Association of T Gamma Delta-CD16+ Cells and Anti-CMV Immunoglobulins in the Prevention of CMV Infection
NCT ID: NCT04934527
Last Updated: 2024-12-24
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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COMPLETED
PHASE2
42 participants
INTERVENTIONAL
2021-11-17
2024-12-19
Brief Summary
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The risk of CMV infection varies according to the serostatus of the donor (D) and recipient (R) at the time of transplantation. In the absence of prophylaxis, CMV infection occurs in 60-80% of D+R-, 50-60% of D+R+ and 25-50% of D-R+.
The humoral anti-CMV response is represented by the production of antibodies to envelope proteins (gB and gH) and to molecules involved in viral attachment and entry into target cells. However, the majority of CMV-specific antibodies do not have antiviral neutralising activity. The investigators have identified a new player in the specific anti-CMV response expressing the Fc RIIIa receptor (CD16), that interacts with anti-CMV immunoglobulins (Ig): the Tgamma-delta V delta 2-negative lymphocyte (LTgdVd2neg). This lymphocyte subpopulation shows persistent expansion in the peripheral blood of kidney transplant patients with CMV infection. These cells express an effector-memory phenotype (CD45RA+/CD27-). This expansion is associated with resolution of infection in patients. The investigators have shown that CD16 is specifically and constitutively expressed on the surface of CMV-induced LTgdVd2neg in healthy volunteers and kidney transplant patients. The investigators have observed that one of the antiviral activities of anti-CMV IgG lies in its binding to the Fc RIIIa receptor (CD16) on the surface of LTgdVd2neg. The anti-CMV IgGs capturing virions thus activate CD16+ LTgdVd2neg with production of IFN interferon which in turn is responsible for inhibition of CMV viral multiplication.
Anti-CMV IgG is a recommended therapeutic option, with a marketing authorisation for the prevention of CMV infection in kidney transplantation in Europe and a Temporary Authorisation for Use in France.
Thus, R+ patients expressing a significant level of LTgdVd2neg CD16+ at D0 of transplantation could be protected against CMV, in the absence of direct antiviral treatment by the addition of anti-CMV Ig.
Detailed Description
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Systematic and frequent monitoring for the occurrence of CMV DNAemia will be performed throughout this study. Real-time quantitative CMV PCR on whole blood (WHO standard provided by the National Institute for Biological Standards and Control) will be performed every week until M3, then every fortnight until 4 months and then at months 5, 6, 9 and 12. CMV infection will be defined by the presence of a positive CMV PCR in whole blood. Universal prophylaxis with VALGANCICLOVIR will be prohibited.
Pre-emptive antiviral treatment will be initiated in case of CMV infection, if the DNAemia reaches the threshold chosen by the centre, which is 5000 IU/ml. The choice of treatment will be left to the discretion of the clinician: IV ganciclovir (5mg/Kg/12H) or valganciclovir (900mg/12H) until viral replication is negated. Doses will be adjusted for kidney function using the Cockcroft-Gault formula, in accordance with laboratory recommendations.
Conditions
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Keywords
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Study Design
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NA
SINGLE_GROUP
TREATMENT
NONE
Study Groups
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Experimental
Patients with positive CMV serology at transplantation will receive 6 infusions of Cytotect every 15 days with the first injection on the day of transplantation. CMV infection will be monitored by quantitative PCR on whole blood every week during 3 months and then every 2 weeks until 4 months and then at months 5 and 6, 9 and 12.
Cytotect
The inclusion visit is conducted by the investigating nephrologist and the patient will receive their first infusion of anti-CMV Ig.
Patients with positive CMV serology at transplantation will receive 6 infusions of 100 units per kilogram of body weight every 15 days with the first injection on the day of transplantation, i.e. at visits D0, S2, S4, S6, S8 and S10. CMV infection will be monitored by quantitative PCR on whole blood every week during 3 months and then every 2 weeks until 4 months and then at months 5 and 6, 9 and 12.
Interventions
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Cytotect
The inclusion visit is conducted by the investigating nephrologist and the patient will receive their first infusion of anti-CMV Ig.
Patients with positive CMV serology at transplantation will receive 6 infusions of 100 units per kilogram of body weight every 15 days with the first injection on the day of transplantation, i.e. at visits D0, S2, S4, S6, S8 and S10. CMV infection will be monitored by quantitative PCR on whole blood every week during 3 months and then every 2 weeks until 4 months and then at months 5 and 6, 9 and 12.
Eligibility Criteria
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Inclusion Criteria
2. Patient candidate for a first transplant or a re-transplantation, registered on the national waiting list of the Biomedicine Agency.
3. CMV seropositive patients (positive serology at pre-transplant assessment or at D0 of transplantation)
4. Patients receiving a kidney transplant from a deceased or living donor.
5. Women of childbearing age with a negative pregnancy test at inclusion and agreeing to the use of effective contraception throughout the study period and two months after the end of the follow-up period.
6. Patient affiliated to or benefiting from a social security scheme.
Exclusion Criteria
2. Historical or current Graft Incompatible Rate (GIR) \> 85%.
3. Patients who have received anti-CMV therapy within 28 days prior to transplantation.
4. Indication for induction therapy with anti-lymphocyte globulin, rituximab, polyvalent intravenous immunoglobulin or any other immunomodulatory molecule, and mTOR inhibitor therapy, which have been described to be associated with a decreased incidence of CMV infection
5. Patients who have received or are receiving a solid organ transplant other than a kidney transplant.
6. Patients known to be seropositive for human immunodeficiency virus (HIV), hepatitis B virus (HBV; HbS Ag positive) or hepatitis C virus (HCV; HCV antibody positive),
7. Known allergy, contraindication or intolerance to specific anti-HCV Ig, mycophenolic acid, basiliximab, corticosteroids, cyclosporine A, tacrolimus or to excipients of these products.
8. Any form of substance abuse, psychiatric disorder or condition that, in the opinion of the investigator, may complicate communication during follow-up.
9. Foreseeable inability to comply with planned protocol visits/reviews.
10. Patients under guardianship/guardianship
11. Pregnant or breastfeeding woman
12. Patients with a contraindication to receiving Cytotect
18 Years
ALL
No
Sponsors
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Biotest
INDUSTRY
University Hospital, Bordeaux
OTHER
Responsible Party
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Locations
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Hopital Pellegrin
Bordeaux, , France
Countries
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Other Identifiers
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CHUBX 2020/26
Identifier Type: -
Identifier Source: org_study_id