Clinical trial NCT04779957: Evaluation of the Safety of Use of Anti-IL6 Receptor Antibodies to Reduce Allo-sensitization Post Allograft Nephrectomy
Official title: Evaluation of the Safety of Use of Anti-IL6 Receptor Antibodies to Reduce Allo-sensitization Post Allograft Nephrectomy ; a Pilot Phase II Study.
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Kidney Transplantation
Graft Failure
Keywords: Kidney transplantation
allosensitization
graft nephrectomy
Donor-Specific Antibodies
Lead sponsor: University Hospital, Toulouse
Sponsor class: OTHER
First posted: 2021-03-03
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

Detailed 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 criteria: 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.

Primary outcomes:
measure: serious infectious complication
timeFrame: 1 year post graft nephrectomy
Secondary outcomes:
measure: Complications after treatment
timeFrame: 1 year post graft nephrectomy
measure: The effectiveness of the treatment
timeFrame: 1 year post graft nephrectomy
Other outcomes:
Locations:
city: Toulouse
country: France
facility: CHU Toulouse
Study officials:
affiliation: University Hospital, Toulouse
name: Arnaud DEL BELLO, MD
role: PRINCIPAL_INVESTIGATOR
References: