Desensitization in Kidney Allograft Using Daratumumab

Kidney Transplant Rejection Clinical Trial

— DARDAR  

Official title:

Desensitization in Kidney Allograft Recipients Before Transplantation Using Daratumumab

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04204980
• Other study ID #: APHP190500
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: February 18, 2020
• Est. completion date: June 1, 2023

Study information

• Verified date: February 2023
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• 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

Related Conditions & MeSH terms

• Allosensitization
• Antibody-mediated Rejection
• Kidney Transplant Rejection

Intervention

Drug:
• Daratumumab dose escalation
- Step I: dose-escalation 3 patients treated weekly during four weeks with 4 mg/kg of daratumumab, then 3 patients treated weekly during four weeks with 8 mg/kg of daratumumab, then 3 patients treated weekly four weeks with 16 mg/kg of daratumumab
• Daratumumab full dose
- Step II: expansion cohort to 13 patients (with 10 new patients included and the last 3 patients from the step I) with eight weekly doses of 16 mg/kg daratumumab

Locations

Country	Name	City	State
France	Henri Mondor	Créteil

Sponsors (2)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris	Janssen, LP

Country where clinical trial is conducted

France, 

Outcome

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