Kidney Transplant Rejection Clinical Trial
— DARDAROfficial title:
Desensitization in Kidney Allograft Recipients Before Transplantation Using Daratumumab
Verified date | February 2023 |
Source | Assistance Publique - Hôpitaux de Paris |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
Patients highly allosensitized against HLA antigen awaiting for a kidney transplant have less compatible transplants to them, increasing their waitlist time and mortality. Current desensitization strategies need to be improved with a high remaining acute rejection rate in this population and a substantial survival benefit which is not uniformly reported in the literature. The investigators propose to use daratumumab, a human IgG1 (Immunoglobulin Gamma-1) monoclonal antibody directed against the CD38 molecule (cluster of differentiation 38) witch induce response in refractory multiple myeloma by depleting plasma cells, as a new agent of desensitization. The study will address the hypothesis that daratumumab can lead to a significant decrease in calculated panel reactive antibodies by elimination of anti-HLA antibodies-producing plasma cells and facilitate the access to transplantation with a safety profile in highly sensitized patients registered in our kidney transplantation center.
Status | Completed |
Enrollment | 21 |
Est. completion date | June 1, 2023 |
Est. primary completion date | June 1, 2023 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years and older |
Eligibility | Inclusion Criteria: - Adults = 18 years awaiting a kidney allograft transplantation - Registration on the French National kidney allograft waiting-list for at least three years - cPRA = 95% for at least three years - COVID-19 vaccination using Pfizer BioNtech vaccine for: Patients who have never been infected with COVID-19, inclusion at least one month after the third dose OR Patients previously infected with COVID-19 proved with PCR or serology, inclusion at least one month after the second injection of Pfizer BioNtech vaccine. - Effective contraception up to three months after the end of treatment - Informed consent obtained in accordance with local regulations; - Affiliation to a social security regime. Exclusion Criteria: - Refusal of COVID-19 vaccination using Pfizer BioNtech vaccine - Hypersensitivity to daratumumab or to any of the excipients), - Known allergy to methylprednisolone and its excipients or to diphenhydramine and its excipients or to acetaminophen and its excipients or to valacyclovir and its excipients. - Severe hepatocellular insufficiency - Psychotic state not yet controlled by treatment - Patient refusal - Pregnant or breastfeeding woman or ineffective contraception - Active neoplasia - Active infection - Active HBV infection, including HBsAg positive at screening - Participation in another interventional study involving human participants or being in the exclusion period at the end of a previous study involving human participants - Persons deprived of their liberty by judicial or administrative decision, - Persons under legal protection/safeguard of justice, - Patients under duress psychiatric care, - Persons admitted to a health or social institution - Patient on AME (state medical aid) - Contraindication to kidney transplantation |
Country | Name | City | State |
---|---|---|---|
France | Henri Mondor | Créteil |
Lead Sponsor | Collaborator |
---|---|
Assistance Publique - Hôpitaux de Paris | Janssen, LP |
France,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Serious adverse events (SAEs) and adverse event (AEs) related and unrelated to the treatment during the dose-escalation step | up to 21 months | ||
Primary | Intra-patient variation of cPRA after daratumumab treatment | Baseline (Day 0) and at six months after daratumumab treatment | ||
Secondary | Patient survival within one year after inclusion | Baseline (Day 0) and at six months after daratumumab treatment | ||
Secondary | Intra-patient variation of sum of mean fluorescence intensity (MFI) of anti-HLA antibodies | Baseline (Day 0) and at one month, three months, six months and 12 months after daratumumab treatment.Baseline (Day 0) and at one, three, six and 12 months after daratumumab treatment. | ||
Secondary | Intra-patient variation of cPRA (calculated panel reactive antibodies) after daratumumab treatment | PRA will be calculated on serum, analyzed with Luminex single antigen assays | Baseline (Day 0) and at one month, three months and 12 months after daratumumab treatment. | |
Secondary | Percentage of patients engrafted | At six months and 12 months after inclusion | ||
Secondary | Variation of immunoglobulin's blood titers | At baseline (Day 0), three months, six months and 12 months after daratumumab treatment | ||
Secondary | Intra-patient variation of ABO antibody titers | ABO antibody titration will be performed by flow cytometry | At baseline (Day 0), three months, six months and 12 months after daratumumab treatment | |
Secondary | Incidence of invasive infections | 6 months and on year after inclusion | ||
Secondary | Incidence of opportunistic infections | 6 months and one year after inclusion | ||
Secondary | Absolute number of Blood plasma cell | At baseline (Day 0), one month, three months , six months and 12 months after daratumumab treatment | ||
Secondary | Percentage of Blood plasma cell | At baseline (Day 0), one month, three months , six months and 12 months after daratumumab treatment |
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