Clinical Study of the Immunogenicity of GSK Biologicals' Influenza Vaccine GSK2186877A in People Aged 65 Years or Older

Phase 3

Completed

Conditions: Influenza

Interventions: Biological: GSK Biologicals' influenza vaccine GSK2186877A
Biological: GSK Biologicals' Fluarix

Registration Number: NCT00765076

Lead Sponsor: GlaxoSmithKline

Brief Summary: This clinical trial aims to study the immunogenicity of GSK Biologicals' influenza vaccine GSK2186877A in people aged 65 years or older.

Detailed Description: The amendment to the protocol posting: minor change in one inclusion criterion and in one secondary outcome measure.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 192

Inclusion Criteria

All subjects must satisfy 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 or known drug or alcohol abuse.
Written informed consent obtained from the subject.
Free of an acute aggravation of the health status as established by medical history and clinical examination before entering into the study.

Elderly adults:

• A man or woman 65 year of age or older at the time of the first vaccination.

Young adults:

Man or woman between the ages of 18 and 40 years, inclusive.
If the subject is female, she must be of non-childbearing potential or be post-menopausal, or if she is of childbearing potential, she must practice adequate contraception for 30 days prior to vaccination, have a negative pregnancy test and continue such precautions for 2 months after vaccination.

Exclusion Criteria

Use of any investigational or non-registered product (drug or vaccine) 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 a vaccine not foreseen by the study protocol up to Visit 4 after vaccination and of an influenza vaccine other than the study vaccines up to Visit 4.
Vaccination against influenza since February 2008 with a seasonal influenza vaccine.
Previous vaccination in the last three years with an investigational adjuvanted vaccine candidate seasonal or pandemic influenza vaccine.
Chronic administration (defined as more than 14 days) of immunosuppressants or other immune-modifying drugs within six months prior to the first vaccine dose.
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) including egg or chicken protein.
Acute (active) clinically significant pulmonary, cardiovascular, hepatic or renal functional abnormality, as determined by clinical evaluation or pre-existing laboratory screening tests.
Acute disease at the time of enrolment.
Administration of immunoglobulins and/or any blood products within the three months preceding the first administration of the study vaccine or planned administration during the study.
Any medical conditions in which intramuscular injections are contraindicated.
Pregnant or lactating female.
Female of childbearing age planning to become pregnant or planning to discontinue contraceptive precautions.
Any medical condition that in the opinion of the investigator precludes the collection of blood volumes as required by the protocol.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
New generation influenza vaccine GSK2186877A Group	GSK Biologicals' influenza vaccine GSK2186877A	Subjects aged ≥ 65 years receiving 1 dose of New generation influenza vaccine GSK2186877A at Day 0
Fluarix elderly Group	GSK Biologicals' Fluarix	Subjects aged \>= 65 years receiving 1 dose of Fluarix vaccine at Day 0
Fluarix young Group	GSK Biologicals' Fluarix	Subjects aged 18-40 years receiving 1 dose of Fluarix vaccine at Day 0

Primary Outcome Measures

Name	Time	Method
The Geometric Mean (GM) Number of Influenza-specific CD4 T-cells Per Million CD4+ T-cells Identified After in Vitro Stimulation With Pooled Vaccine Strains Which Are Producing at Least Two Different Markers	Day 21	The markers assessed were Cluster of Differentiation 40 Ligand (CD40L), interleukin-2 (IL-2), tumor necrosis factor alpha (TNF-α), interferon-gamma (IFN-γ)

Secondary Outcome Measures

Name	Time	Method
Number of Subjects Reporting Any, Grade 3 and Related AEs With a Medically Attended Visit (MAEs)	Day 0-179	For each solicited and unsolicited AE the subject experienced, the subject was asked if they 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 or relation to vaccination, grade 3 was defined as symptom that prevented normal activity and related was event assessed by investigator as causally related to the study vaccination.
The Number of Subjects Seroprotected to HI Antibodies	At Day 0, 21, 42 and 180	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 GM Number of Influenza-specific CD4 T-cells Per Million CD4+ T-cells Identified After in Vitro Stimulation With Pooled Vaccine Strains and With Each Vaccine Strain Separately Which Were Producing at Least Two Different Markers	At Day 0, 21, 42 and 180	The markers assessed were CD40L, IL-2, TNF-α, IFN-γ. The separate vaccine strains tested included A/Brisbane, A/Uruguay, B/Brisbane antigens.
The GM Number of Influenza-specific CD4 T-cells Per Million CD4+ T-cells Identified After in Vitro Stimulation With Pooled Vaccine Strains and With Each Vaccine Strain Separately Producing Each of the Immune Markers Plus Another Immune Marker	At Day 0, 21, 42 and 180	The markers assessed were CD40L, IL-2, TNF-α, IFN-γ. The separate vaccine strains tested included A/Brisbane, A/Uruguay, B/Brisbane antigens.
Haemagglutinin Inhibition (HI) Antibody Titers	At Day 0, 21, 42 and 180	Antibody titers were expressed as Geometric mean titers (GMTs) calculated after invitro stimulation with separate vaccine strains.
The Number of Subjects Seropositive to HI Antibodies Calculated After in Vitro Stimulation With Separate Vaccine Strains.	At Day 0, 21, 42 and 180	Seropositivity was defined as antibody titer greater than or equal to the cut-off value i.e ≥ 1:10
The Number of Subjects Seroconverted to HI Antibodies	At Day 21, 42 and 180	Seroconversion was defined as the number of vaccinees who had either a prevaccination 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.
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 or relation to vaccination, grade 3 was unsolicited symptom that prevented normal activity and related was event assessed by investigator as causally related to the study vaccination.
HI Antibody Seroconversion Factors	At Day 21, 42 and 180	Seroconversion factors were defined as the fold increase in serum HI GMTs post-vaccination compared to Day 0.
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 defined as oral temperature ≥ 39.0°C. For other symptoms 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 \>100mm and grade 3 pain was considerable pain at rest, that prevented normal everyday activity.
Duration of Solicited Local AEs	Day 0 -6	Duration was defined as the number of days with any grade of local symptoms.
Number of Subjects Reporting Any and Related Serious Adverse Events (SAEs)	Day 0-364	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 or relation to vaccination and related was event assessed by investigator as causally related to the study vaccination.
Number of Subjects Reporting Any AEs of Specific Interest (AESI)	Day 0-364	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 or relation to vaccination.