Simulect Versus ATG in Sensitized Renal Transplant Patient

Renal Transplant Rejection Clinical Trial

— SATIR  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02377193
• Other study ID #: 12 484 03
• Status: Completed
• Phase: Phase 4
• First received: June 11, 2014
• Last updated: October 24, 2017
• Start date: September 2013
• Est. completion date: January 2017

Study information

• Verified date: October 2017
• Source: University Hospital, Toulouse
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 60
• Est. completion date: January 2017
• Est. primary completion date: January 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Renal Transplant Rejection

Intervention

Drug:
• Simulect
Simulect IV 40 mg/day D0 and D4 and oral use Tacrolimus 0.1 mg/ kg/ day + Myfortic 720 to 1440mg + Corticosteroids 5mg
• ATG Fresenius
Simulect IV 40 mg/day D0 and D4 and oral use Tacrolimus 0.1 mg/ kg/ day + Myfortic 720 to 1440mg + Corticosteroids 5mg

Locations

Country	Name	City	State
France	UHToulouse	Toulouse

Sponsors (3)

Lead Sponsor	Collaborator
University Hospital, Toulouse	Neovii Biotech, Novartis

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of treatment failure	Incidence of treatment failure (Biopsy Proved Reject, lost to follow up, graft loss or death) at 6 months post transplantation.	6 months
Secondary	feasibility estimating the number of informed consent obtained	Estimating the number of informed consent obtained	12 months
Secondary	treatment efficacy	Treatment failure at 12 months post transplantation.; premature discontinuation of study medication, discontinuation from the study and reasons.; incidence of all acute rejection episodes requiring an anti-T and /or anti-B antibodies treatment within 12 months post transplantation.; Incidence of C4d positive biopsy findings.; Renal function at 3, 6 and 12 months post transplantation (abbreviated MDRD, serum creatinine and adjusted Cockcroft- Gault).	12 months
Secondary	adverse events	Safety: - Adverse Events, Serious Adverse Events	12 months
Secondary	patient enrolled in each center	Estimating the number of patient enrolled in each center and by year	12 months
Secondary	number of patients lost from follow-up	Estimating the number of patients lost from from follow-up before 6 and before 12 months	12 months
Secondary	rejection	acute rejection at 6 and 12 months post transplantation; - Subclinical rejection at the 3 month per protocol renal biopsy.	12 months
Secondary	Donor Specific Antibodies	Donor Specific Antibodies at D0, M3 and M12.	12 months
Secondary	Incidence of BKV viremia	incidence of BKV viremia at 1, 3, 6 and 12 months post transplantation	12 months
Secondary	values of hematologia : hemoglobine, leucocytes, plaquettes, hematies, neutrophiles		12 months
Secondary	Incidence of BKV nephropathy	Incidence of BKV nephropathy at 1, 3, 6 and 12 months post transplantation	12 months
Secondary	incidence of CMV post transplantation	incidence of CMV(PCR) post transplantation at 6, 9 and 12 months	12 months
Secondary	incidence of infections	incidence of infections cancer and PTLD	12 months