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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Kidney Transplant Infection
• Intervention / Treatment: Drug: Belatacept

Detailed 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.

• Study Type: Observational
• Enrollment (Estimated): 28

Contacts and Locations

Study Locations

• France
  • Rouen, France, 76031
    • University Rouen Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

Cohort of kidney transplant recipients seropositive for CMV

Description

Inclusion Criteria:

• Renal transplant follow-up at Rouen University Hospital
• Clinico-biological intolerance to anticalcineurins defined by GFR < 25 mL/min and/or water and sodium overload justifying the prescription of loop diuretics and/or post-transplant diabetes and/or resistant hypertension (requiring at least 3 treatments antihypertensives including a thiazide diuretic to reach an objective ≤ 140/90 mmHg).
• Having performed a graft biopsy < 3 months old finding lesions of fibrous endarteritis ≥ 2 or arteriolar hyalinosis ≥ 2
• Having undergone collegial validation for the initiation of treatment with belatacept 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 Criteria:

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

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To study the quantitative changes in anti-CMV T-lymphocyte immunity to the IE-1 antigen within 6 months of a switch from anticalcineurin treatment to belatacept in a cohort of kidney transplant recipients seropositive for CMV	Number of interferon gamma-producing T lymphocytes in response to the IE-1 antigen determined by ELISPOT at M0, M3 and M6.	6 months

Collaborators and Investigators

• Sponsor: University Hospital, Rouen

Study record dates

Study Major Dates

• Study Start (Actual): November 14, 2023
• Primary Completion (Actual): May 13, 2026
• Study Completion (Estimated): May 31, 2027

Study Registration Dates

• First Submitted: January 23, 2023
• First Submitted That Met QC Criteria: January 23, 2023
• First Posted (Actual): February 1, 2023

Study Record Updates

• Last Update Posted (Actual): May 22, 2026
• Last Update Submitted That Met QC Criteria: May 18, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immunoconjugates; Amino Acids, Peptides, and Proteins; Proteins; Antibodies; Immunoglobulins; Blood Proteins; Serum Globulins; Globulins; Abatacept
• Other Study ID Numbers: 2020/0432/OB

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No