E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Vaccination of adults (18-60 years) and elderly (>60 years) with pandemic flu H5N1 vaccine. |
|
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 injection site reactions and systemic safety profile during the 21 days following each of two primary series and one booster (as applicable) intramuscular (IM) injections in two age groups: subjects aged 18 to 60 years (adults) or >60 years (elderly). • To describe the immune response 21 days after each of two primary series IM injections in two age groups: subjects aged 18 to 60 years (adults) and >60 years (elderly). • To describe the antibody persistence at 6 or 15 months after the first vaccination and prior to the Clade 2 booster vaccination in two age groups: subjects aged 18 to 60 years (adults) or >60 years (elderly). • To describe the immune response 21 days after a booster vaccination administered at either 6 months (Clade 1 booster) or later (Clade 2 booster) after the first vaccination in two age groups: subjects aged 18 to 60 years or >60 years. • To describe any serious adverse events (SAEs) during the whole trial.
|
|
E.2.2 | Secondary objectives of the trial |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1) Aged over 18 years on the day of inclusion. 2) Informed consent form signed. 3) Able to attend all scheduled visits and to comply with all trial procedures. 4) For a woman, inability to bear a child or negative urine pregnancy test. 5) For a woman of child-bearing potential, use of an effective method of contraception or abstinence for at least 4 weeks prior and at least 4 weeks after to each vaccination. 6) Addendum 1 of the informed consent form signed and dated by the subject (this inclusion criteria has to be checked only at V04 for subjects who are to receive a booster at M6 or later). 7) Addendum 2 of the informed consent form signed and dated by the subject (this inclusion criteria has to be checked only at V04_Add for subjects who are to receive a Clade 2 booster).
|
|
E.4 | Principal exclusion criteria |
1) Systemic hypersensitivity to any component of the vaccine or a life-threatening reaction after previous administration of a vaccine containing the same substances (egg proteins, chick proteins, thimerosal, aluminum, neomycin, formaldehyde, and octoxinol 9). 2) Febrile illness (oral temperature ≥37.5°C) on the day of inclusion. 3) Breast-feeding. 4) Previous vaccination with an avian flu vaccine. 5) Participation in a clinical trial (drug, device, or medical procedure) within 4 weeks prior to the first vaccination. 6) Planned participation in another clinical trial during the present trial period. 7) Congenital or acquired immunodeficiency, or receipt of immunosuppressive therapy such as anti-cancer chemotherapy or radiation therapy within the preceding 6 months or long-term systemic corticosteroid therapy. 8) Chronic illness that could interfere with trial conduct or completion (e.g. cardiac, renal, diabetes, or auto-immune disorders). 9) Current alcohol or drug abuse that may interfere with the subject’s ability to comply with trial procedures. 10) Receipt of blood or blood-derived products within the past 3 months. 11) Any vaccination within 4 weeks prior to the first trial vaccination. 12) Vaccination planned within 4 weeks after any trial vaccination. 13) Thrombocytopenia or bleeding disorder contraindicating intramuscular vaccination. 14) Subject deprived of freedom by an administrative or court order, or in an emergency setting, or hospitalized without his/her consent.
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
Safety - The occurrence, time to onset, number of days of occurrence, and severity of solicited (prelisted in the subject diary and Case Report Form [CRF]) injection site reactions and systemic reactions occurring within 7 days following each injection will be reported. - The occurrence, nature (Medical Dictionary for Regulatory Activities [MedDRA] preferred term), time to onset, duration, severity, relationship to vaccination and seriousness of unsolicited (spontaneously reported) adverse events (AEs) within 21 days following each injection will be reported. - The occurrence of the following reactions (MedDRA Preferred Terms given in parentheses) in the 3 days following each injection will be more especially reported (as defined by the European Medicines Agency (EMEA) Note for Guidance [CPMP/BWP/214/96]): - Injection site induration >5 cm observed for more than 3 days. - Injection site ecchymosis (injection site bruising). - Rectal equivalent temperature >38°C for 24 hours or more (pyrexia). - Malaise. - Shivering. - The occurrence, nature, time to onset, and relationship to vaccination of SAEs during the whole trial (including the 6 month follow-up period) will be reported.
Immunogenicity Primary series Hemagglutination inhibition assays will be performed using: 1. Horse erythrocytes (hemagglutination inhibition using horse erythrocytes [HIH] method) for all subjects. 2. Turkey erythrocytes (hemagglutination inhibition using turkey erythrocytes [HIT] method) for a subset of 80 subjects in each formulation group (40 subjects per age sub-group) for one vaccine strain only - A/H5N1 Clade 1: A/Vietnam/1194/2004 (H5N1)_RG14 (henceforth referred to as Clade 1) (Amendment 1). Anti-Hemagglutinin (anti-HA) titers against the A/H5N1 strain will be expressed as described below: - Anti-HA Ab titer obtained in duplicate on D0, D21, and D42, and summarized at the subject level by individual geometric means of duplicates at each timepoint. The following endpoints will be derived: * Individual titer ratios D21/D0, D42/D0, and D42/D21. * Seroprotection (titer ≥40 [turkey] or ≥32 [horse] 1/dilution [dil]) on D0, D21 and D42. * Seroconversion (for subjects with a titer <10 [turkey] or <8 [horse] [1/dil] on D0: post-injection titer ≥40 [turkey] or ≥32 [horse] [1/dil]) or significant increase (for subjects with a titer ≥10 [turkey] or ≥8 [horse] [1/dil]: ≥4-fold increase of the titer) at D21 and D42.
AND - Seroneutralization (SN) titer obtained in duplicate on D0, D21, and D42 and summarized at the subject level by individual geometric mean of duplicates at each timepoint. The following endpoints will be derived: * Individual titer ratios D21/D0, D42/D0, and D42/D21. * 2- and 4-fold increase from D0 to D21 and to D42
Antibody persistence Anti-HA titer (HIH method) and neutralizing Ab titer (SN method) in duplicate (prior to booster vaccination, if applicable) at M6 (D180) (if booster performed at M6) or at M6 and M15 and prior to the booster vaccination (for Clade 2 booster subjects).
Booster vaccination response One of two vaccine clades will be used as the booster strain (see Methodology/Trial Design). The booster Ab response will be assessed against the homologous strain in the vaccine. In addition, the antibody response to heterologous strains may be tested. - Anti-HA Ab titer obtained in duplicate at V04 (M6) and V05 (M6+21 days) (if 6 month booster) or V05 and V06 (if Clade 2 booster), and summarized at the subject level by individual geometric means of duplicates at each timepoint. The following endpoints will be derived: * Individual titer ratios V05/V04 or V06/V05. * Seroprotection (titer ≥32 1/dil) at V04 and V05 or V05 and V06. * Seroconversion (for subjects with a titer <8 [1/dil] at V04 or V05: post injection titer ≥32 [1/dil]) at V05 or V06, or a significant increase (for subjects with a titer ≥8 [1/dil]: ≥4-fold increase of the titer) at V05 or V06.
AND - SN titer obtained in duplicate at V04 and V05 (if 6-month booster) or V05 and V06 (if Clade 2 booster) and summarized at the subject level by individual geometric mean of the duplicates at each timepoint. The following endpoints will be derived: * Individual titer ratios V05/V04 or V06/V05. * 2- and 4-fold increase from V04 to V05 or V05 to V06.
|
|
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) | 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 | 1 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 4 |
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
|
Information provided in the protocol. |
|
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 | 7 |
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 | 7 |