E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Immunization against influenza A and/or B (GSK Biologicals’ influenza candidate vaccine GSK 2321138A) of healthy children aged 6 months to 35 months. |
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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 | 17.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10022000 |
E.1.2 | Term | Influenza |
E.1.2 | System Organ Class | 10021881 - Infections and infestations |
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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 efficacy of FLU D-QIV in the prevention of RT-PCR
confirmed moderate to severe influenza A and/or B disease due to any
seasonal influenza strain, when compared to non-influenza vaccine
controls in children aged 6 to 35 months.
•To evaluate the efficacy of FLU D-QIV in the prevention of RT-PCR confirmed influenza A and/or B disease due to any seasonal influenza strain, when compared to non-influenza vaccine controls in children aged 6 to 35 months. |
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E.2.2 | Secondary objectives of the trial |
-To evaluate the efficacy of FLU D-QIV when compared to non-influenza
vaccine controls in the prevention of:
• lower respiratory illness (LRI) and acute otitis media (AOM) associated
with RT-PCR confirmed influenza A and/or B (at any time starting 7 days
before the onset of LRI and ending 7 days after end of LRI)
• culture confirmed moderate to severe and of any severity influenza A
and/or B disease due to antigenically-matching influenza strains and any
seasonal influenza strain.
• RT-PCR confirmed severe influenza A and/or B disease.
-To evaluate the immunogenicity of FLU D-QIV in terms of HI antibody
response 28 days after completion of vaccination, in an immuno subcohort
of subjects
-To evaluate the reactogenicity of FLU D-QIV and non-influenza vaccine
controls in terms of:
• solicited local and general adverse events (AEs) and unsolicited
symptoms during 7 days and 28 days respectively after each vaccination
• AEs with MAV, SAEs and pIMDs during entire study period |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Subjects who the investigator believes that their parents/ LAR(s) can and will comply with the requirements of the protocol (e.g., completion of the diary cards, report an ILI or MAV using internet access, being available for follow-up phone contacts).
• A male or female between, and including, 6 and 35 months of age at the time of first vaccination; children are eligible regardless of history of influenza vaccination.
• Written informed consent obtained from the parent(s) /LAR(s) of the subject.
• Subjects in stable health as determined by medical history and clinical examination before entering into the study |
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E.4 | Principal exclusion criteria |
• Participation in a previous FLU-D-QIV-004 study (115345) cohort.
• Child in care
• Use of any investigational or non-registered product (drug or vaccine) other than the study vaccines within 30 days preceding the first dose of study vaccine, or planned use during the study period.
• Prior receipt of any influenza vaccine (registered or investigational) within 6 months preceding the first dose of study vaccine, or planned use of such vaccines during the study period.
• Children with underlying illness who are at risk of complications of influenza and for whom yearly (seasonal) influenza vaccination is recommended in their respective country.
• Any confirmed or suspected immunosuppressive or immunodeficient condition (including HIV), based on medical history and physical examination (no laboratory testing required).
• Chronic administration (defined as more than 14 days in total) of immunosuppressants or other immune modifying drugs within six months prior to the first vaccine dose. For corticosteroids, this will mean a dose equivalent to either ≥ 0.5 mg/kg of body weight or maximum of 10 mg/day of prednisone or equivalent. Inhaled and topical steroids are allowed.
• Administration of immunoglobulins and/ or any blood products within 3 months preceding the first dose of study vaccine or planned administration during the study period
• Any known or suspected allergy to any constituent of influenza vaccines (including egg proteins), non-influenza vaccine comparators (including neomycin) and latex; a history of anaphylactic-type reaction to consumption of eggs; or a history of severe adverse reaction to a previous vaccination
• Any contraindication to intramuscular injection
• Acute disease and/or fever at the time of enrolment.
Fever is defined as temperature ≥37.5°C by any root. Subjects with a minor illness (such as mild diarrhoea, mild upper respiratory infection) without fever may, be enrolled at the discretion of the investigator.
• Any other condition which, in the opinion of the Investigator, prevents the subject from participating in the study
Additional criteria for children ≥ 12 months of age:
• Prior receipt of any licensed varicella vaccine* or any licensed hepatitis A vaccine or planned use of these vaccines during the study period. Other routine registered childhood vaccinations are permitted.
*For countries with varicella vaccine administered as 2-dose schedule,prior receipt of a single dose of a varicella vaccine is allowed if administered at least 2 weeks before the first study vaccination
• Any history of hepatitis A or varicella diseases.
Additional criteria for children 6 - 11 months of age in countries without universal mass vaccination recommendation for pneumococcal vaccine:
• Prior receipt of any pneumococcal conjugated vaccine or planned use of this vaccine during the study period. Other routine registered childhood vaccinations are permitted. |
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E.5 End points |
E.5.1 | Primary end point(s) |
• First occurrence of RT-PCR confirmed moderate to severe influenza A
and/or B disease due to any seasonal influenza strain
• First occurrence of RT-PCR confirmed influenza A and/or B disease of
any severity due to any seasonal influenza strain |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
during the surveillance period (approximately 6 to 8 months) |
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E.5.2 | Secondary end point(s) |
Efficacy:
• First occurrence of Lower respiratory illness (LRI) with RT-PCR
confirmed influenza A and/or B infection due to any seasonal influenza
strain identified at any time starting 7 days before the onset of LRI and
ending 7 days after end of LRI
• First occurrence of culture-confirmed moderate to severe influenza A
and/or B disease due to antigenically-matching influenza strains.
• First occurrence of culture-confirmed influenza A and/or B disease of
any severity due to antigenically-matching influenza strains.
• First occurrence of culture-confirmed moderate to severe influenza A
and/or B disease due to any seasonal influenza strain.
• First occurrence of culture-confirmed influenza A and/or B disease of
any severity due to any seasonal influenza strain.
• First occurrence of acute otitis media (AOM) with RT-PCR confirmed
influenza A and/or B infection due to any seasonal influenza strain
identified at any time starting 7 days before the onset of AOM and
ending 7 days after end of AOM
• First occurrence of RT-PCR confirmed severe influenza A and/or B due
to any seasonal influenza strain.
Immunogenicity:
Humoral immune response in terms of haemagglutination-inhibition
(HI) antibody titres against each of four vaccine strains contained in FLU
D-QIV (in immuno sub-cohort of subjects only).
Derived variables:
- Geometric Mean Titres (GMTs) of HI antibody titres
- Seropositivity rates
- Seroconversion rates (SCR)*
- Mean geometric increase (MGI) **
- Seroprotection rates (SPR) ***
*SCR is defined as the percentage of vaccinees that have either a prevaccination
titre < 1:10 and a post-vaccination titre ≥1:40 or a prevaccination
titre ≥1:10 and at least a four-fold increase in postvaccination
titre.
**MGI is defined as the fold increase in serum HI GMTs post-vaccination
compared to prevaccination.
***SPR is defined as the percentage of vaccinees with a serum HI titre ≥
1:40 that usually is accepted as indicating protection in adults. SPR will
be also presented as the percentage of vaccinees with a serum HI titre ≥
1:80 and ≥1:160.
Safety:
• Solicited local and general symptoms
• unsolicited adverse events (AEs)
• AEs with MAV
• SAEs and pIMDs |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Efficacy:
• during the surveillance period (approximately 6 to 8 months)
Immunogenicity
• Geometric Mean Titers (GMTs) of HI antibody titres at Days 0 and 28/56.
• Seropositivity rates at Days 0 and 28/56.
• Seroconversion rates (SCR) at Day 28/56.
• Mean geometric increase (MGI) at Day 28/56.
• Seroprotection rates (SPR) at Days 0 and 28/56.
Safety
• Solicited local and general symptoms within 7 days (Day 0-Day 6)
after each vaccination
• Unsolicited AEs within 28 days (Day 0-Day 27) after each vaccination
• AEs with medically attended visits (MAV), Seriouse adverse events
(SAEs), potential immune-mediated diseases (pIMDs): during the entire
study period (6 to 8 months). |
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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 | No |
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 | No |
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 | Yes |
E.8.1.2 | Open | No |
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 | 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) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
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 | 19 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 64 |
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 | No |
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 |
Bangladesh |
Dominican Republic |
Honduras |
India |
Lebanon |
Philippines |
Poland |
Thailand |
Turkey |
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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 | 3 |
E.8.9.1 | In the Member State concerned months | 4 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 3 |
E.8.9.2 | In all countries concerned by the trial days | 4 |