E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Dengue Fever
Dengue Hemorrhagic Fever
Human Papillomavirus Disease |
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E.1.1.1 | Medical condition in easily understood language |
Dengue Fever
Dengue Hemorrhagic Fever
Human Papillomavirus Disease |
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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 |
- To demonstrate that the humoral immune response (in terms of geometric mean titers[GMTs]) to Gardasil after concomitant administration is non-inferior to sequential administration with the CYD dengue vaccine measured 28 days after the last dose of Gardasil.
- To demonstrate that the humoral immune response to the CYD dengue vaccine after concomitant administration is non-inferior to sequential administration with Gardasil measured 28 days after the last dose of the CYD dengue vaccine.
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E.2.2 | Secondary objectives of the trial |
- To demonstrate that the humoral immune response (in terms of seroconversion) to Gardasil after concomitant administration is non-inferior to sequential administration with the CYD dengue vaccine measured 28 days after the last dose of Gardasil
- To describe the humoral immune response to Gardasil at baseline and after each dose of Gardasil in each and any group
- To describe the humoral immune response to the CYD dengue vaccine at baseline and after each dose of the CYD dengue vaccine in each and any group
- To describe the safety of Gardasil and the CYD dengue vaccine after each and any dose in each group.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Subject aged 9 to 13 years (i.e., from the day of the 9th birthday to the day prior to the 14th birthday) on the day of inclusion
- Informed consent form (ICF) or Assent form (AF) has been signed and dated by the subject (based on local regulations), and/or ICF has been signed and dated by the parent(s) or another legally acceptable representative (and by an independent witness if required by local regulations)
- Subject (or subject and parent[s] or another legally acceptable representative) is (are) able to attend all scheduled visits and to comply with all trial procedures
- Subject in good health, based on medical history, and physical examination. |
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E.4 | Principal exclusion criteria |
- Subject is pregnant, or lactating, or of childbearing potential (to be considered of non-childbearing potential, a female must be pre-menarche, surgically sterile, or using an effective method of contraception or abstinence from at least 4 weeks prior to the first vaccination and until at least 4 weeks after the last vaccination)
- Participation at the time of study enrollment (or in the 4 weeks preceding the first trial vaccination) or planned participation during the present trial period in another clinical trial investigating a vaccine, drug, medical device, or medical procedure
- Planned receipt of any vaccine in the 4 weeks following any trial vaccination
- Previous vaccination against dengue disease with the trial vaccine
- Previous vaccination against HPV disease with either the trial vaccine or another vaccine
- Receipt of immune globulins, blood or blood-derived products in the past 3 months
- Known or suspected congenital or acquired immunodeficiency (including HIV infection with impaired immune function); or receipt of immunosuppressive therapy, such as anti-cancer chemotherapy or radiation therapy, within the preceding 6 months; or long-term systemic corticosteroid therapy (prednisone or equivalent for more than 2 consecutive weeks within the past 3 months)
- History of HPV infection, confirmed either clinically, serologically, or microbiologically as reported by subject or parent(s) or another legally acceptable representative
- Known systemic hypersensitivity to any of the vaccine components, or history of a life-threatening reaction to the vaccines used in the trial or to a vaccine containing any of the same substances
- Thrombocytopenia, contraindicating intramuscular vaccination
- Bleeding disorder, or receipt of anticoagulants in the 3 weeks preceding inclusion, contraindicating intramuscular vaccination
- Deprived of freedom by an administrative or court order, or in an emergency setting, or hospitalized involuntarily
- Current alcohol abuse or drug addiction that, based on investigator's judgment, may interfere with the subject's ability to comply with trial procedures
- Chronic illness that, in the opinion of the Investigator, is at a stage where it might interfere with trial conduct or completion
- Identified as an Investigator or employee of the Investigator with direct involvement in the proposed study, or identified as an immediate family member (i.e., parent, spouse, natural or adopted child) of the Investigator or employee with direct involvement in the proposed study
- Self-reported Hepatitis B, Hepatitis C infection. |
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E.5 End points |
E.5.1 | Primary end point(s) |
- Antibody levels against each Gardasil human papillomavirus quadrivalent (HPV) antigen (HPV 6, HPV 11, HPV 16, and HPV 18) 28 days after the last dose of Gardasil following either a concomitant or sequential administration with CYD dengue vaccine HPV 6, HPV 11, HPV 16, and HPV 18 antibodies will be measured by the competitive Luminex immunoassay.
- Neutralizing antibody titers against each of the four dengue virus serotype at baseline and 28 days after the last CYD dengue vaccine injection. Neutralizing antibody levels against each dengue virus serotype will be measured using dengue 50% plaque reduction neutralization test (PRNT50)
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
1. Time Frame: Day 28 after the last Gardasil injection
2. Time Frame: Day 28 after the last CYD dengue vaccine injection |
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E.5.2 | Secondary end point(s) |
- Percentage of participants with seroconversion against each Gardasil HPV antigen (HPV 6, HPV 11, HPV 16, HPV 18) after the last dose of Gardasil HPV 6, 11, 16 and 18 antibodies will be measured by the competitive Luminex immunoassay
- Neutralizing antibody titers against each of the four dengue virus serotype at baseline and 28 days after each CYD dengue vaccine injection Neutralizing antibody levels against each dengue virus serotype will be measured using dengue 50% plaque reduction neutralization test (PRNT50)
- Antibody levels against each Gardasil HPV antigen (HPV 6, HPV 11, HPV 16, and HPV 18) 28 days after each dose of Gardasil following either a concomitant or Sequential administration with CYD dengue vaccine HPV 6, HPV 11, HPV 16, and HPV 18 antibodies will be measured by the competitive Luminex immunoassay.
- Number of participants reporting solicited injection site reactions Solicited injection site reactions: Pain, Erythema, and Swelling
- Number of participants reporting solicited solicited systemic reactions Solicited systemic reactions: Fever (temperature), Headache, Malaise, Myalgia, and Asthenia |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. Time Frame: Day 28 after the last Gardasil injection
2. Time Frame: Day 28 after each CYD dengue vaccine injection
3. Time Frame: Day 28 after each Gardasil injection
4. Time Frame: Day 0 to Day 7 after each and any injection
5. Time Frame: Day 0 to Day 14 after each and any 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 | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
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 | Yes |
E.6.13.1 | Other scope of the trial description |
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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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | Information not present in EudraCT |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
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 | No |
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 years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 7 |