Trial record 2 of 115 for:    fatty liver | Open Studies | United States

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

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2016 by Conatus Pharmaceuticals Inc.
Sponsor:
Information provided by (Responsible Party):
Conatus Pharmaceuticals Inc.
ClinicalTrials.gov Identifier:
NCT02686762
First received: February 10, 2016
Last updated: July 7, 2016
Last verified: July 2016
  Purpose
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.

Condition Intervention Phase
Non-alcoholic Steatohepatitis
Fibrosis
Liver Diseases
Drug: Emricasan (5 mg)
Drug: Emricasan (50 mg)
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Conatus Pharmaceuticals Inc.:

Primary Outcome Measures:
  • Fibrosis improvement by at least one stage without worsening of steatohepatitis [ Time Frame: Week 72 ] [ Designated as safety issue: No ]
    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 Outcome Measures:
  • Steatohepatitis resolution (based on liver biopsy) [ Time Frame: Baseline & Week 72 ] [ Designated as safety issue: No ]
    The proportion of subjects who resolve steatohepatitis without worsening of fibrosis in the emricasan group compared to placebo

  • Improvement in the Non-alcoholic fatty liver disease (NAFLD) Activity Score [ Time Frame: Baseline & Week 72 ] [ Designated as safety issue: No ]
    The proportion of subjects who improve the NAFLD Activity Score (NAS), its components (steatosis, lobular inflammation, ballooning), and portal inflammation, in the emricasan group compared to placebo

  • Caspase 3/7 Relative Light Units and Alanine aminotransferase (ALT) [ Time Frame: Day 1, week 4, 24, 48, and 72 ] [ Designated as safety issue: No ]
    To asses whether emricasan compared to placebo improves biomarkers Caspase 3/7 RLU and ALT Unit/Liter (U/L) in subjects with NASH fibrosis.


Estimated Enrollment: 330
Study Start Date: January 2016
Estimated Study Completion Date: October 2018
Estimated Primary Completion Date: September 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Emricasan (5 mg)
Subjects with Non-alcoholic Steatohepatitis (NASH) Fibrosis will be administered orally with emricasan (5 mg) twice a day.
Drug: Emricasan (5 mg)
Subjects with Non-alcoholic Steatohepatitis (NASH) Fibrosis will be administered orally with emricasan (5 mg) twice a day.
Other Name: IDN-6556
Active Comparator: Emricasan (50 mg)
Subjects with Non-alcoholic Steatohepatitis (NASH) Fibrosis will be administered orally with emricasan (50 mg) twice a day.
Drug: Emricasan (50 mg)
Subjects with Non-alcoholic Steatohepatitis (NASH) Fibrosis will be administered orally with emricasan (50 mg) twice a day.
Other Name: IDN-6556
Placebo Comparator: Matching Placebo
Subjects with Non-alcoholic Steatohepatitis (NASH) Fibrosis will be administered orally with a matching placebo twice a day.
Drug: Placebo
Subjects with Non-alcoholic Steatohepatitis (NASH) Fibrosis will be administered orally with a matching placebo twice a day.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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 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 103/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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02686762

Contacts
Contact: Lisa Grubbs (858) 376-2627 lgrubbs@conatuspharma.com
Contact: Beth Sheedy (858) 376-2600 bsheedy@conatuspharma.com

  Show 34 Study Locations
Sponsors and Collaborators
Conatus Pharmaceuticals Inc.
Investigators
Study Chair: Dave Hagerty, MD Conatus Pharmaceuticals
  More Information

Responsible Party: Conatus Pharmaceuticals Inc.
ClinicalTrials.gov Identifier: NCT02686762     History of Changes
Other Study ID Numbers: IDN-6556-12 
Study First Received: February 10, 2016
Last Updated: July 7, 2016
Health Authority: United States: Food and Drug Administration
Germany: Federal Institute for Drugs and Medical Devices
Spain: Spanish Agency of Medicines
Individual Participant Data  
Plan to Share IPD: No

Keywords provided by Conatus Pharmaceuticals Inc.:
NASH

Additional relevant MeSH terms:
Liver Diseases
Fatty Liver
Non-alcoholic Fatty Liver Disease
Fibrosis
Pathologic Processes
Digestive System Diseases
Caspase Inhibitors
Cysteine Proteinase Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 24, 2016