E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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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 identify the preferred vaccine formulation (with or without MF59), dosage (of antigen and adjuvant) and schedule (one or two administrations) of the egg-derived H1N1sw monovalent vaccine in healthy children and adolescents based on CHMP criteria and pairwise statistical comparisons for immunogenicity, safety and tolerability. |
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E.2.2 | Secondary objectives of the trial |
Immunogenicity objectives 1. To evaluate immunogenicity of a booster dose of the egg-derived H1N1sw monovalent influenza vaccine administered 12 months after the primary course with respect to CHMP criteria. 2. To evaluate the non-inferiority of the post-vaccination (Day 43) hemagglutination hinibition (HI) geometric mean titer (GMT) of the half dose (3.75 µg of HA + half MF59) of the egg derived H1N1sw monovalent vaccine to the corresponding GMTs of the full dose (7.5 µg of HA + full MF59) of the egg derived H1N1sw monovalent vaccine, after two doses administered 3 weeks apart in the pooled children population.
Safety objectives To evaluate safety and tolerability of the egg-derived H1N1sw monovalent vaccine for 3 weeks after the first and second vaccination. To evaluate safety and tolerability of the egg-derived H1N1sw monovalent vaccine for up to 6 months after the booster dose in the paediatric population. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Males and females 6 months of age to 17 years of age on the day of enrollment; 2. Subject's parents or legal guardians who have given written consent and the subjects has given assent consent, if applicable, after the nature of the study has been explained according to local regulatory requirementsable to comply with all study procedures and requirements; 3. Individuals in good health as determined by the outcome of medical history; physical examination and clinical judgment of the investigator; 4. Subjects, subject's parents or legal guardians that are able to comply with all study procedures and are available for all clinic visits scheduled in the study. 5. Willingness to allow for serum samples to be stored beyond the study period, for potential additional future testing to better characterize immune response. |
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E.4 | Principal exclusion criteria |
1. Subject's parents or legal guardians who are not able to comprehend and to follow all required study procedures for the whole period of the study; 2. Individuals with history or any illness that, in the opinion of the investigator, might interfere with the results of the study or pose additional risk to the subjects due to participation in the study; 3. Individuals with any serious chronic or progressive disease according to judgment of the investigator (neoplasm, insulin dependent diabetes, cardiac, renal or hepatic disease); 4. History of any anaphylaxis, serious vaccine reactions, or hypersensitivity to influenza viral proteins, to any excipients, and to eggs (including ovalbumin), chicken protein; 5. Individuals who have had adjuvanted influenza vaccine or documented confirmed or suspected influenza disease within 3 months prior to Day 1. “Documented-confirmed” includes: a. Positive serology result b. Positive viral culture c. Positive rapid antigen test d. “Suspected” influenza disease includes: subjects with influenza-like illness within the past 3 months with a household/intimate contact with “laboratory-confirmed” influenza disease; 6. Receipt of another investigational agent within 4 weeks prior to enrollment or before completion of the safety follow-up period in this or in another study, unwilling to refuse a participation in another clinical study through the end of this study; 7. Individuals who receive any other vaccine 4 weeks prior to enrolment in this study or who are planning to receive any vaccine within four weeks from the study vaccines; the only exception being plain seasonal influenza vaccines which are allowed until one week prior to and after one week study vaccinations 8. Individuals who have received blood, blood products and/or plasma derivatives or any parenteral immunoglobulin preparation in the past 12 weeks; 9. Individuals with axillary temperature ≥ 38.0 degrees Celsius (≥100.4 F) or oral/rectal temperature ≥ 38.5 degrees Celsius(≥101.3 F) within 3 days of intended study vaccination; 10. Known or suspected impairment/alteration of immune function, for example resulting from: a. receipt of immunosuppressive therapy such as systemic corticosteroids known to be associated with the suppression of hypothalamic-pituitary-adrenal (HPA) axis (15 mg/day of prednisone or its equivalent) or chronic use of inhaled high-potency corticosteroids (e.g. budesonide 800µg/day or fluticasone 750µg/day) within 60 days prior to Visit 1, b. cancer chemotherapy, c. receipt of immunostimulants within 60 days prior to Visit 1, d. receipt of parenteral immunoglobulin preparation, blood products, and/or plasma derivatives within 3 months prior to Visit 1 or planned during the full length of the study, e. known HIV infection or HIV-related disease; 11. History of progressive or severe neurologic disorder (including Guillain-Barré syndrome and convulsion, but excluding febrile convulsion); 12. History of or clinically suspected developmental delay; 13. Bleeding diathesis; 14. Surgery planned during the study period that in the Investigator’s opinion would interfere with the study visits schedule; 15. If female, of childbearing potential, and has not used any of the “acceptable contraceptive methods” for at least 2 months prior to study entry: a. Female of childbearing potential is defined as a post onset of menarche capable of becoming pregnant and not surgically sterile b. Acceptable birth control methods are defined as one or more of the following: i. Hormonal contraceptive (such as oral, injection, transdermal patch, implant, cervical ring) ii. Barrier (condom with spermicide or diaphragm with spermicide) each and every time during intercourse iii. Intrauterine device (IUD) iv. Monogamous relationship with vasectomized partner. Partner must have been vasectomized for at least six months prior to the subject’s study entry; 16. Females who are pregnant or nursing (breastfeeding) mothers, or females of childbearing potential who are sexually active and have not used or do not plan to use acceptable birth control measures during the first 3 weeks after vaccination; 17. Members of research staff or their relatives (research staff are individuals with direct contact with trial subjects, or study site personnel who have access to any study document containing subject information, including: e.g. receptionist, person scheduling appointments or making screening calls, regulatory specialists, laboratory technicians). Hospital personnel, Health Care Professionals and their relatives that are not involved in this clinical study are allowed for inclusion. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Immunogenicity criteria for success for EU licensure will be based on CHMP requirements, even though these criteria apply to subjects ≥18 years of age (for the pediatric population, no CHMP criteria are defined).
The immunogenicity criteria for success, as determined by HI, related to the EMEA/CPMP/VEG/4717/2003-Rev.1 (pandemic guideline) and EMEA/CHMP/VWP/263499/2006 (pre-pandemic guideline) are: • The percentage of subjects with seroconversion or at least 4-fold increase in HI antibody is > 40% • The percentage of subjects achieving an HI titer ≥ 1:40 is > 70%. • The GMR is >2.5
All three criteria as assessed at Day 43 should be met within each age group to fulfill regulatory requirements. Results collected at 21 days after the first dose will also be evaluated against the CHMP criteria as presented above.
Pairwise Comparisons All vaccine groups will be compared two by two by means of geometric mean ratios and difference in proportions and corresponding two-sided 95% confidence intervals. A comparison between one dose versus two doses within each vaccine group and each age group separately will be also performed using the same statistical analysis as above. |
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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 | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | Yes |
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) | 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 | Yes |
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 | Yes |
E.8.1.7.1 | Other trial design description |
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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 | Yes |
E.8.2.3.1 | Comparator description |
Non-adjuvanted H1N1sw Vaccine |
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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 | 10 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 14 |
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 | 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 | 0 |
E.8.9.1 | In the Member State concerned months | 20 |
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 | 20 |
E.8.9.2 | In all countries concerned by the trial days | 0 |