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 | 10059429 |
E.1.2 | Term | Influenza immunisation |
E.1.2 | System Organ Class | 10042613 - Surgical and medical procedures |
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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 describe the level of serum hemagglutination inhibition (HAI) antibody responses induced by trivalent and quadrivalent formulations of FluMist against antigenically matched influenza strains |
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E.2.2 | Secondary objectives of the trial |
To describe the proportion of individuals who shed vaccine viruses; To describe the duration of shedding of vaccine viruses; To quantify the titer of shed vaccine viruses; To describe the level of serum neutralizing antibody responses induced by trivalent and quadrivalent formulations of FluMist against antigenically matched influenza strains; To describe the level of mucosal antibody responses induced by trivalent and quadrivalent formulations of FluMist against antigenically matched influenza strains; To describe the safety and tolerability of trivalent and quadrivalent formulations of FluMist. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
24 months to < 48 months of age; Healthy by medical history and physical examination or presence of stable underlying chronic medical condition for which hospitalization has not been required in the previous year. |
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E.4 | Principal exclusion criteria |
History of allergic disease or reactions likely to be exacerbated by any component of the investigational product; Acute illness or evidence of significant active infection (including fever >/= 100.4 degrees Fahrenheit (F) (38.0 degrees Celsius (C)) at randomization; History of asthma or history of recurrent wheezing; Any known immunosuppressive condition or immune deficiency disease; Current or expected receipt of immunosuppressive medications within a 28 day window around vaccination; Use of aspirin or salicylate-containing medications within 28 days prior to randomization or expected receipt thru 28 days after vaccination; Use of antiviral agents with activity against influenza viruses within 48 hours prior to first dose of investigational product or anticipated use of such agents through the end of the study follow-up period; Receipt of any non-study seasonal influenza vaccine within 90 days of Dose 1 or planned receipt of non-study seasonal influenza vaccine prior to 28 days after last vaccination; Receipt of immunoglobulin or blood products within 90 days before randomization into the study or expected receipt during study participation; Known or suspected mitochondrial encephalomyopathy; History of Guillian-Barre syndrome; dministration of intranasal medications within 10 days prior to randomization, for expected receipt through 10 days after administration of each dose of investigational product. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The proportion of subjects with strain-specific HAI seroconversion rates (≥ 4-fold increase) from baseline through Days 28 and 56 by treatment group. |
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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) |
Shedding endpoints: The proportion of subjects who shed vaccine by formulation, strain, dose number, and baseline serostatus (by quantitative real-time polymerase chain reaction [qRT-PCR]); The number of days of shedding by formulation, strain, dose number, and baseline serostatus (by qRT-PCR); Viral titer by day, strain, dose number, and baseline serostatus (by qRT-PCR);
Immunogenicity (IM) endpoints: The proportion of subjects with strain-specific neutralizing antibody seroconversion rates (≥ 4-fold increase) from baseline through Days 28 and 56, by baseline serostatus; The proportion of subjects with strain-specific nasal Immunoglobulin A (IgA) increase (≥ 2-fold increase) from baseline through Days 28 and 56; The proportion of subjects with any strain-specific antibody response defined as a ≥ 4-fold increase in HAI antibodies or a ≥ 4-fold increase neutralizing antibodies or ≥ 2-fold increase in IgA antibodies;
Safety endpoints: The proportion of subjects with solicited symptoms experienced from administration of investigational product through 14 days post last vaccination; The proportion of subjects with treatment-emergent adverse events (AEs) experienced from administration of investigational product through 28 days post last vaccination; The proportion of subjects with treatment-emergent serious adverse events (SAEs) experienced from administration of investigational product through 28 days post last vaccination. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Shedding endpoints: Days 2, 3, 4, 5, and 7 after dose 1 (Day 1 dose) and on Days 2, 4 and 6 after dose 2 (Day 28 dose)
IM endpoints: Days 28 and 56
Safety endpoints: Day 1 to Day 28 after Day 1 and Day 28 dosing |
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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 | No |
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
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 | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
FluMist trivalent (2015-2016) and FluMist quadrivalent (2015-2016) |
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E.8.2.4 | Number of treatment arms in the trial | 3 |
E.8.3 |
Will this trial be conducted at a single site globally?
| No |
E.8.4 | Will this trial be conducted at multiple sites globally? | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.2 | Trial being conducted completely outside of the EEA | Yes |
E.8.6.3 | Specify the countries outside of the EEA in which trial sites are planned |
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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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The end of the study (“study completion”) is defined as the date of the last protocol-specified visit/assessment (including telephone contact) for the last subject in the study (up to Day 56). |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.2 | In all countries concerned by the trial months | 6 |