E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Vaccination of healthy children aged 6 months to 17 years with pandemic Flu H5N1 vaccine (30µgHA+aluminum hydroxide vaccine) |
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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 describe the safety profiles (injection site reactions and systemic events) during the 21 days following each vaccination in subjects receiving the D0-D21 and the D0-D42 vaccination schedules, and 14 days and 21 days after Vac1 and Vac2, respectively, in subjects aged 9 to 17 years receiving the D0-D14 vaccination schedule • To describe the immune response 21 days after each vaccination in subjects receiving the D0-D21 vaccination schedule
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E.2.2 | Secondary objectives of the trial | |
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
All Subjects:
1) Subject and parent(s)/legal representative able to attend all scheduled visits and to comply with all trial procedures 2) Completion of vaccination according to the national immunization schedule
Subjects Aged ≥2 Years to <18 Years:
3) Aged ≥2 years to <18 years on the day of inclusion. 4) Provision of Informed Consent Form signed by the subject's the parent(s)/legal representative (and by an independent witness if required by local regulations). In addition, provision of Assent Form signed by subjects aged 8 to 11 years, and of Informed Consent Form signed by subjects ≥12 years. 5) For a female of child-bearing potential, avoid becoming pregnant (use of an effective method of contraception or abstinence) for at least 4 weeks prior to each vaccination, until at least 4 weeks after each vaccination.
Subjects Aged ≥6 Months to <2 Years:
6) Aged ≥6 months to <2 years on the day of inclusion. 7) Born at full term of pregnancy (≥37 weeks) with a birth weight ≥2.5 kg. 8) Provision of Informed Consent Form signed by the parent(s) or other legal representative (and by an independent witness if required by local regulations).
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E.4 | Principal exclusion criteria |
All subjects:
1) Participation in another clinical trial investigating a vaccine, drug, medical device, or a medical procedure in the 4 weeks preceding trial vaccination 2) Planned participation in another clinical trial during the present trial period 3) Known or suspected 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 4) Known systemic hypersensitivity to any of the vaccine components or history of a life-threatening reaction to the trial vaccine or to a vaccine containing any of the same substances 5) Chronic illness, at a stage that could interfere with trial conduct or completion, in the opinion of the investigator 6) Current alcohol abuse or drug addiction that may interfere with the subject’s ability to comply with trial procedures 7) Receipt of Blood or blood-derived products in the past 3 months, that might interfere with the assessment of immune response 8) Receipt of any vaccine in the 4 weeks preceding trial vaccination 9) Planned receipt of any vaccine in the 4 weeks following any trial vaccination 10) (Known) Human Immunodeficiency Virus (HIV), HBs antigen or Hepatitis C seropositivity 11) Previous vaccination against avian influenza with either the trial vaccine or another vaccine 12) Thrombocytopenia, bleeding disorder or anticoagulants in the 3 weeks preceding inclusion contraindicating IM vaccination 13) Subjects deprived of freedom by an administrative or court order, or in an emergency setting, or hospitalized without his/her consent 14) Received oral or injected antibiotic therapy within the 72 hours prior to any blood draw
Subjects Aged ≥2 Years to <18 Years:
15) For a female of child-bearing potential, known pregnancy or positive urine pregnancy test 16) Breast-feeding female 17) Febrile illness (temperature ≥37.5°C) or moderate or severe acute illness/infection on the day of vaccination, according to investigator judgment
Subjects Aged ≥6 Months to <2 Years:
18) History of seizures 19) Febrile illness (temperature ≥38°C) or moderate or severe acute illness/infection on the day of vaccination, according to investigator judgment
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E.5 End points |
E.5.1 | Primary end point(s) |
Safety:
• Occurrence, nature, (Medical Dictionary for Regulatory Activities [MedDRA] preferred term), duration, severity (for non-serious AEs), action taken and relationship to vaccination of any unsolicited systemic adverse events (AEs) reported in the 30 minutes after each injection • Occurrence, time to onset, number of days of occurrence, action taken and severity of solicited (pre-listed in the subject diary and Case Report Form [CRF]) injection site reactions and systemic reactions occurring up to 7 days following each injection • Occurrence, nature (MedDRA preferred term), time to onset, duration, severity (for non-serious AEs), action taken and relationship to vaccination of unsolicited (spontaneously reported) AEs within 21 days following each injection, as applicable* • Occurrence, nature, time to onset, duration, seriousness criteria, relationship to vaccination and outcome of serious adverse events (SAEs) during the whole study period • The occurrence of the following reactions (MedDRA Preferred Terms given in parentheses) following each injection will be more especially reported in subjects over 2 years of age (as defined for adults in the European Medicines Agency [EMEA] Note for Guidance [CPMP/BWP/214/96]) • Injection site induration ≥5 cm for at least 4 consecutive days following each injection • Injection site ecchymosis (injection site hemorrhage) in the 3 days following each injection • Temperature >38°C (pyrexia) for 24 hours or more in the 3 days following each injection • Malaise in the 3 days following each injection • Shivering (chills) in the 3 days following each injection * for subjects aged 9 to 17 years receiving the D0-D14 vaccination schedule, unsolicited AEs will only be collected up to 14 days after Vac1, and up to 21 days after Vac2.
Immunogenicity:
Immunogenicity will be assessed in all subjects receiving the D0-D21 vaccination schedule.
• Anti-hemagglutinin (HA) antibody titers against the A/H5N1 strain using the hemagglutination inhibition method with horse erythrocytes (HIH) will be obtained from duplicate testing in the immunogenicity subset prior to Vac1, prior to Vac2 and 21 days after Vac2 (Vac2+21D), and summarized at the subject level by individual geometric mean (GM) of duplicates at each timepoint. The following endpoints will be derived: • Subjects with titer ≥8 (1/dilution) (1/dil) on Vac1, Vac2 and Vac2+21D • Individual titer ratios: Vac2/Vac1, Vac2+21D/Vac1 and Vac2+21D/Vac2 • Proportion of subjects with titer ≥32 (1/dil) on Vac1, Vac2 and Vac2+21D • Seroconversion, i.e. for subjects with a pre-vaccination titer <8 (1/dil), post-vaccination titer ≥32 (1/dil), or significant increase, i.e. for subjects with a pre-vaccination titer ≥8 (1/dil), ≥4-fold increase of the titer post-vaccination, from Vac1 to Vac2, from Vac1 to Vac2+21D
• Neutralizing antibody titer using the seroneutralization (SN) method will be obtained from single testing in the immunogenicity subset, prior to Vac1, prior to Vac2 and on Vac2+21days, and provided at the subject level at each timepoint. The following endpoints will be derived: • Subjects with titer ≥10 (1/dil) on Vac1, Vac2 and Vac2+21D • Individual titer ratios: Vac2/Vac1, Vac2+21D/Vac1 and Vac2+21D/Vac2 • 2- and 4-fold increase from Vac1 to Vac2 and to Vac2+21
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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 | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
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 | No |
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) | No |
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 | 12 |
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 | 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
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Date of the last contact with a trial subject within the scope of the trial (information provided in the protocol) |
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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 | 7 |
E.8.9.1 | In the Member State concerned days | |