| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
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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 |
| To evaluate the safety and tolerability of Immunose™ FLU based on Endocine™ and quadrivalent influenza antigens in older adults (50 to 75 years). |
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| E.2.2 | Secondary objectives of the trial |
To evaluate the immune response to Immunose™ FLU based on Endocine™ and quadrivalent influenza antigens in older adults by measurement of haemagglutination-inhibition (HI), virus neutralization (VN) and single radial haemolysis (SRH) titres in serum, and immunoglobulin A (IgA) titers in nasal secretions.
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| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Signed informed consent prior to any study related procedures.
2. Male or female 50-75 years of age (both inclusive) at screening.
3. Subjects who the Investigator believes will comply with the requirements of the protocol.
4. Judged by the Investigator to have no serious illness based on medical history, physical examination, ECG, vital signs and blood and urine assessments at screening.
5. All females should have been post-menopausal for at least 12 months or use a highly effective contraceptive method to prevent pregnancy. |
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| E.4 | Principal exclusion criteria |
1. Diagnosis of laboratory-confirmed influenza in the 2017/2018 season.
2. Use of any investigational drug product within 3 months before screening or planned use during the study period, including the safety follow-up period.
3. Administration of an influenza vaccine during the 9 months before screening.
4. Previously received another vaccine within 28 days before administration of the study vaccine, or is scheduled to receive another vaccine during the study period, excluding the safety follow-up period.
5. Any contra-indication to intramuscular administration of the influenza vaccine Influsplit Tetra (Fluarix Tetra) according to its SPC.
6. History of any anaphylactic reaction and/or serious allergic reaction following a vaccination, a proven hypersensitivity to any component of the study vaccine (e.g., to eggs or egg product as well as ovalbumin, chicken protein, chicken feathers, influenza viral protein, kanamycin, gentamycin, neomycin sulphate, formaldehyde and sodium deoxycholate).
7. Diagnosis of asthma with poor disease control as assessed by the Investigator.
8. Potent immunosuppressive therapy including cytostatics, antibodies, drugs acting on immunophilins, interferons and other drugs used to prevent rejection of organ transplants, within 6 months before screening.
9. Use of any parenteral or oral corticosteroids within 30 days prior to screening. Inhaled steroids are allowed.
10. Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination.
11. Any progressive or severe neurologic disorder, seizure disorder or Guillain-Barré syndrome.
12. Any history of Guillain-Barré syndrome.
13. Received blood, blood products and/or plasma derivatives or any administration of immunoglobulin preparation within the 3 months prior to Visit 2, or planned during the study.
14. Participation in blood donation within 3 months or plasma donation within 1 month prior to Visit 2.
15. History of substance or alcohol abuse within the past 2 years.
16. History or any illness/condition that, in the opinion of the Investigator, might interfere with the results of the study or pose additional risk to the subjects due to participation in the study.
17. Any positive result on screening for serum hepatitis B surface antigen, hepatitis C antibody or HIV.
18. Pregnant or lactating female or intent to become pregnant during the clinic phase and for 2 months after the last vaccination.
19. History of Bell’s palsy.
20. Ongoing regular use of intranasal sprays including corticosteroids and decongestants.
21. Ongoing cough, sinusitis, allergic rhinitis, nasal polyps or obstruction, including septum deviation significant enough to prevent bilateral administration of study vaccine.
22. Known bleeding diathesis, or any condition that may be associated with a prolonged bleeding time.
23. Subjects that are prone to nosebleed. |
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| E.5 End points |
| E.5.1 | Primary end point(s) |
1. Type and incidence of AEs and SAEs from the time of first study drug administration (Visit 2) until the last visit to the clinic (Visit 4 for group 1 to 6 and Visit 3 for group 7).
2. Type and incidence of SAEs and AEs of special interest during the 6 months safety follow-up.
3. Frequency and severity of discomfort in the nose and throat and/or arm before study drug administration and 15, 30, 60 and 120 minutes after study drug administration. Discomfort in the nose and throat (group 1-6) and/or arm (group 6-7) will be assessed using a non-graded 100 mm visual analogue scale (VAS).
4. Frequency of clinically significant changes in ECG, vital signs, physical examination findings and laboratory variables from baseline to the last visit to the clinic.
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| E.5.1.1 | Timepoint(s) of evaluation of this end point |
1. Visit 2 and until the last visit to the clinic (Visit 4 for group 1 to 6 and Visit 3 for group 7).
2. During the 6 months safety follow-up.
3. Before study drug administration and 15, 30, 60 and 120 minutes after study drug administration.
4. From baseline to the last visit to the clinic. |
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| E.5.2 | Secondary end point(s) |
1. Measurement of HI in blood, including:
- Geometric mean titres (GMTs) and pre-/post-treatment ratios (GMRs)
- Percentage of subjects with seroprotection (i.e., an HI titre ≥40) at pre-treatment and 21 days after each treatment.
- Percentage of subjects with seroconversion (i.e., either a pre-treatment HI titre <10 and a post-treatment titre ≥40 or a pre-treatment HI titre ≥10 and a fourfold increase in titre) at pre-treatment and 21 days after each treatment.
2. Measurement of VN titres in blood (pre-treatment and 21 days after each treatment)
- GMTs and pre-/post-treatment GMRs
3. Analysis of SRH in blood, including:
- GMTs and pre-/post-treatment GMRs
- Percentage of subjects with seroprotection (i.e., a SRH titre >25 mm2) at pre-treatment and 21 days after each treatment.
- Percentage of subjects with seroconversion (i.e., either a negative pre-treatment serum (<4 mm2) and a positive post-treatment serum [area ≥25 mm2] or a significant increase in antibody titre i.e. at least a 50% increase in post-treatment area if pre-treatment is not negative).
4. Measurement of influenza-specific IgA in nasal secretions (pre-treatment and 21 days after each treatment)
- GMTs and pre-/post-treatment GMRs
- Percentage of subjects with a 2-fold, 4-fold and 8-fold increase in influenza-specific IgA
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| E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. At pre-treatment and 21 days after each treatment.
2. At pre-treatment and 21 days after each treatment.
3. At pre-treatment and 21 days after each treatment.
4. At pre-treatment and 21 days after each treatment.
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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 | Yes |
| 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) | Yes |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | Yes |
| E.7.1.3.1 | Other trial type description |
| Evaluate the safety, tolerability and immune response following vaccination with Immunose FLU |
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| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| 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 |
| Partially-blinded; Group 1, 2, 4 and 5. Single blinded; Group 3. Unblinded; Group 6 and 7. |
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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 | Yes |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 7 |
| 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 | 4 |
| E.8.5 | The trial involves multiple Member States | No |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | No |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| 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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| The end of the study is defined as the last subject’s last visit or the last subject’s telephone follow-up call (whichever comes last). |
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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 | 1 |
| E.8.9.1 | In the Member State concerned months | 0 |
| E.8.9.1 | In the Member State concerned days | 0 |
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