Official Title: “A Phase II, Open-Label, Multi-Center, Prospective, Randomized Study of LCP-Tacro Tablets vs. Azathioprine, in Combination With Corticosteroids, for the Treatment of Autoimmune Hepatitis”

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).

Study Type: Interventional

Study Design: Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Safety/Efficacy Study

Study Primary Completion Date: March 2009

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

Patients with histologically confirmed chronic hepatitis who fulfill criteria established by the International Autoimmune Hepatitis Group (IAIHG) and Inclusion and Exclusion criteria will be enrolled after having signed an informed consent document.

Up to 60 patients will be randomized (1:1) to receive treatment with LCP-Tacro + prednisone vs. azathioprine (AZA) + prednisone. - LCP-Tacro will be started at 2 mg once daily (q.d.) with weekly measurement of tacrolimus whole blood trough levels and adjustment of the daily dose of LCP-Tacro to achieve target tacrolimus levels of 3 - 6 ng/mL. Patients with histological evidence of cirrhosis and a Model for End-Stage Liver Disease (MELD) score ≤ 8 will commence LCP-Tacro at a fixed dose of 1 mg once daily, with subsequent dosage adjustments to maintain tacrolimus trough levels at 3 - 6 ng/mL. - AZA will be started at 50 - 100 mg (approximately 1 mg/kg) once daily (q.d.).

Patients will also commence treatment with 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(s) in this Clinical Trial

• Drug: LCP-Tacro + prednisone
  • LCP-Tacro 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.
• Drug: Azathioprine + prednisone
  • 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.

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: 1
  • LCP-Tacro + prednisone
• Active Comparator: 2
  • Azathioprine + prednisone

Primary Measures

• Percent of patients that achieve biochemical remission of (AIH) at Month 6 during treatment with LCP-Tacro + prednisone or azathioprine + prednisone. Biochemical remission is defined as ALT, total bilirubin and gamma globulin within normal limits.
  • Time Frame: 6 months
    Safety Issue?: No

Secondary Measures

• Percent of patients who achieve biochemical remission by Month 3 during treatment with LCP-Tacro + prednisone or azathioprine + prednisone.
  • Time Frame: 3 months
    Safety Issue?: No
• Percents of patients in each treatment group classified as either in remission, having an incomplete response, a treatment failure, or a case of relapse. Each patient will be classified as being one of the four states at Month 6.
  • Time Frame: 6 months
    Safety Issue?: No

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.

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: LifeCycle Pharma A/S

Overall Clinical Trial Officials and Contacts

Gerald Y Minuk, M.D. Principal Investigator University of Manitoba Health Sciences Centre, Winnipeg  

Information obtained from ClinicalTrials.gov on September 05, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00608894

Study ID Number: LCP-Tacro Study 2016

ClinicalTrials.gov Identifier: NCT00608894

Health Authority: United States: Food and Drug Administration