Clinical trial NCT01051661: Safety and Efficacy of H1N1 Vaccines in Children Aged 6 Months to Less Than 10 Years of Age
Official title: A Study to Evaluate the Safety and Efficacy of A/California/7/2009 (H1N1)V-like Vaccines GSK2340274A and GSK2340273A in Children Aged 6 Months to Less Than 10 Years of Age
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Influenza
Keywords: Influenza
H1N1
Pandemic
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2010-01-18
Enrollment: 6154
Sex: ALL
Minimum age (years): 6
Maximum age (years): 9
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The purpose of this study is to characterize the safety and efficacy of GSK Biologicals' H1N1 flu candidate vaccines GSK2340274A and GSK2340273A in children 6 months to less than 10 years of age.


Eligibility criteria: Inclusion Criteria:

* Male or female children 6 months to less than 10 years of age at the time of the first vaccination. "Less than 10 years of age" implies inclusion of children who have not reached their 10th birthday as of Day 0, the day of first vaccine dose under this protocol.
* Written informed consent obtained from the subject's parent(s)/legally acceptable representative(s) (LAR(s)); written informed assent obtained from the subject if appropriate pre local requirements).
* Stable health status as defined by absence of a health event satisfying the definition of a SAE, or a change in an ongoing drug therapy due to therapeutic failure or symptoms of drug toxicity, within 1 month prior to enrolment.
* Parent(s)/LAR(s) available and accessible for active surveillance contacts.
* Parent(s)/LAR(s) and (if age-appropriate, subjects) who, in the investigator's opinion, can and will comply with the requirements of the protocol as documented by signature on the informed consent document.
* Female subjects of non-childbearing potential (pre-menarche) may be enrolled in the study.

Exclusion Criteria:

* Previous vaccination with an A/California/7/2009 (H1N1)v-like virus vaccine.
* Medical history of physician-confirmed infection with an A/California/7/2009 (H1N1)v-like virus.
* Presence of evidence of substance abuse or of neurological or psychiatric diagnoses which, even if stable, are deemed by the investigator to render the potential subject or parent(s)/LAR(s) unable/unlikely to provide accurate safety reports.
* Presence of a temperature ≥ 38.0ºC (≥ 100.4ºF) by any route or method, or acute symptoms greater than "mild" severity on the scheduled date of first vaccination. NOTE: The subject may be vaccinated at a later date, provided symptoms have resolved, vaccination occurs within the window specified by the protocol, and all other eligibility criteria continue to be satisfied.
* Diagnosed with cancer, or treatment for cancer, within 3 years.
* Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination (no laboratory testing required).
* Receipt of systemic glucocorticoids within 1 month prior to study enrollment (first dose of study vaccine), or any other cytotoxic or immunosuppressive drug within 6 months of study enrollment. Topical, intra-articular or inhaled glucocorticoids are allowed.
* Receipt of any immunoglobulins and/or any blood products within 6 months of study enrollment or planned administration of any of these products during the study period.
* Any significant disorder of coagulation or treatment with warfarin derivatives or heparin. Persons receiving individual doses of low molecular weight heparin are eligible if no such doses are given in the 24 hours before a study vaccination. Persons receiving prophylactic antiplatelet medications, e.g., low-dose acetylsalicylic acid, and without a clinically-apparent bleeding tendency, are eligible.
* An acute evolving neurological disorder or history of Guillain-Barré syndrome within 6 weeks of receipt of seasonal influenza vaccine.
* Administration of any licensed live attenuated vaccine within 4 weeks before the first vaccination or of any licensed inactivated vaccine within 2 weeks before the first vaccination.
* Planned administration of any vaccine not foreseen by the study protocol between Day 0 and Day 42. Routine childhood vaccinations are exempted if they cannot be delayed, but they must not be administered on the same day as the H1N1 vaccine candidate.
* Planned use of a pandemic monovalent A/California/7/2009 (H1N1)v-like virus vaccine other than the study vaccines during the study period.
* Planned administration of seasonal trivalent influenza vaccine during the 4 month period following Day 0.
* Use of any investigational or non-registered product (drug or vaccine) other than the study vaccine(s) within 30 days before the first dose of study vaccine, or planned use during the study period.
* Any known or suspected allergy to any constituent of influenza vaccines (including egg proteins or mercurial preservatives); a history of anaphylactic-type reaction to consumption of eggs; or a history of severe adverse reaction to a previous influenza vaccine.
* Child in care.

Primary outcomes:
measure: Number of Subjects Reporting at Least One A/California Influenza Event
timeFrame: From 14 days after first vaccination until study conclusion on Day 385
Secondary outcomes:
measure: Number of Subjects Reporting at Least One A/California Influenza Event
timeFrame: From 42 days after first vaccination until study conclusion on Day 385
measure: Number of Subjects Reporting at Least One A/California Influenza Event
timeFrame: From Day 0 until study conclusion on Day 385
measure: Number of Subjects Reporting at Least One Culture Confirmed A/California Influenza Event
timeFrame: From 14 days after first vaccination until study conclusion on Day 385
measure: Number of Subjects Reporting at Least One Culture Confirmed A/California Influenza Event
timeFrame: From 42 days after first vaccination until study conclusion on Day 385
measure: Number of Subjects Reporting at Least One Culture Confirmed A/California Influenza Event
timeFrame: From Day 0 until study conclusion on Day 385
measure: Number of Subjects With at Least One Pneumonia Event
timeFrame: From 14 days after first vaccination until study conclusion on Day 385
measure: Number of Subjects With at Least One Pneumonia Event
timeFrame: From 42 days after first vaccination until study conclusion on Day 385
measure: Number of Subjects With at Least One Pneumonia Event
timeFrame: From Day 0 after first vaccination until study conclusion on Day 385
measure: Number of Subjects With at Least One Pneumonia Event
timeFrame: From 14 days after first vaccination until study conclusion at Day 385
measure: Number of Subjects With at Least One Pneumonia Event
timeFrame: From 42 days after first vaccination until study conclusion at Day 385
measure: Number of Subjects With at Least One Pneumonia Event
timeFrame: From Day 0 after first vaccination until study conclusion at Day 385
measure: Number of Subjects With Protocol Specified Influenza-like Illness (ILI) Symptoms in All Reported ILI Cases
timeFrame: From Day 0 until study end at Day 385
measure: Number of Subjects With Protocol Specified Influenza-like Illness (ILI) Symptoms in All Reported ILI Cases
timeFrame: From Day 14 until study end at Day 385
measure: Number of Subjects With Protocol Specified ILI Symptoms in RT-qPCR-confirmed A/California Influenza Cases
timeFrame: From Day 0 until study end at Day 385
measure: Number of Subjects With Protocol Specified ILI Symptoms in RT-qPCR-confirmed A/California Influenza Cases
timeFrame: From Day 14 until study end at Day 385
measure: Number of Subjects With Any and Grade 3 Solicited Local Symptoms
timeFrame: During the 7-day follow-up period (Day 0 - Day 6) after each dose and across doses
measure: Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms in Children Aged 6 Months to Less Than 6 Years
timeFrame: During the 7-day follow-up period (Day 0 - Day 6) after each dose and across doses
measure: Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms in Children Aged Between 6 to 10 Years
timeFrame: During the 7-day follow-up period (Day 0 - Day 6) after each dose and across doses
measure: Number of Subjects Reporting Any Potential Immune-mediated Diseases (pIMDs)
timeFrame: Up to Day 385
measure: Number of Subjects With Any Medically-attended Adverse Events (MAEs)
timeFrame: Up to Day 385
measure: Number of Subjects With Any Unsolicited Adverse Events (AEs)
timeFrame: From Day 0 to Day 42
measure: Number of Subjects With Serious Adverse Events (SAEs)
timeFrame: Up to Day 385
measure: Titers for Serum Hemagglutination Inhibition (HI) Antibodies Against Flu A/CAL/7/09 (H1N1) Influenza Strain
timeFrame: At Days 0 and 42
measure: Number of Seropositive Subjects for Hemagglutination Inhibition (HI) Antibodies Against Flu A/CAL/7/09 (H1N1) Influenza Strain
timeFrame: At Days 0 and 42
measure: Number of Seroconverted (SCR) Subjects for Flu A/CAL/7/09 (H1N1) Influenza Strain
timeFrame: At Day 42
measure: Number of Seroprotected (SPR) Subjects Against Flu A/CAL/7/09 (H1N1) Influenza Strain
timeFrame: At Days 0 and 42
measure: Seroconversion Factor for Hemagglutination Inhibition (HI) Antibodies Against Flu A/CAL/7/09 (H1N1) Influenza Strain
timeFrame: At Day 42
measure: Geometric Mean Antibody Titer Ratio Adjusted for Baseline Titers for Serum Hemagglutination Inhibition (HI) Antibodies Against Flu A/CAL/7/09 (H1N1)
timeFrame: At Day 42
measure: Titers for Serum Hemagglutination Inhibition (HI) Antibodies Against Flu A/CAL/7/09 (H1N1)
timeFrame: At Days 0 and 182
measure: Number of Seropositive Subjects for Hemagglutination Inhibition (HI) Antibodies Against Flu A/CAL/7/09 (H1N1) Influenza Strain
timeFrame: At Days 0 and 182
measure: Number of Seroconverted (SCR) Subjects for Flu A/CAL/7/09 (H1N1) Influenza Strain
timeFrame: At Day 182
measure: Number of Seroprotected (SPR) Subjects Against Flu A/CAL/7/09 (H1N1) Influenza Strain
timeFrame: At Days 0 and 182
measure: Seroconversion Factor for Hemagglutination Inhibition (HI) Antibodies Against Flu A/CAL/7/09 (H1N1) Influenza Strain
timeFrame: At Day 182
measure: Titers for Serum Hemagglutination Inhibition (HI) Antibodies Against Flu A/CAL/7/09 (H1N1) Influenza Strain
timeFrame: At Days 0 and 385
measure: Number of Seropositive Subjects for Hemagglutination Inhibition (HI) Antibodies Against Flu A/CAL/7/09 (H1N1) Influenza Strain
timeFrame: At Days 0 and 385
measure: Number of Seroconverted (SCR) Subjects for Flu A/CAL/7/09 (H1N1) Influenza Strain
timeFrame: At Day 385
measure: Number of Seroprotected (SPR) Subjects Against Flu A/CAL/7/09 (H1N1) Influenza Strain
timeFrame: At Days 0 and 385
measure: Seroconversion Factor for Hemagglutination Inhibition (HI) Antibodies Against Flu A/CAL/7/09 (H1N1) Influenza Strain
timeFrame: At Day 385
Other outcomes:
Locations:
city: Kippa Ring
country: Australia
facility: GSK Investigational Site
state: Queensland
city: Carlton
country: Australia
facility: GSK Investigational Site
state: Victoria
city: Florianópolis
country: Brazil
facility: GSK Investigational Site
state: Santa Catarina
city: São Paulo
country: Brazil
facility: GSK Investigational Site
city: São Paulo
country: Brazil
facility: GSK Investigational Site
city: Cali
country: Colombia
facility: GSK Investigational Site
city: San Jose
country: Costa Rica
facility: GSK Investigational Site
city: Cuernavaca
country: Mexico
facility: GSK Investigational Site
state: Morelos
city: Durango
country: Mexico
facility: GSK Investigational Site
city: Mexico city
country: Mexico
facility: GSK Investigational Site
city: Monterrey
country: Mexico
facility: GSK Investigational Site
city: Dasmariñas, Cavite
country: Philippines
facility: GSK Investigational Site
city: Muntinlupa
country: Philippines
facility: GSK Investigational Site
city: Sampaloc, Manila
country: Philippines
facility: GSK Investigational Site
city: Singapore
country: Singapore
facility: GSK Investigational Site
city: Bangkok
country: Thailand
facility: GSK Investigational Site
city: Khon Kaen
country: Thailand
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Nolan T, Roy-Ghanta S, Montellano M, Weckx L, Ulloa-Gutierrez R, Lazcano-Ponce E, Kerdpanich A, Safadi MA, Cruz-Valdez A, Litao S, Lim FS, de Los Santos AM, Weber MA, Tinoco JC, Mezerville MH, Faingezicht I, Kosuwon P, Lopez P, Borja-Tabora C, Li P, Durviaux S, Fries L, Dubin G, Breuer T, Innis BL, Vaughn DW. Relative efficacy of AS03-adjuvanted pandemic influenza A(H1N1) vaccine in children: results of a controlled, randomized efficacy trial. J Infect Dis. 2014 Aug 15;210(4):545-57. doi: 10.1093/infdis/jiu173. Epub 2014 Mar 20.
citation: Taylor S, Lopez P, Weckx L, Borja-Tabora C, Ulloa-Gutierrez R, Lazcano-Ponce E, Kerdpanich A, Angel Rodriguez Weber M, Mascarenas de Los Santos A, Tinoco JC, Safadi MA, Lim FS, Hernandez-de Mezerville M, Faingezicht I, Cruz-Valdez A, Feng Y, Li P, Durviaux S, Haars G, Roy-Ghanta S, Vaughn DW, Nolan T. Respiratory viruses and influenza-like illness: Epidemiology and outcomes in children aged 6 months to 10 years in a multi-country population sample. J Infect. 2017 Jan;74(1):29-41. doi: 10.1016/j.jinf.2016.09.003. Epub 2016 Sep 22.