| 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: To demonstrate absolute vaccine efficacy of aQIV versus non-influenza comparator (Boostrix®) when administered as a single dose to prevent first occurrence RT-PCR-confirmed influenza, due to any strain of influenza regardless of antigenic match to the strains selected for the seasonal vaccine, in subjects ≥ 65 years of age.
- Primary safety objective: To evaluate the safety of aQIV through assessment for local and systemic solicited adverse events through Day 7.
- To evaluate the rates in each vaccine group of medically-attended adverse events within 30 days after the first occurrence RT-PCR confirmed ILI.
- To evaluate the rates in each vaccine group of unsolicited adverse events for 21 days after vaccination and adverse events leading to withdrawal, serious adverse events (SAEs), adverse events of special interest (AESI), and new onset of chronic diseases (NOCD) for 365 days after vaccination. |
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| E.2.2 | Secondary objectives of the trial |
Key secondary efficacy objective: To demonstrate absolute vaccine efficacy of aQIV versus non-influenza comparator when administered as a single dose to prevent first occurrence culture-confirmed influenza, due to strains antigenically matched to the strains selected for the seasonal vaccine
Secondary immunogenicity objectives:
-To evaluate the immunogenicity of aQIV measured by HI titer 21 days after vaccination, against influenza strains homologous to the seasonal vaccine.
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| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1.Males and females ≥ 65 years old who are healthy or have co-morbidities
2.Individuals who or whose legal guardian have voluntarily given written consent after the nature of the study has been explained according to local regulatory requirements, prior to study entry.
3. Ability to attend all scheduled visits and to comply with study procedures including follow-up (and responding to messages and telephone contact). |
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| E.4 | Principal exclusion criteria |
1.Receipt of diphtheria or tetanus toxoid or pertussis (acellular or whole cell) vaccines within the previous 5 years.
2.History of behavioral or cognitive impairment or psychiatric condition that, in the opinion of the investigator, may interfere with the subject's ability to participate in the study.
3.History of any medical condition considered an adverse event of special interest, see Section 7.1.4.1, Adverse Events of Special Interest.
4.Progressive or severe neurological disorder, seizure disorder, or history of Guillain-Barré syndrome.
5.Hypersensitivity, including allergy, to any component of vaccines see Table 6.1-1 and Table 6.1-2 , medicinal products or medical equipment whose use is foreseen in this study.
6.Encephalopathy (e.g. coma, decreased level of consciousness, prolonged seizures) within 7 days of administration of a previous pertussis antigen-containing vaccine.
7.Clinical conditions representing a contraindication to intramuscular vaccination and blood draws, including bleeding diathesis, or any other condition that may be associated with prolonged bleeding.
8.Abnormal function of the immune system resulting from:
a.Clinical conditions.
b.Systemic administration of corticosteroids (PO/IV/IM) at a dose equivalent to 20 mg of prednisone for more than 14 consecutive days within 90 days prior to informed consent.
c.Administration of antineoplastic and immunomodulating agents (e.g. TNF α antagonists or anti-B cell antibodies) or radiotherapy within 1 year prior to informed consent.
9.Receipt of immunoglobulins or any blood products within 180 days prior to informed consent.
10.Receipt of an investigational or non-registered medicinal product within 30 days prior to informed consent or before completion of the safety follow-up period in another study and who are unwilling to refuse participation in another clinical study at any time during the conduct of this study (note: concomitant participation in an observational study not involving drugs, vaccines, or medical devices, is acceptable).
11.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.
12.Receipt of any influenza vaccine within 6 months prior to enrolment in this study or who plan to receive influenza vaccine while participating in the study.
13.Receipt of any inactivated vaccine 14 days or live-attenuated vaccine 28 days prior to enrolment in this study or who are planning to receive any vaccine within 28 days from study vaccination.
14.Fever at the time of screening, defined as oral temperature ≥38.0 degrees Celsius (≥ 100.4° F). Enrolment could be considered if fever is absent for 72 hours.
15.Signs or symptoms of acute respiratory tract infection at the time of screening. Enrolment could be deferred if signs and symptoms are absent for 72 hours.
16.Residence in a chronic care facility (e.g. nursing home).
17.Participation in this trial in a prior season, if applicable.
18.Fatal prognosis of an underlying medical condition (<12 months life expectancy).
19. 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. |
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| E.5 End points |
| E.5.1 | Primary end point(s) |
Primary safety endpoint: Safety objective 2 will be assessed by calculating the percentage of subjects in the solicited safety subset with solicited local and systemic adverse events from Day 1 through Day 7. Solicited local and systemic adverse event data from Day1-7 will be obtained from data collected on subject diary cards. Only subjects randomly selected for participation in the solicited safety subset will be asked to fill out subject diary cards from Day 1-7. Safety objectives 3 and 4 will be assessed based on:
- Percentage of subjects with medically-attended adverse events within 30 days after of first occurrence RT-PCR confirmed ILI.
- Percentages of subjects with any unsolicited AEs and concomitant medications reported from Day 1 through Day 22;
- Percentages of subjects with SAEs, AEs leading to withdrawal from the study, NOCD, AESI reported from Day 1 to Day 366 and all concomitant medications associated with these events.
Primary efficacy endpoint: the time to first-occurrence of RT-PCR-confirmed influenza from 21 through 180 days after vaccination or end of the influenza season, whichever is longer. |
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| E.5.1.1 | Timepoint(s) of evaluation of this end point |
Safety endpoint:
1. Day 1 through Day 7
2. Within 30 days after of first occurrence RT-PCR confirmed ILI.
3. Day 1 through Day 22
4. Day 1 to Day 366
Primary efficacy endpoint: from 21 through 180 days after vaccination or end of influenza season, whichever is longer. |
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| E.5.2 | Secondary end point(s) |
Secondary efficacy endpoint:
Vaccine efficacy will be determined based on either:
-Antigenically matched strains of influenza virus (Secondary Efficacy Objective 1).
-Influenza strains regardless of antigenic match (Secondary Efficacy Objective 2 and 4)
-Antigenically unmatched strains of influenza (Secondary Efficacy Objective 3).
Secondary immunogenicity endpoints:
The measures of immunogenicity used for Objective 5 as determined by the HI assay against homologous strains at Days 1 and 22 (unless indicated otherwise), include the following:
1.Geometric mean HI titers (GMT);
2.GMT ratios (GMRs) at Day 22/Day 1;
3.Percentages of subjects with an HI titer ≥1:40;
4.Percentages of subjects achieving seroconversion (defined as: HI ≥1:40 for subjects sero-negative at baseline [HI titer <1:10]; or a minimum 4-fold increase in HI titer for subjects sero-positive at baseline [HI titer ≥1:10]) on Day 22;
5.Reverse cumulative distributions of HI titers at Day 22. |
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| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| Immunogenicity endpoints:Days 1 and 22 (unless indicated otherwise) |
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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 | 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 |
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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 | 11 |
| 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 |
| Colombia |
| Malaysia |
| Philippines |
| Thailand |
| Austria |
| Estonia |
| Finland |
| Latvia |
| Lithuania |
| Poland |
| Bulgaria |
| Romania |
| Czechia |
| Turkey |
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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 biological samples, to be achieved no later than 8 months after collection of the last biological sample visit 7 (Day 366) |
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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 | |
| 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 | 6 |
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