| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Immunization of female and male children aged 3 to 17 years against influenza |
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| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 12.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10022000 |
| E.1.2 | Term | Influenza |
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| 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 evaluate the immunological non-inferiority (in terms of Geometric Mean Titre (GMT) and Seroconversion Rate (SCR)) of D-QIV versus TIV-1 (Fluarix) and TIV-2 in children (3 to 17 years) at 28 days (primed subjects) or 56 days (unprimed subjects) following first vaccination (28 days after completion of the immunization series).
Criteria to conclude non-inferiority:
•The test of non-inferiority will be based on the analysis of the entire age range in each treatment group. Non-inferiority will be concluded if, for the three strains contained in each TIV formulation:
•The upper limit of the two-sided 95% confidence interval (CI) of the GMT ratio (TIV-1 (Fluarix) / D-QIV and TIV-2 / D-QIV) after completion of the vaccination series does not exceed 1.5 and
•The upper limit of the two-sided 95% CI for the difference in SCR (TIV-1 (Fluarix) minus D-QIV and TIV-2 minus D-QIV) does not exceed 10% for the three strains contained in each TIV formulation |
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| E.2.2 | Secondary objectives of the trial |
- To evaluate the immunological superiority (in terms of GMTs and SCR) of D-QIV versus TIV-1 and TIV-2 in children (3 to 17 years) at 28 days after completion of the immunization series for the B strain not contained in each TIV formulation
- To describe the immunogenicity (in terms of GMT, seroprotection rate, SCR and mean geometric increase) of D-QIV, TIV-1 and TIV-2 for all subjects , and of D-QIV for the 6 to 35 months age group
- To evaluate the safety and reactogenicity of D-QIV, TIV-1 and TIV-2 in the 3 to 17 years age category and to evaluate the safety and reactogenicity of D-QIV for the 6 to 35 months age group, with regard to:
•Solicited local adverse events during the 7-day post-vaccination follow-up
•Solicited general AEs during the 7-day post-vaccination follow-up
•Unsolicited AEs during the 28-day post-vaccination follow-up period
•Serious adverse events, potential immune mediated diseases, AEs with medically attended visit during the entire study period |
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| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
•Subjects who the investigator believes that they and/or their parent(s)/Legally Acceptable Representative(s) [LAR(s)] can and will comply with the requirements of the protocol (e.g. completion of the diary cards, return for follow-up visits).
•For non US countries: A male or female child between 6 months and 17 years inclusive at the time of the first vaccination
For US: A male or female child between 3 and 17 years inclusive at the time of the first vaccination. Children who may not have had previous administration of influenza vaccine in a previous season are acceptable.
•Written informed consent obtained from the subject/from the parent(s)/LAR(s) of the subject.
•Written informed assent obtained from the subject if/as required by local regulations.
•Subjects in stable health as determined by investigator's clinical examination and assessment of subjects' medical history.
•Female subjects of non-childbearing potential may be enrolled in the study.
Non-childbearing potential is defined as pre-menarche, current tubal ligation, hysterectomy or ovariectomy .
•Female subjects of childbearing potential may be enrolled in the study, if the subject:
has practiced adequate contraception for 30 days prior to vaccination, and
has a negative urine pregnancy test on the day of vaccination, and
has agreed to continue adequate contraception during the entire treatment period and for 2 months after completion of the vaccination series. |
|
| E.4 | Principal exclusion criteria |
•Child in care
•Use of any investigational or non-registered product (drug or vaccine) other than the study vaccine within 30 days preceding the first dose of study vaccine, or planned use during the study period.
•Planned administration of any vaccine 30 days prior and 30 days after any study vaccine administration.
•Acute or chronic, clinically-significant pulmonary, cardiovascular, hepatic or renal functional abnormality, as determined by medical history and physical examination.
•Prior receipt of any seasonal or pandemic influenza vaccine (registered or investigational) within 6 months preceding the first dose of study vaccine, or planned use during the study period.
•Chronic administration (defined as more than 14 days) of immunosuppressants or other immune-modifying drugs within 3 months prior to the first vaccination dose. For corticosteroids, this will mean a dose equivalent to either 2 mg/kg of body weight or 20 mg/day of prednisone or equivalent for persons who weigh 10 kg when administered for more than 2 weeks. Inhaled and topical steroids are allowed.
•Administration of immunoglobulins and/or any blood products within the 3 months preceding the first dose of study vaccine or planned administration during the study period
•Any confirmed or suspected immunosuppressive or immunodeficient condition based on medical history and physical examination (no laboratory testing required).
•History of seizures (subject who have had a single uncomplicated febrile convulsion in the past could be included) or preogressive neurological disease.
•History of Guillain-Barré syndrome within 6 weeks of receipt of prior inactivated influenza virus vaccine.
•Concurrently participating in another clinical study, at any time during the study period, in which the subject has been or will be exposed to an investigational or a non-investigational product (pharmaceutical product or device).
•History of hypersensitivity to a previous dose of influenza vaccine, history of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccines.
•Acute disease and/or fever at the time of enrolment.
Fever is defined as temperature ≥37.5°C (99.5°F) on oral or axillary setting, or ≥38.0°C (100.4°F) on rectal setting. The possible route for recording temperature in this study will be oral, axillary or rectal
•Subjects with a minor illness (such as mild diarrhoea, mild upper respiratory infection) without fever may, be enrolled at the discretion of the investigator.
•Ongoing aspirin therapy (to avoid potential cases of Reye's syndrome).
•Pregnant or lactating female .
•Female planning to become pregnant or planning to discontinue contraceptive precautions.
•Any other condition which, in the opinion of the investigator, prevents the subject from participating in the study. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
•Humoral immune response in terms of HI antibodies
•Serum anti-HA antibody titres against the four vaccine strains at Day 0 and 28 days after last vaccine dose in each group will be used to calculate:
•GMTs of HI antibody titres at Day 0 and 28 days after last vaccine dose in each group.
•SCR* 28 days after last vaccine dose
*SCR is defined as the percentage of vaccinees who have either a pre-vaccination HI titre < 1:10 and a post-vaccination titre >= 1:40, or a pre-vaccination titre >= 1:10 and at least a 4-fold increase in post-vaccination titre |
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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 | 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 | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | Yes |
| E.8.1.7.1 | Other trial design description |
| open label arm including children aged 6 to 35 months |
|
| 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 | Yes |
| E.8.2.3.1 | Comparator description |
| GSK Biologicals’ trivalent seasonal influenza vaccine TIV-2 |
|
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 21 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 40 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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| E.8.7 | Trial has a data monitoring committee | No |
| 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.8.9.1 | In the Member State concerned years | 0 |
| E.8.9.1 | In the Member State concerned months | 6 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 0 |
| E.8.9.2 | In all countries concerned by the trial months | 6 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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