E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Dengue Fever
Dengue Hemorrhagic Fever
Human Papillomavirus Disease
|
|
E.1.1.1 | Medical condition in easily understood language |
Dengue Fever
Dengue Hemorrhagic Fever
Human Papillomavirus Disease
|
|
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 Cervarix after concomitant administration with the CYD dengue vaccine is non-inferior to the humoral immune response (in terms of GMTs) after sequential administration with the CYD dengue vaccine measured 28 days after the last dose of Cervarix
To demonstrate that the humoral immune response (in terms of GMTs) to the CYD dengue vaccine after concomitant administration with Cervarix is non-inferior to the humoral immune response (in terms of GMTs) to the CYD dengue vaccine after sequential administration with Cervarix measured 28 days after the last dose of the CYD dengue vaccine
|
|
E.2.2 | Secondary objectives of the trial |
To demonstrate that the humoral immune response (in terms of seroconversion) to Cervarix after concomitant administration with the CYD dengue vaccine is non-inferior to the humoral immune response (in terms of seroconversion) to Cervarix sequential administration with the CYD dengue vaccine measured 28 days after the last dose of Cervarix
To describe the humoral immune response to Cervarix at baseline and after each dose of Cervarix 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 Cervarix and CYD dengue vaccine after each and any dose in each group
|
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Subject aged 9 to 14 years (i.e., from the day of the 9th birthday to the day prior to the 15th 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.
|
|
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.
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
1.Antibody levels against each Cervarix HPV bivalent antigen after the last dose of Cervarix in previously dengue exposed participants
HPV-16 and HPV-18 antibodies will be measured by enzyme linked immunosorbent assay (ELISA)
2.Neutralizing antibody titers against each dengue virus serotype after the last CYD dengue vaccine injection in previously dengue exposed participants
Neutralizing antibody levels against each dengue virus serotype will be measured using dengue 50% plaque reduction neutralization test (PRNT50)
|
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
1.[ Time Frame: Day 28 after the last Cervarix injection ]
2. [ Time Frame: Day 28 after the last CYD dengue vaccine injection ] |
|
E.5.2 | Secondary end point(s) |
1.Antibody levels against each HPV antigen after each dose of Cervarix in previously dengue exposed participants
HPV-16 and HPV-18 antibodies will be measured by ELISA
2.Percentage of participants with seroconversion against each Cervarix HPV antigen after each dose of Cervarix in previously dengue exposed participants
HPV-16 and HPV-18 antibodies will be measured by ELISA. Seroconversion is defined as changing serostatus from seronegative at baseline to seropositive (> lower limit of quantitation of the assay) or ≥ 4-fold rise in antibody titer if seropositive at baseline
3.Neutralizing antibody titers against each dengue virus serotype after each CYD dengue vaccine injection in previously dengue exposed participants
Neutralizing antibody levels against each dengue virus serotype will be measured by dengue PRNT50
4.Neutralizing antibody titers above pre-defined threshold against each and against at least 1, 2, 3, or 4 dengue virus serotypes after each CYD dengue vaccine injection in previously dengue exposed participants
Neutralizing antibody levels against each dengue virus serotype will be measured by dengue PRNT50
5.Number of participants reporting solicited injection site reactions
Solicited injection site reactions: Pain, Erythema, and Swelling
6.Number of participants reporting solicited systemic reactions
Solicited systemic reactions: Fever, Headache, Malaise, Myalgia, and Asthenia
|
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
1.[ Time Frame: 28 days after each Cervarix injection ]
2.[ Time Frame: 28 days after each Cervarix injection ]
3.[ Time Frame: 28 days after each CYD dengue vaccine injection ]
4.[ Time Frame: 28 days after each CYD dengue vaccine injection ]
5. [ Time Frame: 7 days after each vaccine injection ]
6. [ Time Frame: 14 days after each vaccine injection ] |
|
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 | 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 |
|
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 | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
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 |
|
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 | 2 |
E.8.9.2 | In all countries concerned by the trial months | 4 |
E.8.9.2 | In all countries concerned by the trial days | 12 |