Immunogenicity and Safety of Vaccine GSK2340272A (H1N1) and GSK Biologicals Fluarix™ Vaccine When Co-administered in Elderly

Immunogenicity, Safety and Reactogenicity of GSK Biologicals' Influenza GSK2340272A and Fluarix™ 2009-2010 Vaccines When Co-administered in Elderly Subjects Aged 61 Years and Older

The purpose of the present study is to assess the immunogenicity, safety and reactogenicity of a two-dose schedule with vaccine GSK2340272A when co-administered with GSK Biologicals' Fluarix™ vaccine either at the time of first or second vaccination in elderly subjects aged 61 years and older.

Study Overview

• Status: Completed
• Conditions: Influenza
• Intervention / Treatment: Biological: Pandemrix (Influenza vaccine GSK2340272A); Biological: Fluarix™; Biological: Placebo

Detailed Description

The study will be conducted in an open manner regarding the administration of vaccine GSK2340272A.

The study will be observer-blind regarding the administration of Fluarix™ and placebo vaccines.

• Study Type: Interventional
• Enrollment (Actual): 168
• Phase: Phase 2

Contacts and Locations

Study Locations

• Sweden
  • Eskilstuna, Sweden, SE-631 88
    • GSK Investigational Site
  • Örebro, Sweden, SE-703 62
    • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 61 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male or female subjects 61 years of age or older at the time of the first vaccination
• Subjects who the investigator believes that they can and will comply with the requirements of the protocol.
• Written informed consent obtained from the subject.
• Satisfactory baseline medical assessment by history and physical examination.
• Access to a consistent means of telephone contact.

Exclusion Criteria:

• Previous administration of the 2009 Southern Hemisphere or 2009-2010 Northern Hemisphere seasonal influenza vaccine.
• Previous administration of a pandemic influenza vaccine.
• Administration of any vaccine within 30 days before first vaccination.
• Planned administration of a vaccine not foreseen by the study protocol one month (minimum 30 days) after the second vaccination with vaccine GSK2340272A.
• Use of any investigational or non-registered product (drug or vaccine) other than the study vaccine within 30 days preceding the first dose of the study vaccines or planned use during the study period. Potential subjects in the follow-up (i.e., no treatment) phase of a prior investigational study may be enrolled if the investigator's judgment is that it will have no effect on safety, reactogenicity, or immunogenicity endpoints in this study, and that it does not violate the protocol requirements of the prior trial.
• Presence of evidence of substance abuse or of neurological or psychiatric diagnoses which, although stable, are deemed by the investigator to render the potential subject unable/unlikely to provide accurate safety reports.
• Presence of an oral temperature >= 37.5°C, or acute symptoms greater than "mild" severity on the scheduled date of first vaccination.
• Diagnosed with cancer, or treatment for cancer, within 3 years.
• Any confirmed or suspected immunosuppressive or immunodeficient condition including history of human immunodeficiency virus (HIV) infection.
• Chronic administration of immunosuppressants or other immune modifying drugs within six months prior to the first vaccination.
• Receipt of any immunoglobulins and/or any blood products within 3 months preceding the first vaccination or planned administration of any of these products during the entire study period.
• Any significant disorder of coagulation or treatment with warfarin derivatives or heparin. Persons receiving individual doses of low molecular weight heparin outside of 24 hours prior to vaccination are eligible. Persons receiving prophylactic anti-platelet medications, e.g., low-dose aspirin, and without a clinically-apparent bleeding tendency, are eligible.
• An acute evolving neurological disorder or history of Guillain-Barré syndrome.
• Serious chronic disease as determined by medical history and physical examination.
• Acute clinically significant pulmonary, cardiovascular, hepatic or renal functional abnormalities, as determined by physical examination or laboratory screening tests.
• Any known or suspected allergy to any constituent of influenza vaccines.
• History of chronic alcohol consumption and/or drug abuse.
• Clinically or virologically confirmed influenza infection within 6 months preceding the study start.
• Any conditions which, in the opinion of the investigator, prevents the subjects from participating in the study.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Pandemrix+Fluarix and Pandemrix+Placebo; Subjects received two doses of Pandemrix (GSK2340272A) intramuscularly in the deltoid region of the non-dominant arm co-administered with Fluarix™ on Day 0 and with a placebo on Day 21 intramuscularly in the deltoid region of the dominant arm.	Biological: Pandemrix (Influenza vaccine GSK2340272A); Intramuscular injection, 2 doses; Biological: Fluarix™; Intramuscular injection, 1 dose; Other Names: 2009-2010 Northern Hemisphere trivalent seasonal influenza vaccine; Biological: Placebo; Intramuscular injection, 1 dose
Experimental: Pandemrix+Placebo and Pandemrix+Fluarix; Subjects received two doses of Pandemrix (GSK2340272A) intramuscularly in the deltoid region of the non-dominant arm co-administered with a placebo on Day 0 and with Fluarix™ on Day 21 intramuscularly in the deltoid region of the dominant arm.	Biological: Pandemrix (Influenza vaccine GSK2340272A); Intramuscular injection, 2 doses; Biological: Fluarix™; Intramuscular injection, 1 dose; Other Names: 2009-2010 Northern Hemisphere trivalent seasonal influenza vaccine; Biological: Placebo; Intramuscular injection, 1 dose

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Seroconverted Subjects After the Second Dose of Pandemrix and After Vaccination With Fluarix	A seroconverted subject is a subject who had either a pre-vaccination reciprocal hemagglutination inhibition (HI) titer < 10 and a postvaccination reciprocal titer >= 40, or a pre-vaccination reciprocal HI titer >= 10 and at least a 4-fold increase in post vaccination reciprocal titer against the vaccine virus. The Pandemrix vaccine strain was A/Cal/09. The Fluarix vaccine strains were A/Bri/07, A/Uru/07 and B/Bri/08.	21 days after the second dose of Pandemrix (=Day 42) and after vaccination with Fluarix (=Day 21 for Pandemrix+Fluarix and Pandemrix+Placebo Group or Day 42 for Pandemrix+ Placebo and Pandemrix+Fluarix Group)
Number of Seroprotected Subjects After the Second Dose of Pandemrix and After Vaccination With Fluarix	A seroprotected subject was a subject with reciprocal HI titers >= 40 against the vaccine homologous virus. The Pandemrix vaccine strain was A/Cal/09. The Fluarix vaccine strains were A/Bri/07, A/Uru/07 and B/Bri/08.	21 days after the second dose of Pandemrix (=Day 42) and after vaccination with Fluarix (=Day 21 for Pandemrix+Fluarix and Pandemrix+Placebo Group or Day 42 for Pandemrix+ Placebo and Pandemrix+Fluarix Group)
Geometric Mean Fold Rise (GMFR) After the Second Dose of Pandemrix and After Vaccination With Fluarix	The GMFR is defined as the Geometric Mean of the within-subject ratios of the post-vaccination reciprocal HI titer to the pre-vaccination reciprocal HI titer for the vaccine virus. The Pandemrix vaccine strain was A/Cal/09. The Fluarix vaccine strains were A/Bri/07, A/Uru/07 and B/Bri/08.	21 days after the second dose of Pandemrix (=Day 42) and after vaccination with Fluarix (=Day 21 for Pandemrix+Fluarix and Pandemrix+Placebo Group or Day 42 for Pandemrix+ Placebo and Pandemrix+Fluarix Group)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Geometric Mean Titers for Antibodies Against Pandemrix and Fluarix Vaccine Strains	Titers are expressed as GMTs. The Pandemrix vaccine strain was A/Cal/09. The Fluarix vaccine strains were A/Bri/07, A/Uru/07 and B/Bri/08.	Days 0, 21, 42, 182, 364
Number of Seroconverted Subjects	A seroconverted subject is a subject who had either a pre-vaccination reciprocal hemagglutination inhibition (HI) titer < 10 and a postvaccination reciprocal titer >= 40, or a pre-vaccination reciprocal HI titer >= 10 and at least a 4-fold increase in post vaccination reciprocal titer against the vaccine virus. The Pandemrix vaccine strain was A/Cal/09. The Fluarix vaccine strains were A/Bri/07, A/Uru/07 and B/Bri/08.	at Day 21 (for Pandemrix vaccine strain only), Day 182 and Day 364
Number of Seroprotected Subjects	A seroprotected subject is a subject with reciprocal HI titers >= 40 against the vaccine homologous virus. The Pandemrix vaccine strain was A/Cal/09. The Fluarix vaccine strains were A/Bri/07, A/Uru/07 and B/Bri/08.	at Day 21 (for Pandemrix vaccine strain only), Day 182 and Day 364
Geometric Mean Fold Rise (GMFR)	The GMFR is defined as the Geometric Mean of the within-subject ratios of the post-vaccination reciprocal HI titer to the pre-vaccination reciprocal HI titer for the vaccine virus. The Pandemrix vaccine strain was A/Cal/09. The Fluarix vaccine strains were A/Bri/07, A/Uru/07 and B/Bri/08.	at Day 21 (for Pandemrix vaccine strain only), Day 182 and Day 364
Number of Subjects With Titers Equal to or Above Titer 1:10	The cut-off 1:10 was considered as seropositivity. The Pandemrix vaccine strain was A/Cal/09. The Fluarix vaccine strains were A/Bri/07, A/Uru/07 and B/Bri/08.	Days 0, 21, 42, 182, 364
Number of Subjects With Solicited Local and General Symptoms	Solicited local symptoms are pain, redness and swelling at the injection site. They are divided between solicited local symptoms occurring after administration of Pandemrix, Fluarix or Placebo. Solicited general symptoms are fatigue, headache, joint pain at other location, muscle aches, shivering, sweating and temperature (defined as axillary temperature >= 38.0 degrees Celsius).	Within 7 days (Day 0-Day 6) after each vaccination
Number of Subjects With Unsolicited Adverse Events (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	From Day 0 to Day 83
Number of Subjects With Adverse Events of Specific Interest	Adverse events of specific interest include autoimmune diseases and other immune mediated inflammatory disorders.	From Day 0 to Day 364
Number of Subjects With 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.	From Day 0 to Day 364

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Publications and helpful links

General Publications

• Peeters M, Regner S, Vaman T, Devaster JM, Rombo L. Safety and immunogenicity of an AS03-adjuvanted A(H1N1)pmd09 vaccine administered simultaneously or sequentially with a seasonal trivalent vaccine in adults 61 years or older: data from two multicentre randomised trials. Vaccine. 2012 Oct 5;30(45):6483-91. doi: 10.1016/j.vaccine.2012.07.081. Epub 2012 Aug 9.

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: September 12, 2009
• Primary Completion (Actual): September 23, 2010
• Study Completion (Actual): September 23, 2010

Study Registration Dates

• First Submitted: August 27, 2009
• First Submitted That Met QC Criteria: August 27, 2009
• First Posted (Estimate): August 31, 2009

Study Record Updates

• Last Update Posted (Actual): August 20, 2018
• Last Update Submitted That Met QC Criteria: July 4, 2018
• Last Verified: September 1, 2016

More Information

Terms related to this study

• Keywords: GSK Bio's influenza vaccine GSK2340272A; Influenza infection
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Orthomyxoviridae Infections; Influenza, Human; Physiological Effects of Drugs; Immunologic Factors; Vaccines
• Other Study ID Numbers: 113525

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. Annotated Case Report Form
   Information identifier: 113525
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
2. Dataset Specification
   Information identifier: 113525
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
3. Individual Participant Data Set
   Information identifier: 113525
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
4. Statistical Analysis Plan
   Information identifier: 113525
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
5. Informed Consent Form
   Information identifier: 113525
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
6. Study Protocol
   Information identifier: 113525
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
7. Clinical Study Report
   Information identifier: 113525
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register