LCP-Tacro vs. Azathioprine for the Treatment of Autoimmune Hepatitis
Condition: Autoimmune Hepatitis
MeSH terms: Hepatitis A; Hepatitis; Hepatitis, Autoimmune
Intervention: LCP-Tacro (tacrolimus); Azathioprine
Intervention description: LCP-Tacro(tacrolimus)tablets starting at 2 mg once daily, then adjusted to achieve and maintain target whole blood tacrolimus levels of 3 - 6 ng/mL, plus prednisone 30 mg/day for one week, then 20 mg/day for one week, then 15 mg/day for two weeks, then 10 mg/day through Month 6.; Azathioprine tablets 50 - 100 mg (approximately 1 mg/kg) once daily, plus prednisone 30 mg/day for one week, then 20 mg/day for one week, then 15 mg/day for two weeks, then 10 mg/day through Month 6.
Intervention MeSH terms: Prednisone; Azathioprine; Tacrolimus
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 13.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Autoimmune hepatitis; Chronic active hepatitis

Summary:

      An open-label, multi-center, prospective, randomized study to evaluate the efficacy, safety
      and tolerability of LCP-Tacro tablets given once daily vs. azathioprine, each in combination
      with prednisone, for the treatment of autoimmune hepatitis (AIH).
    

Eligibility criteria:

        Inclusion Criteria:

          -  Men and women at least 18 years of age with a diagnosis of definite or probable AIH
             defined by the revised International Autoimmune Hepatitis Group (IAIHG) criteria

          -  Elevation of serum ALT ≥ 1.5 times the upper limit of normal

          -  Liver biopsy showing chronic hepatitis consistent with AIH

          -  Patients able to swallow the study medication

          -  Patients capable of understanding the purposes and risks of the study, who can give
             written informed consent and who are willing to participate in and comply with the
             study

          -  Women of childbearing potential must have a negative serum pregnancy test within seven
             days prior to receiving study medication and agree to use contraceptive measures to
             avoid pregnancy during participation in the trial.

        Exclusion Criteria:

          -  Patients with other concurrent liver disease

          -  Patients with cirrhosis on liver biopsy with a MELD score > 15

          -  Patients with a history or presence of decompensated liver disease

          -  Patients with serum creatinine ≥ 1.5 mg/dL prior to enrollment

          -  Patients positive for HCV RNA or Hepatitis B surface antigen (HBsAg)

          -  Patients with a history of alcohol intake > 25 g/day within the past six months

          -  Patients with TSH outside normal range accompanied by an abnormal T4

          -  Patients with alpha-fetoprotein ≥ 20 ng/mL

          -  Patients with severe anemia (hemoglobin < 8 g/dL), leukopenia (WBC < 4000/mm3), or
             thrombocytopenia (platelet count < 100,000/mm3)

          -  Patients with a history of recent exposure to hepatotoxic drugs

          -  Patients who require therapy with any immunosuppressive agent other than those
             prescribed in the study

          -  Patients unable or unwilling to provide informed consent

          -  Pregnant or nursing women

          -  Patients with reproductive potential who are unwilling/unable to use a double barrier
             method of contraception

          -  Patients who have been treated with another investigational agent in the three months
             prior to enrollment

          -  Patients receiving any drug interfering with tacrolimus metabolism

          -  Patients with current malignancy or a history of malignancy (within the past 5 years),
             except basal or non-metastatic squamous cell carcinoma of the skin that has been
             treated successfully

          -  Patients with uncontrolled concomitant infection, a systemic infection requiring
             treatment, or any other unstable medical condition that could interfere with the study
             objectives

          -  Patients with severe diarrhea, vomiting, active peptic ulcer or gastrointestinal
             disorder that may affect the absorption of tacrolimus

          -  Patients with a known hypersensitivity to azathioprine, corticosteroids or tacrolimus

          -  Patients with any form of current substance abuse, psychiatric disorder or a condition
             that, in the opinion of the Investigator, may invalidate communication with the
             Investigator

          -  Patients who are recipients of an organ transplant or who require treatment with
             immunosuppressives or corticosteroids for any disease other than AIH.