Kidney TransplantationPhase 2SYNTAGMENCT04934527
Association of T Gamma Delta-CD16+ Cells and Anti-CMV Immunoglobulins in the Prevention of CMV Infection
A Phase 2 study testing Cytotect in people with Kidney Transplantation and CMV Infection, run by University Hospital, Bordeaux at 1 site in France.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Kidney Transplantation, CMV Infection
- What is being tested?
- Cytotect
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 42 participants
- Where
- 1 siteFrance
- Study dates
- 17 Nov 2021to 19 Dec 2024
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
- 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.
- Patient affiliated to or benefiting from a social security scheme.
Who cannot join
- 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),
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- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Evaluating a Therapeutic Association Between CMV-specific Immunoglobulin Infusion and Pre-transplant CD16-expressing Gamma Delta Vdelta 2 Negative T-cells in CMV-positive Patients for Preventive Treatment of CMV Infection in Renal Transplantation
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+.
Read more
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.
Read the detailed description
SYNTAGME is a single-centre prospective phase II pilot study. Transplant candidates from our centre who meet the inclusion criteria without exclusion criteria will be offered this study. Anti-CMV Ig infusions will be performed the day of transplantation at 100 units per kilo of body weight and then every 15 days for a total of 6 infusions.
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
- Kidney Transplantation, CMV Infection
- Being tested
- Cytotect
- Keywords
- kidney transplantation, CMV Infection, Tgamma-delta Vdelta2 negativ lymphocyte, Cytotect
- Medical subject headings
- Cytomegalovirus Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CytotectDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Cytotect |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 12 months after inclusion day
Secondary outcomes (4)
Measure the absence of CMV infection in the year following transplantation.
Determining an LTgdCD16+ predictive threshold of an effective therapeutic response to anti-CMV Ig in R+ patients undergoing preventive therapy for post-transplant CMV infection. Thanks to LTgdCD16+ immunophenotyping
Measured: 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.
Thanks to NK cells immunophenotyping and CMV PCR
Measured: 12 months after inclusion day
Assessing kinetics of LTgds and NK cells in patients receiving Ig-anti CMV.
Described phenotypic kinetics of LTgds and NK cells, thanks to NK cells and LTgds immunophenotyping.
Measured: 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.
This outcome will be evaluated by comparing between CMV infection occurring in the first year post-transplant in R+ patients on pre-emptive follow-up receiving CMV Ig and an historical group of R+ patients on the same pre-emptive follow-up but not receiving CMV Ig.
Measured: 12 months after inclusion day
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jun 2021
- Study start17 Nov 2021
- Primary completion19 Dec 2024
- Study completion19 Dec 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Kidney TransplantationStudies of the same condition, open and under way.
- More trials run by University Hospital, BordeauxThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 42 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital, Bordeaux
- Sponsor type
- University, hospital or other
- Collaborators
- Biotest
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04934527
- Sponsor's protocol ID
- CHUBX 2020/26
- Other IDs
- 2020-005582-13
- Acronym
- SYNTAGME
- Status last verified
- Dec 2024
- First submitted
- 16 Apr 2021
- Last updated
- 12 May 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluating a Therapeutic Association Between CMV-specific Immunoglobulin Infusion and Pre-transplant CD16-expressing Gamma Delta Vdelta 2 Negative T-cells in CMV-positive Patients for Preventive Treatment of CMV Infection in Renal Transplantation
- ClinicalTrials.gov ID
- NCT04934527
- Acronym / sponsor ID
- SYNTAGME / CHUBX 2020/26
- Conditions
- Kidney Transplantation, CMV Infection
- Keywords
- kidney transplantation, CMV Infection, Tgamma-delta Vdelta2 negativ lymphocyte, Cytotect
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 42 participants (actual)
- Lead sponsor
- University Hospital, BordeauxUniversity, hospital or other
- Collaborators
- Biotest
- Study start
- 17 Nov 2021 (actual)
- Primary completion
- 19 Dec 2024 (actual)
- Study completion
- 19 Dec 2024 (actual)
- First posted
- 22 Jun 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
SYNTAGME is a single-centre prospective phase II pilot study. Transplant candidates from our centre who meet the inclusion criteria without exclusion criteria will be offered this study. Anti-CMV Ig infusions will be performed the day of transplantation at 100 units per kilo of body weight and then every 15 days for a total of 6 infusions.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Experimental | Experimental | Drug: CytotectPatients 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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.
- 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.
Key exclusion criteria (12 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CytotectThe 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. | Drug | Experimental |
Primary outcome
Occurrence of CMV infection in the year following transplantation.
Time frame: 12 months after inclusion day
Occurrence of CMV infection will assess thanks to LT gdVd2 level 12 months after inclusion day.
4 secondary outcomes
Measure the absence of CMV infection in the year following transplantation.
Time frame: 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.
Time frame: 12 months after inclusion day
Assessing kinetics of LTgds and NK cells in patients receiving Ig-anti CMV.
Time frame: 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.
Time frame: 12 months after inclusion day
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 May 2026.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Cytotect in people with Kidney Transplantation and CMV Infection, run by University Hospital, Bordeaux at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 12 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Occurrence of CMV infection in the year following transplantation. (time frame: 12 months after inclusion day). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 May 2026.