E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Prophylaxis of influenza, especially in those who run an increased risk of associated complications. |
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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 |
The primary objective of this study is to determine the immunogenicity of the trivalent influenza subunit vaccine Influvac for the season 2006/2007, in two groups of healthy subjects: adults aged ≥18 and ≤60 years and elderly ≥61 years of age. The safety objective is to collect data on the safety and tolerability (reactogenicity and overall inconvenience) of Influvac. |
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E.2.2 | Secondary objectives of the trial | |
E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
1. Signed and dated informed consent. 2. Healthy and aged ≥18 and ≤ 60 years or ≥ 61 years of age. 3. Mental health must be good enough to understand the study and the informed consent form and to fill in the questionnaire. |
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E.4 | Principal exclusion criteria |
1. Known to be allergic to eggs, chicken protein, gentamicin or any other constituent of the vaccine. 2. Having fever and/or presenting with an acute infectious episode of the upper and/or lower respiratory airways. 3. Having experienced a documented serious systemic reaction after previous influenza vaccination. 4. Having an auto-immune disorder (e.g. RA, SLE, auto-immune thyroid disorders) or other disorders affecting the immune system, taking immunosuppressive medication (such as systemic corticosteroids) including the four weeks preceding the start of the study (date of informed consent), or having a disease in a terminal stage. 5. Having received vaccination against influenza within the previous six months before Visit 1. Exclusion criteria only for female subjects aged ≥18 and ≤ 60 years and of childbearing potential: 6. Pregnancy (positive urine pregnancy test on Day 1) or breastfeeding. 7. Absence of use of a medically accepted method of birth control (i.e. oral contraceptive, Intra Uterine Device, double barrier method). The rationale for the above exclusion criteria 1 and 3 is that of safety; exclusion criteria 2, 4 and 5 are necessary for eligibility, as they prevent interference with this study’s primary objective (immunogenicity against hemagglutinin of the specified strains of influenza ; also see section 7.8); and although allowed as per label, exclusion criteria 6 and 7 are standard for these clinical studies due to administrative reasons.
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E.5 End points |
E.5.1 | Primary end point(s) |
Serological parameters according to the Note for guidance on Harmonization of Requirements for influenza Vaccines (CPMP/BWP/214/96 1997), derived from the observed HI titers: -the pre and post vaccination protection rates -the proportion of subjects with seroconversion or at least a 4 fold increase in HI titer -the mean fold increase.
Immunogenicity The following serological measures will be derived from the individual HI antibody titers, separately for each strain: -the pre and post vaccination protection rates, with protection defined as HI antibody titer> 40 -the seroconversion rate, with seroconversion defined as a pre vaccination HI titer <10 and a post vaccination HI titer> 40 -the proportion of subjects with at least a 4 fold increase in HI titer, i.e. the proportion of subjects with a pre vaccination titer >10 and a post vaccination relative increase of > 4 fold -the proportion of subjects with seroconversion or at least a 4 fold increase in HI titer -the mean fold increase, which is the geometric mean of the intra-individual increases (i.e. post vaccination HI titer/pre vaccination HI titer).
The results of the serological analysis will be evaluated according to the CHMP Note for Guidance which requires that for both age groups at least one of the following criteria is met for each of the three strains:
Criterion Adults Elderly
proportion of subjects achieving a HI titer >40 : >70% >60%
proportion of subjects with a seroconversion or at least a 4 fold increase : >40% >30% mean fold increase : >2.5 >2
Serology will be analysed for the efficiency sample, which is defined as the sample of all vaccinated volunteers for whom both the pre and post vaccination HI titers are available. Volunteers with an intercurrent confirmed influenza infection will be excluded from the serological analysis. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Information not present in EudraCT |
E.6.2 | Prophylaxis | Information not present in EudraCT |
E.6.3 | Therapy | Information not present in EudraCT |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Information not present in EudraCT |
E.6.7 | Pharmacodynamic | Information not present in EudraCT |
E.6.8 | Bioequivalence | Information not present in EudraCT |
E.6.9 | Dose response | Information not present in EudraCT |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | Information not present in EudraCT |
E.6.12 | Pharmacoeconomic | Information not present in EudraCT |
E.6.13 | Others | Information not present in EudraCT |
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) | No |
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 | No |
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
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
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 | Information not present in EudraCT |
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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Each volunteer should be evaluated at the termination visit (Day 22). Should any adverse event be identified at this visit, the investigator should continue to follow the volunteer as described in section 9.1.2, Follow up of Adverse events of 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 | 1 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 1 |