Trial to Evaluate Safety and Immunogenicity of GSK Biologicals' Influenza Vaccine GSK2584786A in Healthy Children

Study Overview
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Brief Summary
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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.

Official Title
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Observer-blind Immunogenicity and Safety Study of GlaxoSmithKline Biologicals' Adjuvanted Quadrivalent Influenza Candidate Vaccines (GSK2584786A) in Children Aged 6 to 35 Months

Conditions
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Influenza, Influenza Vaccines

Intervention / Treatment
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* Biological: GSK Bio's influenza vaccine GSK2584786A, different formulations
* Biological: GSK Bio's influenza vaccine GSK2321138A
* Biological: Fluarix™


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 6 Months
Maximum Age: 35 Months

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GSK2584786A vaccine 1 dose of Formulation A1 Group<br>Subjects received 1 dose of GSK Biologicals' adjuvanted quadrivalent influenza candidate vaccine (GSK2584786A) Formulation A1. | Biological: GSK Bio's influenza vaccine GSK2584786A, different formulations<br>* Intramuscular injections<br>|
| Experimental: GSK2584786A vaccine 2 doses of Formulation A1 Group<br>Subjects received 2 doses of GSK Biologicals' adjuvanted quadrivalent influenza candidate vaccine (GSK2584786A) Formulation A1. | Biological: GSK Bio's influenza vaccine GSK2584786A, different formulations<br>* Intramuscular injections<br>|
| Experimental: GSK2584786A vaccine 1 dose of Formulation A2 Group<br>Subjects received 1 dose of GSK Biologicals' adjuvanted quadrivalent influenza candidate vaccine (GSK2584786A) Formulation A2. | Biological: GSK Bio's influenza vaccine GSK2584786A, different formulations<br>* Intramuscular injections<br>|
| Experimental: GSK2584786A vaccine 2 doses of Formulation A2 Group<br>Subjects received 2 doses of GSK Biologicals' adjuvanted quadrivalent influenza candidate vaccine (GSK2584786A) Formulation A2. | Biological: GSK Bio's influenza vaccine GSK2584786A, different formulations<br>* Intramuscular injections<br>|
| Experimental: GSK2584786A vaccine 1 dose of Formulation A3 Group<br>Subjects received 1 dose of GSK Biologicals' adjuvanted quadrivalent influenza candidate vaccine (GSK2584786A) Formulation A3. | Biological: GSK Bio's influenza vaccine GSK2584786A, different formulations<br>* Intramuscular injections<br>|
| Experimental: GSK2584786A vaccine 2 doses of Formulation A3 Group<br>Subjects received 2 doses of GSK Biologicals' adjuvanted quadrivalent influenza candidate vaccine (GSK2584786A) Formulation A3. | Biological: GSK Bio's influenza vaccine GSK2584786A, different formulations<br>* Intramuscular injections<br>|
| Experimental: GSK2584786A vaccine 1 dose of Formulation B1 Group<br>Subjects received 1 dose of GSK Biologicals' adjuvanted quadrivalent influenza candidate vaccine (GSK2584786A) Formulation B1. | Biological: GSK Bio's influenza vaccine GSK2584786A, different formulations<br>* Intramuscular injections<br>|
| Experimental: GSK2584786A vaccine 2 doses of Formulation B1 Group<br>Subjects received 2 doses of GSK Biologicals' adjuvanted quadrivalent influenza candidate vaccine (GSK2584786A) Formulation B1. | Biological: GSK Bio's influenza vaccine GSK2584786A, different formulations<br>* Intramuscular injections<br>|
| Experimental: GSK2584786A vaccine 1 dose of Formulation B2 Group<br>Subjects received 1 dose of GSK Biologicals' adjuvanted quadrivalent influenza candidate vaccine (GSK2584786A) Formulation B2. | Biological: GSK Bio's influenza vaccine GSK2584786A, different formulations<br>* Intramuscular injections<br>|
| Experimental: GSK2584786A vaccine 2 doses of Formulation B2 Group<br>Subjects received 2 doses of GSK Biologicals' adjuvanted quadrivalent influenza candidate vaccine (GSK2584786A) Formulation B2. | Biological: GSK Bio's influenza vaccine GSK2584786A, different formulations<br>* Intramuscular injections<br>|
| Experimental: GSK2584786A vaccine 1 dose of Formulation B3 Group<br>Subjects received 1 dose of GSK Biologicals' adjuvanted quadrivalent influenza candidate vaccine (GSK2584786A) Formulation B3. | Biological: GSK Bio's influenza vaccine GSK2584786A, different formulations<br>* Intramuscular injections<br>|
| Experimental: GSK2584786A vaccine 2 doses of Formulation B3 Group<br>Subjects received 2 doses of GSK Biologicals' adjuvanted quadrivalent influenza candidate vaccine (GSK2584786A) Formulation B3. | Biological: GSK Bio's influenza vaccine GSK2584786A, different formulations<br>* Intramuscular injections<br>|
| Experimental: GSK2321138A vaccine Group<br>Subjects received 2 doses of GSK Biologicals' non-adjuvanted quadrivalent influenza candidate vaccine (GSK2321138A). | Biological: GSK Bio's influenza vaccine GSK2321138A<br>* Intramuscular injections<br>|
| Active Comparator: Fluarix Group<br>Subjects received 2 doses of Fluarix Vaccine. | Biological: Fluarix™<br>* Intramuscular injections<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | at Day 28/ Day 56 | 
| Serum Neutralizing Antibody Titers |  | at Day 28/ Day 56 | 
| Geometric Mean Number of All-CD4 Cytokine Positive Cells | Geometric mean of the number of CD4 cytokine positive T cells per million T cells. | at Day 28/ Day 56 | 
| Number of Subjects Reporting Fever of at Least Grade 2 or Higher | Grade 2 fever was defined as axillary temperature above 38 degrees Celcius. | Within 7 days (Day 0 to 6) follow-up period after any dose of study vaccine | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | on Days 0, 28/56 and 180 | 
| 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. | on Days 0, 28/56 and 180 | 
| 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. | during a 7 day follow-up period (Day 0 to 6) after any vaccination | 
| 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. | within 28 days (Day 0 to Day 27) after any vaccination | 
| 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. | From Day 0 to 179 | 
| 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. | From Day 0 to 179 | 
| 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. | From Day 0 to 179 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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vaccine, immunogenicity, safety, Influenza, children