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 |
Safety and reactogenicity
Viremia
Dengue immune responses |
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E.2.2 | Secondary objectives of the trial |
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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) Informed consent form signed by the subject, by two independent witnesses, and by the parent(s) or legal representative(s) for subjects under 18 years old (Scr.).
3) For a woman, inability to bear a child or negative serum pregnancy test at screening (Scr.).
4) Able to attend all scheduled visits and to comply with all trial procedures (Scr.+V01).
5) For a woman of child-bearing potential, use of an effective method of contraception or abstinence for at least four weeks prior to the first vaccination and at least four weeks after each vaccination (Scr.+V01).
6) For a woman, inability to bear a child or negative urine pregnancy test on the day of the first injection (V01). |
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E.4 | Principal exclusion criteria |
1) History of thymic pathology (thymoma), thymectomy, or myasthenia (Scr.).
2) Breast-feeding (Scr.).
3) Systemic hypersensitivity to any of the vaccine components or history of a lifethreatening reaction to the trial vaccine or a vaccine containing the same substances (Scr.).
4) Previous vaccination against flavivirus diseases (including Japanese encephalitis and YF) (Scr.).
5) Current abuse of alcohol or drug addiction that might interfere with the subjects ability to comply with trial procedures (Scr.).
6) Planned participation in another clinical trial during the present trial period (Scr.+V01).
7) History of flavivirus infection (confirmed either clinically, serologically or microbiologically) (Scr.+V01).
8) Congenital or acquired immunodeficiency, immunosuppressive therapy such as anti-cancer chemotherapy or radiation therapy within the preceding 6 months, or long-term systemic corticosteroids therapy (Scr.+V01).
9) Chronic illness at a stage that could interfere with trial conduct or completion (Scr.+V01).
10) Blood or blood-derived products received in the past three months (Scr.+V01).
11) Vaccination planned in the four weeks following any trial vaccination (Scr.+V01).
12) Flavivirus vaccination planned during the present trial period (Scr.+V01).
13) Planned travel during the present trial period to areas with high dengue infection endemicity (Scr.+V01).
14) Subject deprived of freedom by an administrative or court order, or in an emergency setting, or hospitalized without his/her consent (Scr.+V01).
15) Participation in another clinical trial in the four weeks preceding the first trial vaccination (V01).
16) Any vaccination in the four weeks preceding the first trial vaccination (V01).
17) Human Immunodeficiency Virus (HIV), hepatitis B (Ag HBs) or hepatitis C (HC) seropositivity in blood sample taken at Screening (V01).
18) Clinically significant laboratory abnormalities (as determined by the Investigator) in blood sample taken at Screening (V01). |
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E.5 End points |
E.5.1 | Primary end point(s) |
Safety and reactogenicity
Adverse events and biological abnormalities up to day 28 (D28) after each injection and serious adverse events throughout the study.
Viremia
Occurrence and maximum level of the four dengue serotypes in sera collected on the day of each injection, 7 and 14 days following the first and the second injections, and 7 days following the third injection in all the subjects.
Dengue immune responses
- Neutralizing antibody levels against each of the four parental dengue virus serotype strains of ChimeriVax™ dengue tetravalent vaccine constructs and against the Thai Mahidol four dengue virus serotype strains, were measured on sera collected in all the subjects before injection, and 28 days after the first, second, and third injections
- Non-serotype specific Immunoglobulin M (IgM) and Immunoglobulin G (IgG) antibody levels were measured before injection and 28 days after the first, second, and third injections. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Safety:
Adverse events and biological abnormalities up to day 28 (D28) after each injection and serious adverse events throughout the study.
Viremia:
Viremia on D0, D7 after each injection, and D14 after the first and second injections.
Dengue immune responses:
Immune responses (serotype specific neutralizing antibodies, and non-serotype specific immunoglobulines [IgM, IgG]) prior to first injection and on D28 after each injection. |
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E.5.2 | Secondary end point(s) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | 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) | Yes |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | Yes |
E.7.1.3.1 | Other trial type description |
First administration in pediatric population |
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E.7.2 | Therapeutic exploratory (Phase II) | No |
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 |
Observer-blind (first injection), open-label (second and third) |
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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: control vaccine (yellow fever vaccine); At 3.5 and 12 Mos: tested dengue vaccine (PR1) |
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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?
| No |
E.8.4 | Will this trial be conducted at multiple sites globally? | Yes |
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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.2 | In all countries concerned by the trial months | 14 |