substances (including inhaled or injected drugs) or non-prescribed use of prescription drugs within 1 year of screening to the point of interfering with the subject's ability to comply with study procedures and study drug administration in the investigator's judgement

  17. History of or active malignancies, other than those successfully treated with curative intent and believed to be cured

  18. Significant systemic or major illness other than liver disease that in the opinion of the investigator would preclude the subject from participating in and completing the study, including but not limited to acute coronary syndrome or stroke within 6 months of screening or major surgery within 3 months of screening

  19. History or presence of clinically concerning cardiac arrhythmias, or prolongation of Screening (pre-treatment) QTcF interval >480 milliseconds (msec)

  20. Prior or planned (during the time frame of the study) bariatric surgery

  21. If female: planned or known pregnancy, positive urine or serum pregnancy test, or lactating/breastfeeding

  22. Previous treatment with emricasan or active investigational medication in a clinical trial within 6 months prior to Day 1

  23. Prior liver transplant

Trial design

Primary purpose

Treatment

Allocation

Randomized

Interventional model

Parallel Assignment

Masking

Triple Blind

318 participants in 3 patient groups, including a placebo group

Emricasan (5 mg)
Active Comparator group
Description:
Subjects with Non-alcoholic Steatohepatitis (NASH) Fibrosis will be administered orally with emricasan (5 mg) twice a day.
Treatment:
Drug: Emricasan (5 mg)
Emricasan (50 mg)
Active Comparator group
Description:
Subjects with Non-alcoholic Steatohepatitis (NASH) Fibrosis will be administered orally with emricasan (50 mg) twice a day.
Treatment:
Drug: Emricasan (50 mg)
Matching Placebo
Placebo Comparator group
Description:
Subjects with Non-alcoholic Steatohepatitis (NASH) Fibrosis will be administered orally with a matching placebo twice a day.
Treatment:
Drug: Placebo

Trial contacts and locations

103

Loading...

Data sourced from clinicaltrials.gov

Clinical trials

Find clinical trialsTrials by location
© Copyright 2024 Veeva Systems