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

Phase 3

Completed

Conditions: Influenza

Interventions: Biological: Fluviral™

Registration Number: NCT01878825

Lead Sponsor: GlaxoSmithKline

Brief Summary: 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 121

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Fluviral >60 Years Group	Fluviral™	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
Fluviral 18-60 Years Group	Fluviral™	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.

Primary Outcome Measures

Name	Time	Method
Number of Subjects Who Were Seroprotected for HI Antibodies Against Each of the Three Vaccine Influenza Strains.	At Days 0 and Day 21	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).
Mean Geometric Increase (MGI) for Haemagglutination Inhibition (HI) Antibody Titer Against Each of the Three Vaccine Influenza Strains.	At Day 21	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).
Number of Seroconverted Subjects for HI Antibodies Against Each of the Three Vaccine Influenza Strains.	At Day 21	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).
Humoral Immune Response in Terms of Haemagglutination Inhibition (HI) Antibody Titers Against Each of the Three Vaccine Influenza Strains	At Days 0 and 21	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).

Secondary Outcome Measures

Name	Time	Method
Number of Subjects Who Were Seroprotected for HI Antibodies Against Each of the Three Vaccine Influenza Strains.	At Day 0 and Day 21	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.
Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms.	During the 4-day (Days 0-3) post-vaccination period	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
Number of Subjects Reporting Any Serious Adverse Events (SAEs)	During the entire study period (Days 0-20 post vaccination)	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.
Mean Geometric Increase (MGI) for Haemagglutination Inhibition (HI) Antibody Titer Against Each of the Three Vaccine Influenza Strains.	At Day 21	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.
Number of Subjects Reporting Any Unsolicited Adverse Events (AEs)	During the 21-day (Days 0-20) post-vaccination period	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.
Humoral Immune Response in Terms of HI Antibody Titers Against Each of the Three Vaccine Influenza Strains	At Days 0 and Day 21	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.
Number of Subjects Reporting Any and Grade 3 Solicited Local Symptoms.	During the 4-day (Days 0-3) post-vaccination period	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.
Number of Seroconverted Subjects for HI Antibodies Against Each of the Three Vaccine Influenza Strains.	At Day 21	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.