Screening for subclinical antibody mediated rejection and efficacy of belatacept in the context of de novo donor specific antibody after kidney transplantation / BEL-AMR

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Centre Hospitalier Universitaire Rouen

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Digestive System Diseases [C06], Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Therapeutics [E02]

Trial duration

27 May 2026 → ongoing

Decision date (initial)

2025-06-24

Transition trial

No

Low-intervention

Yes

Rare-disease indication

No

Vulnerable population

No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Efficacy

To demonstrate, at 12 months post-biopsy, the efficacy of belatacept combined with standard of care, compared to Tacrolimus combined with standard of care, among kidney transplant recipients with active subclinical antibody mediated rejection (sABMR) detected on initial biopsy to diagnose subclinical de novo donor specific antibodies (dnDSA).

Secondary objectives 11

1. To compare in both randomized arms : 1) the Banff 2019 classification criteria on 12-month biopsy
2. To compare in both randomized arms : 2) the estimated glomerular filtration rate (eGFR) at 12 and 36 months
3. To compare in both randomized arms : 3) the proteinuria/creatinuria ratio at 12 and 36 months
4. To compare in both randomized arms : 4) the bad features on 12-month biopsy (cg>1)
5. To compare in both randomized arms : 5) the rate of T cell mediated rejection during the first year of treatment
6. To compare in both randomized arms : 6) the evolution of mean fluorescence intensity (MFI) of de novo DSA at 12 and 36 months
7. To compare in both randomized arms : 7) the tolerance to treatment
8. To compare in both randomized arms : 8) the graft and patient survival at 12 and 36 months.
9. To compare the patient groups formed at the initial biopsy with respect to : 9) the eGFR and proteinuria/creatinuria ratio at 36 months
10. To compare the patient groups formed at the initial biopsy with respect to : 10) the graft and patient survival at 12 and 36 months
11. 11) Estimation of sABMR incidence at 12 months among patients without sABMR on the initial biopsy (group 1).

Conditions and MedDRA coding

Kidney transplantation

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. Kidney transplant recipient
2. Adult
3. De novo DSA (MFI > 1000 using the Luminex single antigen beads assay or positive with the manufacturer criteria according to the Luminex assay) absent on the day of kidney transplantation and in the sera prior to kidney transplantation
4. No clinical graft dysfunction at time of DSA detection (< 20 % variation of eGFR compared to last 3 months before detection and < 0,5 g/g proteinuria/creatinuria ratio)
5. Randomization inclusion criteria: - Patients with active sABMR, according Banff 2019 classification, with very slight transplant glomerulogathy (cg = 0 or 1).

Exclusion criteria 4

1. Specific treatment for DSA occurrence before kidney graft biopsy: IVIG or rituximab or plasmapheresis or immunoabsorption
2. ABO incompatible kidney transplantation
3. Combined transplantation
4. Randomization exclusion criteria:  No sABMR or chronic active sABMR (cg > 1) on biopsy  Contraindication to Tacrolimus marketed as capsule or tablet pharmaceutical form o Hypersensitivity to tacrolimus or other macrolides o Hypersensitivity to any of the excipients  Contraindication to NULOJIX 250 mg powder for concentrate for solution for infusion: o Transplant recipients who are Epstein-Barr virus (EBV) seronegative or serostatus unknown. o Hypersensitivity to the active substance or to any of the excipients  History of severe opportunistic infection before randomization  History of infection with HBV, HCV or HIV  EBV negative serology  History of post-transplant lymphoproliferative disorder.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Proportion in each arm, at 12 months post-V0 (Biopsy), of patients with: - decrease eGFR > 20% at 12 months post-V0 (Biopsy), according to CKD-EPI formula - or bad features on 12-month protocol biopsy: cg > 1 - or chronic active ABMR according Banff 2019 classification, - or < 50 % MFI reduction of DSA, - or proteinuria/creatinuria ratio > 0.5 g/g, - or death, - or graft loss.

Secondary endpoints 11

1. To compare in both randomized arms: 1) All Banff 2019 elementary lesions of the kidney graft biopsy performed at 12 months after post-V0 (Biopsy)
2. 2) Serum creatinine and calculation of eGFR according to CKD-EPI formula at 12 and 36 months post-V0 (Biopsy)
3. 3) Proteinuria/creatininuria ratio at 12 and 36 months post-V0 (Biopsy)
4. 4) Bad features on 12-month biopsy (cg>1)
5. 5) Biopsy proven acute T cell rejection rate according to Banff 2019 classification
6. 6) MFI of the DSA at 12 months post randomization with a Luminex single antigen assay and at 36 months post-randomization from medical charts
7. 7) Adverse events’ collect (Occurrence of BK virus, CMV and EBV’s viremia, cardiovascular events, hospitalizations)
8. 8) Graft loss and death at 12 and 36 months post-V0 (Biopsy) from medical charts
9. To compare the groups formed at the initial biopsy with respect to: 9) Serum creatinine and calculation of eGFR according CKD-EPI formula, and proteinuria/creatininuria ratio at 12 and 36 months
10. 10) Graft loss and death at 12 and 36 months from medical charts
11. 11) Number of patients with sABMR according to Banff 2019 classification on biopsy performed at 12 months as part of routine care or before in the group without sABMR on initial biopsy divided by the time between initial biopsy and the first biopsy showing sABMR

Investigational products

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

Test 1

Comparator 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Centre Hospitalier Universitaire Rouen

Sponsor organisation

Centre Hospitalier Universitaire Rouen

Address

1 Rue De Germont, Bp 96031 Bp 96031

City

Rouen Cedex

Postcode

76031

Country

France

Scientific contact point

Organisation

Centre Hospitalier Universitaire Rouen

Contact name

Nell Marty

Public contact point

Organisation

Centre Hospitalier Universitaire Rouen

Contact name

Marty

Locations

1 EU/EEA country · 17 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

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

Documents 9 files

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

Application history

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