The Safety/Efficacy Of Daratumumab With Belatacept In Highly HLA-Sensitized Patients Awaiting Kidney Transplantation

Conditions

• Highly Sensitised Dialysis Patients
• Sensitisation

Eligibility Criteria

Sex

ALL

Age

18 Years - 70 Years

Healthy Volunteers

Not accepted

Interventions

• Each patient will undergo in the first step of the study belatacept treatment and in the second apheresis and daratumumab — COMBINATION_PRODUCT
  Four consecutive cohorts each comprising 3 patients are planned. STEP I: Patients receive Belatacept 10mg/kg, administered on days 1, 5, end of week 2, 4 and 8 . Patients without a significant decrease in the global cPRA (cPRA or TGI ≥99%) or significant reduction of anti-HLA Ab MF will continue to the second step. STEP II: (15 weeks) One week after the last injection of belatacept, patients will undergo 4 sessions of apheresis (plasmapheresis (PF) or Immunoadsorption (IA)) which will be given every 48h. At week 11, patients will receive 4 doses of daratumumab (8mg/kg) every two weeks until week 17. Daratumumab will be alternated with 4 additional doses of belatacept 5 mg/kg FOLLOW-UP (24 weeks) All patients exiting the study, either having completed all treatment courses or exiting prematurely (transplanted or not), will be proposed monthly follow-up visits

Study Details

While the number of kidney transplants is increasing worldwide every year, there is a clear imbalance between the high number of patients in the waiting list and those receiving a transplant and importantly, among waitlist patients there is a progressively higher number of highly sensitised patients that have very low or even no chance to receive a compatible organ. These patients remain for very long periods of time on dialysis therapy, having lower quality of life, lower life expectancy and produce higher health-related costs. Unfortunately, current desensitization therapies have shown very poor success and patients usually lose these grafts very fast if transplanted across a positive cross-match. Therefore, there is an urgent need for novel desensitization strategies capable of overcoming this immunological barrier and allow an increasing number of patients to receive a HLA-compatible kidney allograft.This is a non-randomized, single arm study, combination trial designed according to the Recommendations of the Clinical Trial Design Task Force of the NCI Investigational Drug Steering Committee. The study will enroll 12 patients with cPRA or TGI ≥99% on the deceased donor kidney transplant waiting list, who have not received a compatible donor offer for \>3 year. According to inclusion and exclusion criteria patients will be screened to participate in the trial.

Key Dates

Start date

Jan 19, 2022

Status verified

May 2023

Primary completion

Dec 1, 2024

Completion

Oct 10, 2025

Study Design

Enrollment

5 participants (actual)

Allocation

NA

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Arms

• Other: Patients with cPRA ≥99%
  This is a non-randomized, single arm study, combination trial designed according to the Recommendations of the Clinical Trial Design Task Force of the NCI Investigational Drug Steering Committee. The study will enroll 12 patients with cPRA ≥99% on the deceased donor kidney transplant waiting list, who have not received a compatible donor offer for \>3 year. According to inclusion and exclusion criteria patients will be screened to participate in the trial.

Primary Outcome Measure

Proportion of severe or medically significant Adverse and Serious Adverse Events [ Time Frame: end of study ]