Immunogenicity and Safety Study to Evaluate Different Formulations of GSK Biologicals' Influenza Vaccine GSK576389A

• ClinicalTrials.gov Identifier: NCT00540592
• Recruitment Status: Completed
• First Posted: October 8, 2007
• Results First Posted: May 30, 2012
• Last Update Posted: June 8, 2018
• Sponsor: GlaxoSmithKline
• Information provided by (Responsible Party): GlaxoSmithKline

Study Description

Brief Summary:

In order to find the formulation leading to a maximal increase of the immune response while maintaining an acceptable safety profile, this study is designed to evaluate the immunogenicity, safety and reactogenicity of the different formulations of GSK Biologicals' influenza vaccine administered in adults aged 65 years and older compared to Fluarix.

Condition or disease	Intervention/treatment	Phase
Influenza	Biological: GlaxoSmithKline Biologicals' influenza vaccine GSK576389A; Biological: Fluarix	Phase 2

Detailed Description:

There are 10 parallel groups: 9 observer blinded groups with subjects 65 years and older receiving an investigational vaccine or Fluarix, and 1 open group with subjects between 18 and 40 years old receiving Fluarix. CMI response will be determined for a subset only.

The Protocol Posting has been updated in order to comply with the FDA Amendment Act, Sep 2007.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 2007 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Prevention
• Official Title: Observer Blind Immunogenicity and Safety Study of GlaxoSmithKline Biologicals' Influenza Vaccine GSK576389A With Various Formulations in Adults Aged 65 Years and Above
• Study Start Date: October 8, 2007
• Actual Primary Completion Date: June 10, 2008
• Actual Study Completion Date: June 10, 2008

Arms and Interventions

Arm	Intervention/treatment
Experimental: Influenza vaccine GSK576389A formulation 1 Group; Subjects aged ≥65 years received one dose of formulation 1 of the adjuvanted influenza vaccine GSK576389A.	Biological: GlaxoSmithKline Biologicals' influenza vaccine GSK576389A; Single dose, Intramuscular injection, 8 different formulations were tested (one per group)
Experimental: Influenza vaccine GSK576389A formulation 2 Group; Subjects aged ≥65 years received one dose of formulation 2 of the adjuvanted influenza vaccine GSK576389A.	Biological: GlaxoSmithKline Biologicals' influenza vaccine GSK576389A; Single dose, Intramuscular injection, 8 different formulations were tested (one per group)
Experimental: Influenza vaccine GSK576389A formulation 3 Group; Subjects aged ≥65 years received one dose of formulation 3 of the adjuvanted influenza vaccine GSK576389A.	Biological: GlaxoSmithKline Biologicals' influenza vaccine GSK576389A; Single dose, Intramuscular injection, 8 different formulations were tested (one per group)
Experimental: Influenza vaccine GSK576389A formulation 4 Group; Subjects aged ≥65 years received one dose of formulation 4 of the adjuvanted influenza vaccine GSK576389A.	Biological: GlaxoSmithKline Biologicals' influenza vaccine GSK576389A; Single dose, Intramuscular injection, 8 different formulations were tested (one per group)
Experimental: Influenza vaccine GSK576389A formulation 5 Group; Subjects aged ≥65 years received one dose of formulation 5 of the adjuvanted influenza vaccine GSK576389A.	Biological: GlaxoSmithKline Biologicals' influenza vaccine GSK576389A; Single dose, Intramuscular injection, 8 different formulations were tested (one per group)
Experimental: Influenza vaccine GSK576389A formulation 6 Group; Subjects aged ≥65 years received one dose of formulation 6 of the adjuvanted influenza vaccine GSK576389A.	Biological: GlaxoSmithKline Biologicals' influenza vaccine GSK576389A; Single dose, Intramuscular injection, 8 different formulations were tested (one per group)
Experimental: Influenza vaccine GSK576389A formulation 7 Group; Subjects aged ≥65 years received one dose of formulation 7 of the adjuvanted influenza vaccine GSK576389A.	Biological: GlaxoSmithKline Biologicals' influenza vaccine GSK576389A; Single dose, Intramuscular injection, 8 different formulations were tested (one per group)
Experimental: Influenza vaccine GSK576389A formulation 8 Group; Subjects aged ≥65 years received one dose of formulation 8 of the adjuvanted influenza vaccine GSK576389A.	Biological: GlaxoSmithKline Biologicals' influenza vaccine GSK576389A; Single dose, Intramuscular injection, 8 different formulations were tested (one per group)
Active Comparator: Fluarix elderly Group; Subjects aged ≥65 years received one dose of Fluarix vaccine.	Biological: Fluarix; Single dose, Intramuscular injection
Active Comparator: Fluarix young Group; Subjects aged 18-40 years received one dose of Fluarix vaccine.	Biological: Fluarix; Single dose, Intramuscular injection

Outcome Measures

Primary Outcome Measures :

1. Haemagglutination Inhibition (HI) Antibody Titers [ Time Frame: At Day 21 ]
   Antibody titers were expressed as Geometric mean titers (GMTs) against each of the 3 vaccine strains in greater than or equal to 65 years age groups only. The vaccine strains included A/Solomon Islands, A/Wisconsin and B/Malaysia antigens.

Secondary Outcome Measures :

1. HI Antibody Titers at Day 0 and Day 21 [ Time Frame: At Day 0 and 21 ]
   Antibody titers were expressed as GMTs in all the vaccine groups. The vaccine strains included A/Solomon Islands, A/Wisconsin and B/Malaysia antigens.
2. HI Antibody Titers at Day 180 [ Time Frame: At Day 180 ]
   Antibody titers were expressed as GMTs in all the vaccine groups. The vaccine strains included A/Solomon Islands, A/Wisconsin and B/Malaysia antigens.
3. The Number of Subjects Seroconverted to HI Antibodies at Day 21 [ Time Frame: At Day 21 ]
   A seroconverted subject was defined as a subject who had either a pre-vaccination titer below 1:10 and a post-vaccination titer greater than or equal to 1:40 or a pre-vaccination titer greater than or equal to 1:10 and at least a 4-fold increase in post-vaccination titer. The vaccine strains included A/Solomon Islands, A/Wisconsin and B/Malaysia antigens.
4. The Number of Subjects Seroconverted to HI Antibodies at Day 180 [ Time Frame: At Day 180 ]
   A seroconverted subject was defined as a subject who had either a pre-vaccination titer below 1:10 and a post-vaccination titer greater than or equal to 1:40 or a pre-vaccination titer greater than or equal to 1:10 and at least a 4-fold increase in post-vaccination titer. The vaccine strains included A/Solomon Islands, A/Wisconsin and B/Malaysia antigens.
5. HI Antibody Seroconversion Factors at Day 21 [ Time Frame: At Day 21 ]
   Seroconversion factors were defined as the fold increase in serum HI GMTs post-vaccination compared to Day 0. The vaccine strains included A/Solomon Islands, A/Wisconsin and B/Malaysia antigens.
6. HI Antibody Seroconversion Factors at Day 180 [ Time Frame: At Day 180 ]
   Seroconversion factors were defined as the fold increase in serum HI GMTs post-vaccination compared to Day 0. The vaccine strains included A/Solomon Islands, A/Wisconsin and B/Malaysia antigens.
7. The Number of Subjects Seroprotected to HI Antibodies at Day 0 and 21 [ Time Frame: At Day 0 and 21 ]
   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 vaccine strains included A/Solomon Islands, A/Wisconsin and B/Malaysia antigens.
8. The Number of Subjects Seroprotected to HI Antibodies at Day 180 [ Time Frame: At Day 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 vaccine strains included A/Solomon Islands, A/Wisconsin and B/Malaysia antigens.
9. The Geometric Mean (GM) Number of Influenza-specific CD4 T-cells Per Million CD4+ T-cells for Each Vaccine Strain Producing at Least Two Different Immune Markers or Producing Each of the Immune Markers Plus Another Immune Marker at Days 0 and 21 [ Time Frame: At Days 0 and 21 ]
   The markers assessed were Cluster of Differentiation 4-All doubles i.e. CD4-All doubles, CD4-CD40Ligand(L), CD4-interferon gamma (CD4-IFNγ), CD4-interleukin 2 (CD4-IL2) and CD4-tumor necrosis factor alpha (CD4-TNFα). The vaccine strains included A/Solomon Islands, A/Wisconsin and B/Malaysia antigens.
10. The GM Number of Influenza-specific CD4 T-cells Per Million CD4+ T-cells for Each Vaccine Strain Producing at Least Two Different Immune Markers or Producing Each of the Immune Markers Plus Another Immune Marker at Day 180 [ Time Frame: At Day 180 ]
    The markers assessed were CD4-All doubles, CD4-CD40L, CD4-IFNγ, CD4-IL2 and CD4-TNFα. The vaccine strains included A/Solomon Islands, A/Wisconsin and B/Malaysia antigens.
11. The GM Number of Influenza-specific CD8 T-cells Per Million CD8+ T-cells for Each Vaccine Strain Producing at Least Two Different Immune Markers or Producing Each of the Immune Markers Plus Another Immune Marker at Days 0 and 21 [ Time Frame: At Days 0 and 21 ]
    The markers assessed were Cluster of Differentiation 8-All doubles i.e. CD8-All doubles, CD8-CD40L, CD8-IFNγ, CD8-IL2 and CD8-TNFα. The vaccine strains included A/Solomon Islands, A/Wisconsin and B/Malaysia antigens.
12. The GM Number of Influenza-specific CD8 T-cells Per Million CD8+ T-cells for Each Vaccine Strain Producing at Least Two Different Immune Markers or Producing Each of the Immune Markers Plus Another Immune Marker at Day 180 [ Time Frame: At Day 180 ]
    The markers assessed were CD8-All doubles, CD8-CD40L, CD8-IFNγ, CD8-IL2 and CD8-TNFα. The vaccine strains included A/Solomon Islands, A/Wisconsin and B/Malaysia antigens.
13. Number of Subjects Reporting Any and Grade 3 Solicited Local Adverse Events (AEs) [ Time Frame: During a 7-day follow-up period (Day 0-6) after vaccination ]
    Grade 3 ecchymosis, pain, redness and swelling was greater than 100 millimeter (mm) i.e. > 100 mm and grade 3 pain was considerable pain at rest that prevented normal everyday activities. Any was occurrence of any local symptom regardless of their intensity grade. Any for ecchymosis, redness and swelling was >20mm.
14. Duration of Solicited Local AEs [ Time Frame: During a 7-day follow-up period (Day 0-6) after vaccination ]
    Duration was defined as number of days with any grade of local symptoms.
15. Number of Subjects Reporting Any, Grade 3 and Related Solicited General AEs [ Time Frame: During a 7-day follow-up period (Day 0-6) after vaccination ]
    Any Fever was defined as axillary temperature greater than or equal to 38.0 degree centigrade i.e.≥ 38.0°C, grade 3 fever was axillary temperature >40°C. For other symptoms, any was defined as occurrence of any general symptom regardless of intensity grade or relation to vaccination and grade 3 was defined as a general symptom that prevented normal activity. Related was a general symptom assessed by the investigator as causally related to the study vaccination.
16. Duration of Solicited General AEs [ Time Frame: During a 7-day follow-up period (Day 0-6) after vaccination ]
    Duration was defined as number of days with any grade of general symptoms.
17. Number of Subjects Reporting Any, Grade 3 and Related Unsolicited AEs [ Time Frame: During a 21-day follow-up period (Day 0-20) after vaccination ]
    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. Grade 3 was an event that prevented normal activities and related was defined as an unsolicited AE assessed by the investigator to be causally related to the study vaccination.
18. Number of Subjects Reporting Any, Grade 3 and Related Adverse Events Resulting in Medically Attended Visit Between Day 0 and Day 20 [ Time Frame: Between Day 0 and Day 20 after vaccination ]
    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 or relation to vaccination and grade 3 was defined as a symptom that prevented normal activity. Related was a symptom assessed by the investigator as causally related to the study vaccination.
19. Number of Subjects Reporting Any, Grade 3 and Related Adverse Events Resulting in Medically Attended Visit Between Day 21 and Day 179 [ Time Frame: Between Day 21 and Day 179 after vaccination ]
    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 or relation to vaccination and grade 3 was defined as a symptom that prevented normal activity. Related was a symptom assessed by the investigator as causally related to the study vaccination.
20. Number of Subjects Reporting Any and Related Serious Adverse Events (SAEs) Between Day 0 and Day 20 [ Time Frame: Between Day 0 and Day 20 after vaccination ]
    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 or relation to vaccination and related was an event assessed by the investigator as causally related to the study vaccination.
21. Number of Subjects Reporting Any and Related Serious Adverse Events (SAEs) Between Day 21 and Day 179 [ Time Frame: Between Day 21 and Day 179 after vaccination ]
    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 or relation to vaccination and related was an event assessed by the investigator as causally related to the study vaccination.

Eligibility Criteria

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

Criteria

Inclusion Criteria:

• Subjects who the investigator believes that they can and will comply with the requirements of the protocol should be enrolled in the study.
• A male or female aged 18-40 years old or 65 years or older at the time of the vaccination.
• Written informed consent obtained from the subject.
• Free of an acute aggravation of the health status as established by clinical evaluation (medical history and medical history directed examination) before entering into the study.
• If the subject is female, she must be of non-childbearing potential 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 completion of the vaccination series.

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 during the entire study period.
• Planned administration of an influenza vaccine other than the study vaccines during the entire study period.
• Vaccination against influenza since January 2007 (with 2007/2008 or 2006/2007 influenza vaccine).
• Administration of more than 14 days of immunosuppressants or other immune-modifying drugs within 6 months prior to the administration of the study vaccine.
• Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination
• Hypersensitivity to a previous dose of influenza vaccine.
• Allergy to any component of the vaccine.
• Acute (active) clinically significant pulmonary, cardiovascular, hepatic or renal functional abnormality.
• Acute disease at the time of enrolment. (Acute disease is defined as the presence of a moderate or severe illness with or without fever. All vaccines can be administered to persons with a minor illness such as diarrhoea, mild upper respiratory infection with or without low-grade febrile illness, i.e. axillary temperature<37.5ºC (99.5ºF).
• 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 IM injections are contraindicated.
• Lactating female or female planning to become pregnant or to discontinue contraceptive precautions

Contacts and Locations

Locations

Germany

GSK Investigational Site

Gueglingen, Baden-Wuerttemberg, Germany, 74363

GSK Investigational Site

Mannheim, Baden-Wuerttemberg, Germany, 68161

GSK Investigational Site

Rudersberg, Baden-Wuerttemberg, Germany, 73635

GSK Investigational Site

Weinheim, Baden-Wuerttemberg, Germany, 69469

GSK Investigational Site

Augsburg, Bayern, Germany, 86150

GSK Investigational Site

Essen, Nordrhein-Westfalen, Germany, 45359

GSK Investigational Site

Koeln, Nordrhein-Westfalen, Germany, 51069

GSK Investigational Site

Mainz, Rheinland-Pfalz, Germany, 55131

GSK Investigational Site

Rhaunen, Rheinland-Pfalz, Germany, 55624

GSK Investigational Site

Magdeburg, Sachsen-Anhalt, Germany, 39112

GSK Investigational Site

Wolmirstedt, Sachsen-Anhalt, Germany, 39326

GSK Investigational Site

Dresden, Sachsen, Germany, 01067

GSK Investigational Site

Freital, Sachsen, Germany, 01705

GSK Investigational Site

Leipzig, Sachsen, Germany, 04103

GSK Investigational Site

Berlin, Germany, 10435

GSK Investigational Site

Berlin, Germany, 12627

GSK Investigational Site

Berlin, Germany, 13347

GSK Investigational Site

Berlin, Germany, 13359

GSK Investigational Site

Hamburg, Germany, 22335

GSK Investigational Site

Hamburg, Germany, 22415

Netherlands

GSK Investigational Site

Rotterdam, Netherlands, 3011 EN

GSK Investigational Site

Rotterdam, Netherlands, 3015 GE

Sweden

GSK Investigational Site

Eskilstuna, Sweden, SE-631 88

GSK Investigational Site

Karlskrona, Sweden, SE-371 41

GSK Investigational Site

Uppsala, Sweden, SE-751 85

United Kingdom

GSK Investigational Site

Reading, Berkshire, United Kingdom, RG2 0TG

GSK Investigational Site

Buckshaw Village, Chorley, Lancashire, United Kingdom, PR7 7NA

GSK Investigational Site

Clydebank, Glasgow, United Kingdom, G81 2DR

GSK Investigational Site

Edgbaston, Birmingham, United Kingdom, B15 2SQ

GSK Investigational Site

Waterloo, Liverpool, United Kingdom, L22 0LG

Sponsors and Collaborators

GlaxoSmithKline

Investigators

• Study Director: GSK Clinical Trials; GlaxoSmithKline

More Information

Additional Information:

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 Data/Documents: Annotated Case Report Form 

Identifier: 110847
For additional information about this study please refer to the GSK Clinical Study Register

Informed Consent Form 

Identifier: 110847
For additional information about this study please refer to the GSK Clinical Study Register

Statistical Analysis Plan 

Identifier: 110847
For additional information about this study please refer to the GSK Clinical Study Register

Clinical Study Report 

Identifier: 110847
For additional information about this study please refer to the GSK Clinical Study Register

Individual Participant Data Set 

Identifier: 110847
For additional information about this study please refer to the GSK Clinical Study Register

Dataset Specification 

Identifier: 110847
For additional information about this study please refer to the GSK Clinical Study Register

Study Protocol 

Identifier: 110847
For additional information about this study please refer to the GSK Clinical Study Register

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Rümke HC, Richardus JH, Rombo L, Pauksens K, Plaßmann G, Durand C, Devaster JM, Dewé W, Oostvogels L. Selection of an adjuvant for seasonal influenza vaccine in elderly people: modelling immunogenicity from a randomized trial. BMC Infect Dis. 2013 Jul 26;13:348. doi: 10.1186/1471-2334-13-348.

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT00540592
• Other Study ID Numbers: 110847
• First Posted: October 8, 2007
• Results First Posted: May 30, 2012
• Last Update Posted: June 8, 2018
• Last Verified: October 2016

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• 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.

Keywords provided by GlaxoSmithKline:

Influenza vaccine GSK576389A; Influenza infection; Fluarix

Additional relevant MeSH terms:

Influenza, Human; Respiratory Tract Infections; Infections; Orthomyxoviridae Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases