Influenza, Influenza Vaccines
Conditions
Keywords
immunogenicity, safety, Influenza, children, vaccine
Brief summary
The purpose of this observer-blind study is to evaluate the safety and immunogenicity of GlaxoSmithKline Biologicals' influenza vaccine GSK2584786A in healthy children 6 to 35 months of age.
Interventions
BIOLOGICALGSK Bio's influenza vaccine GSK2584786A, different formulations
Intramuscular injections
BIOLOGICALGSK Bio's influenza vaccine GSK2321138A
Intramuscular injections
BIOLOGICALFluarix™
Intramuscular injections
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
6 Months to 35 Months
Healthy volunteers
Yes
Inclusion criteria
All subjects must satisfy ALL the following criteria at study entry: * Subjects who the investigator believes that parent(s)/Legally Acceptable Representative(s) \[LAR(s)\] can and will comply with the requirements of the protocol * Children, male or female between, and including, 6 and 35 months of age at the time of the first vaccination. * Written informed consent obtained from the parent(s)/LAR(s) of the subject. * Healthy subjects as established by medical history and clinical examination before entering into the study. * Age appropriate scheduled childhood vaccinations completed to the best of parent(s)/LAR(s) knowledge. * Born after gestation period of 36 to 42 weeks inclusive
Exclusion criteria
The following criteria should be checked at the time of study entry. If ANY exclusion criterion applies, the subject must not be included in the study: * Child in care * Use of any investigational or non-registered product other than the study vaccine(s) within 30 days preceding the first dose of study vaccine, or planned use during the study period. * Prior receipt of any influenza vaccination or planned administration during the study period. * Planned administration of any vaccine 30 days prior and 30 days after any study vaccine administration. * Chronic administration of immunosuppressants or other immune-modifying drugs within six months prior to the first vaccine dose. * Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination. * A family history of congenital or hereditary immunodeficiency. * A family history of febrile seizures or/and epilepsy * Any known or suspected allergy to any constituent of influenza or routine paediatric vaccines, a history of severe adverse reaction to any previous vaccination; or a history of anaphylactic-type reaction to any constituent of influenza vaccine. * History of any progressive neurological disorders or seizures. * Acute or chronic, clinically-significant pulmonary, cardiovascular, hepatic or renal functional abnormality, as determined by medical history or physical examination. * Acute disease and/or fever at the time of enrolment: * \- Fever is defined as temperature ≥ 37.5°C on oral, axillary or tympanic setting, or ≥38.0°C on rectal setting. * Subjects with a minor illness without fever might be enrolled at the discretion of the investigator. * Administration of immunoglobulins and/or any blood products within the 3 month preceding the first dose of study vaccine or planned administration during the study period. * Any condition which, in the opinion of the investigator, render the subject unfit for participation in the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Serum Haemagglutination-inhibition (HI) Antibody Titers | at Day 28/ Day 56 | Titers were planned to be expressed as Geometric Mean Titers (GMTs). Analysis was planned to be done for antibodies against all 4 vaccine strains. |
| Serum Neutralizing Antibody Titers | at Day 28/ Day 56 | — |
| Geometric Mean Number of All-CD4 Cytokine Positive Cells | at Day 28/ Day 56 | Geometric mean of the number of CD4 cytokine positive T cells per million T cells. |
| Number of Subjects Reporting Fever of at Least Grade 2 or Higher | Within 7 days (Day 0 to 6) follow-up period after any dose of study vaccine | Grade 2 fever was defined as axillary temperature above 38 degrees Celcius. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects Reporting Adverse Events With Medically Attended Visits | From Day 0 to 179 | A mediaclly attended visit is defined as hospitalisation, an emergency room visit or a visit to or from medical personnel (medical doctor) for any reason. |
| Serum HI Antibody Titers | on Days 0, 28/56 and 180 | Titers were planned to be expressed as Geometric Mean Titers (GMTs). Analysis was planned to be done for antibodies against all 4 vaccine strains. |
| Number of Subjects Reporting Serious Adverse Events | From Day 0 to 179 | 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. |
| Number of Subjects Reporting Potential Immune-mediated Diseases | From Day 0 to 179 | Potential Immune-Mediated Diseases (pIMDs) are a subset of AEs that include both clearly autoimmune diseases and also other inflammatory and/or neurologic disorders which may or may not have an autoimmune etiology. |
| Serum Neutralising Antibody Titers | on Days 0, 28/56 and 180 | Titers were planned to be expressed as Geometric Mean Titers (GMTs). Analysis was planned to be done for antibodies against all 4 vaccine strains. |
| Number of Subjects Reporting Solicited Local and General Symptoms | during a 7 day follow-up period (Day 0 to 6) after any vaccination | Solicited local symptoms included pain, redness and swelling at the injection site. Solicited general symptoms included drowsiness, fever, irritability and loss of appetite. |
| Number of Subjects Reporting Unsolicited Adverse Events (AEs) | within 28 days (Day 0 to Day 27) after any vaccination | Unsolicited AE 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. |
Countries
Spain
Participant flow
Recruitment details
Since this study was prematurely terminated (not because of safety issues or lack of immunogenicity but for logistic reasons) only 4 of 1120 planned subjects were enrolled.
Participants by arm
| Arm | Count |
|---|---|
| GSK2584786A Vaccine 1 Dose of Formulation A1 Group Subjects received 1 dose of GSK Biologicals' adjuvanted quadrivalent influenza candidate vaccine (GSK2584786A) Formulation A1. | 0 |
| GSK2584786A Vaccine 2 Doses of Formulation A1 Group Subjects received 2 doses of GSK Biologicals' adjuvanted quadrivalent influenza candidate vaccine (GSK2584786A) Formulation A1. | 0 |
| GSK2584786A Vaccine 1 Dose of Formulation A2 Group Subjects received 1 dose of GSK Biologicals' adjuvanted quadrivalent influenza candidate vaccine (GSK2584786A) Formulation A2. | 0 |
| GSK2584786A Vaccine 2 Doses of Formulation A2 Group Subjects received 2 doses of GSK Biologicals' adjuvanted quadrivalent influenza candidate vaccine (GSK2584786A) Formulation A2. | 0 |
| GSK2584786A Vaccine 1 Dose of Formulation A3 Group Subjects received 1 dose of GSK Biologicals' adjuvanted quadrivalent influenza candidate vaccine (GSK2584786A) Formulation A3. | 1 |
| GSK2584786A Vaccine 2 Doses of Formulation A3 Group Subjects received 2 doses of GSK Biologicals' adjuvanted quadrivalent influenza candidate vaccine (GSK2584786A) Formulation A3. | 0 |
| GSK2584786A Vaccine 1 Dose of Formulation B1 Group Subjects received 1 dose of GSK Biologicals' adjuvanted quadrivalent influenza candidate vaccine (GSK2584786A) Formulation B1. | 0 |
| GSK2584786A Vaccine 2 Doses of Formulation B1 Group Subjects received 2 doses of GSK Biologicals' adjuvanted quadrivalent influenza candidate vaccine (GSK2584786A) Formulation B1. | 1 |
| GSK2584786A Vaccine 1 Dose of Formulation B2 Group Subjects received 1 dose of GSK Biologicals' adjuvanted quadrivalent influenza candidate vaccine (GSK2584786A) Formulation B2. | 0 |
| GSK2584786A Vaccine 2 Doses of Formulation B2 Group Subjects received 2 doses of GSK Biologicals' adjuvanted quadrivalent influenza candidate vaccine (GSK2584786A) Formulation B2. | 0 |
| GSK2584786A Vaccine 1 Dose of Formulation B3 Group Subjects received 1 dose of GSK Biologicals' adjuvanted quadrivalent influenza candidate vaccine (GSK2584786A) Formulation B3. | 0 |
| GSK2584786A Vaccine 2 Doses of Formulation B3 Group Subjects received 2 doses of GSK Biologicals' adjuvanted quadrivalent influenza candidate vaccine (GSK2584786A) Formulation B3. | 1 |
| GSK2321138A Vaccine Group Subjects received 2 doses of GSK Biologicals' non-adjuvanted quadrivalent influenza candidate vaccine (GSK2321138A). | 0 |
| Fluarix Group Subjects received 2 doses of Fluarix Vaccine. | 1 |
| Total | 4 |
Baseline characteristics
| Characteristic | GSK2584786A Vaccine 1 Dose of Formulation A3 Group | GSK2584786A Vaccine 2 Doses of Formulation B1 Group | GSK2584786A Vaccine 2 Doses of Formulation B3 Group | Fluarix Group | Total |
|---|---|---|---|---|---|
| Age, Continuous Months | 28 Months | 17 Months | 14 Months | 14 Months | 18.25 Months STANDARD_DEVIATION 6.65 |
| Sex: Female, Male Female | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 2 Participants |
| Sex: Female, Male Male | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk | EG011 affected / at risk | EG012 affected / at risk | EG013 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 1 | 0 / 0 | 0 / 0 | 1 / 1 | 0 / 0 | 0 / 0 | 0 / 0 | 1 / 1 | 0 / 0 | 1 / 1 |
| serious Total, serious adverse events | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 1 | 0 / 0 | 0 / 0 | 0 / 1 | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 1 | 0 / 0 | 0 / 1 |
Outcome results
Primary
Geometric Mean Number of All-CD4 Cytokine Positive Cells
Geometric mean of the number of CD4 cytokine positive T cells per million T cells.
Time frame: at Day 28/ Day 56
Population: This outcome measure was not assessed for any of the study groups since the study was terminated prematurely.
Primary
Number of Subjects Reporting Fever of at Least Grade 2 or Higher
Grade 2 fever was defined as axillary temperature above 38 degrees Celcius.
Time frame: Within 7 days (Day 0 to 6) follow-up period after any dose of study vaccine
Population: This outcome measure was not assessed for any of the study groups since the study was terminated prematurely.
Primary
Serum Haemagglutination-inhibition (HI) Antibody Titers
Titers were planned to be expressed as Geometric Mean Titers (GMTs). Analysis was planned to be done for antibodies against all 4 vaccine strains.
Time frame: at Day 28/ Day 56
Population: This outcome measure was not assessed for any of the study groups since the study was terminated prematurely.
Primary
Serum Neutralizing Antibody Titers
Time frame: at Day 28/ Day 56
Population: This outcome measure was not assessed for any of the study groups since the study was terminated prematurely.
Secondary
Number of Subjects Reporting Adverse Events With Medically Attended Visits
A mediaclly attended visit is defined as hospitalisation, an emergency room visit or a visit to or from medical personnel (medical doctor) for any reason.
Time frame: From Day 0 to 179
Population: This outcome measure was not assessed for any of the study groups since the study was terminated prematurely.
Secondary
Number of Subjects Reporting Potential Immune-mediated Diseases
Potential Immune-Mediated Diseases (pIMDs) are a subset of AEs that include both clearly autoimmune diseases and also other inflammatory and/or neurologic disorders which may or may not have an autoimmune etiology.
Time frame: From Day 0 to 179
Population: This outcome measure was not assessed for any of the study groups since the study was terminated prematurely.
Secondary
Number of Subjects Reporting Serious Adverse Events
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.
Time frame: From Day 0 to 179
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| GSK2584786A Vaccine 1 Dose of Formulation A3 Group | Number of Subjects Reporting Serious Adverse Events | 0 Subjects |
| GSK2584786A Vaccine 2 Doses of Formulation B1 Group | Number of Subjects Reporting Serious Adverse Events | 0 Subjects |
| GSK2584786A Vaccine 2 Doses of Formulation B3 Group | Number of Subjects Reporting Serious Adverse Events | 0 Subjects |
| Fluarix Group | Number of Subjects Reporting Serious Adverse Events | 0 Subjects |
Secondary
Number of Subjects Reporting Solicited Local and General Symptoms
Solicited local symptoms included pain, redness and swelling at the injection site. Solicited general symptoms included drowsiness, fever, irritability and loss of appetite.
Time frame: during a 7 day follow-up period (Day 0 to 6) after any vaccination
Population: This outcome measure was not assessed for any of the study groups since the study was terminated prematurely.
Secondary
Number of Subjects Reporting Unsolicited Adverse Events (AEs)
Unsolicited AE 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.
Time frame: within 28 days (Day 0 to Day 27) after any vaccination
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| GSK2584786A Vaccine 1 Dose of Formulation A3 Group | Number of Subjects Reporting Unsolicited Adverse Events (AEs) | 0 Subjects |
| GSK2584786A Vaccine 2 Doses of Formulation B1 Group | Number of Subjects Reporting Unsolicited Adverse Events (AEs) | 1 Subjects |
| GSK2584786A Vaccine 2 Doses of Formulation B3 Group | Number of Subjects Reporting Unsolicited Adverse Events (AEs) | 1 Subjects |
| Fluarix Group | Number of Subjects Reporting Unsolicited Adverse Events (AEs) | 1 Subjects |
Secondary
Serum HI Antibody Titers
Titers were planned to be expressed as Geometric Mean Titers (GMTs). Analysis was planned to be done for antibodies against all 4 vaccine strains.
Time frame: on Days 0, 28/56 and 180
Population: This outcome measure was not assessed for any of the study groups since the study was terminated prematurely.
Secondary
Serum Neutralising Antibody Titers
Titers were planned to be expressed as Geometric Mean Titers (GMTs). Analysis was planned to be done for antibodies against all 4 vaccine strains.
Time frame: on Days 0, 28/56 and 180
Population: This outcome measure was not assessed for any of the study groups since the study was terminated prematurely.