Immunogenicity and Safety Study of GlaxoSmithKline (GSK) Biologicals' Fluviral® (2012/2013 Season) in Adults

Study Overview
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Brief Summary
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This study is designed to test the immunogenicity in terms of Hemagglutination Inhibition (HI) antibodies against each of the three vaccine influenza strains and reactogenicity and safety of Fluviral® containing the influenza strains recommended for the 2012-2013 season.

Official Title
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Immunogenicity and Safety Study of GSK Biologicals' Trivalent Split Virion Influenza Vaccine (GSK1536489A) Fluviral® (2012/2013 Season) in Adults Aged 18 Years and Older

Conditions
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Influenza

Intervention / Treatment
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* Biological: Fluviral®


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects who, in the opinion of the investigator, can and will comply with the requirements of the protocol. A male or female 18 years of age and older at the time of the first vaccination. Written informed consent obtained from the subject. Healthy subjects as established by medical history and clinical examination before entering into the study. Female subjects of non-childbearing potential may be enrolled in the study. 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 the vaccination. Exclusion Criteria: 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. Administration of any influenza vaccine within 6 months preceding the study start or planned use of such vaccines during the study period. Administration of any other vaccine(s) within 30 days prior to study enrolment or during the 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 enrolment. Significant acute or chronic, uncontrolled medical or psychiatric or neurological illness. Any confirmed or suspected immunosuppressive or immunodeficient condition. Acute or chronic, clinically significant pulmonary, cardiovascular, hepatic or renal functional abnormality, as determined by physical examination or laboratory screening tests. Insulin-dependent diabetes mellitus. Presence of blood dyscrasias, including hemoglobinopathies and myelo- or lymphoproliferative disorder. Chronic administration of immunosuppressants or other immune-modifying drugs within six months prior to the vaccine dose. A history of any demyelinating disease including Multiple Sclerosis and Guillain-Barré syndrome. History of chronic alcohol abuse and/or drug abuse as deemed by the investigator to render the potential subject unable/unlikely to provide accurate safety reports. Any significant disorder of coagulation that increases the risk of intramuscular injections or treatment with coumadin derivatives or heparin. Persons receiving prophylactic antiplatelet medications, e.g. low-dose aspirin, and without a clinically-apparent bleeding tendency are eligible. Administration of immunoglobulins and/or any blood products within the three months preceding the administration of the study vaccine or planned during the study. Any known or suspected allergy to any constituent of Fluviral® and/or a history of anaphylactic type reaction to consumption of eggs, and/or reactions to products containing mercury. A history of severe adverse reaction to a previous influenza vaccination. Pregnant and/or lactating/nursing female. Any condition which, in the opinion of the investigator, prevents the subject from participation in the study.

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: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Fluviral Adults Group<br>Subjects 18-60 years of age received 1 dose of Fluviral® vaccine, administered intramuscularly in the deltoid of the non-dominant arm, at Day 0. | Biological: Fluviral®<br>* 1 dose administered intramuscularly in deltoid region of non-dominant arm at Day 0<br>|
| Experimental: Fluviral Elderly Group<br>Subjects above 60 years of age received 1 dose of Fluviral® vaccine, administered intramuscularly in the deltoid of the non-dominant arm, at Day 0. | Biological: Fluviral®<br>* 1 dose administered intramuscularly in deltoid region of non-dominant arm at Day 0<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Haemagglutination Inhibition (HI) Antibody Titers, Against Each of the Vaccine Influenza Virus Strains. | Antibody titers were expressed as Geometric mean titers (GMTs). The vaccine influenza strains included Flu A/CAL/7/09 (H1N1), Flu A/Victoria/361/11 (H3N2) and Flu B/Hubei-Wujiagang/158/09 (Yamagata) antigens. | At Day 0 and Day 21 | 
| Number of Subjects Seroprotected for HI Antibodies Against Each of the Three Vaccine Influenza Strains. | A seroprotected subject was defined as a subject with serum HI titer greater than or equal to (≥) 1:40 that usually is accepted as indicating protection in adults. The influenza vaccine strains included Flu A/CAL/7/09 (H1N1), Flu A/Victoria/361/11 (H3N2) and Flu B/Hubei-Wujiagang/158/09 (Yamagata) antigens. | At Day 0 and Day 21 | 
| Number of Seroconverted Subjects for HI Antibodies Against Each of the Three Vaccine Influenza Strains. | A seroconverted subject was defined as a subject who had 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 influenza strains included Flu A/CAL/7/09 (H1N1), Flu A/Victoria/361/11 (H3N2) and Flu B/Hubei-Wujiagang/158/09 (Yamagata) antigens. | At Day 21 | 
| Mean Geometric Increase (MGI) for HI Antibody Titer Against Each of the Three Vaccine Influenza Strains. | MGI was defined as the fold increase in serum HI GMTs post-vaccination (Day 21) compared to pre-vaccination (Day 0). | At Day 21 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 occurrence of any specified solicited local symptoms reported irrespective of intensity grade. Grade 3 pain was defined as considerable pain that prevented normal everyday activities. Grade 3 ecchymosis, induration, redness and swelling were defined as ecchymosis, induration, redness and swelling above 100 millimeters (mm). | 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, sweating and fever [oral temperature ≥38.0 degrees Celsius (°C)]. Gastrointestinal symptoms included nausea, vomiting, diarrhea and/or abdominal pain. Any =occurrence of any specified solicited general symptoms reported irrespective of intensity grade or relationship to vaccination, Any fever = oral temperature ≥38.0 degrees Celsius (°C). Grade 3 symptoms = symptoms that prevented normal activities. Grade 3 fever = oral temperature ≥39.0°C. Related = symptoms considered by the investigator to have a causal relationship to vaccination | During the 4-day (Days 0-3) post-vaccination period | 
| Number of Subjects Reporting Any 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. | During the 21-day (Days 0-20) post-vaccination period. | 
| Number of Subjects Reporting Any and Related Serious Adverse Events (SAEs) | SAEs assessed included medical occurrences that resulted in death, was life threatening, required hospitalization or prolongation of 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 (Day 0 - Day 20 after vaccination). | 

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