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

Observer-blind Immunogenicity Study of GSK Biologicals' Influenza Vaccine GSK2186877A in Elderly Subjects

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

Study Overview

• Status: Completed
• Conditions: Influenza
• Intervention / Treatment: Biological: GSK Biologicals' influenza vaccine GSK2186877A; Biological: GSK Biologicals' Fluarix

Detailed Description

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

• Study Type: Interventional
• Enrollment (Actual): 192
• Phase: Phase 3

Contacts and Locations

Study Locations

• Spain
  • Barcelona, Spain, 08035
    • GSK Investigational Site
  • Madrid, Spain, 28046
    • GSK Investigational Site
  • Marid, Spain, 28040
    • GSK Investigational Site
• United States
  • Texas
    • Houston, Texas, United States, 77030
      • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: New generation influenza vaccine GSK2186877A Group; Subjects aged ≥ 65 years receiving 1 dose of New generation influenza vaccine GSK2186877A at Day 0	Biological: GSK Biologicals' influenza vaccine GSK2186877A; One intramuscular injection at Day 0
Active Comparator: Fluarix elderly Group; Subjects aged >= 65 years receiving 1 dose of Fluarix vaccine at Day 0	Biological: GSK Biologicals' Fluarix; One intramuscular injection at Day 0
Active Comparator: Fluarix young Group; Subjects aged 18-40 years receiving 1 dose of Fluarix vaccine at Day 0	Biological: GSK Biologicals' Fluarix; One intramuscular injection at Day 0

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	The markers assessed were Cluster of Differentiation 40 Ligand (CD40L), interleukin-2 (IL-2), tumor necrosis factor alpha (TNF-α), interferon-gamma (IFN-γ)	Day 21

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	The markers assessed were CD40L, IL-2, TNF-α, IFN-γ. The separate vaccine strains tested included A/Brisbane, A/Uruguay, B/Brisbane antigens.	At Day 0, 21, 42 and 180
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	The markers assessed were CD40L, IL-2, TNF-α, IFN-γ. The separate vaccine strains tested included A/Brisbane, A/Uruguay, B/Brisbane antigens.	At Day 0, 21, 42 and 180
Haemagglutinin Inhibition (HI) Antibody Titers	Antibody titers were expressed as Geometric mean titers (GMTs) calculated after invitro stimulation with separate vaccine strains.	At Day 0, 21, 42 and 180
The Number of Subjects Seropositive to HI Antibodies Calculated After in Vitro Stimulation With Separate Vaccine Strains.	Seropositivity was defined as antibody titer greater than or equal to the cut-off value i.e ≥ 1:10	At Day 0, 21, 42 and 180
The Number of Subjects Seroconverted to HI Antibodies	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.	At Day 21, 42 and 180
HI Antibody Seroconversion Factors	Seroconversion factors were defined as the fold increase in serum HI GMTs post-vaccination compared to Day 0.	At Day 21, 42 and 180
The Number of Subjects Seroprotected to HI Antibodies	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.	At Day 0, 21, 42 and 180
Number of Subjects Reporting Any and Grade 3 Solicited Local Adverse Events (AEs)	Grade 3 ecchymosis, redness and swelling was >100mm and grade 3 pain was considerable pain at rest, that prevented normal everyday activity.	Day 0 -6
Duration of Solicited Local AEs	Duration was defined as the number of days with any grade of local symptoms.	Day 0 -6
Number of Subjects Reporting Any, Grade 3 and Related Solicited General AEs	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.	Day 0 -6
Duration of Solicited General AEs	Duration was defined as number of days with any grade of general symptoms.	Day 0 -6
Number of Subjects Reporting Any, Grade 3 and Related Unsolicited 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 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.	Day 0-20
Number of Subjects Reporting Any, Grade 3 and Related AEs With a Medically Attended Visit (MAEs)	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.	Day 0-179
Number of Subjects Reporting Any AEs of Specific Interest (AESI)	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.	Day 0-364
Number of Subjects Reporting Any and Related Serious Adverse Events (SAEs)	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.	Day 0-364

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Publications and helpful links

General Publications

• Couch RB, Bayas JM, Caso C, Mbawuike IN, Lopez CN, Claeys C, El Idrissi M, Herve C, Laupeze B, Oostvogels L, Moris P. Superior antigen-specific CD4+ T-cell response with AS03-adjuvantation of a trivalent influenza vaccine in a randomised trial of adults aged 65 and older. BMC Infect Dis. 2014 Jul 30;14:425. doi: 10.1186/1471-2334-14-425.

Helpful Links

• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

Study record dates

Study Major Dates

• Study Start: October 16, 2008
• Primary Completion (Actual): December 4, 2009
• Study Completion (Actual): December 4, 2009

Study Registration Dates

• First Submitted: October 1, 2008
• First Submitted That Met QC Criteria: October 1, 2008
• First Posted (Estimate): October 2, 2008

Study Record Updates

• Last Update Posted (Actual): July 31, 2018
• Last Update Submitted That Met QC Criteria: July 2, 2018
• Last Verified: October 1, 2016

More Information

Terms related to this study

• Keywords: Elderly; Influenza; Vaccine
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Orthomyxoviridae Infections; Influenza, Human
• Other Study ID Numbers: 112147

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.

Study Data/Documents

1. Dataset Specification
   Information identifier: 112147
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
2. Clinical Study Report
   Information identifier: 112147
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
3. Informed Consent Form
   Information identifier: 112147
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
4. Individual Participant Data Set
   Information identifier: 112147
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
5. Study Protocol
   Information identifier: 112147
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
6. Statistical Analysis Plan
   Information identifier: 112147
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register