Evolution of CMV Antiviral T-cell Immunity Over the Next Six Months Initiation of Treatment With Belatacept.

Phase

N/A

Condition

N/A

Treatment

Belatacept

Clinical Study ID

NCT05708534

2020/0432/OB

Ages > 18
All Genders

Study Summary

Belatacept inhibits T cell activation by blocking the costimulatory signal. In kidney transplantation, it limits the use of anticalcineurins while ensuring a satisfactory level of immunosuppression.

Eligibility Criteria

Inclusion

Inclusion Criteria:

Renal transplant follow-up at Rouen University Hospital
Clinico-biological intolerance to anticalcineurins defined by GFR < 25 mL/min and/orwater and sodium overload justifying the prescription of loop diuretics and/orpost-transplant diabetes and/or resistant hypertension (requiring at least 3treatments antihypertensives including a thiazide diuretic to reach an objective ≤ 140/90 mmHg).
Having performed a graft biopsy < 3 months old finding lesions of fibrousendarteritis ≥ 2 or arteriolar hyalinosis ≥ 2
Having undergone collegial validation for the initiation of treatment withbelatacept combined with 3-month anti-CMV prophylaxis with oral Valganciclovir.
Absence of contraindication to belatacept
Patient who has never received belatacept
Having a positive CMV serological status

Exclusion

Exclusion Criteria:

Patient with symptomatic infection
Pregnant or parturient or breast-feeding woman or lack of proven effectivecontraception
Person deprived of liberty by an administrative or judicial decision or personplaced under legal safeguard / sub-tutorship or curatorship
Patient participating in another therapeutic trial or having participated in anothertrial within 1 month

Study Design

Belatacept

November 14, 2023

December 31, 2026

Study Description

The Rouen strategy consists of offering belatacept to kidney transplant patients with clinical and laboratory intolerance to anticalcineurins with histological toxicity. This strategy improves or stabilizes the graft's glomerular filtration rate (GFR) in patients with poor renal function. However, a high incidence of opportunistic infections (12.1%), mainly due to CMV, has been observed in elderly patients with a GFR less than 25 ml/min. Two-thirds of CMV infections occur within one year of belatacept initiation and can be particularly severe and life-threatening for both patients and the graft. These results led to the implementation of systematic 3-month antiviral prophylaxis with valganciclovir upon the introduction of belatacept.

CMV immune control depends primarily on virus-specific effector/memory T cells. The impact of costimulation blockade on certain persistent viral infections has been studied experimentally. It is significant when the infection is established, but appears variable in the chronic phase depending on the virus type. Viral load appears to be a determining factor in the size of the antiviral T cell repertoire and its functions (lymphocyte exhaustion). In the case of CMV, the consequences of blocking costimulation on the specific effector/memory T cell pool are unknown.

The hypothesis of this project is that, under belatacept, the influence of CMV on the immune system induces quantitative changes in the effector/memory T cell pool (inflation or, conversely, contraction) and/or functional exhaustion, likely leading to a loss of control of viral replication. This study therefore proposes to investigate the evolution of the anti-CMV response in terms of amplitude, specificity, and functionality, after the introduction of belatacept in CMV-positive patients.

Connect with a study center

University Rouen Hospital
Rouen, 76031
France
Active - Recruiting

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