A Randomized, Open-label, Comparative Evaluation of Conversion from Calcineurin Inhibitor Treatment to Sirolimus Treatment Versus Continued Calcineurin Inhibitor Treatment in Liver Allograft Recipients Undergoing Maintenance Therapy.

Phase 1

Active, not recruiting

• Conditions: iver allograft recipients under maintenance therapy

• Registration Number: EUCTR2004-000935-27-CZ
• Lead Sponsor: Wyeth Research Division of Wyeth Pharmaceuticals Inc.Clinical Research & Development Department

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2005-05-04
• Study Completion: 2008-08-23
• Last Update Posted: 2022-04-04

Recruitment & Eligibility

• Status: Not Recruiting
• Sex: All
• Target Recruitment: 600

Inclusion Criteria

1. Age >=13 years (>=18 years in Austria, Czech Republic, Denmark, Finland, France, Germany, Norway, Poland, Sweden, Switzerland, United Kingdom and as required by local regulation or ethical committees) and weight >=40 kg.
2. Women of childbearing potential must have a negative serum pregnancy test result before random assignment and must agree to use a medically acceptable method of contraception throughout the treatment period and for 3 months after discontinuation of randomly assigned treatment. Any woman becoming pregnant during the treatment period must withdraw from the study.
3. Subjects receiving immunosuppressive therapy with a stable regimen of CI or a combination of CI with CS and/or antimetabolite therapy for a minimum of 4 weeks prior to randomization.
4. Treatment with the same CI for at least 4 weeks before random assignment.
5. Six (6) to 144 months after orthotopic liver transplantation.
6. Cockcroft-Gault GFR values >=40 mL/min and <=90 mL/min at screening.
7. Doppler ultrasound performed within 4 weeks before random assignment showing no evidence of thrombosis or of clinically significant stenosis of hepatic artery, hepatic vein, or portal vein.
8. Total white blood cell count >3.0 x 10 9/L (>3,000/mm3), platelet count >75 x 10 9/L (>75,000/mm3 ), fasting triglycerides <3.95 mmol/L (<350 mg/dL), fasting cholesterol <7.8 mmol/L (<300 mg/dL). If subjects are currently untreated for elevated cholesterol and/or triglycerides and are excluded from the study based on the above criteria, subjects may be initiated on antihyperlipidemic therapy and re-screened.
9. Liver function test (LFT) results (ie, aspartate aminotransferase [AST], alanine aminotransferase [ALT], total bilirubin, and alkaline phosphatase) <3 times the upper limit of normal on 2 consecutive determinations within 3 months before random assignment. For subjects who are Hepatitis C positive (determined by PCR), AST and ALT values must be < 5 times the upper limit of normal on 2 consecutive determinations within 3 months before random assignment.
10. Subjects with any LFT (AST, ALT, total bilirubin, or alkaline phosphatase) >2 times the upper limit of normal (on 2 consecutive determinations within 3 months before random assignment) must have a liver biopsy performed within 3 months before random assignment showing no evidence of acute rejection unless a clear alternative etiology is apparent for elevated LFTs.
Subjects who are Hepatitis C positive (determined by PCR) with total bilirubin or alkaline phosphatase values > 2 times the upper limit of normal on 2 consecutive determinations less than 3 months before random assignment, must have a liver biopsy performed less than 3 months before random assignment to exclude rejection unless a clear alternative etiology for elevated LFT(s) is apparent. Prior discussion with the medical monitor about the alternative etiology is required before randomizing any patient who meets this criteria.
11. All Hepatitis C positive subjects (as determined by PCR) must have a liver biopsy performed within 6 months before random assignment showing no evidence of acute rejection or Liver Fibrosis score 4, 5 or 6 (Banff 1997) or correlating Metavir score of F3 or F4 (See Attachment 10).
12. Subjects undergoing therapy for Hepatitis C infection who completed a full course of therapy must be at least 6 months post therapy. Subjects who were non-responders or who failed HCV therapy, must be at least 4 weeks post discontinuation of

Exclusion Criteria

1. History of nonhepatic transplantation.
2. Serum creatinine at the time of screening that has increased > 30% above the last value obtained at least 8 weeks prior to screening. Subjects with values that deviate from this exclusion criterion may be enrolled only with the approval of the Wyeth Research (WR) global medical monitor.
3. Concomitant therapy with an immunosuppressive agent other than CI, CS, or antimetabolite therapy (MMF or AZA) within 4 weeks before random assignment.
4. Evidence of systemic infection (ie, sepsis, bacteremia, pneumonia, etc.) at time of random assignment.
5. Biopsy performed within 3 months before random assignment showing Banff 1997 grade I or II acute rejection or biopsy performed within 12 months before random assignment showing grade III rejection.
6. Any treatment for suspected or biopsy-confirmed acute rejection within 3 months before random assignment or treatment with anti-lymphocyte antibody for suspected or biopsy-confirmed acute rejection within 12 months before random assignment.
7. Stage 4, 5 or 6 hepatic fibrosis score using Banff 1997 scoring criteria or correlating Metavir fibrosis grade F3 or F4 on any posttransplant biopsy and/or in the opinion of the investigators, signs of decompensated liver disease of the current liver allograft.
8. Therapy for recurrent Hepatitis B infection received within 4 weeks before random assignment (excluding approved prophylaxis).
9. Known or suspected malignancy <= 5 years before random assignment (with the exception of adequately treated basal cell or squamous cell carcinomas of the skin or malignant liver tumors [primary hepatocellular carcinoma] as specified in inclusion criteria 13 and 14).
10. History of posttransplant lymphoproliferative disease.
11. Use of any investigational drugs within 4 weeks before random assignment.
12. Prior or current use of SRL or any of its derivatives (unless prior approval from WR medical monitor).
13. Treatment with any renal replacement therapy within 2 weeks before random assignment.
14. Presence of unstable angina or use of ongoing maintenance therapy for a life-threatening arrhythmia.
15. History of documented human immunodeficiency virus infection.
16. Hypercoagulable states or any history of deep vein thrombosis, HAT, or portal vein thrombosis . (Exception: incidental vascular thrombosis at time of liver explant which, in the opinion of the investigator, does not place the subject at increased risk of thrombotic event).
17. Requirement for the administration of terfenadine, cisapride, pimozide, astemizole, (oral) ketoconazole, voriconazole or cimetidine after random assignment.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified