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Effect of Age and Prior Immunity to Response to Seasonal Influenza Vaccines in Children

Primary Purpose

Influenza

Status

Completed

Phase

Phase 4

Locations

United States

Study Type

Interventional

Intervention

Live attenuated Influenza vaccine

Trivalent Influenza Vaccine

TIV followed by LAIV

LAIV followed by TIV

About this trial

This is an interventional treatment trial for Influenza focused on measuring Influenza, A/California/7/2009-like (2009 H1N1), A/Perth/16/2009-like (H3N2), B/Brisbane/60/2008-like (B/Victoria lineage)

Eligibility Criteria

2 Years - 9 Years (Child)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

Aged between 2 and 9 years, inclusive.
No prior history of laboratory documented infection with novel H1N1 virus
The subject must be in good health, as determined by: vital signs (heart rate <140 bpm; blood pressure: systolic ≥ 90 mm Hg and ≤140 mm Hg; diastolic ≤ 90 mm Hg; oral temperature <100.0ºF (fahrenheit); medical history; and targeted physical examination, when necessary, based on medical history. Stable medical condition is defined as: no recent increase in prescription medication, dose, or frequency of medication in the last 3 months and health outcomes of the specific disease are considered to be within acceptable limits in the last 6 months.
The subject/parents are able to understand and comply with the planned study procedures, including being available for all study visits.
The subject/parents have provided informed consent prior to any study procedures. (An assent will be obtained for all children as required by the institutional IRB (Institutional Review Board.)

Exclusion Criteria:

Subjects with a laboratory documented history of previous novel H1N1 infection.
History of egg allergy or allergy to other components of vaccine.
History of wheezing.
The subject is immunosuppressed as a result of an underlying illness or treatment with immunosuppressive or cytotoxic drugs, or use of anticancer chemotherapy or radiation therapy.
The subject has an active neoplastic disease.
The subject has long-term (greater than 2 weeks) use of oral or parenteral steroids, or high-dose inhaled steroids (>800 mg/day of beclomethasone dipropionate or equivalent) within the preceding 6 months (nasal and topical steroids are allowed).
The subject received immunoglobulin or another blood product within the 3 months prior to enrollment in this study.
The subject has received an inactivated vaccine within the 2 weeks or a live vaccine within the 4 weeks prior to enrollment in this study or plans to receive another vaccine within the next 28 days (or 56 days for vaccine naïve recipients).
The subject has an acute or chronic medical condition that, in the opinion of the investigator, would render vaccination unsafe or would interfere with the evaluation of responses. These conditions include chronic conditions recognized as risk factors for influenza complications or as contraindications for live vaccination, including chronic cardiac (exclusive of hypertension) or pulmonary conditions (including asthma), diabetes mellitus, or renal impairment.
The subject has an acute illness or an oral temperature greater than 99.9 degreesF (37.7 degrees C) within 3 days prior to enrollment or vaccination. Subjects who had an acute illness that was treated symptoms resolved are eligible to enroll as long as treatment is completed and symptoms resolve > 3 days prior to enrollment.
The subject is currently participating or plans to participate in a study that involves an experimental agent (vaccine, drug, biologic, device, blood product, or medication) or has received an experimental agent within 1 month prior to enrollment in this study, or expects to receive another experimental agent during participation in this study, or intends to donate blood during the study period.
The subject has any condition that would, in the opinion of the site investigator, place the subject at an unacceptable risk of injury or render the subject unable to meet the requirements of the protocol.
The subject has a known human immunodeficiency virus, hepatitis B, or hepatitis C infection.
The subject has a previous history of Guillain-Barré syndrome within 6 weeks of receipt of influenza vaccination.
The subject has any condition that the principal investigator (PI) believes may interfere with successful completion of the study.

Sites / Locations

Dartmouth-Hitchcock Medical Center
Vaccine Research Unit Room 3-5000

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Active Comparator

Arm Label

Live Attenuated Influenza vaccine

Trivalent Influenza Vaccine 2010-2011

TIV followed by LAIV

LAIV followed by TIV

Arm Description

LAIV 0.2 ml will be given intranasally followed by LAIV 0.2 mg given intranasally 28 days later

TIV will be given in a dose of .25mg 2 years to 36 months of age or .5 ml ages 37 months to 8 years intramuscularly followed by a second dose of .25mg 2 years to 36 months of age or .5 ml ages 37 months to 9 years intramuscularly 28 days later

TIV will be given in a dose of .25mg 2 years to 36 months of age or .5 ml ages 37 months to 9 years intramuscularly followed by LAIV given in a dose of .2 ml intranasally 28 days later

LAIV will be given in a dose of .2 ml intranasally followed by a dose of TIV given in a dose of .25 ml 2 years to 36 months or .5 ml 37 months to 9 years intramuscularly 28 days later

Outcomes

Primary Outcome Measures

Number of Subjects Shedding Vaccine Virus of Each Subtype by PCR

Nasal washes were collected on days 2, 4 and 7 after vaccination. Nasal swab specimens were tested for the presence of vaccine viruses by quantitative viral culture in MDCK cells at 33º C and by real-time quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR) amplification. The limit of detection of vaccine viruses was 10^0.6 tissue culture infectious doses (50%)/ml for virus culture and 10^0.4 tissue culture infectious doses (50%)/ml for qRT-PCR.

Secondary Outcome Measures

Mean Peak H1N1 Virus Titer, Dose 1

After the first dose of vaccine, the virus titer from nasal secretions was measured in tissue culture on days 2, 4 and 7 and the highest titer from one of those three time points was reported.

Mean Peak H3N2 Virus Titer, Dose 1

After the first dose of vaccine, the virus titer from nasal secretions was measured in tissue culture on days 2, 4 and 7 and the highest titer from one of those three time points was reported.

Mean Peak Influenza B Virus Titer, Dose 1

After the first dose of vaccine, the virus titer from nasal secretions was measured in tissue culture on days 2, 4 and 7 and the highest titer from one of those three time points was reported.

Mean Peak H1N1 Virus Titer, Dose 2

After the second dose of vaccine, the virus titer from nasal secretions was measured in tissue culture on days 2, 4 and 7 and the highest titer from one of those three time points was reported.

Mean Peak H3N2 Virus Titer, Dose 2

After the second dose of vaccine, the virus titer from nasal secretions was measured in tissue culture on days 2, 4 and 7 and the highest titer from one of those three time points was reported.

Mean Peak Influenza B Virus Titer, Dose 2

After the second dose of vaccine, the virus titer from nasal secretions was measured in tissue culture on days 2, 4 and 7 and the highest titer from one of those three time points was reported.

Full Information

NCT ID

NCT01246999

First Posted

November 22, 2010

Last Updated

November 10, 2016

Sponsor

University of Rochester

Collaborators

National Institutes of Health (NIH), Dartmouth-Hitchcock Medical Center

1. Study Identification

Unique Protocol Identification Number

NCT01246999

Brief Title

Effect of Age and Prior Immunity to Response to Seasonal Influenza Vaccines in Children

Official Title

Evaluation of the Effect of Age and Prior Immunity on the Response to Live or Inactivated Seasonal (A/California/7/2009-like, A/Perth/16/2009-like, and B/Brisbane/60/2008-like (B/Victoria Lineage) Influenza Vaccines in Children

Study Type

Interventional

2. Study Status

Record Verification Date

November 2016

Overall Recruitment Status

Completed

Study Start Date

October 2010 (undefined)

Primary Completion Date

January 2013 (Actual)

Study Completion Date

June 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

University of Rochester

Collaborators

National Institutes of Health (NIH), Dartmouth-Hitchcock Medical Center

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

A total of 88 children between 2 and 9 years of age will be randomized to receive a two dose schedule of either licensed live attenuated trivalent seasonal influenza vaccine (LAIV) or licensed inactivated seasonal influenza vaccine (TIV)or TIV followed by LAIV or LAIV followed by TIV separated by 28 days. Children with a laboratory documented history of prior H1N1 infection will be excluded.

Detailed Description

The study will be conducted as a randomized, prospective, open-label evaluation of the clinical tolerability, vaccine virus shedding, and serum and mucosal antibody response to vaccination with either live trivalent influenza vaccine (LAIV) or trivalent influenza vaccine (TIV) in healthy children between the ages of 2 and 9 years. Children will be screened for antibody to A/Brisbane/57/07 (H1N1) and A/California/07/09 (H1N1), A/Perth/16/2009 (H3N2) and B/Brisbane/60/2008 before and at indicated times after the start of the study. They will not be randomized based on antibody levels. Children with prior documented infection with the 2009 pandemic H1N1 virus will be excluded. Vaccine will be administered on days 0 and 28. Safety of vaccination will be assessed using symptoms collected by parents for 7 days after each dose of vaccine. Serum will be obtained prior to and on day 28 following each dose of vaccine and assessed for antibody by HAI, ELISA, and neutralization techniques. Nasal secretions will be obtained by nasal wick prior to and on day 28 after each dose and assessed for HA-specific IgA (immune globulin A) and IgG (immune globulin G)antibody by ELISA. Nasal swabs will be obtained on days 2, 4, and 7 after each dose of live vaccine and assessed for the presence and magnitude of vaccine virus shedding of the live attenuated vaccine by rtRT-PCR (real-time reverse transcriptase polymerase chain reaction)and TCID50 (50% tissue culture infectious doses)on MDCK(Madin Darby Canine Kidney) cells.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Influenza

Keywords

Influenza, A/California/7/2009-like (2009 H1N1), A/Perth/16/2009-like (H3N2), B/Brisbane/60/2008-like (B/Victoria lineage)

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 4

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

34 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Live Attenuated Influenza vaccine

Arm Type

Active Comparator

Arm Description

LAIV 0.2 ml will be given intranasally followed by LAIV 0.2 mg given intranasally 28 days later

Arm Title

Trivalent Influenza Vaccine 2010-2011

Arm Type

Active Comparator

Arm Description

Arm Title

TIV followed by LAIV

Arm Type

Active Comparator

Arm Description

TIV will be given in a dose of .25mg 2 years to 36 months of age or .5 ml ages 37 months to 9 years intramuscularly followed by LAIV given in a dose of .2 ml intranasally 28 days later

Arm Title

LAIV followed by TIV

Arm Type

Active Comparator

Arm Description

LAIV will be given in a dose of .2 ml intranasally followed by a dose of TIV given in a dose of .25 ml 2 years to 36 months or .5 ml 37 months to 9 years intramuscularly 28 days later

Intervention Type

Biological

Intervention Name(s)

Live attenuated Influenza vaccine

Other Intervention Name(s)

FluMist

Intervention Description

0.2 mL dose delivered through nasal spray, 0.1 ml in each nostril, 2 doses separated by 28 days

Intervention Type

Biological

Intervention Name(s)

Trivalent Influenza Vaccine

Other Intervention Name(s)

Seasonal Influenza Vaccine

Intervention Description

.25 mL given intramuscularly to children 24 to 36 months of age, 2 doses given 28 days apart, .5 mL given intramuscularly to children 37 months to 9 years of age, 2 doses given 28 day s apart.

Intervention Type

Biological

Intervention Name(s)

TIV followed by LAIV

Other Intervention Name(s)

Seasonal Influenza Vaccines

Intervention Description

TIV .25 mL given intramuscularly to children 24 to 36 months of age or .5 mL given intramuscularly to children 37 months to 9 years of age, followed by FluMist 0.2 mL delivered by nasal spray (.1 mL in each nostril)28 days later

Intervention Type

Biological

Intervention Name(s)

LAIV followed by TIV

Other Intervention Name(s)

Seasonal Influenza Vaccines

Intervention Description

LAIV .2 mL given through nasal spray (.1 mL in each nostril) Followed by TIV .25 mL given intramuscularly to children 24 to 25 months of age or .5 mL given intramuscularly to children 36 months to 9 years of age 28 days later

Primary Outcome Measure Information:

Title

Number of Subjects Shedding Vaccine Virus of Each Subtype by PCR

Description

Time Frame

baseline to day 7

Secondary Outcome Measure Information:

Title

Mean Peak H1N1 Virus Titer, Dose 1

Description

After the first dose of vaccine, the virus titer from nasal secretions was measured in tissue culture on days 2, 4 and 7 and the highest titer from one of those three time points was reported.

Time Frame

days 2, 4 and 7

Title

Mean Peak H3N2 Virus Titer, Dose 1

Description

After the first dose of vaccine, the virus titer from nasal secretions was measured in tissue culture on days 2, 4 and 7 and the highest titer from one of those three time points was reported.

Time Frame

days 2, 4 and 7

Title

Mean Peak Influenza B Virus Titer, Dose 1

Description

After the first dose of vaccine, the virus titer from nasal secretions was measured in tissue culture on days 2, 4 and 7 and the highest titer from one of those three time points was reported.

Time Frame

days 2, 4 and 7

Title

Mean Peak H1N1 Virus Titer, Dose 2

Description

After the second dose of vaccine, the virus titer from nasal secretions was measured in tissue culture on days 2, 4 and 7 and the highest titer from one of those three time points was reported.

Time Frame

days 2, 4 and 7

Title

Mean Peak H3N2 Virus Titer, Dose 2

Description

After the second dose of vaccine, the virus titer from nasal secretions was measured in tissue culture on days 2, 4 and 7 and the highest titer from one of those three time points was reported.

Time Frame

days 2, 4 and 7

Title

Mean Peak Influenza B Virus Titer, Dose 2

Description

After the second dose of vaccine, the virus titer from nasal secretions was measured in tissue culture on days 2, 4 and 7 and the highest titer from one of those three time points was reported.

Time Frame

days 2, 4 and 7

10. Eligibility

Sex

All

Minimum Age & Unit of Time

2 Years

Maximum Age & Unit of Time

9 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Aged between 2 and 9 years, inclusive. No prior history of laboratory documented infection with novel H1N1 virus The subject must be in good health, as determined by: vital signs (heart rate <140 bpm; blood pressure: systolic ≥ 90 mm Hg and ≤140 mm Hg; diastolic ≤ 90 mm Hg; oral temperature <100.0ºF (fahrenheit); medical history; and targeted physical examination, when necessary, based on medical history. Stable medical condition is defined as: no recent increase in prescription medication, dose, or frequency of medication in the last 3 months and health outcomes of the specific disease are considered to be within acceptable limits in the last 6 months. The subject/parents are able to understand and comply with the planned study procedures, including being available for all study visits. The subject/parents have provided informed consent prior to any study procedures. (An assent will be obtained for all children as required by the institutional IRB (Institutional Review Board.) Exclusion Criteria: Subjects with a laboratory documented history of previous novel H1N1 infection. History of egg allergy or allergy to other components of vaccine. History of wheezing. The subject is immunosuppressed as a result of an underlying illness or treatment with immunosuppressive or cytotoxic drugs, or use of anticancer chemotherapy or radiation therapy. The subject has an active neoplastic disease. The subject has long-term (greater than 2 weeks) use of oral or parenteral steroids, or high-dose inhaled steroids (>800 mg/day of beclomethasone dipropionate or equivalent) within the preceding 6 months (nasal and topical steroids are allowed). The subject received immunoglobulin or another blood product within the 3 months prior to enrollment in this study. The subject has received an inactivated vaccine within the 2 weeks or a live vaccine within the 4 weeks prior to enrollment in this study or plans to receive another vaccine within the next 28 days (or 56 days for vaccine naïve recipients). The subject has an acute or chronic medical condition that, in the opinion of the investigator, would render vaccination unsafe or would interfere with the evaluation of responses. These conditions include chronic conditions recognized as risk factors for influenza complications or as contraindications for live vaccination, including chronic cardiac (exclusive of hypertension) or pulmonary conditions (including asthma), diabetes mellitus, or renal impairment. The subject has an acute illness or an oral temperature greater than 99.9 degreesF (37.7 degrees C) within 3 days prior to enrollment or vaccination. Subjects who had an acute illness that was treated symptoms resolved are eligible to enroll as long as treatment is completed and symptoms resolve > 3 days prior to enrollment. The subject is currently participating or plans to participate in a study that involves an experimental agent (vaccine, drug, biologic, device, blood product, or medication) or has received an experimental agent within 1 month prior to enrollment in this study, or expects to receive another experimental agent during participation in this study, or intends to donate blood during the study period. The subject has any condition that would, in the opinion of the site investigator, place the subject at an unacceptable risk of injury or render the subject unable to meet the requirements of the protocol. The subject has a known human immunodeficiency virus, hepatitis B, or hepatitis C infection. The subject has a previous history of Guillain-Barré syndrome within 6 weeks of receipt of influenza vaccination. The subject has any condition that the principal investigator (PI) believes may interfere with successful completion of the study.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

John J. Treanor, M.D.

Organizational Affiliation

University of Rochester

Official's Role

Principal Investigator

Facility Information:

Facility Name

Dartmouth-Hitchcock Medical Center

City

Lebanon

State/Province

New Hampshire

ZIP/Postal Code

03756

Country

United States

Facility Name

Vaccine Research Unit Room 3-5000

City

Rochester

State/Province

New York

ZIP/Postal Code

14642

Country

United States

12. IPD Sharing Statement

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Effect of Age and Prior Immunity to Response to Seasonal Influenza Vaccines in Children

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