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 | LLT |
E.1.2 | Classification code | 10016794 |
E.1.2 | Term | Flu vaccination |
E.1.2 | System Organ Class | 100000004865 |
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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 |
Safety: To assess M-001 Safety by solicited local and systemic reactogenicity events occurring between 0 and 7 days following receipt of each of the two doses of M-001 or placebo and to assess SAEs, and new-onset of chronic medical illnesses (NOCIs) during period from Day 0 until end of first passive surveillance period in each group. Clinical Efficacy: To assess efficacy of M-001 in the prevention of influenza disease by comparing the occurrence of culture confirmed influenza in the M-001 experimental group vs. placebo caused by any influenza A or B virus in association with a protocol defined Influenza Like Illness (ILI) |
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E.2.2 | Secondary objectives of the trial |
1. Compare the occurrence of qualitative PCR confirmed influenza in the M-001 experimental group vs. placebo (≥ 15 days after the second vaccination until epidemiological levels of influenza are low as defined by the medical director) caused by any influenza A or B virus in association with a protocol defined ILI. 2. Reduction of either qRT-PCR or Culture-confirmed influenza illness severity: The reduction due to M-001 in the average number of days with respiratory or systemic symptoms during the first laboratory-confirmed influenza illness episode 3. The percentage of subjects having ILI symptoms in the experimental and control group. 4. The change from baseline in the percentage of CD4+ lymphocytes producing Th1 cytokine (e.g. INF-γ) in response to any of the 9 peptides in M-001. This endpoint will be assessed within a randomly selected subset of participants from pre-selected sites participating to the substudy in Year 2. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Subjects eligible to participate in this study must meet all of the following inclusion criteria: 1. Male and female subjects 50 years of age (inclusive) or older, mentally competent, willing and able to give the written informed consent prior to study entry. 2. Able to comply with the trial procedures and be available for all study visits including answering phone calls and coming to the site as defined by the Protocol. 3. Medically stable (subjects may have underlying systemic chronic conditions such as hypertension, diabetes, ischemic heart disease, or hypothyroidism, as long as their symptoms/signs are controlled; if they are on systemic pharmacological treatment for such condition, the treatment must have been stable for at least 3 months preceding first vaccination). 4. Women of childbearing potential (not surgically sterile or postmenopausal for greater than or equal to one year) and men must agree to practice adequate effective contraception - barrier or hormone-based methods or intra uterine device (IUD) for women and a condom for males -whose female partner has childbearing potential - throughout the study treatment and for at least up to day 81 (for females) and day 111 (for males) of the trial (i.e. 60 (for females) and 90 (for males) days after the last dose of the IMP). In addition, women of childbearing potential must have practiced the contraception for a minimum of 30 days prior to study product exposure. 5. Female subjects of childbearing potential must have a negative urine or serum pregnancy test within 24 hours prior to both study vaccinations. |
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E.4 | Principal exclusion criteria |
Subjects eligible to participate in this study must not meet any of the following exclusion criteria: 1. History of neurological symptoms or signs, or anaphylactic shock following administration of any vaccine. 2. Known or suspected (or have a high risk of developing) significant impairment/alteration of immune function (excluding that normally associated with advanced age as) judged by PI/SI. 3. Receipt of: a) Current (including within 60 days before Visit 1 or planned during the study) daily use of immunosuppressive drugs: i) systemic glucocorticoids ≥ 10 mg prednisone per day ii) cytotoxic drugs b) Investigational drugs within 30 days before, or planned during, the study c) Blood products within 3 months before, or planned during, the study d) Influenza vaccine within 6 months before the study or planned during the study e) Other vaccines within 30 days before, or planned during, the study. 4. Any serious disease such as: cancer, autoimmune disease, advanced arteriosclerotic disease or complicated diabetes mellitus, chronic obstructive pulmonary disease (COPD) that requires oxygen therapy, acute or progressive hepatic disease, acute or progressive renal disease, or congestive heart failure, as judged by the PI. 5. An acute illness, including body temperature greater than 37.5ºC (axillary or forehead) or greater than 38.0 ºC (oral), or greater than 38.5ºC (ear/tympanic or rectal) , occurred within 1 week before first vaccination. 6. Anatomical deficiencies which exclude possibility of taking NP swab. 7. Women who are breastfeeding or planning pregnancy during the period of the study. 8. Institutionalized subjects or subjects unable to come to the study site as expected by the Protocol |
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E.5 End points |
E.5.1 | Primary end point(s) |
Safety: To assess M-001 Safety by solicited local and systemic reactogenicity events occurring between 0 and 7 days following receipt of each of the two doses of M-001 or placebo and to assess SAEs, Medically Attended AEs (MAAEs) and new-onset of chronic medical illnesses (NOCIs) during period from Day 0 until end of first passive surveillance period in each group.
Clinical Efficacy: Compare the occurrence of culture confirmed influenza in the M-001 experimental group vs. placebo (≥ 15 days after the second vaccination until epidemiological levels of influenza are low as defined by the medical director) caused by any influenza A or B virus in association with a protocol defined Influenza Like Illness (ILI is defined as symptoms that interfere with normal daily activities and that include one of the following respiratory symptoms (sore throat, cough, sputum production, nasal discharge, wheezing or difficult breathing) and at least one additional systemic symptom [fever (oral temperature >37.2°C), headache, myalgia and/or arthralgia, chills, and fatigue (tiredness for at least 12 hours)]. NP (Nasopharyngeal) swab will be collected from participants who meet the ILI definitions for qualitative PCR analysis of influenza A and/or B virus. Influenza positive samples by PCR will be further analysed for culture confirmation. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
1. Compare the occurrence of qualitative PCR confirmed influenza in the M-001 experimental group vs. placebo (≥ 15 days after the second vaccination until epidemiological levels of influenza are low as defined by the medical director) caused by any influenza A or B virus in association with a protocol defined ILI. Nasopharyngeal swab will be collected from participants who meet the ILI definitions within 24 hours from ILI being reported to or identified by study personnel for qRT-PCR confirmation of influenza A and/or B virus (a nasal and throat sample can be collected as alternative method), and the samples identified with qRT-PCR as positive for influenza A or B virus will be verified with virus culture. 2. Reduced Severity of influenza illness Reduction of either qRT-PCR or Culture-confirmed influenza illness severity: The reduction due to M-001 in the average number of days with respiratory or systemic symptoms during the first laboratory-confirmed influenza illness episode. 3. The percentage of subjects having ILI symptoms in the experimental and control group. 4. The change from baseline in the percentage of CD4+ lymphocytes producing Th1 cytokine (e.g. INF-γ) in response to any of the 9 peptides in M-001. This endpoint will be assessed within a randomly selected subset of participants from pre-selected sites participating to the substudy in Year 2. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | No |
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 | No |
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 | No |
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) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
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 | 15 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 85 |
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 |
Bulgaria |
Croatia |
Georgia |
Hungary |
Latvia |
Poland |
Ukraine |
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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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last subject last contact |
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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 | 3 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
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 | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |