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

Overview

  • Study type

    Interventional
  • Study phase

    II
  • Study IDs

  • Describes the nature of a clinical study. Types include:

    • Observational study — observes people and measures outcomes without affecting results.
    • Interventional study (clinical trial) — studies new tests, treatments, drugs, surgical procedures or devices.
    • Medical records research — uses historical information collected from medical records of large groups of people to study how diseases progress and which treatments and surgeries work best.
  • During the early phases (phases 1 and 2), researchers assess safety, side effects, optimal dosages and risks/benefits. In the later phase (phase 3), researchers study whether the treatment works better than the current standard therapy. They also compare the safety of the new treatment with that of current treatments. Phase 3 trials include large numbers of people to make sure that the result is valid. There are also less common very early (phase 0) and later (phase 4) phases. Phase 0 trials are small trials that help researchers decide if a new agent should be tested in a phase 1 trial. Phase 4 trials look at long-term safety and effectiveness, after a new treatment has been approved and is on the market.

  • Site IRB
    • Rochester, Minnesota: 16-004187
    NCT ID: NCT02686762
    Sponsor Protocol Number: IDN-6556-12

About this study

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.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. If you need assistance understanding the eligibility criteria, please contact the study team.

See eligibility criteria

Inclusion Criteria

  • Male or female 
  • 18 years or older
  • Able to provide written informed consent
  • 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
    • Confirmed by central histopathologist
    • Using 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 
    • 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, 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
    • 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
    • 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
    • Primary sclerosing cholangitis
    • Wilson's disease
    • Alpha-1-antitrypsin deficiency
    • Hemochromatosis or iron overload
    • Drug-induced liver disease
    • Other biliary liver disease
  • 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)
  • Alpha-fetoprotein >200 ng/mL
  • Hemoglobin <10 g/dL
  • White blood cell count <2.0 x 10^3/mm3
  • Estimated creatinine clearance <30 mL/min
  • 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
    • Some combination of these medications
  • Symptoms of biliary colic e.g. due to symptomatic gallstones, within the last 6 months, unless resolved following cholecystectomy
  • Inability to safely obtain a liver biopsy
  • Known human immunodeficiency virus (HIV) infection
  • Weight loss ≥ 10% within 6 months of day 1
  • 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
  • History of or active malignancies, other than those successfully treated with curative intent and believed to be cured
  • 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
    • Major surgery within 3 months of screening
  • History or presence of clinically concerning cardiac arrhythmias, or prolongation of screening (pre-treatment) QTcF interval >480 milliseconds (msec)
  • Prior or planned (during the time frame of the study) bariatric surgery
  • Planned or known pregnancy, positive urine or serum pregnancy test, or lactating/breastfeeding
  • Previous treatment with emricasan or active investigational medication in a clinical trial within 6 months prior to day 1
  • Prior liver transplant

Participating Mayo Clinic locations

Study statuses change often. Please contact us for help.

Mayo Clinic Location Status Contact

Rochester, Minn.

Mayo Clinic principal investigator

Harmeet Malhi, M.B.B.S.

Closed for enrollment

Contact information:

Jeanine Bauer

(507)284-0141

Bauer.Jeanine@mayo.edu

.
CLS-20258289

Mayo Clinic Footer