E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Immunization of healthy adults against influenza |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Virus Diseases [C02] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10059430 |
E.1.2 | Term | Influenza immunization |
E.1.2 | System Organ Class | 100000004865 |
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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 evaluate the humoral response [anti- Haemagglutinin (HA) antibodies tested by Haemagglutination Inhibition (HI)] against each vaccine strain in adults 18-60 years and >60 years of age, 21 days after vaccination with Fluarix/Influsplit SSW 2013/2014. |
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E.2.2 | Secondary objectives of the trial |
1) To describe the reactogenicity and safety of Fluarix/Influsplit SSW 2013/2014 in adults 18-60 years and >60 years of age, in terms of solicited adverse events (AEs), unsolicited AEs and serious adverse events (SAEs).
2) To evaluate the humoral response (anti-HA antibodies tested by HI) against each vaccine strain, 21 days after vaccination, in adults 18-60 years and >60 years of age who have and who have not received an influenza vaccine during the 2 influenza seasons prior to season 2012/2013
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Subjects who the investigator believes can and will comply with the requirements of the protocol
• A male or female aged 18 years or above at the time of vaccination.
• Written informed consent obtained from the subject.
• Healthy subjects or subjects with well-controlled chronic diseases as established by medical history and clinical examination before entering the study.
• Female subjects of non-childbearing potential may be enrolled in the study
- Non-childbearing potential is defined as pre-menarche, current tubal ligation, hysterectomy, ovariectomy or post-menopause
• Female subjects of childbearing potential may be enrolled in the study, if the subject:
-has practiced adequate contraception for 30 days prior to vaccination, and
-has a negative pregnancy test on the day of vaccination, and
-has agreed to continue adequate contraception during the entire treatment period and for 2 months after completion of vaccination
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E.4 | Principal exclusion criteria |
• Participation in previous year’s Fluarix registration study (116663)
• Use of any investigational or non-registered product (drug or vaccine) other than the study vaccine within 30 days preceding the dose of study vaccine, or planned use during the study period.
• Chronic administration of immunosuppressants or other immune-modifying drugs within the six months prior to vaccination. Inhaled and topical steroids are allowed.
• Any administration of a long-acting immune-modifying drug within 6 months before study start, or planned administration during the study period.
• Administration of immunoglobulins and/or any blood products within the three months preceding the administration of the study vaccine or planned administration during the study period.
• Administration of an influenza vaccine within the twelve months preceding the study vaccination.
• Receipt of a vaccine other than the study vaccine within 30 days before study vaccination and/or plan to receive any vaccine other than the study vaccine during the entire study period.
• Clinically or virologically confirmed influenza infection within the six months preceding the study vaccination.
• Acute disease and/or fever at the time of enrolment.
- Fever is defined as temperature ≥ 37.5°C/99.5°F on oral, axillary or tympanic setting, or ≥ 38.0°C/100.4°F on rectal setting. The preferred route for recording temperature in this study will be axillary.
- Subjects with a minor illness (such as mild diarrhoea, mild upper respiratory infection) without fever may be enrolled at the discretion of the investigator.
• Acute, clinically significant pulmonary, cardiovascular, hepatic or renal functional abnormality, as determined by physical examination or laboratory screening tests.
• Chronic underlying disease (such as cancer, chronic obstructive pulmonary disease under oxygen therapy, insulin-dependent diabetes mellitus), not stabilized or clinically serious.
• History of chronic alcohol consumption and/or drug abuse.
• Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination (no laboratory testing required).
• History of Guillain-Barré syndrome.
• History of allergic disease or reactions likely to be exacerbated by any component of the vaccine including latex.
• Anaphylaxis following the administration of vaccine(s).
• Pregnant or lactating female.
• Female planning to become pregnant or planning to discontinue contraceptive precautions.
• Any condition which, in the opinion of the investigator, prevents the subject from participating in the study or would make intramuscular injection unsafe.
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E.5 End points |
E.5.1 | Primary end point(s) |
Humoral immune response in terms of anti-HA antibodies against each of the three vaccine influenza strains.
The following parameters will be calculated with 95% confidence intervals (CIs):
- Geometric mean titres (GMT) of anti-HA antibody titres
- Seroprotection rates (SPR)*
*SPR is defined as the percentage of vaccinees with serum HI titre ≥ 1:40; usually accepted as indicating protection in at least 50% of the vaccinees.
The following parameters will be calculated with 95% confidence intervals (CIs):
- Seroconversion rates (SCR)*.
- Mean geometric increase ([MGI] also known as the Seroconversion factor [SCF])**.
- Seroprotection power (SPP)***.
*SCR is defined as the percentage of vaccinees with either a pre-vaccination titre < 1:10 and a post-vaccination titre ≥ 1:40 or a pre-vaccination titre ≥ 1:10 and at least 4-fold increase in post-vaccination titre.
**MGI or SCF is defined as the fold increase in serum HI geometric mean titres post-vaccination compared to Day 0.
***SPP is defined as the percentage of subjects who have a pre-vaccination titre < 1:40 and a post-vaccination titre ≥ 1:40
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
At Day 0 and Day 21 post-vaccination for Geometric Mean Titres and Seroprotection Rates
At Day 21 post-vaccination for Seroconversion Rates, Mean Geometric Increases (Seroconversion Factors), and Seroprotection Powers. |
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E.5.2 | Secondary end point(s) |
1) Reactogenicity:
• Occurrence of solicited local and general symptoms
- Percentage, intensity and duration of solicited local symptoms
- Percentage, intensity, duration and relationship to vaccination of solicited general symptoms
• Occurrence of unsolicited symptoms
- Percentage, intensity and relationship to vaccination of unsolicited symptoms
• Occurrence of serious adverse events (SAEs)
- Percentage, intensity and relationship to vaccination of SAEs
2) Humoral immune response in terms of anti-HA antibodies against each of the three vaccine influenza strains, in subjects aged 18-60 years and >60 years who have and who have not received an influenza vaccine during the 2 influenza seasons prior to season 2012/2013.
• The following parameters will be calculated with 95% CIs:
- GMTs of anti-HA antibody titres and SPRs, in subjects who have and who have not received an influenza vaccine during the 2 influenza seasons prior to season 2012/2013.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
• Solicited local and general symptoms: During a 4-day follow-up period after vaccination (Days 0-3) (i.e. day of vaccination and 3 subsequent days).
• Unsolicited symptoms: During a 21-day follow-up period after vaccination (Days 0-20) (i.e. day of vaccination and 20 subsequent days).
• Serious adverse events: During the entire study period (Day 0-Day 21)
• Humoral immune response in subjects who have and who have not received an influenza vaccine during the 2 influenza seasons prior to season 2012/2013: At Day 0 and Day 21 post-vaccination |
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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 | Yes |
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) | 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 | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
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 | 4 |
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 | No |
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 | 0 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 21 |