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Comparison of Flu Vaccine Doses in Children

Primary Purpose

Influenza

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Trivalent Inactivated Influenza Vaccine
Sponsored by
National Institute of Allergy and Infectious Diseases (NIAID)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Influenza focused on measuring influenza, pediatric, vaccine

Eligibility Criteria

6 Months - 35 Months (Child)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

All Subjects

  • Healthy children 6-35 months of age (naïve cohort) or 12-35 months of age (fully primed cohort)
  • Free of obvious health problems as established by medical history and clinical examination before entering the study
  • Parent/legal guardian willing and capable of signing written informed consent
  • Parent/legal guardian expected to be available for entire study
  • Parent/legal guardian can be reached by telephone

Fully Primed Cohort

-Have received two doses of 2009-2010 H1N1 and two doses of trivalent inactivated influenza vaccine (TIV) at anytime in the past as defined for the purpose of this study.

Exclusion Criteria:

All Subjects:

  • Have known allergy to eggs or other components of the vaccine. *Refer to the Fluzone package insert for a list of vaccine components.
  • Known or suspected latex allergy.
  • Former premature infants (<32 weeks).
  • History of bronchodilator use more than 2 times per week within 28 days of vaccination.
  • Significant underlying chronic illness (e.g., congenital heart disease, bronchopulmonary dysplasia).
  • Immunodeficiency disease or use of immunosuppressive therapy by the participant, including perinatal exposure to or infection with human immunodeficiency virus (HIV), or known infection with hepatitis B or hepatitis C.
  • Any other condition that, in the clinical judgment of the investigator, may interfere with vaccine evaluation. Children receiving antibiotics are eligible for enrollment.
  • Have long term use of glucocorticoids including oral, parenteral or high-dose inhaled steroids (>800 mcg/day of beclomethasone dipropionate or equivalent) within the preceding 6 months. (Nasal and topical steroids are allowed.)
  • Previous, exposure to an investigational drug or investigational vaccine within 28 days prior to vaccination in this trial.
  • Plans for participation in another clinical trial with an investigational drug or investigational vaccine for the duration of this study.
  • History of Guillain-Barré syndrome or any other neuromuscular disease.
  • History of seizures (including febrile seizures).

Naïve Cohort:

  • Any prior influenza vaccination.
  • History of documented laboratory-confirmed influenza infection.

Fully primed Cohort:

  • Have not received two doses of 2009-2010 H1N1 and two doses of trivalent inactivated influenza vaccine (TIV) at anytime in the past as defined for the purpose of this study.
  • Allergic response to prior receipt of influenza vaccine.

Criteria for temporarily delaying vaccine administration for both groups:

The following conditions are temporary or self-limiting and a subject may be included in the study once the condition(s) has/have resolved, provided that the subject is otherwise eligible:

  • Receipt of blood products in the previous 90 days
  • Fever (axillary temperature > 100.0 degrees Fahrenheit/37.8 degrees Celsius), or an acute illness within 48 hours of enrollment.
  • Receipt of any live vaccines within four weeks or any inactivated vaccines within two weeks of study vaccination.

Sites / Locations

  • Emory Children's Center - Pediatric Infectious Diseases
  • Emory University School of Medicine - Emory Children's Center - Pediatric Infectious Diseases
  • University of Iowa - Infectious Disease Clinic
  • University of Maryland School of Medicine - Center for Vaccine Development - Baltimore
  • Saint Louis University - Center for Vaccine Development
  • Cincinnati Children's Hospital Medical Center - Infectious Diseases
  • Vanderbilt University - Pediatric - Infectious Diseases

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Group 2, 0.5 mL TIV

Group 1, 0.25 mL TIV

Arm Description

Naive cohort participants (n=180) receive 0.25 mLTrivalent Inactivated Vaccine (TIV) in two intramuscular doses 28-42 days apart. Fully Primed cohort participants (previously vaccinated) (n=40) will receive 0.5 mL Trivalent Inactivated Influenza Vaccine (TIV) in one intramuscular dose.

Naive cohort participants (n=90) receive 0.25 mLTrivalent Inactivated Vaccine (TIV) in two intramuscular doses 28-42 days apart. Fully Primed cohort participants (previously vaccinated) (n=20) will receive 0.25 mL Trivalent Inactivated Influenza Vaccine (TIV) in one intramuscular dose

Outcomes

Primary Outcome Measures

Incidence of local and systemic side effects in children receiving the standard dose (0.25ml) or increased dose (0.5 ml) of Trivalent Inactivated Influenza Vaccine.
Incidence of adverse events in children receiving the standard dose (0.25ml) or increased dose (0.5 ml) of Trivalent Inactivated Influenza Vaccine (TIV).

Secondary Outcome Measures

Percent of children who develop hemagglutinin inhibition (HAI) antibody titers greater than or equal to 1:40 (presumed protective titers) and the percent with 4-fold rises.
Geometric mean titer (GMT) of the hemagglutinin inhibition (HAI) antibody responses to each of the components of the Trivalent Inactivated Influenza Vaccine (TIV).

Full Information

First Posted
July 15, 2010
Last Updated
April 25, 2013
Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
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1. Study Identification

Unique Protocol Identification Number
NCT01164553
Brief Title
Comparison of Flu Vaccine Doses in Children
Official Title
A Randomized, Double-Blind, Phase I Study Comparing an Increased Dose(s) (0.5 ml) of Trivalent Inactivated Influenza Vaccine (TIV) With Standard Dose(s) (0.25 ml) TIV in Children 6-35 Months of Age
Study Type
Interventional

2. Study Status

Record Verification Date
October 2012
Overall Recruitment Status
Completed
Study Start Date
October 2010 (undefined)
Primary Completion Date
October 2012 (Actual)
Study Completion Date
October 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)

4. Oversight

5. Study Description

Brief Summary
The purpose of this study is to evaluate the possibility that giving an increased dose of flu vaccine to children 6 through 35 months of age will improve protection against influenza without increasing side effects. Investigators will evaluate the body's response to the vaccine. Male and female participants' ages 6-35 months, who have never received flu vaccine, and those ages 12-35 months, who have been previously vaccinated, will participate in the study for about 7 months. Vaccine naïve study participants will receive two doses of flu vaccine, either the 0.25 mL dose (Group 1) or 0.5 mL dose (Group 2). Previously vaccinated subjects will receive one dose of flu vaccine, either the 0.25 mL dose (Group 1) or 0.5 mL dose (Group 2). Study procedures include physical examination, memory aids, blood sampling and a follow-up phone call about 6 months after the last vaccine dose.
Detailed Description
Influenza is an important cause of morbidity and mortality among both children and adults. Influenza A and/or B viruses cause yearly epidemics in the United States with an average of 36,000 deaths and 114,000 hospitalizations annually. Children have the highest rates of infection. Influenza is also associated with substantial numbers of hospitalizations among young infants. Because of the limited data available and the variability of reported seroresponses to doses of 0.25 ml in children 6-35 months of age, investigators hypothesize that a higher dose will be more consistently immunogenic. In addition, since currently licensed trivalent inactivated influenza (TIV) vaccines are well tolerated with minimal systemic and local adverse events, investigators hypothesize that administering a higher dose of 0.5 ml to this age group will be well-tolerated. Therefore, investigators propose to compare the safety and immunogenicity of 0.25 ml doses of TIV to that of 0.5 ml doses of TIV when administered to children 6-35 months of age. The proposed study is a phase I, two-arm, 1:2 randomized, double-blinded trial comparing the safety and immunogenicity of increased dose(s) (0.5 ml) with standard dose (0.25 ml) of TIV in children 6-35 months of age with and without a history of previous TIV vaccination. The population will include a Naïve Cohort: 270 healthy male and female children who are 6-35 months of age and have never received an influenza vaccination; and a Fully Primed Cohort: 60 healthy male and female children who are 12-35 months of age and have received two doses of 2009-2010 H1N1 and two doses of TIV at anytime in the past as defined for purposes of this study. Either a standard pediatric dose (0.25 ml) or a larger dose (0.5 ml) of TIV will be administered intramuscularly in the anterolateral thigh with a 25 gauge 1" needle. The primary objective is to evaluate the safety of administering an increased dose(s) (0.5 ml) of TIV to children 6-35 months of age as compared to standard dose(s) (0.25 ml) of TIV. The secondary objective is to compare the humoral immune responses to TIV antigens in children 6-35 months of age who receive the increased dose(s) of TIV to those who receive the standard dose(s) of TIV.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Influenza
Keywords
influenza, pediatric, vaccine

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
243 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Group 2, 0.5 mL TIV
Arm Type
Experimental
Arm Description
Naive cohort participants (n=180) receive 0.25 mLTrivalent Inactivated Vaccine (TIV) in two intramuscular doses 28-42 days apart. Fully Primed cohort participants (previously vaccinated) (n=40) will receive 0.5 mL Trivalent Inactivated Influenza Vaccine (TIV) in one intramuscular dose.
Arm Title
Group 1, 0.25 mL TIV
Arm Type
Active Comparator
Arm Description
Naive cohort participants (n=90) receive 0.25 mLTrivalent Inactivated Vaccine (TIV) in two intramuscular doses 28-42 days apart. Fully Primed cohort participants (previously vaccinated) (n=20) will receive 0.25 mL Trivalent Inactivated Influenza Vaccine (TIV) in one intramuscular dose
Intervention Type
Biological
Intervention Name(s)
Trivalent Inactivated Influenza Vaccine
Intervention Description
Either a standard pediatric dose (0.25 ml) or a larger dose (0.5 ml) of Trivalent Inactivated Influenza Vaccine (TIV) (Fluzone®) administered intramuscularly (IM) in the thigh with a 25 gauge 1 inch needle. Naive cohort (enrolled over two influenza seasons (2010-11 and 2011-12)) will receive vaccine in two IM doses 28-42 days apart, Fully Primed cohort (enrolled in one influenza season (2010-11)) will receive vaccine in one IM dose.
Primary Outcome Measure Information:
Title
Incidence of local and systemic side effects in children receiving the standard dose (0.25ml) or increased dose (0.5 ml) of Trivalent Inactivated Influenza Vaccine.
Time Frame
In the week after each vaccination.
Title
Incidence of adverse events in children receiving the standard dose (0.25ml) or increased dose (0.5 ml) of Trivalent Inactivated Influenza Vaccine (TIV).
Time Frame
In the 4 weeks after each vaccination.
Secondary Outcome Measure Information:
Title
Percent of children who develop hemagglutinin inhibition (HAI) antibody titers greater than or equal to 1:40 (presumed protective titers) and the percent with 4-fold rises.
Time Frame
Approximately 30 days after one or two standard (0.25 ml) or increased (0.5 ml) doses of Trivalent Inactivated Influenza Vaccine (TIV) in fully primed and naive children.
Title
Geometric mean titer (GMT) of the hemagglutinin inhibition (HAI) antibody responses to each of the components of the Trivalent Inactivated Influenza Vaccine (TIV).
Time Frame
Approximately 30 days after one or two standard (0.25 ml) or increased (0.5 ml) doses of Trivalent Inactivated Influenza Vaccine in fully primed and naïve children.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
6 Months
Maximum Age & Unit of Time
35 Months
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: All Subjects Healthy children 6-35 months of age (naïve cohort) or 12-35 months of age (fully primed cohort) Free of obvious health problems as established by medical history and clinical examination before entering the study Parent/legal guardian willing and capable of signing written informed consent Parent/legal guardian expected to be available for entire study Parent/legal guardian can be reached by telephone Fully Primed Cohort -Have received two doses of 2009-2010 H1N1 and two doses of trivalent inactivated influenza vaccine (TIV) at anytime in the past as defined for the purpose of this study. Exclusion Criteria: All Subjects: Have known allergy to eggs or other components of the vaccine. *Refer to the Fluzone package insert for a list of vaccine components. Known or suspected latex allergy. Former premature infants (<32 weeks). History of bronchodilator use more than 2 times per week within 28 days of vaccination. Significant underlying chronic illness (e.g., congenital heart disease, bronchopulmonary dysplasia). Immunodeficiency disease or use of immunosuppressive therapy by the participant, including perinatal exposure to or infection with human immunodeficiency virus (HIV), or known infection with hepatitis B or hepatitis C. Any other condition that, in the clinical judgment of the investigator, may interfere with vaccine evaluation. Children receiving antibiotics are eligible for enrollment. Have long term use of glucocorticoids including oral, parenteral or high-dose inhaled steroids (>800 mcg/day of beclomethasone dipropionate or equivalent) within the preceding 6 months. (Nasal and topical steroids are allowed.) Previous, exposure to an investigational drug or investigational vaccine within 28 days prior to vaccination in this trial. Plans for participation in another clinical trial with an investigational drug or investigational vaccine for the duration of this study. History of Guillain-Barré syndrome or any other neuromuscular disease. History of seizures (including febrile seizures). Naïve Cohort: Any prior influenza vaccination. History of documented laboratory-confirmed influenza infection. Fully primed Cohort: Have not received two doses of 2009-2010 H1N1 and two doses of trivalent inactivated influenza vaccine (TIV) at anytime in the past as defined for the purpose of this study. Allergic response to prior receipt of influenza vaccine. Criteria for temporarily delaying vaccine administration for both groups: The following conditions are temporary or self-limiting and a subject may be included in the study once the condition(s) has/have resolved, provided that the subject is otherwise eligible: Receipt of blood products in the previous 90 days Fever (axillary temperature > 100.0 degrees Fahrenheit/37.8 degrees Celsius), or an acute illness within 48 hours of enrollment. Receipt of any live vaccines within four weeks or any inactivated vaccines within two weeks of study vaccination.
Facility Information:
Facility Name
Emory Children's Center - Pediatric Infectious Diseases
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322-1014
Country
United States
Facility Name
Emory University School of Medicine - Emory Children's Center - Pediatric Infectious Diseases
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Facility Name
University of Iowa - Infectious Disease Clinic
City
Iowa City
State/Province
Iowa
ZIP/Postal Code
52242-1009
Country
United States
Facility Name
University of Maryland School of Medicine - Center for Vaccine Development - Baltimore
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21201-1509
Country
United States
Facility Name
Saint Louis University - Center for Vaccine Development
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63104-1015
Country
United States
Facility Name
Cincinnati Children's Hospital Medical Center - Infectious Diseases
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45231
Country
United States
Facility Name
Vanderbilt University - Pediatric - Infectious Diseases
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232
Country
United States

12. IPD Sharing Statement

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Comparison of Flu Vaccine Doses in Children

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