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NOT YET RECRUITING

NCT06886646

PHASE2

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

Sponsor: Assistance Publique - Hôpitaux de Paris

View on ClinicalTrials.gov

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.

Official title: SCARR: Allogeneic Umbilical Cord Mesenchymal Stromal Cells for the Treatment of Chronic Antibody-Mediated Rejection (cABMR) in Kidney Transplantation

Key Details

Gender

All

Age Range

18 Years - Any

Study Type

INTERVENTIONAL

Enrollment

Start Date

2025-09-15

Completion Date

2029-10-15

Last Updated

2025-06-26

Healthy Volunteers

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.

Inclusion Criteria: * Male or Female aged ≥18 years * Renal transplant recipient for ≥1 year and \<10 years * Chronic humoral rejection diagnosed by renal biopsy (Banff 2017) within the last 6 months (cpt+g score ≥ 2) with donor-specific anti-HLA antibodies (MFI\<10000) and unresponsive to 3 monthly IV-IG treatments (2 g/kg) (persistence of histological lesions of Chronic Humoral Rejection; no improvement in eGFR \>20%; proteinuria/creatinine ratio not regressed by more than 50% and DSA not regressed by 50%) * eGFR (CDK-epi) \> 30ml/min * Proteinuria \>1 g/24h or proteinuria/creatinine ratio \>150 mg/mmol * Patient able to attend follow-up consultations * Patient capable of understanding and following the protocol * Signed informed consent from the patient * Affiliation to a social security system Exclusion Criteria: * Multiple transplant * HIV-positive patient or patient with an acute or chronic uncontrolled viral infection such as hepatitis B or C * Patient with an active bacterial infection * Patient with decompensated heart failure or known ejection fraction \<40% * Patient with known liver cirrhosis or liver failure (Factor 5 \<50%) or hepatic cytolysis (ALT \>5N) * Patient treated for a solid tumor or hematopoietic malignancy in the past 5 years, excluding skin tumors (except melanoma) (less than 3 skin tumors) BK virus nephropathy diagnosed by renal biopsy or presumed (2 BK virus PCR \> 10\^4 for 3 weeks) at the time of inclusion * Pregnant woman or woman of childbearing age not using effective contraception during her participation in the study * Patient with a known or suspected contraindication to the administration of any product used in the study, including the active substance or any excipients * Patient deprived of liberty by judicial or administrative decision * Adult patient under legal protection (guardianship, curatorship, or legal safeguard) * Patient receiving psychiatric care and not stabilized * Participation in another interventional clinical trial involving humans or in the exclusion period following a previous clinical trial involving humans (corresponding to the half-life of the experimental drug) * Patient who received treatment with Rituximab or Velcade within the 12 months prior to inclusion and has chronic humoral rejection resistant within the past year * Patient under state medical assistance (AME)

Locations (1)

Hôpital Henri Mondor

Créteil, Créteil, France