Evaluate the Shedding and Immunogencity of Different Formulations of FluMist in Children 24 to <48 Months of Age - FluMist

Study identifier:D2560C00013

ClinicalTrials.gov identifier:NCT03143101

EudraCT identifier:N/A

CTIS identifier:N/A

Study Complete

Official Title

A Phase 4 Double-blind Study to Evaluate the Shedding and Immunogenicity of Trivalent and Quadrivalent Formulations of FluMist in Children 24 to < 48 Months of Age

Medical condition

Influenza, Healthy

Phase

Phase 4

Healthy volunteers

Yes

Study drug

Sex

All

Actual Enrollment

200

Study type

Interventional

Age

24 Months - 47 Months

Date

Study Start Date: 08 May 2017

Primary Completion Date: 29 Sept 2017

Study Completion Date: 29 Sept 2017

Study design

Allocation: Randomized
Endpoint Classification: -
Intervention Model: Parallel Assignment
Masking: Double Blind
Primary Purpose: Prevention

Verification:

Verified 01 Nov 2018 by MedImmune, LLC

Collaborators

AstraZeneca

Inclusion and exclusion criteria

Location

Research Site

Tomball, TX, United States, 77375

Location

Research Site

Binghamton, NY, United States, 13901

Location

Research Site

Savannah, GA, United States, 31405

Location

Research Site

Salt Lake City, UT, United States, 84124

Location

Research Site

Dakota Dunes, SD, United States, 57049

Location

Research Site

Omaha, NE, United States, 68134

Location

Research Site

Ft. Worth, TX, United States, 76104

Location

Research Site

Bardstown, KY, United States, 40004

Arms	Assigned Interventions
Experimental: FluMist trivalent (2015-2016) Participants will receive intranasal spray of 0.2 milliliter (mL) (total dose in both nostrils) FluMist trivalent vaccine on Days 1 and 28. Each 0.2 mL dose contained 10^7±0.5 fluorescent focus units (FFU) of each vaccine strain. Strains included in the trivalent vaccine were: A/H1N1 (A/Bolivia/559/2013), A/H3N2 (A/Switzerland/9715293/2013), and B/Phuket/3073/2013 (B/Yamagata-lineage).	Biological/Vaccine: FluMist trivalent (2015-2016) 0.2 mL (total dose in both nostrils) on Days 1 and 28. Each 0.2 mL dose will contain 10^7±0.5 FFU of each vaccine strain.
Experimental: FluMist Quadrivalent (2015-2016) Participants will receive intranasal spray of 0.2 mL (total dose in both nostrils) FluMist quadrivalent vaccine on Days 1 and 28. Each 0.2 mL dose contained 10^7±0.5 FFU of each vaccine strain. Strains included in the vaccine were A/H1N1 (A/Bolivia/559/2013), A/H3N2 (A/Switzerland/9715293/2013), B/Phuket/3073/2013 (B/Yamagata-lineage), and B/Brisbane/60/2008 (B/Victoria-lineage).	Biological/Vaccine: FluMist Quadrivalent (2015-2016) 0.2 mL (total dose in both nostrils) on Days 1 and 28. Each 0.2 mL dose will contain 10^7±0.5 FFU of each vaccine strain.
Experimental: FluMist Quadrivalent (2017-2018) Participants will receive intranasal spray of 0.2 mL (total dose in both nostrils) FluMist quadrivalent vaccine on Days 1 and 28. Each 0.2 mL dose contained 10^7±0.5 FFU of each vaccine strain. Strains included in the vaccine were the new A/H1N1 (A/Slovenia/2903/2015), A/H3N2 (A/New Caledonia/71/2014), B/Phuket/3073/2013 (B/Yamagata-lineage), and B/Brisbane/60/2008 (B/Victoria-lineage).	Biological/Vaccine: FluMist Quadrivalent (2017-2018) 0.2 mL (total dose in both nostrils) on Days 1 and 28. Each 0.2 mL dose will contain 10^7±0.5 FFU of each vaccine strain.

Participant Flow

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
The study was conducted from 08 May 2017 through 29 Sep 2017 in the USA.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
A total of 200 participants were randomized and participated in the study.

Reporting Groups

	Description
FluMist trivalent (2015-2016)	Participants received intranasal spray of 0.2 milliliter (mL) (total dose in both nostrils) FluMist trivalent vaccine on Days 1 and 28. Each 0.2 mL dose contained 10^7±0.5 fluorescent focus units (FFU) of each vaccine strain. Strains included in the trivalent vaccine were: A/H1N1 (A/Bolivia/559/2013), A/H3N2 (A/Switzerland/9715293/2013), and B/Phuket/3073/2013 (B/Yamagata-lineage).
FluMist Quadrivalent (2015-2016)	Participants received intranasal spray of 0.2 mL (total dose in both nostrils) FluMist quadrivalent vaccine on Days 1 and 28. Each 0.2 mL dose contained 10^7±0.5 FFU of each vaccine strain. Strains included in the vaccine were A/H1N1 (A/Bolivia/559/2013), A/H3N2 (A/Switzerland/9715293/2013), B/Phuket/3073/2013 (B/Yamagata-lineage), and B/Brisbane/60/2008 (B/Victoria-lineage).
FluMist Quadrivalent (2017-2018)	Participants received intranasal spray of 0.2 mL (total dose in both nostrils) FluMist quadrivalent vaccine on Days 1 and 28. Each 0.2 mL dose contained 10^7±0.5 FFU of each vaccine strain. Strains included in the vaccine were the new A/H1N1 (A/Slovenia/2903/2015), A/H3N2 (A/New Caledonia/71/2014), B/Phuket/3073/2013 (B/Yamagata-lineage), and B/Brisbane/60/2008 (B/Victoria-lineage).

Participant Flow: Overall Study

	FluMist trivalent (2015-2016)	FluMist Quadrivalent (2015-2016)	FluMist Quadrivalent (2017-2018)
STARTED	67	66	67
COMPLETED	65	63	67
NOT COMPLETED	2	3	0
Withdrawal by Subject	0	1	0
Lost to Follow-up	2	2	0

Baseline Characteristics

Analysis Population Description -- Explanation of how the number of participants for analysis was determined.

As-treated population included all participants who received any investigational drug.

Reporting Groups

	Description
FluMist trivalent (2015-2016)	Participants received intranasal spray of 0.2 mL (total dose in both nostrils) FluMist trivalent vaccine on Days 1 and 28. Each 0.2 mL dose contained 10^7±0.5 FFU of each vaccine strain. Strains included in the trivalent vaccine were: A/H1N1 (A/Bolivia/559/2013), A/H3N2 (A/Switzerland/9715293/2013), and B/Phuket/3073/2013 (B/Yamagata-lineage).
FluMist Quadrivalent (2015-2016)	Participants received intranasal spray of 0.2 mL (total dose in both nostrils) FluMist quadrivalent vaccine on Days 1 and 28. Each 0.2 mL dose contained 10^7±0.5 FFU of each vaccine strain. Strains included in the vaccine were A/H1N1 (A/Bolivia/559/2013), A/H3N2 (A/Switzerland/9715293/2013), B/Phuket/3073/2013 (B/Yamagata-lineage), and B/Brisbane/60/2008 (B/Victoria-lineage).
FluMist Quadrivalent (2017-2018)	Participants received intranasal spray of 0.2 mL (total dose in both nostrils) FluMist quadrivalent vaccine on Days 1 and 28. Each 0.2 mL dose contained 10^7±0.5 FFU of each vaccine strain. Strains included in the vaccine were the new A/H1N1 (A/Slovenia/2903/2015), A/H3N2 (A/New Caledonia/71/2014), B/Phuket/3073/2013 (B/Yamagata-lineage), and B/Brisbane/60/2008 (B/Victoria-lineage).

Baseline Measures

	FluMist trivalent (2015-2016)	FluMist Quadrivalent (2015-2016)	FluMist Quadrivalent (2017-2018)	Total
Number of Participants [units: Participants]	67	66	67	200
Age Continuous [units: months] Mean ± Standard Deviation	35.96 ± 6.41	34.96 ± 6.78	34.94 ± 6.80	35.29 ± 6.65
Sex: Female, Male [units: Participants]
Female	27	32	35	94
Male	40	34	32	106
Race (NIH/OMB) [units: Participants]
American Indian or Alaska Native	0	1	0	1
Asian	1	0	0	1
Native Hawaiian or Other Pacific Islander	2	0	1	3
Black or African American	9	9	13	31
White	52	55	49	156
More than one race	3	1	3	7
Unknown or Not Reported	0	0	1	1
Ethnicity (NIH/OMB) [units: Participants]
Hispanic or Latino	11	9	14	34
Not Hispanic or Latino	56	57	53	166
Unknown or Not Reported	0	0	0	0

Outcome Measures

1. Primary Outcome Measure: Percentage of Participants With A/H1N1 Hemagglutination Inhibition (HAI) Antibody Seroconversion Rate at Day 28 [ Time Frame: Day 28 ]

Measure Type	Primary
Measure Name	Percentage of Participants With A/H1N1 Hemagglutination Inhibition (HAI) Antibody Seroconversion Rate at Day 28
Measure Description	Seroconversion rate is defined as at least (>=) 4-fold rise from baseline in A/H1N1 HAI antibody titer. Percentage of participants with >= 4-fold rise in A/H1N1 HAI antibody titer at Day 28 is reported. Comparative statistical analysis was planned only for 'FluMist Quadrivalent (2015-2016)' and 'FluMist Quadrivalent (2017-2018)' arms.
Time Frame	Day 28
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Immunogenicity population included all participants in the as-treated population (ATP) who had no major protocol deviations judged to have the potential to interfere with the generation or interpretation of an immune response to investigational product. Here, "N" signifies number of participants analyzed for this outcome measure.

Reporting Groups

	Description
FluMist trivalent (2015-2016)	Participants received intranasal spray of 0.2 mL (total dose in both nostrils) FluMist trivalent vaccine on Days 1 and 28. Each 0.2 mL dose contained 10^7±0.5 FFU of each vaccine strain. Strains included in the trivalent vaccine were: A/H1N1 (A/Bolivia/559/2013), A/H3N2 (A/Switzerland/9715293/2013), and B/Phuket/3073/2013 (B/Yamagata-lineage).
FluMist Quadrivalent (2015-2016)	Participants received intranasal spray of 0.2 mL (total dose in both nostrils) FluMist quadrivalent vaccine on Days 1 and 28. Each 0.2 mL dose contained 10^7±0.5 FFU of each vaccine strain. Strains included in the vaccine were A/H1N1 (A/Bolivia/559/2013), A/H3N2 (A/Switzerland/9715293/2013), B/Phuket/3073/2013 (B/Yamagata-lineage), and B/Brisbane/60/2008 (B/Victoria-lineage).
FluMist Quadrivalent (2017-2018)	Participants received intranasal spray of 0.2 mL (total dose in both nostrils) FluMist quadrivalent vaccine on Days 1 and 28. Each 0.2 mL dose contained 10^7±0.5 FFU of each vaccine strain. Strains included in the vaccine were the new A/H1N1 (A/Slovenia/2903/2015), A/H3N2 (A/New Caledonia/71/2014), B/Phuket/3073/2013 (B/Yamagata-lineage), and B/Brisbane/60/2008 (B/Victoria-lineage).

Measured Values

	FluMist trivalent (2015-2016)	FluMist Quadrivalent (2015-2016)	FluMist Quadrivalent (2017-2018)
Number of Participants Analyzed [units:participants]	60	56	64
Percentage of Participants With A/H1N1 Hemagglutination Inhibition (HAI) Antibody Seroconversion Rate at Day 28 [units: Percentage of participants] Number (95% Confidence Interval)	10.0 (3.8 to 20.5)	5.4 (1.1 to 14.9)	23.4 (13.8 to 35.7)

Statistical Analysis 1 for Percentage of Participants With A/H1N1 Hemagglutination Inhibition (HAI) Antibody Seroconversion Rate at Day 28

Groups^[1]	FluMist Quadrivalent (2015-2016), FluMist Quadrivalent (2017-2018)
Method^[3]	Cochran-Mantel-Haenszel
P-Value^[4]	0.006
Mean Difference (Net)^[5]	18.1
95% Confidence Interval	( 4.8 to 30.9 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	p-value is calculated from the Cochran-Mantel-Haenszel (CMH) test adjusting for the prior influenza vaccination status.
[5]	Other relevant estimation information:
	No text entered.

2. Primary Outcome Measure: Percentage of Participants With A/H3N2 HAI Antibody Seroconversion Rate at Day 28 [ Time Frame: Day 28 ]

Measure Type	Primary
Measure Name	Percentage of Participants With A/H3N2 HAI Antibody Seroconversion Rate at Day 28
Measure Description	Seroconversion rate is defined as >= 4-fold rise from baseline in A/H3N2 HAI antibody titer. Percentage of participants with >= 4-fold rise in A/H3N2 HAI antibody titer at Day 28 is reported.
Time Frame	Day 28
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Immunogenicity population included all participants in the ATP who had no major protocol deviations judged to have the potential to interfere with the generation or interpretation of an immune response to investigational product. Here, "N" signifies number of participants analyzed for this outcome measure.

Reporting Groups

	Description
FluMist trivalent (2015-2016)	Participants received intranasal spray of 0.2 mL (total dose in both nostrils) FluMist trivalent vaccine on Days 1 and 28. Each 0.2 mL dose contained 10^7±0.5 FFU of each vaccine strain. Strains included in the trivalent vaccine were: A/H1N1 (A/Bolivia/559/2013), A/H3N2 (A/Switzerland/9715293/2013), and B/Phuket/3073/2013 (B/Yamagata-lineage).
FluMist Quadrivalent (2015-2016)	Participants received intranasal spray of 0.2 mL (total dose in both nostrils) FluMist quadrivalent vaccine on Days 1 and 28. Each 0.2 mL dose contained 10^7±0.5 FFU of each vaccine strain. Strains included in the vaccine were A/H1N1 (A/Bolivia/559/2013), A/H3N2 (A/Switzerland/9715293/2013), B/Phuket/3073/2013 (B/Yamagata-lineage), and B/Brisbane/60/2008 (B/Victoria-lineage).
FluMist Quadrivalent (2017-2018)	Participants received intranasal spray of 0.2 mL (total dose in both nostrils) FluMist quadrivalent vaccine on Days 1 and 28. Each 0.2 mL dose contained 10^7±0.5 FFU of each vaccine strain. Strains included in the vaccine were the new A/H1N1 (A/Slovenia/2903/2015), A/H3N2 (A/New Caledonia/71/2014), B/Phuket/3073/2013 (B/Yamagata-lineage), and B/Brisbane/60/2008 (B/Victoria-lineage).

Measured Values

	FluMist trivalent (2015-2016)	FluMist Quadrivalent (2015-2016)	FluMist Quadrivalent (2017-2018)
Number of Participants Analyzed [units:participants]	60	56	64
Percentage of Participants With A/H3N2 HAI Antibody Seroconversion Rate at Day 28 [units: Percentage of participants] Number (95% Confidence Interval)	51.7 (38.4 to 64.8)	64.3 (50.4 to 76.6)	31.3 (20.2 to 44.1)

No statistical analysis provided for Percentage of Participants With A/H3N2 HAI Antibody Seroconversion Rate at Day 28

3. Primary Outcome Measure: Percentage of Participants With B/Yamagata HAI Antibody Seroconversion Rate at Day 28 [ Time Frame: Day 28 ]

Measure Type	Primary
Measure Name	Percentage of Participants With B/Yamagata HAI Antibody Seroconversion Rate at Day 28
Measure Description	Seroconversion rate is defined as >= 4-fold rise from baseline in B/Yamagata HAI antibody titer. Percentage of participants with >= 4-fold rise in B/Yamagata HAI antibody titer at Day 28 is reported.
Time Frame	Day 28
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Immunogenicity population included all participants in the ATP who had no major protocol deviations judged to have the potential to interfere with the generation or interpretation of an immune response to investigational product. Here, "N" signifies number of participants analyzed for this outcome measure.

Reporting Groups

	Description
FluMist trivalent (2015-2016)	Participants received intranasal spray of 0.2 mL (total dose in both nostrils) FluMist trivalent vaccine on Days 1 and 28. Each 0.2 mL dose contained 10^7±0.5 FFU of each vaccine strain. Strains included in the trivalent vaccine were: A/H1N1 (A/Bolivia/559/2013), A/H3N2 (A/Switzerland/9715293/2013), and B/Phuket/3073/2013 (B/Yamagata-lineage).
FluMist Quadrivalent (2015-2016)	Participants received intranasal spray of 0.2 mL (total dose in both nostrils) FluMist quadrivalent vaccine on Days 1 and 28. Each 0.2 mL dose contained 10^7±0.5 FFU of each vaccine strain. Strains included in the vaccine were A/H1N1 (A/Bolivia/559/2013), A/H3N2 (A/Switzerland/9715293/2013), B/Phuket/3073/2013 (B/Yamagata-lineage), and B/Brisbane/60/2008 (B/Victoria-lineage).
FluMist Quadrivalent (2017-2018)	Participants received intranasal spray of 0.2 mL (total dose in both nostrils) FluMist quadrivalent vaccine on Days 1 and 28. Each 0.2 mL dose contained 10^7±0.5 FFU of each vaccine strain. Strains included in the vaccine were the new A/H1N1 (A/Slovenia/2903/2015), A/H3N2 (A/New Caledonia/71/2014), B/Phuket/3073/2013 (B/Yamagata-lineage), and B/Brisbane/60/2008 (B/Victoria-lineage).

Measured Values

	FluMist trivalent (2015-2016)	FluMist Quadrivalent (2015-2016)	FluMist Quadrivalent (2017-2018)
Number of Participants Analyzed [units:participants]	60	56	64
Percentage of Participants With B/Yamagata HAI Antibody Seroconversion Rate at Day 28 [units: Percentage of participants] Number (95% Confidence Interval)	50.0 (36.8 to 63.2)	42.9 (29.7 to 56.8)	57.8 (44.8 to 70.1)

No statistical analysis provided for Percentage of Participants With B/Yamagata HAI Antibody Seroconversion Rate at Day 28

4. Primary Outcome Measure: Percentage of Participants With B/Victoria HAI Antibody Seroconversion Rate at Day 28 [ Time Frame: Day 28 ]

Measure Type	Primary
Measure Name	Percentage of Participants With B/Victoria HAI Antibody Seroconversion Rate at Day 28
Measure Description	Seroconversion rate is defined as >= 4-fold rise from baseline in B/Victoria HAI antibody titer. Percentage of participants with >= 4-fold rise in B/Victoria HAI antibody titer at Day 28 is reported.
Time Frame	Day 28
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Immunogenicity population. B/Victoria strain was not included in the 'FluMist trivalent (2015-2016)' arm. Here, "N" signifies number of participants analyzed for this outcome measure.

Reporting Groups

	Description
FluMist trivalent (2015-2016)	Participants received intranasal spray of 0.2 mL (total dose in both nostrils) FluMist trivalent vaccine on Days 1 and 28. Each 0.2 mL dose contained 10^7±0.5 FFU of each vaccine strain. Strains included in the trivalent vaccine were: A/H1N1 (A/Bolivia/559/2013), A/H3N2 (A/Switzerland/9715293/2013), and B/Phuket/3073/2013 (B/Yamagata-lineage).
FluMist Quadrivalent (2015-2016)	Participants received intranasal spray of 0.2 mL (total dose in both nostrils) FluMist quadrivalent vaccine on Days 1 and 28. Each 0.2 mL dose contained 10^7±0.5 FFU of each vaccine strain. Strains included in the vaccine were A/H1N1 (A/Bolivia/559/2013), A/H3N2 (A/Switzerland/9715293/2013), B/Phuket/3073/2013 (B/Yamagata-lineage), and B/Brisbane/60/2008 (B/Victoria-lineage).
FluMist Quadrivalent (2017-2018)	Participants received intranasal spray of 0.2 mL (total dose in both nostrils) FluMist quadrivalent vaccine on Days 1 and 28. Each 0.2 mL dose contained 10^7±0.5 FFU of each vaccine strain. Strains included in the vaccine were the new A/H1N1 (A/Slovenia/2903/2015), A/H3N2 (A/New Caledonia/71/2014), B/Phuket/3073/2013 (B/Yamagata-lineage), and B/Brisbane/60/2008 (B/Victoria-lineage).

Measured Values

	FluMist trivalent (2015-2016)	FluMist Quadrivalent (2015-2016)	FluMist Quadrivalent (2017-2018)
Number of Participants Analyzed [units:participants]	0	56	64
Percentage of Participants With B/Victoria HAI Antibody Seroconversion Rate at Day 28 [units: Percentage of participants] Number (95% Confidence Interval)		14.3 (6.4 to 26.2)	35.9 (24.3 to 48.9)

No statistical analysis provided for Percentage of Participants With B/Victoria HAI Antibody Seroconversion Rate at Day 28

5. Primary Outcome Measure: Percentage of Participants With A/H1N1 HAI Antibody Seroconversion Rate at Day 56 [ Time Frame: Day 56 ]

Measure Type	Primary
Measure Name	Percentage of Participants With A/H1N1 HAI Antibody Seroconversion Rate at Day 56
Measure Description	Seroconversion rate is defined as >= 4-fold rise from baseline in A/H1N1 HAI antibody titer. Percentage of participants with >= 4-fold rise in A/H1N1 HAI antibody titer at Day 56 is reported. Comparative statistical analysis was planned only for 'FluMist Quadrivalent (2015-2016)' and 'FluMist Quadrivalent (2017-2018)' arms.
Time Frame	Day 56
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Immunogenicity population included all participants in the ATP who had no major protocol deviations judged to have the potential to interfere with the generation or interpretation of an immune response to investigational product. Here, "N" signifies number of participants analyzed for this outcome measure.

Reporting Groups

	Description
FluMist trivalent (2015-2016)	Participants received intranasal spray of 0.2 mL (total dose in both nostrils) FluMist trivalent vaccine on Days 1 and 28. Each 0.2 mL dose contained 10^7±0.5 FFU of each vaccine strain. Strains included in the trivalent vaccine were: A/H1N1 (A/Bolivia/559/2013), A/H3N2 (A/Switzerland/9715293/2013), and B/Phuket/3073/2013 (B/Yamagata-lineage).
FluMist Quadrivalent (2015-2016)	Participants received intranasal spray of 0.2 mL (total dose in both nostrils) FluMist quadrivalent vaccine on Days 1 and 28. Each 0.2 mL dose contained 10^7±0.5 FFU of each vaccine strain. Strains included in the vaccine were A/H1N1 (A/Bolivia/559/2013), A/H3N2 (A/Switzerland/9715293/2013), B/Phuket/3073/2013 (B/Yamagata-lineage), and B/Brisbane/60/2008 (B/Victoria-lineage).
FluMist Quadrivalent (2017-2018)	Participants received intranasal spray of 0.2 mL (total dose in both nostrils) FluMist quadrivalent vaccine on Days 1 and 28. Each 0.2 mL dose contained 10^7±0.5 FFU of each vaccine strain. Strains included in the vaccine were the new A/H1N1 (A/Slovenia/2903/2015), A/H3N2 (A/New Caledonia/71/2014), B/Phuket/3073/2013 (B/Yamagata-lineage), and B/Brisbane/60/2008 (B/Victoria-lineage).

Measured Values

	FluMist trivalent (2015-2016)	FluMist Quadrivalent (2015-2016)	FluMist Quadrivalent (2017-2018)
Number of Participants Analyzed [units:participants]	59	56	62
Percentage of Participants With A/H1N1 HAI Antibody Seroconversion Rate at Day 56 [units: Percentage of participants] Number (95% Confidence Interval)	23.7 (13.6 to 36.6)	12.5 (5.2 to 24.1)	45.2 (32.5 to 58.3)

Statistical Analysis 1 for Percentage of Participants With A/H1N1 HAI Antibody Seroconversion Rate at Day 56

Groups^[1]	FluMist Quadrivalent (2015-2016), FluMist Quadrivalent (2017-2018)
Method^[3]	Cochran-Mantel-Haenszel
P-Value^[4]	<0.001
Mean Difference (Net)^[5]	32.7
95% Confidence Interval	( 14.4 to 47.8 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	p-value is calculated from the CMH test adjusting for the prior influenza vaccination status.
[5]	Other relevant estimation information:
	No text entered.

6. Primary Outcome Measure: Percentage of Participants With A/H3N2 HAI Antibody Seroconversion Rate at Day 56 [ Time Frame: Day 56 ]

Measure Type	Primary
Measure Name	Percentage of Participants With A/H3N2 HAI Antibody Seroconversion Rate at Day 56
Measure Description	Seroconversion rate is defined as >= 4-fold rise from baseline in A/H3N2 HAI antibody titer. Percentage of participants with >= 4-fold rise in A/H3N2 HAI antibody titer at Day 56 is reported.
Time Frame	Day 56
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Immunogenicity population included all participants in the ATP who had no major protocol deviations judged to have the potential to interfere with the generation or interpretation of an immune response to investigational product. Here, "N" signifies number of participants analyzed for this outcome measure.

Reporting Groups

	Description
FluMist trivalent (2015-2016)	Participants received intranasal spray of 0.2 mL (total dose in both nostrils) FluMist trivalent vaccine on Days 1 and 28. Each 0.2 mL dose contained 10^7±0.5 FFU of each vaccine strain. Strains included in the trivalent vaccine were: A/H1N1 (A/Bolivia/559/2013), A/H3N2 (A/Switzerland/9715293/2013), and B/Phuket/3073/2013 (B/Yamagata-lineage).
FluMist Quadrivalent (2015-2016)	Participants received intranasal spray of 0.2 mL (total dose in both nostrils) FluMist quadrivalent vaccine on Days 1 and 28. Each 0.2 mL dose contained 10^7±0.5 FFU of each vaccine strain. Strains included in the vaccine were A/H1N1 (A/Bolivia/559/2013), A/H3N2 (A/Switzerland/9715293/2013), B/Phuket/3073/2013 (B/Yamagata-lineage), and B/Brisbane/60/2008 (B/Victoria-lineage).
FluMist Quadrivalent (2017-2018)	Participants received intranasal spray of 0.2 mL (total dose in both nostrils) FluMist quadrivalent vaccine on Days 1 and 28. Each 0.2 mL dose contained 10^7±0.5 FFU of each vaccine strain. Strains included in the vaccine were the new A/H1N1 (A/Slovenia/2903/2015), A/H3N2 (A/New Caledonia/71/2014), B/Phuket/3073/2013 (B/Yamagata-lineage), and B/Brisbane/60/2008 (B/Victoria-lineage).

Measured Values

	FluMist trivalent (2015-2016)	FluMist Quadrivalent (2015-2016)	FluMist Quadrivalent (2017-2018)
Number of Participants Analyzed [units:participants]	59	56	62
Percentage of Participants With A/H3N2 HAI Antibody Seroconversion Rate at Day 56 [units: Percentage of participants] Number (95% Confidence Interval)	54.2 (40.8 to 67.3)	66.1 (52.2 to 78.2)	40.3 (28.1 to 53.6)

No statistical analysis provided for Percentage of Participants With A/H3N2 HAI Antibody Seroconversion Rate at Day 56

7. Primary Outcome Measure: Percentage of Participants With B/Yamagata HAI Antibody Seroconversion Rate at Day 56 [ Time Frame: Day 56 ]

Measure Type	Primary
Measure Name	Percentage of Participants With B/Yamagata HAI Antibody Seroconversion Rate at Day 56
Measure Description	Seroconversion rate is defined as >= 4-fold rise from baseline in B/Yamagata HAI antibody titer. Percentage of participants with >= 4-fold rise in B/Yamagata HAI antibody titer at Day 56 is reported.
Time Frame	Day 56
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Immunogenicity population included all participants in the ATP who had no major protocol deviations judged to have the potential to interfere with the generation or interpretation of an immune response to investigational product. Here, "N" signifies number of participants analyzed for this outcome measure.

Reporting Groups

	Description
FluMist trivalent (2015-2016)	Participants received intranasal spray of 0.2 mL (total dose in both nostrils) FluMist trivalent vaccine on Days 1 and 28. Each 0.2 mL dose contained 10^7±0.5 FFU of each vaccine strain. Strains included in the trivalent vaccine were: A/H1N1 (A/Bolivia/559/2013), A/H3N2 (A/Switzerland/9715293/2013), and B/Phuket/3073/2013 (B/Yamagata-lineage).
FluMist Quadrivalent (2015-2016)	Participants received intranasal spray of 0.2 mL (total dose in both nostrils) FluMist quadrivalent vaccine on Days 1 and 28. Each 0.2 mL dose contained 10^7±0.5 FFU of each vaccine strain. Strains included in the vaccine were A/H1N1 (A/Bolivia/559/2013), A/H3N2 (A/Switzerland/9715293/2013), B/Phuket/3073/2013 (B/Yamagata-lineage), and B/Brisbane/60/2008 (B/Victoria-lineage).
FluMist Quadrivalent (2017-2018)	Participants received intranasal spray of 0.2 mL (total dose in both nostrils) FluMist quadrivalent vaccine on Days 1 and 28. Each 0.2 mL dose contained 10^7±0.5 FFU of each vaccine strain. Strains included in the vaccine were the new A/H1N1 (A/Slovenia/2903/2015), A/H3N2 (A/New Caledonia/71/2014), B/Phuket/3073/2013 (B/Yamagata-lineage), and B/Brisbane/60/2008 (B/Victoria-lineage).

Measured Values

	FluMist trivalent (2015-2016)	FluMist Quadrivalent (2015-2016)	FluMist Quadrivalent (2017-2018)
Number of Participants Analyzed [units:participants]	60	56	62
Percentage of Participants With B/Yamagata HAI Antibody Seroconversion Rate at Day 56 [units: Percentage of participants] Number (95% Confidence Interval)	50.0 (36.8 to 63.2)	53.6 (39.7 to 67.0)	54.8 (41.7 to 67.5)

No statistical analysis provided for Percentage of Participants With B/Yamagata HAI Antibody Seroconversion Rate at Day 56

8. Primary Outcome Measure: Percentage of Participants With B/Victoria HAI Antibody Seroconversion Rate at Day 56 [ Time Frame: Day 56 ]

Measure Type	Primary
Measure Name	Percentage of Participants With B/Victoria HAI Antibody Seroconversion Rate at Day 56
Measure Description	Seroconversion rate is defined as >= 4-fold rise from baseline in B/Victoria HAI antibody titer. Percentage of participants with >= 4-fold rise in B/Victoria HAI antibody titer at Day 56 is reported.
Time Frame	Day 56
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Immunogenicity population. B/Victoria strain was not included in the 'FluMist trivalent (2015-2016)' arm. Here, "N" signifies number of participants analyzed for this outcome measure.

Reporting Groups

	Description
FluMist trivalent (2015-2016)	Participants received intranasal spray of 0.2 mL (total dose in both nostrils) FluMist trivalent vaccine on Days 1 and 28. Each 0.2 mL dose contained 10^7±0.5 FFU of each vaccine strain. Strains included in the trivalent vaccine were: A/H1N1 (A/Bolivia/559/2013), A/H3N2 (A/Switzerland/9715293/2013), and B/Phuket/3073/2013 (B/Yamagata-lineage).
FluMist Quadrivalent (2015-2016)	Participants received intranasal spray of 0.2 mL (total dose in both nostrils) FluMist quadrivalent vaccine on Days 1 and 28. Each 0.2 mL dose contained 10^7±0.5 FFU of each vaccine strain. Strains included in the vaccine were A/H1N1 (A/Bolivia/559/2013), A/H3N2 (A/Switzerland/9715293/2013), B/Phuket/3073/2013 (B/Yamagata-lineage), and B/Brisbane/60/2008 (B/Victoria-lineage).
FluMist Quadrivalent (2017-2018)	Participants received intranasal spray of 0.2 mL (total dose in both nostrils) FluMist quadrivalent vaccine on Days 1 and 28. Each 0.2 mL dose contained 10^7±0.5 FFU of each vaccine strain. Strains included in the vaccine were the new A/H1N1 (A/Slovenia/2903/2015), A/H3N2 (A/New Caledonia/71/2014), B/Phuket/3073/2013 (B/Yamagata-lineage), and B/Brisbane/60/2008 (B/Victoria-lineage).

Measured Values

	FluMist trivalent (2015-2016)	FluMist Quadrivalent (2015-2016)	FluMist Quadrivalent (2017-2018)
Number of Participants Analyzed [units:participants]	0	56	62
Percentage of Participants With B/Victoria HAI Antibody Seroconversion Rate at Day 56 [units: Percentage of participants] Number (95% Confidence Interval)		25.0 (14.4 to 38.4)	40.3 (28.1 to 53.6)

No statistical analysis provided for Percentage of Participants With B/Victoria HAI Antibody Seroconversion Rate at Day 56

9. Secondary Outcome Measure: Percentage of Participants Who Shed Vaccine Virus by Formulation, Strain, Dose Number, and Baseline Serostatus as Measured by Quantitative Reverse Transcriptase Polymerase Chain Reaction (qRT-PCR) [ Time Frame: 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) ]

Measure Type	Secondary
Measure Name	Percentage of Participants Who Shed Vaccine Virus by Formulation, Strain, Dose Number, and Baseline Serostatus as Measured by Quantitative Reverse Transcriptase Polymerase Chain Reaction (qRT-PCR)
Measure Description	Quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) was used to measure viral shedding from the nasopharyngeal swabs. Percentage of participants who shed virus are reported.
Time Frame	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)
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Immunogenicity population. B/Victoria strain was not included in the 'FluMist trivalent (2015-2016)' arm.

Reporting Groups

	Description
FluMist trivalent (2015-2016)	Participants received intranasal spray of 0.2 mL (total dose in both nostrils) FluMist trivalent vaccine on Days 1 and 28. Each 0.2 mL dose contained 10^7±0.5 FFU of each vaccine strain. Strains included in the trivalent vaccine were: A/H1N1 (A/Bolivia/559/2013), A/H3N2 (A/Switzerland/9715293/2013), and B/Phuket/3073/2013 (B/Yamagata-lineage).
FluMist Quadrivalent (2015-2016)	Participants received intranasal spray of 0.2 mL (total dose in both nostrils) FluMist quadrivalent vaccine on Days 1 and 28. Each 0.2 mL dose contained 10^7±0.5 FFU of each vaccine strain. Strains included in the vaccine were A/H1N1 (A/Bolivia/559/2013), A/H3N2 (A/Switzerland/9715293/2013), B/Phuket/3073/2013 (B/Yamagata-lineage), and B/Brisbane/60/2008 (B/Victoria-lineage).
FluMist Quadrivalent (2017-2018)	Participants received intranasal spray of 0.2 mL (total dose in both nostrils) FluMist quadrivalent vaccine on Days 1 and 28. Each 0.2 mL dose contained 10^7±0.5 FFU of each vaccine strain. Strains included in the vaccine were the new A/H1N1 (A/Slovenia/2903/2015), A/H3N2 (A/New Caledonia/71/2014), B/Phuket/3073/2013 (B/Yamagata-lineage), and B/Brisbane/60/2008 (B/Victoria-lineage).

Measured Values

	FluMist trivalent (2015-2016)	FluMist Quadrivalent (2015-2016)	FluMist Quadrivalent (2017-2018)
Number of Participants Analyzed [units:participants]	67	66	67
Percentage of Participants Who Shed Vaccine Virus by Formulation, Strain, Dose Number, and Baseline Serostatus as Measured by Quantitative Reverse Transcriptase Polymerase Chain Reaction (qRT-PCR) [units: Percentage of participants]
A/H1N1/HAI seronegative/Dose 1	86.7	81.4	94.9
A/H1N1/HAI seronegative/Dose 2	17.2	25.6	46.2
A/H1N1/HAI seropositive/Dose 1	86.1	63.6	71.4
A/H1N1/HAI seropositive/Dose 2	22.9	23.8	29.6
A/H3N2/HAI seronegative/Dose 1	100.0	100.0	95.8
A/H3N2/HAI seronegative/Dose 2	55.0	60.0	79.2
A/H3N2/HAI seropositive/Dose 1	95.6	83.3	95.3
A/H3N2/HAI seropositive/Dose 2	47.7	44.8	59.5
B/Yamagata/HAI seronegative/Dose 1	100.0	98.1	100.0
B/Yamagata/HAI seronegative/Dose 2	42.0	39.6	31.4
B/Yamagata/HAI seropositive/Dose 1	73.3	81.8	93.8
B/Yamagata/HAI seropositive/Dose 2	50.0	54.5	53.3
B/Victoria/HAI seronegative/Dose 1		100.0	100.0
B/Victoria/HAI seronegative/Dose 2		44.8	53.8
B/Victoria/HAI seropositive/Dose 1		83.3	100.0
B/Victoria/HAI seropositive/Dose 2		50.0	37.0

No statistical analysis provided for Percentage of Participants Who Shed Vaccine Virus by Formulation, Strain, Dose Number, and Baseline Serostatus as Measured by Quantitative Reverse Transcriptase Polymerase Chain Reaction (qRT-PCR)

10. Secondary Outcome Measure: Number of Days of Vaccine Virus Shedding by Formulation, Strain, Dose Number, and Baseline Serostatus as Measured by qRT-PCR [ Time Frame: 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) ]

Measure Type	Secondary
Measure Name	Number of Days of Vaccine Virus Shedding by Formulation, Strain, Dose Number, and Baseline Serostatus as Measured by qRT-PCR
Measure Description	Quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) was used to measure viral shedding from the nasopharyngeal swabs. Number of days of virus shedding are reported.
Time Frame	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)
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Participants included in immunogenicity population and who shed vaccine virus were analyzed for this outcome measure. B/Victoria strain was not included in the 'FluMist trivalent (2015-2016)' arm.

Reporting Groups

	Description
FluMist trivalent (2015-2016)	Participants received intranasal spray of 0.2 mL (total dose in both nostrils) FluMist trivalent vaccine on Days 1 and 28. Each 0.2 mL dose contained 10^7±0.5 FFU of each vaccine strain. Strains included in the trivalent vaccine were: A/H1N1 (A/Bolivia/559/2013), A/H3N2 (A/Switzerland/9715293/2013), and B/Phuket/3073/2013 (B/Yamagata-lineage).
FluMist Quadrivalent (2015-2016)	Participants received intranasal spray of 0.2 mL (total dose in both nostrils) FluMist quadrivalent vaccine on Days 1 and 28. Each 0.2 mL dose contained 10^7±0.5 FFU of each vaccine strain. Strains included in the vaccine were A/H1N1 (A/Bolivia/559/2013), A/H3N2 (A/Switzerland/9715293/2013), B/Phuket/3073/2013 (B/Yamagata-lineage), and B/Brisbane/60/2008 (B/Victoria-lineage).
FluMist Quadrivalent (2017-2018)	Participants received intranasal spray of 0.2 mL (total dose in both nostrils) FluMist quadrivalent vaccine on Days 1 and 28. Each 0.2 mL dose contained 10^7±0.5 FFU of each vaccine strain. Strains included in the vaccine were the new A/H1N1 (A/Slovenia/2903/2015), A/H3N2 (A/New Caledonia/71/2014), B/Phuket/3073/2013 (B/Yamagata-lineage), and B/Brisbane/60/2008 (B/Victoria-lineage).

Measured Values

	FluMist trivalent (2015-2016)	FluMist Quadrivalent (2015-2016)	FluMist Quadrivalent (2017-2018)
Number of Participants Analyzed [units:participants]	66	65	67
Number of Days of Vaccine Virus Shedding by Formulation, Strain, Dose Number, and Baseline Serostatus as Measured by qRT-PCR [units: Days] Mean (Standard Deviation)
A/H1N1/HAI seronegative/Dose 1	2.2 (1.2)	2.2 (1.0)	2.8 (1.3)
A/H1N1/HAI seronegative/Dose 2	1.2 (0.4)	1.4 (0.7)	1.3 (0.5)
A/H1N1/HAI seropositive/Dose 1	2.2 (1.0)	1.9 (0.7)	2.0 (1.3)
A/H1N1/HAI seropositive/Dose 2	1.1 (0.4)	1.0 (0.0)	1.1 (0.4)
A/H3N2/HAI seronegative/Dose 1	4.5 (1.0)	4.5 (0.9)	3.9 (1.2)
A/H3N2/HAI seronegative/Dose 2	1.3 (0.6)	1.1 (0.4)	1.7 (0.8)
A/H3N2/HAI seropositive/Dose 1	3.8 (1.5)	3.4 (1.6)	2.5 (1.4)
A/H3N2/HAI seropositive/Dose 2	1.3 (0.6)	1.5 (0.8)	1.4 (0.6)
B/Yamagata/HAI seronegative/Dose 1	3.6 (1.3)	3.6 (1.3)	4.0 (1.1)
B/Yamagata/HAI seronegative/Dose 2	1.3 (0.6)	1.3 (0.7)	1.1 (0.3)
B/Yamagata/HAI seropositive/Dose 1	2.5 (1.2)	3.3 (1.0)	3.1 (1.6)
B/Yamagata/HAI seropositive/Dose 2	1.1 (0.4)	1.0 (0.0)	1.3 (0.5)
B/Victoria/HAI seronegative/Dose 1		3.9 (1.2)	4.6 (0.8)
B/Victoria/HAI seronegative/Dose 2		1.4 (0.6)	1.4 (0.6)
B/Victoria/HAI seropositive/Dose 1		2.0 (1.0)	3.5 (1.5)
B/Victoria/HAI seropositive/Dose 2		1.0 (0.0)	1.1 (0.3)

No statistical analysis provided for Number of Days of Vaccine Virus Shedding by Formulation, Strain, Dose Number, and Baseline Serostatus as Measured by qRT-PCR

11. Secondary Outcome Measure: Viral Titer by Day, Strain, Dose Number, and Baseline Serostatus as Measured by qRT-PCR [ Time Frame: Day (D) 2, D3, D4, D5, and D7 after Dose 1 (D1 dose) and on D2, D4 and D6 after Dose 2 (D28 dose) ]

Measure Type	Secondary
Measure Name	Viral Titer by Day, Strain, Dose Number, and Baseline Serostatus as Measured by qRT-PCR
Measure Description	Quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) was used to measure viral titer from the nasopharyngeal swabs. Viral titers are reported.
Time Frame	Day (D) 2, D3, D4, D5, and D7 after Dose 1 (D1 dose) and on D2, D4 and D6 after Dose 2 (D28 dose)
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Participants included in immunogenicity population and who shed vaccine virus were analyzed for this outcome measure. B/Victoria strain was not included in the 'FluMist trivalent (2015-2016)' arm.

Reporting Groups

	Description
FluMist trivalent (2015-2016)	Participants received intranasal spray of 0.2 mL (total dose in both nostrils) FluMist trivalent vaccine on Days 1 and 28. Each 0.2 mL dose contained 10^7±0.5 FFU of each vaccine strain. Strains included in the trivalent vaccine were: A/H1N1 (A/Bolivia/559/2013), A/H3N2 (A/Switzerland/9715293/2013), and B/Phuket/3073/2013 (B/Yamagata-lineage).
FluMist Quadrivalent (2015-2016)	Participants received intranasal spray of 0.2 mL (total dose in both nostrils) FluMist quadrivalent vaccine on Days 1 and 28. Each 0.2 mL dose contained 10^7±0.5 FFU of each vaccine strain. Strains included in the vaccine were A/H1N1 (A/Bolivia/559/2013), A/H3N2 (A/Switzerland/9715293/2013), B/Phuket/3073/2013 (B/Yamagata-lineage), and B/Brisbane/60/2008 (B/Victoria-lineage).
FluMist Quadrivalent (2017-2018)	Participants received intranasal spray of 0.2 mL (total dose in both nostrils) FluMist quadrivalent vaccine on Days 1 and 28. Each 0.2 mL dose contained 10^7±0.5 FFU of each vaccine strain. Strains included in the vaccine were the new A/H1N1 (A/Slovenia/2903/2015), A/H3N2 (A/New Caledonia/71/2014), B/Phuket/3073/2013 (B/Yamagata-lineage), and B/Brisbane/60/2008 (B/Victoria-lineage).

Measured Values

	FluMist trivalent (2015-2016)	FluMist Quadrivalent (2015-2016)	FluMist Quadrivalent (2017-2018)
Number of Participants Analyzed [units:participants]	66	65	67
Viral Titer by Day, Strain, Dose Number, and Baseline Serostatus as Measured by qRT-PCR [units: log10 viral particles/mL] Mean (Standard Deviation)
A/H1N1/HAI seronegative/Dose1D2	3.79 (0.56)	3.76 (0.71)	3.70 (0.49)
A/H1N1/HAI seronegative/Dose1D3	3.66 (0.55)	3.81 (0.83)	4.21 (0.97)
A/H1N1/HAI seronegative/Dose1D4	3.63 (0.34)	3.34 (0.56)	3.81 (0.94)
A/H1N1/HAI seronegative/Dose1D5	3.12 (0.16)	3.17 (0.10)	3.85 (0.48)
A/H1N1/HAI seronegative/Dose1D7	3.17 (0.40)		2.93 (0.23)
A/H1N1/HAI seronegative/Dose2D2	3.68 (0.88)	3.29 (0.30)	3.90 (1.04)
A/H1N1/HAI seronegative/Dose2D4		3.49 (0.37)	4.02 (1.24)
A/H1N1/HAI seronegative/Dose2D6
A/H1N1/HAI seropositive/Dose1D2	3.66 (0.46)	3.48 (0.62)	3.14 (0.45)
A/H1N1/HAI seropositive/Dose1D3	3.39 (0.57)	4.03 (0.91)	3.99 (0.84)
A/H1N1/HAI seropositive/Dose1D4	3.09 (0.62)	3.39 (0.25)	3.97 (0.73)
A/H1N1/HAI seropositive/Dose1D5	3.35 (0.64)		3.73 (0.62)
A/H1N1/HAI seropositive/Dose1D7	3.10 (NA)^[1]
A/H1N1/HAI seropositive/Dose2D2	3.38 (0.78)	2.86 (NA)^[1]	3.36 (0.56)
A/H1N1/HAI seropositive/Dose2D4			3.65 (NA)^[1]
A/H1N1/HAI seropositive/Dose2D6
A/H3N2/HAI seronegative/Dose1D2	4.20 (0.99)	4.15 (0.93)	3.52 (0.77)
A/H3N2/HAI seronegative/Dose1D3	5.20 (1.12)	5.39 (1.19)	4.34 (0.86)
A/H3N2/HAI seronegative/Dose1D4	4.86 (0.99)	4.51 (1.14)	4.51 (1.05)
A/H3N2/HAI seronegative/Dose1D5	4.04 (1.09)	4.16 (1.20)	3.67 (1.06)
A/H3N2/HAI seronegative/Dose1D7	4.10 (0.97)	4.12 (0.88)	3.58 (1.26)
A/H3N2/HAI seronegative/Dose2D2	3.67 (1.03)	3.33 (0.67)	3.01 (0.49)
A/H3N2/HAI seronegative/Dose2D4		3.41 (0.26)	3.68 (0.70)
A/H3N2/HAI seronegative/Dose2D6		2.72 (NA)^[1]	3.05 (0.61)
A/H3N2/HAI seropositive/Dose1D2	3.80 (1.07)	3.98 (1.02)	3.19 (0.67)
A/H3N2/HAI seropositive/Dose1D3	4.79 (1.29)	5.06 (1.20)	3.54 (0.98)
A/H3N2/HAI seropositive/Dose1D4	4.34 (1.03)	4.45 (1.14)	4.00 (1.24)
A/H3N2/HAI seropositive/Dose1D5	3.99 (1.05)	4.01 (0.98)	3.98 (0.72)
A/H3N2/HAI seropositive/Dose1D7	3.92 (1.06)	4.10 (1.36)	3.30 (0.55)
A/H3N2/HAI seropositive/Dose2D2	3.30 (0.89)	3.55 (0.93)	3.54 (0.78)
A/H3N2/HAI seropositive/Dose2D4	2.71 (0.62)	3.38 (0.90)	3.26 (0.60)
A/H3N2/HAI seropositive/Dose2D6	3.82 (NA)^[1]	2.32 (NA)^[1]	3.17 (NA)^[1]
B/Yamagata/HAI seronegative/Dose1D2	3.93 (0.40)	4.09 (0.53)	4.16 (0.58)
B/Yamagata/HAI seronegative/Dose1D3	4.10 (0.60)	4.60 (0.77)	4.72 (0.92)
B/Yamagata/HAI seronegative/Dose1D4	4.04 (0.61)	4.60 (0.83)	4.72 (0.88)
B/Yamagata/HAI seronegative/Dose1D5	4.56 (0.53)	4.42 (0.72)	4.59 (0.80)
B/Yamagata/HAI seronegative/Dose1D7	4.37 (0.86)	3.93 (0.50)	3.98 (0.62)
B/Yamagata/HAI seronegative/Dose2D2	3.92 (0.31)	4.10 (0.55)	3.80 (0.35)
B/Yamagata/HAI seronegative/Dose2D4	3.74 (0.60)	3.85 (0.52)
B/Yamagata/HAI seronegative/Dose2D6	3.83 (0.35)
B/Yamagata/HAI seropositive/Dose1D2	3.93 (0.20)	3.57 (0.19)	4.15 (0.78)
B/Yamagata/HAI seropositive/Dose1D3	3.93 (0.58)	3.92 (0.51)	4.67 (0.79)
B/Yamagata/HAI seropositive/Dose1D4	3.46 (0.04)	4.60 (1.44)	4.94 (1.28)
B/Yamagata/HAI seropositive/Dose1D5	3.84 (NA)^[1]	5.01 (NA)^[1]	4.82 (0.65)
B/Yamagata/HAI seropositive/Dose1D7	5.46 (NA)^[1]		3.91 (0.63)
B/Yamagata/HAI seropositive/Dose2D2		3.38 (NA)^[1]	3.70 (0.11)
B/Yamagata/HAI seropositive/Dose2D4
B/Yamagata/HAI seropositive/Dose2D6	3.92 (NA)^[1]
B/Victoria/HAI seronegative/Dose1D2		3.41 (0.58)	3.49 (0.72)
B/Victoria/HAI seronegative/Dose1D3		4.12 (1.02)	4.39 (0.98)
B/Victoria/HAI seronegative/Dose1D4		4.02 (1.13)	4.58 (1.24)
B/Victoria/HAI seronegative/Dose1D5		3.98 (1.05)	4.09 (1.02)
B/Victoria/HAI seronegative/Dose1D7		3.57 (0.79)	4.14 (0.84)
B/Victoria/HAI seronegative/Dose2D2		3.43 (1.01)	2.94 (0.36)
B/Victoria/HAI seronegative/Dose2D4		3.48 (0.88)	2.67 (0.29)
B/Victoria/HAI seronegative/Dose2D6
B/Victoria/HAI seropositive/Dose1D2		2.73 (0.01)	3.10 (0.53)
B/Victoria/HAI seropositive/Dose1D3		3.09 (0.42)	3.96 (1.08)
B/Victoria/HAI seropositive/Dose1D4		2.73 (NA)^[1]	4.40 (0.98)
B/Victoria/HAI seropositive/Dose1D5			4.26 (0.90)
B/Victoria/HAI seropositive/Dose1D7			4.00 (0.96)
B/Victoria/HAI seropositive/Dose2D2			3.41 (0.51)
B/Victoria/HAI seropositive/Dose2D4
B/Victoria/HAI seropositive/Dose2D6

No statistical analysis provided for Viral Titer by Day, Strain, Dose Number, and Baseline Serostatus as Measured by qRT-PCR

12. Secondary Outcome Measure: Percentage of Participants With Strain-specific Neutralizing Antibody Seroconversion Rates From Baseline Through Days 28 and 56 by Baseline Serostatus [ Time Frame: Days 28 and 56 ]

Measure Type	Secondary
Measure Name	Percentage of Participants With Strain-specific Neutralizing Antibody Seroconversion Rates From Baseline Through Days 28 and 56 by Baseline Serostatus
Measure Description	Seroconversion rate is defined as >= 4-fold rise from baseline in strain specific microneutralizing antibody titer. Baseline microneutralization values of less than or equal to (<=) 10 were considered as microneutralization status negative and values greater than (>) 10 were considered microneutralization positive. Percentage of participants with >= 4-fold rise in strain specific neutralizing antibody titer at Days 28 and 56 are reported.
Time Frame	Days 28 and 56
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Immunogenicity population. B/Victoria strain was not included in the 'FluMist trivalent (2015-2016)' arm.

Reporting Groups

	Description
FluMist trivalent (2015-2016)	Participants received intranasal spray of 0.2 mL (total dose in both nostrils) FluMist trivalent vaccine on Days 1 and 28. Each 0.2 mL dose contained 10^7±0.5 FFU of each vaccine strain. Strains included in the trivalent vaccine were: A/H1N1 (A/Bolivia/559/2013), A/H3N2 (A/Switzerland/9715293/2013), and B/Phuket/3073/2013 (B/Yamagata-lineage).
FluMist Quadrivalent (2015-2016)	Participants received intranasal spray of 0.2 mL (total dose in both nostrils) FluMist quadrivalent vaccine on Days 1 and 28. Each 0.2 mL dose contained 10^7±0.5 FFU of each vaccine strain. Strains included in the vaccine were A/H1N1 (A/Bolivia/559/2013), A/H3N2 (A/Switzerland/9715293/2013), B/Phuket/3073/2013 (B/Yamagata-lineage), and B/Brisbane/60/2008 (B/Victoria-lineage).
FluMist Quadrivalent (2017-2018)	Participants received intranasal spray of 0.2 mL (total dose in both nostrils) FluMist quadrivalent vaccine on Days 1 and 28. Each 0.2 mL dose contained 10^7±0.5 FFU of each vaccine strain. Strains included in the vaccine were the new A/H1N1 (A/Slovenia/2903/2015), A/H3N2 (A/New Caledonia/71/2014), B/Phuket/3073/2013 (B/Yamagata-lineage), and B/Brisbane/60/2008 (B/Victoria-lineage).

Measured Values

	FluMist trivalent (2015-2016)	FluMist Quadrivalent (2015-2016)	FluMist Quadrivalent (2017-2018)
Number of Participants Analyzed [units:participants]	66	65	67
Percentage of Participants With Strain-specific Neutralizing Antibody Seroconversion Rates From Baseline Through Days 28 and 56 by Baseline Serostatus [units: Percentage of participants] Number (95% Confidence Interval)
A/H1N1/Baseline serostatus:negative/Day 28	0.0 (0.0 to 36.9)	10.0 (1.2 to 31.7)
A/H1N1/Baseline serostatus:negative/Day 56	37.5 (8.5 to 75.5)	25.0 (8.7 to 49.1)
A/H1N1/Baseline serostatus:positive/Day 28	3.8 (0.5 to 13.2)	2.8 (0.1 to 14.5)	15.9 (7.9 to 27.3)
A/H1N1/Baseline serostatus:positive/Day 56	11.8 (4.4 to 23.9)	2.8 (0.1 to 14.5)	31.7 (20.3 to 45.0)
A/H3N2/Baseline serostatus:negative/Day 28	100.0 (76.8 to 100.0)	100.0 (87.2 to 100.0)	46.7 (21.3 to 73.4)
A/H3N2/Baseline serostatus:negative/Day 56	93.8 (69.8 to 99.8)	100.0 (86.8 to 100.0)	84.6 (54.6 to 98.1)
A/H3N2/Baseline serostatus:positive/Day 28	47.8 (32.9 to 63.1)	34.5 (17.9 to 54.3)	25.0 (13.6 to 39.6)
A/H3N2/Baseline serostatus:positive/Day 56	44.2 (29.1 to 60.1)	43.3 (25.5 to 62.6)	14.9 (6.2 to 28.3)
B/Yamagata/Baseline serostatus:negative/Day 28	59.1 (43.2 to 73.7)	45.7 (30.9 to 61.0)	58.0 (43.2 to 71.8)
B/Yamagata/Baseline serostatus:negative/Day 56	77.3 (62.2 to 88.5)	68.1 (52.9 to 80.9)	75.5 (61.1 to 86.7)
B/Yamagata/Baseline serostatus:positive/Day 28	18.8 (4.0 to 45.6)	0.0 (0.0 to 30.8)	14.3 (1.8 to 42.8)
B/Yamagata/Baseline serostatus:positive/Day 56	18.8 (4.0 to 45.6)	0.0 (0.0 to 33.6)	7.7 (0.2 to 36.0)
B/Victoria/Baseline serostatus:negative/Day 28		20.8 (10.5 to 35.0)	18.9 (9.4 to 32.0)
B/Victoria/Baseline serostatus:negative/Day 56		16.3 (7.3 to 29.7)	23.5 (12.8 to 37.5)
B/Victoria/Baseline serostatus:positive/Day 28		12.5 (0.3 to 52.7)	10.0 (0.3 to 44.5)
B/Victoria/Baseline serostatus:positive/Day 56		14.3 (0.4 to 57.9)	11.1 (0.3 to 48.2)

No statistical analysis provided for Percentage of Participants With Strain-specific Neutralizing Antibody Seroconversion Rates From Baseline Through Days 28 and 56 by Baseline Serostatus

13. Secondary Outcome Measure: Percentage of Participants With Strain-specific Nasal Immunoglobulin A (IgA) seroconversion Rate From Baseline Through Days 28 and 56 [ Time Frame: Days 28 and 56 ]

Measure Type	Secondary
Measure Name	Percentage of Participants With Strain-specific Nasal Immunoglobulin A (IgA) seroconversion Rate From Baseline Through Days 28 and 56
Measure Description	Seroconversion rate is defined as >= 2-fold rise from baseline in strain speciific nasal IgA antibody titer. Percentage of participants with >= 2-fold rise in strain speciific nasal IgA antibody titer at Days 28 and 56 are reported for this outcome.
Time Frame	Days 28 and 56
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Immunogenicity population. B/Victoria strain was not included in the 'FluMist trivalent (2015-2016)' arm.

Reporting Groups

	Description
FluMist trivalent (2015-2016)	Participants received intranasal spray of 0.2 mL (total dose in both nostrils) FluMist trivalent vaccine on Days 1 and 28. Each 0.2 mL dose contained 10^7±0.5 FFU of each vaccine strain. Strains included in the trivalent vaccine were: A/H1N1 (A/Bolivia/559/2013), A/H3N2 (A/Switzerland/9715293/2013), and B/Phuket/3073/2013 (B/Yamagata-lineage).
FluMist Quadrivalent (2015-2016)	Participants received intranasal spray of 0.2 mL (total dose in both nostrils) FluMist quadrivalent vaccine on Days 1 and 28. Each 0.2 mL dose contained 10^7±0.5 FFU of each vaccine strain. Strains included in the vaccine were A/H1N1 (A/Bolivia/559/2013), A/H3N2 (A/Switzerland/9715293/2013), B/Phuket/3073/2013 (B/Yamagata-lineage), and B/Brisbane/60/2008 (B/Victoria-lineage).
FluMist Quadrivalent (2017-2018)	Participants received intranasal spray of 0.2 mL (total dose in both nostrils) FluMist quadrivalent vaccine on Days 1 and 28. Each 0.2 mL dose contained 10^7±0.5 FFU of each vaccine strain. Strains included in the vaccine were the new A/H1N1 (A/Slovenia/2903/2015), A/H3N2 (A/New Caledonia/71/2014), B/Phuket/3073/2013 (B/Yamagata-lineage), and B/Brisbane/60/2008 (B/Victoria-lineage).

Measured Values

	FluMist trivalent (2015-2016)	FluMist Quadrivalent (2015-2016)	FluMist Quadrivalent (2017-2018)
Number of Participants Analyzed [units:participants]	66	65	67
Percentage of Participants With Strain-specific Nasal Immunoglobulin A (IgA) seroconversion Rate From Baseline Through Days 28 and 56 [units: Percentage of participants] Number (95% Confidence Interval)
A/H1N1/Day 28	33.9 (22.3 to 47.0)	31.7 (20.6 to 44.7)	40.3 (28.5 to 53.0)
A/H1N1//Day 56	40.6 (28.5 to 53.6)	46.7 (33.7 to 60.0)	67.7 (54.9 to 78.8)
A/H3N2//Day 28	79.4 (67.3 to 88.5)	79.0 (66.8 to 88.3)	44.8 (32.6 to 57.4)
A/H3N2/Day 56	89.1 (78.8 to 95.5)	88.5 (77.8 to 95.3)	55.4 (42.5 to 67.7)
B/Yamagata//Day 28	69.8 (57.0 to 80.8)	79.4 (67.3 to 88.5)	77.6 (65.8 to 86.9)
B/Yamagata//Day 56	81.3 (69.5 to 89.9)	88.5 (77.8 to 95.3)	86.4 (75.7 to 93.6)
B/Victoria//Day 28		73.0 (60.3 to 83.4)	79.1 (67.4 to 88.1)
B/Victoria//Day 56		91.8 (81.9 to 97.3)	84.8 (73.9 to 92.5)

No statistical analysis provided for Percentage of Participants With Strain-specific Nasal Immunoglobulin A (IgA) seroconversion Rate From Baseline Through Days 28 and 56

14. Secondary Outcome Measure: Percentage of Participants With Any Post Dose Strain-specific Antibody Response [ Time Frame: Days 28 and 56 ]

Measure Type	Secondary
Measure Name	Percentage of Participants With Any Post Dose Strain-specific Antibody Response
Measure Description	Strain specific antibody response defined as >= 4-fold increase in HAI antibodies or >= 4-fold increase in neutralizing antibodies or >= 2-fold increase in IgA antibodies.
Time Frame	Days 28 and 56
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Immunogenicity population. B/Victoria strain was not included in the 'FluMist trivalent (2015-2016)' arm.

Reporting Groups

	Description
FluMist trivalent (2015-2016)	Participants received intranasal spray of 0.2 mL (total dose in both nostrils) FluMist trivalent vaccine on Days 1 and 28. Each 0.2 mL dose contained 10^7±0.5 FFU of each vaccine strain. Strains included in the trivalent vaccine were: A/H1N1 (A/Bolivia/559/2013), A/H3N2 (A/Switzerland/9715293/2013), and B/Phuket/3073/2013 (B/Yamagata-lineage).
FluMist Quadrivalent (2015-2016)	Participants received intranasal spray of 0.2 mL (total dose in both nostrils) FluMist quadrivalent vaccine on Days 1 and 28. Each 0.2 mL dose contained 10^7±0.5 FFU of each vaccine strain. Strains included in the vaccine were A/H1N1 (A/Bolivia/559/2013), A/H3N2 (A/Switzerland/9715293/2013), B/Phuket/3073/2013 (B/Yamagata-lineage), and B/Brisbane/60/2008 (B/Victoria-lineage).
FluMist Quadrivalent (2017-2018)	Participants received intranasal spray of 0.2 mL (total dose in both nostrils) FluMist quadrivalent vaccine on Days 1 and 28. Each 0.2 mL dose contained 10^7±0.5 FFU of each vaccine strain. Strains included in the vaccine were the new A/H1N1 (A/Slovenia/2903/2015), A/H3N2 (A/New Caledonia/71/2014), B/Phuket/3073/2013 (B/Yamagata-lineage), and B/Brisbane/60/2008 (B/Victoria-lineage).

Measured Values

	FluMist trivalent (2015-2016)	FluMist Quadrivalent (2015-2016)	FluMist Quadrivalent (2017-2018)
Number of Participants Analyzed [units:participants]	66	65	67
Percentage of Participants With Any Post Dose Strain-specific Antibody Response [units: Percentage of participants]
A/H1N1/HAI response/Day 28	10.0	5.4	23.4
A/H1N1/Microneutralization response/Day 28	3.3	5.4	15.9
A/H1N1/Nasal IgA response/Day 28	46.0	52.4	35.8
A/H1N1/HAI response/Day 56	23.7	12.5	45.2
A/H1N1/Microneutralization response/Day 56	15.3	10.7	31.7
A/H1N1/Nasal IgA response/Day 56	46.9	53.3	61.5
A/H3N2/HAI response/Day 28	51.7	64.3	31.3
A/H3N2/Microneutralization response/Day 28	60.0	66.1	30.2
A/H3N2/Nasal IgA response/Day 28	81.3	85.5	38.8
A/H3N2/HAI response/Day 56	54.2	66.1	40.3
A/H3N2/Microneutralization response/Day 56	57.6	69.6	30.0
A/H3N2/Nasal IgA response/Day 56	76.6	82.0	50.8
B/Yamagata/HAI response/Day 28	50.0	42.9	57.8
B/Yamagata/Microneutralization response/Day 28	48.3	37.5	48.4
B/Yamagata/Nasal IgA response/Day 28	65.6	87.3	61.2
B/Yamagata/HAI response/Day 56	50.0	53.6	54.8
B/Yamagata/Microneutralization response/Day 56	61.7	57.1	61.3
B/Yamagata/Nasal IgA response/Day 56	70.3	83.6	77.3
B/Victoria/HAI response/Day 28		14.3	35.9
B/Victoria/Microneutralization response/Day 28		19.6	17.5
B/Victoria/Nasal IgA response/Day 28		76.2	55.2
B/Victoria/HAI response/Day 56		25.0	40.3
B/Victoria/Microneutralization response/Day 56		16.1	21.7
B/Victoria/Nasal IgA response/Day 56		83.6	78.8

No statistical analysis provided for Percentage of Participants With Any Post Dose Strain-specific Antibody Response

15. Secondary Outcome Measure: Percentage of Participants With Any Solicited Symptoms [ Time Frame: Day 1 through Day 14 after Dose 1 (Day 1 dose) and Dose 2 (Day 28 dose) ]

Measure Type	Secondary
Measure Name	Percentage of Participants With Any Solicited Symptoms
Measure Description	Solicited symptoms included fever by any route (temperature >= 100.4 degrees Fahrenheit), runny/stuffy nose, sore throat, cough, headache, generalized muscle aches, lethargy or tiredness/weakness, and decreased appetite.
Time Frame	Day 1 through Day 14 after Dose 1 (Day 1 dose) and Dose 2 (Day 28 dose)
Safety Issue?	Yes

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
ATP included all participants who received any investigational drug.

Reporting Groups

	Description
FluMist trivalent (2015-2016)	Participants received intranasal spray of 0.2 mL (total dose in both nostrils) FluMist trivalent vaccine on Days 1 and 28. Each 0.2 mL dose contained 10^7±0.5 FFU of each vaccine strain. Strains included in the trivalent vaccine were: A/H1N1 (A/Bolivia/559/2013), A/H3N2 (A/Switzerland/9715293/2013), and B/Phuket/3073/2013 (B/Yamagata-lineage).
FluMist Quadrivalent (2015-2016)	Participants received intranasal spray of 0.2 mL (total dose in both nostrils) FluMist quadrivalent vaccine on Days 1 and 28. Each 0.2 mL dose contained 10^7±0.5 FFU of each vaccine strain. Strains included in the vaccine were A/H1N1 (A/Bolivia/559/2013), A/H3N2 (A/Switzerland/9715293/2013), B/Phuket/3073/2013 (B/Yamagata-lineage), and B/Brisbane/60/2008 (B/Victoria-lineage).
FluMist Quadrivalent (2017-2018)	Participants received intranasal spray of 0.2 mL (total dose in both nostrils) FluMist quadrivalent vaccine on Days 1 and 28. Each 0.2 mL dose contained 10^7±0.5 FFU of each vaccine strain. Strains included in the vaccine were the new A/H1N1 (A/Slovenia/2903/2015), A/H3N2 (A/New Caledonia/71/2014), B/Phuket/3073/2013 (B/Yamagata-lineage), and B/Brisbane/60/2008 (B/Victoria-lineage).

Measured Values

	FluMist trivalent (2015-2016)	FluMist Quadrivalent (2015-2016)	FluMist Quadrivalent (2017-2018)
Number of Participants Analyzed [units:participants]	67	66	67
Percentage of Participants With Any Solicited Symptoms [units: Percentage of participants]
Fever: Dose 1	3.0	1.5	10.4
Fever: Dose 2	3.2	8.2	6.3
Runny/Stuffy Nose: Dose 1	34.3	41.5	43.3
Runny/Stuffy Nose: Dose 2	33.3	36.7	34.4
Sore Throat: Dose 1	6.0	1.5	4.5
Sore Throat: Dose 2	3.2	3.3	4.7
Cough: Dose 1	19.4	15.4	10.4
Cough: Dose 2	19.0	21.7	10.9
Headache: Dose 1	1.5	4.6	6.0
Headache: Dose 2	3.2	5.0	3.1
Generalized Muscle Aches: Dose 1	4.5	4.6	1.5
Generalized Muscle Aches: Dose 2	0.0	3.3	0.0
Lethargy/Tiredness/Weakness: Dose 1	13.4	13.8	16.4
Lethargy/Tiredness/Weakness: Dose 2	12.7	11.7	7.8
Decreased Appetite: Dose 1	13.4	12.3	11.9
Decreased Appetite: Dose 2	9.5	8.3	7.8

No statistical analysis provided for Percentage of Participants With Any Solicited Symptoms

16. Secondary Outcome Measure: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) [ Time Frame: Day 1 through Day 28 after Dose 1 (Day 1 dose) and Dose 2 (Day 28 dose) ]

Measure Type	Secondary
Measure Name	Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)
Measure Description	An Adverse Event (AE) is any unfavourable and unintended sign, symptoms, or diseases temporally associated with use of study drug, whether or not considered related to study drug. A serious adverse event (SAE) is an AE that results in death, initial or prolonged inpatient hospitalization, life-threatening, persistent or significant disability/incapacity, congenital anomaly/birth defect, or an important medical event. TEAEs and TESAEs are defined as AEs and SAEs present at baseline that worsened in intensity after administration of study drug, or events absent at baseline that emerged after administration of study drug.
Time Frame	Day 1 through Day 28 after Dose 1 (Day 1 dose) and Dose 2 (Day 28 dose)
Safety Issue?	Yes

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
ATP included all participants who received any investigational drug.

Reporting Groups

	Description
FluMist trivalent (2015-2016)	Participants received intranasal spray of 0.2 mL (total dose in both nostrils) FluMist trivalent vaccine on Days 1 and 28. Each 0.2 mL dose contained 10^7±0.5 FFU of each vaccine strain. Strains included in the trivalent vaccine were: A/H1N1 (A/Bolivia/559/2013), A/H3N2 (A/Switzerland/9715293/2013), and B/Phuket/3073/2013 (B/Yamagata-lineage).
FluMist Quadrivalent (2015-2016)	Participants received intranasal spray of 0.2 mL (total dose in both nostrils) FluMist quadrivalent vaccine on Days 1 and 28. Each 0.2 mL dose contained 10^7±0.5 FFU of each vaccine strain. Strains included in the vaccine were A/H1N1 (A/Bolivia/559/2013), A/H3N2 (A/Switzerland/9715293/2013), B/Phuket/3073/2013 (B/Yamagata-lineage), and B/Brisbane/60/2008 (B/Victoria-lineage).
FluMist Quadrivalent (2017-2018)	Participants received intranasal spray of 0.2 mL (total dose in both nostrils) FluMist quadrivalent vaccine on Days 1 and 28. Each 0.2 mL dose contained 10^7±0.5 FFU of each vaccine strain. Strains included in the vaccine were the new A/H1N1 (A/Slovenia/2903/2015), A/H3N2 (A/New Caledonia/71/2014), B/Phuket/3073/2013 (B/Yamagata-lineage), and B/Brisbane/60/2008 (B/Victoria-lineage).

Measured Values

	FluMist trivalent (2015-2016)	FluMist Quadrivalent (2015-2016)	FluMist Quadrivalent (2017-2018)
Number of Participants Analyzed [units:participants]	67	66	67
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) [units: Participants]
TEAEs	29	31	34
TESAEs	0	0	0

No statistical analysis provided for Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)

Serious Adverse Events

Time Frame	Day 1 through Day 28 after Dose 1 (Day 1 dose) and Dose 2 (Day 28 dose)
Additional Description	ATP included all participants who received any investigational drug.

Reporting Groups

	Description
FluMist trivalent (2015-2016)	Participants received intranasal spray of 0.2 mL (total dose in both nostrils) FluMist trivalent vaccine on Days 1 and 28. Each 0.2 mL dose contained 10^7±0.5 FFU of each vaccine strain. Strains included in the trivalent vaccine were: A/H1N1 (A/Bolivia/559/2013), A/H3N2 (A/Switzerland/9715293/2013), and B/Phuket/3073/2013 (B/Yamagata-lineage).
FluMist Quadrivalent (2015-2016)	Participants received intranasal spray of 0.2 mL (total dose in both nostrils) FluMist quadrivalent vaccine on Days 1 and 28. Each 0.2 mL dose contained 10^7±0.5 FFU of each vaccine strain. Strains included in the vaccine were A/H1N1 (A/Bolivia/559/2013), A/H3N2 (A/Switzerland/9715293/2013), B/Phuket/3073/2013 (B/Yamagata-lineage), and B/Brisbane/60/2008 (B/Victoria-lineage).
FluMist Quadrivalent (2017-2018)	Participants received intranasal spray of 0.2 mL (total dose in both nostrils) FluMist quadrivalent vaccine on Days 1 and 28. Each 0.2 mL dose contained 10^7±0.5 FFU of each vaccine strain. Strains included in the vaccine were the new A/H1N1 (A/Slovenia/2903/2015), A/H3N2 (A/New Caledonia/71/2014), B/Phuket/3073/2013 (B/Yamagata-lineage), and B/Brisbane/60/2008 (B/Victoria-lineage).

Serious Adverse Events

	FluMist trivalent (2015-2016)	FluMist Quadrivalent (2015-2016)	FluMist Quadrivalent (2017-2018)
Total, serious adverse events
# participants affected / at risk	0/67 (0.00%)	0/66 (0.00%)	0/67 (0.00%)

Other Adverse Events

Time Frame	Day 1 through Day 28 after Dose 1 (Day 1 dose) and Dose 2 (Day 28 dose)
Additional Description	ATP included all participants who received any investigational drug.

Frequency Threshold

Threshold above which other adverse events are reported	0%

Reporting Groups

	Description
FluMist trivalent (2015-2016)	Participants received intranasal spray of 0.2 mL (total dose in both nostrils) FluMist trivalent vaccine on Days 1 and 28. Each 0.2 mL dose contained 10^7±0.5 FFU of each vaccine strain. Strains included in the trivalent vaccine were: A/H1N1 (A/Bolivia/559/2013), A/H3N2 (A/Switzerland/9715293/2013), and B/Phuket/3073/2013 (B/Yamagata-lineage).
FluMist Quadrivalent (2015-2016)	Participants received intranasal spray of 0.2 mL (total dose in both nostrils) FluMist quadrivalent vaccine on Days 1 and 28. Each 0.2 mL dose contained 10^7±0.5 FFU of each vaccine strain. Strains included in the vaccine were A/H1N1 (A/Bolivia/559/2013), A/H3N2 (A/Switzerland/9715293/2013), B/Phuket/3073/2013 (B/Yamagata-lineage), and B/Brisbane/60/2008 (B/Victoria-lineage).
FluMist Quadrivalent (2017-2018)	Participants received intranasal spray of 0.2 mL (total dose in both nostrils) FluMist quadrivalent vaccine on Days 1 and 28. Each 0.2 mL dose contained 10^7±0.5 FFU of each vaccine strain. Strains included in the vaccine were the new A/H1N1 (A/Slovenia/2903/2015), A/H3N2 (A/New Caledonia/71/2014), B/Phuket/3073/2013 (B/Yamagata-lineage), and B/Brisbane/60/2008 (B/Victoria-lineage).

Other Adverse Events

FluMist trivalent (2015-2016)

FluMist Quadrivalent (2015-2016)

FluMist Quadrivalent (2017-2018)

Total, other (not including serious) adverse events

# participants affected / at risk

29/67 (43.28%)

31/66 (46.97%)

34/67 (50.75%)

Ear and labyrinth disorders

Tympanic membrane perforation¹,^†

# participants affected / at risk

1/67 (1.49%)

0/66 (0.00%)

0/67 (0.00%)

# events

Eye disorders

Eye oedema¹,^†

# participants affected / at risk

0/67 (0.00%)

1/66 (1.52%)

0/67 (0.00%)

# events

Eye disorders

Ocular hyperaemia¹,^†

# participants affected / at risk

0/67 (0.00%)

1/66 (1.52%)

0/67 (0.00%)

# events

Eye disorders

Strabismus¹,^†

# participants affected / at risk

1/67 (1.49%)

0/66 (0.00%)

0/67 (0.00%)

# events

Gastrointestinal disorders

Abdominal discomfort¹,^†

# participants affected / at risk

0/67 (0.00%)

0/66 (0.00%)

1/67 (1.49%)

# events

Gastrointestinal disorders

Abdominal pain¹,^†

# participants affected / at risk

0/67 (0.00%)

0/66 (0.00%)

1/67 (1.49%)

# events

Gastrointestinal disorders

Abdominal pain upper¹,^†

# participants affected / at risk

0/67 (0.00%)

0/66 (0.00%)

1/67 (1.49%)

# events

Gastrointestinal disorders

Constipation¹,^†

# participants affected / at risk

1/67 (1.49%)

1/66 (1.52%)

0/67 (0.00%)

# events

Gastrointestinal disorders

Dental caries¹,^†

# participants affected / at risk

0/67 (0.00%)

0/66 (0.00%)

1/67 (1.49%)

# events

Gastrointestinal disorders

Diarrhoea¹,^†

# participants affected / at risk

9/67 (13.43%)

5/66 (7.58%)

4/67 (5.97%)

# events

Gastrointestinal disorders

Haematochezia¹,^†

# participants affected / at risk

0/67 (0.00%)

0/66 (0.00%)

1/67 (1.49%)

# events

Gastrointestinal disorders

Mouth haemorrhage¹,^†

# participants affected / at risk

0/67 (0.00%)

1/66 (1.52%)

0/67 (0.00%)

# events

Gastrointestinal disorders

Nausea¹,^†

# participants affected / at risk

0/67 (0.00%)

0/66 (0.00%)

1/67 (1.49%)

# events

Gastrointestinal disorders

Oral discomfort¹,^†

# participants affected / at risk

0/67 (0.00%)

1/66 (1.52%)

0/67 (0.00%)

# events

Gastrointestinal disorders

Oral pain¹,^†

# participants affected / at risk

0/67 (0.00%)

2/66 (3.03%)

0/67 (0.00%)

# events

Gastrointestinal disorders

Toothache¹,^†

# participants affected / at risk

0/67 (0.00%)

1/66 (1.52%)

0/67 (0.00%)

# events

Gastrointestinal disorders

Vomiting¹,^†

# participants affected / at risk

3/67 (4.48%)

5/66 (7.58%)

4/67 (5.97%)

# events

General disorders and administration site conditions

Chills¹,^†

# participants affected / at risk

1/67 (1.49%)

0/66 (0.00%)

0/67 (0.00%)

# events

General disorders and administration site conditions

Developmental delay¹,^†

# participants affected / at risk

0/67 (0.00%)

0/66 (0.00%)

1/67 (1.49%)

# events

General disorders and administration site conditions

Pyrexia¹,^†

# participants affected / at risk

1/67 (1.49%)

7/66 (10.61%)

2/67 (2.99%)

# events

Immune system disorders

Allergy to arthropod bite¹,^†

# participants affected / at risk

0/67 (0.00%)

1/66 (1.52%)

0/67 (0.00%)

# events

Immune system disorders

Seasonal allergy¹,^†

# participants affected / at risk

0/67 (0.00%)

0/66 (0.00%)

2/67 (2.99%)

# events

Infections and infestations

Cellulitis¹,^†

# participants affected / at risk

1/67 (1.49%)

0/66 (0.00%)

0/67 (0.00%)

# events

Infections and infestations

Conjunctivitis¹,^†

# participants affected / at risk

1/67 (1.49%)

0/66 (0.00%)

2/67 (2.99%)

# events

Infections and infestations

Croup infectious¹,^†

# participants affected / at risk

3/67 (4.48%)

0/66 (0.00%)

0/67 (0.00%)

# events

Infections and infestations

Ear infection¹,^†

# participants affected / at risk

3/67 (4.48%)

1/66 (1.52%)

1/67 (1.49%)

# events

Infections and infestations

Escherichia urinary tract infection¹,^†

# participants affected / at risk

0/67 (0.00%)

1/66 (1.52%)

0/67 (0.00%)

# events

Infections and infestations

Folliculitis¹,^†

# participants affected / at risk

1/67 (1.49%)

0/66 (0.00%)

0/67 (0.00%)

# events

Infections and infestations

Gastroenteritis viral¹,^†

# participants affected / at risk

1/67 (1.49%)

0/66 (0.00%)

1/67 (1.49%)

# events

Infections and infestations

Hand-foot-and-mouth disease¹,^†

# participants affected / at risk

1/67 (1.49%)

0/66 (0.00%)

0/67 (0.00%)

# events

Infections and infestations

Herpes simplex¹,^†

# participants affected / at risk

0/67 (0.00%)

0/66 (0.00%)

1/67 (1.49%)

# events

Infections and infestations

Localised infection¹,^†

# participants affected / at risk

0/67 (0.00%)

0/66 (0.00%)

1/67 (1.49%)

# events

Infections and infestations

Otitis media acute¹,^†

# participants affected / at risk

1/67 (1.49%)

1/66 (1.52%)

3/67 (4.48%)

# events

Infections and infestations

Pharyngitis¹,^†

# participants affected / at risk

1/67 (1.49%)

0/66 (0.00%)

0/67 (0.00%)

# events

Infections and infestations

Pharyngitis streptococcal¹,^†

# participants affected / at risk

0/67 (0.00%)

0/66 (0.00%)

3/67 (4.48%)

# events

Infections and infestations

Pneumonia¹,^†

# participants affected / at risk

0/67 (0.00%)

0/66 (0.00%)

1/67 (1.49%)

# events

Infections and infestations

Upper respiratory tract infection¹,^†

# participants affected / at risk

4/67 (5.97%)

2/66 (3.03%)

2/67 (2.99%)

# events

Infections and infestations

Viral pharyngitis¹,^†

# participants affected / at risk

1/67 (1.49%)

0/66 (0.00%)

2/67 (2.99%)

# events

Infections and infestations

Viral upper respiratory tract infection¹,^†

# participants affected / at risk

0/67 (0.00%)

0/66 (0.00%)

1/67 (1.49%)

# events

Injury, poisoning and procedural complications

Arthropod bite¹,^†

# participants affected / at risk

2/67 (2.99%)

2/66 (3.03%)

1/67 (1.49%)

# events

Injury, poisoning and procedural complications

Laceration¹,^†

# participants affected / at risk

1/67 (1.49%)

0/66 (0.00%)

0/67 (0.00%)

# events

Injury, poisoning and procedural complications

Radial head dislocation¹,^†

# participants affected / at risk

0/67 (0.00%)

1/66 (1.52%)

0/67 (0.00%)

# events

Injury, poisoning and procedural complications

Thermal burn¹,^†

# participants affected / at risk

0/67 (0.00%)

1/66 (1.52%)

0/67 (0.00%)

# events

Metabolism and nutrition disorders

Decreased appetite¹,^†

# participants affected / at risk

0/67 (0.00%)

1/66 (1.52%)

0/67 (0.00%)

# events

Musculoskeletal and connective tissue disorders

Neck pain¹,^†

# participants affected / at risk

0/67 (0.00%)

0/66 (0.00%)

1/67 (1.49%)

# events

Nervous system disorders

Headache¹,^†

# participants affected / at risk

1/67 (1.49%)

1/66 (1.52%)

0/67 (0.00%)

# events

Nervous system disorders

Lethargy¹,^†

# participants affected / at risk

1/67 (1.49%)

0/66 (0.00%)

0/67 (0.00%)

# events

Psychiatric disorders

Insomnia¹,^†

# participants affected / at risk

0/67 (0.00%)

0/66 (0.00%)

1/67 (1.49%)

# events

Psychiatric disorders

Irritability¹,^†

# participants affected / at risk

1/67 (1.49%)

2/66 (3.03%)

1/67 (1.49%)

# events

Respiratory, thoracic and mediastinal disorders

Bronchial hyperreactivity¹,^†

# participants affected / at risk

0/67 (0.00%)

0/66 (0.00%)

1/67 (1.49%)

# events

Respiratory, thoracic and mediastinal disorders

Cough¹,^†

# participants affected / at risk

4/67 (5.97%)

5/66 (7.58%)

4/67 (5.97%)

# events

Respiratory, thoracic and mediastinal disorders

Dysphonia¹,^†

# participants affected / at risk

1/67 (1.49%)

0/66 (0.00%)

0/67 (0.00%)

# events

Respiratory, thoracic and mediastinal disorders

Epistaxis¹,^†

# participants affected / at risk

3/67 (4.48%)

3/66 (4.55%)

1/67 (1.49%)

# events

Respiratory, thoracic and mediastinal disorders

Nasal congestion¹,^†

# participants affected / at risk

1/67 (1.49%)

1/66 (1.52%)

1/67 (1.49%)

# events

Respiratory, thoracic and mediastinal disorders

Paranasal sinus discomfort¹,^†

# participants affected / at risk

1/67 (1.49%)

0/66 (0.00%)

0/67 (0.00%)

# events

Respiratory, thoracic and mediastinal disorders

Pharyngeal erythema¹,^†

# participants affected / at risk

1/67 (1.49%)

1/66 (1.52%)

0/67 (0.00%)

# events

Respiratory, thoracic and mediastinal disorders

Rhinorrhoea¹,^†

# participants affected / at risk

4/67 (5.97%)

7/66 (10.61%)

9/67 (13.43%)

# events

Respiratory, thoracic and mediastinal disorders

Sneezing¹,^†

# participants affected / at risk

0/67 (0.00%)

1/66 (1.52%)

1/67 (1.49%)

# events

Respiratory, thoracic and mediastinal disorders

Tonsillar hypertrophy¹,^†

# participants affected / at risk

0/67 (0.00%)

0/66 (0.00%)

1/67 (1.49%)

# events

Skin and subcutaneous tissue disorders

Cold sweat¹,^†

# participants affected / at risk

0/67 (0.00%)

0/66 (0.00%)

1/67 (1.49%)

# events

Skin and subcutaneous tissue disorders

Dermatitis diaper¹,^†

# participants affected / at risk

3/67 (4.48%)

0/66 (0.00%)

1/67 (1.49%)

# events

Skin and subcutaneous tissue disorders

Pruritus¹,^†

# participants affected / at risk

0/67 (0.00%)

1/66 (1.52%)

0/67 (0.00%)

# events

Skin and subcutaneous tissue disorders

Rash¹,^†

# participants affected / at risk

0/67 (0.00%)

0/66 (0.00%)

1/67 (1.49%)

# events

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA 20.0

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The agreement is:

	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days . The sponsor cannot require changes to the communication and cannot extend the embargo.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. Restriction Description: MedImmune has 60 days to review results communications prior to public release and may delete information that compromises on-going studies or is considered proprietary. This restriction is not intended to compromise the objective scientific integrity of the manuscript, it being understood that results shall be published regardless of outcome.

Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.

Results Point of Contact

Name/Title:	Raburn Mallory
Organization:	MedImmune, LLC
Phone	+1-301-398-5799
E-mail:	[email protected]

Documents available

CSP in PDF-A
Download
Statistical Analysis Plan (SAP) in PDF-A
Download
Trial Results Summaries
Available here

Contacts

Contact

AstraZeneca Clinical Study Information Center

1-877-240-9479

information.center@astrazeneca.com

Sponsors

Collaborators

Inclusion Criteria

Exclusion Criteria

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

CSP in PDF-A

Statistical Analysis Plan (SAP) in PDF-A

Trial Results Summaries