Healthy
Conditions
Keywords
children, FluMist, shedding,
Brief summary
Open label, single arm, multicenter study of the shedding and safety of a single dose of trivalent, influenza virus vaccine live, intranasal in children 6 to \< 60 months of age, with 28-day shedding follow-up and 180-day safety follow-up.
Detailed description
This was a Phase 2, open-label, single-arm, multicenter study designed to evaluate vaccine virus shedding and safety of trivalent influenza virus vaccine live, intranasal in children 6 to \< 60 months of age. Enrollment of approximately 200 participants was stratified by age, with 100 participants 6 to \< 24 months of age (who reached their sixth month but not their second year birthday) and 100 participants 24 to \< 60 months of age (who reached their second year but not their fifth year birthday). Baseline medical history data collection included the participants prior receipt of influenza vaccine or history of laboratory-confirmed influenza illness in the previous influenza season.
Interventions
BIOLOGICALTrivalent influenza virus vaccine live, intranasal
A single, intranasal dose of 0.2 mL (approximately 0.1 mL in each nostril) FluMist trivalent influenza virus vaccine live on Day 0 of the study. Each dose of FluMist vaccine contained 10\^7 FFU of three influenza virus strains.
Sponsors
MedImmune LLC
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
6 Months to 59 Months
Healthy volunteers
Yes
Inclusion criteria
* Male or female, 6 months to less than 60 months of age (reached their 6th month but not yet reached their 5th year birthday) at the time of study vaccination * Written informed consent and Health Insurance Portability and Accountability Act (HIPAA) authorization obtained from the participants parent/legal representative * Ability of the participants parent/legal representative to understand and comply with the requirements of the study * Participants parent/legal representative available by telephone * Ability to complete follow-up period of 180 days after study vaccination as required by the protocol
Exclusion criteria
* History of hypersensitivity to any component of trivalent influenza virus vaccine live, intranasal, including egg or egg products, monosodium glutamate, or porcine gelatin * History of hypersensitivity to gentamicin * History of Guillain-Barré syndrome * Medically diagnosed wheezing, bronchodilator use, or steroid use (systemic or inhaled), by parent/legal representative report or chart review, within the 42 days prior to study vaccination (i.e., children with recent persistent asthma were excluded); or history of severe persistent asthma according to the criteria described in the National Asthma Education and Prevention Program (NAEPP) Expert Panel Report * Acute febrile (greater than or equal to \[\>=\] 100.0 degree Fahrenheit \[°F\] oral or equivalent) and/or clinically significant respiratory illness (e.g., cough or sore throat) within 72 hours prior to study vaccination * Any known immunosuppressive condition or immune deficiency disease (including human immunodeficiency virus \[HIV\] infection), or ongoing receipt of any immunosuppressive therapy * Household contact who was immunocompromised (participants were also to avoid close contact with immunocompromised individuals for at least 21 days after study vaccination) * Use of aspirin or aspirin-containing products within the 30 days prior to study vaccination, or expected receipt through 180 days after study vaccination * Use of anti-influenza medications (including amantadine, rimantadine, oseltamivir, and zanamivir) within the 14 days prior to study vaccination, or expected receipt through 28 days after study vaccination * Use of any intranasal medication within the 14 days prior to study vaccination, or expected receipt through 28 days after study vaccination * Administration of any live virus vaccine within the 30 days prior to study vaccination, or expected receipt through 30 days after study vaccination * Administration of any inactivated (i.e., non-live) vaccine within the 14 days prior to study vaccination, or expected receipt through 14 days after study vaccination * Receipt of any investigational agent within the 30 days prior to study vaccination, or expected receipt through 180 days after study vaccination (use of licensed agents for indications not listed in the package insert was permitted) * Receipt of any blood product within the 90 days prior to study vaccination, or expected receipt through 28 days after study vaccination * Family member or household contact who was an employee of the research center or otherwise involved with the conduct of the study * Any condition that in the opinion of the investigator would have interfered with evaluation of the vaccine or interpretation of study results
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Shed Any Vaccine Virus | Days 1-28 after study vaccination (up to Day 28) | Viral shedding is defined as the detection of virus by viral culture and vaccine-type virus was confirmed by polymerase chain reaction (PCR) based assays. Viral shedding (A/New Caledonia/20/99 \[H1N1\]; A/Wyoming/03/2003 \[H3N2\] (A/Fujian/411/2002-like); B/Jilin/20/2003 B/Shanghai/361/2002-like\]) was measured from samples obtained from nasal swabs daily from Days 1 to 7 post vaccination and approximately every other day thereafter from Days 9 to 28. Participants whose Day 25 or 28 shedding sample was positive for vaccine virus had additional shedding samples collected approximately every 7 days, or as soon as possible upon awareness of culture positivity, until 2 consecutive samples were negative for vaccine virus. |
| Percentage of Participants Who Shed A/H1N1 Vaccine Virus | Days 1-28 after study vaccination (up to Day 28) | Viral shedding is defined as the detection of virus by viral culture and vaccine-type virus was confirmed by PCR based assays. Viral shedding (A/New Caledonia/20/99 \[H1N1\]; A/Wyoming/03/2003 \[H3N2\] (A/Fujian/411/2002-like); B/Jilin/20/2003 B/Shanghai/361/2002-like\]) was measured from samples obtained from nasal swabs daily from Days 1 to 7 post vaccination and approximately every other day thereafter from Days 9 to 28. Participants whose Day 25 or 28 shedding sample was positive for vaccine virus had additional shedding samples collected approximately every 7 days, or as soon as possible upon awareness of culture positivity, until 2 consecutive samples were negative for vaccine virus. |
| Percentage of Participants Who Shed A/H3N2 Vaccine Virus | Days 1-28 after study vaccination (up to Day 28) | Viral shedding is defined as the detection of virus by viral culture and vaccine-type virus was confirmed by PCR based assays. Viral shedding (A/New Caledonia/20/99 \[H1N1\]; A/Wyoming/03/2003 \[H3N2\] (A/Fujian/411/2002-like); B/Jilin/20/2003 B/Shanghai/361/2002-like\]) was measured from samples obtained from nasal swabs daily from Days 1 to 7 post vaccination and approximately every other day thereafter from Days 9 to 28. Participants whose Day 25 or 28 shedding sample was positive for vaccine virus had additional shedding samples collected approximately every 7 days, or as soon as possible upon awareness of culture positivity, until 2 consecutive samples were negative for vaccine virus. |
| Percentage of Participants Who Shed B Vaccine Virus | Days 1-28 after study vaccination (up to Day 28) | Viral shedding is defined as the detection of virus by viral culture and vaccine-type virus was confirmed by PCR based assays. Viral shedding (A/New Caledonia/20/99 \[H1N1\]; A/Wyoming/03/2003 \[H3N2\] (A/Fujian/411/2002-like); B/Jilin/20/2003 B/Shanghai/361/2002-like\]) was measured from samples obtained from nasal swabs daily from Days 1 to 7 post vaccination and approximately every other day thereafter from Days 9 to 28. Participants whose Day 25 or 28 shedding sample was positive for vaccine virus had additional shedding samples collected approximately every 7 days, or as soon as possible upon awareness of culture positivity, until 2 consecutive samples were negative for vaccine virus. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Quantitation of Confirmed A/H1N1 Shed Vaccine Virus on Any Day | Days 1-28 after study vaccination (up to Day 28) | Quantitation of confirmed A/H1N1 shed vaccine virus was evaluated using the log transformed median tissue culture infectious dose (TCID50) per (/) millilitre (mL) for A/H1N1 vaccine strain and summarized for all participants who shed vaccine virus. |
| Quantitation of Confirmed A/H3N2 Shed Vaccine Virus on Any Day | Days 1-28 after study vaccination (up to Day 28) | Quantitation of confirmed A/H3N2 shed vaccine virus was evaluated using the log (TCID50)/mL for A/H3N2 vaccine strain and summarized for all participants who shed vaccine virus. |
| Quantitation of Confirmed B Shed Vaccine Virus on Any Day | Days 1-28 after study vaccination (up to Day 28) | Quantitation of confirmed B shed vaccine virus was evaluated using the log (TCID50)/mL for B vaccine strain and summarized for all participants who shed vaccine virus. |
| Number of Participants With Genotypic and Phenotypic Stability of A/H1N1 Shed Vaccine Virus | Days 1-28 after study vaccination (up to Day 28) | The genetic and phenotypic stability of shed vaccine virus was evaluated by determination of genomic sequence and assessment of the cold-adapted (ca) and temperature-sensitive (ts) phenotypes. Viruses were considered ts if their titer at 39 degrees Celsius (°C) was at least two logs (100-fold) lower than their titer at 33°C. Viruses were considered ca if they replicated at 25°C to a titer that was no more than two logs (100-fold) lower than the titer at 33°C. After additional phenotypic and genotypic analyses, all evaluable samples retained the ca and ts phenotypes. |
| Duration of Any Vaccine Virus Shedding | Days 1-28 after study vaccination (up to Day 28) | The number of days of shedding was summarized for all participants who shed any vaccine virus. |
| Number of Participants With Genotypic and Phenotypic Stability of B Shed Vaccine Virus | Days 1-28 after study vaccination (up to Day 28) | The genetic and phenotypic stability of shed vaccine virus was evaluated by determination of genomic sequence and assessment of the ca and ts phenotypes. Viruses were considered ts if their titer at 37°C was at least two logs (100-fold) lower than their titer at 33°C. Viruses were considered ca if they replicated at 25°C to a titer that was no more than two logs (100-fold) lower than the titer at 33°C. After additional phenotypic and genotypic analyses, all evaluable samples retained the ca and ts phenotypes. |
| Number of Participants With Reactogenicity Events (REs) and Adverse Events (AEs) Through 28 Days Post Vaccination | Days 0-28 after vaccination (up to Day 28) | REs were predefined solicited events that could potentially occur after vaccination. The REs for this study were fever, runny/stuffy nose, sore throat, cough, vomiting, headache, abdominal pain (stomach ache), muscle ache, chills, decreased activity level (lethargy), decreased appetite, and irritability. An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. |
| Number of Participants With Serious Adverse Events (SAEs) and Significant New Medical Conditions (SNMC) Through 180 Days Post Vaccination | Days 0-180 after vaccination (up to 6.5 months) | An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. An SNMC is defined as a newly diagnosed medical condition that was of a chronic, ongoing nature and was assessed by the investigator as medically significant. SNMCs included, but were not limited to, diabetes, asthma, autoimmune disease (lupus, rheumatoid arthritis), and neurological disease (epilepsy, autism). |
| Number of Participants With REs in Relation to Any Vaccine Virus Shedding | Days 0-28 after study vaccination (up to Day 28) | REs were predefined solicited events that could potentially occur after vaccination. The REs for this study were fever, runny/stuffy nose, sore throat, cough, vomiting, headache, abdominal pain (stomach ache), muscle ache, chills, decreased activity level (lethargy), decreased appetite, and irritability. |
| Number of Participants With Genotypic and Phenotypic Stability of A/H3N2 Shed Vaccine Virus | Days 1-28 after study vaccination (up to Day 28) | The genetic and phenotypic stability of shed vaccine virus was evaluated by determination of genomic sequence and assessment of the ca and ts phenotypes. Viruses were considered ts if their titer at 39°C was at least two logs (100-fold) lower than their titer at 33°C. Viruses were considered ca if they replicated at 25°C to a titer that was no more than two logs (100-fold) lower than the titer at 33°C. After additional phenotypic and genotypic analyses, all evaluable samples retained the ca and ts phenotypes. |
| Duration of Confirmed A/H1N1 Vaccine Virus Shedding | Days 1-28 after study vaccination (up to Day 28) | The number of days of shedding was summarized for all participants who shed confirmed A/H1N1 strain virus. |
| Duration of Confirmed A/H3N2 Vaccine Virus Shedding | Days 1-28 after study vaccination (up to Day 28) | The number of days of shedding was summarized for all participants who shed confirmed A/H3N2 strain virus. |
| Duration of Confirmed B Vaccine Virus Shedding | Days 1-28 after study vaccination (up to Day 28) | The number of days of shedding was summarized for all participants who shed confirmed B strain virus. |
Countries
United States
Participant flow
Recruitment details
A total of 200 participants were enrolled in the study from 15-May-2006 through 22-Jun-2006 at 16 sites in the United States of America.
Pre-assignment details
A total of 200 participants were stratified on the basis of their age into two cohorts: Cohort 1 (participants aged between 6 to less than \[\<\] 24 months) and Cohort 2 (participants aged between 24 to \< 60 months).
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1: Participants Between 6 to < 24 Months Age Participants received a single, intranasal dose of 0.2 millilitre (mL) (approximately 0.1 mL in each nostril FluMist trivalent influenza virus vaccine live on Day 0 of the study. Each dose of FluMist vaccine contained 10\^7 fluorescent focus units (FFU) of three influenza virus strains namely, A/New Caledonia/20/99 (H1N1), A/Wyoming/03/2003 (H3N2) (A/Fujian/411/2002-like) and B/Jilin/20/2003 (B/Shanghai/361/2002-like). | 100 |
| Cohort 2: Participants Between 24 to < 60 Months Age Participants received a single, intranasal dose of 0.2 mL (approximately 0.1 mL in each nostril) FluMist trivalent influenza virus vaccine live on Day 0 of the study. Each dose of FluMist vaccine contained 10\^7 FFU of three influenza virus strains namely, A/New Caledonia/20/99 (H1N1), A/Wyoming/03/2003 (H3N2) (A/Fujian/411/2002-like) and B/Jilin/20/2003 (B/Shanghai/361/2002-like). | 100 |
| Total | 200 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 2 | 0 |
| Overall Study | Participant was not contacted in window | 0 | 1 |
Baseline characteristics
| Characteristic | Cohort 1: Participants Between 6 to < 24 Months Age | Cohort 2: Participants Between 24 to < 60 Months Age | Total |
|---|---|---|---|
| Age, Continuous | 14.87 months STANDARD_DEVIATION 5.5 | 41.31 months STANDARD_DEVIATION 9.98 | 28.09 months STANDARD_DEVIATION 15.5 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 7 Participants | 15 Participants | 22 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 93 Participants | 85 Participants | 178 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| History of laboratory-confirmed influenza illness in previous influenza season No | 99 participants | 98 participants | 197 participants |
| History of laboratory-confirmed influenza illness in previous influenza season Yes | 1 participants | 2 participants | 3 participants |
| History of receiving an influenza vaccine No | 57 participants | 27 participants | 84 participants |
| History of receiving an influenza vaccine Yes | 43 participants | 73 participants | 116 participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 14 Participants | 7 Participants | 21 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 86 Participants | 89 Participants | 175 Participants |
| Sex: Female, Male Female | 51 Participants | 53 Participants | 104 Participants |
| Sex: Female, Male Male | 49 Participants | 47 Participants | 96 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 48 / 100 | 25 / 100 |
| serious Total, serious adverse events | 1 / 100 | 0 / 100 |
Outcome results
Primary
Percentage of Participants Who Shed A/H1N1 Vaccine Virus
Viral shedding is defined as the detection of virus by viral culture and vaccine-type virus was confirmed by PCR based assays. Viral shedding (A/New Caledonia/20/99 \[H1N1\]; A/Wyoming/03/2003 \[H3N2\] (A/Fujian/411/2002-like); B/Jilin/20/2003 B/Shanghai/361/2002-like\]) was measured from samples obtained from nasal swabs daily from Days 1 to 7 post vaccination and approximately every other day thereafter from Days 9 to 28. Participants whose Day 25 or 28 shedding sample was positive for vaccine virus had additional shedding samples collected approximately every 7 days, or as soon as possible upon awareness of culture positivity, until 2 consecutive samples were negative for vaccine virus.
Time frame: Days 1-28 after study vaccination (up to Day 28)
Population: Shedding population included all participants who received a full dose of study drug and had assay results from nasal specimens obtained at any post-dosing time point. Here, number of participants analyzed signified those participants who were evaluable for this outcome.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1: Participants Between 6 to < 24 Months Age | Percentage of Participants Who Shed A/H1N1 Vaccine Virus | 76.8 percentage of participants |
| Cohort 2: Participants Between 24 to < 60 Months Age | Percentage of Participants Who Shed A/H1N1 Vaccine Virus | 52.0 percentage of participants |
Primary
Percentage of Participants Who Shed A/H3N2 Vaccine Virus
Viral shedding is defined as the detection of virus by viral culture and vaccine-type virus was confirmed by PCR based assays. Viral shedding (A/New Caledonia/20/99 \[H1N1\]; A/Wyoming/03/2003 \[H3N2\] (A/Fujian/411/2002-like); B/Jilin/20/2003 B/Shanghai/361/2002-like\]) was measured from samples obtained from nasal swabs daily from Days 1 to 7 post vaccination and approximately every other day thereafter from Days 9 to 28. Participants whose Day 25 or 28 shedding sample was positive for vaccine virus had additional shedding samples collected approximately every 7 days, or as soon as possible upon awareness of culture positivity, until 2 consecutive samples were negative for vaccine virus.
Time frame: Days 1-28 after study vaccination (up to Day 28)
Population: Shedding population included all participants who received a full dose of study drug and had assay results from nasal specimens obtained at any post-dosing time point. Here, number of participants analyzed signified those participants who were evaluable for this outcome.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1: Participants Between 6 to < 24 Months Age | Percentage of Participants Who Shed A/H3N2 Vaccine Virus | 57.6 percentage of participants |
| Cohort 2: Participants Between 24 to < 60 Months Age | Percentage of Participants Who Shed A/H3N2 Vaccine Virus | 15.0 percentage of participants |
Primary
Percentage of Participants Who Shed Any Vaccine Virus
Viral shedding is defined as the detection of virus by viral culture and vaccine-type virus was confirmed by polymerase chain reaction (PCR) based assays. Viral shedding (A/New Caledonia/20/99 \[H1N1\]; A/Wyoming/03/2003 \[H3N2\] (A/Fujian/411/2002-like); B/Jilin/20/2003 B/Shanghai/361/2002-like\]) was measured from samples obtained from nasal swabs daily from Days 1 to 7 post vaccination and approximately every other day thereafter from Days 9 to 28. Participants whose Day 25 or 28 shedding sample was positive for vaccine virus had additional shedding samples collected approximately every 7 days, or as soon as possible upon awareness of culture positivity, until 2 consecutive samples were negative for vaccine virus.
Time frame: Days 1-28 after study vaccination (up to Day 28)
Population: Shedding population included all participants who received a full dose of study drug and had assay results from nasal specimens obtained at any post-dosing time point. Here, number of participants analyzed signified those participants who were evaluable for this outcome.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1: Participants Between 6 to < 24 Months Age | Percentage of Participants Who Shed Any Vaccine Virus | 88.9 percentage of participants |
| Cohort 2: Participants Between 24 to < 60 Months Age | Percentage of Participants Who Shed Any Vaccine Virus | 69.0 percentage of participants |
Primary
Percentage of Participants Who Shed B Vaccine Virus
Viral shedding is defined as the detection of virus by viral culture and vaccine-type virus was confirmed by PCR based assays. Viral shedding (A/New Caledonia/20/99 \[H1N1\]; A/Wyoming/03/2003 \[H3N2\] (A/Fujian/411/2002-like); B/Jilin/20/2003 B/Shanghai/361/2002-like\]) was measured from samples obtained from nasal swabs daily from Days 1 to 7 post vaccination and approximately every other day thereafter from Days 9 to 28. Participants whose Day 25 or 28 shedding sample was positive for vaccine virus had additional shedding samples collected approximately every 7 days, or as soon as possible upon awareness of culture positivity, until 2 consecutive samples were negative for vaccine virus.
Time frame: Days 1-28 after study vaccination (up to Day 28)
Population: Shedding population included all participants who received a full dose of study drug and had assay results from nasal specimens obtained at any post-dosing time point. Here, number of participants analyzed signified those participants who were evaluable for this outcome.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1: Participants Between 6 to < 24 Months Age | Percentage of Participants Who Shed B Vaccine Virus | 37.4 percentage of participants |
| Cohort 2: Participants Between 24 to < 60 Months Age | Percentage of Participants Who Shed B Vaccine Virus | 37.0 percentage of participants |
Secondary
Duration of Any Vaccine Virus Shedding
The number of days of shedding was summarized for all participants who shed any vaccine virus.
Time frame: Days 1-28 after study vaccination (up to Day 28)
Population: Shedding population included all participants who received a full dose of study drug and had assay results from nasal specimens obtained at any post-dosing time point. Here, number of participants analyzed signified those participants who shed any confirmed strain virus.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1: Participants Between 6 to < 24 Months Age | Duration of Any Vaccine Virus Shedding | 3.0 days | Standard Deviation 1.5 |
| Cohort 2: Participants Between 24 to < 60 Months Age | Duration of Any Vaccine Virus Shedding | 2.7 days | Standard Deviation 1.6 |
Secondary
Duration of Confirmed A/H1N1 Vaccine Virus Shedding
The number of days of shedding was summarized for all participants who shed confirmed A/H1N1 strain virus.
Time frame: Days 1-28 after study vaccination (up to Day 28)
Population: Shedding population included all participants who received a full dose of study drug and had assay results from nasal specimens obtained at any post-dosing time point. Here, number of participants analyzed signified those participants who shed any confirmed strain virus.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1: Participants Between 6 to < 24 Months Age | Duration of Confirmed A/H1N1 Vaccine Virus Shedding | 2.1 days | Standard Deviation 1 |
| Cohort 2: Participants Between 24 to < 60 Months Age | Duration of Confirmed A/H1N1 Vaccine Virus Shedding | 2.2 days | Standard Deviation 1.3 |
Secondary
Duration of Confirmed A/H3N2 Vaccine Virus Shedding
The number of days of shedding was summarized for all participants who shed confirmed A/H3N2 strain virus.
Time frame: Days 1-28 after study vaccination (up to Day 28)
Population: Shedding population included all participants who received a full dose of study drug and had assay results from nasal specimens obtained at any post-dosing time point. Here, number of participants analyzed signified those participants who shed any confirmed strain virus.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1: Participants Between 6 to < 24 Months Age | Duration of Confirmed A/H3N2 Vaccine Virus Shedding | 1.8 days | Standard Deviation 0.9 |
| Cohort 2: Participants Between 24 to < 60 Months Age | Duration of Confirmed A/H3N2 Vaccine Virus Shedding | 1.7 days | Standard Deviation 0.8 |
Secondary
Duration of Confirmed B Vaccine Virus Shedding
The number of days of shedding was summarized for all participants who shed confirmed B strain virus.
Time frame: Days 1-28 after study vaccination (up to Day 28)
Population: Shedding population included all participants who received a full dose of study drug and had assay results from nasal specimens obtained at any post-dosing time point. Here, number of participants analyzed signified those participants who shed any confirmed strain virus.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1: Participants Between 6 to < 24 Months Age | Duration of Confirmed B Vaccine Virus Shedding | 2.1 days | Standard Deviation 1.5 |
| Cohort 2: Participants Between 24 to < 60 Months Age | Duration of Confirmed B Vaccine Virus Shedding | 1.8 days | Standard Deviation 1.2 |
Secondary
Number of Participants With Genotypic and Phenotypic Stability of A/H1N1 Shed Vaccine Virus
The genetic and phenotypic stability of shed vaccine virus was evaluated by determination of genomic sequence and assessment of the cold-adapted (ca) and temperature-sensitive (ts) phenotypes. Viruses were considered ts if their titer at 39 degrees Celsius (°C) was at least two logs (100-fold) lower than their titer at 33°C. Viruses were considered ca if they replicated at 25°C to a titer that was no more than two logs (100-fold) lower than the titer at 33°C. After additional phenotypic and genotypic analyses, all evaluable samples retained the ca and ts phenotypes.
Time frame: Days 1-28 after study vaccination (up to Day 28)
Population: Shedding population: all participants who received a full dose of study drug and had assay results from nasal specimens obtained at any post-dosing time point. Here, number of participants analyzed signified those participants who were evaluable for this outcome and n signified those participants who were evaluable for a specified category.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 1: Participants Between 6 to < 24 Months Age | Number of Participants With Genotypic and Phenotypic Stability of A/H1N1 Shed Vaccine Virus | Genotypic Stability (n=0) | NA participants |
| Cohort 1: Participants Between 6 to < 24 Months Age | Number of Participants With Genotypic and Phenotypic Stability of A/H1N1 Shed Vaccine Virus | Phenotypic Stability (n=93) | 90 participants |
Secondary
Number of Participants With Genotypic and Phenotypic Stability of A/H3N2 Shed Vaccine Virus
The genetic and phenotypic stability of shed vaccine virus was evaluated by determination of genomic sequence and assessment of the ca and ts phenotypes. Viruses were considered ts if their titer at 39°C was at least two logs (100-fold) lower than their titer at 33°C. Viruses were considered ca if they replicated at 25°C to a titer that was no more than two logs (100-fold) lower than the titer at 33°C. After additional phenotypic and genotypic analyses, all evaluable samples retained the ca and ts phenotypes.
Time frame: Days 1-28 after study vaccination (up to Day 28)
Population: Shedding population: all participants who received a full dose of study drug and had assay results from nasal specimens obtained at any post-dosing time point. Here, number of participants analyzed signified those participants who were evaluable for this outcome and n signified those participants who were evaluable for a specified category.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 1: Participants Between 6 to < 24 Months Age | Number of Participants With Genotypic and Phenotypic Stability of A/H3N2 Shed Vaccine Virus | Genotypic Stability (n=0) | NA participants |
| Cohort 1: Participants Between 6 to < 24 Months Age | Number of Participants With Genotypic and Phenotypic Stability of A/H3N2 Shed Vaccine Virus | Phenotypic Stability (n=39) | 37 participants |
Secondary
Number of Participants With Genotypic and Phenotypic Stability of B Shed Vaccine Virus
The genetic and phenotypic stability of shed vaccine virus was evaluated by determination of genomic sequence and assessment of the ca and ts phenotypes. Viruses were considered ts if their titer at 37°C was at least two logs (100-fold) lower than their titer at 33°C. Viruses were considered ca if they replicated at 25°C to a titer that was no more than two logs (100-fold) lower than the titer at 33°C. After additional phenotypic and genotypic analyses, all evaluable samples retained the ca and ts phenotypes.
Time frame: Days 1-28 after study vaccination (up to Day 28)
Population: Shedding population: all participants who received a full dose of study drug and had assay results from nasal specimens obtained at any post-dosing time point. Here, number of participants analyzed signified those participants who were evaluable for this outcome and n signified those participants who were evaluable for a specified category.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 1: Participants Between 6 to < 24 Months Age | Number of Participants With Genotypic and Phenotypic Stability of B Shed Vaccine Virus | Genotypic Stability (n=33) | 33 participants |
| Cohort 1: Participants Between 6 to < 24 Months Age | Number of Participants With Genotypic and Phenotypic Stability of B Shed Vaccine Virus | Phenotypic Stability (n=61) | 29 participants |
Secondary
Number of Participants With Reactogenicity Events (REs) and Adverse Events (AEs) Through 28 Days Post Vaccination
REs were predefined solicited events that could potentially occur after vaccination. The REs for this study were fever, runny/stuffy nose, sore throat, cough, vomiting, headache, abdominal pain (stomach ache), muscle ache, chills, decreased activity level (lethargy), decreased appetite, and irritability. An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship.
Time frame: Days 0-28 after vaccination (up to Day 28)
Population: Safety population included all participants who received any study drug and had experienced any follow-up for safety.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 1: Participants Between 6 to < 24 Months Age | Number of Participants With Reactogenicity Events (REs) and Adverse Events (AEs) Through 28 Days Post Vaccination | Any REs | 84 participants |
| Cohort 1: Participants Between 6 to < 24 Months Age | Number of Participants With Reactogenicity Events (REs) and Adverse Events (AEs) Through 28 Days Post Vaccination | AEs | 48 participants |
| Cohort 2: Participants Between 24 to < 60 Months Age | Number of Participants With Reactogenicity Events (REs) and Adverse Events (AEs) Through 28 Days Post Vaccination | Any REs | 77 participants |
| Cohort 2: Participants Between 24 to < 60 Months Age | Number of Participants With Reactogenicity Events (REs) and Adverse Events (AEs) Through 28 Days Post Vaccination | AEs | 31 participants |
Secondary
Number of Participants With REs in Relation to Any Vaccine Virus Shedding
REs were predefined solicited events that could potentially occur after vaccination. The REs for this study were fever, runny/stuffy nose, sore throat, cough, vomiting, headache, abdominal pain (stomach ache), muscle ache, chills, decreased activity level (lethargy), decreased appetite, and irritability.
Time frame: Days 0-28 after study vaccination (up to Day 28)
Population: Safety population included all participants who received any study drug and had experienced any follow-up for safety. Here, number of participants analyzed signified those participants who had REs.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1: Participants Between 6 to < 24 Months Age | Number of Participants With REs in Relation to Any Vaccine Virus Shedding | 75 participants |
| Cohort 2: Participants Between 24 to < 60 Months Age | Number of Participants With REs in Relation to Any Vaccine Virus Shedding | 55 participants |
Secondary
Number of Participants With Serious Adverse Events (SAEs) and Significant New Medical Conditions (SNMC) Through 180 Days Post Vaccination
An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. An SNMC is defined as a newly diagnosed medical condition that was of a chronic, ongoing nature and was assessed by the investigator as medically significant. SNMCs included, but were not limited to, diabetes, asthma, autoimmune disease (lupus, rheumatoid arthritis), and neurological disease (epilepsy, autism).
Time frame: Days 0-180 after vaccination (up to 6.5 months)
Population: Safety population included all participants who received any study drug and had experienced any follow-up for safety.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 1: Participants Between 6 to < 24 Months Age | Number of Participants With Serious Adverse Events (SAEs) and Significant New Medical Conditions (SNMC) Through 180 Days Post Vaccination | SAEs | 1 participants |
| Cohort 1: Participants Between 6 to < 24 Months Age | Number of Participants With Serious Adverse Events (SAEs) and Significant New Medical Conditions (SNMC) Through 180 Days Post Vaccination | SNMC | 1 participants |
| Cohort 2: Participants Between 24 to < 60 Months Age | Number of Participants With Serious Adverse Events (SAEs) and Significant New Medical Conditions (SNMC) Through 180 Days Post Vaccination | SAEs | 0 participants |
| Cohort 2: Participants Between 24 to < 60 Months Age | Number of Participants With Serious Adverse Events (SAEs) and Significant New Medical Conditions (SNMC) Through 180 Days Post Vaccination | SNMC | 1 participants |
Secondary
Quantitation of Confirmed A/H1N1 Shed Vaccine Virus on Any Day
Quantitation of confirmed A/H1N1 shed vaccine virus was evaluated using the log transformed median tissue culture infectious dose (TCID50) per (/) millilitre (mL) for A/H1N1 vaccine strain and summarized for all participants who shed vaccine virus.
Time frame: Days 1-28 after study vaccination (up to Day 28)
Population: Shedding population included all participants who received a full dose of study drug and had assay results from nasal specimens obtained at any post-dosing time point. Here, number of participants analyzed signified those participants who shed any confirmed strain virus.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1: Participants Between 6 to < 24 Months Age | Quantitation of Confirmed A/H1N1 Shed Vaccine Virus on Any Day | 2.14 log (TCID50)/mL | Standard Deviation 0.98 |
| Cohort 2: Participants Between 24 to < 60 Months Age | Quantitation of Confirmed A/H1N1 Shed Vaccine Virus on Any Day | 2.62 log (TCID50)/mL | Standard Deviation 0.97 |
Secondary
Quantitation of Confirmed A/H3N2 Shed Vaccine Virus on Any Day
Quantitation of confirmed A/H3N2 shed vaccine virus was evaluated using the log (TCID50)/mL for A/H3N2 vaccine strain and summarized for all participants who shed vaccine virus.
Time frame: Days 1-28 after study vaccination (up to Day 28)
Population: Shedding population included all participants who received a full dose of study drug and had assay results from nasal specimens obtained at any post-dosing time point. Here, number of participants analyzed signified those participants who shed any confirmed strain virus.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1: Participants Between 6 to < 24 Months Age | Quantitation of Confirmed A/H3N2 Shed Vaccine Virus on Any Day | 1.59 log (TCID50)/mL | Standard Deviation 0.95 |
| Cohort 2: Participants Between 24 to < 60 Months Age | Quantitation of Confirmed A/H3N2 Shed Vaccine Virus on Any Day | 1.10 log (TCID50)/mL | Standard Deviation 0.53 |
Secondary
Quantitation of Confirmed B Shed Vaccine Virus on Any Day
Quantitation of confirmed B shed vaccine virus was evaluated using the log (TCID50)/mL for B vaccine strain and summarized for all participants who shed vaccine virus.
Time frame: Days 1-28 after study vaccination (up to Day 28)
Population: Shedding population included all participants who received a full dose of study drug and had assay results from nasal specimens obtained at any post-dosing time point. Here, number of participants analyzed signified those participants who shed any confirmed strain virus.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1: Participants Between 6 to < 24 Months Age | Quantitation of Confirmed B Shed Vaccine Virus on Any Day | 1.70 log (TCID50)/mL | Standard Deviation 1.09 |
| Cohort 2: Participants Between 24 to < 60 Months Age | Quantitation of Confirmed B Shed Vaccine Virus on Any Day | 1.24 log (TCID50)/mL | Standard Deviation 0.68 |