Immunogenicity and Safety Study of GlaxoSmithKline (GSK) Biologicals' Influenza Vaccine When Administered in Children Who Previously Participated in Study 115345

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT01702454
First received: October 4, 2012
Last updated: July 10, 2014
Last verified: June 2014
  Purpose

The purpose of this study is to assess the safety and immunogenicity of GSK Biologicals' investigational vaccine GSK2321138A in children who previously participated in study 115345 (FLU D-QIV-004 PRI) (NCT01439360).


Condition Intervention Phase
Influenza
Biological: Fluarix Quadrivalent
Phase 3

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: Immunogenicity, Safety and Reactogenicity Study of GSK Biologicals' Quadrivalent Seasonal Influenza Candidate Vaccine GSK2321138A, Administered to Children Who Previously Participated in Study 115345

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Serum Hemagglutination Inhibition (HI) Antibody Titers Against Each of the Four Vaccine Strains After 1 Dose of Fluarix Quadrivalent Vaccine [ Time Frame: At Day 0 and Day 7 ] [ Designated as safety issue: No ]
    Antibody titers were expressed as Geometric Mean Titers (GMTs). The vaccine strains included A/Christchurch/16/2010 ( H1N1), A/Victoria/361/2011 (H3N2), B/Brisbane/60/2008 (Victoria) and B/Hubei-Wujiagang/158/2009 (Yamagata) antigens.

  • Number of Seropositive Subjects Against Each of the Four Vaccine Strains After 1 Dose of Fluarix Quadrivalent Vaccine [ Time Frame: At Day 0 and Day 7 ] [ Designated as safety issue: No ]
    Seropositivity was defined as number of subjects with antibody titers greater than or equal to (≥) 1:10. The vaccine strains included A/Christchurch/16/2010 ( H1N1), A/Victoria/361/2011 (H3N2), B/Brisbane/60/2008 (Victoria) and B/Hubei-Wujiagang/158/2009 (Yamagata) antigens.

  • Number of Subjects Seroconverted for HI Antibodies Against Against Each of the Four Vaccine Strains After 1 Dose of Fluarix Quadrivalent Vaccine. [ Time Frame: At Day 7 ] [ Designated as safety issue: No ]
    A seroconverted subject was defined as a subject who had either a pre-vaccination titer below 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 vaccine strains included A/Christchurch/16/2010 ( H1N1), A/Victoria/361/2011 (H3N2), B/Brisbane/60/2008 (Victoria) and B/Hubei-Wujiagang/158/2009 (Yamagata) antigens.

  • Mean Geometric Increase (MGI) for HI Antibody Titer Against Each of the Four Vaccine Strains After 1 Dose of Fluarix Quadrivalent Vaccine. [ Time Frame: At Day 7 ] [ Designated as safety issue: No ]
    MGI was defined as the fold increase in serum HI GMT post-vaccination compared to Day 0. The vaccine strains included A/Christchurch/16/2010 ( H1N1), A/Victoria/361/2011 (H3N2), B/Brisbane/60/2008 (Victoria) and B/Hubei-Wujiagang/158/2009 (Yamagata) antigens.

  • Number of Subjects Seroprotected for Anti-HA Antibodies Against Each of the Four Vaccine Strains After 1 Dose of Fluarix Quadrivalent Vaccine. [ Time Frame: At Day 0 and Day 7 ] [ Designated as safety issue: No ]
    Seroprotection rate SPR was defined as the number of vaccinees with serum haemagglutination inhibition (HI) titer ≥ 1:40 that usually is accepted as indicating protection in adults. The vaccine strains included A/Christchurch/16/2010 ( H1N1), A/Victoria/361/2011 (H3N2), B/Brisbane/60/2008 (Victoria) and B/Hubei-Wujiagang/158/2009 (Yamagata) antigens.


Secondary Outcome Measures:
  • Number of Subjects With HI Antibody Titers Against Each of the Four Vaccine Strains After 1 Dose of Fluarix Quadrivalent Vaccine. [ Time Frame: At Day 0 and Day 7 ] [ Designated as safety issue: No ]
    The cut-off values assessed were less than (<) 1:10, 1:10 to < 1:40 and ≥ 1:40. The vaccine strains included A/Christchurch/16/2010 ( H1N1), A/Victoria/361/2011 (H3N2), B/Brisbane/60/2008 (Victoria) and B/Hubei-Wujiagang/158/2009 (Yamagata) antigens.

  • Serum Neutralising Antibody Titers Against Each of the Vaccine Strains After 1 Dose of Fluarix Quadrivalent Vaccine [ Time Frame: At Day 0 and Day 7 ] [ Designated as safety issue: No ]
    Antibody titers were expressed as Geometric mean titers (GMTs). The vaccine strains included A/Christchurch/16/2010 ( H1N1), A/Victoria/361/2011 (H3N2), B/Brisbane/60/2008 (Victoria) and B/Hubei-Wujiagang/158/2009 (Yamagata) antigens.

  • Serum Anti-neuraminidase Antibody Titers Against Each of the Vaccine Strains After 1 Dose of Fluarix Quadrivalent Vaccine [ Time Frame: At Day 0 and Day 7 ] [ Designated as safety issue: No ]
    Antibody titers were expressed as GMTs. The vaccine strains included A/Christchurch/16/2010 ( H1N1), A/Victoria/361/2011 (H3N2), B/Brisbane/60/2008 (Victoria) and B/Hubei-Wujiagang/158/2009 (Yamagata) antigens.

  • Vaccine Response Rate (VRR) for Neutralising Antibody Titers Against Each of the Four Vaccine Strains. [ Time Frame: At Day 7 post dose 1 ] [ Designated as safety issue: No ]
    VRR was defined as the number of vaccinees who had either a pre-vaccination titer <cut-off and a post-vaccination titer ≥ 4-fold of half of the cut-off or a pre-vaccination titer ≥cut-off and at least a 4-fold increase in post-vaccination titers. The vaccine strains included A/Christchurch/16/2010 ( H1N1), A/Victoria/361/2011 (H3N2), B/Brisbane/60/2008 (Victoria) and B/Hubei-Wujiagang/158/2009 (Yamagata) antigens.

  • MGI for Neutralising Antibodies Titres Against Each of the Four Vaccine Strains. [ Time Frame: At Day 7 ] [ Designated as safety issue: No ]
    MGI was defined as the fold increase in serum HI GMT post-vaccination compared to Day 0.

  • VRR for Anti-neuraminidase Antibody Titers Against Each of the Four Vaccine Strains. [ Time Frame: At Day 7 post dose 1 ] [ Designated as safety issue: No ]
    VRR was defined as the number of vaccinees who had either a pre-vaccination titer <cut-off and a post-vaccination titer ≥ 4-fold of half of the cut-off or a pre-vaccination titer ≥cut-off and at least a 4-fold increase in post-vaccination titers. The vaccine strains included A/Christchurch/16/2010 ( H1N1), A/Victoria/361/2011 (H3N2), B/Brisbane/60/2008 (Victoria) and B/Hubei-Wujiagang/158/2009 (Yamagata) antigens.

  • MGI for Anti-neuraminidase Antibodies Titers Against Each of the Four Vaccine Strains. [ Time Frame: At Day 7 post dose 1 ] [ Designated as safety issue: No ]
    MGI was defined as the fold increase in serum HI GMT post-vaccination compared to Day 0. The vaccine strains included A/Christchurch/16/2010 ( H1N1), A/Victoria/361/2011 (H3N2), B/Brisbane/60/2008 (Victoria) and B/Hubei-Wujiagang/158/2009 (Yamagata) antigens.

  • Number of Subjects Reporting Any and Grade 3 Solicited Local Adverse Events (AEs) [ Time Frame: During a 7-day (Day 0 to 6) follow-up period after first vaccination ] [ Designated as safety issue: No ]
    Solicited local AEs assessed were pain, redness and swelling. Any = any solicited local AE reported irrespective of intensity grade. Grade 3 pain = cried when limb was moved/spontaneously painful. Grade 3 redness and swelling was defined as redness/swelling above 50 millimeter (mm).

  • Duration of Solicted Symptoms [ Time Frame: During the 7-day (Days 0-6) post-vaccination Dose 1 period ] [ Designated as safety issue: No ]
    Duration was defined as number of days with any grade of solicted local and/or general symptoms

  • Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms. [ Time Frame: During the 7 days (Days 0 - 6) post dose 1 vaccination ] [ Designated as safety issue: No ]
    Solicited general symptoms assessed were drowsiness, Irritability/Fussiness, loss of appetite and Temperature. Any Temperature = axillary temperature ≥37.5 degrees Celsius (°C). Any = any solicited general symptom reported irrespective of intensity and relationship to vaccination. Related = symptoms considered by the investigator to have a causal relationship to vaccination. Grade 3 symptoms = symptoms that prevented normal activity. Grade 3 Irritability/Fussiness = Crying that could not be comforted/prevented normal activity. Grade 3 loss of appetite = did not eat at all. Grade 3 temperature = axillary temperature > 39.0°C.

  • Number of Subjects Reporting AEs With Medically Attended Visits (MAV) [ Time Frame: During the entire study period (Day 0 - Day 179) ] [ Designated as safety issue: No ]
    MAVs were defined as an AEs with a medically-attended visits i.e. prompting emergency room (ER) visits, hospitalizations or physician visits and that were not routine visits for physical examination or vaccination. Any MAV was defined as at least one MAV experienced. Grade 3 was a MAV that prevented normal activities and related was defined as a MAV assessed by the investigator to be causally related to the study vaccination.

  • Number of Subjects Reporting Potential Immune-Mediated Diseases (pIMDs) [ Time Frame: During the entire study period (Days 0 - 179) ] [ Designated as safety issue: No ]
    pIMDs were defined as a subset of AEs that included autoimmune diseases and other inflammatory and/or neurologic disorders of interest which may or may not have had an autoimmune aetiology.

  • Number of Subjects Reporting Any, Grade 3 and Related Unsolicited AEs. [ Time Frame: Within 28 days (Days 0-27) after first vaccination ] [ Designated as safety issue: No ]
    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.

  • Number of Subjects Reporting Any and Related Serious Adverse Events (SAEs) [ Time Frame: During the entire study period (Day 0 - Day 179) ] [ Designated as safety issue: No ]
    A serious adverse event was any untoward medical occurrence that: resulted in death, was life-threatening, required hospitalization or prolongation of existing hospitalization, resulted in disability/incapacity or was 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.


Enrollment: 470
Study Start Date: October 2012
Study Completion Date: June 2013
Primary Completion Date: June 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Fluarix Quadrivalent Primed Group
Subjects in this group were previously primed with 2 doses of Fluarix Quadrivalent vaccine in the primary study 115345 (NCT01439360) and received 1 dose of Fluarix Quadrivalent vaccine at Day 0 in the current study. The vaccine was administered intramuscularly in the deltoid region of arm.
Biological: Fluarix Quadrivalent
1 or 2 doses administered intramuscularly (IM) in deltoid region depending on the priming status
Experimental: Fluarix Quadrivalent Unprimed Group
Subjects in this group were unprimed in the primary study 115345 (NCT01439360) and received 2 doses of Fluarix Quadrivalent vaccine at Days 0 and 28 in the current study. The vaccine was administered intramuscularly in the deltoid region of arm.
Biological: Fluarix Quadrivalent
1 or 2 doses administered intramuscularly (IM) in deltoid region depending on the priming status

  Eligibility

Ages Eligible for Study:   17 Months to 48 Months
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Subjects who the investigator believes that parent(s)/LAR(s) can and will comply with the requirements of the protocol.
  • Children, male or female who received a 2-dose vaccination in the study 115345 (NCT01439360).
  • Written informed consent obtained from the parent(s)/LAR(s) of the subject.
  • Subjects in stable health as determined by medical history and clinical examination before entering into the study.

Exclusion Criteria:

  • Child in care.
  • Use of any investigational or non-registered product (drug or vaccine) other than the study vaccines within 30 days preceding the first dose of study vaccine, or planned use during the study period.
  • Since the start of study 115345 (NCT01439360), receipt of any seasonal influenza vaccine other than the study vaccines of study 115345 or planned administration of any influenza vaccine other than the study vaccine during the study.
  • Administration of any vaccine not foreseen by the study protocol within 4 weeks preceding the first dose of study vaccine or planned use until Visit 2.
  • Laboratory confirmed influenza infection outside of the 115345 (NCT01439360) study.
  • Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination.
  • Chronic administration (defined as more than 14 days) of immunosuppressants or other immune-modifying drugs within 6 months prior to enrolment in the study or planned administration during the study period. Inhaled and topical steroids are allowed.
  • Administration of immunoglobulins and/ or any blood products within 3 months preceding the first dose of study vaccine or planned administration during the study period.
  • History of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccine.
  • Any contraindication to intramuscular injection.
  • Acute disease and/or fever at the time of enrollment:

    • Fever is defined as temperature ≥ 37.5°C by any route.
    • Subjects with a minor illness (such as mild diarrhoea, mild upper respiratory infection) without fever may be enrolled at the discretion of the investigator.
  • Any other condition which, in the opinion of the Investigator, prevents the subject from participating in the study.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01702454

Locations
Czech Republic
GSK Investigational Site
Decin, Czech Republic, 405 01
GSK Investigational Site
Jindrichuv Hradec, Czech Republic, 37701
GSK Investigational Site
Lipnik nad Becvou, Czech Republic, 75131
GSK Investigational Site
Nachod, Czech Republic, 547 01
GSK Investigational Site
Odolena voda, Czech Republic, 25070
GSK Investigational Site
Ostrava - Poruba, Czech Republic, 70800
GSK Investigational Site
Pardubice, Czech Republic, 532 03
GSK Investigational Site
Praha 6, Czech Republic, 1600
GSK Investigational Site
Tabor, Czech Republic, 390 02
Poland
GSK Investigational Site
Debica, Poland, 39-200
GSK Investigational Site
Katowice, Poland, 40-018
GSK Investigational Site
Siemianowice Slaskie, Poland, 41-103
Spain
GSK Investigational Site
Antequera/Málaga, Spain, 29200
GSK Investigational Site
Blanes (Girona), Spain, 17300
GSK Investigational Site
Castellón, Spain, 12530
GSK Investigational Site
Castellón, Spain, 12004
GSK Investigational Site
Centelles (Barcelona), Spain, 08540
GSK Investigational Site
Madrid, Spain, 28046
GSK Investigational Site
Paiporta, Valencia, Spain, 46200
GSK Investigational Site
Quart de Poblet, Valencia, Spain, 46930
GSK Investigational Site
Santiago de Compostela, Spain, 15706
GSK Investigational Site
Sevilla, Spain, 41014
GSK Investigational Site
Valencia, Spain, 46024
GSK Investigational Site
Valencia, Spain, 46011
United Kingdom
GSK Investigational Site
St Austell, Cornwall, United Kingdom, PL26 7RL
GSK Investigational Site
Coventry, Warwickshire, United Kingdom, CV6 4DD
GSK Investigational Site
Belfast, United Kingdom, BT7 2EB
GSK Investigational Site
Bristol, United Kingdom, BS2 8AE
GSK Investigational Site
Exeter, United Kingdom, EX2 5DW
GSK Investigational Site
Gloucester, United Kingdom, GL1 3NN
GSK Investigational Site
London, United Kingdom, SW17 0QT
GSK Investigational Site
Oxford, United Kingdom, OX3 7LJ
GSK Investigational Site
Southampton, United Kingdom, SO16 6YD
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT01702454     History of Changes
Other Study ID Numbers: 116023, 2012-001230-34
Study First Received: October 4, 2012
Results First Received: June 5, 2014
Last Updated: July 10, 2014
Health Authority: Spain: Agencia Española del Medicamento y Productos Sanitarios
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Poland: Drug Institute for Registration of Medicinal Products
Czech Republic: State Institute for Drug Control

Keywords provided by GlaxoSmithKline:
GSK Biologicals quadrivalent influenza vaccine
Influenza
Children
Safety
Immunogenicity

Additional relevant MeSH terms:
Influenza, Human
Orthomyxoviridae Infections
RNA Virus Infections
Virus Diseases
Respiratory Tract Infections
Respiratory Tract Diseases

ClinicalTrials.gov processed this record on July 20, 2014