Clinical trial NCT02377193: Simulect Versus ATG in Sensitized Renal Transplant Patient
Official title: Prospective, Multicenter, Randomized, Evaluating Two Induction Therapies With Simulect® Versus ATG® Fresenius Associated With Tacrolimus and Myfortic® in the Prevention of Treatment Failure, in Sensitized Renal Transplant
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Renal Transplant Rejection
Keywords: kidney transplant
luminex method
simulect ATG
immunosuppression
Lead sponsor: University Hospital, Toulouse
Sponsor class: OTHER
Collaborators: name: Neovii Biotech
name: Novartis
First posted: 2015-03-03
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Induction therapy by either T-cell depleting polyclonal antibodies such as anti-thymocyte globulins (ATG) or non-depleting anti-interleukine 2 receptor monoclonal antibodies (anti-CD25 moAb: basiliximab or daclizumab) are used to prevent acute rejection, especially in highly sensitized patients. Both induction therapy regimens have a different tolerance profile. Infections and haematological side-effects are more frequently reported in patients receiving ATG.

The aim of the pilot study is to evaluate ATG and basiliximab induction therapy in de novo sensitized kidney-transplant patients (incompatible grafts rate ≥ 50%) without donor specific antibodies (DSAs) detected by Luminex.

Detailed description: Acute rejection after kidney transplantation can lead to graft loss by irreversible acute rejection or to interstitial fibrosis/ tubular atrophy that can induce graft loss. Induction therapy by either T-cell depleting polyclonal antibodies such as Anti-Thymocyte Globulins (ATG) or non-depleting anti-interleukine 2 receptor monoclonal antibodies (anti-CD25 moAb: basiliximab or daclizumab) are used to prevent acute rejection, especially in highly sensitized patients. Both induction therapy regimens have a different tolerance profile. Infections and haematological side-effects are more frequently reported in patients receiving ATG. With respect to the efficacy, no comparison exists between both induction therapy regimens in high risk immunological patients as actually defined. Within the last few years, the development of new immunological screening tools, i.e. Luminex assay, had lead to a better evaluation of the immunological status of candidates for kidney transplantation, mainly those who were considered as highly sensitized. The aim of our pilot study is to evaluate ATG and basiliximab induction therapy in de novo sensitized kidney-transplant patients (incompatible grafts rate ≥ 50%) without Donor Specific Antibodies (DSAs) detected by Luminex. Maintenance immunosuppressive regimen will be based on the combination of tacrolimus, mycophenolate sodium and steroids. The primary endpoint is a composite of biopsy-proven acute rejection, graft loss, loss of follow up, or death at 6 months post-transplant. The secondary endpoints are the efficacy of the therapy at month 12 posttransplant, and safety parameters (CMV infection, BK virus nephropathy, haematological tolerance, Adverse Events (AE)and Serious Adverse Events (SAE)). Our hypothesis is that basiliximab induction therapy may be sufficiently effective to prevent acute rejection in sensitized patients without DSA. This may reduce the post-transplant immunosuppression-induced side-effects.

Eligibility criteria: Inclusion Criteria:

* Male or female patients aged from 18 to 70 years
* Recipient of a deceased or living donor kidney transplant with the following criteria:
* Incompatible grafts rate ≥ 50% for the last available serum before transplantation \< 3 months
* Anti-HLA antibodies positive
* Negative DSA by luminex method on historical serum and day serum
* T and B negative Cross match on historical and day serum
* Females capable of becoming pregnant must have a negative serum pregnancy test within 7 days prior to or at screening, and are required to practice an approved and reliable method of birth control for the duration of the study and for a period of 2 months after study medication discontinuation, even where there has been a history of infertility
* Patients who are willing and able to participate in the full course of the study and from whom written informed consent has been obtained.
* Patients affiliated to, or recipients of, a social security system

Exclusion Criteria:

* Recipients of a multi-organ transplantation, including dual kidneys, or who have previously received non renal transplanted organs
* Recipients of a kidney from non-heart beating donor, or with ABO incompatibility against the donor or with a T positive cross match
* Patients with severe uncontrolled systemic infection or severe allergy requiring acute or chronic treatment
* Aspartate aminotransferase (ASAT), Alanine Amino Transferase (ALAT) or bilirubin ≥ 3 upper limit of the normal range (ULN)
* Known hypersensitivity or contra-indication to rabbit proteins, basiliximab, tacrolimus, mycophenolic acid or any of the product excipients
* Patients who are Hepatitis C positive (positive PCR and normal hepatic test may be included), HIV positive, or Hepatitis B surface antigen positive (AgHBs).
* Patients with thrombocytopenia \< 75,000/mm3, an absolute neutrophils count \< 1,500/mm3, leukocytopenia \< 2,500/mm3, and/or hemoglobin \< 8g/dL at inclusion visit
* Patients with any past or present malignancy within the last five years except excised squamous or basal cell carcinoma of the skin and treated in situ cervix uteri cancer
* Any surgical or medical condition, excluding transplantation which compromise the inclusion of the patient (investigator's opinion)
* Female patients who are pregnant, breast feeding or capable to become pregnant and not wishing or capable to practice a medically approved and reliable method of birth control
* Patients with symptoms of significant somatic or mental illness. Inability to cooperate or communicate with the investigator

Primary outcomes:
measure: Incidence of treatment failure
timeFrame: 6 months
Secondary outcomes:
measure: feasibility estimating the number of informed consent obtained
timeFrame: 12 months
measure: treatment efficacy
timeFrame: 12 months
measure: adverse events
timeFrame: 12 months
measure: patient enrolled in each center
timeFrame: 12 months
measure: number of patients lost from follow-up
timeFrame: 12 months
measure: rejection
timeFrame: 12 months
measure: Donor Specific Antibodies
timeFrame: 12 months
measure: Incidence of BKV viremia
timeFrame: 12 months
measure: values of hematologia : hemoglobine, leucocytes, plaquettes, hematies, neutrophiles
timeFrame: 12 months
measure: Incidence of BKV nephropathy
timeFrame: 12 months
measure: incidence of CMV post transplantation
timeFrame: 12 months
measure: incidence of infections
timeFrame: 12 months
Other outcomes:
Locations:
city: Toulouse
country: France
facility: UHToulouse
Study officials:
affiliation: University Hospital, Toulouse
name: Nassim Kamar, MD PhD
role: STUDY_CHAIR
References: