E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Profylaxis for Influenza virus |
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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 |
- Primary Efficacy Objective(s):
To demonstrate absolute vaccine efficacy of QIVc versus a non-influenza comparator determined by first occurrence RT-PCR or culture confirmed influenza, due to any influenza Type A and B strain in subjects ≥2 years to <18 years of age.
In case of successful demonstration of the primary efficacy objective:
- Co-Primary Efficacy Objective(s):
To demonstrate absolute vaccine efficacy of QIVc versus a non-influenza comparator determined by first occurrence RT-PCR or culture confirmed influenza, due to any influenza Type A and B strain in subjects ≥3 years to <18 years of age. |
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E.2.2 | Secondary objectives of the trial |
The following secondary objectives will be evaluated in specific age cohorts:
*Efficacy:
Demonstrate absolute vaccine efficacy of QIVc determined in 4 ways:
1. determined by first occurrence RT-PCR or culture confirmed influenza, due to any influenza Type A and B strain.
2. determined by first occurrence RT-PCR influenza, due to any influenza Type A and B strain.
3. determined by first occurrence culture confirmed influenza, due to any influenza Type A and B strain.
4. determined by first occurrence culture confirmed influenza, caused by influenza strains antigenically matched
*Immunogenicity:
To characterize the immunogenicity of QIVc by HI assay.
*Safety:
Assess the safety and tolerability of QIVc. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Males or females ≥2 years to <18 years of age on the day of first study vaccination;
2. Individual has and/or has (a) parent(s) or legal guardian(s) who has/have given informed consent/assent after the nature of the study has been explained in accordance with the practices described in protocol and according to local regulatory requirements;
3. If the individual is of an age where, according to local regulations, informed assent is required, that individual has provided assent to participate in the study.
4. Individual and individual’s parent or legal guardian can comply with study procedures and are available for follow-up;
5. Individual is in generally good health as per the Investigator’s medical judgement; |
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E.4 | Principal exclusion criteria |
1. Individual with clinical signs of fever and/or an oral temperature of ≥ 100.4 F (38.0 degrees Celsius) within three days prior to vaccination;
2. Individuals with a known history of any anaphylaxis, serious vaccine reactions or hypersensitivity to any of the vaccine components described in investigator brochure, or having any of the contraindications listed in the package insert of the comparator vaccine;
3. Individuals with history of Guillain-Barré syndrome or other demyelinating diseases such as encephalomyelitis and transverse myelitis;
4. Female subject “of childbearing potential”, sexually active, and not used any of the “acceptable contraceptive method” for at least 2 months prior to study entry and intend to use until the end of subject participation;
5. Individual is pregnant or breast feeding female;
6. Individual and/or individual’ parent/guardians who are not able to comprehend or follow all required study procedures for the whole period of the study;
7. Individual has received prior Meningococcal ACWY vaccination that conflicts with national recommendations or local practices for timing of primary or booster vaccination
8. Individual has received influenza vaccination or has had documented influenza disease in the last 6 months;
9. Known or suspected congenital or acquired immunodeficiency; or receipt immunosuppressive therapy, such as anti-cancer chemotherapy or radiation therapy, within the preceding 6 months; or systemic corticosteroid therapy (prednisone or equivalent) at any dose for more than 2 consecutive weeks (14 days) within the past 3months. Topical, inhaled and intranasal corticosteroids are permitted. Intermittent use (one dose in 30 days) of intra-articular corticosteroids is also permitted;
10. Administration of immunoglobulin and/or any blood products within the 3 months preceding vaccination, or planned administration during the study;
11. Individual has participated in any clinical trial with another investigational product 30 days prior to first study visit or intent to participate in another clinical study at any time during the conduct of this study. Concomitant participation in an observational study (not involving drugs, vaccines, or medical devices) is acceptable;
12. Medical conditions or treatments contraindicating intramuscular vaccination due to increased risk of bleeding. These may include known bleeding disorders (such as thrombocytopenia), or treatment with anticoagulants (such as warfarin) in the 3 weeks preceding vaccination. However, antiplatelet agents such as low-dose aspirin, ticlopidine (Ticlid) and clopidogrel (Plavix) are permitted;
13. Evidence, or history (within the previous 12 months) of drug or alcohol abuse;
14. Study personnel or immediate family members (brother, sister, child, parent), the spouse of study personnel or individuals who are financially or emotionally dependent on study staff
15. Participation in this trial in a prior season, if applicable.
16. Any 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 |
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E.5 End points |
E.5.1 | Primary end point(s) |
- Primary Efficacy Endpoint(s)
The primary efficacy endpoint is the time from the last study vaccination to the onset of the first occurrence confirmed influenza by either RT-PCR-confirmed or culture-confirmed, due to any influenza Type A or B strain regardless of antigenic match to the strains selected for the seasonal vaccine, occurring >14 days after the last vaccination and until the end of the influenza season. |
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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 Safety Endpoint(s)
Safety will be assessed by calculating:
* The percentage of subjects with solicited local and systemic adverse events for 7 days following vaccination at Day 1 (“previously vaccinated” subjects) or Day1 and Day 29, (“not previously vaccinated” subjects) in the QIVc group and the non-influenza comparator vaccine group.
* The percentage of subjects with all unsolicited AEs will be assessed from Day 1 to Day 22 for “previously vaccinated” subjects or Day 1 to Day 50 for “not previously vaccinated” subjects in the QIVc group and in non-influenza comparator vaccine group.
* Percentage of subjects with SAEs, AEs leading to withdrawal from the study and NOCDs reported during the subject’s entire participation in the study, i.e. from Day 1 to Day 181 (for “previously vaccinated” subjects) or to Day 209 (for “not previously vaccinated” subjects), or until the end of influenza season, whichever is longer, and all medications associated with these events.
* Percentage of subjects with medically-attended adverse events within 30 days after of first occurrence RT-PCR confirmed ILI.
- Secondary Efficacy Endpoint(s)
* The efficacy endpoint for secondary objective 1 is the time from the last study vaccination to the onset of the first occurrence confirmed influenza by either RT-PCR confirmed or culture-confirmed, due to any influenza Type A or B strain regardless of antigenic match to the strains selected for the seasonal vaccine, occurring at >14 days after the last vaccination and until the end of the influenza season.
* The efficacy endpoint for secondary objective 2 is the time from the last study vaccination to the onset of the first-occurrence confirmed influenza by RT-PCR confirmed, due to any influenza Type A or B strain regardless of antigen match to the strains selected for the seasonal vaccine, (occurring at >14 days after the last vaccination and until the end of the influenza season).
* The efficacy endpoint for secondary objective 3 is time from the last study vaccination to the onset of the first-occurrence confirmed influenza by culture confirmed, due to any influenza Type A or B strain regardless of antigenic match to the strains selected for the seasonal vaccine, (occurring at >14 days after the last vaccination and until the end of the influenza season).
* The efficacy endpoint for secondary objective 4 is the time from the last study vaccination to the onset of the first-occurrence confirmed influenza by culture-confirmed, due to influenza Type A or B strain antigenic matched to the strains selected for the seasonal vaccine, (occurring at >14 days after the last vaccination and until the end of the influenza season).
- Secondary Immunogenicity Endpoints
The measures for assessing immunogenicity as determined by HI are as follows:
* HI Geometric mean titers (GMTs) on Day 1 (all subjects), Day 22 (all “previously vaccinated” subjects receiving a single vaccine dose) or Days 29 and 50 (all “not previously vaccinated” subjects receiving 2 doses) for all 4 influenza strains.
* Percentage of subjects achieving seroconversion (defined as: either a prevaccination HI titer < 1:10 and a post-vaccination HI titer ≥ 1:40 or a prevaccination HI titer ≥ 1:10 and a ≥ 4-fold increase in post-vaccination HI titer) on Day 22 (all “previously vaccinated” subjects receiving a single vaccine dose) or Days 29 and 50 (all “not previously vaccinated” subjects receiving 2 doses) for all 4 influenza strains.
* HI Geometric Mean Ratio (GMR) of Day 22/Day 1 (all “previously vaccinated” subjects receiving a single vaccine dose) or Day 29/Day 1 and Day 50/Day 1 (all “not previously vaccinated” subjects receiving 2 doses) for all 4 influenza strains.
* Percentage of subjects with HI titer ≥ 1:40 on Day 22 (all “previously vaccinated” subjects receiving a single vaccine dose) or Days 29 and 50 (all “not previously vaccinated” subjects receiving 2 doses) for all 4 influenza strains. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
See above for specific timepoints per endpoint |
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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) | Yes |
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) | 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 |
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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 | 7 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 26 |
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 |
Australia |
Finland |
Lithuania |
Philippines |
Poland |
Spain |
Thailand |
Estonia |
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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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End of study is defined as the completion of the testing of such biological samples, to be achieved no later than 8 months after last subject last visit. |
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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 | 2 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
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 | 0 |