| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated | |
| E.1.1.1 | Medical condition in easily understood language |
Influenza A infects the respiratory tract causing fever, cough, headache
and myalgia. Severity varies however in the infection can sometimes lead to severe illness, hospitalisation and even death. |
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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 | 14.1 |
| 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 |
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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 characterise the safety and tolerability profile of Vaccine FP-01.1. |
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| E.2.2 | Secondary objectives of the trial |
Efficacy
To compare the incidence, severity and duration of signs and symptoms of influenza-like illness after virus challenge between subjects pre-vaccinated with Vaccine FP-01.1 and subjects pre-vaccinated with placebo.
Pharmacodynamics
To compare the incidence, magnitude and duration of viral shedding after virus challenge between subjects pre-vaccinated with Vaccine FP-01.1 and subjects pre-vaccinated with placebo.
Immunogenicity
-To further characterise the immunological response (both humoral and CMI) to vaccination by Vaccine FP-01.1;
-To explore the relationship between the immunological response to vaccination and the clinical and pharmacodynamic response to challenge.
Safety
To further characterise the safety and tolerability profile of Vaccine FP-01.1.
Exploratory Objective
Exploratory analysis of host gene expression using microarray technology. Any results from this analysis will be reported separately from the clinical study report.
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| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
•Male or female aged 18 to 45 years inclusive, with a body mass index of 18.0 to 32.0 kg/m2 inclusive and body weight of 50.0 to 110.0 kg inclusive;
•Subjects who are able and willing to give written informed consent to participate;
•Healthy, as determined by medical history, physical examination, vital signs, 12-lead ECG, and clinical safety laboratory examinations at screening (Visit 2) and Day C-1 (prior to virus challenge), as determined by the Investigator;
•Absent or low levels of detectable pre-existing antibodies to the challenge H1N1 virus (HI titre of ≤10) and predicted seasonal H3N2 virus (HI titre of ≤40) prior to vaccination;
•Subjects who are non-smokers for at least 3 months preceding screening (Visit 2) and able to refrain from smoking until after the completion of Visit 9 [Day C29];
•Females of non-childbearing potential or female subjects of childbearing potential who are using medically acceptable methods of contraception;
•Comprehension of the study requirements, expressed availability for the required study period, and ability to be quarantined for up to 10 days and to attend the scheduled follow-up visits (Day C29 and Day 209);
•Negative alcohol and urine drug screening tests on screening (Visit 2) and prior to entering quarantine (Day C-1);
•Being willing to adhere to the prohibitions and restrictions specified in the protocol.
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| E.4 | Principal exclusion criteria |
•Receipt of any influenza vaccine after 31 August 2011;
•Significant adulthood history of seasonal hay fever or a seasonal allergic rhinitis or perennial allergic rhinitis or chronic or nasal or sinus condition such as chronic sinusitis;
•Abnormal nasal structure including septal deviation and nasal polyps;
•History of asthma (childhood asthma allowed), bronchiectasis, emphysema, chronic obstructive pulmonary disease or any other chronic lung disease in the last 10 years;
•Current use or use within the last 7 days from screening day (Visit 2) of intranasal corticosteroids;
•Subjects who have a clinically relevant history or presence of respiratory, gastrointestinal, renal, hepatic, haematological, lymphatic, neurological, cardiovascular, psychiatric, musculoskeletal, genitourinary, immunological, dermatological, connective tissue diseases or disorders;
•Subjects who do not agree to use medically acceptable methods of contraception
•Female subjects who are pregnant, trying to become pregnant or are breast feeding;
•Diastolic blood pressure (BP) <50 or >90 mmHg, a systolic BP <100 or >150 mmHg, a pulse <40 or >100 beats per minute (bpm) after resting for 5 minutes;
•FEV1 ≤80% of predicted FEV1;
•Blood haemoglobin A1c >6.0%;
•Positive serology for human immunodeficiency virus (HIV) 1 or HIV 2, hepatitis B surface antigen (HBsAg) or hepatitis C virus (HCV) antibodies;
•Cancer or treatment for cancer, within 5 years of Visit 2, excluding basal cell carcinoma of the skin, which is allowed;
•Presence of immunosuppression or any medical condition that may be associated with impaired immune responsiveness, including, but not limited to, diabetes mellitus and inflammatory bowel disease;
•Presently receiving (or history of receiving) or during the 3-month period prior to screening, any medications or other treatments that may adversely affect the immune system.
•A17. Anticipated presence of a household contact with documented severe immunosuppression (including but not limited to HIV, anyone who has haematological malignancy or is taking immunosuppressant medication), either as a result of disease and/or therapy within 2 weeks following discharge from the virus challenge quarantine period;
•Anticipated presence of a household contact age 5 years or younger, within 2 weeks following virus challenge quarantine period;
•Anticipated presence of a household contact age 65 years or older, within 2 weeks following virus challenge;
•Anticipated presence of a household contact with diagnosed emphysema, chronic obstructive pulmonary disease, severe lung disease or a lung transplant, within 2 weeks following virus challenge quarantine period;
•Current professional activity as a carer or healthcare workers who will return to work within 2 weeks following virus challenge;
•Anticipated presence of a pregnant household contact, within 2 weeks following virus challenge;
•History of anaphylactic type reaction to egg or egg protein ;
•History of Guillain-Barré syndrome;
•History of drug or chemical/alcohol abuse in the year before the study (Visit 2);
•Receipt of any investigational virus product or any IMP within 3 months prior to first vaccination, or currently enrolled in any investigational drug study or intends to enrol in such a study within the ensuing study period;
•Receipt of blood or blood products 6 months prior to first vaccination or planned administration during the study period;
•Blood donation in the 3 months prior to screening (Visit 2);
•Acute disease within 72 hours prior to vaccination, defined as the presence of a moderate or severe illness with or without fever (as determined by the Investigator through medical history and physical examination), or presence of a fever (>37.7 C oral temperature);
•Elevated white cell count >9.5 x 10^9/L, absolute neutrophil count >6.9 x 10^9/L or serum C-reactive protein concentration >10.0 mg/L at screening (Visit 2) or Day C-1;
•Any condition that, in the opinion of the Investigator, might interfere with the primary study objective;
•Known or suspected intolerance or hypersensitivity to the IMP or closely related compounds, known allergy to egg or egg protein or any of the stated excipients;
•Known or suspected intolerance or hypersensitivity to Tamiflu or Relenza;
•Subject with suspected recent (≤6 months) experience of influenza-like illness (fever [>37.7 C ] and cough and/or sore throat >2 days, in the absence of a known cause other than influenza);
•Subjects who have significant scarring, tattoos, abrasions, cuts or infections, that in the opinion of the Investigator could interfere with evaluation of injection site local reactions, over the deltoid region of both arms as these will be the dose site;
•Subjects who are vegans or have medical dietary restrictions;
•Subjects who cannot communicate reliably with the Investigator.
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| E.5 End points |
| E.5.1 | Primary end point(s) |
| Primary endpoints of safety and tolerability will be monitored throughout the study by assessment of AEs, concomitant medications, clinical laboratory safety tests (serum biochemistry and haematology), physical examinations, vital signs (blood pressure, pulse rate, respiratory rate), 12-lead ECGs, spirometry and local injection site reactions |
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| E.5.1.1 | Timepoint(s) of evaluation of this end point |
Adverse events and monitoring of concomitant medications will be conducted throughout the trial, from screening through to the last visit.
Clinical laboratory safety tests (which include serum biochemistry and haematology) will be conducted at visits 2 (days -28 to -2), 3 (day 1), 5 (day 8), 6 (day29±1), 8 (day 36), 9 (days 43±1 – 52, virus challenge quarantine period) and visit 10 (day 57±1[non-challenge] or 72±1[challenge]).
Physical examinations and vital signs tests will be conducted at visits 2, 3, 6, 9 and 10.
12 lead ECGs will be conducted at visits 2, 9 and 10.
Spirometry tests will be conducted at visits 2 and 9.
Local injection site reactions will be monitored through visits 3 to 8.
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| E.5.2 | Secondary end point(s) |
| Efficacy evaluations following viral challenge will be based on the incidence of laboratory confirmed illness (viral shedding) and the signs and symptoms of influenza (targeted physical examinations, oral temperature and subject symptom scores). Pharmacodynamic evaluations will be based on the magnitude and duration of viral shedding and immunogenicity evaluations will be based on the T cell (PBMC assay) and antibody immunological response to vaccination (HI assays). Exploratory investigation into the changes in gene expression following vaccination and/or challenge will be based on microarray studies. |
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| E.5.2.1 | Timepoint(s) of evaluation of this end point |
Viral shedding tests for Efficacy will be conducted throughout the quarantine period (visit 9). Subject symptom scoring and oral temperature tests will be conducted during visit 9. Blood samples for T cell and HI assays, serum and cellular immunoanalysis will be conducted at one or more of the panel screening and visits 2, 3, 5, 8, 9 and 10.
Optional blood samples will be taken from subjects providing consent for exploratory genomic analysis at visits 3 (day 1), 7 (day 30) and 9.
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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 | Yes |
| 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) | 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 | 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
| Yes |
| E.8.4 | The trial involves multiple sites in the Member State concerned | No |
| 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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| 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 | 10 |
| E.8.9.1 | In the Member State concerned days | 0 |
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