E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Prophylaxis of influenza virus infection |
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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 | 20.0 |
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 |
EFFICACY: To demonstrate the absolute vaccine efficacy of QIVc versus a non-influenza vaccine to prevent at least one of the following: - RT-PCR confirmed illness caused by any influenza Type A and/or Type B virus, regardless of antigenic match. - Culture confirmed illness caused by influenza virus strains antigenically matched to the influenza strains selected for the seasonal influenza vaccine. |
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E.2.2 | Secondary objectives of the trial |
EFFICACY: Efficacy objectives evaluating QIVc compared to a non-influenza vaccine: - Prevention of culture confirmed illness caused by influenza virus strains antigenically dissimilar to the influenza strains selected for the seasonal vaccine. - Prevention of culture confirmed illness caused by any Type A and/or Type B virus. - Prevention of RT-PCR confirmed moderate-to-severe influenza caused by any influenza Type A and/or Type B virus.
IMMUNOGENICITY: To evaluate the immune response after vaccination with QIVc, 4 weeks after last vaccination in a sub-set of subjects 6 months through 47 months of age in each study vaccine group.
SAFETY: To evaluate the safety and tolerability of QIVc among subjects 6 months through 47 months of age in the QIVc group and comparator group. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Individuals of 6 through 47 months of age on the day of informed consent. 2. Individuals whose parent(s)/LAR have voluntarily given written informed consent after the nature of the study has been explained according to local regulatory requirements, prior to study entry. 3. Individuals who can comply with study procedures including follow-up. 4. Individuals in generally good health as per the Investigator's medical judgement. |
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E.4 | Principal exclusion criteria |
1. Acute (severe) febrile illness. Enrollment could be considered if the fever is absent for 72 hours. 2. History of any anaphylaxis, serious vaccine reactions or hypersensitivity, including allergic reactions, to any component of vaccine or medical equipment whose use is foreseen in this study. 3. Clinical conditions representing a contraindication to intramuscular vaccination and blood draws. These may include known bleeding disorders, or treatment with anticoagulants in the 3 weeks preceding vaccination. 4. A known history of Guillain-Barré Syndrome or other demyelinating diseases such as encephalomyelitis and transverse myelitis. 5. Abnormal function of the immune system resulting from clinical conditions, which include: a. Known or suspected congenital or acquired immunodeficiency. b. Systemic administration of corticosteroids (PO/IV/IM) at any dose for more than 14 days, within 90 days prior to informed consent. Topical, inhaled and intranasal corticosteroids are permitted. Intermittent use (one dose in 30 days) of intra-articular corticosteroids is also permitted. c. Administration of antineoplastic and immunomodulating agents or radiotherapy within 90 days prior to informed consent. 6. Received immunoglobulins or any blood products within 180 days prior to informed consent. 7. Received an investigational or non-registered medicinal product within 30 days prior to informed consent, or intend to participate in another clinical trial during the study. 8. Participated in this trial in a prior season or is discontinued after randomization in the current season. 9. Study personnel, family and household members of study personnel should not participate. 10. Any other clinical condition that, in the opinion of the investigator, might interfere with the results of the study or pose additional risk to the subject due to participation in the study. 11. Received influenza vaccination or has had documented influenza disease in the last 6 months prior to informed consent. 12. Prior vaccination to prevent Neisseria meningitidis serogroup C disease or prior infection caused by this organism. 13. Received any other vaccines than influenza vaccine within 14 days (for inactivated vaccines) or 28 days (for live vaccines) prior to study vaccination or who are planning to receive any vaccine within 28 days after study vaccination. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Efficacy Endpoints evaluating QIVc compared to a non-influenza vaccine: 1a. First occurrence of RT-PCR confirmed influenza, due to any influenza Type A and/or B virus regardless of antigenic match to the influenza strains selected for the seasonal influenza vaccine, occurring at > 14 days after the last vaccination and until the end of the influenza season, in association with protocol-defined ILI symptoms. 1b. First occurrence of culture confirmed influenza, due to influenza Type A and/or B virus antigenically matched by ferret antigenicity testing to the influenza strains selected for the seasonal influenza vaccine, occurring at > 14 days after the last vaccination and until the end of the influenza season, in association with protocol defined ILI symptoms. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
> 14 days after the last vaccination and until the end of the influenza season. |
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E.5.2 | Secondary end point(s) |
Secondary Efficacy endpoints evaluating QIVc compared to a non-influenza vaccine: 1. First occurrence of culture confirmed influenza caused by influenza virus strains antigenically dissimilar to the influenza strains selected for the seasonal vaccine occurring at > 14 days after the last vaccination and until the end of the influenza season, in association with protocol defined ILI symptoms; 2. First occurrence of culture confirmed influenza due to any influenza Type A and/or Type B virus regardless of antigenic match to the influenza strains selected for the seasonal influenza vaccine, occurring at > 14 days after the last vaccination and until the end of the influenza season, in association with protocol-defined ILI symptoms; 3. First occurrence of RT-PCR confirmed moderate-to-severe influenza due to any influenza Type A and/or Type B virus regardless of antigenic match to the influenza strains selected for the seasonal influenza vaccine, occurring at > 14 days after the last vaccination and until the end of the influenza season.
Secondary Immunogenicity endpoints. The measures for immunogenicity are determined by a haemagglutination inhibition [HI] and a microneutralisation [MN] assay prior to vaccination (Visit 1) and 28 days after last vaccination for all four influenza strains. For each assay the measures include: 1. Pre and post-vaccination geometric mean titers (GMTs); 2. Seroconversion rates (SCR): Defined as the percentage of subjects with either a prevaccination HI (or MN) titer < 1:10 and a postvaccination HI (or MN) titer ≥ 1:40, or a prevaccination HI (or MN) titer ≥ 1:10 and a ≥ 4-fold increase in postvaccination HI (or MN) titer; 3. Geometric mean ratio (GMR): GMR is the geometric mean of the fold increase of post-vaccination HI (or MN) titer over the pre-vaccination HI (or MN) titer.
Secondary Safety endpoints: 1. Percentage of subjects with solicited local and systemic adverse events (AEs) will be assessed for 7 days following each vaccination in the QIVc group and the comparator group; 2. Percentage of subjects with unsolicited AEs will be assessed in the QIVc group and in the comparator group until 28 days after each vaccination; 3. Percentage of subjects with SAEs, NOCDs, AE leading to withdrawal from the study or vaccination and all medications associated with these events will be reported in the QIVc group and in the comparator group; 4. Percentage of subjects with medically attended AEs within 30 days after ILI onset will be reported in the QIVc group and in the comparator group. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Efficacy endpoints 1, 2 and 3: > 14 days after the last vaccination and until the end of the influenza season. Immunogenicity endpoints 1, 2 and 3: Day 1 and 28 days after last vaccination. Safety endpoint 1: Day 1 to 7 days after each vaccination; Safety endpoint 2: Day 1 to 28 days after last vaccination; Safety endpoint 3: Day 1 to LSLV Safety endpoint 4: Day of ILI onset to 30 days after ILI onset |
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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 | 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 | Yes |
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) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
Non-flu vaccine comparator and saline for injection (placebo) |
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E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
Will this trial be conducted at a single site globally?
| No |
E.8.4 | Will this trial be conducted at multiple sites globally? | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | Specify the countries outside of the EEA in which trial sites are planned |
Honduras |
Malaysia |
New Zealand |
Philippines |
Thailand |
Ukraine |
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E.8.7 | Trial has a data monitoring committee | Yes |
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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For the purpose of this protocol, end of study is defined as the completion of the testing of such biological samples, to be achieved no later than 8 months after the date of last unscheduled visit by a subject who manifested signs of influenza-like-illness (ILI) during the protocol defined influenza season and from whom a NP sample was taken. |
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E.8.9 Initial estimate of the duration of the trial |
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 | 1 |