E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Chronic renal failure patients who are receiving a kidney transplant. Different immunosuppressive protocls are awailable. However, current strategies for the medical management of transplant patients are largely focused on the prevention and treatment of T-cell mediated processes. However, there is an increasing evidence that B cells may significantly contribute to post-transplant morbidity in addition to their role in acute humoral rejection. |
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MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective of the study is to determine the effect of one dose of rituximab as induction therapy together with a conventional tacrolimus, mycophenolate mofetil, prednisolone immunosuppressive protocol on the incidence of treatment failure (biopsy-proven acute rejection, graft loss or death) at 6 months post transplant.
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E.2.2 | Secondary objectives of the trial |
To assess the effect of rituximab induction on renal function at 6 months post transplant, measured as creatinine clearance.
To assess the incidence and severity of infections (CMV, BKV, fungal and bacterial) in the two groups. Creatinine clearance determined by the iohexol technique at 6 months Incidence of opportunistic infections (CMV, BK, fungus) Incidence of urinary tract infections and septicemia Incidence of rituximab-related adverse events Incidence of malignancies All adverse events including clinically significant abnormalities and clinical and laboratory parameters
Additional parameters to be assessed peroperatively and at 6 months Number of CD19+, CD20+ lymphocytes in blood Immunoglobulin G and M levels Anti-tetanus IgG Anti-CMV IgG Cystatin C Iohexol clearance (at 6 months only) Transplant biopsy
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
Patients aged 18 years or above Recipients of first or second renal transplant Recipients from living or cadaveric donors Single organ recipients (kidney only) Patients providing written informed consent Patients cooperative and able to complete all the assessment procedures
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E.4 | Principal exclusion criteria |
HLA-identical siblings Patients receiving immunosuppressive therapy within the preceding 28 days PRA >50% within 6 months prior to enrolment Previous exposure to murine antibodies History of malignancy (except localised non-melanotic skin cancer) or the presence of any active malignancy at the time of transplant Active infection (HCV, HBV, HIV) Pregnant or lactating females Women of child bearing potential not willing to use reliable form of contraception
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint will be a composite endpoint defined as treatment failure, including the occurrence of any of the following: biopsy-proven acute rejection, graft loss or death during the first 6 months following transplantation.
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | Yes |
E.6.3 | Therapy | No |
E.6.4 | Safety | No |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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When all patients have fulfilled 6 month with one additional month safety follow-up, in all 7 months after the transplant proceedure. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 1 |
E.8.9.1 | In the Member State concerned days | |