Evaluation of the Immune Response and the Safety of a Pandemic Influenza Candidate Vaccine (H1N1)

Study Overview
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Brief Summary
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The objective of the study is to evaluate the immunogenicity and safety of GSK Biologicals' investigational vaccine GSK2340272A.

Official Title
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Immunogenicity and Safety of GSK Biologicals' Pandemic Influenza Candidate Vaccine GSK2340272A

Conditions
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Influenza

Intervention / Treatment
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* Biological: Pandemrix (GSK investigational influenza GSK2340272A vaccine)
* 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 (stable health status with no exclusionary medical or psychiatric conditions). Stable health status is defined as the absence of health event satisfying the definition of a serious adverse event, or a change in an ongoing drug therapy due to therapeutic failure or symptoms of drug toxicity, within one month prior to enrolment. Exclusion Criteria: Previous administration of the 2009 Southern Hemisphere or 2009-2010 Northern Hemisphere 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 the GSK2340272A candidate vaccine. Use of any investigational or non-registered product 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 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 axillary temperature >= 37.5°C, or acute symptoms greater than mild severity on the scheduled date of first vaccination. NOTE: The subject may be vaccinated at a later date, provided symptoms have resolved, vaccination occurs within the window specified by the protocol, and all other eligibility criteria continue to be satisfied. Diagnosed with cancer, or treatment for cancer, within 3 years. Persons with a history of cancer who are disease-free without treatment for 3 years or more are eligible. Persons with a history of histological-confirmed basal cell carcinoma of the skin successfully treated with local excisions only are eligible and may be enrolled within 3 years of diagnosis, but other histological types of skin cancer require a 3-year untreated and disease-free window as above. Women who are disease free for 3 years or more after the treatment of breast cancer and receiving long-term prophylactic tamoxifen are eligible and may be enrolled. 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 and during the entire study period. 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 antiplatelet 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 including any medically significant chronic pulmonary, cardiovascular, renal, neurological, psychiatric or metabolic disorder, as determined by medical history and physical examination. (Subjects suffering from seasonal allergies or asthma under inhalative treatment can be included, as well as subjects with well controlled underlying diseases). 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; a history of anaphylactic-type reaction to any constituent of influenza vaccines; or a history of severe adverse reaction to a previous influenza vaccine. 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: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Placebo-Pandemrix-Fluarix Group<br>Subjects received one dose of placebo intramuscularly in the deltoid region of the dominant arm at Day -21, 2 doses of Pandemrix (GSK2340272A) intramuscularly in the deltoid region of the non-dominant arm at Day 0 and Day 21, and 1 dose of Fluarix intramuscularly in the deltoid region of the dominant arm at Day 42. | Biological: Pandemrix (GSK investigational influenza GSK2340272A vaccine)<br>* 2 doses intramuscular injections<br>Biological: Fluarix™<br>* 1 dose intramuscular injection<br>Biological: Placebo<br>* 1 dose intramuscular injection<br>|
| Experimental: Fluarix-Pandemrix-Placebo Group<br>Subjects received 1 dose of Fluarix intramuscularly in the deltoid region of the dominant arm at Day -21, 2 doses of Pandemrix (GSK2340272A) intramuscularly in the deltoid of the non-dominant arm at Day 0 and 21, and 1 dose of placebo intramuscularly in the deltoid of the non-dominant arm at Day 42. | Biological: Pandemrix (GSK investigational influenza GSK2340272A vaccine)<br>* 2 doses intramuscular injections<br>Biological: Fluarix™<br>* 1 dose intramuscular injection<br>Biological: Placebo<br>* 1 dose intramuscular injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Geometric Mean Titers (GMTs) of Antibodies Against Pandemrix Vaccine Strain | Titers were expressed as GMTs. The Pandemrix vaccine strain was A/Cal/7/09. | At Day 42 | 
| Number of Subjects With a Titer Greater Than or Equal to 1:10 for Antibodies Against Pandemrix Vaccine Strain | The Pandemrix vaccine strain was A/Cal/7/09. The cut-off was a titer of 1:10 and this titer was considered as seropositivity. | At Day 42 | 
| Number of Seroconverted Subjects for Antibodies Against Pandemrix Vaccine Strain | The Pandemrix vaccine strain was A/Cal/7/09. A subject seroconverted for haemagglutination inhibition (HI) antibodies was defined as a subject with either a prevaccination (Day 0) HI antibody titer below 1:10 and a post-vaccination titer greater than or equal to 1:40 or a prevaccination titer greater than or equal to 1:10 and at least a 4-fold increase in post-vaccination titer. | At Day 42 | 
| Seroconversion Factor for Antibodies Against Pandemrix Vaccine Strain | Seroconversion Factor (SCF) is defined as the fold increase in serum HI antibody GMTs post-vaccination compared to prevaccination (Day 0). The Pandemrix vaccine strain was A/Cal/7/09. | At Day 42 | 
| Number of Seroprotected Subjects for Antibodies Against Pandemrix Vaccine Strain | The Pandemrix vaccine strain was A/Cal/7/09. A seroprotected subject was defined as a subject with a serum HI antibody titer greater than or equal to 1:40. | At Day 42 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Geometric Mean Titers (GMTs) of Antibodies Against Pandemrix Vaccine Strain and Fluarix Vaccine Strains | Pandemrix vaccine strain (A/Cal/7/09) data were assessed up to Month 12. Note that Day 42 data for Pandemrix vaccine strain were already addressed as a primary outcome measure. Fluarix vaccine strains (A/Bri/59/07, B/Bri/60/08, and A/Uru/716/07) data were only assessed up to Day 63. | Day -21, Day 0, Day 21, Day 42, Day 63, Month 6 and Month 12 | 
| Number of Subjects With a Titer Greater Than or Equal to 1:10 for Antibodies Against Pandemrix Vaccine Strain and Fluarix Vaccine Strains | The cut-off was a titer of 1:10 and this titer was considered as seropositivity. Pandemrix vaccine strain (A/Cal/7/09) data were assessed up to Month 12. Note that Day 42 data for Pandemrix vaccine strain were already addressed as a primary outcome measure. Fluarix vaccine strains (A/Bri/59/07, B/Bri/60/08, and A/Uru/716/07) data were only assessed up to Day 63. | At Day -21, Day 0, Day 21, Day 42, Day 63, Month 6 and Month 12 | 
| Number of Seroconverted Subjects for Antibodies Against Pandemrix Vaccine Strain and Fluarix Vaccine Strains | A seroconverted subject was defined as a subject with either a prevaccination (Day 0) HI antibody titer below 1:10 and a post-vaccination titer greater than or equal to 1:40 or a prevaccination titer greater than or equal to 1:10 and at least a 4-fold increase in post-vaccination titer. Pandemrix vaccine strain (A/Cal/7/09) data were generated for Day 21, Month 6 and Month 12. Fluarix vaccine strains (A/Bri/59/07, B/Bri/60/08, and A/Uru/716/07) data were generated at 21 days after Fluarix administration, i.e. depending on the group at Day 0 or Day 63 (Day 0/Day 63). | At Day 21, Month 6 and Month 12 for Pandemrix vaccine strain, and at Day 0/Day 63 for Fluarix vaccine strains. | 
| Seroconversion Factor for Antibodies Against Pandemrix Vaccine Strain and Fluarix Vaccine Strains | For the definition of seroconversion factor, please refer to the primary outcome measure. Pandemrix vaccine strain (A/Cal/7/09) data were generated for Day 21, Month 6 and Month 12. Fluarix vaccine strains (A/Bri/59/07, B/Bri/60/08, and A/Uru/716/07) data were generated at 21 days after Fluarix administration, i.e. depending on the group at Day 0 or Day 63 (Day 0/Day 63). | At Day 21, Month 6 and Month 12 for Pandemrix vaccine strain, and at Day 0/Day 63 for Fluarix vaccine strains. | 
| Number of Seroprotected Subjects for Antibodies Against Pandemrix Vaccine Strain and Fluarix Vaccine Strains | A seroprotected subject was defined as a subject with a serum HI antibody titer greater than or equal to 1:40. Pandemrix vaccine strain (A/Cal/7/09) data were assessed up to Month 12. Note that Day 42 data for Pandemrix vaccine strain were already addressed as a primary outcome measure. Fluarix vaccine strains (A/Bri/59/07, B/Bri/60/08, and A/Uru/716/07) data were only assessed up to Day 63. | Day -21, Day 0, Day 21, Day 42, Day 63, Month 6 and Month 12 | 
| Number of Subjects With Solicited Local and General Symptoms After Administration of Pandemrix | Solicited local symptoms were pain, redness and swelling at the injection site. Solicited general symptoms were fatigue, headache, joint pain at other location, muscle aches, shivering, sweating, temperature (defined as axillary temperature equal to or above 37.5 degrees Celsius). | During a 7-Day (Day 0-6) follow-up period after each administration of Pandemrix | 
| Number of Subjects With Solicited Local and General Symptoms After Administration of Placebo or Fluarix | Solicited local symptoms were pain, redness and swelling at the injection site. General symptoms were fatigue, headache, joint pain at other location, muscle aches, shivering, sweating, temperature (defined as axillary temperature equal to or above 37.5 degrees Celsius) | During a 7-Day (Day 0-6) follow-up period after each administration of (at Day -21 and at Day 42) placebo or Fluarix | 
| Number of Subjects With Any, Grade 3 and Related 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. Any: any unsolicited AE regardless of intensity or relationship to vaccination. Grade 3: unsolicited AE that prevented normal everyday activity Related: unsolicited AE assessed by the investigator as related to the vaccination | During 21 days (Day 0-20) after each vaccination | 
| 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. | During the entire study period (Day 0-364) | 
| Number of Subjects With AEs of Specific Interest | Adverse events of specific interest included auto-immune diseases and other immune mediated disorders. | During the entire study period (Day 0-364) | 

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