Study Evaluating the Efficacy and Safety of Obeticholic Acid in Subjects With Compensated Cirrhosis Due to Nonalcoholic Steatohepatitis

Overview

  • Study type

    Interventional
  • Study phase

    III
  • 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
    • Scottsdale/Phoenix, Arizona: 17-008061
    • Jacksonville, Florida: 17-008061
    NCT ID: NCT03439254
    Sponsor Protocol Number: 747-304

About this study

The primary objective of this study is to evaluate whether obeticholic acid (OCA; INT-747) can lead to histological improvement in fibrosis with no worsening of NASH in adults with compensated cirrhosis due to NASH.

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:

  • Subjects ≥ 18 years of age.
  • Subjects with a confirmed diagnosis of NASH and a fibrosis score of 4 based upon the NASH CRN scoring system determined by central reading of a liver biopsy obtained no more than 12 months before Day 1.
  • Contraception: Female subjects of childbearing potential must use ≥ 1 effective method (≤ 1% failure rate) of contraception during the study until 4 weeks following the last dose of investigational product (including OLE doses). Female subjects are considered as being of childbearing potential; i.e., fertile, following menarche and until becoming postmenopausal, unless permanently sterile. Permanent sterilization methods include hysterectomy, bilateral salpingectomy, and bilateral oophorectomy. A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. A high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a post-menopausal state in women not using hormonal contraception or hormonal replacement therapy. However, in the absence of 12 months of amenorrhea, a single FSH measurement is insufficient.
  • Effective methods of contraception are listed below:
    • Barrier method; i.e., (a) condom (male or female) with spermicide or (b) diaphragm with spermicide; or
    • Intrauterine device; or
    • Vasectomy (partner); or
    • Hormonal (e.g., contraceptive pill, patch, intramuscular implant or injection); or
    • Abstinence, if in line with the preferred and usual lifestyle of the subject (where abstinence is defined as refraining from heterosexual intercourse).
  • Must provide written informed consent and agree to comply with the study protocol.

Exclusion Criteria:

 

  • Criteria with exclusionary laboratory values are to be based on the most recent laboratory result available prior to randomization. For alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin for which if  Screening Visit 1 and Visit 2 values differ by ≥ 30% and either of the lab values is > upper limit of normal (ULN), then a third sample will be collected at an unscheduled visit as a confirmatory sample. Subjects who satisfy any of the following exclusion criteria will be ineligible for enrollment:
  • Current or past history of hepatic decompensation such as clinically significant ascites (requiring medical intervention), variceal bleeding, spontaneous bacterial peritonitis, hepatic encephalopathy (Grade I or greater based on West Haven classification), or hepatorenal/hepatopulmonary syndromes.
  • Current or past history of hepatic function impairment with CP score ≥ 7 points.
  • MELD score > 12.
  • Hospitalization within 1 year of Day 1 for complications of cirrhosis.
  • Documented presence of varices based on prior endoscopy performed within 6 months of Day 1.
  • AST ≥ 5× ULN.
  • ALT ≥ 5× ULN.
  • Calculated creatinine clearance < 60 mL/min using Cockcroft-Gault method at Screening.
  • Platelet count ≤ 100 000/mm^3 at Screening.
  • Total bilirubin > 2 mg/dL (subjects with an established diagnosis of Gilbert’s syndrome and a normal hemoglobin and reticulocyte count may be enrolled despite a total bilirubin level > 2 mg/dL if their conjugated (direct) bilirubin is < 2× ULN).
  • Conjugated bilirubin ≥ 1.5x ULN.
  • Albumin < 3.5 g/dL.
  • International normalized ratio (INR) ≥ 1.7 (subjects with a known inherited blood disorder and INR ≥ 1.7 may be enrolled and subjects on anticoagulant/anti-aggregant treatment and INR ≥ 1.7 may be enrolled by approval of Medical Monitor).
  • Current or history of significant alcohol consumption for a period of more than

    3 consecutive months within 1 year before Day 1 (significant alcohol consumption is

    defined as more than 2 units/day for females and more than 4 units/day for males, on

    average)

    15. Prior (at any point) or planned (during the study period) ileal resection, or prior (within

    5 years before Screening) or planned (during the study period) bariatric surgery

    (eg, gastric bands, gastroplasty, roux-en-Y gastric bypass)

    16. Inability to safely undergo a liver biopsy

    17. History of biliary diversion

    18. Evidence of other known forms of chronic liver disease including:

    − Positive test result at Screening for hepatitis B surface antigen

    − Active hepatitis C virus (HCV) infection (positive for HCV ribonucleic acid

    [RNA] at Screening); or confirmed history of a positive HCV RNA test result(s)

    − PBC, primary sclerosing cholangitis, autoimmune hepatitis, or overlap syndrome

    − Alcoholic liver disease

    − Wilson disease, hemochromatosis, or iron overload

    − Alpha-1-antitrypsin (A1AT) deficiency as defined by diagnostic features in liver

    histology (confirmed by A1AT level below the lower limit of normal or exclusion

    at the Investigator’s discretion)

    − Prior known drug-induced liver injury within 5 years before Day 1

    − Known or suspected HCC

    19. History of liver transplant, current placement on a liver transplant list

    20. HbA1c ≥9.5% within 60 days before Day 1

    21. LDL cholesterol≥190 mg/dL and already on a stable dose of statin and/or proprotein

    convertase subtilisin/kexin type 9 inhibitor (PCSK9) for ≥30 days at Screening

    22. LDL cholesterol <50 mg/dL (irrespective of statin use)

    23. Known positivity for human immunodeficiency virus infection

    24. Subjects with recent history (within 1 year of Day 1) of significant atherosclerotic

    cardiovascular disease (myocardial infarction, unstable angina, acute coronary syndrome,

    cerebrovascular accident [stroke], cerebrovascular ischemia, transient ischemic attack, or

    peripheral vascular disease requiring intervention). Such subjects may be identified by

    different means, including, but not limited to, an abnormal 12-lead ECG, a history or

    planned cardiovascular intervention such as coronary revascularization (eg, percutaneous

    coronary intervention or coronary artery bypass graft), coronary angioplasty, stenting,

    carotid atherectomy, or placement of a cardiac pacemaker or defibrillator

    − Controlled hypertension without other recent manifestations of significant

    atherosclerotic cardiovascular disease and placement of cardiac pacemaker or

    defibrillator for reasons other than atherosclerotic cardiovascular disease (eg, for

    treatment of atrial fibrillation subsequent to nodal ablation) is not exclusionary

    25. Current acute cholecystitis or acute biliary obstruction

    26. Other medical conditions that may diminish life expectancy to <2 years, including known

    cancers (except carcinomas in situ or other stable, relatively benign carcinomas)

    27. Known substance abuse in the year before Screening

    28. Chronic use (≥12 months) of drugs historically associated with drug-induced NAFLD

    within the 5 years before Day 1 (eg, amiodarone, methotrexate, systemic glucocorticoids,

    tetracyclines, tamoxifen, estrogens at doses greater than those used for hormone

    replacement, anabolic steroids, valproic acid, and other known hepatotoxins; see

    Section 9.3).

    29. Pregnancy, planned pregnancy, potential for pregnancy (ie, unwillingness to use effective

    birth control during the study), or current or planned breast feeding

    30. Participated in a clinical research study and received any active investigational product

    being evaluated for the treatment of diabetes, weight loss, or NASH in the 6 months

    before Day 1

    31. Concurrent participation in any other interventional clinical trial.

    32. Received any investigational product from Screening to Day 1, within 30 days before

    Day 1, or within 5 half-lives of the compound (whichever was longer) before Day 1

    33. Previous exposure to OCA within 12 months of Day 1

    34. Mental instability or incompetence, such that the validity of informed consent or ability

    to be compliant with the study, is uncertain

    35. History of known or suspected clinically significant hypersensitivity to OCA or any of its

    components

    36. Any other condition that, in the opinion of the Investigator, might confound the results, or

    would impede compliance or hinder completion of the study

     

Participating Mayo Clinic locations

Study statuses change often. Please contact us for help.

Mayo Clinic Location Status Contact

Scottsdale/Phoenix, Ariz.

Mayo Clinic principal investigator

Elizabeth Carey, M.D.

Open for enrollment

Contact information:

Kelly Clark B.S., M.S., CCRP

(480)342-2536

Clark.Kelly2@mayo.edu

Jacksonville, Fla.

Mayo Clinic principal investigator

Maria Yataco, M.D.

Open for enrollment

Contact information:

Katelyn Register

127or7838503

Register.Katelyn@mayo.edu

More information

Publications

Publications are currently not available

Study Results Summary

Not yet available

Supplemental Study Information

Not yet available

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CLS-20425953

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