Efficacy and Safety of ATG-Fresenius Following a Renal Transplantation, Without Corticosteroids

Study Overview
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Brief Summary
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The main objective of the study is the assessment of the overall graft rejection rate (acute, chronic and subclinical) between a treatment with ATG-Fresenius administered in addition to standard treatment consisting of CellCept® or Myfortic®/TAC and without corticosteroids and a treatment consisting of CellCept® or Myfortic®/TAC and corticosteroids during the first year after renal transplantation.

Official Title
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Prospective, Randomized, Multi-center, Open Label, Phase III Study to Evaluate the Efficacy and Safety of Immunosuppression Following a Heart-beating Cadaveric Renal Transplantation Based on the Use of Rabbit Anti-T-lymphocyte Serum, Tacrolimus and Mycophenolate, Free of Concomitant Corticosteroids From the Start of Immunosuppression

Conditions
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Renal Transplant Rejection

Intervention / Treatment
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* Drug: ATG-Fresenius S


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Signed and dated informed consent form, End-stage renal disease, Candidates for a first transplantation, Re-transplant patients are eligible if a graft loss after transplantation was NOT due to immunological reasons, Availability of a heart-beating cadaveric donor up to 70 years of age with a cold ischemia time shorter than 36 hours, Male or female patients between 18 to 75 years of age inclusive, Patients able to comply with all study related requirements, Patients able to receive oral medication, Women of childbearing age with a safe contraceptive method throughout the study. Exclusion Criteria Women who are pregnant or breast feeding, Known Human Immunodeficiency Virus, Hepatitis B Virus or Hepatitis C Virus infection, Severe actual viral, bacterial or fungal infection not adequately controlled, Patients with anamnestically known hypersensitivity to rabbit immunoglobulin antibodies or positive rabbit immunoglobulin skin test or known allergies to any component of the immunosuppressive drugs per protocol, Patients at high immunological risk defined as current PRA > 25% or historical PRA > 50%, Patients receiving pre-transplant immunosuppressive treatment, including corticosteroids, Patients with current or history of malignancies (exception basal cell carcinoma or squamous cell carcinoma in remission), Patients with previous transplantation except 1st graft loss due to surgical complications, Patients receiving combined transplantation, Patients with major organ dysfunctions, Serious psychiatric or psychological disorders, Pre-transplant thrombocytopenia: < 50,000 thrombocytes/µl, Pre-transplant leukopenia: < 2,000 leukocytes/µl, Unable or unwilling to comply fully with the protocol, Participation in another study of an investigational medicinal product concurrently or within the last 30 days.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Study Group<br>immunosuppressive treatment consisting of ATG-Fresenius/TAC/MMF or Myfortic | Drug: ATG-Fresenius S<br>* Dosage: Single high-dose of 9 mg/kg pre-operatively, followed by 3 mg/kg/d at day +2 and +4. ATG-Fresenius treatment at Days 0, +2, and +4 is mandatory. (In case of persisting DGF, the treatment is left to the discretion of the investigator. Treatment options include the continuation of ATG-Fresenius treatment with 3 mg/kg/d at Day +6 and if deemed necessary also at Day +8 - but without corticosteroids).<br>|
| No Intervention: Control Group<br>immunosuppressive treatment consisting of TAC, MMF or Myfortic, and corticosteroids. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The primary endpoint is the incidence of biopsy-proven acute allograft rejection after 12 months, including all types of rejections like: • acute rejection • chronic rejection • subclinical rejection |  | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time of onset, histological severity and incidence of steroid resistance of acute and chronic rejections |  | 1 year | 
| Incidence and duration of initial DGF |  | 1 year | 
| Renal function |  | 1 year | 
| Patient and Graft survival |  | 1 year | 
| Safety endpoints are the incidence of AEs/SAEs and ADRs |  | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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acute rejection, chronic rejection, subclinical rejection, renal transplantation, steroid-free, kidney transplantation