Belatacept as a Replacement for CNIs 3 to 12 Months Post-transplantation in Patients With Early Graft Dysfunction

NCT05562869 | Recruiting Phase 3 DMC

• 1 other identifier: RC21_0587
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

Calcineurin inhibitors (CNI) remain the standard treatment in renal transplantation to prevent rejection. Currently the main limitation of kidney transplantation is the occurrence of chronic graft dysfunction due to the CNI nephrotoxicity. Thus, strategies to minimize or stop CNI have been developed as belatacept, a fusion protein (CTLA4-Ig) blocking the ligand of the main CD28 costimulatory molecule. In the original phase III trial, used de novo in combination with MMF (without CNI) belatacept allowed to obtain a better renal function as soon as 1 year and a better graft and patient survival after 7 years. Despite these excellent results, belatacept has not become the gold standard due to a higher incidence of early rejection. In addition, belatacept is not covered by the french social security policy, because benefits are considered insufficient with respect to the cost. Patients with poor early graft function are a preferred indication of belatacept. It is then used instead of CNI at 3 months post-transplant allowing to improve kidney function without over-risk of rejection. Currently after conversion, belatacept is maintained indefinitely due to the supposed CNI chronic nephrotoxicity. However this one is more and more questionable. Thus, the investigators assume that in patients with poor function at 3 months posttransplantation the belatacept's benefit could be obtained by a transient replacement of CNI by belatacept from 3 to 12 months post-transplantation. It is the feasibility of this strategy and its medico-economic impact that the investigators wish to study.

Conditions

Chronic Kidney Failure

Outcome Measures

Primary Outcomes (1)

• Feasibility of a transient replacement of CNIs by belatacept in renal transplant patients with early graft dysfunction. Creatinine clearance did not decrease by more than 25% from the cessation of belatacept 6 months after reintroduction of CNI.

  Feasibility was defined by preserved renal function and good tolerance 6 months after reintroduction of CNI. Renal function was defined as preserved if creatinine clearance (according to Chronic Kidney Disease - Epidemiology Collaboration (CKD-EPI)) did not decrease by more than 25% from the cessation of belatacept. The good tolerance of CNI was defined by the absence of complications leading to the cessation of treatment.

  Month 15

Secondary Outcomes (6)

• Evaluate the effectiveness of belatacept treatment on renal function (creatinine clairance) and to prevent rejection. (Number of rejection épisodes)

  Day 0, Month 3, Month 6, Month 9

• Evaluate the tolerance of treatments (belatacept during phase 1 and CNI during phase 2). Number of adverse events.

  Month 3, Month 6, Month 9, Month 12, Month 15

• Estimate the cost of care (from 3 months to 18 months post-transplant) and compare with the cost of a theoretical arm benefiting from belatacept continuously and a theoretical arm benefiting from CNIs continuously.

  Month 3, Month 6, Month 9, Month 12, Month 15

• Evaluate the evolution of the quality of life during the 15 months of follow-up and compare it to a theoretical arm benefiting from belatacept continuously, and a theoretical arm benefiting from CNIs continuously: generic EuroQol-5D scale

  Month 3, Month 6, Month 9, Month 12, Month 15

• Evaluate the differential impact of SNFs and belatacept on cell populations of the immune system

  Month 3, Month 6, Month 9, Month 12, Month 15

Study Arms (1)

Experimental: transient belatacept

EXPERIMENTAL

IV, 5mg/Kg days 1, 15, 30, 45 and 60 then every months

Drug: Belatacept 250 Milligram Intravenous Powder for Solution

Interventions

Belatacept 250 Milligram Intravenous Powder for Solution DRUG

Phase 1 (from 3 to 12 months post transplantation): conversion to belatacept (IV, 5mg/Kg days 1, 15,30, 45, 60 then every months) and CNI withdrawal. Phase 2 (from 12 to 18 months post transplantation) : belatacept arrest and CNI resumption (tacrolimus target 6 ng/ml)

Experimental: transient belatacept

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• adult older than 18 years old.
• transplantation of a deceased or living donor kidney (non-human leukocyte antigen(HLA)-identical) with blood type (ABO) compatibility
• no contraindication to the protocol graft biopsy (10 weeks post transplant)
• treatment by CNI / MPA +/- prednisone
• renal function estimated by creatinine clearance according to CKD-EPI \<30 ml / min / 1.73m2.
• having no difficulty in understanding and communicating with the investigator and his representatives.
• Agreeing to give informed written consent
• benefiting from a Social Security policy.
• results of the 10-week post-transplant renal biopsy finding no rejection or BK virus (member of the polyomavirus family) nephropathy, no recurrence, no thrombotic microangiopathy, no cortical necrosis.
• Seropositivity for Epstein-Barr virus (EBV)
• negative pregnancy test and agreement on the use of effective contraception throughout the study

You may not qualify if:

• Presence of Donor Specific Antibody during kidney transplant or appeared at 3 months post-transplantation.
• seropositivity for HIV
• another history of other solid organ transplants (outside the kidney)
• primary non-function (persistence of a need for dialysis at 3 months post-transplantation)
• participation in progress to another interventional clinical study
• any clinical condition that the investigator considers incompatible with the course of the study.
• contraindication to belatacept and Tacrolimus
• Pregnant or breastfeeding woman
• Inability of the patient to comply with study procedures
• Person placed under guardianship or curatorship, under safeguard of justice

Sponsors & Collaborators

• Nantes University Hospital: lead

Study Sites (1)

CHU Nantes

Nantes, Loire Atlantique, 44093, France

RECRUITING

Related Publications (2)

• Le Meur Y, Aulagnon F, Bertrand D, Heng AE, Lavaud S, Caillard S, Longuet H, Sberro-Soussan R, Doucet L, Grall A, Legendre C. Effect of an Early Switch to Belatacept Among Calcineurin Inhibitor-Intolerant Graft Recipients of Kidneys From Extended-Criteria Donors. Am J Transplant. 2016 Jul;16(7):2181-6. doi: 10.1111/ajt.13698. Epub 2016 Mar 2.

  PMID: 26718625 RESULT

• Vincenti F. Belatacept and Long-Term Outcomes in Kidney Transplantation. N Engl J Med. 2016 Jun 30;374(26):2600-1. doi: 10.1056/NEJMc1602859. No abstract available.

  PMID: 27355541 RESULT

MeSH Terms

Conditions

Kidney Failure, Chronic

Interventions

Solutions

Condition Hierarchy (Ancestors)

Renal Insufficiency, Chronic; Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Pharmaceutical Preparations

Central Study Contacts

Simon VILLE, PH

CONTACT

0240087453; simon.ville@chu-nantes.fr

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 28, 2022
• First Posted: October 3, 2022
• Study Start: May 3, 2024
• Primary Completion (Estimated): May 3, 2027
• Study Completion (Estimated): May 3, 2027
• Last Updated: May 9, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)