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| ID | Type | Description | Link |
|---|---|---|---|
| 2023-504594-20-00 | Other Identifier | EuCT number |
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| Name | Class |
|---|---|
| Vaccine Research Institute (VRI), France | UNKNOWN |
| EnnoDc (previously known as LinKinVax) | UNKNOWN |
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The goal of this clinical trial, on healthy volunteers, is to learn more about safety and reactogenicity of the CD40.RBDv vaccine.
The main questions that will be studied are :
Phase 1/2a randomized, multicentre trial with four cohorts of two arms in two parts.
Part 1:
Cohort 1: Low dose (LD) CD40.RBDv vaccine non adjuvanted or mRNA vaccine (5:1 ratio)
Cohort 2: LD CD40.RBDv vaccine adjuvanted or mRNA vaccine (5:1 ratio)
Cohort 3: High dose (HD) CD40.RBDv vaccine non adjuvanted or mRNA vaccine (5:1 ratio)
Cohort 4: SC injection of HD CD40.RBDv vaccine adjuvanted or mRNA vaccine (5:1 ratio)
A substancial amendment (January 2025) has removed the randomisation to mRNA vaccine from the study design
Go-criterion for opening enrolment within cohorts are detailed into the protocol.
Part 2 at Month 3 :
Group 1: Volunteers who received mRNA vaccine in Part 1 will not receive any vaccine
Group 2: Volunteers who received a first dose of CD40.RBDv vaccine (adjuvanted or not) in Part 1 but randomized (1:1) to receive no further dose of vaccine in Part 2.
Group 3: Volunteers who received a first dose of CD40.RBDv vaccine (adjuvanted or not) in Part 1 and randomized (1:1) to receive an additional dose of CD40.RBDv vaccine (adjuvanted or not)
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 1-CD40.RBDv non adjuvanted or mRNA vaccine (5:1 ratio) | Experimental | Low dose (LD) CD40.RBDv vaccine non adjuvanted or mRNA vaccine (5:1 ratio). If randomized to receive LD CD40.RBDv vaccine non adjuvanted in part 1, the subject will be randomised a second time to receive LD CD40.RBDv vaccine non adjuvanted (1:1) in part 2. Following a substancial amendment the randomization to mRNA vaccine has been removed from study design |
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| 2-CD40.RBDv vaccine adjuvanted or mRNA vaccine (5:1 ratio) | Experimental | LD CD40.RBDv vaccine adjuvanted or mRNA vaccine (5:1 ratio) If randomized to receive LD CD40.RBDv vaccine adjuvanted in part 1, the subject will be randomised a second time to receive LD CD40.RBDv vaccine adjuvanted (1:1) in part 2. Following a substancial amendment the randomization to mRNA vaccine has been removed from study design |
|
| 3-High dose (HD) CD40.RBDv vaccine non adjuvanted or mRNA vaccine (5:1 ratio) | Experimental | High dose (HD) CD40.RBDv vaccine non adjuvanted or mRNA vaccine (5:1 ratio) If randomized to receive HD CD40.RBDv vaccine non adjuvanted in part 1, the subject will be randomised a second time to receive HD CD40.RBDv vaccine non adjuvanted (1:1) in part 2. Following a substancial amendment the randomization to mRNA vaccine has been removed from study design |
|
| 4-High dose (HD) CD40.RBDv vaccine adjuvanted or mRNA vaccine | Experimental |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| CD40.RBDv vaccin (SARS-Cov2 Vaccin) | Drug | 1 or 2 injection(s) of CD40.RBDv vaccine (or mRNA vaccine 1 injection (5:1)) |
|
| Measure | Description | Time Frame |
|---|---|---|
| Proportion of participants without any grade 3 or 4 biological or clinical solicited local/systemic or unsolicited AEs between D1 and Month 3 after each IMP/vaccine administration and considered to be related or possibly related to IMP administration | These proportions of participants will be described with its 95% two-sided confidence interval. | Month 3 |
| Neutralization antibodies titers (anti-RBD) against the original strain D614G and the relevant strain circulating at time of the study Month 1 | The primary immunogenecity endpoint is the neutralization antibodies titers (anti -RBD) against the original strain D614G and the relevant strain circulating at time of the study Month 1 after each dose The geometric mean titers (GMTs) with 95% confidence intervals (CIs) will be calculated at baseline and at Month 1 after each dose. | Month 1 |
| Measure | Description | Time Frame |
|---|---|---|
| Number of volunteers with solicited local and systemic Adverse Reactions (ARs) | The original verbatim terms used by investigators to identify adverse events in the eCRF will be mapped to preferred terms using the MedDRA dictionary. The adverse events will then be grouped by MedDRA preferred terms into frequency tables according to system organ class. All reported adverse events, as well as adverse events judged by the investigator as at least possibly related to study vaccine, will be summarized according to system organ class and preferred term within system organ class and by interval of study observation. When an adverse event occurs more than once for a participants, the maximal severity and strongest relationship to the vaccine group will be chosen. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Yves Levy, MD | Contact | +33149814442 | yves.levy@aphp.fr |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Hopital Henri Mondor | Recruiting | Créteil | 94000 | France |
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This is an open label study. Immunological assessors, only, will remain blinded.
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HD CD40.RBDv vaccine adjuvanted or mRNA vaccine (5:1 ratio) If randomized to receive HD CD40.RBDv vaccine adjuvanted in part 1, the subject will be randomised a second time to receive HD CD40.RBDv vaccine adjuvanted (1:1) in part 2.
Following a substancial amendment the randomization to mRNA vaccine has been removed from study design
|
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| Day 8 |
| Number of volunteers with Adverse Events (AEs) other than solicited adverse events | The original verbatim terms used by investigators to identify adverse events in the eCRF will be mapped to preferred terms using the MedDRA dictionary. The adverse events will then be grouped by MedDRA preferred terms into frequency tables according to system organ class. All reported adverse events, as well as adverse events judged by the investigator as at least possibly related to study vaccine, will be summarized according to system organ class and preferred term within system organ class and by interval of study observation. When an adverse event occurs more than once for a participants, the maximal severity and strongest relationship to the vaccine group will be chosen. | Day 1 to Months 3 after each dose |
| Number of volunteers with Serious Adverse Events (SAEs), grade 3 and grade 4 | The original verbatim terms used by investigators to identify adverse events in the eCRF will be mapped to preferred terms using the MedDRA dictionary. The adverse events will then be grouped by MedDRA preferred terms into frequency tables according to system organ class. All reported adverse events, as well as adverse events judged by the investigator as at least possibly related to study vaccine, will be summarized according to system organ class and preferred term within system organ class and by interval of study observation. When an adverse event occurs more than once for a participants, the maximal severity and strongest relationship to the vaccine group will be chosen. | Day 1 to Months 3 after each dose |
| Number of volunteers with events leading to discontinuation of the vaccine regimen | The original verbatim terms used by investigators to identify adverse events in the eCRF will be mapped to preferred terms using the MedDRA dictionary. The adverse events will then be grouped by MedDRA preferred terms into frequency tables according to system organ class. All reported adverse events, as well as adverse events judged by the investigator as at least possibly related to study vaccine, will be summarized according to system organ class and preferred term within system organ class and by interval of study observation. When an adverse event occurs more than once for a participants, the maximal severity and strongest relationship to the vaccine group will be chosen. Separate summaries will be produced for the following categories:
| Through study completion, an average of 15 months |
| Seroconversion rate defined by an increase of 4 folds between day1 (baseline before vaccination) and Month 1 in anti-RBD IgG binding titers | • The seroconversion rate defined by an increase of 4 folds between day1 (baseline before vaccination) and Month 1 in anti-RBD IgG binding titers will be described with its 95% two-sided confidence interval. | Month 1 |
| To assess the cross-neutralization against the most relevant VOCs at the time of the study | • To assess the cross-neutralization against the most relevant VOCs, The geometric mean titers (GMTs) with 95% confidence intervals (CIs) will be calculated at each timepoint. | Day 1 (before each vaccination) day 8, day 14 and M1 after each vaccination, M3, M6, M12 (ie. 12 months after 1st dose and 9 months after 2nd dose) and M15 (ie. 15 months after 1st dose and 12 months after 2nd dose) |
| To analyze the correlation between the magnitude of CD4+ specific T cell responses and levels of IgG specific responses | • Correlation between the magnitude of CD4+ specific T cell responses and levels of igG specific responses will be estimated at each timepoint using Pearson or Spearman correlation coefficients, depending on variables distribution. | Day 1 (before each vaccination) day 14 after each vaccination, M3, M6, M12 (ie. 12 months after 1st dose and 9 months after 2nd dose) and M15 (ie. 15 months after 1st dose and 12 months after 2nd dose) |
| To characterize the vaccine efficacy by evaluating the number of COVID-19 infections (PCR+) and severity (based on CDC definition) in participants throughout the study follow-up. | • Number of COVID-19 infections (PCR+) and severity (based on CDC definition) throughout the study follow-up. | Through study completion, an average of 15 months |
| To evaluate the Cytokine expression patterns of CD4 and CD8 T cells as measured by intracellular cytokine staining assay | • Cytokine expression patterns of CD4 and CD8 T cells, measured by intracellular cytokine staining assay, will be described at each timepoint. | Day 1 (before each vaccination) day 14 after each vaccination, M3, M6, M12 (ie. 12 months after 1st dose and 9 months after 2nd dose) and M15 (ie. 15 months after 1st dose and 12 months after 2nd dose) |
| Percentages of T cells producing at least one cytokine after in vitro stimulation | • Recall memory T cell responses, following in vitro restimulation (Epimax technology) on residual samples and depending on the results obtained in the analysis of intracellular cytokine staining assay, will be described. | Through study completion, an average of 15 months |
| Concentration (pg/mL) of cytokines produced by stimulated PBMC | • Cytokines produced by stimulated PBMC (Luminex assay) on samples evaluated by Epimax technology will be described. | Through study completion, an average of 15 months |
| Hôpital Cochin | Recruiting | Paris | 75014 | France |
|
| ID | Term |
|---|---|
| D000086382 | COVID-19 |
| ID | Term |
|---|---|
| D011024 | Pneumonia, Viral |
| D011014 | Pneumonia |
| D012141 | Respiratory Tract Infections |
| D007239 | Infections |
| D014777 | Virus Diseases |
| D018352 | Coronavirus Infections |
| D003333 | Coronaviridae Infections |
| D030341 | Nidovirales Infections |
| D012327 | RNA Virus Infections |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
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| ID | Term |
|---|---|
| C000722934 | CVnCoV COVID-19 vaccine |
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