| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Prophylactic H3N2(A/Brisbane/10/2007) monovalent influenza vaccine, Bris10 M2SR, for protection against influenza disease caused by seasonal influenza A viruses. |
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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 | HLT |
| E.1.2 | Classification code | 10022005 |
| E.1.2 | Term | Influenza viral infections |
| 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 |
1. To assess the effect of vaccination with Bris10/2007 M2SR (H3N2) vaccine on influenza viral shedding after intranasal challenge with a drifted H3N2 virus, A/Belgium/4217/2015.
2. To assess the safety of the Bris10 M2SR (H3N2) vaccine during the period from study vaccine administration until influenza virus challenge.
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| E.2.2 | Secondary objectives of the trial |
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| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Give written informed consent to participate.
2. Age 18 – 55 years old, inclusive.
3. Judged suitable by the Principal Investigator, as determined by medical history, physical examination, vital signs, and clinical safety laboratory examinations.
4. Negative test for pregnancy at screening visit, on Day-28 and at Day -2.
5. Negative test for alcohol (breath) and drugs of abuse (urine).
6. Negative test for influenza prior to vaccination.
7. Female subjects should fulfill one of the following criteria:
a. Post-menopausal status defined as no menses for 12 months without an alternative medical cause and/or high follicle-stimulating hormone (FSH) level (>30 mIU/mL) prior to screening.
b. Surgically sterile.
c. Willing to use oral, implantable, transdermal or injectable contraceptives, as outlined in inclusion criteria 8, from screening and until 28 days after challenge infection.
8. Female subjects of childbearing potential must agree to use a reliable form of contraception approved by the Investigator (e.g., oral, implantable, transdermal, or injectable contraception, combined oral, intrauterine device [IUD], or a sterile sexual partner) from screening and until 28 days after challenge infection. Non-surgically sterile male subjects who are sexually active with a female partner(s) of childbearing potential (i.e. males who have not been sterilized by vasectomy for at least 6 months prior to screening) must be willing to use condoms from screening and until 28 days after challenge infection.
9. Willing to adhere to the requirements of the study and willing and able to communicate with the Investigator and understand the requirements of the study.
10. Willing to be confined during the challenge portion of the study.
11. Non-smoker (including prior smokers having stopped smoking for more than 1 year at time of screening) or non-habitual smoker (non-habitual smokers are persons who smoke fewer than 4 cigarettes or other tobacco products on a weekly basis) who agrees to not use tobacco products during the challenge phase of the study.
12. Absent or low levels of detectable pre-existing antibodies to influenza virus H3N2 subtype, strain A/Belgium/4217/2015, as determined by a MN titer of ≤20 at screening.
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| E.4 | Principal exclusion criteria |
1.Any subject who is a family member of a) study site personnel, b) personnel involved in conduct or monitoring of study, or c) Sponsor.
2.Has a BMI at screening of less than or equal to 19.0 kg/m2 or greater than or equal to 32.0 kg/m2.
3.Any condition that would limit the subject’s ability to complete the study based on the opinion of the Investigator
4.Abnormal screening hematology or chemistry value per the FDA
5.Pulse rate, blood pressure, or ECG outside the reference range for this study population and considered as clinically significant by the Investigator.
6.Has an acute or chronic medical condition or history of a medical condition
7. Has been vaccinated against influenza within the last 6 months or plans to be inoculated with an influenza vaccine (other than study vaccine) until one month after completion of in-person follow up.
8.Had a flu-like illness, influenza treatment, or prophylactic influenza viral drug administered in the previous 6 months before screening.
9Positive screening test or known infection with HIV, HBV and HCV.
10.History of cancer within 5 years prior to screening
11.Presence or history of lung disease, asthma, chronic obstructive pulmonary disease, or otherwise poor lung function. Childhood asthma that resolved by age 12 years is not criteria for exclusion.
12.Having a forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) ratio <0.70 and FEV1 <80 % at screening. The interpretation of the spirometry result is at the investigator’s discretion. At the discretion of the investigator or designee, subjects with up to 10% deviation from these values may be included.
13.Any significant abnormality altering the anatomy of the nose or nasopharynx. A test swabbing by mock swab may be performed at screening at the Investigator’s discretion.
14.Any confirmed or suspected immunosuppressive or immunodeficient state including: asplenia, recurrent severe infections and chronic immunosuppressant medication within the last 6 months.
15.Use of immunosuppressive medications, such as allergy shots, immune globulin, interferon, immunomodulators, in the past 6 months or planned to be used during the course of the trial.
16.Use of intranasal corticosteroids within the last 7 days before screening.
17.Significant adulthood history of seasonal hay fever, a seasonal allergic rhinitis, perennial allergic rhinitis, chronic nasal or sinus condition such as sinusitis, at the discretion of the investigator.
18.Received any licensed vaccine within 1 month before screening or planned receipt during the 30 days post challenge.
19. Received or planned administration of another investigational vaccine or drug during the period from 90 days prior to Day 1 to 1 month after completion of in-person follow up.
20.History of allergy/hypersensitivity to any vaccine or virus challenge component challenge agent component or material in nasal delivery device
21.Experienced a life-threatening reaction(s) after a previous administration of any vaccine, or experienced an allergic reaction after a previous administration of any influenza vaccine or component.
22.A history or prior diagnosis of Guillain-Barré Syndrome.
23.Presence of household member or close personal or professional contact for 14 days post-inoculation who:
a.is a child under one year of age;
b.is pregnant;
c.has known immunodeficiency or is receiving immunosuppressant medication;
d.is undergoing or soon to undergo cancer chemotherapy;
e.has been diagnosed with emphysema, COPD, or other severe lung disease and resides in a nursing home;
f.has received a bone marrow or solid organ transplant.
24.History of drug or alcohol abuse in the 6 months before the study.
25.Concomitant use of any prescription, OTC medications, herbal medications, or supplement starting 7 days prior to vaccination. Note, please see list of permitted medications that can be administered post-vaccination to treat vaccination related signs and symptoms. Permitted medications include contraceptive pills, implants, transdermal or injections in female subjects.
26.Receipt of blood products or immunoglobulin within 6 months before study entry or planned for within 180 days after the vaccination.
27.Donation of blood or blood products within 30 days before study entry or at any time during the 30 days post vaccination.
28.Females who are pregnant or lactating
29.Acute febrile illness within 72 hours prior to vaccination, defined as the presence of a moderate or severe illness with or without fever, or presence of a fever >38ºC orally. Vaccination should be delayed until the subject has recovered. Persons with a minor illness, such as diarrhea, or mild upper respiratory tract infection with or without low-grade fever may be considered for enrollment after resolution of the illness.
30.Any condition that, in the opinion of the Investigator, might interfere with the primary study objectives for safety of the study subject.
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| E.5 End points |
| E.5.1 | Primary end point(s) |
1. Area under the curve (AUC) of the influenza RNA log10 viral load by real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) from nasopharyngeal swabs of study subjects from the time of challenge inoculation with A/Belgium/4217/2015 until discharge (10 days after inoculation) in the vaccine and placebo groups.
2. Number and proportions of study subjects reporting solicited and unsolicited adverse events (AEs) and serious adverse events (SAEs) from the time of administration of the vaccine or placebo until administration of challenge virus.
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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. Proportion of study subjects in vaccine and placebo groups with infection following challenge with A/Belgium/4217/2015 as determined by qRT-PCR. Infection is defined as at least two consecutive qRT-PCR positive swabs starting on the second day after challenge (Day 3).
2. Proportion of study subjects in vaccine and placebo groups with infection AND influenza illness following intranasal challenge with A/Belgium/4217/2015. Influenza illness is defined as either at least one respiratory symptom on two consecutive days OR at least one respiratory and at least one systemic symptom on two consecutive days.
3. Number (%) of vaccine and placebo study subjects reporting occurrence of solicited local reactions and systemic events during the 8-day period that includes the day of vaccination and the following 7 days. The intensity and duration of these reactions and events will be described.
4. Nasal vaccine virus shedding at 72 hours post-vaccination and every 24 hours thereafter until PCR negative.
5. Number (%) of study subjects reporting treatment-emergent solicited and unsolicited AEs and SAEs.
6. Number (%) of study subjects reporting challenge-emergent solicited and unsolicited AEs and SAEs.
7. Viral load (qRT-PCR) and viral titer (TCID50), in samples of upper respiratory tract secretions collected following influenza virus challenge with A/Belgium/4217/2015 (time to start, time to peak, and time to cessation of viral shedding) in the vaccine and placebo groups.
8. Following administration of investigational product (IP, vaccine or placebo):
a. Influenza-specific serum antibody responses measured at immunogenicity serum sampling time points;
b. Influenza-specific mucosal IgA antibody responses measured at immunogenicity nasal swab sampling time points;
c. Influenza-specific cellular immune responses measured by cytokine enzyme-linked immunospot (ELISPOT) at immunogenicity peripheral blood mononuclear cell (PBMC) sampling time points.
9. Following challenge with A/Belgium/4217/2015:
a. Influenza-specific serum antibody responses measured at immunogenicity serum sampling time points;
b. Influenza-specific mucosal IgA antibody responses measured at immunogenicity nasal swab sampling time points;
c. Influenza-specific cellular immune responses measured by cytokine ELISPOT at immunogenicity PBMC sampling time points.
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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 | 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 | 9 |
| E.8.9.1 | In the Member State concerned days | |
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