A Study of Immunogenicity and Safety of GSK Biologicals' Influenza Vaccine FLU-Q-QIV in Adults Aged 18 Years and Older

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to evaluate the immunogenicity and the safety of GlaxoSmithKline (GSK) Biologicals' investigational quadrivalent split virion influenza vaccine FLU-Q-QIV in adults 18 years of age and older.

Official Title
-----------------
A Phase IIIA Study of Immunogenicity and Safety of GSK Biologicals' Quadrivalent Split Virion Influenza Vaccine FLU-Q-QIV in Adults Aged 18 Years and Older

Conditions
-----------------
Influenza

Intervention / Treatment
-----------------
* Biological: FLULAVAL® QUADRIVALENT


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Subjects who the investigator believes that they can and will comply with the requirements of the protocol. Written informed consent obtained from the subject Male and female adults, 18 years of age and older in stable health as determined by investigator's clinical examination and assessment of subjects' medical history. 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: 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. 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. Acute disease and/or fever at the time of enrolment. Significant acute or chronic, uncontrolled medical or psychiatric illness. Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination. Acute, clinically significant pulmonary, cardiovascular, hepatic or renal functional abnormality, based on history and physical examination. 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 study vaccine dose. A history of any demyelinating disease including Multiple Sclerosis and Guillain-Barré syndrome. Presence of an active neurological disorder. 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 anti-platelet 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 FLU-Q-QIV 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
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

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: FLULAVAL QUADRIVALENT Adult Group<br>Subjects 18-60 years of age received 1 dose of FLULAVAL® QUADRIVALENT vaccine at Day 0. The vaccine was administered intramuscularly in the deltoid of the non-dominant arm. | Biological: FLULAVAL® QUADRIVALENT<br>* Intramuscular injection, 1 dose each in FLULAVAL QUADRIVALENT Adults and FLULAVAL QUADRIVALENT Elderly Groups<br>|
| Experimental: FLULAVAL QUADRIVALENT Elderly Group<br>Subjects above 60 years of age received 1 dose of FLULAVAL® QUADRIVALENT vaccine at Day 0. The vaccine was administered intramuscularly in the deltoid of the non-dominant arm. | Biological: FLULAVAL® QUADRIVALENT<br>* Intramuscular injection, 1 dose each in FLULAVAL QUADRIVALENT Adults and FLULAVAL QUADRIVALENT Elderly Groups<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Humoral Immune Response in Terms of Hemagglutination Inhibition (HI) Antibodies Against Each of the 4 Vaccine Influenza Strains. | Antibody titres were expressed as Geometric mean titers (GMTs). The vaccine strains assessed were Flu B/Florida/4/06 (Yamagata), FluB/Bri/60/08 (Victoria), Flu A/CAL/7/09 (H1N1) and Flu A/Victoria/210/09 (H3N2) antigens. | At Day 0 and Day 21 | 
| Number of Subjects Who Were Seroprotected for HI Antibodies Against Each of the 4 Vaccine Influenza Strains. | A seroprotected subject was defined as a subject with a serum HI titer greater than or equal to 1:40 that usually is accepted as indicating protection. The vaccine strains assessed were Yamagata, Victoria, H1N1 and H3N2 antigens. | At Day 0 and Day 21 | 
| Number of Seroconverted Subjects for HI Antibodies Against Each of the 4 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 strains assessed were Yamagata, Victoria, H1N1 and H3N2 antigens. | At Day 21 | 
| HI Antibody Seroconversion Factors (SCFs) Against Each of the 4 Vaccine Influenza Strains. | SCFs were defined as the fold increase in serum HI GMTs post-vaccination compared to Day 0. The vaccine strains assessed were Yamagata, Victoria, H1N1 and H3N2 antigens. | 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 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 redness and swelling were defined as redness/swelling 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 chest tightness, chills, cough, fatigue, headache, joint pain at other location, muscle pain, red eyes, sore throat, swelling of the face and fever [oral temperature ≥ 38.0 degrees Celsius (°C)]. 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). | An unsolicited AE was defined as any AE (i.e. any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with use of a medicinal product, whether or not considered related to the medicinal product) 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) | A serious adverse event was any untoward medical occurrence 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
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Influenza, Phase III, Seasonal influenza