Immunogenicity and Safety Study of GlaxoSmithKline (GSK) Biologicals' Influenza Vaccine, Fluarix®/Influsplit SSW® (2013/2014 Season), in Adults 18 Years of Age and Older

Study Overview
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Brief Summary
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The purpose of this study is to assess, in adults 18 years of age and above, the immunogenicity and reactogenicity of the seasonal influenza vaccine, Fluarix/Influsplit SSW 2013/2014, containing the three vaccine influenza strains (two A strains and one B strain) for the 2013/2014 season.

Official Title
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Study for Evaluation of Immunogenicity and Reactogenicity of Fluarix/Influsplit SSW 2013/2014 in People 18 Years of Age and Above

Conditions
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Influenza

Intervention / Treatment
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* Biological: Fluarix/Influsplit SSW® (2013-2014 season)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects who the investigator believes can and will comply with the requirements of the protocol. A male or female aged 18 years or above at the time of vaccination. Written informed consent obtained from the subject. Healthy subjects or subjects with well-controlled chronic diseases as established by medical history and clinical examination before entering the study. Female subjects of non-childbearing potential may be enrolled in the study. Non-childbearing potential is defined as pre-menarche, current tubal ligation, hysterectomy, ovariectomy or post-menopause. Female subjects of childbearing potential may be enrolled in the study, if the subject: has practiced adequate contraception for 30 days prior to vaccination, and has a negative pregnancy test on the day of vaccination, and has agreed to continue adequate contraception during the entire treatment period and for 2 months after completion of vaccination. Exclusion Criteria: Participation in previous year's Fluarix registration study (116663). Use of any investigational or non-registered product (drug or vaccine) other than the study vaccine within 30 days preceding the dose of study vaccine, or planned use during the study period. Chronic administration of immunosuppressants or other immune-modifying drugs within the six months prior to vaccination. Inhaled and topical steroids are allowed. Any administration of a long-acting immune-modifying drug within 6 months before study start, or planned administration during the study period. Administration of immunoglobulins and/or any blood products within the three months preceding the administration of the study vaccine or planned administration during the study period. Administration of an influenza vaccine within the twelve months preceding the study vaccination. Receipt of a vaccine other than the study vaccine within 30 days before study vaccination and/or plan to receive any vaccine other than the study vaccine during the entire study period. Clinically or virologically confirmed influenza infection within the six months preceding the study vaccination. Acute disease and/or fever at the time of enrollment. Fever is defined as temperature ≥ 37.5°C/99.5°F on oral, axillary or tympanic setting, or ≥ 38.0°C/100.4°F on rectal setting. The preferred route for recording temperature in this study will be axillary. Subjects with a minor illness (such as mild diarrhoea, mild upper respiratory infection) without fever may be enrolled at the discretion of the investigator. Acute, clinically significant pulmonary, cardiovascular, hepatic or renal functional abnormality, as determined by physical examination or laboratory screening tests. Chronic underlying disease (such as cancer, chronic obstructive pulmonary disease under oxygen therapy, insulin-dependent diabetes mellitus), not stabilized or clinically serious. History of chronic alcohol consumption and/or drug abuse. Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination (no laboratory testing required). History of Guillain-Barré syndrome. History of allergic disease or reactions likely to be exacerbated by any component of the vaccine including latex. Anaphylaxis following the administration of vaccine(s). Pregnant or lactating female. Female planning to become pregnant or planning to discontinue contraceptive precautions. Any condition which, in the opinion of the investigator, prevents the subject from participating in the study or would make intramuscular injection unsafe.

Ages Eligible for Study
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Minimum Age: 18 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: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Fluarix/Influsplit 18-60 Years Group<br>Subjects 18-60 years of age received 1 dose of Fluarix/Influsplit SSW 2013-2014 vaccine at Day 0. The vaccine was administered intramuscularly in the deltoid of the non-dominant arm. | Biological: Fluarix/Influsplit SSW® (2013-2014 season)<br>* 1 dose administered intramuscularly (or deeply subcutaneously) in the deltoid region of the non-dominant arm<br>|
| Experimental: Fluarix/Influsplit > 60 Years Group<br>Subjects above 60 years of age received 1 dose of Fluarix/Influsplit SSW 2013-2014 vaccine at Day 0. The vaccine was administered intramuscularly in the deltoid of the non-dominant arm. | Biological: Fluarix/Influsplit SSW® (2013-2014 season)<br>* 1 dose administered intramuscularly (or deeply subcutaneously) in the deltoid region of the non-dominant arm<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Humoral Immune Response in Terms of Haemagglutination Inhibition (HI) Antibody Titers Against Each of the Three Vaccine Influenza Strains | Antibody titers were expressed as Geometric mean titers (GMTs). The vaccine strains assessed were Flu A/Christchurch/16/2010 (H1N1), Flu A/Texas/50/2012 (H3N2) and Flu B/Massachusetts/2/2012 (Yamagata). | At Day 0 and Day 21 | 
| Number of Subjects Who Were Seroprotected for Anti-HI Antibodies Against Each of the Three Vaccine Influenza Strains. | A seroprotected subject was defined as a vaccinated subject with a serum HI titer greater than or equal to (≥) 1:40 that usually is accepted as indicating protection in adults. The vaccine strains assessed were Flu A/Christchurch/16/2010 (H1N1), Flu A/Texas/50/2012 (H3N2) and Flu B/Massachusetts/2/2012 (Yamagata). | At Day 0 and Day 21 | 
| Number of Seroconverted Subjects for Anti-HA Antibodies Against Each of the Three Vaccine Influenza Strains. | A seroconverted subjects was defined as a vaccinated subject with either a pre-vaccination titer less than (<) 1:10 and a post-vaccination titer ≥ 1:40, or a pre-vaccination titer ≥ 1:10 and at least a 4-fold increase in post-vaccination titer. The vaccine strains assessed were Flu A/Christchurch/16/2010 (H1N1), Flu A/Texas/50/2012 (H3N2) and Flu B/Massachusetts/2/2012 (Yamagata). | At Day 21 | 
| Mean Geometric Increase (MGI) for Haemagglutination Inhibition (HI) Antibody Titer Against Each of the Three Vaccine Influenza Strains. | MGI was defined as the fold increase in serum HI GMTs post-vaccination compared to pre-vaccination (Day 0). The vaccine strains assessed were Flu A/Christchurch/16/2010 (H1N1), Flu A/Texas/50/2012 (H3N2) and Flu B/Massachusetts/2/2012 (Yamagata). | At Day 21 | 
| Number of Subjects With Seroprotection Power (SPP) for HI Antibody Titer Against Each of the Three Vaccine Influenza Strains Above the Cut-off Value. | SPP was defined as the number of vaccinated subjects with a pre-vaccination titer < 1:40 and a post-vaccination titer ≥ 1:40. The vaccine strains assessed were Flu A/Christchurch/16/2010 (H1N1), Flu A/Texas/50/2012 (H3N2) and Flu B/Massachusetts/2/2012 (Yamagata). | At Day 21 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Humoral Immune Response in Terms of HI Antibody Titers Against Each of the Three Vaccine Influenza Strains | Antibody titers were expressed as Geometric mean titers (GMTs). The vaccine strains assessed were Flu A/Christchurch/16/2010 (H1N1), Flu A/Texas/50/2012 (H3N2) and Flu B/Massachusetts/2/2012 (Yamagata). This outcome measure was assessed by influenza vaccination status in subjects (18-60 years and >60 years) who had and who had not received an influenza vaccine during the 2 influenza seasons prior to season 2012/2013. | At Days 0 and 21 | 
| Number of Subjects Who Were Seroprotected for Anti-HI Antibodies Against Each of the Three Vaccine Influenza Strains. | A seroprotected subject was defined as a vaccinated subject with a serum HI titer greater than or equal to (≥) 1:40 that usually is accepted as indicating protection in adults. The vaccine strains assessed were Flu A/Christchurch/16/2010 (H1N1), Flu A/Texas/50/2012 (H3N2) and Flu B/Massachusetts/2/2012 (Yamagata). This outcome measure was assessed by influenza vaccination status in subjects (18-60 years and >60 years) who had and who had not received an influenza vaccine during the 2 influenza seasons prior to season 2012/2013. | At Day 0 and Day 21 | 
| Number of Seroconverted Subjects for Anti-HA Antibodies Against Each of the Three Vaccine Influenza Strains. | A seroconverted subject was defined as a vaccinated subject with either a pre-vaccination titer less than (<) 1:10 and a post-vaccination titer ≥ 1:40, or a pre-vaccination titer ≥ 1:10 and at least a 4-fold increase in post-vaccination titer. The vaccine strains assessed were Flu A/Christchurch/16/2010 (H1N1), Flu A/Texas/50/2012 (H3N2) and Flu B/Massachusetts/2/2012 (Yamagata). This outcome measure was assessed by influenza vaccination status in subjects (18-60 years and >60 years) who had and who had not received an influenza vaccine during the 2 influenza seasons prior to season 2012/2013. | At Day 21 | 
| Mean Geometric Increase (MGI) for Haemagglutination Inhibition (HI) Antibody Titer Against Each of the Three Vaccine Influenza Strains. | MGI was defined as the fold increase in serum HI GMTs post-vaccination compared to pre-vaccination (Day 0). The vaccine strains assessed were Flu A/Christchurch/16/2010 (H1N1), Flu A/Texas/50/2012 (H3N2) and Flu B/Massachusetts/2/2012 (Yamagata). This outcome measure was assessed by influenza vaccination status in subjects (18-60 years and >60 years) who had and who had not received an influenza vaccine during the 2 influenza seasons prior to season 2012/2013. | At Day 21 | 
| Number of Subjects Reporting Any and Grade 3 Solicited Local Symptoms. | Solicited local symptoms assessed were ecchymosis, induration, pain, redness and swelling. Any was defined as any solicited local symptom reported irrespective of intensity. Grade 3 pain was defined as pain that prevented normal everyday activities. Grade 3 ecchymosis, induration, redness and swelling was greater than 100 millimeters (mm) i.e. >100mm. | During the 4-day (Days 0-3) post-vaccination period | 
| Duration of Solicited Local Symptoms. | Duration was defined as number of days with any grade of local symptoms. | During the 4-day (Days 0-3) post-vaccination period | 
| Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms. | Solicited general symptoms assessed were arthralgia, fatigue, gastrointestinal symptoms, headache, myalgia, shivering, increased sweating and fever [axillary temperature above 37.5 degrees Celsius (°C)]. Gastrointestinal symptoms included nausea, vomiting, diarrhea and/or abdominal pain. Any = any solicited general symptom reported irrespective of intensity and relationship to vaccination. Related = symptoms considered by the investigator to have a causal relationship to vaccination. Grade 3 symptoms = symptoms that prevented normal activity. Grade 3 fever = axillary temperature above 39.0°C | During the 4-day (Days 0-3) post-vaccination period | 
| Duration of Solicited General Symptoms. | Duration was defined as number of days with any grade of general symptoms. | During the 4-day (Days 0-3) post-vaccination period | 
| Number of Subjects Reporting 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 was defined as occurrence of any unsolicited symptom regardless of intensity grade or relation to vaccination. Grade 3 was an event that prevented normal activities and related was defined as an unsolicited AE assessed by the investigator to be causally related to the study vaccination. | During the 21-day (Days 0-20) post-vaccination period | 
| Number of Subjects Reporting Any and Related Serious Adverse Events (SAEs) | A serious adverse event was any untoward medical occurrence that: resulted in death, was life-threatening, required hospitalization or prolongation of existing hospitalization, resulted in disability/incapacity or was a congenital anomaly/birth defect in the offspring of a study subject. Any was defined as occurrence of any symptom regardless of intensity grade or relation to vaccination and related was an event assessed by the investigator as causally related to the study vaccination. | During the entire study period (Days 0-180) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Elderly, Influenza, Safety, Adults, Immunogenicity