Clinical trial NCT00608894: LCP-Tacro vs. Azathioprine for the Treatment of Autoimmune Hepatitis
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Autoimmune Hepatitis
Keywords: Autoimmune hepatitis
Chronic active hepatitis
Lead sponsor: Veloxis Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2008-02-06
Enrollment: 13
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Biochemical Remission of (AIH) at Month 6.
timeFrame: 6 months
Secondary outcomes:
measure: Biochemical Remission by Month 3.
timeFrame: 3 months
measure: Incomplete Response, Treatment Failure, or a Case of Relapse at 6 Months
timeFrame: 6 months
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Mayo Clinic - Phoenix
state: Arizona
city: Jacksonville
country: United States
facility: Mayo Clinic - Jacksonville
state: Florida
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: New York
country: United States
facility: Mount Sinai Medical Center
state: New York
city: Houston
country: United States
facility: St. Luke's Advanced Liver Therapies
state: Texas
city: Richmond
country: United States
facility: Virginia Commonwealth University
state: Virginia
city: Calgary
country: Canada
facility: Heritage Medical Research Clinic
state: Alberta
city: Edmonton
country: Canada
facility: Zeildler Ledcor Centre
state: Alberta
city: Winnipeg
country: Canada
facility: John Buhler Research Centre, University of Manitoba Health Sciences Centre
state: Manitoba
city: Halifax
country: Canada
facility: Queen Elizabeth II Health Sciences Centre
state: Nova Scotia
Study officials:
affiliation: University of Manitoba Health Sciences Centre, Winnipeg
name: Gerald Y Minuk, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Alberta, Edmonton
name: Andrew Mason, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Mayo Clinic, Rochester, MN
name: Russell H Wiesner, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Baylor College of Medicine
name: John M Vierling, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Virginia Commonwealth University, Richmond, VA
name: Velimir A Luketic, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Mount Sinai Medical Center, New York, NY
name: Joseph A Odin, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Mayo Clinic
name: Elizabeth Carey, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Minnesota
name: John R Lake, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Mayo Clinic
name: Barry G Rosser, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Northwestern University
name: Steven L Flamm, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Queen Elizabeth II Health Sciences Centre
name: Kevork M Peltekian, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Calgary
name: Mark G Swain, MD
role: PRINCIPAL_INVESTIGATOR
References: