Immunogenicity and Safety Study of GlaxoSmithKline (GSK) Biologicals' Trivalent Split Virion Influenza Vaccine Fluviral™ (2013-2014 Season) in Adults Aged 18 Years and Older

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the immunogenicity, reactogenicity and safety of Fluviral™ containing the influenza strains recommended for the 2013-2014 season in adults aged 18 years and older.

Official Title
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Immunogenicity and Safety Study of GSK Biologicals' Trivalent Split Virion Influenza Vaccine (GSK1536489A) Fluviral™ (2013-2014 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 or subjects with well-controlled chronic disease, 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. 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 the vaccination dose. Exclusion Criteria: Use of any investigational or non-registered product (drug or vaccine) other than the study vaccine 30 days preceding the dose of study vaccine, or planned use during the study period. Chronic administration (defined as more than 14 days in total) of immunosuppressants or other immune-modifying drugs within six months prior to the vaccine dose. For corticosteroids, this will mean prednisone ≥ 20 mg/day, or equivalent. Inhaled and topical steroids are allowed. Any administration of a long-acting immune-modifying drug (e.g. rituximab, infliximab etc.) within 6 months before study start, or planned administration 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 enrollment or during the study period. Clinically or virologically confirmed influenza infection within the 6 months preceding the study vaccination. Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination (no laboratory testing required): History of human immunodeficiency virus (HIV) infection, Cancer or treatment for cancer, within 3 years of study enrollment. Persons with a history of cancer who are disease-free without treatment for 3 years or more are eligible. Acute disease and/or fever at the time of enrollment. Acute disease is defined as the presence of a short term, moderate or severe illness, with or without fever. Fever is defined as temperature ≥ 38.0°C/100.4°F for oral, axillary or tympanic route. The preferred route for recording temperature in this study will be oral. Subjects with a minor illness (such as mild diarrhea, mild upper respiratory infection) without fever may, be enrolled at the discretion of the investigator. Significant acute or chronic, uncontrolled medical or psychiatric or neurological illness. Uncontrolled is defined as: Requiring institution of new medical or surgical treatment within one month prior to study enrollment, or Requiring the re-institution of a previously discontinued medication or medical treatment within one month prior to study enrollment, or Requiring a change in medication dosage in the one month prior to study enrollment due to uncontrolled symptoms or drug toxicity (elective dosage adjustments in stable subjects are acceptable), or Hospitalization or an event fulfilling the definition of a SAE within one month prior to study enrollment. Acute or chronic, clinically significant pulmonary, cardiovascular, hepatic or renal functional abnormality, as determined by physical examination or laboratory screening tests. Subjects who participated in the registration trial [116664 (FLU Q-TIV-014)] for Fluviral™ 2012/2013 conducted in the 2012-2013 season. Presence of blood dyscrasias, including hemoglobinopathies and myelo- or lymphoproliferative disorder. A history of any demyelinating disease including Multiple Sclerosis and Guillain-Barré syndrome. Administration of immunoglobulins and/or any blood products within the 3 months preceding the dose of study vaccine or planned administration during the study period. 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 or lactating female. History of chronic alcohol consumption and/or drug abuse as deemed by the investigator to render the potential subject unable/unlikely to provide accurate safety reports. Any condition which, in the opinion of the investigator, prevents the subject from participation in the study or would make the 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: Fluviral 18-60 Years Group<br>Subjects aged between 18 and 60 years, received 1 dose of Fluviral™ vaccine on Day 0. The vaccine was administered intramuscularly in the deltoid region of the non-dominant arm. | Biological: Fluviral™<br>* 1 dose administered intramuscularly in deltoid region of non-dominant arm.<br>|
| Experimental: Fluviral >60 Years Group<br>Subjects aged > 60 years, received 1 dose of Fluviral™ vaccine on Day 0. The vaccine was administered intramuscularly in the deltoid region of the non-dominant arm | Biological: Fluviral™<br>* 1 dose administered intramuscularly in deltoid region of 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/California/7/2009 (H1N1), Flu A/Texas/50/2012 (H3N2) and Flu B/Massachusetts/2/2012 (Yamagata). | At Days 0 and 21 | 
| Number of Seroconverted Subjects for HI 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 greater than or equal to (≥) 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/California/7/2009 (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/California/7/2009 (H1N1), Flu A/Texas/50/2012 (H3N2) and Flu B/Massachusetts/2/2012 (Yamagata). | At Day 21 | 
| Number of Subjects Who Were Seroprotected for 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/California/7/2009 (H1N1), Flu A/Texas/50/2012 (H3N2) and Flu B/Massachusetts/2/2012 (Yamagata). | At Days 0 and 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/California/7/2009 (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 2012/2013 influenza season. | At Days 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 vaccinated subject with either a pre-vaccination titer less than (<) 1:10 and a post-vaccination titer greater than or equal to (≥) 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/California/7/2009 (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 2012/2013 influenza season. | 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/California/7/2009 (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 2012/2013 influenza season. | At Day 21 | 
| Number of Subjects Who Were Seroprotected for 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/California/7/2009 (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 2012/2013 influenza season. | At Day 0 and 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 | 
| 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 [oral 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 = oral temperature above 39.0°C | 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 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. | During the entire study period (Days 0-20 post vaccination) | 

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