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Evaluation of the Safety of Use of Anti-IL6 Receptor Antibodies to Reduce Allo-sensitization Post Allograft Nephrectomy

Evaluation of the Safety of Use of Anti-IL6 Receptor Antibodies to Reduce Allo-sensitization Post Allograft Nephrectomy

Recruiting
18 years and older
All
Phase 2

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Overview

Graft nephrectomy is associated with massive allo-sensitization following this event. The occurrence of anti-HLA antibodies is a major barrier to perform a second kidney transplantation. Investigators propose here to evaluate in a phase II pilot study, the safety of the use of a single dose of Tocilizumab immediately before or after graft nephrectomy. The primary endpoint evaluated here is the occurrence of serious infectious complications following graft nephrectomy, with a treatment by Tocilizumab. Secondary endpoints evaluated here are - to evaluate all complications after graft nephrectomy, - and the Tocilizumab effectiveness to reduce anti-HLA antibodies at one year post nephrectomy.

Description

Background: graft nephrectomy is associated with massive allo-sensitization following this event The occurrence of anti-HLA antibodies is a major barrier to perform a second kidney transplantation. Moreover, a systemic inflammatory response syndrome can occur which could lead to serious patient's complications, in case of early graft thrombosis. To date, no treatment or strategy is available to reduce these risks, after graft nephrectomy. IL-6 is a key cytokine in inflammation, but also in the development of T and B cells activation. This treatment previously demonstrated a major role in the occurrence of allo-antibodies. Tocilizumab is a monoclonal antibody blocking IL6 receptor, previously used with success in kidney transplantation to reduce anti-HLA antibodies mediated rejection.

Objectives: Investigators hypothesize that Tocilizumab is useful to prevent allo-sensitization post graft nephrectomy. They propose here to evaluate in a phase II pilot study, the safety of the use of a single dose of Tocilizumab immediately before or after graft nephrectomy.

Eligibility

Inclusion Criteria:

  • Adult recipients,
  • affiliated to the social security
  • requiring a graft nephrectomy, with a project to retransplantation

Exclusion Criteria:

  • combined transplantations, PRA >20%.
  • Patient under protective measures,
  • Rituximab used for immunosuppression induction
  • Previous transplants not removed,
  • Active infectious complications at graft nephrectomy, need for immunosuppressive treatments after graft nephrectomy,
  • Participation to another interventional studies using Rituximab, polyclonal antibodies, Eculizumab, or Tocilizumab.
  • adults under guardianship or other legal protection, deprived of their liberty by judicial or administrative decision,
  • pregnancy or breastfeeding.

Study details
    Kidney Transplantation
    Graft Failure

NCT04779957

University Hospital, Toulouse

26 January 2024

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