Study to Evaluate the Safety and Immunogenicity of GlaxoSmithKline Biologicals' Influenza Vaccine in Elderly People

Phase 3

Completed

Conditions: Influenza

Interventions: Biological: FluarixTM
Biological: GSK investigational vaccine 2186877A

Registration Number: NCT00992784

Lead Sponsor: GlaxoSmithKline

Brief Summary: The purpose of the study is to evaluate the safety of GSK Biologicals' influenza vaccine. Elderly subjects were randomized in the primary study (NCT00760617) and will now receive the same vaccine for the third time. For this study the masking is "observer-blind" for elderly subjects and "open" for young adult subjects.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 370

Inclusion Criteria

All subjects must satisfy ALL the following criteria at study entry:

Subjects who the investigator believes that they can and will comply with the requirements of the protocol should be enrolled in the study. Specific attention should be given to the compliance potential of subjects with suspected drug or alcohol abuse.
A male or female aged 19-43 years or >=66 years at the time of the vaccination and who participated in the study NCT00760617 and completed the 6-month follow-up.
Written informed consent obtained from the subject.
Free of an acute aggravation of the health status as established by clinical evaluation 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 for 2 months after the vaccination.

Exclusion Criteria

The following criteria should be checked at the time of study entry. If ANY exclusion criterion applies, the subject must not be included in the study:

Use of any investigational or non-registered product other than the study vaccine(s) within 30 days prior to vaccination, or planned use during the study period.
Administration of other licensed vaccines within 2 weeks (for inactivated vaccines) or 4 weeks (for live vaccines) prior to enrolment in this study. Planned administration of an influenza vaccine other than the study vaccines or of a vaccine not foreseen in the study protocol during the entire study period.
Vaccination against influenza since January 2009 with a seasonal influenza vaccine.
Chronic administration of immunosuppressants or other immune-modifying drugs within six months prior to the administration of the study vaccine.
Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination.
History of hypersensivity to a previous dose of influenza vaccine.
History of allergy or reactions likely to be exacerbated by any component of the vaccine(s).
Acute clinically significant pulmonary, cardiovascular, hepatic, renal, neurological and psychiatric disorders, as determined by clinical evaluation or pre-existing laboratory screening tests.
Acute disease and/or fever at the time of enrolment.
- Fever is defined as temperature >=37.5°C on oral setting.
- Subjects with a minor illness without fever may be enrolled at the discretion of the investigator.
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.
Any medical conditions in which IM injections are contraindicated
Pregnant or lactating female.
Female planning to become pregnant or planning to discontinue contraceptive precautions.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Fluarix young Group	FluarixTM	Subjects aged 19-43 years receiving 1 dose of Fluarix vaccine
New generation influenza vaccine GSK2186877A Group	GSK investigational vaccine 2186877A	Subjects aged ≥ 66 years receiving 1 dose of New generation influenza vaccine GSK2186877A
Fluarix elderly Group	FluarixTM	Subjects aged ≥ 66 years receiving 1 dose of Fluarix vaccine

Primary Outcome Measures

Name	Time	Method
Duration of Solicited Local AEs	Day 0-6	Duration was defined as number of days with any grade of local symptoms.
Number of Subjects Reporting Any, Grade 3 and Related Solicited General AEs	Day 0-6	Any fever was defined as oral temperature ≥ 38.0 degree centigrade (°C), grade 3 fever was oral temperature ≥ 39.0°C-≤ 40.0°C. For other symptoms, any was defined as occurrence of any general symptom regardless of intensity grade, grade 3 was defined as general symptom that prevented normal activity and related was general symptom assessed by the investigator as causally related to the study vaccination.
Number of Subjects Reporting Any and Grade 3 Solicited Local Adverse Events (AEs)	Day 0-6	Grade 3 ecchymosis, redness and swelling was ≥ 100 millimeter (mm) and grade 3 pain was considerable pain at rest, that prevented normal everyday activities.
Number of Subjects Reporting AEs of Specific Interest (AESI)	Day 0-179	AESI for safety monitoring are a subset of AEs that include both clearly autoimmune diseases and also other inflammatory and/or neurologic disorders which may or may not have an autoimmune etiology. Any was defined as occurrence of any symptom regardless of intensity grade, grade 3 was defined as symptom that prevented normal activity and related was general symptom assessed by the investigator as causally related to the study vaccination.
Number of Subjects Reporting Any, Grade 3 and Related AEs With a Medically Attended Visit	Day 0-179	For each solicited and unsolicited AE the subject experienced, the subject was asked if they had received medical attention defined as hospitalization, an emergency room visit or a visit to or from medical personnel (medical doctor) for any reason. Any was defined as occurrence of any symptom regardless of intensity grade, grade 3 was defined as symptom that prevented normal activity and related was general symptom assessed by the investigator as causally related to the study vaccination.
Number of Subjects Reporting Any and Related Serious Adverse Events (SAEs) up to Day 180	Up to Day 180	SAEs assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization, result in disability/incapacity or are a congenital anomaly/birth defect in the offspring of a study subject. Any was defined as occurrence of any symptom regardless of intensity grade and related was event assessed by the investigator as causally related to the study vaccination.
Duration of Solicited General AEs	Day 0-6	Duration was defined as number of days with any grade of general symptoms.
Number of Subjects Reporting Any, Grade 3 and Related Unsolicited AEs	Day 0-20	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, grade 3 was unsolicited symptom that prevented normal activity and related was event assessed by the investigator as causally related to the study vaccination.
Number of Subjects Reporting Any and Related Serious Adverse Events (SAEs) After Day 180	After Day 180	SAEs assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization, result in disability/incapacity or are a congenital anomaly/birth defect in the offspring of a study subject. Any was defined as occurrence of any symptom regardless of intensity grade and related was event assessed by the investigator as causally related to the study vaccination.

Secondary Outcome Measures

Name	Time	Method
The Number of Subjects Seroconverted to HI Antibodies at Day 180	Day 180	A seroconverted subject was defined as a subject who had either a pre-vaccination titer \< 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 Number of Subjects Seroconverted to HI Antibodies at Day 21	Day 21	A seroconverted subject was defined as a subject who had either a pre-vaccination titer \< 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.
HI Antibody SCF at Day 180	At Day 180	SCF was defined as the fold increase in serum HI GMTs post-vaccination compared to Day 0.
HI Antibody Titers at Day 180	Day 180	Antibody titers were expressed as GMTs against separate vaccine strains. The vaccine strains included A/Brisbane, A/Uruguay and B/Brisbane antigens.
The Number of Subjects Seroprotected to HI Antibodies at Days 0 and 21	At Day 0 and Day 21	A seroprotected subject was defined as a subject with a serum HI titer ≥ to 1:40 that usually is accepted as indicating protection.
The Number of Subjects Seropositive to HI Antibodies at Days 0 and 21	Day 0 and Day 21	Seropositivity was defined as antibody titer greater than or equal to the cut-off value i.e ≥ 1:10.
The Number of Subjects Seropositive to HI Antibodies at Day 180	Day 180	Seropositivity was defined as antibody titer greater than or equal to the cut-off value i.e ≥ 1:10.
The Number of Subjects Seroprotected to HI Antibodies at Day 180	At Day 180	A seroprotected subject was defined as a subject with a serum HI titer ≥ 1:40 that usually is accepted as indicating protection.
The GM Number of Influenza Specific Cluster of Differentiation 4 (CD4) T-cells Per Million CD4 T-cells for Each Vaccine Strain Expressing at Least Two Different Markers or Expressing Different Combinations of Markers at Day 180	At Day 180	The markers assessed were CD40L, IL-2, TNF-α and IFN-γ and vaccine strains tested included A/Brisbane, A/Uruguay and B/Brisbane antigens.
Haemagglutination Inhibition (HI) Antibody Titers at Days 0 and 21	Day 0 and Day 21	Antibody titers were expressed as Geometric mean titers (GMTs) against separate vaccine strains. The vaccine strains included A/Brisbane, A/Uruguay and B/Brisbane antigens.
HI Antibody Seroconversion Factors (SCF) at Day 21	At Day 21	SCF was defined as the fold increase in serum HI GMTs post-vaccination compared to Day 0.
The Geometric Mean (GM) Number of Influenza Specific Cluster of Differentiation 4 (CD4) T-cells Per Million CD4 T-cells for Each Vaccine Strains Expressing at Least Two Different Markers or Expressing Different Combinations of Markers at Days 0 and 21	At Day 0 and Day 21	The markers assessed were Cluster of Differentiation 40 Ligand (CD40L), interleukin 2 (IL-2), tumour necrosis factor alpha (TNF-α) and interferon gamma (IFN-γ) and vaccine strains tested included A/Brisbane, A/Uruguay and B/Brisbane antigens.