E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Prevention of symptomatic dengue disease |
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E.1.1.1 | Medical condition in easily understood language |
Prevention of dengue disease with clinical symptoms |
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E.1.1.2 | Therapeutic area | Diseases [C] - Virus Diseases [C02] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Efficacy of dengue vaccine after three injections in preventing symptomatic virologically-confirmed dengue cases, regardless of the severity, due to any of the four serotypes |
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E.2.2 | Secondary objectives of the trial |
Efficacy throughout the study in all subjects:
- Symptomatic virologically-confirmed dengue cases classified as severe and due to any of the 4 serotypes > 28 days after third injection up to the end of the active phase.
- Symptomatic virologically-confirmed dengue cases due to any of the 4 serotypes after at least two injections and after at least one injection.
- Symptomatic virologically-confirmed dengue cases after each injection according to virus serotype.
- Hospitalized dengue cases.
- Duration of clinical syndrome and hospitalization for symptomatic virologically-confirmed dengue cases.
Safety in all subjects and reactogenicity in a subset
Dengue immune responses in a subset |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1) Aged 4 to 11 years on the day of inclusion.
2) Subject in good health, based on medical history and physical examination.
3) Provision of assent form signed by the subject (for subjects ≥ 7 years old) and informed consent form signed by the parent or another legally acceptable representative.
4) Subject and parent/legally acceptable representative able to attend all scheduled visits and to comply with all trial procedures.
5) Subject attending one of the schools involved in the trial and living in the Ratchaburi Province.
6) For a female subject of child-bearing potential (girls post-menarche), avoid becoming pregnant (use of an effective method of contraception or abstinence) for at least 4 weeks prior to first vaccination, until at least 4 weeks after the last vaccination. |
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E.4 | Principal exclusion criteria |
1) Febrile illness (temperature ≥ 37.5°C) or moderate or severe acute illness/infection on the day of vaccination, according to Investigator judgment.
2) For a female subject of child-bearing potential (girls post-menarche), known pregnancy or positive urine pregnancy test on the day of the first trial vaccination.
3) Personal or family history of thymic pathology (thymoma), thymectomy, or myasthenia.
4) Planned participation in another clinical trial during the present trial period.
5) Known or suspected congenital or acquired immunodeficiency, immunosuppressive therapy such as anti-cancer chemotherapy or radiation therapy, or long-term systemic corticosteroids therapy.
6) Known systemic hypersensitivity to any of the vaccine components or history of a life-threatening reaction to the trial vaccines or to a vaccine containing any of the same substances.
7) Chronic illness at a stage that could interfere with trial conduct or completion, in the opinion of the Investigator.
8) Receipt of blood or blood-derived products in the past 3 months.
9) Subject deprived of freedom by an administrative or court order, or in an emergency setting, or hospitalized without his/her consent.
10) Participation in another clinical trial investigating a vaccine, drug, medical device, or a medical procedure in the 4 weeks preceding the first trial vaccination.
11) Receipt of any vaccine in the 4 weeks preceding the first trial vaccination.
12) Planned receipt of any vaccine in the 4 weeks following the first trial vaccination.
13) Subject who planned to attend another school (outside the trial area) or move to another city in the coming 30 months. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Symptomatic virollogically confirmed dengue cases due to any of the 4 serotypes > 28 days after third injection up to the end of the active phase |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
> 28 days after third injection up to the end of the active phase (1 year after third vaccination) |
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E.5.2 | Secondary end point(s) |
Efficacy:
- Symptomatic virologically-confirmed dengue cases classified as severe and due to any of the 4 serotypes > 28 days after third injection up to the end of the active phase.
- Symptomatic virologically-confirmed dengue cases due to any of the 4 serotypes after at least two injections and after at least one injection.
- Symptomatic virologically-confirmed dengue cases after each injection according to virus serotype.
- Hospitalized dengue cases.
- Duration of clinical syndrome and hospitalization for symptomatic virologically-confirmed dengue cases.
Safety:
Serious adverse events (SAEs) throughout the study as follows: all SAEs up to 6 months after the third injection. Related and/or fatal SAEs from 6 months after the third injection until the end of the study in all subjects.
Reactogenicity:
Adverse events up to D28 after each injection in the reactogenicity subset.
Dengue immune responses:
Dengue immune response (serotype specfic neutralizing antibodies) prior to and 28 days (D28) after each injection in an immunogenicity subset. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Efficacy:
> 28 days after third injection up to the end of the active phase for severe cases
After at least two injections and after at least one injection
After each injection according to virus serotype
Throughout the study for Hospitalized dengue cases and Duration of clinical syndrome and hospitalization for symptomatic virologically-confirmed dengue cases
Safety:
All SAEs up to 6 months after the third injection
Related and/or fatal SAEs from 6 months after the third injection until the end of the study
Reactogenicity:
Up to D28 after each injection
Dengue immune responses:
Prior to and 28 days (D28) after each injection. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | Yes |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
At 0 Mo: Rabies vaccine (Cohort 1) or placebo (NaCl 0.9%); At 6 and 12 Mos: Placebo |
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E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
Will this trial be conducted at a single site globally?
| Yes |
E.8.4 | Will this trial be conducted at multiple sites globally? | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.2 | Trial being conducted completely outside of the EEA | Yes |
E.8.6.3 | Specify the countries outside of the EEA in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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LVLS of the Active Phase of CYD23
Following a request from the Ethics Committee, the Passive Phase was not conducted as initially planned in CYD23 study, which was stopped after the end of the Active Phase. Hospitalized dengue cases and long-term safety follow-up up to 5 years after the third injection are being collected in a separate study (i.e., CYD57 study). |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.2 | In all countries concerned by the trial years | 3 |