| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Healthy volunteers (Active immunization of adults and children against influenza) |
| Zdraví dobrovolníci (očkování dospělých a dětí proti chřipce) |
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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 | 17.0 |
| 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.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 17.0 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10022002 |
| E.1.2 | Term | Influenza A virus infection |
| E.1.2 | System Organ Class | 100000004862 |
|
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 17.0 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10022003 |
| E.1.2 | Term | Influenza B virus infection |
| E.1.2 | System Organ Class | 100000004862 |
|
| 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 describe the safety of 1 dose of FLU D-QIV vaccine produced by the IP and 1 dose of FLU D-QIV vaccine produced by the LP in terms of solicited (7 days after vaccination) and unsolicited adverse events (AEs) 21 days after vaccination in subjects aged 18-49 years.
•To demonstrate the immunogenic non-inferiority of FLU D-QIV IP as compared to FLU D-QIV LP in terms of haemagglutination inhibition (HI) geometric mean titer (GMT) ratio at 28 days after completion of the vaccination series in subjects aged 3-17 years.
•To demonstrate the immunogenic non-inferiority of FLU D-QIV IP as compared to FLU D-QIV LP in terms of HI GMT ratio at 28 days after completion of the vaccination series in subjects aged 6-35 months.
•To demonstrate there is no significant increase of fever ≥38ºC after any dose with FLU D-QIV IP compared to FLU D-QIV LP during the 7 days post-vaccination in subjects aged 6-35 months. |
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| E.2.2 | Secondary objectives of the trial |
To describe the immunogenicity of the FLU D-QIV IP vaccine and of FLU D-QIV LP vaccine:
-at 21 days after vaccine in subjects aged 18-49 years
-at 28 days after completion of the vaccination series in subjects aged 3-17 years.
- at 28 days after completion of the vaccination series in subjects aged 6-35 month
To describe
-The Relative Risk (RR) of myalgia after Dose 1 or Dose 2 (overall per subject) of FLU D-QIV IP compared to FLU D-QIV LP within 7 days post-vaccination in subjects aged 5-17 years
-The RR of fever ≥ 38ºC (100.4ºF) and > 39ºC (102.2ºF) after Dose 1 or Dose 2 (overall per subject) in the FLU D-QIV IP compared to FLU D-QIV LP occurring within 2 days post-vaccination in subjects aged 6 months to < 5 years of age (pooling of 2 independent cohorts).
-To describe the reactogenicity/safety of FLU D-QIV IP vaccine and of FLU D-QIV LP vaccine, including the symptoms of ORS over 3 days post vaccination, in subjects aged 6-35 months. |
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| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
All subjects
•Subjects who the investigator believes that they/their parent(s)/Legally Acceptable Representatives (LAR(s)) can and will comply with the requirements of the protocol (e.g., completion of the diary cards, return for follow-up visits).
•Written informed consent obtained from the subject/their parent(s)/LAR(s) before any study procedure.
•Written informed assent obtained from the subject if/as required by local regulations.
•Subjects in stable health as determined by the investigator's clinical examination and assessment of subject's medical history.
•Subjects are eligible regardless of history of administration of influenza vaccine in a previous season.
•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 for 2 months after vaccination.
Pediatric cohort
United States:
•A male or female subject between, and including, the ages of 3 and 17 years in the United States.
Rest of the World:
•A male or female subject between, and including, the ages of 6 months to 17 years all countries with the exception of the United States.
All participating countries:
•Subjects who the investigator believes that they/their parent(s)/Legally Acceptable Representatives (LAR(s)) can and will comply with the requirements of the protocol.
•Written informed consent obtained from the subject/parent(s)/LAR(s) of the subject.
•Written informed assent obtained from the subject if/as required by local regulations.
•Healthy subjects or those with chronic well-controlled disease as established by medical history and clinical examination before entering into 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.
•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 the vaccination series. |
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| E.4 | Principal exclusion criteria |
Adults aged 18-49 years cohort
•Child in care.
•Use of any investigational or non-registered product (drug or vaccine) other than the study vaccine within 30 days preceding the first dose of study vaccine, or planned use during the study period.
•Concurrently participating in another clinical study, at any time during the study period, in which the subject has been or will be exposed to an investigational or a non-investigational product (pharmaceutical or device).
•Chronic administration (defined as more than 14 days in total) of immunosuppressants or other immune-modifying drugs within 6 months prior to the first vaccine dose. Inhaled and topical steroids are allowed.
•Any confirmed or suspected immunosuppressive or immunodeficient condition based on medical history and physical examination.
•Any administration of a long-acting immune-modifying drug within 6 months before study start, or planned administration during the study period.
•Administration of an influenza vaccine during the 6 months preceding entry into the study.
•Administration of a vaccine not foreseen by the study protocol within 30 days before vaccination or planned administration during the study period.
•Administration of immunoglobulins and/or any blood products within the 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); a history of anaphylactic-type reaction to consumption of eggs; or a history of severe adverse reaction to a previous influenza vaccine.
•Acute or un-controlled, clinically significant pulmonary, cardiovascular, hepatic or renal functional abnormality, as determined by physical examination or laboratory tests.
•Any history of Guillain-Barré Syndrome.
•Acute disease and/or fever at the time of enrolment. Fever is defined as temperature ≥ 38.0ºC/100.4ºF.
•Pregnant or lactating female.
•Female planning to become pregnant or planning to discontinue contraceptive precautions.
•History of chronic alcohol consumption and/or drug abuse.
•Any contra-indication to intramuscular administration of influenza vaccines.
•Any other condition which, in the opinion of the investigator, prevents the subject from participating in the study.
Pediatric cohort
•Child in care.
•Use of any investigational or non-registered product (drug or vaccine) other than the study vaccine within 30 days preceding the first dose of study vaccine, or planned use during the study period.
•Concurrently participating in another clinical study, at any time during the study period, in which the subject has been or will be exposed to an investigational or a non-investigational product (pharmaceutical or device).
•Chronic administration (defined as more than 14 days in total) of immunosuppressants or other immune-modifying drugs within 6 months prior to the first vaccination dose. Inhaled and topical steroids are allowed.
•Any confirmed or suspected immunosuppressive or immunodeficient condition based on medical history and physical examination.
•Any administration of a long-acting immune-modifying drug within 6 months before study start, or planned administration during the study period.
•Administration of an influenza vaccine during the 6 months preceding entry into the study.
•Administration of a vaccine not foreseen by the study protocol within 30 days before vaccination or planned administration during the study period.
•Administration of immunoglobulins and/or any blood products within the 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); a history of anaphylactic-type reaction to consumption of eggs; or a history of severe adverse reaction to a previous influenza vaccine.
•Acute or un-controlled, clinically significant pulmonary, cardiovascular, hepatic or renal functional abnormality, as determined by physical examination or laboratory tests.
•Any history of Guillain-Barré Syndrome.
•Acute disease and/or fever at the time of enrolment. Fever is defined as temperature ≥ 38.0ºC/100.4ºF.
•Pregnant or lactating female.
•Female planning to become pregnant or planning to discontinue contraceptive precautions.
•History of chronic alcohol consumption and/or drug abuse.
•Any contra-indication to intramuscular administration of influenza vaccines.
•Any other condition which, in the opinion of the investigator, prevents the subject from participating in the study.
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|
| E.5 End points |
| E.5.1 | Primary end point(s) |
Subjects aged 18-49 years
-Occurrence of solicited local and general adverse events (AEs)
-Occurrence of oculorespiratory syndrome (ORS).
-Occurrence of medically attended events (MAEs) and serious adverse events (SAEs)
Subjects aged 3-17 years old
-Haemagglutination inhibition (HI) titers for each of the 4 influenza strains
-Occurrence of solicited local and general AEs in subjects aged 3-4 years and 5-17 years
-Occurrence of symptoms of ORS
-Occurrence of unsolicited AEs
-Occurrence of MAEs and SAEs
Subjects aged 6-35 months
-HI antibody titers for each of the 4 influenza strains
-Occurrence of fever ≥38ºC (100.4ºF) after Dose 1 or Dose 2 (overall per subject)
|
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
Adults aged 18-49 years
-During 7 days (Days 0-6) post-vaccination
-During 3 days (Days 0-2) post-vaccination
-During a 21-days (Days 0-20) follow-up period after vaccination
-During the entire study period (Days 0-20)
Subjects aged 3-17 years
-Days 0 and 28
-During 7 days (Days 0-6) post-vaccination
-During 3 days (Days 0-2) post-vaccination
-During a 28-days (Days 0-27) follow-up period after vaccination
-During the entire study period (Days 0-28)
Subjects aged 6-35 months
-Days 0 and 56
-During 7 days (Days 0-6) post-vaccination |
|
| E.5.2 | Secondary end point(s) |
Adults aged 18-49 years
-Humoral immune response in terms of HI antibodies
Children aged 3-17 years
-Humoral immune response in terms of HI antibodies
-Occurrence of myalgia in subjects aged 5-17 years
Children aged 6-35 months
-Occurrence of fever ≥ 38°C (100.4ºF)
-Humoral immune response in terms of HI antibodies
--Occurrence of solicited local and general AEs
-Occurrence of ORS
-Occurrence of MAEs and SAEs |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
Adults aged 18-49 years
-Days 0 and 21
Children aged 3-17 years
-Day 0 and 28 days after completion of the vaccine series
-During 7 days (Days 0-6) post-vaccination
Children aged 6-35 months
-Day 0 and 28 days after completion of the vaccine series
-During 7 days (Days 0-6) post-vaccination
-During 3 days (Days 0-2) post-vaccination
-During a 28-days (Days 0-27) follow-up period after vaccination
-During the entire study period (Days 0-56) |
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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 | No |
| 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 |
| Efficacy - immunogenicity |
|
| 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 | Yes |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| 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 | 6 |
| 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 | 12 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 51 |
| 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 |
| Czech Republic |
| France |
| Germany |
| Korea, Republic of |
| Poland |
| Spain |
| United States |
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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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| LVLS |
| Poslední návštěva posledního subjektu |
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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 | |
| E.8.9.1 | In the Member State concerned months | 5 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial months | 5 |
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