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

Influenza Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01702454
• Other study ID #: 116023
• Secondary ID: 2012-001230-34
• Status: Completed
• Phase: Phase 3
• Start date: October 6, 2012
• Est. completion date: June 5, 2013

Study information

• Verified date: July 2017
• Source: GlaxoSmithKline
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 470
• Est. completion date: June 5, 2013
• Est. primary completion date: May 6, 2013
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 17 Months to 48 Months

Eligibility

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.

Related Conditions & MeSH terms

• Influenza
• Influenza, Human

Intervention

Biological:
• Fluarix Quadrivalent
1 or 2 doses administered intramuscularly (IM) in deltoid region depending on the priming status

Locations

Country	Name	City	State
Czechia	GSK Investigational Site	Decin
Czechia	GSK Investigational Site	Jindrichuv Hradec
Czechia	GSK Investigational Site	Lipnik nad Becvou
Czechia	GSK Investigational Site	Nachod
Czechia	GSK Investigational Site	Odolena voda
Czechia	GSK Investigational Site	Ostrava - Poruba
Czechia	GSK Investigational Site	Pardubice
Czechia	GSK Investigational Site	Praha 6
Czechia	GSK Investigational Site	Tabor
Poland	GSK Investigational Site	Debica
Poland	GSK Investigational Site	Katowice
Poland	GSK Investigational Site	Siemianowice Slaskie
Spain	GSK Investigational Site	Antequera/Málaga
Spain	GSK Investigational Site	Blanes (Girona)
Spain	GSK Investigational Site	Castellón
Spain	GSK Investigational Site	Castellón
Spain	GSK Investigational Site	Centelles (Barcelona)
Spain	GSK Investigational Site	Madrid
Spain	GSK Investigational Site	Paiporta, Valencia
Spain	GSK Investigational Site	Quart De Poblet, Valencia
Spain	GSK Investigational Site	Santiago de Compostela
Spain	GSK Investigational Site	Sevilla
Spain	GSK Investigational Site	Valencia
Spain	GSK Investigational Site	Valencia
United Kingdom	GSK Investigational Site	Belfast
United Kingdom	GSK Investigational Site	Bristol
United Kingdom	GSK Investigational Site	Coventry	Warwickshire
United Kingdom	GSK Investigational Site	Exeter
United Kingdom	GSK Investigational Site	Gloucester
United Kingdom	GSK Investigational Site	London
United Kingdom	GSK Investigational Site	Oxford
United Kingdom	GSK Investigational Site	Southampton
United Kingdom	GSK Investigational Site	St Austell	Cornwall

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Countries where clinical trial is conducted

Czechia,  Poland,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Serum Hemagglutination Inhibition (HI) Antibody Titers Against Each of the Four Vaccine Strains After 1 Dose of Fluarix Quadrivalent Vaccine	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.	At Day 0 and Day 7
Primary	Number of Seropositive Subjects Against Each of the Four Vaccine Strains After 1 Dose of Fluarix Quadrivalent Vaccine	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.	At Day 0 and Day 7
Primary	Number of Subjects Seroconverted for HI Antibodies Against Each of the Four Vaccine Strains After 1 Dose of Fluarix Quadrivalent Vaccine.	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.	At Day 7 post dose 1
Primary	Mean Geometric Increase (MGI) for HI Antibody Titer Against Each of the Four Vaccine Strains After 1 Dose of Fluarix Quadrivalent Vaccine.	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.	At Day 7 post dose 1
Primary	Number of Subjects Seroprotected for Anti-HA Antibodies Against Each of the Four Vaccine Strains After 1 Dose of Fluarix Quadrivalent Vaccine.	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.	At Day 0 and Day 7
Primary	Serum Hemagglutination Inhibition (HI) Antibody Titers Against Each of the Four Vaccine Strains After 1 Dose of Fluarix Quadrivalent Vaccine.	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.	At Day 0 and Day 7
Primary	Number of Subjects Seropositive for HI Antibody Titers Against Each of the Four Vaccine Strains After Dose 1 of Fluarix Quadrivalent Vaccine	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.	At Day 0 and Day 7
Primary	Number of Subjects Seroconverted for HI Antibodies Against Each of the Four Vaccine Strains After 1 Dose of Fluarix Quadrivalent Vaccine.	A seroconverted subject was defined as a subject who had either a pre-vaccination titer <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 four-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.	At Day 7 post dose 1
Primary	Mean Geometric Increase (MGI) for HI Antibody Titers Against Each of the Four Vaccine Strains After 1 Dose of Fluarix Quadrivalent Vaccine.	Mean geometric increase was defined as the geometric mean of the within subject ratios of the post-vaccination reciprocal HI titer to the Day 0 reciprocal HI 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.	At Day 7 post dose 1
Primary	Number of Subjects Seroprotected for HI Antibodies Against Each of the Four Vaccine Strains After 1 Dose of Fluarix Quadrivalent Vaccine.	Seroprotection rate was defined as the number of vaccinees with a serum HI titer greater than or equal to(=) 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.	At Day 0 and Day 7
Secondary	Number of Subjects With HI Antibody Titers Against Each of the Four Vaccine Strains After 1 Dose of Fluarix Quadrivalent Vaccine.	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.	At Day 0 and Day 7
Secondary	Serum Neutralising Antibody Titers Against Each of the Vaccine Strains After 1 Dose of Fluarix Quadrivalent Vaccine	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.	At Day 0 and Day 7
Secondary	Serum Anti-neuraminidase Antibody Titers Against Each of the Vaccine Strains After 1 Dose of Fluarix Quadrivalent Vaccine	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.	At Day 0 and Day 7
Secondary	Vaccine Response Rate (VRR) for Neutralising Antibody Titers Against Each of the Four Vaccine Strains.	VRR was defined as the number of vaccinees who had either a pre-vaccination titer	At Day 7 post dose 1
Secondary	MGI for Neutralising Antibodies Titers Against Each of the Four Vaccine Strains After 1 Dose of Fluarix Quadrivalent Vaccine.	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.	At Day 7 post dose 1
Secondary	Vaccine Response Rate(VRR) for Anti-neuraminidase Antibody Titers Against Each of the Four Vaccine Strains.	VRR was defined as the number of vaccinees who had either a pre-vaccination titer	At Day 7 post dose 1
Secondary	MGI for Anti-neuraminidase Antibodies Titers Against Each of the Four Vaccine Strains After 1 Dose of Fluarix Quadrivalent Vaccine.	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.	At Day 7 post dose 1
Secondary	Number of Subjects With HI Antibody Titers Against Each of the Four Vaccine Strains After 1 Dose of Fluarix Quadrivalent Vaccine.	The cut-off values assessed were less than (<) 1:10, 1:10 to < 1:40,= 1:40, =1:60 and =1:80 . 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.	At Day 0 and Day 7
Secondary	Serum Micro Neutralizing(MN) Antibody Titers Against Each of the Four Vaccine Strains After 1 Dose of Fluarix Quadrivalent Vaccine.	MN 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.	At Day 0 and Day 7
Secondary	Serum Anti-neuraminidase Antibody Titers Against Each of the Vaccine Strains After 1 Dose of Fluarix Quadrivalent Vaccine	NI (Neuraminidase inhibitor) 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.	At Day 0 and Day 7
Secondary	Vaccine Response Rate(VRR) for Serum Neutralising Antibody Titers Against Each of the Four Vaccine Strains	VRR was defined as the number of vaccinees who had either a pre-vaccination titer	At Day 7 post dose 1
Secondary	MGI for Neutralising Antibodies Titers Against Each of the Four Vaccine Strains After 1 Dose of Fluarix Quadrivalent Vaccine.	MGI was defined as the fold increase in GMTs 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.	At Day 7 post dose 1
Secondary	Vaccine Response Rate(VRR) for Anti-neuraminidase Antibodies Against Each of the Four Vaccine Strains.	VRR was defined as the percentage of vaccinees who had either a pre-vaccination titer	At Day 7 post dose 1
Secondary	MGI for Anti-neuraminidase Antibodies Titers Against Each of the Four Vaccine Strains After 1 Dose of Fluarix Quadrivalent Vaccine	MGI was defined as the fold increase in GMTs 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.	At Day 7 post dose 1
Secondary	Serum Neutralising Antibody Titers Against Each of the Vaccine Strains After 1 Dose of Fluarix Quadrivalent Vaccine by Age Strata.	Antibody titers were expressed as geometric mean titers. The vaccine strains included A/Christchurch/16/2010 (H1N1),A/Victoria/361/2011 (H3N2), A/Victoria/361/2011 and B/Hubei-Wujiagang/158/2009)(Yamagata) antigens. The humoral response in terms of neutralising antibodies for all vaccine strains were calculated by age stratum which included 17-29 months and 30-48 months age groups for both the Fluarix primed and unprimed groups.	At Day 0 and Day 7
Secondary	Serum Anti-neuraminidase Antibody Titers Against Each of the Vaccine Strains After 1 Dose of Fluarix Quadrivalent Vaccine by Age Strata	Antibody titers were expressed as geometric mean 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. The humoral response in terms of anti-neuraminidase antibodies for all vaccine strains were calculated by age stratum which included 17-29 months and 30-48 months age groups for both the Fluarix primed and unprimed groups.	At Day 0 and Day 7
Secondary	Vaccine Response Rate(VRR) for Serum Neutralising Antibody Titers Against Each of the Four Vaccine Strains by Age Strata	VRR was defined as the percentage of vaccinees who had either a pre-vaccination titer	At Day 7 post dose 1
Secondary	MGI for Neutralising Antibodies Titers Against Each of the Four Vaccine Strains After 1 Dose of Fluarix Quadrivalent Vaccine by Age Strata	MGI was defined as the fold increase in GMTs 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.The humoral response in terms of neutralising antibodies for all vaccine strains were calculated by age stratum which included 17-29 months and 30-48 months age groups for both the Fluarix primed and unprimed groups.	At Day 7 post dose 1
Secondary	Vaccine Response Rate(VRR) for Anti-neuraminidase Antibody Titers Against Each of the Four Vaccine Strains by Age Strata.	VRR was defined as the percentage of vaccinees who had either a pre-vaccination titer	At Day 7 post dose 1
Secondary	MGI for Anti-neuraminidase Antibodies Titers Against Each of the Four Vaccine Strains After 1 Dose of Fluarix Quadrivalent Vaccine by Age Strata.	MGI was defined as the fold increase in GMTs 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. The humoral response in terms of anti-neuraminidase antibodies for all vaccine strains were calculated by age stratum which included 17-29 months and 30-48 months age groups for both the Fluarix primed and unprimed groups.	At Day 7 post dose 1
Secondary	Number of Subjects Reporting Any and Grade 3 Solicited Local Adverse Events (AEs)	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).	During a 7-day (Day 0 to 6) follow-up period after first vaccination
Secondary	Duration of Solicted Symptoms	Duration was defined as number of days with any grade of solicted local and/or general symptoms	During the 7-day (Days 0-6) post-vaccination Dose 1 period
Secondary	Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms.	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.	During the 7 days (Days 0 - 6) post dose 1 vaccination
Secondary	Number of Subjects Reporting AEs With Medically Attended Visits (MAV)	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.	During the entire study period (Day 0 - Day 179)
Secondary	Number of Subjects Reporting Potential Immune-Mediated Diseases (pIMDs)	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. Any pIMDs= Any AEs that occured regardless of the relation with vaccination. Related pIMDs= Any pIMD assessed by the investigator as casually related to the study vaccination.	During the entire study period (Days 0 - 179)
Secondary	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 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.	Within 28 days (Days 0-27) after first vaccination
Secondary	Number of Subjects Reporting Any and Related Serious Adverse Events (SAEs)	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.	During the entire study period (Day 0 - Day 179)

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