E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Prevention of symptomatic dengue disease |
|
E.1.1.1 | Medical condition in easily understood language |
Prevention of dengue disease with clinical symptoms |
|
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 |
Humoral immune response to dengue before and after each vaccination with CYD dengue vaccine
Persistence of antibodies (Abs) against dengue during 5 years after the first vaccination with CYD dengue vaccine
Safety and reactogenicity |
|
E.2.2 | Secondary objectives of the trial |
Detection of symptomatic dengue cases occurring at any time in the study |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1) Aged 2 to 45 years on the day of inclusion. (Scr.)
2) Provision of Informed Consent/Assent Form signed by the subject (and/or by the parent or another legally acceptable representative for subjects <18 years). (Scr.)
3) Subject (and parent/guardian for subjects <18 years) able to attend all scheduled visits and to comply with all trial procedures. (Scr. + V01)
4) For a female subject of child-bearing potential, avoid becoming pregnant (use of an effective method of contraception or abstinence) for at least 4 weeks prior to the first vaccination, until at least 4 weeks after the last vaccination. (Scr. + V01)
5) Subject in good health, based on medical history, physical examination and laboratory parameters. (Scr. + V01) |
|
E.4 | Principal exclusion criteria |
1) Personal or family history of thymic pathology (thymoma), thymectomy, or myasthenia. (Scr.)
2) For a female subject of child-bearing potential, known pregnancy or positive serum pregnancy test at Screening. (Scr.)
3) For a female subject of child-bearing potential, known pregnancy or positive urine pregnancy test on the day of the first injection. (V01)
4) Breast-feeding female subject. (Scr.)
5) Receipt of any vaccine in the 4 weeks preceding the first trial vaccination. (Scr.)
6) Human immunodeficiency virus, hepatitis B, or hepatitis C seropositivity in the blood sample taken at screening. (V01)
7) Planned participation in another clinical trial during the first year of the study. (Scr.)
8) Known or suspected congenital or acquired immunodeficiency, immunosuppressive therapy such as anti-cancer chemotherapy or radiation therapy within the past 6 months, or long-term systemic corticosteroids therapy. (Scr.)
9) 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. (Scr.)
10) Chronic illness at a stage that could interfere with trial conduct or completion, in the opinion of the Investigator. (Scr.)
11) Current alcohol abuse or drug addiction that may interfere with the subject’s ability to comply with trial procedures. (Scr.)
12) Receipt of blood or blood-derived products in the past 3 months that might interfere with the assessment of immune response. (Scr.)
13) Subject deprived of freedom by an administrative or court order, or in an emergency setting, or hospitalized without his/her consent. (Scr.)
14) Laboratory abnormalities of at least moderate severity or clinically significant according to the Investigator in blood sample taken at screening. (V01)
15) Participation in another clinical trial investigating a vaccine, drug, medical device, or a medical procedure in the 4 weeks preceding the first trial vaccination. (Scr. + V01)
16) Planned receipt of any vaccine in the 4 weeks following the first trial vaccination. (V01)
17) Familial atopy medical history (parents, brothers, or sisters). (Scr.)
18) Previous vaccination with meningococcal A + C or typhoid vaccines within 3 years prior to inclusion. (Scr.)
The exclusion criterion #18 was modified at the time of Amendment 1 (protocol Version 3.0 dated 08 April 2008) for accuracy.
19) History of meningococcal or typhoid infections (confirmed either clinically, serologically or microbiologically). (Scr.) |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Humoral immune response and Persistence of antibodies: Dengue immune response (serotype specific neutralizing antibodies)
Safety and reactogenicity: adverse events, and serious adverse events |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Humoral immune response: Prior to and 28 days (D28) after each injection
Persistence of antibodies each year during 5 years after the first injection
Safety and reactogenicity:
- Up to day 28 (D28) after each CYD dengue vaccine injection for AEs
- Throughout the trial for SAEs 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 |
|
E.5.2 | Secondary end point(s) |
Detection of symptomatic dengue cases |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
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 | No |
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 |
|
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: Meningococcal Polysaccharide Vaccine A+C; At 6 Mo: Placebo; At 12 Mo: Typhim Vi |
|
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 |
|
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
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.2 | In all countries concerned by the trial years | 5 |