Influenza Vaccine Dose-Response in Infants and Toddlers: Immunogenicity and Reactogenicity

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00710866

Acronym

TITRE

Enrollment

262

Registered

2008-07-08

Start date

2008-08-31

Completion date

2009-03-31

Last updated

2011-08-04

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Influenza

Keywords

Influenza Vaccines, Infant, Dose-Response Relationship, Immunologic

Brief summary

The purpose of this study is to compare the antibody response and reaction rates in children age 6-23 months when they are given either the currently recommended schedule of two 0.25ml doses of influenza vaccine one month apart or two 0.5ml doses of influenza vaccine, one month apart.

Interventions

BIOLOGICALInactivated Influenza Vaccine Trivalent Types A and B (Split Virion)

Arm 1 (experimental group) received two spaced injections of the 0.5 mL (full) dose while arm 2 (comparison group) received the currently recommended two spaced injections of 0.25mL (half) dose of trivalent inactivated split virion influenza vaccine (VAXIGRIP®) manufactured by Sanofi Pasteur, Lyon, France.

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

PREVENTION

Masking

TRIPLE (Subject, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender

ALL

Age

6 Months to 23 Months

Healthy volunteers

Yes

Inclusion criteria

* Child healthy (stable chronic conditions acceptable) as established by health assessment interview and verbal history-directed health examination * Child between and including 6 months of age and 23 months of age (up to and including the day before 24 months of age) * Child is available and can complete all relevant procedures during the entire study period * Parent or legal guardian is available and can be reached by phone during the entire study period * Parent/guardian provides written informed consent * Parent/guardian is fluent in English

Exclusion criteria

* Child has history of laboratory-confirmed influenza * Child has history of any prior influenza immunization * Child has history of anaphylactic reaction to any component of the vaccine (i.e. egg) * Child has received immune globulin or other blood products within the prior six weeks * Child has received injected or oral steroids within the prior six weeks (inhaled or topical steroids allowed) * Child has a bleeding diathesis or condition associated with prolonged bleeding time that would contraindicate intramuscular injection (thrombocytopenia, coagulation disorder, anti-coagulant therapy) * Child is or will be enrolled in any other clinical trial of a drug, vaccine or medical device during the study period * Child is scheduled to receive a live vaccine (notably measles, mumps, rubella or varicella vaccines) during the study period * Child has a health condition which, in the opinion of the investigator, would interfere with the evaluation or pose a health risk to the child

Design outcomes

Primary

Measure	Time frame	Description
Seroprotection Rate Infants (6-11 Months)-A/Brisbane/59/07(H1N1)	27-46 days after the second dose	Seroprotection rate: HI titers =\>40
Seroprotection Rate Toddlers(12-23 Months)-A/Brisbane/59/07(H1N1)	27-46 days after the second dose	Seroprotection rate: HI titers =\>40
Seroprotection Rate Infants(6-11 Months)-A/Brisbane/10/07(H3N2)	27-46 days after the second dose	Seroprotection rate: HI titers =\>40
Seroprotection Rate Toddlers(12-23 Months)-A/Brisbane/10/07(H3N2)	27-46 days after the second dose	Seroprotection rate: HI titers =\>40
Seroprotection Rate Infants (6-11 Months)-B/Florida/4/06(Yamagata)	27-46 days after the second dose	—
Seroprotection Rate Toddlers (12-23 Months)-B/Florida/4/06(Yamagata)	27-46 days after the second dose	Seroprotection rate: HI titers =\>40
Adverse Events: Fever After Either Dose - Infants 6-11 Months	3 days after immunization	Fever defined as temperature \>= 38 C
Adverse Events: Fever After Either Dose - Toddlers(12-23 Months)-	3 days after immunization	Fever defined as temperature \>= 38 C

Countries

Canada

Participant flow

Participants by arm

Arm	Count
0.5mL VAXIGRIP® 2 doses 0.5mL VAXIGRIP® at months 0, 1	124
0.25mL VAXIGRIP® 2 doses 0.25mL VAXIGRIP® at months 0, 1	128
Total	252

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Failed to meet eligibility	1	1
Overall Study	Lost to Follow-up	1	0
Overall Study	Protocol Violation	5	4
Overall Study	Withdrawal by Subject	2	1

Baseline characteristics

Characteristic	0.25mL VAXIGRIP®	0.5mL VAXIGRIP®	Total
Age, Categorical <=18 years	128 Participants	124 Participants	252 Participants
Age, Categorical >=65 years	0 Participants	0 Participants	0 Participants
Age, Categorical Between 18 and 65 years	0 Participants	0 Participants	0 Participants
Age Continuous	1.1 years STANDARD_DEVIATION 0.4	1.1 years STANDARD_DEVIATION 0.4	1.1 years STANDARD_DEVIATION 0.4
Region of Enrollment Canada	128 participants	124 participants	252 participants
Sex: Female, Male Female	71 Participants	63 Participants	134 Participants
Sex: Female, Male Male	57 Participants	61 Participants	118 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	— / —	— / —
other Total, other adverse events	108 / 124	107 / 126
serious Total, serious adverse events	0 / 124	1 / 128

Outcome results

Primary

Adverse Events: Fever After Either Dose - Infants 6-11 Months

Fever defined as temperature \>= 38 C

Time frame: 3 days after immunization

Population: Per Protocol

Arm	Measure	Value (NUMBER)
0.5mL VAXIGRIP®	Adverse Events: Fever After Either Dose - Infants 6-11 Months	1 participants
0.25mL VAXIGRIP®	Adverse Events: Fever After Either Dose - Infants 6-11 Months	7 participants

Primary

Adverse Events: Fever After Either Dose - Toddlers(12-23 Months)-

Fever defined as temperature \>= 38 C

Time frame: 3 days after immunization

Population: Per Protocol

Arm	Measure	Value (NUMBER)
0.5mL VAXIGRIP®	Adverse Events: Fever After Either Dose - Toddlers(12-23 Months)-	6 participants
0.25mL VAXIGRIP®	Adverse Events: Fever After Either Dose - Toddlers(12-23 Months)-	9 participants

Primary