E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Immunization of healthy children aged 3-9 years against (H5N1) influenza. |
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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 evaluate the humoral immune response induced by the H5N1 vaccine candidate in terms of anti-haemagglutinin antibody titer. •To evaluate the safety and reactogenicity of the H5N1 vaccine candidate in terms of solicited local and general adverse events, unsolicited adverse events and serious adverse events
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E.2.2 | Secondary objectives of the trial |
•To evaluate the humoral immune response induced by the H5N1 vaccine candidate in terms of neutralizing antibody titer. •To evaluate the cell-mediated immune response induced by the H5N1 vaccine candidate in terms of the expression of Th1 markers (CD40L, IFNgamma, IL 2, and TNFalpha) after in vitro re-stimulation of influenza-specific CD4/CD8 T lymphocytes.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
•Children who the investigator believes that their parents/guardians can and will comply with the requirements of the protocol (e.g., completion of the diary cards, return for follow-up visits) should be enrolled in the study. •Children aged between and including 3 and 9 years of age at the time of first vaccination. •Written informed consent obtained from the parent or guardian of the subject. •Healthy children as established by medical history and history-directed clinical examination before entering the study. •Subjects who are likely to reside in the vicinity of the study center for the duration of the study.
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E.4 | Principal exclusion criteria |
•Use of any investigational or non-registered product (drug or vaccine) other than the H5N1 vaccine candidate within 30 days prior to the enrolment in this study, or planned use during the study period. •Administration of licensed vaccines within 2 weeks (for inactivated vaccines) or 4 weeks (for live vaccines) prior to enrolment in this study. Planned administration of a vaccine not foreseen by the study protocol up to 30 days after the second vaccination, with the exception of routine childhood inoculations which cannot be delayed, but which must not be administered on the same day as the H5N1 vaccine candidate. •Administration of the interpandemic influenza vaccine (NH 2006/2007 or SH 2007) prior to Day 0 or planned during the study. However, study participants eligible to receive the annual interpandemic influenza vaccine (in accordance with DOH recommendations), may receive the annual vaccination at least 21 days prior to Day 0 or after Day 51 and up to Day 159. •Chronic administration (defined as more than 14 days) of immunosuppressants or other immune-modifying drugs within six months prior to the enrolment in this study. (For corticosteroids, this will mean prednisone, or equivalent, <= 0.5 mg/kg/day. Inhaled and topical steroids are allowed). •Any chronic drug therapy to be continued during the study period, with the exception of inhalative treatment for seasonal allergies or asthma. •Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination (no laboratory testing required). •Acute or chronic clinically significant pulmonary, cardiovascular, hepatic or renal functional abnormality, as determined by medical history and physical examination. •History of hypersensitivity to vaccines. •History of allergic disease or reactions likely to be exacerbated by any component of the vaccines such as egg protein or thiomersal. •History of any neurological disorders or seizures. •Acute disease at the time of enrolment. (Acute disease is defined as the presence of a moderate or severe illness with or without fever. All vaccines can be administered to persons with a minor illness such as diarrhoea, mild upper respiratory infection with or without low-grade febrile illness, i.e. axillary temperature <37.5°C). •Administration of immunoglubulins and/or any blood products within the three months prior to the enrolment in this study or planned during the study. •Any condition which, in the opinion of the investigator, renders the subject unfit for participation in the study.
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E.5 End points |
E.5.1 | Primary end point(s) |
For the humoral immune response: Observed variables at days 0, 21, 42 and 180: serum anti-HA antibody titers tested against the H5N1 influenza strain. Derived variables (with 95 % confidence intervals): Geometric mean titers (GMTs) of serum antibodies at days 0, 21, 42 and 180. Seroconversion rates at days 21, 42 and 180. Seroconversion factors at days 21, 42 and 180. Seroprotection rates at days 0, 21, 42 and 180.
For the safety and reactogenicity evaluation: •Percentage, intensity and relationship to vaccination of solicited local and general signs and symptoms during a 7 day follow-up period, i.e. day of vaccination and 6 subsequent days after each vaccination. •Percentage, intensity and relationship to vaccination of solicited local and general signs and symptoms during a 21 day follow-up period after the first vaccination, during a 30-day follow-up period after the second vaccination. •Occurrence of serious adverse events during the entire study.
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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 |
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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) | 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 | 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.8.3 |
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 | 2 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
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.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | 10 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 10 |