Combining Daratumumab and Belatacept for Highly Sensitized Kidney Transplant Patients
Non-Randomized, Single-Center Pilot Trial Assessing The Safety/Efficacy Of Targeting Peripheral And Central Humoral Alloimmune Memory With Daratumumab And With Belatacept In Highly HLA-Sensitized Patients Awaiting Kidney Transplantation
This study is testing a new treatment combining two medications to see if it can help highly sensitized kidney transplant patients find a compatible donor and improve their chances of getting a transplant.
Quick facts
| Phase | Not applicable |
|---|---|
| Study type | Interventional |
| Enrollment | 12 (estimated) |
| Ages | 18 Years to 70 Years |
| Sex | All |
| Sponsor | University Hospital, Grenoble Academic / other |
| Drugs / interventions | daratumumab |
| Locations | 1 site (La Tronche) |
| Trial ID | NCT05145296 on ClinicalTrials.gov |
What this trial studies
This study investigates the safety and efficacy of combining daratumumab with belatacept in patients who are highly sensitized and awaiting kidney transplantation. It aims to enroll 12 patients who have been on the deceased donor kidney transplant waiting list for over three years and have a calculated panel reactive antibody (cPRA) of 99% or higher. The intervention involves initial treatment with belatacept followed by apheresis and daratumumab to potentially improve transplant compatibility. The goal is to develop a novel desensitization strategy to increase the chances of successful kidney transplantation for these patients.
Who should consider this trial
Good fit: Ideal candidates are adults aged 18-70 with end-stage renal disease on dialysis, listed for a deceased donor kidney transplant, and who have not received a compatible donor offer for at least three years.
Not a fit: Patients with active infections, serious uncontrolled organ diseases, or those unable to comply with the study protocol may not benefit from this study.
Why it matters
Potential benefit: If successful, this approach could significantly improve the chances of kidney transplantation for highly sensitized patients, enhancing their quality of life and life expectancy.
How similar studies have performed: While current desensitization therapies have shown limited success, this combination approach is novel and has not been extensively tested in similar studies.
Eligibility criteria
Show full inclusion / exclusion criteria
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
Where this trial is running
La Tronche
- Chu Grenoble — La Tronche, France (Recruiting)
Study contacts
- Principal investigator: Paolo Malvezzi, MD — University Hospital, Grenoble
- Study coordinator: Paolo Malvezzi, MD
- Email: pmalvezzi@chu-grenoble.fr
- Phone: 0476765460
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.