Simulect Versus ATG in Sensitized Renal Transplant Patient

NCT ID: NCT02377193

Last Updated: 2025-12-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-09-30
• Study Completion Date: 2017-01-31

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.

Conditions

Renal Transplant Rejection

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Simulect

Simulect IV 40 mg D0 and D4

Group Type: EXPERIMENTAL

Simulect

Intervention Type: DRUG

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

ATG IV min dose 3 mg/ kg/ day D0, D1, D3, D5

Group Type: ACTIVE_COMPARATOR

ATG Fresenius

Intervention Type: DRUG

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

Interventions

Simulect

Simulect IV 40 mg/day D0 and D4

and oral use Tacrolimus 0.1 mg/ kg/ day + Myfortic 720 to 1440mg + Corticosteroids 5mg

Intervention Type: DRUG

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

Intervention Type: DRUG

Other Intervention Names

Simulect IV 40 mg/day D0 and D4; and oral use Tacrolimus 0.1 mg/ kg/ day +; Myfortic 720 to 1440mg +; Corticosteroids 5mg; Simulect IV 40 mg/day D0 and D4; and oral use Tacrolimus 0.1 mg/ kg/ day +; Myfortic 720 to 1440mg +; Corticosteroids 5mg

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Neovii Biotech

INDUSTRY

Sponsor Role: collaborator

Novartis

INDUSTRY

Sponsor Role: collaborator

University Hospital, Toulouse

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Nassim Kamar, MD PhD

Role: STUDY_CHAIR

University Hospital, Toulouse

Locations

UHToulouse

Toulouse, France, France

Countries

France

References

Kamar N, Lepage B, Couzi L, Albano L, Durrbach A, Pernin V, Esposito L, Hebral AL, Darres A, Lequintrec M, Cassuto E, Merville P, Congy N, Del Bello A. A Randomized Prospective Study Comparing Anti-T-Lymphocyte Igs to Basiliximab in Highly Sensitized Kidney Transplant Patients. Kidney Int Rep. 2020 Jun 2;5(8):1207-1217. doi: 10.1016/j.ekir.2020.05.020. eCollection 2020 Aug.

Reference Type: RESULT

PMID: 32775820 (View on PubMed)

Other Identifiers

12 484 03

Identifier Type: -

Identifier Source: org_study_id