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

Primary Purpose

Autoimmune Hepatitis

Status

Terminated

Phase

Phase 2

Locations

International

Study Type

Interventional

Intervention

LCP-Tacro (tacrolimus)

Azathioprine

About this trial

This is an interventional treatment trial for Autoimmune Hepatitis focused on measuring Autoimmune hepatitis, Chronic active hepatitis

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Mayo Clinic - Phoenix
Mayo Clinic - Jacksonville
Northwestern University
University of Minnesota
Mayo Clinic
Mount Sinai Medical Center
St. Luke's Advanced Liver Therapies
Virginia Commonwealth University
Heritage Medical Research Clinic
Zeildler Ledcor Centre
John Buhler Research Centre, University of Manitoba Health Sciences Centre
Queen Elizabeth II Health Sciences Centre

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

LCP-Tacro

Azathioprine

Arm Description

LCP-Tacro tablets(1,2,and 5mg tacrolimus)+ prednisone tablets(5mg)

Azathioprine tablets(50mg)+ prednisone tablets(5mg)

Outcomes

Primary Outcome Measures

Biochemical Remission of (AIH) at Month 6.

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

Biochemical Remission by Month 3.

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

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)

Full Information

NCT ID

NCT00608894

First Posted

January 23, 2008

Last Updated

March 6, 2020

Sponsor

Veloxis Pharmaceuticals

1. Study Identification

Unique Protocol Identification Number

NCT00608894

Brief Title

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

2. Study Status

Record Verification Date

March 2020

Overall Recruitment Status

Terminated

Why Stopped

Study was discontinued due to slow enrollment

Study Start Date

December 2007 (Actual)

Primary Completion Date

April 2009 (Actual)

Study Completion Date

July 2009 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Veloxis Pharmaceuticals

4. Oversight

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Autoimmune Hepatitis

Keywords

Autoimmune hepatitis, Chronic active hepatitis

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

13 (Actual)

8. Arms, Groups, and Interventions

Arm Title

LCP-Tacro

Arm Type

Experimental

Arm Description

LCP-Tacro tablets(1,2,and 5mg tacrolimus)+ prednisone tablets(5mg)

Arm Title

Azathioprine

Arm Type

Active Comparator

Arm Description

Azathioprine tablets(50mg)+ prednisone tablets(5mg)

Intervention Type

Drug

Intervention Name(s)

LCP-Tacro (tacrolimus)

Other Intervention Name(s)

1,2,and 5mg tacrolimus tablets

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.

Intervention Type

Drug

Intervention Name(s)

Azathioprine

Other Intervention Name(s)

50mg azathioprine tablets + 5mg prednisone tablets

Intervention Description

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.

Primary Outcome Measure Information:

Title

Biochemical Remission of (AIH) at Month 6.

Description

Time Frame

6 months

Secondary Outcome Measure Information:

Title

Biochemical Remission by Month 3.

Description

Time Frame

3 months

Title

Incomplete Response, Treatment Failure, or a Case of Relapse at 6 Months

Description

Time Frame

6 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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.

Overall Study Officials: