AzTrials
AzTrials

AllosensitizationPhase 1/2DARDARNCT04204980

Desensitization in Kidney Allograft Using Daratumumab

A Phase 1/2 study testing Daratumumab dose escalation and Daratumumab full dose in people with Allosensitization and Kidney Transplant Rejection, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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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… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Daratumumab dose escalation and Daratumumab full dose
Could I receive a placebo?
No, everyone receives an active treatment
How many people
21 participants
Where
1 siteFrance
Study dates
18 Feb 2020to 1 Jun 2023
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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
Show all 17Show fewer
  • 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

Trial locations and contacts

1 site in 1 country.

France1 site

  • Henri Mondor

    Créteil, 94000

Other trials in France

About this study

Official title: Desensitization in Kidney Allograft Recipients Before Transplantation Using Daratumumab

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.

Being tested
Daratumumab dose escalation, Daratumumab full dose
Keywords
Allosensitization, Kidney Transplantation

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Daratumumab dose escalationDrug

    • 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 doseDrug

    • 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
Study groups in NCT04204980
Study groupRoleWhat they receive
Dose escalation and full doseExperimentalStep 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 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
Receives: Drug: Daratumumab dose escalation; Drug: Daratumumab full dose

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Serious adverse events (SAEs) and adverse event (AEs) related and unrelated to the treatment during the dose-escalation step

    Measured: up to 21 months

  2. Intra-patient variation of cPRA after daratumumab treatment

    Measured: Baseline (Day 0) and at six months after daratumumab treatment

Secondary outcomes (10)

  1. Patient survival within one year after inclusion

    Measured: Baseline (Day 0) and at six months after daratumumab treatment

  2. Intra-patient variation of sum of mean fluorescence intensity (MFI) of anti-HLA antibodies

    Measured: 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.

  3. Intra-patient variation of cPRA (calculated panel reactive antibodies) after daratumumab treatment

    PRA will be calculated on serum, analyzed with Luminex single antigen assays

    Measured: Baseline (Day 0) and at one month, three months and 12 months after daratumumab treatment.

  4. Percentage of patients engrafted

    Measured: At six months and 12 months after inclusion

  5. Variation of immunoglobulin's blood titers

    Measured: At baseline (Day 0), three months, six months and 12 months after daratumumab treatment

  6. Intra-patient variation of ABO antibody titers

    ABO antibody titration will be performed by flow cytometry

    Measured: At baseline (Day 0), three months, six months and 12 months after daratumumab treatment

  7. Incidence of invasive infections

    Measured: 6 months and on year after inclusion

  8. Incidence of opportunistic infections

    Measured: 6 months and one year after inclusion

  9. Absolute number of Blood plasma cell

    Measured: At baseline (Day 0), one month, three months , six months and 12 months after daratumumab treatment

  10. Percentage of Blood plasma cell

    Measured: At baseline (Day 0), one month, three months , six months and 12 months after daratumumab treatment

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted19 Dec 2019
  2. Study start18 Feb 2020
  3. Primary completion1 Jun 2023
  4. Study completion1 Jun 2023

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Sequential
Model description
* 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 * 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 daratumumabProvide
Masking
None (open label)
Enrolment
21 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04204980
Sponsor's protocol ID
APHP190500
Acronym
DARDAR
Status last verified
Feb 2023
First submitted
9 Dec 2019
Last updated
19 Mar 2024
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No: DATAS ARE OWN BY ASSISTANCE PUBLIQUE - HOPITAUX DE PARIS, PLEASE CONTACT SPONSOR FOR FURTHER INFORMATION

Publications

  • Torija A, Matignon M, Vincenti F, Casanova-Ferrer F, Pilon C, Tambur AR, Donadeu L, Crespo E, Kervella D, Meneghini M, Torres IB, Hafkamp F, Martinez-Lacalle A, Carrera C, Zuniga J, Brar A, Cruzado J, Gaber AO, Lee H, Montgomery RA, Stegall M, Carmagnat M, Usureau C, Moreso F, Grimbert P, Bestard O. Anti-HLA serologic response to CD38-targeting desensitization therapy is challenged by peripheral memory B cells in highly sensitized kidney transplant candidates. Am J Transplant. 2025 Jan;25(1):88-101. doi: 10.1016/j.ajt.2024.08.004. Epub 2024 Aug 10.

    PubMed 39134120

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Daratumumab dose escalation and Daratumumab full dose in people with Allosensitization and Kidney Transplant Rejection, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 19 Mar 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Serious adverse events (SAEs) and adverse event (AEs) related and unrelated to the treatment during the dose-escalation step (time frame: up to 21 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04204980, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Mar 2024.

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