Immunogenicity and Safety of Vaccine GSK2340272A (H1N1) and GSK Biologicals Fluarix™ Vaccine When Co-administered in Elderly

Study Overview
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Brief Summary
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The purpose of the present study is to assess the immunogenicity, safety and reactogenicity of a two-dose schedule with vaccine GSK2340272A when co-administered with GSK Biologicals' Fluarix™ vaccine either at the time of first or second vaccination in elderly subjects aged 61 years and older.

Detailed Description
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The study will be conducted in an open manner regarding the administration of vaccine GSK2340272A. The study will be observer-blind regarding the administration of Fluarix™ and placebo vaccines.

Official Title
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Immunogenicity, Safety and Reactogenicity of GSK Biologicals' Influenza GSK2340272A and Fluarix™ 2009-2010 Vaccines When Co-administered in Elderly Subjects Aged 61 Years and Older

Conditions
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Influenza

Intervention / Treatment
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* Biological: Pandemrix (Influenza vaccine GSK2340272A)
* Biological: Fluarix™
* Biological: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female subjects 61 years of age or older at the time of the first vaccination Subjects who the investigator believes that they can and will comply with the requirements of the protocol. Written informed consent obtained from the subject. Satisfactory baseline medical assessment by history and physical examination. Access to a consistent means of telephone contact. Exclusion Criteria: Previous administration of the 2009 Southern Hemisphere or 2009-2010 Northern Hemisphere seasonal influenza vaccine. Previous administration of a pandemic influenza vaccine. Administration of any vaccine within 30 days before first vaccination. Planned administration of a vaccine not foreseen by the study protocol one month (minimum 30 days) after the second vaccination with vaccine GSK2340272A. Use of any investigational or non-registered product (drug or vaccine) other than the study vaccine within 30 days preceding the first dose of the study vaccines or planned use during the study period. Potential subjects in the follow-up (i.e., no treatment) phase of a prior investigational study may be enrolled if the investigator's judgment is that it will have no effect on safety, reactogenicity, or immunogenicity endpoints in this study, and that it does not violate the protocol requirements of the prior trial. Presence of evidence of substance abuse or of neurological or psychiatric diagnoses which, although stable, are deemed by the investigator to render the potential subject unable/unlikely to provide accurate safety reports. Presence of an oral temperature >= 37.5°C, or acute symptoms greater than mild severity on the scheduled date of first vaccination. Diagnosed with cancer, or treatment for cancer, within 3 years. Any confirmed or suspected immunosuppressive or immunodeficient condition including history of human immunodeficiency virus (HIV) infection. Chronic administration of immunosuppressants or other immune modifying drugs within six months prior to the first vaccination. Receipt of any immunoglobulins and/or any blood products within 3 months preceding the first vaccination or planned administration of any of these products during the entire study period. Any significant disorder of coagulation or treatment with warfarin derivatives or heparin. Persons receiving individual doses of low molecular weight heparin outside of 24 hours prior to vaccination are eligible. Persons receiving prophylactic anti-platelet medications, e.g., low-dose aspirin, and without a clinically-apparent bleeding tendency, are eligible. An acute evolving neurological disorder or history of Guillain-Barré syndrome. Serious chronic disease as determined by medical history and physical examination. Acute clinically significant pulmonary, cardiovascular, hepatic or renal functional abnormalities, as determined by physical examination or laboratory screening tests. Any known or suspected allergy to any constituent of influenza vaccines. History of chronic alcohol consumption and/or drug abuse. Clinically or virologically confirmed influenza infection within 6 months preceding the study start. Any conditions which, in the opinion of the investigator, prevents the subjects from participating in the study.

Ages Eligible for Study
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Minimum Age: 61 Years

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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pandemrix+Fluarix and Pandemrix+Placebo<br>Subjects received two doses of Pandemrix (GSK2340272A) intramuscularly in the deltoid region of the non-dominant arm co-administered with Fluarix™ on Day 0 and with a placebo on Day 21 intramuscularly in the deltoid region of the dominant arm. | Biological: Pandemrix (Influenza vaccine GSK2340272A)<br>* Intramuscular injection, 2 doses<br>Biological: Fluarix™<br>* Intramuscular injection, 1 dose<br>* Other names: 2009-2010 Northern Hemisphere trivalent seasonal influenza vaccine;Biological: Placebo<br>* Intramuscular injection, 1 dose<br>|
| Experimental: Pandemrix+Placebo and Pandemrix+Fluarix<br>Subjects received two doses of Pandemrix (GSK2340272A) intramuscularly in the deltoid region of the non-dominant arm co-administered with a placebo on Day 0 and with Fluarix™ on Day 21 intramuscularly in the deltoid region of the dominant arm. | Biological: Pandemrix (Influenza vaccine GSK2340272A)<br>* Intramuscular injection, 2 doses<br>Biological: Fluarix™<br>* Intramuscular injection, 1 dose<br>* Other names: 2009-2010 Northern Hemisphere trivalent seasonal influenza vaccine;Biological: Placebo<br>* Intramuscular injection, 1 dose<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Seroconverted Subjects After the Second Dose of Pandemrix and After Vaccination With Fluarix | A seroconverted subject is a subject who had either a pre-vaccination reciprocal hemagglutination inhibition (HI) titer < 10 and a postvaccination reciprocal titer >= 40, or a pre-vaccination reciprocal HI titer >= 10 and at least a 4-fold increase in post vaccination reciprocal titer against the vaccine virus. The Pandemrix vaccine strain was A/Cal/09. The Fluarix vaccine strains were A/Bri/07, A/Uru/07 and B/Bri/08. | 21 days after the second dose of Pandemrix (=Day 42) and after vaccination with Fluarix (=Day 21 for Pandemrix+Fluarix and Pandemrix+Placebo Group or Day 42 for Pandemrix+ Placebo and Pandemrix+Fluarix Group) | 
| Number of Seroprotected Subjects After the Second Dose of Pandemrix and After Vaccination With Fluarix | A seroprotected subject was a subject with reciprocal HI titers >= 40 against the vaccine homologous virus. The Pandemrix vaccine strain was A/Cal/09. The Fluarix vaccine strains were A/Bri/07, A/Uru/07 and B/Bri/08. | 21 days after the second dose of Pandemrix (=Day 42) and after vaccination with Fluarix (=Day 21 for Pandemrix+Fluarix and Pandemrix+Placebo Group or Day 42 for Pandemrix+ Placebo and Pandemrix+Fluarix Group) | 
| Geometric Mean Fold Rise (GMFR) After the Second Dose of Pandemrix and After Vaccination With Fluarix | The GMFR is defined as the Geometric Mean of the within-subject ratios of the post-vaccination reciprocal HI titer to the pre-vaccination reciprocal HI titer for the vaccine virus. The Pandemrix vaccine strain was A/Cal/09. The Fluarix vaccine strains were A/Bri/07, A/Uru/07 and B/Bri/08. | 21 days after the second dose of Pandemrix (=Day 42) and after vaccination with Fluarix (=Day 21 for Pandemrix+Fluarix and Pandemrix+Placebo Group or Day 42 for Pandemrix+ Placebo and Pandemrix+Fluarix Group) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Geometric Mean Titers for Antibodies Against Pandemrix and Fluarix Vaccine Strains | Titers are expressed as GMTs. The Pandemrix vaccine strain was A/Cal/09. The Fluarix vaccine strains were A/Bri/07, A/Uru/07 and B/Bri/08. | Days 0, 21, 42, 182, 364 | 
| Number of Seroconverted Subjects | A seroconverted subject is a subject who had either a pre-vaccination reciprocal hemagglutination inhibition (HI) titer < 10 and a postvaccination reciprocal titer >= 40, or a pre-vaccination reciprocal HI titer >= 10 and at least a 4-fold increase in post vaccination reciprocal titer against the vaccine virus. The Pandemrix vaccine strain was A/Cal/09. The Fluarix vaccine strains were A/Bri/07, A/Uru/07 and B/Bri/08. | at Day 21 (for Pandemrix vaccine strain only), Day 182 and Day 364 | 
| Number of Seroprotected Subjects | A seroprotected subject is a subject with reciprocal HI titers >= 40 against the vaccine homologous virus. The Pandemrix vaccine strain was A/Cal/09. The Fluarix vaccine strains were A/Bri/07, A/Uru/07 and B/Bri/08. | at Day 21 (for Pandemrix vaccine strain only), Day 182 and Day 364 | 
| Geometric Mean Fold Rise (GMFR) | The GMFR is defined as the Geometric Mean of the within-subject ratios of the post-vaccination reciprocal HI titer to the pre-vaccination reciprocal HI titer for the vaccine virus. The Pandemrix vaccine strain was A/Cal/09. The Fluarix vaccine strains were A/Bri/07, A/Uru/07 and B/Bri/08. | at Day 21 (for Pandemrix vaccine strain only), Day 182 and Day 364 | 
| Number of Subjects With Titers Equal to or Above Titer 1:10 | The cut-off 1:10 was considered as seropositivity. The Pandemrix vaccine strain was A/Cal/09. The Fluarix vaccine strains were A/Bri/07, A/Uru/07 and B/Bri/08. | Days 0, 21, 42, 182, 364 | 
| Number of Subjects With Solicited Local and General Symptoms | Solicited local symptoms are pain, redness and swelling at the injection site. They are divided between solicited local symptoms occurring after administration of Pandemrix, Fluarix or Placebo. Solicited general symptoms are fatigue, headache, joint pain at other location, muscle aches, shivering, sweating and temperature (defined as axillary temperature >= 38.0 degrees Celsius). | Within 7 days (Day 0-Day 6) after each vaccination | 
| Number of Subjects With 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 | From Day 0 to Day 83 | 
| Number of Subjects With Adverse Events of Specific Interest | Adverse events of specific interest include autoimmune diseases and other immune mediated inflammatory disorders. | From Day 0 to Day 364 | 
| Number of Subjects With Serious Adverse Events (SAEs) | 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 Day 364 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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GSK Bio's influenza vaccine GSK2340272A, Influenza infection