Clinical Study in Children, 6 Months to 3 Years of Age, to Assess Two Dose Levels of an Experimental Flu Vaccine, Using a Licensed Influenza Virus Vaccine, Vaxigrip® as the Control

Phase 2

Completed

Conditions: Influenza

Interventions: Biological: Vaxigrip
Biological: GSK Biologicals' influenza vaccine GSK1557482A

Registration Number: NCT00778895

Lead Sponsor: GlaxoSmithKline

Brief Summary: Children younger than 5 years of age are at high risk for severe influenza disease (flu) and hospitalization due to flu. Scientists are in the process of re-evaluating the dosing initially based on whole virus vaccines to improve their efficacy in infants. In this study, we will compare two different dose levels of GSK1557482A flu vaccine. Another already approved flu vaccine made by a different company will be used as a control.

Detailed Description: This is a study of two different dose levels of a new formulation of flu vaccine for the 2008/2009 flu season using the World Health Organization recommended virus strains. Subjects will be randomly put into one of three different groups to receive either one or two doses of:

0.25 mL dose of the new flu vaccine, or 0.5 mL dose of the new flu vaccine or the licensed Vaxigrip flu vaccine (control) The parents of the subjects and the study doctor and nurses will not know the group of their child until the study is completed.

The children will be vaccinated with either one dose or two doses depending on whether or not they have received a flu vaccine before. The doctor will decide on the schedule for each child based on the information provided by the parents. The active phase of the study will last approximately two months for children receiving two doses and one month for those receiving a single dose. An extended safety follow-up will continue until Study Month 6.

Two blood samples will be taken from each subject. These will be used to evaluate how well the vaccine works in the children and which dose level works best compared to the control.

The parents will fill in a diary card for four days to record any reactions or symptoms which may occur after vaccination. Parents will also keep a record of other symptoms that may occur between vaccinations and up to six months after the first vaccination and will keep a record of any medication their child takes in this time period.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 390

Inclusion Criteria

A male or female child 6 months to < 3 years of age at the time of the vaccination, regardless of previous administration of influenza vaccine in a previous season;
Subjects must be in good health established by medical history and physical examination before entering into the study;
Subjects having a parent/guardian who the investigator believes can and will comply with the requirements of the protocol should be enrolled in the study;
Written informed consent obtained from the subject's parent/guardian.
Parents/guardian access to a consistent means of telephone contact, land line or mobile

Exclusion Criteria

Use of any investigational or non-registered product (drug or vaccine) within 30 days preceding the administration of the study vaccine or planned use during the study period. Routine, registered childhood vaccinations are not an exclusion criterion;
History of hypersensitivity to any vaccine;
History of allergy to or reactions likely to be exacerbated by, any component of the vaccine including egg, chicken protein, formaldehyde, or sodium deoxycholate;
History of any congenital, acquired, or iatrogenic immunodeficiency state (current or potential) including HIV infection, disorders of the lymphoid system or bone marrow, or chronic administration (defined as more than 14 consecutive days) of immunosuppressant or other immune-modifying drugs within 3 months prior to the administration of the study vaccine.
Acute disease at the time of enrolment.
History of Guillain Barré syndrome within 6 weeks of receipt of prior inactivated influenza virus vaccine;
Any significant disorder of blood coagulation or treatment with vitamin K antagonists; or any known disorder of hemostasis;
Receipt of any immunoglobulins and/or any blood products within three months of study enrollment or planned administration of any of these products during the study period.
Receipt of a non-study related influenza vaccine outside of this study and during the current (2008-09) influenza immunization campaign.
Any use of analgesics/antipyretics 12 hours before receipt of vaccine.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Vaxigrip Group	Vaxigrip	Subjects 6 months to 3 years of age received if primed, 1 dose of Vaxigrip vaccine at Day 0 and if unprimed, 2 doses of Vaxigrip vaccine at Day 0 and approximately Day 28. The vaccine was administered intramuscularly in the anterolateral part of the thigh (if the subject was less than 12 months) or in the deltoid region of the arm.
Fluviral F2 Group	GSK Biologicals' influenza vaccine GSK1557482A	Subjects 6 months to 3 years of age received if primed, 1 dose of formulation 2 of Fluviral vaccine at Day 0 and if unprimed, 2 doses of formulation 1 of Fluviral vaccine at Day 0 and approximately Day 28. The vaccine was administered intramuscularly in the anterolateral part of the thigh (if the subject was less than 12 months) or in the deltoid region of the arm.
Fluviral F1 Group	GSK Biologicals' influenza vaccine GSK1557482A	Subjects 6 months to 3 years of age received if primed, 1 dose of formulation 1 of Fluviral vaccine at Day 0 and if unprimed, 2 doses of formulation 1 of Fluviral vaccine at Day 0 and approximately Day 28. The vaccine was administered intramuscularly in the anterolateral part of the thigh (if the subject was less than 12 months) or in the deltoid region of the arm.

Primary Outcome Measures

Name	Time	Method
Number of Subjects With Any and Grade 3 Solicited Local Symptoms After Vaccination	During the 4-day follow-up period (Days 0-3) after any vaccination	Solicited local symptoms assessed were pain, redness and swelling. Any was defined as any solicited local symptom reported regardless of intensity grade. Grade 3 pain = Cried when limb was moved/spontaneously painful. Grade 3 redness and swelling were defined as redness/swelling above 50 millimeters (mm). This primary outcome measure was assessed for Fluviral F1 Group and Fluviral F2 Group respectively as per the study protocol.
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms After Vaccination	During the 4-day follow-up period (Days 0-3) after any vaccination	Symptoms assessed were drowsiness, irritability, loss of appetite and fever. Any was defined as occurrence of any general symptom regardless of their intensity grade or relationship to vaccination. Any fever = Axillary temperature ≥ 38.0 degrees Celsius (°C). Grade 3 fever = Axillary temperature ≥ 39.0°C. For other symptoms, grade 3 was defined as an adverse event which prevented normal everyday activities. Related = A general symptom assessed by the investigator as causally related to vaccination. This primary outcome measure was assessed for Fluviral F1 Group and Fluviral F2 Group respectively as per the study protocol.
Number of Subjects With Any, Grade 3 and Related Unsolicited Adverse Events (AEs) After Vaccination	During the 28-day follow-up period (Days 0-27) after vaccination	Unsolicited AEs covers any AE reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms. Any = Occurrence of any unsolicited symptom regardless of intensity grade or relation to vaccination. Grade 3 = Occurrence of any unsolicited AE that prevented normal, everyday activities. Related = Occurrence of an unsolicited AE assessed by the investigator to be causally related to study vaccination. This primary outcome measure was assessed for Fluviral F1 Group and Fluviral F2 Group respectively as per the study protocol.
Number of Subjects With Any and Related Serious Adverse Events (SAEs) After Vaccination	During the 6-month safety follow up after vaccination	SAEs assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization, result in disability/incapacity or are a congenital anomaly/birth defect in the offspring of a study subject. Any SAE(s) = Occurrence of any SAE(s) regardless of intensity grade or relation to vaccination. Related SAE(s) = Occurrence of any SAE(s) assessed by the investigator as causally related to vaccination. This primary outcome measure was assessed for Fluviral F1 Group and Fluviral F2 Group respectively as per the study protocol.
Number of Subjects With Any, Grade 3 and Related Medically-attended Adverse Events (MAEs) After Vaccination	During the 6-month safety follow up after vaccination	MAEs were defined as events for which the subject received medical attention defined as hospitalization, an emergency room visit, or a visit to or from medical personnel (medical doctor) for any reason. Any MAE(s) = Occurrence of any MAE(s) regardless of intensity grade or relation to vaccination. Analysis of intensity and relationship to vaccination of MAEs was not performed. This primary outcome measure was assessed for Fluviral F1 Group and Fluviral F2 Group respectively as per the study protocol.

Secondary Outcome Measures

Name	Time	Method
Number of Subjects With Any and Grade 3 Solicited Local Symptoms After Vaccination	During the 4-day follow-up period (Days 0-3) after any vaccination	Solicited local symptoms assessed were pain, redness and swelling. Any was defined as any solicited local symptom reported regardless of intensity grade. Grade 3 pain = Cried when limb was moved/spontaneously painful. Grade 3 redness and swelling were defined as redness/swelling above 50 millimeters (mm). This secondary outcome measure was assessed for the Vaxigrip Group as per the study protocol.
Number of Subjects With Any and Related Serious Adverse Events (SAEs) After Vaccination	During the 6-month safety follow up after vaccination	SAEs assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization, result in disability/incapacity or are a congenital anomaly/birth defect in the offspring of a study subject. Any SAE(s) = Occurrence of any SAE(s) regardless of intensity grade or relation to vaccination. Related SAE(s) = Occurrence of any SAE(s) assessed by the investigator as causally related to vaccination. This secondary outcome measure was assessed for the Vaxigrip Group as per the study protocol.
Number of Subjects Seroprotected Against HI Antibodies	At Day 0 [PRE] and at Day 28 (for primed subjects) and at Day 56 (for unprimed subjects) [POST]	A seroprotected subject was defined as a vaccinated subject with serum HI titer ≥ 1:40. The flu strains assessed were the A/Brisbane (H1N1), A/Uruguay (H3N2) and B/Florida.
Number of Subjects With Any, Grade 3 and Related Unsolicited Adverse Events (AEs) After Vaccination	During the 28-day follow-up period (Days 0-27) after vaccination	Unsolicited AEs covers any AE reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms. Any = Occurrence of any unsolicited symptom regardless of intensity grade or relation to vaccination. Grade 3 = Occurrence of any unsolicited AE that prevented normal, everyday activities. Related = Occurrence of an unsolicited AE assessed by the investigator to be causally related to study vaccination. This secondary outcome measure was assessed for the Vaxigrip Group as per the study protocol.
Number of Subjects Seroconverted to HI Antibodies	At Day 28 (for primed subjects) and at Day 56 (for unprimed subjects) [POST]	A seroconverted subject was defined as a vaccinated subject who had either a pre-vaccination titer \< 1:10 and a post-vaccination titer ≥1:40, or a pre-vaccination titer ≥1:10 and at least a four-fold increase in post-vaccination titer. The flu strains assessed were the A/Brisbane (H1N1), A/Uruguay (H3N2) and B/Florida.
Seroconversion Factor for HI Antibodies	At Day 28 (for primed subjects) and at Day 56 (for unprimed subjects) [POST]	The seroconversion factor (SCF) was defined as the fold increase in serum HI geometric mean titers (GMTs) post-vaccination (at Day 28 for primed subjects and at Day 56 for unprimed subjects) compared to pre-vaccination (Day 0). The flu strains assessed were the A/Brisbane (H1N1), A/Uruguay (H3N2) and B/Florida.
Number of Subjects With Any, Grade 3 and Related Medically-attended Adverse Events (MAEs) After Vaccination	During the 6-month safety follow up after vaccination	MAEs were defined as events for which the subject received medical attention defined as hospitalization, an emergency room visit, or a visit to or from medical personnel (medical doctor) for any reason. Any MAE(s) = Occurrence of any MAE(s) regardless of intensity grade or relation to vaccination. Analysis of intensity and relationship to vaccination of MAEs was not performed. This secondary outcome measure was assessed for the Vaxigrip Group as per the study protocol.
Titers for Serum Hemagglutination Inhibition (HI) Antibodies	At Day 0 [PRE] and at Day 28 (for primed subjects) and Day 56 (for unprimed subjects) [POST]	Titers are presented as geometric mean titers (GMTs). The reference cut-off value was the seropositivity cut-off of 1:10. Antibodies assessed were antibodies against the A/Brisbane (H1N1), A/Uruguay (H3N2) and B/Florida flu strains.
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms After Vaccination	During the 4-day follow-up period (Days 0-3) after any vaccination	Symptoms assessed were drowsiness, irritability, loss of appetite and fever. Any was defined as occurrence of any general symptom regardless of their intensity grade or relationship to vaccination. Any fever = Axillary temperature ≥ 38.0 degrees Celsius (°C). Grade 3 fever = Axillary temperature ≥ 39.0°C. For other symptoms, grade 3 was defined as an adverse event which prevented normal everyday activities. Related = A general symptom assessed by the investigator as causally related to vaccination. This secondary outcome measure was assessed for the Vaxigrip Group as per the study protocol.