Desensitization in Kidney Allograft Using Daratumumab

NCT04204980 | Completed Phase 1 DMC

• 1 other identifier: APHP190500
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Allosensitization; Kidney Transplant Rejection; Antibody-mediated Rejection

Keywords

Allosensitization; Kidney Transplantation

Outcome Measures

Primary Outcomes (2)

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

  up to 21 months

• Intra-patient variation of cPRA after daratumumab treatment

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

Secondary Outcomes (10)

• Patient survival within one year after inclusion

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

• 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.

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

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

• Percentage of patients engrafted

  At six months and 12 months after inclusion

• Variation of immunoglobulin's blood titers

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

Study Arms (1)

Dose escalation and full dose

EXPERIMENTAL

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 daratumumab

Drug: Daratumumab dose escalation; Drug: Daratumumab full dose

Interventions

Daratumumab dose escalation DRUG

\- 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

Dose escalation and full dose

Daratumumab full dose DRUG

\- 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

Dose escalation and full dose

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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.

You may not qualify if:

• 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
• 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)

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead
• Janssen, LP: collaborator

Study Sites (1)

Henri Mondor

Créteil, 94000, France

Location

Study Officials

• Marie Matignon, MD

  Assistance Publique - Hôpitaux de Paris

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: * 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

Study Record Dates

• First Submitted: December 9, 2019
• First Posted: December 19, 2019
• Study Start: February 18, 2020
• Primary Completion: June 1, 2023
• Study Completion: June 1, 2023
• Last Updated: March 19, 2024

Record last verified: 2023-02

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)