Phase II Open-Label, Multi-Center, Prospective, Randomized Study of LCP-Tacro vs. Azathioprine for the Treatment of Autoimmune Hepatitis
Information source: LifeCycle Pharma A/S
Information obtained from ClinicalTrials.gov on June 20, 2008
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Autoimmune Hepatitis
Intervention: LCP-Tacro + prednisone (Drug); Azathioprine + prednisone (Drug)
Phase: Phase 2
Status: Enrolling by invitation
Sponsored by: LifeCycle Pharma A/S Official(s) and/or principal investigator(s):
Gerald Y Minuk, M.D., Principal Investigator, Affiliation: University of Manitoba Health Sciences Centre, Winnipeg
Andrew Mason, MD, Principal Investigator, Affiliation: University of Alberta, Edmonton
Russell H Wiesner, MD, Principal Investigator, Affiliation: Mayo Clinic - Rochester, MN
John M Vierling, MD, Principal Investigator, Affiliation: Baylor College of Medicine
Velimir A Luketic, MD, Principal Investigator, Affiliation: Virginia Commonwealth University, Richmond, VA
Joseph A Odin, MD, PhD, Principal Investigator, Affiliation: Mount Sinai Medical Center, New York, NY
Elizabeth Carey, MD, Principal Investigator, Affiliation: Mayo Clinic - Phoenix
John R Lake, MD, Principal Investigator, Affiliation: University of Minnesota
Barry G Rosser, MD, Principal Investigator, Affiliation: Mayo Clinic
Steven L Flamm, MD, Principal Investigator, Affiliation: Northwestern University
Kevork M Peltekian, MD, Principal Investigator, Affiliation: Queen Elizabeth II Health Sciences Centre
Mark G Swain, MD, Principal Investigator, Affiliation: University of Calgary
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).
Clinical Details
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 design: Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Safety/Efficacy Study
Primary outcome: 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: Percent of patients who achieve biochemical remission by Month 3 during treatment with LCP-Tacro + prednisone or azathioprine + prednisone.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.
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
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): Both.
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.
Locations and Contacts
Zeildler Ledcor Centre, Edmonton, Alberta T6G 2X8, Canada
Heritage Medical Research Clinic, Calgary, Alberta T2N 4N1, Canada
Mayo Clinic - Phoenix, Phoenix, Arizona 85054, United States
Mayo Clinic - Jacksonville, Jacksonville, Florida 32216, United States
Northwestern University, Chicago, Illinois 60611, United States
John Buhler Research Centre, University of Manitoba Health Sciences Centre, Winnipeg, Manitoba R3E 3P4, Canada
Mayo Clinic, Rochester, Minnesota 55905, United States
University of Minnesota, Minneapolis, Minnesota 55455, United States
Mount Sinai Medical Center, New York, New York 10029, United States
Queen Elizabeth II Health Sciences Centre, Halifax, Nova Scotia B3H 2Y9, Canada
St. Luke's Advanced Liver Therapies, Houston, Texas 77030, United States
Virginia Commonwealth University, Richmond, Virginia 23298, United States
Additional Information
Starting date: December 2007
Ending date: March 2009
Last updated: June 6, 2008
|
