An Efficacy Study of GlaxoSmithKline (GSK) Biologicals' Candidate Influenza Vaccine GSK2321138A in Children

Influenza Clinical Trial

Official title:

An Efficacy Study of GSK Biologicals' Quadrivalent Influenza Vaccine GSK2321138A (FLU D-QIV) When Administered in Children

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01439360
• Other study ID #: 115345
• Secondary ID: 2011-000758-41
• Status: Completed
• Phase: Phase 3
• Start date: October 1, 2011
• Est. completion date: December 31, 2014

Study information

• Verified date: August 2018
• Source: GlaxoSmithKline
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to evaluate the efficacy, immunogenicity and safety of GSK Biologicals' influenza candidate vaccine GSK2321138A when compared to non-influenza vaccine comparators in children 6 to 35 months of age. Recruitment will encompass at least 4 independent cohorts: a first cohort in the Northern Hemisphere (2011-2012), a second cohort in subtropical countries (2012), third cohort in the Northern Hemisphere (2012-2013) and a fourth cohort and additional independent cohorts possibly in NH countries (end 2013) and subtropical countries (beginning 2014).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 12046
• Est. completion date: December 31, 2014
• Est. primary completion date: October 31, 2014
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 6 Months to 35 Months

Eligibility

Inclusion Criteria:

• Subjects who the investigator believes that their parents/Legally Acceptable Representative (LARs) can and will comply with the requirements of the protocol.

• A male or female between, and including, 6 and 35 months of age at the time of first vaccination; children are eligible regardless of history of influenza vaccination.

• 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:

• Participation in a previous FLU-D-QIV-004 study (115345) cohort.

• Child in care.

• Use of any investigational or non-registered product other than the study vaccines within 30 days preceding the first dose of study vaccine, or planned use during the study period.

• Prior receipt of any influenza vaccine within 6 months preceding the first dose of study vaccine, or planned use of such vaccines during the study period.

• Children with underlying illness who are at risk of complications of influenza and for whom yearly (seasonal) influenza vaccination is recommended in their respective country.

• Any confirmed or suspected immunosuppressive or immunodeficient condition (including HIV), based on medical history and physical examination.

• Chronic administration of immunosuppressants or other immune modifying drugs within six months prior to the first vaccine dose. 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.

• Any known or suspected allergy to any constituent of influenza vaccines, non-influenza vaccine comparators and latex; a history of anaphylactic-type reaction to consumption of eggs; or a history of severe adverse reaction to a previous vaccination.

• Any contraindication to intramuscular injection.

• Acute disease and/or fever at the time of enrolment.

• Any other condition which, in the opinion of the Investigator, prevents the subject from participating in the study.

• Additional criteria for children = 12 months of age:

• Prior receipt of any licensed varicella vaccine* or any licensed hepatitis A vaccine or planned use of these vaccines during the study period. Other routine registered childhood vaccinations are permitted.

• For countries with varicella vaccine administered as 2-dose schedule, prior receipt of a single dose of a varicella vaccine is allowed if administered at least 2 weeks before the first study vaccination.

• Any history of hepatitis A or varicella diseases.

• Additional criteria for children 6 - 11 months of age in countries without universal mass vaccination recommendation for pneumococcal vaccine:

• Prior receipt of any pneumococcal conjugated vaccine or planned use of this vaccine during the study period. Other routine registered childhood vaccinations are permitted.

Related Conditions & MeSH terms

• Influenza
• Influenza, Human

Intervention

Biological:
• Quadrivalent seasonal influenza vaccine(Flu D-QIV) GSK2321138A
Intramuscular injection
• Havrix Junior
Intramuscular injection administered to subjects aged 12 months or older
• Prevenar 13
Intramuscular injection administered to subjects less than 12 months of age
• Varivax/ProVarivax
Intramuscular injection administered to subjects more than 12 months of age
• Varilrix
Subcutaneous injection administered to subjects more than 12 months of age

Locations

Country	Name	City	State
Bangladesh	GSK Investigational Site	Dhaka
Belgium	GSK Investigational Site	Antwerpen
Belgium	GSK Investigational Site	Antwerpen
Belgium	GSK Investigational Site	Bruxelles
Belgium	GSK Investigational Site	Mechelen
Belgium	GSK Investigational Site	Namur
Belgium	GSK Investigational Site	Roeselaere
Belgium	GSK Investigational Site	Turnhout
Czechia	GSK Investigational Site	Decin
Czechia	GSK Investigational Site	Humpolec
Czechia	GSK Investigational Site	Jindrichuv Hradec
Czechia	GSK Investigational Site	Liberec
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
Dominican Republic	GSK Investigational Site	Santo Domingo
Dominican Republic	GSK Investigational Site	Santo Domingo, Distrito Nacional
Honduras	GSK Investigational Site	San Pedro Sula
Honduras	GSK Investigational Site	Tegucigalpa
India	GSK Investigational Site	Faridabad
India	GSK Investigational Site	Pune
India	GSK Investigational Site	Pune
Lebanon	GSK Investigational Site	Beirut
Philippines	GSK Investigational Site	Manila
Philippines	GSK Investigational Site	Manila
Philippines	GSK Investigational Site	Metro Manila
Philippines	GSK Investigational Site	Muntinlupa
Philippines	GSK Investigational Site	Quezon City
Philippines	GSK Investigational Site	Sampaloc, Manila
Poland	GSK Investigational Site	Bydgoszcz
Poland	GSK Investigational Site	Bydgoszcz
Poland	GSK Investigational Site	Bydgoszcz
Poland	GSK Investigational Site	Debica
Poland	GSK Investigational Site	Gdansk
Poland	GSK Investigational Site	Grudziadz
Poland	GSK Investigational Site	Katowice
Poland	GSK Investigational Site	Katowice
Poland	GSK Investigational Site	Krakow
Poland	GSK Investigational Site	Leczna
Poland	GSK Investigational Site	Lodz
Poland	GSK Investigational Site	Lublin
Poland	GSK Investigational Site	Oborniki
Poland	GSK Investigational Site	Poznan
Poland	GSK Investigational Site	Poznan
Poland	GSK Investigational Site	Siemianowice Slaskie
Poland	GSK Investigational Site	Tarnow
Poland	GSK Investigational Site	Torun
Poland	GSK Investigational Site	Warszawa
Poland	GSK Investigational Site	Wola
Poland	GSK Investigational Site	Wroclaw
Spain	GSK Investigational Site	Antequera/Málaga
Spain	GSK Investigational Site	Barcelona
Spain	GSK Investigational Site	Barcelona
Spain	GSK Investigational Site	Blanes (Girona)
Spain	GSK Investigational Site	Boadilla del Monte
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	Madrid
Spain	GSK Investigational Site	Madrid
Spain	GSK Investigational Site	Madrid
Spain	GSK Investigational Site	Pozuelo De Alarcón/Madrid
Spain	GSK Investigational Site	Quart De Poblet, Valencia
Spain	GSK Investigational Site	Santiago de Compostela
Spain	GSK Investigational Site	Sevilla
Spain	GSK Investigational Site	Sevilla
Spain	GSK Investigational Site	Torrelodones (Madrid)
Spain	GSK Investigational Site	Valencia
Spain	GSK Investigational Site	Valencia
Spain	GSK Investigational Site	Valencia
Spain	GSK Investigational Site	Valencia
Spain	GSK Investigational Site	Vic/ Barcelona
Spain	GSK Investigational Site	Xativa/Valencia
Thailand	GSK Investigational Site	Bangkok
Thailand	GSK Investigational Site	Khon Kaen
Turkey	GSK Investigational Site	Bursa
Turkey	GSK Investigational Site	Eskisehir
Turkey	GSK Investigational Site	Istanbul
United Kingdom	GSK Investigational Site	Atherstone	Warwickshire
United Kingdom	GSK Investigational Site	Axbridge	Somerset
United Kingdom	GSK Investigational Site	Bath	Somerset
United Kingdom	GSK Investigational Site	Belfast
United Kingdom	GSK Investigational Site	Bolton, Nr Manchester
United Kingdom	GSK Investigational Site	Bristol
United Kingdom	GSK Investigational Site	Co Antrim
United Kingdom	GSK Investigational Site	Coventry	Warwickshire
United Kingdom	GSK Investigational Site	Crumpsall, Manchester
United Kingdom	GSK Investigational Site	Exeter
United Kingdom	GSK Investigational Site	Gloucester
United Kingdom	GSK Investigational Site	London
United Kingdom	GSK Investigational Site	Manchester
United Kingdom	GSK Investigational Site	Nottingham
United Kingdom	GSK Investigational Site	Oxford
United Kingdom	GSK Investigational Site	Southampton	Hampshire
United Kingdom	GSK Investigational Site	St Austell	Cornwall
United Kingdom	GSK Investigational Site	Taunton, Somerset
United Kingdom	GSK Investigational Site	Westminster Bridge Road
United Kingdom	GSK Investigational Site	Yeovil	Somerset

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Countries where clinical trial is conducted

Bangladesh,  Belgium,  Czechia,  Dominican Republic,  Honduras,  India,  Lebanon,  Philippines,  Poland,  Spain,  Thailand,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Subjects With Moderate to Severe RT-PCR Confirmed Influenza.	Attack rate (AR) was defined as the number/percentage of subjects with at least 1 RT-PCR confirmed influenza event.	During the surveillance period (approximately 6 to 8 months)
Primary	Number of Subjects With RT-PCR Confirmed Influenza of Any Severity.	Attack rate (AR) was defined as the number/percentage of subjects with at least 1 RT-PCR confirmed influenza event.	During the surveillance period (approximately 6 to 8 months)
Secondary	Number of Subjects With First Occurrence of Lower Respiratory Illness (LRI) With RT-PCR Confirmed Influenza.	Attack rate (AR) was defined as the number/percentage of subjects with at least 1 RT-PCR confirmed influenza event.	At any time starting 7 days before the onset of LRI and ending 7 days after end of LRI during the surveillance period (approximately 6 to 8 months)
Secondary	Number of Subjects With First Occurrence of Culture-confirmed Moderate to Severe Influenza A and/or B Disease Due to Antigenically-matching Influenza Strains.	Attack rate (AR) was defined as the number/percentage of subjects with at least 1 RT-PCR confirmed influenza event.	During the surveillance period (approximately 6 to 8 months)
Secondary	Number of Subjects With First Occurrence of Culture-confirmed Influenza A and/or B Disease of Any Severity Due to Antigenically-matching Influenza Strains	Attack rate (AR) was defined as the number/percentage of subjects with at least 1 RT-PCR confirmed influenza event.	During the surveillance period (approximately 6 to 8 months)
Secondary	Number of Subjects With First Occurrence of Culture-confirmed Moderate to Severe Influenza A and/or B Disease Due to Any Seasonal Influenza Strain.	Attack rate (AR) was defined as the number/percentage of subjects with at least 1 RT-PCR confirmed influenza event.	During the surveillance period (approximately 6 to 8 months)
Secondary	Number of Subjects With First Occurrence of Culture-confirmed Influenza A and/or B Disease of Any Severity Due to Any Seasonal Influenza Strain.	Attack rate (AR) was defined as the number/percentage of subjects with at least 1 RT-PCR confirmed influenza event.	During the surveillance period (approximately 6 to 8 months)
Secondary	Number of Subjects With First Occurrence of Acute Otitis Media (AOM) With RT-PCR Confirmed Influenza A and/or B Infection Due to Any Seasonal Influenza Strain.	Attack rate (AR) was defined as the number/percentage of subjects with at least 1 RT-PCR confirmed influenza event.	At any time starting 7 days before the onset of LRI and ending 7 days after end of LRI during the surveillance period (approximately 6 to 8 months)
Secondary	Number of Subjects With First Occurrence of RT-PCR Confirmed Severe Influenza A and/or B Due to Any Seasonal Influenza Strain.	Attack rate (AR) was defined as the number/percentage of subjects with at least 1 RT-PCR confirmed influenza event.	During the surveillance period (approximately 6 to 8 months)
Secondary	Humoral Immune Response in Terms of Haemagglutination-inhibition (HI) Antibody Titres Against Each of Four Vaccine Strains Contained in the D-QIV (in Immuno Subcohort of Subjects Only)	Titers were expressed as geometric mean antibody titers (GMTs). The vaccine strains assessed were A/California/7/2009 (H1N1), A/Victoria/210/2009 (H3N2), B/Brisbane/60/2008 (Victoria) and B/Brisbane/3/2007 (Yamagata).; PRE= Pre-vaccination at Day 0; POST = Post-vaccination 1 at Day 28 for primed subjects or post-vaccination 2 at Day 56 for unprimed subjects	At Days 0 and 28/56
Secondary	Number of Seropositive Subjects for HI Antibodies Against Each of the 4 Influenza Strains Contained in the D-QIV Vaccine (in Immuno Subcohort of Subjects Only)	A seropositive subject was a subject whose HI antibody titer was greater than or equal to the assay cut-off value of 1:10. The vaccine strains assessed were A/California/7/2009 (H1N1), A/Victoria/210/2009 (H3N2), B/Brisbane/60/2008 (Victoria) and B/Brisbane/3/2007 (Yamagata).; PRE= Pre-vaccination at Day 0; POST = Post-vaccination 1 at Day 28 for primed subjects or post-vaccination 2 at Day 56 for unprimed subjects.	At Day 0 and Day 28/56
Secondary	Number of Seroconverted Subjects for HI Antibodies Against Each of the 4 Influenza Strains Contained in the D-QIV Vaccine (in Immuno Subcohort of Subjects Only)	Seroconversion rate (SCR) was defined as the number of subjects who have either a pre-vaccination reciprocal HI titer < 1:10 and a post-vaccination reciprocal titer = 1:40, or a pre-vaccination reciprocal HI titer = 10 and at least a 4 fold increase in post vaccination reciprocal titer against the vaccine virus.; PRE= Pre-vaccination at Day 0; POST = Post-vaccination 1 at Day 28 for primed subjects or post-vaccination 2 at Day 56 for unprimed subjects	At Day 28/56 (POST)
Secondary	Mean Geometric Increase (MGI) for HI Antibody Titer Against Each of the 4 Vaccine Influenza Strains Contained in the D-QIV Vaccine (in Immuno Subcohort of Subjects Only).	MGI also known as the seroconversion factor [SCF] was defined as the fold increase in serum HI GMTs post vaccination compared to pre-vaccination (Day 0). The vaccine strains assessed were A/California/7/2009 (H1N1), A/Victoria/210/2009 (H3N2), B/Brisbane/60/2008 (Victoria) and B/Brisbane/3/2007 (Yamagata).; POST = Post-vaccination 1 at Day 28 for primed subjects or post-vaccination 2 at Day 56 for unprimed subjects.	At Day 28/56 (POST)
Secondary	Number of Seroprotected Subjects for HI Antibodies Against Each of the 4 Influenza Strains Contained in the D-QIV Vaccine (in Immuno Subcohort of Subjects Only)	Seroprotection rate (SPR) was defined as the number of subjects with H1N1 reciprocal HI titers = 1:40 against the tested vaccine virus.The vaccine strains assessed were A/California/7/2009 (H1N1), A/Victoria/210/2009 (H3N2), B/Brisbane/60/2008 (Victoria) and B/Brisbane/3/2007 (Yamagata).; PRE= Pre-vaccination at Day 0; POST = Post-vaccination 1 at Day 28 for primed subjects or post-vaccination 2 at Day 56 for unprimed subjects	At Day 0 and Day 28/56
Secondary	Number of Subjects Reporting Any and Grade 3 Solicited Local Symptoms.	Solicited local symptoms assessed were pain, redness and swelling. Any was defined as any solicited local symptom reported irrespective of intensity. Grade 3 pain was defined as pain that resulted crying when limb was moved/ spontaneously painful. Grade 3 redness and swelling was greater than 50 millimeters (mm) i.e. >50mm.	During the 7-day post-vaccination period (Days 0-6 for Dose 1, Days 28-34 for Dose 2)
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 (Axillary). Any was defined as any general symptom reported irrespective of intensity or relationship to vaccination. Grade 3 was defined as symptoms that prevented normal activity. Related was defined as general symptom assessed by the investigator to have a causal relationship to vaccination.	During the 7-day post-vaccination period (Days 0-6 for Dose 1, Days 28-34 for Dose 2)
Secondary	Duration of Solicited Local Symptoms	Duration was defined as number of days with any grade of local symptoms.	During the 7-day post-vaccination period (Days 0-6 for Dose 1, Days 28-34 for Dose 2)
Secondary	Duration of Solicited General Symptoms	Duration was defined as number of days with any grade of general symptoms.	During the 7-day post-vaccination period (Days 0-6 for Dose 1, Days 28-34 for Dose 2)
Secondary	Number of Subjects Reporting Any, Grade 3 and Related 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. 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.	During the 28-day (Days 0-27) post-vaccination period
Secondary	Number of Subjects Reporting Any, Grade 3 and Related AEs With Medically Attended Visits (MAVs)	MAVs were defined as AEs with a medically-attended visit 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 defined as MAVs that prevented normal activities and related was defined as MAVs assessed by the investigator to be causally related to the study vaccination.	During the entire study period (approximately 6- 8 months per subject)
Secondary	Number of Subjects Reporting Any, Grade 3 and Related Potential Immune-mediated Diseases (pIMDs).	pIMDs are a subset of adverse events (AEs) that include both clearly autoimmune diseases and also other inflammatory and/or neurologic disorders which may or may not have an autoimmune etiology. Grade 3 = pIMDs that prevented normal activities. Related = symptom assed by the investigator as causally related to the study vaccination.	During the entire study period (approximately 6- 8 months per subject)
Secondary	Number of Subjects Reporting Any and Related Serious Adverse Events (SAEs).	SAEs assessed include medical occurrences that results in death, are life threatening, require hospitalization or prolongation of hospitalization, results in disability/incapacity or are a congenital anomaly/birth defect in the offspring of a study subjects. Related = symptom assessed by the investigator as causally related to the study vaccination.	During the entire study period (approximately 6- 8 months per subject)

External Links

•   IPD for this study will be made available via the Clinical Study Data Request site.