LCP-Tacro vs. Azathioprine for the Treatment of Autoimmune Hepatitis

Phase 2

Terminated

Conditions: Autoimmune Hepatitis

Interventions: Drug: LCP-Tacro (tacrolimus)
Drug: Azathioprine

Registration Number: NCT00608894

Lead Sponsor: Veloxis Pharmaceuticals

Brief 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).

Detailed Description: 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.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 13

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
LCP-Tacro	LCP-Tacro (tacrolimus)	LCP-Tacro tablets(1,2,and 5mg tacrolimus)+ prednisone tablets(5mg)
Azathioprine	Azathioprine	Azathioprine tablets(50mg)+ prednisone tablets(5mg)

Primary Outcome Measures

Name	Time	Method
Biochemical Remission of (AIH) at Month 6.	6 months	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.

Secondary Outcome Measures

Name	Time	Method
Biochemical Remission by Month 3.	3 months	Percent of patients who achieve biochemical remission by Month 3 during treatment with LCP-Tacro + prednisone or azathioprine + prednisone. Biochemical remission is defined as ALT, total bilirubin and gamma globulin within normal limits.
Incomplete Response, Treatment Failure, or a Case of Relapse at 6 Months	6 months	Percents of patients in each treatment group classified as having an incomplete response (defined as some or no improvement during therapy), a treatment failure (defined as permanent discontinuation of the regimen originally randomized to), or a case of relapse (recurrence following achievement of remission)

Trial Locations

Locations (12): Mayo Clinic - Jacksonville
🇺🇸
Jacksonville, Florida, United States
Mayo Clinic
🇺🇸
Rochester, Minnesota, United States
Mount Sinai Medical Center
🇺🇸
New York, New York, United States
Zeildler Ledcor Centre
🇨🇦
Edmonton, Alberta, Canada
Virginia Commonwealth University
🇺🇸
Richmond, Virginia, United States
Heritage Medical Research Clinic
🇨🇦
Calgary, Alberta, Canada
John Buhler Research Centre, University of Manitoba Health Sciences Centre
🇨🇦
Winnipeg, Manitoba, Canada
Mayo Clinic - Phoenix
🇺🇸
Phoenix, Arizona, United States
Northwestern University
🇺🇸
Chicago, Illinois, United States
University of Minnesota
🇺🇸
Minneapolis, Minnesota, United States
St. Luke's Advanced Liver Therapies
🇺🇸
Houston, Texas, United States
Queen Elizabeth II Health Sciences Centre
🇨🇦
Halifax, Nova Scotia, Canada