Trial Outcomes & Findings for Influenza Immunity in Children (NCT NCT02559505)

NCT ID: NCT02559505

Last Updated: 2021-09-02

Results Overview

% H3- and nucleoprotein (NP)-specific CD4 T cells were measured using intracellular cytokine staining

Recruitment status

COMPLETED

Study phase

Target enrollment

134 participants

Primary outcome timeframe

Visit 2 (day 8-14 post enrollment)

Results posted on

2021-09-02

Participant Flow

Participant milestones

Participant milestones
Measure	Acute Children enrolled on presentation to their primary care provider with a natural influenza infection.	Vaccinated Seasonal IIV 0.25 mL dose: Fluzone (Sanofi Pasteur) 0.25 mL administered intramuscularly to children between 6 and 35 months of age
Overall Study STARTED	49	84
Overall Study COMPLETED	22	62
Overall Study NOT COMPLETED	27	22

Reasons for withdrawal

Reasons for withdrawal
Measure	Acute Children enrolled on presentation to their primary care provider with a natural influenza infection.	Vaccinated Seasonal IIV 0.25 mL dose: Fluzone (Sanofi Pasteur) 0.25 mL administered intramuscularly to children between 6 and 35 months of age
Overall Study Lost to Follow-up	23	20
Overall Study Withdrawal by Subject	4	2

Baseline Characteristics

Influenza Immunity in Children

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	6-12 Months of Age: Vaccinated n=13 Participants Children 6 - 12 months of age vaccinated with seasonal IIV Seasonal IIV 0.25 mL dose: Fluzone (Sanofi Pasteur) 0.25 mL administered intramuscularly to children between 6 and 35 months of age	3-12 Months of Age: Acute n=8 Participants Children 3-12 months of age presenting with natural influenza infection Natural influenza infection: Children enrolled on presentation to their primary care provider with a natural influenza infection Seasonal IIV 0.5 mL dose: Fluzone (Sanofi Pasteur) 0.25 mL administered intramuscularly to children between 6 and 35 months of age	13-35 Months of Age: Vaccinated n=30 Participants Children 13-35 months of age vaccinated with seasonal IIV Seasonal IIV 0.25 mL dose: Fluzone (Sanofi Pasteur) 0.25 mL administered intramuscularly to children between 6 and 35 months of age	13-35 Months of Age: Acute n=19 Participants Children 13-35 months of age presenting with natural influenza infection Natural influenza infection: Children enrolled on presentation to their primary care provider with a natural influenza infection Seasonal IIV 0.5 mL dose: Fluzone (Sanofi Pasteur) 0.25 mL administered intramuscularly to children between 6 and 35 months of age	3-5 Years of Age: Vaccinated n=18 Participants Children 3-5 years of age vaccinated with seasonal IIV Seasonal IIV 0.5 mL dose: Fluzone (Sanofi Pasteur) 0.25 mL administered intramuscularly to children between 6 and 35 months of age	3-5 Years of Age: Acute n=12 Participants Children 3-5 years of age presenting with natural influenza infection Natural influenza infection: Children enrolled on presentation to their primary care provider with a natural influenza infection Seasonal IIV 0.5 mL dose: Fluzone (Sanofi Pasteur) 0.25 mL administered intramuscularly to children between 6 and 35 months of age	6-8 Years of Age: Vaccinated n=23 Participants Children 6-8 years of age vaccinated with seasonal IIV Seasonal IIV 0.5 mL dose: Fluzone (Sanofi Pasteur) 0.25 mL administered intramuscularly to children between 6 and 35 months of age	6-8 Years of Age: Acute n=9 Participants Children 6-8 years of age presenting with natural influenza infection Natural influenza infection: Children enrolled on presentation to their primary care provider with a natural influenza infection Seasonal IIV 0.5 mL dose: Fluzone (Sanofi Pasteur) 0.25 mL administered intramuscularly to children between 6 and 35 months of age	Total n=132 Participants Total of all reporting groups
Age, Customized	13 participants n=93 Participants	8 participants n=4 Participants	30 participants n=27 Participants	19 participants n=483 Participants	18 participants n=36 Participants	12 participants n=10 Participants	23 participants n=115 Participants	9 participants n=40 Participants	132 participants n=8 Participants
Sex: Female, Male Female	9 Participants n=93 Participants	3 Participants n=4 Participants	14 Participants n=27 Participants	8 Participants n=483 Participants	8 Participants n=36 Participants	6 Participants n=10 Participants	10 Participants n=115 Participants	6 Participants n=40 Participants	64 Participants n=8 Participants
Sex: Female, Male Male	4 Participants n=93 Participants	5 Participants n=4 Participants	16 Participants n=27 Participants	11 Participants n=483 Participants	10 Participants n=36 Participants	6 Participants n=10 Participants	13 Participants n=115 Participants	3 Participants n=40 Participants	68 Participants n=8 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	3 Participants n=93 Participants	0 Participants n=4 Participants	3 Participants n=27 Participants	4 Participants n=483 Participants	0 Participants n=36 Participants	2 Participants n=10 Participants	0 Participants n=115 Participants	3 Participants n=40 Participants	15 Participants n=8 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	10 Participants n=93 Participants	8 Participants n=4 Participants	27 Participants n=27 Participants	15 Participants n=483 Participants	18 Participants n=36 Participants	10 Participants n=10 Participants	23 Participants n=115 Participants	6 Participants n=40 Participants	117 Participants n=8 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants	0 Participants n=36 Participants	0 Participants n=10 Participants	0 Participants n=115 Participants	0 Participants n=40 Participants	0 Participants n=8 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=93 Participants	0 Participants n=4 Participants	1 Participants n=27 Participants	0 Participants n=483 Participants	0 Participants n=36 Participants	0 Participants n=10 Participants	0 Participants n=115 Participants	0 Participants n=40 Participants	1 Participants n=8 Participants
Race (NIH/OMB) Asian	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants	0 Participants n=36 Participants	0 Participants n=10 Participants	0 Participants n=115 Participants	0 Participants n=40 Participants	0 Participants n=8 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants	0 Participants n=36 Participants	0 Participants n=10 Participants	0 Participants n=115 Participants	0 Participants n=40 Participants	0 Participants n=8 Participants
Race (NIH/OMB) Black or African American	4 Participants n=93 Participants	3 Participants n=4 Participants	12 Participants n=27 Participants	11 Participants n=483 Participants	0 Participants n=36 Participants	3 Participants n=10 Participants	1 Participants n=115 Participants	5 Participants n=40 Participants	39 Participants n=8 Participants
Race (NIH/OMB) White	6 Participants n=93 Participants	4 Participants n=4 Participants	10 Participants n=27 Participants	3 Participants n=483 Participants	14 Participants n=36 Participants	8 Participants n=10 Participants	15 Participants n=115 Participants	2 Participants n=40 Participants	62 Participants n=8 Participants
Race (NIH/OMB) More than one race	2 Participants n=93 Participants	1 Participants n=4 Participants	7 Participants n=27 Participants	3 Participants n=483 Participants	4 Participants n=36 Participants	0 Participants n=10 Participants	7 Participants n=115 Participants	1 Participants n=40 Participants	25 Participants n=8 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	2 Participants n=483 Participants	0 Participants n=36 Participants	1 Participants n=10 Participants	0 Participants n=115 Participants	1 Participants n=40 Participants	5 Participants n=8 Participants
Region of Enrollment United States	13 participants n=93 Participants	8 participants n=4 Participants	30 participants n=27 Participants	19 participants n=483 Participants	18 participants n=36 Participants	12 participants n=10 Participants	23 participants n=115 Participants	9 participants n=40 Participants	132 participants n=8 Participants

PRIMARY outcome

Timeframe: Visit 2 (day 8-14 post enrollment)

Population: 6 acute participants were infected with influenza strains that were not H3 and therefore were not included in the data analyzed for the primary outcome. Only vaccinated participants that age matched to the acute subjects were analyzed, resulting in 16 acutely infected and 28 vaccinated subjects included in the data analysis.

% H3- and nucleoprotein (NP)-specific CD4 T cells were measured using intracellular cytokine staining

Outcome measures

Outcome measures
Measure	Acute Infected n=16 Participants Children enrolled on presentation to their primary care provider with a natural influenza infection	Vaccinated n=28 Participants Seasonal IIV 0.25 mL dose: Fluzone (Sanofi Pasteur) 0.25 mL administered intramuscularly to children between 6 and 35 months of age	Vaccinated Age Subset (3-5 yr) Seasonal IIV 0.25 mL dose: Fluzone (Sanofi Pasteur) 0.25 mL administered intramuscularly to children between 3 - 5 years.	Vaccinated Age Subset (6-8 yr) Seasonal IIV 0.25 mL dose: Fluzone (Sanofi Pasteur) 0.25 mL administered intramuscularly to children between 6 - 8 years.
Mean Percent of IFNg+ CD69+ CD4 T Cells Between Acute (H3N2) Infected and Vaccinated Subjects Nucleoprotein	.010 percentage of T cells Standard Deviation 0.0023	0.003 percentage of T cells Standard Deviation 0.0018	—	—
Mean Percent of IFNg+ CD69+ CD4 T Cells Between Acute (H3N2) Infected and Vaccinated Subjects H3 protein	0.009 percentage of T cells Standard Deviation 0.0019	0.002 percentage of T cells Standard Deviation 0.0015	—	—

PRIMARY outcome

Timeframe: Visit 3 (day 20-28 post enrollment)

% H3- and nucleoprotein (NP)-specific CD4 T cells were measured using intracellular cytokine staining

Outcome measures

Outcome measures
Measure	Acute Infected n=16 Participants Children enrolled on presentation to their primary care provider with a natural influenza infection	Vaccinated n=28 Participants Seasonal IIV 0.25 mL dose: Fluzone (Sanofi Pasteur) 0.25 mL administered intramuscularly to children between 6 and 35 months of age	Vaccinated Age Subset (3-5 yr) Seasonal IIV 0.25 mL dose: Fluzone (Sanofi Pasteur) 0.25 mL administered intramuscularly to children between 3 - 5 years.	Vaccinated Age Subset (6-8 yr) Seasonal IIV 0.25 mL dose: Fluzone (Sanofi Pasteur) 0.25 mL administered intramuscularly to children between 6 - 8 years.
Mean Percent of IFNg+ CD69+ CD4 T Cells Between Acute (H3N2) Infected and Vaccinated Subjects Nucleoprotein	0.012 Percentage of T cells Standard Deviation 0.0025	0.003 Percentage of T cells Standard Deviation 0.0017	—	—
Mean Percent of IFNg+ CD69+ CD4 T Cells Between Acute (H3N2) Infected and Vaccinated Subjects H3 Protein	0.006 Percentage of T cells Standard Deviation 0.0021	0.004 Percentage of T cells Standard Deviation 0.0014	—	—

PRIMARY outcome

Timeframe: Visit 4 (day of vaccination year 2)

% H3- and nucleoprotein (NP)-specific CD4 T cells were measured using intracellular cytokine staining

Outcome measures

Outcome measures
Measure	Acute Infected n=16 Participants Children enrolled on presentation to their primary care provider with a natural influenza infection	Vaccinated n=28 Participants Seasonal IIV 0.25 mL dose: Fluzone (Sanofi Pasteur) 0.25 mL administered intramuscularly to children between 6 and 35 months of age	Vaccinated Age Subset (3-5 yr) Seasonal IIV 0.25 mL dose: Fluzone (Sanofi Pasteur) 0.25 mL administered intramuscularly to children between 3 - 5 years.	Vaccinated Age Subset (6-8 yr) Seasonal IIV 0.25 mL dose: Fluzone (Sanofi Pasteur) 0.25 mL administered intramuscularly to children between 6 - 8 years.
Mean Percent of IFNg+ CD69+ CD4 T Cells Between Acute (H3N2) Infected and Vaccinated Subjects Nucleoprotein	0.003 Percentage of T cells Standard Deviation 0.0030	0.003 Percentage of T cells Standard Deviation 0.0018	—	—
Mean Percent of IFNg+ CD69+ CD4 T Cells Between Acute (H3N2) Infected and Vaccinated Subjects H3 Protein	0.007 Percentage of T cells Standard Deviation 0.0022	0.003 Percentage of T cells Standard Deviation 0.0015	—	—

PRIMARY outcome

Timeframe: Visit 5 (day 8-14 post-vaccination year 2)

% H3 protein- and nucleoprotein (NP)-specific CD4 T cells were measured using intracellular cytokine staining

Outcome measures

Outcome measures
Measure	Acute Infected n=16 Participants Children enrolled on presentation to their primary care provider with a natural influenza infection	Vaccinated n=28 Participants Seasonal IIV 0.25 mL dose: Fluzone (Sanofi Pasteur) 0.25 mL administered intramuscularly to children between 6 and 35 months of age	Vaccinated Age Subset (3-5 yr) Seasonal IIV 0.25 mL dose: Fluzone (Sanofi Pasteur) 0.25 mL administered intramuscularly to children between 3 - 5 years.	Vaccinated Age Subset (6-8 yr) Seasonal IIV 0.25 mL dose: Fluzone (Sanofi Pasteur) 0.25 mL administered intramuscularly to children between 6 - 8 years.
Mean Percent of IFNg+ CD69+ CD4 T Cells Between Acute (H3N2) Infected and Vaccinated Subjects Nucleoprotein	0.010 Percentage of T cells Standard Deviation 0.0031	0.003 Percentage of T cells Standard Deviation 0.0018	—	—
Mean Percent of IFNg+ CD69+ CD4 T Cells Between Acute (H3N2) Infected and Vaccinated Subjects H3 Protein	0.008 Percentage of T cells Standard Deviation 0.0026	0.004 Percentage of T cells Standard Deviation 0.0015	—	—

PRIMARY outcome

Timeframe: Visit 6 (day 20-28 post-vaccination year 2)

% H3 Protein- and nucleoprotein (NP)-specific CD4 T cells were measured using intracellular cytokine staining

Outcome measures

Outcome measures
Measure	Acute Infected n=16 Participants Children enrolled on presentation to their primary care provider with a natural influenza infection	Vaccinated n=28 Participants Seasonal IIV 0.25 mL dose: Fluzone (Sanofi Pasteur) 0.25 mL administered intramuscularly to children between 6 and 35 months of age	Vaccinated Age Subset (3-5 yr) Seasonal IIV 0.25 mL dose: Fluzone (Sanofi Pasteur) 0.25 mL administered intramuscularly to children between 3 - 5 years.	Vaccinated Age Subset (6-8 yr) Seasonal IIV 0.25 mL dose: Fluzone (Sanofi Pasteur) 0.25 mL administered intramuscularly to children between 6 - 8 years.
Mean Percent of IFNg+ CD69+ CD4 T Cells Between Acute (H3N2) Infected and Vaccinated Subjects Nucleoprotein	0.014 Percentage of T cells Standard Deviation 0.0029	0.003 Percentage of T cells Standard Deviation 0.0019	—	—
Mean Percent of IFNg+ CD69+ CD4 T Cells Between Acute (H3N2) Infected and Vaccinated Subjects H3 Protein	0.008 Percentage of T cells Standard Deviation 0.0024	0.007 Percentage of T cells Standard Deviation 0.0015	—	—

SECONDARY outcome

Timeframe: Baseline to day 24 study year 1

Population: Statistical analysis was completed on all patients who attended all six clinical visits in addition to those who had 3 or more visits that had withdrawn later.

CD4 T cell quantity and specificity will be measured using intracellular cytokine staining. We report here the mean change in percent of cells reactive to the influenza HA protein and H3 protein.

Outcome measures

Outcome measures
Measure	Acute Infected n=8 Participants Children enrolled on presentation to their primary care provider with a natural influenza infection	Vaccinated n=12 Participants Seasonal IIV 0.25 mL dose: Fluzone (Sanofi Pasteur) 0.25 mL administered intramuscularly to children between 6 and 35 months of age	Vaccinated Age Subset (3-5 yr) n=14 Participants Seasonal IIV 0.25 mL dose: Fluzone (Sanofi Pasteur) 0.25 mL administered intramuscularly to children between 3 - 5 years.	Vaccinated Age Subset (6-8 yr) n=22 Participants Seasonal IIV 0.25 mL dose: Fluzone (Sanofi Pasteur) 0.25 mL administered intramuscularly to children between 6 - 8 years.
Mean Change in Percent of IFNg+ CD69+ CD4 T Cells Between Vaccinated Subjects in Different Age Subsets HAB	0.00112 Mean Percent change Standard Deviation 0.00290	0.00497 Mean Percent change Standard Deviation 0.00966	0.00622 Mean Percent change Standard Deviation 0.01098	0.01713 Mean Percent change Standard Deviation 0.02657
Mean Change in Percent of IFNg+ CD69+ CD4 T Cells Between Vaccinated Subjects in Different Age Subsets H3	0.0006729 Mean Percent change Standard Deviation 0.0017802	0.0002589 Mean Percent change Standard Deviation 0.005017	0.0053456 Mean Percent change Standard Deviation 0.0101449	0.001674 Mean Percent change Standard Deviation 0.008319

SECONDARY outcome

Timeframe: Baseline to day 24 study year 2

Population: Statistical analysis was completed on all patients who attended all six clinical visits in addition to those who had 3 or more visits that had withdrawn later.

CD4 T cell quantity and specificity will be measured using intracellular cytokine staining. We report here the mean change in percent of cells reactive to the influenza HA protein and H3 protein.

Outcome measures

Outcome measures
Measure	Acute Infected n=8 Participants Children enrolled on presentation to their primary care provider with a natural influenza infection	Vaccinated n=12 Participants Seasonal IIV 0.25 mL dose: Fluzone (Sanofi Pasteur) 0.25 mL administered intramuscularly to children between 6 and 35 months of age	Vaccinated Age Subset (3-5 yr) n=14 Participants Seasonal IIV 0.25 mL dose: Fluzone (Sanofi Pasteur) 0.25 mL administered intramuscularly to children between 3 - 5 years.	Vaccinated Age Subset (6-8 yr) n=22 Participants Seasonal IIV 0.25 mL dose: Fluzone (Sanofi Pasteur) 0.25 mL administered intramuscularly to children between 6 - 8 years.
Mean Change in Percent of IFNg+ CD69+ CD4 T Cells Between Vaccinated Subjects in Different Age Subsets HAB	0.00552 Mean Percent Change Standard Deviation 0.01436	0.00331 Mean Percent Change Standard Deviation 0.01216	0.00003 Mean Percent Change Standard Deviation 0.01096	0.005698 Mean Percent Change Standard Deviation 0.01729
Mean Change in Percent of IFNg+ CD69+ CD4 T Cells Between Vaccinated Subjects in Different Age Subsets H3	0.00350 Mean Percent Change Standard Deviation 0.00372	0.00177 Mean Percent Change Standard Deviation 0.00371	0.00188 Mean Percent Change Standard Deviation 0.00650	-0.0017093 Mean Percent Change Standard Deviation 0.01015

OTHER_PRE_SPECIFIED outcome

Timeframe: Days 10 and 24 post vaccination

Changes in PBMC gene expression patterns due to prior influenza exposure will be assessed using RNA-seq analysis

Outcome measures

Other adverse events

Adverse event data not reported

Additional Information

Dr. Jennifer Nayak

University Of Rochester

Phone: 5852767404

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place