Clinical trial NCT01439360: An Efficacy Study of GlaxoSmithKline (GSK) Biologicals' Candidate Influenza Vaccine GSK2321138A in Children
Official title: An Efficacy Study of GSK Biologicals' Quadrivalent Influenza Vaccine GSK2321138A (FLU D-QIV) When Administered in Children
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Influenza
Keywords: Vaccine
Seasonal Flu
Efficacy
Children
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2011-09-23
Enrollment: 12046
Sex: ALL
Minimum age (years): 6
Maximum age (years): 35
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief 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).


Eligibility criteria: 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.

Primary outcomes:
measure: Number of Subjects With Moderate to Severe RT-PCR Confirmed Influenza.
timeFrame: During the surveillance period (approximately 6 to 8 months)
measure: Number of Subjects With RT-PCR Confirmed Influenza of Any Severity.
timeFrame: During the surveillance period (approximately 6 to 8 months)
Secondary outcomes:
measure: Number of Subjects With First Occurrence of Lower Respiratory Illness (LRI) With RT-PCR Confirmed Influenza.
timeFrame: 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)
measure: Number of Subjects With First Occurrence of Culture-confirmed Moderate to Severe Influenza A and/or B Disease Due to Antigenically-matching Influenza Strains.
timeFrame: During the surveillance period (approximately 6 to 8 months)
measure: Number of Subjects With First Occurrence of Culture-confirmed Influenza A and/or B Disease of Any Severity Due to Antigenically-matching Influenza Strains
timeFrame: During the surveillance period (approximately 6 to 8 months)
measure: Number of Subjects With First Occurrence of Culture-confirmed Moderate to Severe Influenza A and/or B Disease Due to Any Seasonal Influenza Strain.
timeFrame: During the surveillance period (approximately 6 to 8 months)
measure: Number of Subjects With First Occurrence of Culture-confirmed Influenza A and/or B Disease of Any Severity Due to Any Seasonal Influenza Strain.
timeFrame: During the surveillance period (approximately 6 to 8 months)
measure: 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.
timeFrame: 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)
measure: Number of Subjects With First Occurrence of RT-PCR Confirmed Severe Influenza A and/or B Due to Any Seasonal Influenza Strain.
timeFrame: During the surveillance period (approximately 6 to 8 months)
measure: 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)
timeFrame: At Days 0 and 28/56
measure: 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)
timeFrame: At Day 0 and Day 28/56
measure: 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)
timeFrame: At Day 28/56 (POST)
measure: 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).
timeFrame: At Day 28/56 (POST)
measure: 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)
timeFrame: At Day 0 and Day 28/56
measure: Number of Subjects Reporting Any and Grade 3 Solicited Local Symptoms.
timeFrame: During the 7-day post-vaccination period (Days 0-6 for Dose 1, Days 28-34 for Dose 2)
measure: Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms.
timeFrame: During the 7-day post-vaccination period (Days 0-6 for Dose 1, Days 28-34 for Dose 2)
measure: Duration of Solicited Local Symptoms
timeFrame: During the 7-day post-vaccination period (Days 0-6 for Dose 1, Days 28-34 for Dose 2)
measure: Duration of Solicited General Symptoms
timeFrame: During the 7-day post-vaccination period (Days 0-6 for Dose 1, Days 28-34 for Dose 2)
measure: Number of Subjects Reporting Any, Grade 3 and Related Unsolicited Adverse Events (AEs)
timeFrame: During the 28-day (Days 0-27) post-vaccination period
measure: Number of Subjects Reporting Any, Grade 3 and Related AEs With Medically Attended Visits (MAVs)
timeFrame: During the entire study period (approximately 6- 8 months per subject)
measure: Number of Subjects Reporting Any, Grade 3 and Related Potential Immune-mediated Diseases (pIMDs).
timeFrame: During the entire study period (approximately 6- 8 months per subject)
measure: Number of Subjects Reporting Any and Related Serious Adverse Events (SAEs).
timeFrame: During the entire study period (approximately 6- 8 months per subject)
Other outcomes:
Locations:
city: Dhaka
country: Bangladesh
facility: GSK Investigational Site
city: Antwerpen
country: Belgium
facility: GSK Investigational Site
city: Antwerpen
country: Belgium
facility: GSK Investigational Site
city: Bruxelles
country: Belgium
facility: GSK Investigational Site
city: Mechelen
country: Belgium
facility: GSK Investigational Site
city: Namur
country: Belgium
facility: GSK Investigational Site
city: Roeselaere
country: Belgium
facility: GSK Investigational Site
city: Turnhout
country: Belgium
facility: GSK Investigational Site
city: Decin
country: Czechia
facility: GSK Investigational Site
city: Humpolec
country: Czechia
facility: GSK Investigational Site
city: Jindrichuv Hradec
country: Czechia
facility: GSK Investigational Site
city: Liberec
country: Czechia
facility: GSK Investigational Site
city: Lipnik nad Becvou
country: Czechia
facility: GSK Investigational Site
city: Nachod
country: Czechia
facility: GSK Investigational Site
city: Odolena voda
country: Czechia
facility: GSK Investigational Site
city: Ostrava - Poruba
country: Czechia
facility: GSK Investigational Site
city: Pardubice
country: Czechia
facility: GSK Investigational Site
city: Praha 6
country: Czechia
facility: GSK Investigational Site
city: Tabor
country: Czechia
facility: GSK Investigational Site
city: Santo Domingo, Distrito Nacional
country: Dominican Republic
facility: GSK Investigational Site
city: Santo Domingo
country: Dominican Republic
facility: GSK Investigational Site
city: San Pedro Sula
country: Honduras
facility: GSK Investigational Site
city: Tegucigalpa
country: Honduras
facility: GSK Investigational Site
city: Faridabad
country: India
facility: GSK Investigational Site
city: Pune
country: India
facility: GSK Investigational Site
city: Pune
country: India
facility: GSK Investigational Site
city: Beirut
country: Lebanon
facility: GSK Investigational Site
city: Manila
country: Philippines
facility: GSK Investigational Site
city: Manila
country: Philippines
facility: GSK Investigational Site
city: Metro Manila
country: Philippines
facility: GSK Investigational Site
city: Muntinlupa
country: Philippines
facility: GSK Investigational Site
city: Quezon City
country: Philippines
facility: GSK Investigational Site
city: Sampaloc, Manila
country: Philippines
facility: GSK Investigational Site
city: Bydgoszcz
country: Poland
facility: GSK Investigational Site
city: Bydgoszcz
country: Poland
facility: GSK Investigational Site
city: Bydgoszcz
country: Poland
facility: GSK Investigational Site
city: Debica
country: Poland
facility: GSK Investigational Site
city: Gdansk
country: Poland
facility: GSK Investigational Site
city: Grudziadz
country: Poland
facility: GSK Investigational Site
city: Katowice
country: Poland
facility: GSK Investigational Site
city: Katowice
country: Poland
facility: GSK Investigational Site
city: Krakow
country: Poland
facility: GSK Investigational Site
city: Leczna
country: Poland
facility: GSK Investigational Site
city: Lodz
country: Poland
facility: GSK Investigational Site
city: Lublin
country: Poland
facility: GSK Investigational Site
city: Oborniki
country: Poland
facility: GSK Investigational Site
city: Poznan
country: Poland
facility: GSK Investigational Site
city: Poznan
country: Poland
facility: GSK Investigational Site
city: Siemianowice Slaskie
country: Poland
facility: GSK Investigational Site
city: Tarnow
country: Poland
facility: GSK Investigational Site
city: Torun
country: Poland
facility: GSK Investigational Site
city: Warszawa
country: Poland
facility: GSK Investigational Site
city: Wola
country: Poland
facility: GSK Investigational Site
city: Wroclaw
country: Poland
facility: GSK Investigational Site
city: Antequera/Málaga
country: Spain
facility: GSK Investigational Site
city: Barcelona
country: Spain
facility: GSK Investigational Site
city: Barcelona
country: Spain
facility: GSK Investigational Site
city: Blanes (Girona)
country: Spain
facility: GSK Investigational Site
city: Boadilla del Monte
country: Spain
facility: GSK Investigational Site
city: Castellón
country: Spain
facility: GSK Investigational Site
city: Castellón
country: Spain
facility: GSK Investigational Site
city: Centelles (Barcelona)
country: Spain
facility: GSK Investigational Site
city: Madrid
country: Spain
facility: GSK Investigational Site
city: Madrid
country: Spain
facility: GSK Investigational Site
city: Madrid
country: Spain
facility: GSK Investigational Site
city: Madrid
country: Spain
facility: GSK Investigational Site
city: Pozuelo De Alarcón/Madrid
country: Spain
facility: GSK Investigational Site
city: Quart De Poblet, Valencia
country: Spain
facility: GSK Investigational Site
city: Santiago de Compostela
country: Spain
facility: GSK Investigational Site
city: Sevilla
country: Spain
facility: GSK Investigational Site
city: Sevilla
country: Spain
facility: GSK Investigational Site
city: Torrelodones (Madrid)
country: Spain
facility: GSK Investigational Site
city: Valencia
country: Spain
facility: GSK Investigational Site
city: Valencia
country: Spain
facility: GSK Investigational Site
city: Valencia
country: Spain
facility: GSK Investigational Site
city: Valencia
country: Spain
facility: GSK Investigational Site
city: Vic/ Barcelona
country: Spain
facility: GSK Investigational Site
city: Xativa/Valencia
country: Spain
facility: GSK Investigational Site
city: Bangkok
country: Thailand
facility: GSK Investigational Site
city: Khon Kaen
country: Thailand
facility: GSK Investigational Site
city: Bursa
country: Turkey
facility: GSK Investigational Site
city: Eskisehir
country: Turkey
facility: GSK Investigational Site
city: Istanbul
country: Turkey
facility: GSK Investigational Site
city: St Austell
country: United Kingdom
facility: GSK Investigational Site
state: Cornwall
city: Southampton
country: United Kingdom
facility: GSK Investigational Site
state: Hampshire
city: Axbridge
country: United Kingdom
facility: GSK Investigational Site
state: Somerset
city: Bath
country: United Kingdom
facility: GSK Investigational Site
state: Somerset
city: Yeovil
country: United Kingdom
facility: GSK Investigational Site
state: Somerset
city: Atherstone
country: United Kingdom
facility: GSK Investigational Site
state: Warwickshire
city: Coventry
country: United Kingdom
facility: GSK Investigational Site
state: Warwickshire
city: Belfast
country: United Kingdom
facility: GSK Investigational Site
city: Bolton, Nr Manchester
country: United Kingdom
facility: GSK Investigational Site
city: Bristol
country: United Kingdom
facility: GSK Investigational Site
city: Co Antrim
country: United Kingdom
facility: GSK Investigational Site
city: Crumpsall, Manchester
country: United Kingdom
facility: GSK Investigational Site
city: Exeter
country: United Kingdom
facility: GSK Investigational Site
city: Gloucester
country: United Kingdom
facility: GSK Investigational Site
city: London
country: United Kingdom
facility: GSK Investigational Site
city: Manchester
country: United Kingdom
facility: GSK Investigational Site
city: Nottingham
country: United Kingdom
facility: GSK Investigational Site
city: Oxford
country: United Kingdom
facility: GSK Investigational Site
city: Taunton, Somerset
country: United Kingdom
facility: GSK Investigational Site
city: Westminster Bridge Road
country: United Kingdom
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Danier J, Callegaro A, Soni J, Carmona A, Kosalaraska P, Rivera L, Friel D, Pu W, Vantomme V, Dbaibo G, Innis BL, Schuind A, Zaman K, Wilson J. Association Between Hemagglutination Inhibition Antibody Titers and Protection Against Reverse-Transcription Polymerase Chain Reaction-Confirmed Influenza Illness in Children 6-35 Months of Age: Statistical Evaluation of a Correlate of Protection. Open Forum Infect Dis. 2021 Sep 25;9(2):ofab477. doi: 10.1093/ofid/ofab477. eCollection 2022 Feb.
citation: Dbaibo G, Amanullah A, Claeys C, Izu A, Jain VK, Kosalaraksa P, Rivera L, Soni J, Yanni E, Zaman K, Acosta B, Ariza M, Arroba Basanta ML, Bavdekar A, Carmona A, Cousin L, Danier J, Diaz A, Diez-Domingo J, Dinleyici EC, Faust SN, Garcia-Sicilia J, Gomez-Go GD, Gonzales MLA, Hacimustafaoglu M, Hughes SM, Jackowska T, Kant S, Lucero M, Mares Bermudez J, Martinon-Torres F, Montellano M, Prymula R, Puthanakit T, Ruzkova R, Sadowska-Krawczenko I, Szymanski H, Ulied A, Woo W, Schuind A, Innis BL; Flu4VEC Study Group. Quadrivalent Influenza Vaccine Prevents Illness and Reduces Healthcare Utilization Across Diverse Geographic Regions During Five Influenza Seasons: A Randomized Clinical Trial. Pediatr Infect Dis J. 2020 Jan;39(1):e1-e10. doi: 10.1097/INF.0000000000002504.
citation: Danier J, Rivera L, Claeys C, Dbaibo G, Jain VK, Kosalaraksa P, Woo W, Yanni E, Zaman K, Acosta B, Amanullah A, Ariza M, Luisa Arroba Basanta M, Bavdekar A, Carmona A, Cousin L, Diaz A, Diez-Domingo J, Cagri Dinleyici E, Faust SN, Garcia-Sicilia J, Gomez-Go GD, Antionette Gonzales L, Hacimustafaoglu M, Hughes SM, Izu A, Jackowska T, Kant S, Lucero M, Mares Bermudez J, Martinon-Torres F, Montellano M, Prymula R, Puthanakit T, Ruzkova R, Sadowska-Krawczenko I, Soni J, Szymanski H, Ulied A, Schuind A, Innis BL; Flu4VEC Study Group. Clinical Presentation of Influenza in Children 6 to 35 Months of Age: Findings From a Randomized Clinical Trial of Inactivated Quadrivalent Influenza Vaccine. Pediatr Infect Dis J. 2019 Aug;38(8):866-872. doi: 10.1097/INF.0000000000002387.
citation: Claeys C, Chandrasekaran V, Garcia-Sicilia J, Prymula R, Diez-Domingo J, Brzostek J, Mares-Bermudez J, Martinon-Torres F, Pollard AJ, Ruzkova R, Carmona Martinez A, Ulied A, Miranda Valdivieso M, Faust SN, Snape MD, Friel D, Ollinger T, Soni J, Schuind A, Li P, Innis BL, Jain VK. Anamnestic Immune Response and Safety of an Inactivated Quadrivalent Influenza Vaccine in Primed Versus Vaccine-Naive Children. Pediatr Infect Dis J. 2019 Feb;38(2):203-210. doi: 10.1097/INF.0000000000002217.