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

Grenoble Alpes University Hospital Center (CHU)

Status and phase: Terminated; Phase 2

Conditions: Sensitisation; Highly Sensitised Dialysis Patients

Treatments: Combination Product: Each patient will undergo in the first step of the study belatacept treatment and in the second apheresis and daratumumab

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT05145296

38RC21.171

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 5 patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Males and females age 18-70 years
• End Stage Renal Disease (ESRD) on dialysis
• Patient listed and active for a deceased donor kidney transplant and have not received compatible donor offer for ≥3 year.
• Calculated PRA ≥ 99%
• Positive CMV serology
• Positive EBV serology
• Current vaccination for more than one month for diphtheria, tetanus, poliomyelitis, influenza, pneumococcus, meningococcus, herpes zoster and SARS CoV-2.
• Patient affiliated to social security insurance or beneficiary of social security insurance

Exclusion criteria

• Inability or unwillingness of a participant to give written informed consent or comply with study protocol

  • Known active current or history of recurrent bacterial, viral, fungal, mycobacterial or other infections (including HIV, hepatitis B, hepatitis C, zoster)
  • Patient with positive hepatitis core antigen and/or positive hepatitis B surface antigen
  • Serious uncontrolled concomitant major organ disease
  • Any infection requiring hospitalization and intravenous antibiotics within 4 weeks of screening or Per os antibiotics within 2 weeks
  • Primary or secondary immunodeficiency
  • History of active tuberculosis (TB) (even if treated) or untreated latent TB
  • Malignancy within the last 5 years except documented and treated basal and squamous cell cancer of the skin
  • Alcohol, drug or chemical abuse within 1 year
  • Difficult peripheral venous access
  • Negative EBV serology
  • Negative CMV serology
  • Neutropenia (ANC <1000/uL) or thrombocytopenia (platelet count <100,000/uL) within 4 weeks prior to study entry
  • Patient previously treated with investigational products (belatacept, daratumumab)
  • Severe allergic or anaphylactic reactions to human, humanized or murine monoclonal antibodies
  • Hypersensitivity to any active substance or component of the investigational medicinal products
  • Any contra-indication to premedication drugs (paracetamol, dexchlorpheniramine, cetirizine, dexamethasone, montelukast) or post-medication drugs (corticosteroids, bronchodilators, valaciclovir)
  • Immunization with live vaccine within 2 months of study entry
  • Dry body weight ≥75kg.
  • Pregnancy or lactation
  • Females with childbearing status, defined as a premenopausal female capable of becoming pregnant, and not using an effective form of birth control. Effective birth control methods include oral, implant or patch hormone contraception; intrauterine device; abstinence and outercourse; tubal ligation; vasectomy.
  • Participant involved in another interventional clinical study
  • Person deprived of liberty by judicial order
  • Person under guardianship or curatorship

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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5 participants in 1 patient group

Patients with cPRA ≥99%

Other group

Description:

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.

Treatment:

Combination Product: Each patient will undergo in the first step of the study belatacept treatment and in the second apheresis and daratumumab