E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Immunization against influenza disease during pandemic in subjects aged 18 to 60 years. |
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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 assess if the humoral immune response induced by a booster dose of the candidate vaccine given 6 months after a priming vaccination with a single dose of the candidate vaccine formulated from an heterologous strain fulfils the criteria established for influenza vaccines by the European Committee for Medicinal Products for Human Use (CHMP). •To evaluate the safety/reactogenicity of the candidate vaccine in terms of solicited local and general symptoms, unsolicited symptoms 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 vaccines (anti-haemagglutinin and neutralizing antibody titers) *21 days after vaccination(s) for the priming administration(s). *7 and 21 days after vaccination for the booster administration. •To evaluate the persistence of the humoral immune response 6 and 12 months after the priming administration(s) •To evaluate the persistence of the humoral immune response 6 or 12 months after the booster •To compare the humoral immune response induced by a booster dose of the candidate vaccine given following priming with either one or two doses of the candidate vaccine formulated from the homologous strain. •To compare the humoral immune response induced by a booster dose of the candidate vaccine given following priming with either one or two doses of the candidate vaccine formulated from a heterologous strain. •To evaluate the cell-mediated immune response after the booster administration of the candidate vaccines.
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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 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. •A male or female between, and including, 18 and 60 years of age at the time of the first vaccination. •Written informed consent obtained from the subject. •Healthy subjects as established by medical history and clinical examination before entering into the study. •If the subject is female, she must be of non-childbearing potential, i.e., either surgically sterilized or one year post-menopausal; or, if of childbearing potential, she must be abstinent or have used adequate contraceptive precautions (i.e., intrauterine contraceptive device; oral contraceptives; diaphragm or condom in combination with contraceptive jelly, cream or foam) for 30 days prior to first vaccination, have a negative pregnancy test and must agree to continue such precautions for two months after completion of the vaccination series.
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E.4 | Principal exclusion criteria |
•Administration of licensed vaccines within 2 weeks (for inactivated vaccines) or 4 weeks (for live vaccines) prior to enrolment in this study. •History of vaccination with investigational influenza pandemic vaccine. •History of administration of an experimental/licensed vaccine containing squalene and/or tocopherol (Vitamin E) •Planned administration of a vaccine not foreseen by the study protocol during the following periods: from Day 0 up to Day 51; from 2 weeks (for inactivated vaccines) or 4 weeks (for live vaccines) prior to Month 6 and Month 12; from Month 6 up to Month 6 + 30 days; from Month 12 up to Month 12 + 30 days. •Chronic administration (defined as more than 14 days) of immunosuppressants or other immune-modifying drugs within six months prior to the first administration of the candidate vaccines. (For corticosteroids, this will mean prednisone, or equivalent, >= 0.5 mg/kg/day. Inhaled and topical steroids are allowed.) •Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination (no laboratory testing required). •History of hypersensitivity to vaccines. •History of allergic disease or reactions likely to be exacerbated by any component of the vaccine. •History of chronic alcohol consumption and/or drug abuse. •Acute clinically significant pulmonary, cardiovascular, hepatic or renal functional abnormality, as determined by physical examination or laboratory screening tests. •Serious chronic disease including any medically significant chronic pulmonary, cardiovascular, renal, neurological, psychiatric or metabolic disorder, as determined by medical history and physical examination. (Subjects suffering from seasonal allergies or asthma under inhalative treatment can be included). •Acute disease at the time of enrolment. (Acute disease is defined as the presence of a moderate or severe illness with or without fever (defined as axillary temperature >=37.5°C)). •Administration of immunoglobulins and/or any blood products within the three months preceding the first administration of the candidate vaccine or during the study. •Lactating women. •Use of any investigational or non-registered product (drug or vaccine) other than the study vaccine(s) within 30 days prior to the first vaccination, or planned use during the study period. •Any condition which, in the opinion of the investigator, prevents the subject from 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 Day 0, Month 6, Month 6+ 7 Days, Month 6 + 21 Days, serum anti-HA (Indonesia strain) antibody titers, in VT/IN/6Mo group. Derived variables (with 95% confidence intervals): •Geometric mean titres (GMTs) of H5N1 antibody titres at Day 0, Month 6, Month 6+ 7 Days, Month 6+ 21 Days •Seroconversion rates at Month 6, Month 6+ 7 Days, Month 6+ 21 Days •Seroconversion factors at Month 6, Month 6+ 7 Days, Month 6+ 21 Days •Seroprotection rates at Day 0, Month 6, Month 6+ 7 Days, Month 6+ 21 Days
For the safety/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 and overall. •Percentage, intensity and relationship to vaccination of unsolicited local and general signs and symptoms during a 30-day follow-up period after priming vaccination(s) and booster vaccination, and overall. •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) | 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 | 11 |
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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 6 |