Sequential Targeting of Cluster of Differentiation 52 (CD52) and Tumor Necrosis Factor (TNF) Allows Early Minimization Therapy in Kidney Transplantation

Study Overview
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Brief Summary
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The aim of the study is to evaluate the efficacy of new immunosuppressive protocol based on two applications of anti-CD52 MabCampath (Alemtuzumab) a single dose of anti-TNF-α Remicade (infliximab) monoclonal antibodies in the early posttransplant period followed by either monotherapy based on tacrolimus or sirolimus.

Official Title
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A Pilot, Open Single Centre, Prospective, Parallel Trail to Evaluate the Efficacy and Safety of Immunosuppressive Regimen Without Calcineurin Inhibitors and Steroids After Induction of Anti-CD52 and Anti-TNF-α Monoclonal Antibodies in Kidney Transplant Recipients

Conditions
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Kidney Transplantation

Intervention / Treatment
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* Drug: MabCampath,
* Drug: Remicade
* Drug: Sirolimus
* Drug: Tacrolimus


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: First deceased-donor kidney transplantation Age >18 years Donor <65 years Cytomegalovirus (CMV)/ Epstein-Barr virus (EBV) seropositivity panel reactive antibodies (PRA) <10% Written consent Exclusion criteria: Retransplantation, combined transplantation Prior immunosuppression less than 6 months prior transplantation Induction therapy with antibodies Leukopenia < 4000, thrombocytopenia < 100 000, Haemoglobin < 80 g/l History of antithymoglobulin (ATG) or anti-cluster of differentiation 3 (CD3) monoclonals or anti-TNF-α Tuberculosis history Anti-hepatitis C virus (HCV) positivity, HBsAg HIV positivity Malignancy history Allergy to study medication Fertile women without contraception Pregnancy, breastfeeding mothers

Ages Eligible for Study
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Minimum Age: 18 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: Screening
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Sirolimus<br>Patients received two applications of anti-CD52 MabCampath (Alemtuzumab), a single dose of anti-TNF-α Remicade (Infliximab) monoclonal antibodies in the early posttransplant period. First 14 days patients received tacrolimus monotherapy, at post-operative day (POD) 14, they were randomized to sirolimus monotherapy. | Drug: MabCampath,<br>* Primary deceased donor kidney transplant recipients received 2x20 mg Alemtuzumab (day 0/day 1) followed by 5 mg/kg Infliximab (day 2). For 14 days all patients received only tacrolimus, then they were randomized to either receive tacrolimus (TAC, n=13) or sirolimus (SIR, n=7) monotherapy, respectively.<br>* Other names: Alemtuzumab;Drug: Remicade<br>* Primary deceased donor kidney transplant recipients received 2x20 mg Alemtuzumab (day 0/day 1) followed by 5 mg/kg Infliximab (day2). For 14 days all patients received only tacrolimus, then they were randomized to either receive tacrolimus (TAC, n=13) or sirolimus (SIR, n=7) monotherapy, respectively.<br>* Other names: Infliximab;Drug: Sirolimus<br>* Primary deceased donor kidney transplant recipients received 2x20 mg Alemtuzumab (day 0/day 1) followed by 5 mg/kg Infliximab (day 2). For 14 days all patients received only tacrolimus, then they were randomized to either receive tacrolimus (TAC, n=13) or sirolimus (SIR, n=7) monotherapy, respectively.<br>Drug: Tacrolimus<br>* Primary deceased donor kidney transplant recipients received 2x20 mg Alemtuzumab (day 0/day 1) followed by 5 mg/kg Infliximab (day 2). For 14 days all patients received only tacrolimus, then they were randomized to either receive tacrolimus (TAC, n=13) or sirolimus (SIR, n=7) monotherapy, respectively.<br>|
| Active Comparator: Tacrolimus<br>Patients received two applications of anti-CD52 MabCampath (Alemtuzumab), a single dose of anti-TNF-α Remicade (Infliximab) monoclonal antibodies in the early posttransplant period. First 14 days patients received tacrolimus monotherapy, at POD 14, they were randomized to tacrolimus monotherapy. | Drug: MabCampath,<br>* Primary deceased donor kidney transplant recipients received 2x20 mg Alemtuzumab (day 0/day 1) followed by 5 mg/kg Infliximab (day 2). For 14 days all patients received only tacrolimus, then they were randomized to either receive tacrolimus (TAC, n=13) or sirolimus (SIR, n=7) monotherapy, respectively.<br>* Other names: Alemtuzumab;Drug: Remicade<br>* Primary deceased donor kidney transplant recipients received 2x20 mg Alemtuzumab (day 0/day 1) followed by 5 mg/kg Infliximab (day2). For 14 days all patients received only tacrolimus, then they were randomized to either receive tacrolimus (TAC, n=13) or sirolimus (SIR, n=7) monotherapy, respectively.<br>* Other names: Infliximab;Drug: Tacrolimus<br>* Primary deceased donor kidney transplant recipients received 2x20 mg Alemtuzumab (day 0/day 1) followed by 5 mg/kg Infliximab (day 2). For 14 days all patients received only tacrolimus, then they were randomized to either receive tacrolimus (TAC, n=13) or sirolimus (SIR, n=7) monotherapy, respectively.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| number of patients with functional graft |  | 1 year | 
| number of patients alive |  | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| kidney graft function (measured by serum creatinine and glomerular filtration) |  | 1 year | 
| the number of bioptically verified rejection episodes and their severity |  | 1 year | 
| fibrosis grade and presence of subclinical rejection in protocol biopsy at 12 months |  | 1 year | 
| intragraft gene expression (inflammatory cytokines, chemokines and protective factors) |  | 1 year | 
| peripheral blood gene expression (inflammatory cytokines, chemokines and protective factors) |  | 1 year |