Randomized Study of Immune Response to Licensed Influenza Vaccines in Children and Adolescents

• Sponsor: Marshfield Clinic Research Foundation (Other)
• Overall Status: Completed
• CT.gov ID: NCT02250274
• Collaborator: Centers for Disease Control and Prevention (U.S. Fed), University of Wisconsin, Madison (Other)
• Enrollment: 131
• Location: 1
• Arms: 2
• Duration (Months): 7
• Patients Per Site Per Month: 18.8

Study Details

Study Description

Brief Summary

The purpose of this study is to assess the serologic and cell-mediated immune response to licensed live attenuated influenza vaccine (LAIV) and inactivated influenza vaccine (IIV) in children 5-17 years old. The effects of prior infection and or prior season vaccination will be examined. Children will be followed during the influenza season to identify laboratory-confirmed influenza (i.e. vaccine failure).

Condition or Disease	Intervention/Treatment	Phase
Immune Response to Influenza Vaccine; Influenza A Virus Infection; Influenza B Virus Infection	Biological: LAIV; Biological: IIV	Phase 4

Detailed Description

All children will have baseline blood samples drawn and will then be vaccinated with licensed and approved influenza vaccines. Following the recommendation from the Advisory Committee on Immunization Practices, children 5-8 years old will preferentially receive live attenuated influenza vaccine (LAIV). Children aged 9-17 will be randomized to receive either LAIV or inactivated influenza vaccine (IIV). Children with a medical contraindication to any licensed influenza vaccine will be excluded from the study.

The children will have their blood drawn between 2 and 4 times total over the course of two months in order to test their immune response to the vaccine. Between approximately December and April, study participants will be contacted weekly to monitor for any new respiratory illnesses with cough, and if present, nasal and throat swabs will be collected to test for influenza.

Study Design

• Study Type: Interventional
• Actual Enrollment: 131 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• Official Title: Prospective Randomized Study of Immune Response to Licensed Influenza Vaccines in Children and Adolescents
• Study Start Date: Sep 1, 2014
• Actual Primary Completion Date: Dec 1, 2014
• Actual Study Completion Date: Apr 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Other: LAIV 2014-15 Will receive LAIV this year. Includes 5-8 year olds and approximately half of the 9-17 year olds. Prior history includes vaccine failures, vaccinated/uninfected and unvaccinated/uninfected last year. PBMC available for those who were infected last year, all ages.	Biological: LAIV; Licensed and approved Live Attenuated Influenza Vaccination (LAIV) will be preferentially given to all children aged 5-8 years old as recommended by Advisory Committee on Immunization Practices. A modified randomization scheme in which every other child aged 9-17 years enrolled in the study will be given LAIV will be used. The rest of the children aged 9-17 years old will receive IIV.; Other Names: FluMist
Other: IIV 2014-15 Will receive IIV this year. Includes only 9-17 year olds (unless shortages of LAIV encountered). Prior history includes vaccine failures, vaccinated/uninfected and unvaccinated/uninfected last year. PBMC available for those who were infected last year, only 9-17 year olds.	Biological: IIV; A modified randomization scheme in which every other child aged 9-17 years enrolled in the study will be given IIV will be used. The rest of the children 9-17 years old will receive LAIV. [Note: Although we do not anticipate exhausting the supply of LAIV, should this occur, children aged 5-8 will be offered IIV as it is also approved in this age group and should be used if LAIV is unavailable.]; Other Names: FluZone

Outcome Measures

Primary Outcome Measures

1. Hemagglutination Inhibition (HI) Titer Response to Vaccine and Circulating Strains of Influenza [Change from Baseline to 28 days]

Secondary Outcome Measures

1. Polymerase Chain Reaction (PCR) Confirmed Influenza Illness [Onset >13 days after vaccination and before April 1, 2015]

2. Antibody Dependent Cellular Cytotoxicity (ADCC) Titers [Change from Baseline to 28 days]

3. Ratio Between Immunoglobulin A (IgA):Immunoglobulin G (IgG) [Day 7]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 5 Years to 17 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Aged 5-17 years for the duration of the study period (Sept 1, 2014-Apr 1, 2015)

• Enrolled in either the immune response study or the vaccine effectiveness study conducted at the site in the 2013-14 influenza season

• If enrolled in the vaccine effectiveness study the previous season must have either been vaccinated and infected with influenza or unvaccinated and uninfected with influenza

Exclusion Criteria:

• Children with contraindications to either the quadrivalent live attenuated influenza vaccine or to the trivalent inactivated influenza vaccine will be excluded.

• Anyone unwilling or unable to complete all required study activities including informed consent

• Subjects who already received the influenza vaccine for the 2014-15 season

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Marshfield Clinic - Marshfield Center	Marshfield	Wisconsin	United States	54449

Sponsors and Collaborators

• Marshfield Clinic Research Foundation
• Centers for Disease Control and Prevention
• University of Wisconsin, Madison

Investigators

• Principal Investigator: Edward A Belongia, MD, Marshfield Clinic Research Foundation - Center for Clinical Epidemiology & Population Health

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Edward Belongia, Director of Center for Clinical Epidemiology and Population Health, Marshfield Clinic Research Foundation
• ClinicalTrials.gov Identifier: NCT02250274
• Other Study ID Numbers: 5U01IP000471-04
• First Posted: Sep 26, 2014
• Last Update Posted: Apr 26, 2018
• Last Verified: Mar 1, 2018

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Edward Belongia, Director of Center for Clinical Epidemiology and Population Health, Marshfield Clinic Research Foundation: Immune response to influenza vaccine; PCR confirmed Influenza A virus; PCR confirmed Influenza B virus
• Additional relevant MeSH terms: Infections; Communicable Diseases; Virus Diseases; Influenza, Human; Herpesviridae Infections

Study Results

Participant Flow

Arm/Group Title	LAIV 2014-15	IIV 2014-15
Arm/Group Description	Will receive LAIV this year. Includes 5-8 year olds and approximately half of the 9-17 year olds. Prior history includes vaccine failures, vaccinated/uninfected and unvaccinated/uninfected last year. PBMC available for those who were infected last year, all ages. LAIV: Licensed and approved Live Attenuated Influenza Vaccination (LAIV) will be preferentially given to all children aged 5-8 years old as recommended by Advisory Committee on Immunization Practices. A modified randomization scheme in which every other child aged 9-17 years enrolled in the study will be given LAIV will be used. The rest of the children aged 9-17 years old will receive IIV.	Will receive IIV this year. Includes only 9-17 year olds (unless shortages of LAIV encountered). Prior history includes vaccine failures, vaccinated/uninfected and unvaccinated/uninfected last year. PBMC available for those who were infected last year, only 9-17 year olds. IIV: A modified randomization scheme in which every other child aged 9-17 years enrolled in the study will be given IIV will be used. The rest of the children 9-17 years old will receive LAIV. [Note: Although we do not anticipate exhausting the supply of LAIV, should this occur, children aged 5-8 will be offered IIV as it is also approved in this age group and should be used if LAIV is unavailable.]
Period Title: Overall Study
STARTED	85	46
COMPLETED	78	40
NOT COMPLETED	7	6

Baseline Characteristics

Arm/Group Title	LAIV 2014-15	IIV 2014-15	Total
Arm/Group Description	Will receive LAIV this year. Includes 5-8 year olds and approximately half of the 9-17 year olds. Prior history includes vaccine failures, vaccinated/uninfected and unvaccinated/uninfected last year. PBMC available for those who were infected last year, all ages. LAIV: Licensed and approved Live Attenuated Influenza Vaccination (LAIV) will be preferentially given to all children aged 5-8 years old as recommended by Advisory Committee on Immunization Practices. A modified randomization scheme in which every other child aged 9-17 years enrolled in the study will be given LAIV will be used. The rest of the children aged 9-17 years old will receive IIV.	Will receive IIV this year. Includes only 9-17 year olds (unless shortages of LAIV encountered). Prior history includes vaccine failures, vaccinated/uninfected and unvaccinated/uninfected last year. PBMC available for those who were infected last year, only 9-17 year olds. IIV: A modified randomization scheme in which every other child aged 9-17 years enrolled in the study will be given IIV will be used. The rest of the children 9-17 years old will receive LAIV. [Note: Although we do not anticipate exhausting the supply of LAIV, should this occur, children aged 5-8 will be offered IIV as it is also approved in this age group and should be used if LAIV is unavailable.]	Total of all reporting groups
Overall Participants	85	46	131
Age (YEARS) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [YEARS]	10 (3.2)	12 (2.5)	11 (3.2)
Sex: Female, Male (Count of Participants)
Female	35 41.2%	21 45.7%	56 42.7%
Male	50 58.8%	25 54.3%	75 57.3%

Outcome Measures

1. Primary Outcome

Title	Hemagglutination Inhibition (HI) Titer Response to Vaccine and Circulating Strains of Influenza
Time Frame	Change from Baseline to 28 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	LAIV 2014-15	IIV 2014-15
Arm/Group Description	Will receive LAIV this year. Includes 5-8 year olds and approximately half of the 9-17 year olds. Prior history includes vaccine failures, vaccinated/uninfected and unvaccinated/uninfected last year. PBMC available for those who were infected last year, all ages. LAIV: Licensed and approved Live Attenuated Influenza Vaccination (LAIV) will be preferentially given to all children aged 5-8 years old as recommended by Advisory Committee on Immunization Practices. A modified randomization scheme in which every other child aged 9-17 years enrolled in the study will be given LAIV will be used. The rest of the children aged 9-17 years old will receive IIV.	Will receive IIV this year. Includes only 9-17 year olds (unless shortages of LAIV encountered). Prior history includes vaccine failures, vaccinated/uninfected and unvaccinated/uninfected last year. PBMC available for those who were infected last year, only 9-17 year olds. IIV: A modified randomization scheme in which every other child aged 9-17 years enrolled in the study will be given IIV will be used. The rest of the children 9-17 years old will receive LAIV. [Note: Although we do not anticipate exhausting the supply of LAIV, should this occur, children aged 5-8 will be offered IIV as it is also approved in this age group and should be used if LAIV is unavailable.]
Measure Participants	78	40
H3N2 Day 28 HI Titer	99	295
H3N2 Baseline HI Titer	96	100

2. Secondary Outcome

Title	Polymerase Chain Reaction (PCR) Confirmed Influenza Illness
Time Frame	Onset >13 days after vaccination and before April 1, 2015

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	LAIV 2014-15	IIV 2014-15
Arm/Group Description	Will receive LAIV this year. Includes 5-8 year olds and approximately half of the 9-17 year olds. Prior history includes vaccine failures, vaccinated/uninfected and unvaccinated/uninfected last year. PBMC available for those who were infected last year, all ages. LAIV: Licensed and approved Live Attenuated Influenza Vaccination (LAIV) will be preferentially given to all children aged 5-8 years old as recommended by Advisory Committee on Immunization Practices. A modified randomization scheme in which every other child aged 9-17 years enrolled in the study will be given LAIV will be used. The rest of the children aged 9-17 years old will receive IIV.	Will receive IIV this year. Includes only 9-17 year olds (unless shortages of LAIV encountered). Prior history includes vaccine failures, vaccinated/uninfected and unvaccinated/uninfected last year. PBMC available for those who were infected last year, only 9-17 year olds. IIV: A modified randomization scheme in which every other child aged 9-17 years enrolled in the study will be given IIV will be used. The rest of the children 9-17 years old will receive LAIV. [Note: Although we do not anticipate exhausting the supply of LAIV, should this occur, children aged 5-8 will be offered IIV as it is also approved in this age group and should be used if LAIV is unavailable.]
Measure Participants	85	46
Number [participants]	13 15.3%	5 10.9%

3. Secondary Outcome

Title	Antibody Dependent Cellular Cytotoxicity (ADCC) Titers
Time Frame	Change from Baseline to 28 days

Outcome Measure Data

Analysis Population Description

Fold change in NK cell degranulation

Arm/Group Title	IIV-IIV	IIV-LAIV	LAIV-IIV	LAIV-LAIV	Unvax-IIV	Unvax-LAIV
Arm/Group Description	Participants receiving IIV in 2013-14 and IIV again in 2014-15.	Participants receiving IIV in 2013-14 and LAIV in 2014-15.	Participants receiving LAIV in 2013-14 and IIV in 2014-15.	Participants receiving LAIV in 2013-14 and LAIV in 2014-15.	Participants unvaccinated in 2013-14 and receiving IIV in 2014-15.	Participants unvaccinated in 2013-14 and receiving LAIV in 2014-15.
Measure Participants	19	31	13	28	7	10
Fold change in NK cell degranulation to SW antigen	1.02	0.99	1.47	0.86	1.31	1.08
Fold change in NK cell degranulation to TX antigen	1.10	0.95	1.39	1.01	1.13	1.33

4. Secondary Outcome

Title	Ratio Between Immunoglobulin A (IgA):Immunoglobulin G (IgG)
Time Frame	Day 7

Outcome Measure Data

Analysis Population Description

There were too few samples collected within each group to conduct a reasonable analysis of this outcome. The samples collected are being stored for potential future use.

Arm/Group Title	LAIV 2014-15	IIV 2014-15
Arm/Group Description	Will receive LAIV this year. Includes 5-8 year olds and approximately half of the 9-17 year olds. Prior history includes vaccine failures, vaccinated/uninfected and unvaccinated/uninfected last year. PBMC available for those who were infected last year, all ages. LAIV: Licensed and approved Live Attenuated Influenza Vaccination (LAIV) will be preferentially given to all children aged 5-8 years old as recommended by Advisory Committee on Immunization Practices. A modified randomization scheme in which every other child aged 9-17 years enrolled in the study will be given LAIV will be used. The rest of the children aged 9-17 years old will receive IIV.	Will receive IIV this year. Includes only 9-17 year olds (unless shortages of LAIV encountered). Prior history includes vaccine failures, vaccinated/uninfected and unvaccinated/uninfected last year. PBMC available for those who were infected last year, only 9-17 year olds. IIV: A modified randomization scheme in which every other child aged 9-17 years enrolled in the study will be given IIV will be used. The rest of the children 9-17 years old will receive LAIV. [Note: Although we do not anticipate exhausting the supply of LAIV, should this occur, children aged 5-8 will be offered IIV as it is also approved in this age group and should be used if LAIV is unavailable.]
Measure Participants	0	0

Adverse Events

Arm/Group Title	LAIV 2014-15		IIV 2014-15
Arm/Group Description	Will receive LAIV this year. Includes 5-8 year olds and approximately half of the 9-17 year olds. Prior history includes vaccine failures, vaccinated/uninfected and unvaccinated/uninfected last year. PBMC available for those who were infected last year, all ages. LAIV: Licensed and approved Live Attenuated Influenza Vaccination (LAIV) will be preferentially given to all children aged 5-8 years old as recommended by Advisory Committee on Immunization Practices. A modified randomization scheme in which every other child aged 9-17 years enrolled in the study will be given LAIV will be used. The rest of the children aged 9-17 years old will receive IIV.		Will receive IIV this year. Includes only 9-17 year olds (unless shortages of LAIV encountered). Prior history includes vaccine failures, vaccinated/uninfected and unvaccinated/uninfected last year. PBMC available for those who were infected last year, only 9-17 year olds. IIV: A modified randomization scheme in which every other child aged 9-17 years enrolled in the study will be given IIV will be used. The rest of the children 9-17 years old will receive LAIV. [Note: Although we do not anticipate exhausting the supply of LAIV, should this occur, children aged 5-8 will be offered IIV as it is also approved in this age group and should be used if LAIV is unavailable.]
All Cause Mortality
	LAIV 2014-15		IIV 2014-15
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	LAIV 2014-15		IIV 2014-15
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/85 (0%)		0/46 (0%)
Other (Not Including Serious) Adverse Events
	LAIV 2014-15		IIV 2014-15
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/85 (0%)		0/46 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

There is NOT 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.