Protocol Calcineurin Inhibitor (CNI) Weaning

Prospective, Multicenter, Randomized, Double-blind, Controlled Parallel Group Study Designed to Assess the Risk-benefit Balance of the Gradual Withdrawal of a Calcineurin Inhibitor (Tacrolimus) in Renal Transplant Patients Over 4 Years and Clinically Selected

The main objective of this study is to demonstrate the benefit of the withdrawal of Tacrolimus (Prograf®) on renal function in patients one year after the end of the weaning period. The secondary objectives will focus on assessing the risks and consequences of withdrawal of Tacrolimus (Prograf®).

Pre-inclusion criteria :

• Male or female aged between 18 and 80 years (inclusive),
• Having received a deceased donor transplant or living with ABO compatibility,
• First renal allograft for at least 4 years and under 10 years,
• Presenting a stable renal function : serum creatinine with a variation of ± 25% of the average of the year before inclusion,
• Treated with tacrolimus (Prograf®) in combination with MPA (Cellcept® and Myfortic®) + / - steroids (between 5 and 10 mg per day),
• Patient has given informed consent,
• Patient insured,
• Patient (of childbearing age) with effective contraception.

Inclusion Criteria:

• Glomerular Filtration Rate (GFR), defined by the dosage of cystatin C ≥ 40 ml/min/1, 73m²,
• Proteinuria ≤ 0,5 g / day,
• Patient with serum levels of Tacrolimus between 5 to 10 ng / ml on average during the last 6 months (inclusive). It is accepted that 25% of the assays performed during the last 6 months, serum levels of tacrolimus are outside the limits mentioned above (5-10 ng / ml). They must nevertheless be between 3.5 to 12.5 ng / ml (inclusive).
• Patient with serum levels of MPA (Cellcept® and Myfortic®) higher ≥ 30 mg / ml,
• No anti-HLA antibodies at the time of inclusion, verified using highly sensitive techniques (Luminex HD),
• Lack of histological evidence of cellular or humoral acute or chronic or subclinical rejection on renal graft according to the latest classification of Banff 2009.

Exclusion Criteria:

• Patients under age 18 or over 80 years,
• Transplanted from less than 4 years and over 10 years,
• Patients re-transplanted,
• Transplantation of several organs,
• Patient not treated with tacrolimus as maintenance therapy,
• Serum levels of Tacrolimus patient <5 or >10 ng / ml,
• Serum levels of MPA of the patient <30 mg / ml,
• Patients treated with other immunosuppressive drugs that Tacrolimus (Prograf®), MPA (Cellcept® and Myfortic®) and steroids,
• Patient not having a stable graft function at baseline (change in serum creatinine > 25% of the average of the year before inclusion in the study), with a GFR defined by the dosage of cystatin C <40 ml/min/1, 73m² at the time of inclusion,- Patients with proteinuria > 0.5 g at study entry,
• Patient with HLA antibodies at study entry,
• Patient non-compliant,
• Presence of histological evidence of cellular or humoral acute or chronic or subclinical rejection on renal graft according to the latest classification of Banff 2009,
• History of lymphoproliferative disorders,
• Diagnosis of a malignancy within 5 years before enrollment,
• Significantly abnormal hematologic data of a clinical standpoint, as determined by the investigator for hematocrit, hemoglobin, white blood cell count or platelets,
• Data significantly abnormal blood biochemistry of a clinical standpoint, as determined by the investigator,
• Abuse of significant drug or alcohol at the time of inclusion, determined by the investigator,
• Patient positive for antibodies to hepatitis C or hepatitis B surface antigen of hepatitis B (HBsAg) or HIV infection,
• Participation in a clinical study within 3 months,
• Pregnancy, Breastfeeding.