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Allogeneic Umbilical Cord Mesenchymal Stromal Cells for the Treatment of Chronic Antibody-Mediated Rejection in Kidney Transplantation

NCT06886646 · Status: NOT_YET_RECRUITING · Phase: PHASE2 · Type: INTERVENTIONAL · Enrollment: 22

Last updated 2025-06-26

No results posted yet for this study

Summary

Kidney transplantation is the best treatment for end-stage chronic kidney disease (CKD), improving survival and quality of life, while reducing treatment costs. However, immunosuppressive therapies reduce acute rejection but have not significantly improved graft survival (60% at 10 years). Graft loss is largely due to chronic antibody-mediated rejection (cABMR), which remains a major challenge with no specific treatment. In our center, 20 cABMR cases confirmed by biopsy were identified in 2018-2019, with 40% of patients returning to dialysis.

Cellular therapies aiming at graft tolerance induction are promising strategies. The European consortium The-One-Study conducts Phase II trials using non-mesenchymal immunoregulatory cells to reduce immunosuppressive treatment and/or prevent infections or tumors. Mesenchymal Stromal Cells (MSCs), not part of this consortium, modulate the function of cells involved in acute or chronic rejection. In kidney transplantation (living donor), MSCs reduce acute rejection by 64% at 6 months, infections by 36%, with lower doses of immunosuppressants.

A recent randomized trial showed that injecting MSCs one and a half months after kidney transplantation allowed discontinuation of calcineurin inhibitors without increased rejection risk. At 6 months, there were no differences in renal function or tissue damage, indicating the potential to stop calcineurin inhibitors following MSC injection. Additionally, a significantly higher level of regulatory lymphocytes was observed. Previous attempts to discontinue calcineurin inhibitors early showed increased rejection risk.

A recent study (Neptune Phase Ib) with allogeneic MSCs demonstrated that tacrolimus doses could be reduced without acute or chronic rejection. In the cABMR model, MSC injection reduced creatinine by 45%, proteinuria by 70%, and fibrotic lesions. A study by Wei et al. showed that allogeneic bone marrow MSCs improved renal function in chronic rejection.

Given the easier availability of umbilical cord MSCs, which also have more significant paracrine activities, our goal is to demonstrate that allogeneic umbilical cord MSCs can serve as a treatment for cABMR.

Conditions

  • Chronic Antibody-mediated Rejection (cABMR)

Interventions

OTHER

Allogeneic Mesenchymal Stromal Cell Therapy

Patients in this arm will receive 4 injections of allogeneic mesenchymal stromal cells (CSM) derived from human umbilical cord. The doses will be 1.106 cells/kg administered intravenously at days 0, 7, 14, and 21. The injections are given after thawing, washing, resuspension, and adjusting the dose. The CSM treatment aims to control chronic active antibody-mediated rejection (cABMR), improve renal function, reduce proteinuria, and increase graft survival without changing the immunosuppressive regimen.

OTHER

Placebo (NaCl 0.9%) Treatment

Patients in this arm will receive placebo treatments, which will consist of 150 mL of saline (NaCl 0.9%) administered intravenously at the same intervals as the CSM group (days 0, 7, 14, and 21). The placebo will be administered under the same conditions as the treatment, and the participants and investigators will remain blinded to the group allocation. Like the CSM group, no changes will be made to the patients' immunosuppressive regimen.

Sponsors & Collaborators

  • Assistance Publique - Hôpitaux de Paris

    lead OTHER

Study Design

Allocation
RANDOMIZED
Purpose
OTHER
Masking
TRIPLE
Model
PARALLEL

Eligibility

Min Age
18 Years
Sex
ALL
Healthy Volunteers
No

Timeline & Regulatory

Start
2025-09-15
Primary Completion
2027-09-15
Completion
2029-10-15

Countries

  • France

Study Locations

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Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT06886646 on ClinicalTrials.gov