Influenza Vaccine Feasibility Study in Children With Persistent Asthma

• Sponsor: Vanderbilt University Medical Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT02967393
• Collaborator: Centers for Disease Control and Prevention (U.S. Fed), Duke University (Other), Children's Hospital Medical Center, Cincinnati (Other)
• Enrollment: 40
• Locations: 4
• Arms: 2
• Actual Duration (Months): 3.7
• Patients Per Site: 10
• Patients Per Site Per Month: 2.7

Study Details

Study Description

Brief Summary

This study is designed to note whether a larger safety study using quadrivalent live attenuated influenza vaccine (LAIV4) versus quadrivalent inactivated influenza vaccine (IIV4)(FLUARIX®), would be feasible in children with persistent asthma. Half of the patients in this study will receive the FLUARIX® influenza vaccine, while the other half will receive a cell cultured quadrivalent inactivated influenza vaccine (ccIIV4)(Flucelvax®) being used as a surrogate for LAIV4.

Condition or Disease	Intervention/Treatment	Phase
Asthmatic	Drug: ccIIV4; Drug: IIV4	Phase 4

Detailed Description

The association of an increased risk in wheezing following receipt of a live-attenuated influenza vaccine in children at least 2 years of age with a prior history of asthma or wheeze remains unclear.

The Centers for Disease Control (CDC) and Prevention's Clinical Immunization Safety Assessment (CISA) planned to address a data safety gap regarding use of LAIV4 vaccine in children with asthma by conducting a 3-site randomized, non-inferiority prospective study. The main goal was to compare the safety of LAIV4 versus IIV4 in children 5-11 years with persistent asthma during the 2016-2017 influenza season. CDC and the CISA study sites developed a protocol and associated materials, and were poised to begin enrollment early during the 2016-2017 influenza season. However, after the June 22, 2016 Advisory Committee on Immunization Practices (ACIP) vote recommending against use of LAIV4 during the 2016-2017 influenza season, CDC and study investigators decided to defer implementing a study using LAIV4 during the 2016-2017 influenza season. Investigators will reconsider initiating this study during the 2017-2018 influenza season if ACIP votes to reinstate LAIV4 use or new data become available; ACIP makes recommendations annually.

The planned LAIV4 study had unique features in its design that previously had not been implemented in vaccine safety studies, including: 1) enrolling a substantial proportion of children with moderate-severe asthma 2) using digital peak flow meters and 3) collecting clinical data through multiple, complementary, measures for 42 days after vaccination. To capitalize on progress made during development of the study protocol and associated documents and procedures, CISA is proposing to carry out a study at the three sites to assess the feasibility of recruiting, enrolling, retaining, and collecting clinical data on children 5-11 years with persistent asthma of varied levels of severity in an influenza vaccine safety study. Findings from this proposed feasibility study will facilitate improving the LAIV4 study in the future if it goes forward through the CISA Project or in another venue. In 2016-2017 season, FDA approved a new influenza vaccine for use in persons aged 4 years and older, Flucelvax® Quadrivalent (ccIIV4); ACIP incorporated this vaccine into its recommendations for the 2016-2017 influenza season. Therefore ccIIV4 will be used in place of LAIV4 for this feasibility study. There is no evidence that Flucelvax® increases the risk of wheezing in asthmatic children. The feasibility study also offers an opportunity to gain some additional descriptive safety data for this new vaccine in asthmatic children.

Study Design

• Study Type: Interventional
• Actual Enrollment: 40 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Other
• Official Title: Feasibility Study to Assess the Safety of Quadrivalent, Live Attenuated Influenza Vaccine (LAIV4) Versus Quadrivalent Inactivated Influenza Vaccine (IIV4) in Children Aged 5-11 Years With Persistent Asthma of Varied Severity (Cell Culture Quadrivalent IIV Used as Surrogate for LAIV4)
• Actual Study Start Date: Oct 10, 2016
• Actual Primary Completion Date: Feb 1, 2017
• Actual Study Completion Date: Feb 1, 2017

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: IIV4 0.5 mL intramuscular injection	Drug: IIV4; Other Names: Fluarix
Active Comparator: cc IIV4 0.5 mL intramuscular injection	Drug: ccIIV4; Other Names: Flucelvax

Outcome Measures

Primary Outcome Measures

1. Feasibility Benchmark: Number of Parents That Complete the Memory Aid 1. [15 days]

   Memory aid 1 is a diary completed by the subjects Parent. Daily symptoms, peak flow and requires the parent to record daily symptoms, peak flow, days, post-vaccination asthma clinical symptoms and symptom scores, adverse event, fever and concomitant medication administration data for 14 days (until day 15) after vaccination.

2. Feasibility Benchmark: Number of Parent Completing Collection of Adverse Event Data [Day 16 to 43]

   Parent will collect the following data: need for new prescription or nonprescription medications for the control of asthma, an unscheduled healthcare provider visit or consultation within 42 days after vaccination, any other clinically significant event occurring at any point during the study period. Serious Adverse Events (SAEs) will also be monitored through 42 days after vaccination and will include events that result in death, were life threatening, result in subject hospitalization or prolongation of existing hospitalization, result in persistent or significant disability or incapacity. Additionally, important medical events that may not have resulted in death, were not life threatening, or did not require hospitalization might be considered SAEs when, according to appropriate medical judgment, they jeopardize the patient or subject and require medical or surgical intervention to prevent one of the outcomes listed above.

3. Feasibility Benchmark: Number of Parents That Perform and Document All Home Digital Peak Flow Measurements [15 days]

   Number of parents that perform and document all home digital peak flow measurements at least 11 days out of the 15-day monitoring period.

4. Feasibility Benchmark: Number of Parents That Perform and Document the Digital Peak Flow for Day 42 [Day 42]

   Parent will perform and document the digital peak flow for Day 42

5. Feasibility Benchmark: Number of Parents That Document Nighttime Awakenings [15 days]

   Number of parents that document nighttime awakenings for at least 11 of the 15-day monitoring period.

6. Feasibility Benchmark: Number of Parents That Respond to Day 4 Call and Provide Requested Data [Day 3 to 6]

   Number of parents that respond to Day 4 ( -1 day or + 2 days) call and provide requested data

7. Feasibility Benchmark: Number of Parents That Respond to Day 8 Call and Provide Requested Data. [Day 8-10]

   Number of parents that respond to Day 8 (plus 2 days) call and provide requested data.

8. Feasibility Benchmark: Number of Parents That Respond to Day 15 Call and Provide Requested Data [Day 14 to 17]

   Number of parents that respond to Day 15 (minus 1 or plus 2 days) call and provide requested data

9. Feasibility Benchmark: Number of Parents That Respond to Day 29 Call and Provide Requested Data. [Day 29-31]

   Number of Parents that respond to Day 29 ( Plus 2 Days) call and provide requested data.

10. Feasibility Benchmark: Number of Parents That Respond to Day 44 Call [Day 44-47]

    Number of parents that respond to Day 44 ( Plus 3 Days) call and provide requested data.

11. Feasibility Benchmark: Number of Parents Completing a Satisfaction Survey [42 days]

    Parent of each participant will be asked to complete a at the end of the study

Secondary Outcome Measures

1. Severe Local Reactogenicity Events During the 14 Days Post-vaccination [14 days]

   Number of severe local reactogenicity events for 14 days after vaccination between recipients of ccIIV4 and IIV4.

2. Severe Systemic Reactogenicity Events During the 14 Days Post-vaccination [14 days]

   Number of solicited severe (not serious) systemic reactogenicity events for 14 days after vaccination between recipients of ccIIV4 and IIV4.

3. Unsolicited and Severe Adverse Events [42 days]

   The nature and frequency of the unsolicited and Severe adverse events will be described in children receiving ccIIV4 and IIV4 during the 42 days after vaccination.

4. Number of Asthma Exacerbations Requiring Steroids [42 days]

   For the purpose of this study, asthma exacerbation will be defined as: any acute episode of progressively worsening shortness of breath/dyspnea, cough, wheezing, chest tightness, and/or respiratory distress during the 42 days post-vaccination (until day 43) for which the patient receives a new prescription for systemic corticosteroids..

5. Number Participants With Asthma Exacerbations Requiring Medical Attention [42 days]

   For the purpose of this study, asthma exacerbation will be defined as: any acute episode of progressively worsening shortness of breath/dyspnea, cough, wheezing, chest tightness, and/or respiratory distress during the 42 days post-vaccination (until day 43) for which the patient seeks unscheduled medical attention (e.g., healthcare provider office or Emergency Department visit or hospitalization)

Eligibility Criteria

Criteria

• Ages Eligible for Study: 5 Years to 11 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Children between 5-11 years of age, inclusive, at enrollment.

• Participant must have a current diagnosis of persistent asthma.

• Parent/legal guardian must provide written informed consent and subject must provide assent as appropriate for age prior to initiation of study procedures and according to local Institutional Review Board (IRB) requirement.

• Parent/legal guardian and subject must be willing and able to comply with planned study procedures and be available for all study visits.

• Children aged 5-8 years must have received at least 2 doses of seasonal trivalent or quadrivalent influenza vaccine prior to the current influenza season. Children 9-11 years must have received at least 1 dose of seasonal trivalent or quadrivalent influenza vaccine prior to the current influenza season.

• Is in good health, other than their asthma, as determined by medical history and targeted physical examination based on medical history.

• English or Spanish literate.

• Intention of being available for entire study period and complete all relevant study procedures, including follow-up phone calls and collection of information.

Exclusion Criteria:

• Acute illness and/or a reported oral temperature of ≥ 100.4°F within 72 hours prior to enrollment (this may result in a temporary delay of vaccination.

• Use of antipyretic medication during the preceding 24 hours that might mask a fever (temporary deferral).

• History of a severe allergic reaction (e.g., anaphylaxis) to any component of study influenza vaccines or a known allergy to eggs.

• Receipt of any licensed vaccine within 14 days (for inactivated vaccines) or 28 days (for live vaccines) prior to vaccination or planned receipt of any licensed vaccine within 42 days after vaccination.

• Receipt of current year's licensed influenza vaccine.

• Received an investigational agent (licensed or unlicensed vaccine, drug, biologic, device, blood product, or medication) in the 28 days prior to enrollment or planned receipt before 42 days after vaccination.

• Has immunosuppression as a result of an underlying illness or treatment, or use of anticancer chemotherapy or radiation therapy within the preceding 36 months.

• Has taken ≥ 20mg/day of prednisone or its equivalent, for 14 days or more within the past 28 days.

• Has know active neoplasm or a history of any hematologic malignancy.

• Has had a previous exacerbation of their asthma symptoms requiring systemic steroids within the prior 28 days, or has had a life-threatening exacerbation of asthma in the past two years (e.g. hypoxic seizure, mechanical ventilation).

• History of Guillian-Barre syndrome within 6 weeks of previous influenza vaccination.

• Has any condition that, in the opinion of the investigator, would interfere with the evaluation of the responses or would place the participant at unacceptable risk of injury.

• Has any diagnosis, current or past, of schizophrenia, bipolar disease, or other major psychiatric disorder.

• Currently taking aspirin or aspirin-containing products.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Centers for Disease Control and Prevention	Atlanta	Georgia	United States	30329
2	Duke Clinical Vaccine Unit	Durham	North Carolina	United States	27705
3	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio	United States	45229
4	Vanderbilt Vaccine Research Program	Nashville	Tennessee	United States	37232

Sponsors and Collaborators

• Vanderbilt University Medical Center
• Centers for Disease Control and Prevention
• Duke University
• Children's Hospital Medical Center, Cincinnati

Investigators

• Principal Investigator: Kathryn M Edwards, MD, Vanderbilt Vaccine Research Program

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Aug 19, 2016

More Information

Publications

None provided.

• Responsible Party: Kathryn Edwards, Sarah H. Sell and Cornelius Vanderbilt Professor of Pediatrics, Vanderbilt University Medical Center
• ClinicalTrials.gov Identifier: NCT02967393
• Other Study ID Numbers: IIV4/LAIV4/CDC
• First Posted: Nov 18, 2016
• Last Update Posted: Apr 23, 2018
• Last Verified: Mar 1, 2018

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Additional relevant MeSH terms: Influenza, Human; Asthma

Study Results

Participant Flow

Pre-assignment Detail	Feasibility Measures are done by the parent/guardian of the participants. Feasibility Measure data will be reported as a single group. Participant data (vaccine data) will be reported by the type of vaccination received.

Arm/Group Title	ccIIV4	IIV4
Arm/Group Description	0.5 mL intramuscular injection ccIIV4	0.5 mL intramuscular injection IIV4
Period Title: Overall Study
STARTED	20	20
COMPLETED	20	20
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	ccIIV4	IIV4	Total
Arm/Group Description	0.5 mL intramuscular injection ccIIV4	0.5 mL intramuscular injection IIV4	Total of all reporting groups
Overall Participants	20	20	40
Age (Count of Participants)
<=18 years	20 100%	20 100%	40 100%
Between 18 and 65 years	0 0%	0 0%	0 0%
>=65 years	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	6 30%	10 50%	16 40%
Male	14 70%	10 50%	24 60%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	4 20%	4 10%
Not Hispanic or Latino	20 100%	16 80%	36 90%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	9 45%	6 30%	15 37.5%
White	9 45%	9 45%	18 45%
More than one race	2 10%	5 25%	7 17.5%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (Count of Participants)
United States	20 100%	20 100%	40 100%

Outcome Measures

1. Primary Outcome

Title	Feasibility Benchmark: Number of Parents That Complete the Memory Aid 1.
Description	Memory aid 1 is a diary completed by the subjects Parent. Daily symptoms, peak flow and requires the parent to record daily symptoms, peak flow, days, post-vaccination asthma clinical symptoms and symptom scores, adverse event, fever and concomitant medication administration data for 14 days (until day 15) after vaccination.
Time Frame	15 days

Outcome Measure Data

Analysis Population Description

Feasibility Measures are done by the parent/guardian of the participants and results are not dependent on the type of vaccine received. Feasibility Measure data will be reported as a single group.

Arm/Group Title	All Parents
Arm/Group Description	Parents of participants from both arms
Measure Participants	40
Count of Participants [Participants]	35 175%

2. Primary Outcome

Title	Feasibility Benchmark: Number of Parent Completing Collection of Adverse Event Data
Description	Parent will collect the following data: need for new prescription or nonprescription medications for the control of asthma, an unscheduled healthcare provider visit or consultation within 42 days after vaccination, any other clinically significant event occurring at any point during the study period. Serious Adverse Events (SAEs) will also be monitored through 42 days after vaccination and will include events that result in death, were life threatening, result in subject hospitalization or prolongation of existing hospitalization, result in persistent or significant disability or incapacity. Additionally, important medical events that may not have resulted in death, were not life threatening, or did not require hospitalization might be considered SAEs when, according to appropriate medical judgment, they jeopardize the patient or subject and require medical or surgical intervention to prevent one of the outcomes listed above.
Time Frame	Day 16 to 43

Outcome Measure Data

Analysis Population Description

Feasibility Measures are done by the parent/guardian of the participants and results are not dependent on the type of vaccine received. Feasibility Measure data will be reported as a single group.

Arm/Group Title	All Participants
Arm/Group Description	Participants from both arms
Measure Participants	40
Count of Participants [Participants]	37 185%

3. Primary Outcome

Title	Feasibility Benchmark: Number of Parents That Perform and Document All Home Digital Peak Flow Measurements
Description	Number of parents that perform and document all home digital peak flow measurements at least 11 days out of the 15-day monitoring period.
Time Frame	15 days

Outcome Measure Data

Analysis Population Description

Feasibility Measures are done by the parent/guardian of the participants and results are not dependent on the type of vaccine received. Feasibility Measure data will be reported as a single group.

Arm/Group Title	All Participants
Arm/Group Description	Participants from both arms
Measure Participants	40
Count of Participants [Participants]	37 185%

4. Primary Outcome

Title	Feasibility Benchmark: Number of Parents That Perform and Document the Digital Peak Flow for Day 42
Description	Parent will perform and document the digital peak flow for Day 42
Time Frame	Day 42

Outcome Measure Data

Analysis Population Description

Feasibility Measures are done by the parent/guardian of the participants and results are not dependent on the type of vaccine received.. Feasibility Measure data will be reported as a single group.

Arm/Group Title	All Participants
Arm/Group Description	Participants from both arms
Measure Participants	40
Count of Participants [Participants]	37 185%

5. Primary Outcome

Title	Feasibility Benchmark: Number of Parents That Document Nighttime Awakenings
Description	Number of parents that document nighttime awakenings for at least 11 of the 15-day monitoring period.
Time Frame	15 days

Outcome Measure Data

Analysis Population Description

Feasibility Measures are done by the parent/guardian of the participants and results are not dependent on the type of vaccine received. Feasibility Measure data will be reported as a single group.

Arm/Group Title	All Participants
Arm/Group Description	Participants from both arms
Measure Participants	40
Count of Participants [Participants]	37 185%

6. Primary Outcome

Title	Feasibility Benchmark: Number of Parents That Respond to Day 4 Call and Provide Requested Data
Description	Number of parents that respond to Day 4 ( -1 day or + 2 days) call and provide requested data
Time Frame	Day 3 to 6

Outcome Measure Data

Analysis Population Description

Feasibility Measures are done by the parent/guardian of the participants and results are not dependent on the type of vaccine received. Feasibility Measure data will be reported as a single group.

Arm/Group Title	All Participants
Arm/Group Description	Participants from both arms
Measure Participants	40
Count of Participants [Participants]	39 195%

7. Primary Outcome

Title	Feasibility Benchmark: Number of Parents That Respond to Day 8 Call and Provide Requested Data.
Description	Number of parents that respond to Day 8 (plus 2 days) call and provide requested data.
Time Frame	Day 8-10

Outcome Measure Data

Analysis Population Description

Feasibility Measures are done by the parent/guardian of the participants and results are not dependent on the type of vaccine received. Feasibility Measure data will be reported as a single group.

Arm/Group Title	All Participants
Arm/Group Description	Participants from both arms
Measure Participants	40
Count of Participants [Participants]	39 195%

8. Primary Outcome

Title	Feasibility Benchmark: Number of Parents That Respond to Day 15 Call and Provide Requested Data
Description	Number of parents that respond to Day 15 (minus 1 or plus 2 days) call and provide requested data
Time Frame	Day 14 to 17

Outcome Measure Data

Analysis Population Description

Feasibility Measures are done by the parent/guardian of the participants and results are not dependent on the type of vaccine received. Feasibility Measure data will be reported as a single group.

Arm/Group Title	All Participants
Arm/Group Description	Participants from both arms
Measure Participants	40
Count of Participants [Participants]	39 195%

9. Primary Outcome

Title	Feasibility Benchmark: Number of Parents That Respond to Day 29 Call and Provide Requested Data.
Description	Number of Parents that respond to Day 29 ( Plus 2 Days) call and provide requested data.
Time Frame	Day 29-31

Outcome Measure Data

Analysis Population Description

Feasibility Measures are done by the parent/guardian of the participants and results are not dependent on the type of vaccine received. Feasibility Measure data will be reported as a single group.

Arm/Group Title	All Participants
Arm/Group Description	Participants from both arms
Measure Participants	40
Count of Participants [Participants]	37 185%

10. Primary Outcome

Title	Feasibility Benchmark: Number of Parents That Respond to Day 44 Call
Description	Number of parents that respond to Day 44 ( Plus 3 Days) call and provide requested data.
Time Frame	Day 44-47

Outcome Measure Data

Analysis Population Description

Feasibility Measures are done by the parent/guardian of the participants and results are not dependent on the type of vaccine received. Feasibility Measure data will be reported as a single group.

Arm/Group Title	All Participants
Arm/Group Description	Participants from both arms
Measure Participants	40
Count of Participants [Participants]	36 180%

11. Primary Outcome

Title	Feasibility Benchmark: Number of Parents Completing a Satisfaction Survey
Description	Parent of each participant will be asked to complete a at the end of the study
Time Frame	42 days

Outcome Measure Data

Analysis Population Description

Feasibility Measures are done by the parent/guardian of the participants and results are not dependent on the type of vaccine received. Feasibility Measure data will be reported as a single group.

Arm/Group Title	All Participants
Arm/Group Description	Participants from both arms
Measure Participants	40
Count of Participants [Participants]	36 180%

12. Secondary Outcome

Title	Severe Local Reactogenicity Events During the 14 Days Post-vaccination
Description	Number of severe local reactogenicity events for 14 days after vaccination between recipients of ccIIV4 and IIV4.
Time Frame	14 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	ccIIV4	IIV4
Arm/Group Description	0.5 mL intramuscular injection ccIIV4	0.5 mL intramuscular injection IIV4
Measure Participants	20	20
Number [number of events]	0	2

13. Secondary Outcome

Title	Severe Systemic Reactogenicity Events During the 14 Days Post-vaccination
Description	Number of solicited severe (not serious) systemic reactogenicity events for 14 days after vaccination between recipients of ccIIV4 and IIV4.
Time Frame	14 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	ccIIV4	IIV4
Arm/Group Description	0.5 mL intramuscular injection ccIIV4	0.5 mL intramuscular injection IIV4
Measure Participants	20	20
Number [number of events]	1	1

14. Secondary Outcome

Title	Unsolicited and Severe Adverse Events
Description	The nature and frequency of the unsolicited and Severe adverse events will be described in children receiving ccIIV4 and IIV4 during the 42 days after vaccination.
Time Frame	42 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	ccIIV4	IIV4
Arm/Group Description	0.5 mL intramuscular injection ccIIV4	0.5 mL intramuscular injection IIV4
Measure Participants	20	20
wheezing	1	0
hand foot and mouth virus	1	0

15. Secondary Outcome

Title	Number of Asthma Exacerbations Requiring Steroids
Description	For the purpose of this study, asthma exacerbation will be defined as: any acute episode of progressively worsening shortness of breath/dyspnea, cough, wheezing, chest tightness, and/or respiratory distress during the 42 days post-vaccination (until day 43) for which the patient receives a new prescription for systemic corticosteroids..
Time Frame	42 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	ccIIV4	IIV4
Arm/Group Description	0.5 mL intramuscular injection ccIIV4	0.5 mL intramuscular injection IIV4
Measure Participants	20	20
Number [number of events]	3	1

16. Secondary Outcome

Title	Number Participants With Asthma Exacerbations Requiring Medical Attention
Description	For the purpose of this study, asthma exacerbation will be defined as: any acute episode of progressively worsening shortness of breath/dyspnea, cough, wheezing, chest tightness, and/or respiratory distress during the 42 days post-vaccination (until day 43) for which the patient seeks unscheduled medical attention (e.g., healthcare provider office or Emergency Department visit or hospitalization)
Time Frame	42 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	ccIIV4	IIV4
Arm/Group Description	0.5 mL intramuscular injection ccIIV4	0.5 mL intramuscular injection IIV4
Measure Participants	20	20
Count of Participants [Participants]	6 30%	4 20%

Adverse Events

Time Frame	42 days from vaccination
Arm/Group Title	ccIIV4		IIV4
Arm/Group Description	0.5 mL intramuscular injection ccIIV4		0.5 mL intramuscular injection IIV4
All Cause Mortality
	ccIIV4		IIV4
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/20 (0%)		0/20 (0%)
Serious Adverse Events
	ccIIV4		IIV4
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/20 (5%)		0/20 (0%)
Respiratory, thoracic and mediastinal disorders
Wheezing	1/20 (5%)	1	0/20 (0%)	0
Skin and subcutaneous tissue disorders
Hand foot and mouth disease	1/20 (5%)	1	0/20 (0%)	0
Other (Not Including Serious) Adverse Events
	ccIIV4		IIV4
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	19/20 (95%)		19/20 (95%)
Gastrointestinal disorders
Stomache Ache	6/20 (30%)	6	7/20 (35%)	7
Vomiting	0/20 (0%)	0	3/20 (15%)	3
General disorders
Headache	7/20 (35%)	7	7/20 (35%)	7
Muscles Aches	2/20 (10%)	2	5/20 (25%)	5
Bone Pain	2/20 (10%)	2	4/20 (20%)	4
Fatigue	6/20 (30%)	6	12/20 (60%)	12
Decrease Appetite	4/20 (20%)	4	8/20 (40%)	8
Irritability	7/20 (35%)	7	11/20 (55%)	11
Immune system disorders
Local Reaction to Vaccine	19/20 (95%)	19	19/20 (95%)	19
Feverish	4/20 (20%)	4	5/20 (25%)	5
Respiratory, thoracic and mediastinal disorders
Asthma Exacerbations	6/20 (30%)	6	4/20 (20%)	4

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.