SCARR : « Allogenic Umbilical Cord Mesenchymal Stromal Cells for the treatment of chronic renal (cABMR) graft rejection »

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Assistance Publique Hopitaux De Paris

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

Decision date (initial)

2025-02-18

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

DGOS

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Efficacy

To evaluate the effectiveness of allogeneic UC-MSC injections on renal function at 24 months in patients with cABMR.

Secondary objectives 7

1. Evaluation of the tolerance of the UC-MSC injection after each injection (D0, D7, D14, and D21)
2. Assessment of renal function on D0, M1, M2, M6, M12, M18 and M24
3. Evaluation of graft survival at 12 months and 24 months
4. Assessment of proteinuria on D0, M1, M2, M6, M12, M18 and M24
5. Evaluation of anti-HLA antibodies against graft HLA and UC-MSC HLA at D0, M2, M6, M12, and M24
6. Evolution of renal fibrosis based on a renal biopsy (PBR) at 6 months
7. Evolution of the phenotype of T and B lymphocytes between D0, M2, M6

Conditions and MedDRA coding

Adult Patients kidney transplant recipients who have developed chronic humoral rejection, diagnosed through a kidney biopsy (Banff 2017 Classification), resistant to conventional treatment (3 injections at one-month intervals of 2g/kg of IVIG)

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. Man or woman aged ≥18
2. Kidney transplant ≥ 1 year and < 10 years
3. Chronic humoral rejection diagnosed on a renal biopsy (Banff 2017) less than 6 months before (cpt+g score greater than or equal to 2) and having donor-specific anti-HLA antibodies (MFI<20000) and not responding to 3 monthly courses of IV-IG (2 g/kg) (persistence of histological lesions of cABMR; absence of improvement in eGFR>20%; proteinuria/creatininuria ratio has not decreased by more than 50% and DSA has not decreased by 50%)
4. eGFR > 30ml/min
5. Proteinuria >1 g/24 h or proteinuria/creatininuria >150 mg/mmol
6. Patient able to attend follow-up consultations
7. Signed informed consent by the patient
8. Affiliation to a social security system
9. Patient able to understand and follow the protocol

Exclusion criteria 14

1. Multiple transplants
2. HIV-positive patient or with an uncontrolled acute or chronic viral infection such as hepatitis B or C
3. Patient with an active bacterial infection
4. Patients with decompensated heart failure or with a cardiac heart dysfunction (ejection fraction <40%).
5. Patients with known hepatic cirrhosis or hepatic failure (Factor V <50%) or hepatic cytolysis ALT >5N.
6. Patient having been treated for a solid or hematopoietic tumor in the last 5 years, excluding skin tumors (apart from melanoma) (less than 3 skin tumors)
7. BK virus nephropathy demonstrated on a renal biopsy or presumed (2 BK virus PCR > 104 for 3 weeks) at the time of inclusion
8. Pregnant woman or woman of childbearing age not taking effective contraception
9. Patient deprived of liberty by judicial or administrative decision
10. Adult patients subject to a legal protection measure (guardianship, curatorship, and safeguard of justice)
11. Patient undergoing psychiatric care and not stabilized
12. Participation in another interventional research involving humans or being in the exclusion period following previous research involving humans (corresponding to the ½ life of the experimental Medication)
13. Patient having received treatment with Rituximab or Velcade and having chronic resistant humoral rejection less than one year.
14. Patient under AME (state medical aid)

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Change in renal function (estimated glomerular filtration rate CDK-EPI) (eGFR) between D0 and M24

Secondary endpoints 7

1. Safety of UC-MSC injection (after injection for 4 hours): Measurement of pulsed oxygen saturation, dyspnea, blood pressure, eGFR, CRP, cellular infiltration (BANFF 2017 criteria for the evaluation of acute rejection)
2. Variation in renal function (eGFR) on D0, M1, and respectively M2, M6, and M12, M18 and M24
3. Cumulative incidence of patients requiring dialysis at 12 and 24 months.
4. Evolution of 24-hour proteinuria and the proteinuria/creatininuria ratio between D0 and M1, M2, M6 and M12, M18 and M24
5. Luminex assay for donor-specific anti-HLA antibodies (single antigen) on D0, M2, M6, M12, M24
6. Quantification of Interstitial Fibrosis and Tubular Atrophy, glomerulitis, and capillaritis on histological section. Quantification of fibrosis by Syrius Red and immunohistochemistry at 6 months
7. T and B lymphocyte phenotyping (% of T and B regs) on D0, M2, M6

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Assistance Publique Hopitaux De Paris

Sponsor organisation

Assistance Publique Hopitaux De Paris

Address

Porte 23, 1 Avenue Claude Vellefaux 1 Avenue Claude Vellefaux

City

Paris Cedex 10

Postcode

75475

Country

France

Scientific contact point

Organisation

Assistance Publique Hopitaux De Paris

Contact name

Pr Antoine DURRBACH

Public contact point

Organisation

Assistance Publique Hopitaux De Paris

Contact name

Mme Wafa FETHALLAH

Locations

1 EU/EEA country · 3 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 5 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications