| 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 |
|
| 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 | 19.0 |
| 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 |
|
| 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 determine the effect of FLU-v on reducing the incidence of Mild to Moderate Influenza Disease (MMID) defined as detectable viral shedding plus at least one symptom of influenza |
|
| E.2.2 | Secondary objectives of the trial |
| To determine the overall effect of FLU-v on measurements of disease severity |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1) Healthy males and females aged ≥18 and ≤55 years of age at the point of enrolment.
2) Willingness to remain in isolation for the duration of viral shedding and to 3) comply with all study requirements.
The following criteria are applicable to subjects in a heterosexual relationship and female subjects in a same sex relationship (i.e., the criteria do not apply to male subjects in a same sex relationship):
- True abstinence- when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence [e.g. calendar, ovulation, symptothermal, post-ovulation methods] and withdrawal are not acceptable methods of contraception).
Or
- Two forms of effective contraceptive methods among (between) the couple, which are defined as:
For males: condom with spermicidal foam/gel/film/cream, sterilisation (with the appropriate post-vasectomy documentation of the absence of sperm in the ejaculate. This applies only to males participating in the study).
For females:
§ Women no longer of child bearing potential (post-menopausal females are defined as having a history of amenorrhea for at least 2 years, otherwise they should have documented status as being surgically sterile or post hysterectomy. The latter applies only to females participating in the study).
§ If of childbearing potential, then acceptable forms of contraception include:
§ Established (a minimum of 2 weeks prior to admission) use of oral, injected or implanted hormonal methods of contraception.
· Placement of an intrauterine device (IUD) or intrauterine system (IUS).
· Barrier methods of contraception or occlusive cap (diaphragm or cervical/vault caps), both with one of the following - spermicidal foam/gel/film/cream/suppository.
The longevity of contraception is as follows:
§ Males: ·Comply with agreed contraception at entry to quarantine, and continuing until 90 days after the date of viral challenge/last dosing with IMP (whichever occurs last).
· Must not donate sperm following discharge from quarantine until 90 days after the date of viral challenge/last dosing with IMP (whichever occurs last).
§ Females: If of childbearing potential must have a negative pregnancy test at screening and just prior to the date of Viral Challenge, and must be using contraception consisting of two forms of birth control (one of which must be a barrier method) starting from at least 2 weeks prior to entry to quarantine and continuing until 90 days after the date of Viral Challenge/last dosing with IMP (whichever occurs last).
4) Willing to have samples stored for future research.
5) Sero-suitable to the study challenge virus within 90 days of Day 0.
6) Agrees to abstain from alcohol intake 24 hours before admission on Day -2 and all other outpatient visits.
7) Agrees to not use prescription or over-the-counter medications (including aspirin, decongestants, antihistamines, and other NSAIDs), and herbal medication (including, but not limited to, Vitamin C, Vitamin D, immune booster products, herbal tea, St. John’s Wort), within 14 days prior to study vaccine administration through the final follow-up visit, unless approved by the investigator and sponsor medical monitor.
8) An informed consent document signed and dated by the subject and the Investigator.
9) A history of childhood asthma before the age of 12 years is acceptable provided the subject is asymptomatic without treatment. Subjects with a single episode of wheezing (lasting less than 2 weeks) after the age of 12 years can be included at the Investigator’s discretion provided the episode was more than 1 year ago and did not require a hospital admission and/or oral/intravenous steroids.
10) In good health with no history of major medical conditions that will interfere with subject safety, as defined by medical history, physical examination, and routine laboratory tests and determined by the Investigator at a screening evaluation.
· A subject with a history of Herpes type 1 or 2 infection may be included if there are no active lesions present and the subject is not taking active medication.
· A subject with or without any evidence of atopy including any history of allergic rhinitis, dermatitis, and conjunctivitis will be included as long as they do not conflict with exclusion criteria.
Mild to moderate arthritis of non-inflammatory origin may be allowed if the subject is not at risk from relative immobility in the Quarantine Unit and does not require regular medication.
11) A documented medical history for a minimum of the last 2 years prior to inoculation. |
|
| E.4 | Principal exclusion criteria |
1) For information on smoking and how it affects participation in the trial, please see Protocol Section 7.3 – Exclusion Criteria
2) Presence of self-reported or medically documented significant medical condition. For more detailed information, please see Protocol Section 7.3 - Exclusion Criteria
3) Individual with body mass index (BMI) ≤18 and ≥35.
4) Acute illness within 7 days of first vaccine administration day.
5) Clinically significant abnormal electrocardiogram (ECG) and/or parameters, as determined by the Investigator
6) Subjects with clinically significant abnormal systolic and diastolic blood pressure or clinically significant abnormal pulse rate.
7) Subject has abnormal pulmonary function as measured by spirometry defined as a forced vital capacity or forced expiratory volume in 1 second (FEV1) < 80% of predicted or peripheral arterial oxygen saturation (SpO2) < 92% on room air.
8) Known allergy to treatments for influenza (including but not limited to oseltamivir, nonsteroidals).
9) For more information on participant allergies and how they might affect their participation, please see Protocol Section 7.3 - Exclusion Criteria.
10) Daily or household contact with vulnerable populations as defined by 5.2.4.1
11) (a) Receipt of any investigational drug within 3 months prior to the planned date of Viral Challenge/first dosing with IMP (whichever occurs first) (b) Receipt of three or more investigational drugs within the previous 12 months prior to the planned date of Viral Challenge/first dosing with IMP (whichever occurs first). (c) Prior inoculation with a virus from the same virus-family as the Challenge Virus. (d) Prior participation in another Human Viral Challenge study with a respiratory virus in the preceding 12 months taken from the date of Viral Challenge/first dosing with IMP (whichever occurs first) in the previous study to the date of expected Viral Challenge in this study.
12) Receipt of any vaccine within 6 months of enrolment.
13) Self-reported or known history of alcoholism or drug abuse (including marijuana) within 6 months prior to enrolment, or positive urine/serum test for drugs of abuse during the study.
14) Self-reported or known history of psychiatric or psychological issues that require treatment and are deemed by the PI to be a contraindication to protocol participation.
15) History of a previous severe allergic reaction with generalized urticaria, angioedema, or anaphylaxis.
16) Any condition or event that, in the judgment of the PI, is a contraindication to protocol participation or impairs the volunteer’s ability to give informed consent.
17) History or evidence of autoimmune disease or known immunodeficiency of any cause – with the exception of atopic dermatitis/eczema and atopic rhinitis.
18) Subjects with any history of physician diagnosed and/or objective test confirmed asthma (except as per inclusion criteria 10, reactive airway disease, COPD, pulmonary hypertension, or chronic lung condition of any aetiology.
19) Positive human immunodeficiency virus (HIV) within 60 days of first vaccination visit, active hepatitis A (HAV), B (HBV), or C (HCV) test.
20) Any significant abnormality altering the anatomy of the nose or nasopharynx (including significant nasal polyps).
21) Venous access deemed inadequate for the phlebotomy and cannulation demands of the study.
22) Any nasal or sinus surgery within 6 months of Viral Challenge.
23) Recurrent history of fainting.
24) Those employed or immediate relatives of those employed at hVIVO or the Sponsor.
25) Any clinically significant history of epistaxis (nosebleeds) within the last 12 months and/or history of being hospitalized due to epistaxis on any previous occasion.
26) Any influenza vaccine in the last 6 months
27) Females who: Are breastfeeding, or have been pregnant within 6 months prior to the study, or
Have a positive pregnancy test at any point during screening or prior to first dosing with IMP.
28) Presence of fever, defined as subject presenting with a temperature reading of > 38.0°C on Day -43
29) Receipt of blood or blood products, or loss (including blood donations) of 470 mL or more of blood during the 3 months prior to the planned date of first dosing with IMP or planned during the 3 months after the final visit.
30) Receipt of systemic (intravenous and/or oral) glucocorticoids or systemic antiviral drugs within 6 months prior to the planned date of first dosing with IMP.
31) Any other finding that, in the opinion of the Investigator, deems the subject unsuitable for the study.
|
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Incidence of Mild to Moderate Influenza Disease |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| E.5.2 | Secondary end point(s) |
• Viral shedding duration
• Viral shedding quantitation
• Symptom duration
• Total number of symptoms experienced
• Symptom severity score as measured by FLU-PRO
• Incidence of vaccine related adverse events (diary card for 21 days after each vaccine) |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| up to day 35 (+/- 3 days) |
|
| 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 | 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) | 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 | 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 | Yes |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 3 |
| 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 | 3 |
| 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
|
|
| 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 | 6 |
| E.8.9.1 | In the Member State concerned days | 2 |
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