Association of T Gamma Delta-CD16+ Cells and Anti-CMV Immunoglobulins in the Prevention of CMV Infection

NCT04934527 | Completed Phase 2

• 1 other identifier: CHUBX 2020/26
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 1

Brief Summary

CMV infection in transplantation remains the most frequent infectious complication causing increased morbidity and mortality. International recommendations advocate prevention of this infection by instituting direct antiviral treatment or monitoring viral replication by PCR with the start of curative antiviral treatment when the DNAemia is positive. 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.

Conditions

Kidney Transplantation; CMV Infection

Keywords

kidney transplantation; CMV Infection; Tgamma-delta Vdelta2 negativ lymphocyte; Cytotect

Outcome Measures

Primary Outcomes (1)

• Occurrence of CMV infection in the year following transplantation.

  Occurrence of CMV infection will assess thanks to LT gdVd2 level 12 months after inclusion day.

  12 months after inclusion day

Secondary Outcomes (4)

• Measure the absence of CMV infection in the year following transplantation.

  12 months after inclusion day

• Determined the percentage of NK cells in peripheral blood expressing CD16, which may be associated with protection from CMV infection after anti-CMV Ig infusion.

  12 months after inclusion day

• Assessing kinetics of LTgds and NK cells in patients receiving Ig-anti CMV.

  12 months after inclusion day

• Assessing the incidence of CMV infection occurring in the first year post-transplant in R+ patients on pre-emptive follow-up receiving CMV Ig.

  12 months after inclusion day

Study Arms (1)

Experimental

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.

Drug: Cytotect

Interventions

Cytotect DRUG

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.

Experimental

Eligibility Criteria

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

You may qualify if:

• Male or female over 18 years of age,
• Patient candidate for a first transplant or a re-transplantation, registered on the national waiting list of the Biomedicine Agency.
• CMV seropositive patients (positive serology at pre-transplant assessment or at D0 of transplantation)
• Patients receiving a kidney transplant from a deceased or living donor.
• Patient affiliated to or benefiting from a social security scheme.

You may not qualify if:

• CMV negative (R-) patients.
• Historical or current Graft Incompatible Rate (GIR) \> 85%.
• Patients who have received anti-CMV therapy within 28 days prior to transplantation.
• 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
• Patients who have received or are receiving a solid organ transplant other than a kidney transplant.
• 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),
• Known allergy, contraindication or intolerance to specific anti-HCV Ig, mycophenolic acid, basiliximab, corticosteroids, cyclosporine A, tacrolimus or to excipients of these products.
• Any form of substance abuse, psychiatric disorder or condition that, in the opinion of the investigator, may complicate communication during follow-up.
• Foreseeable inability to comply with planned protocol visits/reviews.
• Patients under guardianship/guardianship
• Pregnant or breastfeeding woman
• Patients with a contraindication to receiving Cytotect

Sponsors & Collaborators

• University Hospital, Bordeaux: lead
• Biotest: collaborator

Study Sites (1)

Hopital Pellegrin

Bordeaux, 33000, France

Location

MeSH Terms

Conditions

Cytomegalovirus Infections

Interventions

cytomegalovirus-specific hyperimmune globulin

Condition Hierarchy (Ancestors)

Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 16, 2021
• First Posted: June 22, 2021
• Study Start: November 17, 2021
• Primary Completion: December 19, 2024
• Study Completion: December 19, 2024
• Last Updated: December 24, 2024

Record last verified: 2024-12

Locations

FR (1)