BELASBRIDGE : Belatacept as a replacement for CNIs 3 to 12 months post-transplantation in patients with early graft dysfunction

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Centre Hospitalier Universitaire De Nantes

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Pathological Conditions, Signs and Symptoms [C23]

Trial duration

3 May 2024 → ongoing

Decision date (initial)

2022-05-19

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Nantes University Hospital

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

To study the feasibility of transient (9 months, 3-12 months post-transplant) replacement of CNIs with belatacept in renal transplant patients with early graft dysfunction.

Secondary objectives 6

1. To assess the efficacy of belatacept treatment on renal function and prevention of rejection episodes.
2. To evaluate the tolerance of the treatments (belatacept during phase 1 and CNI during phase 2).
3. To estimate the cost of management, according to the societal perspective and a time horizon of 15 months (from 3 months to 18 months post-transplant) and to compare it with the cost of management for a theoretical arm receiving continuous belatacept and for a theoretical arm receiving continuous CNIs (reference treatment currently recommended by the HAS).
4. To evaluate the evolution of quality of life during the 15 months of follow-up and to compare it to a theoretical arm receiving continuous belatacept and a theoretical arm receiving continuous CNIs.
5. To assess the differential impact of CNIs and belatacept on immune system cell populations
6. To assess the differential impact of CNIs and belatacept on the anti-CMV cellular immune response.

Conditions and MedDRA coding

Kidney transplant

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 11

1. Adult over 18 years of age.
2. Transplantation from a deceased or living donor kidney (non-HLA-identical) with ABO compatibility
3. No contraindication to graft biopsy at between 8 to 10 weeks post-transplant.
4. Maintenance treatment with CNI/MPA +/- prednisone
5. Renal function estimated by CKD-EPI creatinine clearance < 40 ml/min/1.73m2.
6. Willing to give written informed consent after information.
7. Results of the 10-week post-transplant renal biopsy showing no rejection or BK virus nephropathy, no recurrence of the initial disease, no thrombotic microangiopathy and no cortical necrosis.
8. EBV seropositivity
9. Negative pregnancy test for patients of childbearing age, and agreement to use effective contraception throughout the study
10. Have no difficulty understanding and communicating with the investigator and his representatives
11. Affiliated with French social security system or beneficiary from such system

Exclusion criteria 9

1. Presence of DSA at the time of renal transplantation or at 3 months post-transplant.
2. Positive HIV serology.
3. History of other solid organ transplantation (other than kidney)
4. Primary non-function (still needing for dialysis at 3 months post-transplant).
5. Ongoing participation in another clinical trial
6. Any clinical condition that the investigator considers incompatible with the safe conduct of the trial (in particular active infection, active cardiovascular complication, active neoplastic disease)
7. Contraindication to Belatacept (referring to the SmPC).
8. Pregnant or breastfeeding woman
9. Person under guardianship or curatorship, under court protection

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The feasibility of reintroduction of CNIs will be defined by preserved renal function and good tolerance at 6months post reintroduction (15months follow-up) in patients who have been switched back to CNI at M9.Renal function will be defined as preserved if creatinine clearance (according to CKD-EPI) does not decrease by more than 25% after discontinuation of belatacept.Good tolerance of the reinstatement of CNIs will be defined by absence of complications leading to discontinuation of treatment.

Secondary endpoints 6

1. Longitudinal monitoring of renal function (M0, M3, M6, M9), collection of rejection events.
2. Collection of infectious episodes and neoplasia.
3. Number of care resources consumed in relation to treatments (drugs, hospitalisation, transport, consultations, biological procedures, medical procedures, possible home help) and associated costs over 15 months of follow-up, and collection of cost data from the literature for comparison.
4. Measurement of quality of life scores (generic EQ-5D scale) every 3 months for 15 months and collection of quality of life data from the literature for comparison.
5. Differential analysis (before and after belatacept discontinuation) of cell populations by standardised flow cytometry combined with unbiased analysis.
6. Differential analysis (before and after belatacept discontinuation) of the anti-CMV cellular immune response.

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Centre Hospitalier Universitaire De Nantes

Sponsor organisation

Centre Hospitalier Universitaire De Nantes

Address

5 Allee De L Ile Gloriette, Cs 69301 Cs 69301

City

Nantes Cedex 1

Postcode

44093

Country

France

Scientific contact point

Organisation

Centre Hospitalier Universitaire De Nantes

Contact name

Simon VILLE

Public contact point

Organisation

Centre Hospitalier Universitaire De Nantes

Contact name

Simon VILLE

Locations

1 EU/EEA country · 1 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 10 files

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

Application history

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