Clinical trial NCT00976820: Safety and Immunogenicity of H1N1 Vaccines in Children Aged 6 Months to Less Than 9 Years of Age
Official title: A Study to Evaluate the Safety and Immunogenicity of A/California/7/2009 (H1N1)V-like Vaccines GSK2340274A and GSK2340273A in Children 6 Months to Less Than 9 Years of Age
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Influenza
Keywords: influenza infection
Influenza Vaccines
GSK Bio's influenza vaccine GSK2340273A
GSK Bio's influenza vaccine GSK2340274A
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2009-09-14
Enrollment: 323
Sex: ALL
Minimum age (years): 6
Maximum age (years): 8
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 immune response of the H1N1 (swine) flu vaccines GSK2340274A and GSK2340273A in children 6 months to less than 9 years of age.

This Protocol Posting has been updated following the Protocol amendment 1 \& 2, September and October 2009. The sections impacted are study design, objectives and analysis methods.

Detailed description: Collaborators: United States Department of Health and Human Services, Office of Biomedical Advanced Research and Development Authority

Eligibility criteria: Inclusion Criteria:

* Male or female children 6 months to less than 9 years of age at the time of the first vaccination.
* Written informed consent obtained from the subject's parent/ legally acceptable representative (LAR); written informed assent obtained from the subject if appropriate.
* Good general health as established by medical history and clinical examination before entering into the study.
* Safety laboratory test results within the parameters specified in the protocol.
* Parent/ LAR access to a consistent means of telephone contact, land line or mobile, but NOT a pay phone or other multiple-user device.
* Subjects who the investigator believes that their parent(s)/ LAR can and will comply with the requirements of the protocol.
* Female subjects of non-childbearing potential (pre-menarche) may be enrolled in the study.

Exclusion Criteria:

* Previous vaccination with an H1N1v-like virus vaccine or a medical history of physician-confirmed infection with an H1N1v-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.
* 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
* Receipt of systemic glucocorticoids within 1 month prior to study enrollment, 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 3 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 vaccine within 4 weeks before the first dose of study vaccine, with the exception of seasonal influenza vaccine.
* Planned administration of any vaccine not foreseen by the study protocol between Day 0 and the Day 42 phlebotomy, including seasonal influenza vaccine. 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.
* Use of any investigational or non-registered product (drug or vaccine) other than the study vaccine(s) within 30 days preceding the first dose of study vaccine, or planned use during the study period.
* Any known or suspected allergy to any constituent of influenza vaccines a history of anaphylactic-type reaction to any constituent of influenza vaccines; or a history of severe adverse reaction to a previous influenza vaccine.
* Child in care.

Primary outcomes:
measure: Number of Seroconverted Subjects Against Flu A/CAL/7/09 Influenza Strain - Preliminary Analysis
timeFrame: At Day 21
measure: Number of Seroconverted Subjects Against Flu A/CAL/7/09 Influenza Strain - First Analysis
timeFrame: At Day 21
measure: Number of Seroconverted Subjects Against Flu A/CAL/7/09 Influenza Strain - Second Analysis
timeFrame: At Day 21
measure: Number of Seroconverted Subjects Against Flu A/CAL/7/09 Influenza Strain - First Analysis
timeFrame: At Day 42
measure: Number of Seroconverted Subjects Against Flu A/CAL/7/09 Influenza Strain - Second Analysis
timeFrame: At Day 42
measure: Number of Seroprotected Subjects Against Flu A/CAL/7/09 Influenza Strain - Preliminary Analysis
timeFrame: At Day 0
measure: Number of Seroprotected Subjects Against Flu A/CAL/7/09 Influenza Strain - Preliminary Analysis
timeFrame: At Day 21
measure: Number of Seroprotected Subjects Against Flu A/CAL/7/09 Influenza Strain - First Analysis
timeFrame: At Day 0
measure: Number of Seroprotected Subjects Against Flu A/CAL/7/09 Influenza Strain - First Analysis
timeFrame: At Day 21
measure: Number of Seroprotected Subjects Against Flu A/CAL/7/09 Influenza Strain - Second Analysis
timeFrame: At Day 0
measure: Number of Seroprotected Subjects Against Flu A/CAL/7/09 Influenza Strain - Second Analysis
timeFrame: At Day 21
measure: Number of Seroprotected Subjects Against Flu A/CAL/7/09 Strain - First Analysis
timeFrame: At Day 0
measure: Number of Seroprotected Subjects Against Flu A/CAL/7/09 Influenza Strain - First Analysis
timeFrame: At Day 42
measure: Number of Seroprotected Subjects Against Flu A/CAL/7/09 Strain - Second Analysis
timeFrame: At Day 0
measure: Number of Seroprotected Subjects Against Flu A/CAL/7/09 Influenza Strain - Second Analysis
timeFrame: At Day 42
measure: Seroconversion Factor (SCF) for HI Antibodies Against Flu A/CAL/7/09 Influenza Strain - Preliminary Analysis
timeFrame: At Day 21
measure: Seroconversion Factor (SCF) for HI Antibodies Against Flu A/CAL/7/09 Influenza Strain - First Analysis
timeFrame: At Day 21
measure: Seroconversion Factor (SCF) for HI Antibodies Against Flu A/CAL/7/09 Influenza Strain - Second Analysis
timeFrame: At Day 21
measure: Seroconversion Factor (SCF) for HI Antibodies Against Flu A/CAL/7/09 Influenza Strain - First Analysis
timeFrame: At Day 42
measure: Seroconversion Factor (SCF) for HI Antibodies Against Flu A/CAL/7/09 Influenza Strain - Second Analysis
timeFrame: At Day 42
Secondary outcomes:
measure: Number of Seropositive Subjects for HI Antibodies - Preliminary Analysis
timeFrame: At Day 0 (PRE) and at Day 21
measure: Number of Seropositive Subjects for HI Antibodies - First Analysis
timeFrame: At Day 0 (PRE) and at Day 21
measure: Number of Seropositive Subjects for HI Antibodies - Second Analysis
timeFrame: At Day 0 (PRE) and at Day 21
measure: Number of Seropositive Subjects for HI Antibodies - First Analysis
timeFrame: At Day 0 (PRE) and at Day 42
measure: Number of Seropositive Subjects for HI Antibodies - Second Analysis
timeFrame: At Day 0 (PRE) and at Day 42
measure: Number of Seropositive Subjects for HI Antibodies
timeFrame: At Day 0 (PRE) and at Day 182
measure: Titers for Serum Hemagglutination Inhibition (HI) Antibodies Against the Flu A/CAL/7/09 Influenza Strain - Preliminary Analysis
timeFrame: At Day 0 (PRE) and at Day 21
measure: Titers for Serum Hemagglutination Inhibition (HI) Antibodies Against the Flu A/CAL/7/09 Influenza Strain - First Analysis
timeFrame: At Day 0 (PRE) and at Day 21
measure: Titers for Serum Hemagglutination Inhibition (HI) Antibodies Against the Flu A/CAL/7/09 Influenza Strain - Second Analysis
timeFrame: At Day 0 (PRE) and at Day 21
measure: Titers for Serum Hemagglutination Inhibition (HI) Antibodies Against the Flu A/CAL/7/09 Influenza Strain - First Analysis
timeFrame: At Day 0 (PRE) and at Day 42
measure: Titers for Serum Hemagglutination Inhibition (HI) Antibodies Against the Flu A/CAL/7/09 Influenza Strain - Second Analysis
timeFrame: At Day 0 (PRE) and at Day 42
measure: Titers for Serum Hemagglutination Inhibition (HI) Antibodies Against the Flu A/CAL/7/09 Influenza Strain
timeFrame: At Day 0 (PRE) and at Day 182
measure: Number of Seroconverted Subjects Against Flu A/CAL/7/09 Influenza Strain
timeFrame: At Day 182
measure: Number of Seroprotected Subjects Against Flu A/CAL/7/09 Influenza Strain
timeFrame: At Day 0 (PRE) and at Day 182
measure: Seroconversion Factor (SCF) for HI Antibodies Against Flu A/CAL/7/09 Influenza Strain
timeFrame: At Day 182
measure: Number of Seropositive Subjects for Neutralizing Antibodies Against Flu A/Neth/602/09 Influenza Strain
timeFrame: At Day 0 (PRE) and at Day 21
measure: Titers for Neutralizing Antibodies Against the Flu A/Neth/602/09 Influenza Strain
timeFrame: At Day 0 (PRE) and at Day 21
measure: Number of Seropositive Subjects for Neutralizing Antibodies Against Flu A/Neth/602/09 Influenza Strain
timeFrame: At Day 0 (PRE) and at Day 42
measure: Titers for Neutralizing Antibodies Against the Flu A/Neth/602/09 Influenza Strain
timeFrame: At Day 0 (PRE) and at Day 42
measure: Number of Subjects With Vaccine Responses for Neutralizing Antibody Concentrations
timeFrame: At Day 0 (PRE) and at Day 21
measure: Number of Subjects With Vaccine Responses for Neutralizing Antibody Concentrations
timeFrame: At Day 0 (PRE) and at Day 42
measure: Number of Subjects With Any and Grade 3 Solicited Local Symptoms - Preliminary Analysis
timeFrame: During the 7-day (Days 0-6) post-vaccination period
measure: Number of Subjects With Any and Grade 3 Solicited Local Symptoms - First Analysis
timeFrame: During the 7-day (Days 0-6) post-vaccination period following each dose and across doses
measure: Number of Subjects With Any and Grade 3 Solicited Local Symptoms - Second Analysis
timeFrame: During the 7-day (Days 0-6) post-vaccination period following each dose and across doses
measure: Number of Subjects Less Than 6 Years Old With Any, Grade 3 and Related Solicited General Symptoms - Preliminary Analysis
timeFrame: During the 7-day (Days 0-6) post-vaccination period
measure: Number of Subjects Aged Between 6 to Less Than 9 Years With Any, Grade 3 and Related Solicited General Symptoms - Preliminary Analysis
timeFrame: During the 7-day (Days 0-6) post-vaccination period
measure: Number of Subjects Less Than 6 Years Old With Any, Grade 3 and Related Solicited General Symptoms - First Analysis
timeFrame: During the 7-day (Days 0-6) post-vaccination period following each dose and across doses
measure: Number of Subjects Aged Between 6 to Less Than 9 Years With Any, Grade 3 and Related Solicited General Symptoms - First Analysis
timeFrame: During the 7-day (Days 0-6) post-vaccination period following each dose and across doses
measure: Number of Subjects Less Than 6 Years Old With Any, Grade 3 and Related Solicited General Symptoms - Second Analysis
timeFrame: During the 7-day (Days 0-6) post-vaccination period following each dose and across doses
measure: Number of Subjects Aged Between 6 and 9 Years With Any, Grade 3 and Related Solicited General Symptoms- Second Analysis
timeFrame: During the 7-day (Days 0-6) post-vaccination period following each dose and across doses
measure: Number of Subjects With Haematological Laboratory Abnormalities - Preliminary Analysis
timeFrame: At Day 0 (PRE), at Day 7 and at Day 21
measure: Number of Subjects With Biochemical Laboratory Abnormalities - Preliminary Analysis
timeFrame: At Day 0 (PRE), at Day 7 and at Day 21
measure: Number of Subjects With Haematological Laboratory Abnormalities - First Analysis
timeFrame: At Day 0 (PRE), at Day 7, at Day 21 and at Day 42
measure: Number of Subjects With Biochemical Laboratory Abnormalities - First Analysis
timeFrame: At Day 0 (PRE), at Day 7, at Day 21 and at Day 42
measure: Number of Subjects With Haematological Laboratory Abnormalities - Second Analysis
timeFrame: At Day 0 (PRE), at Day 7 and at Day 21
measure: Number of Subjects With Biochemical Laboratory Abnormalities - Second Analysis
timeFrame: At Day 0 (PRE), at Day 7, at Day 21 and at Day 42
measure: Number of Subjects With Haematological Laboratory Abnormalities
timeFrame: At Day 182
measure: Number of Subjects With Biochemical Laboratory Abnormalities
timeFrame: At Day 182
measure: Number of Subjects With Any Unsolicited Adverse Events (AEs) - Preliminary Analysis
timeFrame: Within 21 days (Days 0-20) post vaccination
measure: Number of Subjects With Any Unsolicited Adverse Events (AEs) - First Analysis
timeFrame: Within 42 days (Days 0-41) post vaccination
measure: Number of Subjects With Any Unsolicited Adverse Events (AEs) - Second Analysis
timeFrame: Within 41 days (Days 0-40) post vaccination
measure: Number of Subjects With Any Unsolicited Adverse Events (AEs)
timeFrame: Within 84 days (Days 0-83) post vaccination
measure: Number of Subjects With Any Medically-attended Adverse Events (MAEs) - Preliminary Analysis
timeFrame: Within 21 days (Days 0-20) post vaccination
measure: Number of Subjects With Any Medically-attended Adverse Events (MAEs) - First Analysis
timeFrame: Within 41 days (Days 0-40) post vaccination
measure: Number of Subjects With Any Medically-attended Adverse Events (MAEs) - Second Analysis
timeFrame: Within 42 days (Days 0-41) post vaccination
measure: Number of Subjects With Any Medically-attended Adverse Events (MAEs)
timeFrame: Within 182 days (Days 0-181) post vaccination
measure: Number of Subjects With Any Medically-attended Adverse Events (MAEs)
timeFrame: Throughout the entire study period (Day 0 - Day 385)
measure: Number of Subjects Reporting Any Potential Immune-mediated Diseases (pIMDs) - Preliminary Analysis
timeFrame: Within 21 days (Days 0-20) post vaccination
measure: Number of Subjects Reporting Any Potential Immune-mediated Diseases (pIMDs) - First Analysis
timeFrame: Within 42 days (Days 0-41) post vaccination
measure: Number of Subjects Reporting Any Potential Immune-mediated Diseases (pIMDs) - Second Analysis
timeFrame: Within 42 days (Days 0-41) post vaccination
measure: Number of Subjects Reporting Any Potential Immune-mediated Diseases (pIMDs)
timeFrame: Within 182 days (Days 0-181) post vaccination
measure: Number of Subjects Reporting Any Potential Immune-mediated Diseases (pIMDs)
timeFrame: Throughout the entire study period (Day 0 - Day 385)
measure: Number of Subjects With Serious Adverse Events (SAEs) - Preliminary Analysis
timeFrame: Within 21 days (Days 0-20) post vaccination
measure: Number of Subjects With Serious Adverse Events (SAEs) - First Analysis
timeFrame: Within 42 days (Days 0-41) post vaccination
measure: Number of Subjects With Serious Adverse Events (SAEs) - Second Analysis
timeFrame: Within 42 days (Day 0-41) post vaccination
measure: Number of Subjects With Serious Adverse Events (SAEs)
timeFrame: Within 182 days (Days 0-181) post vaccination
measure: Number of Subjects With Serious Adverse Events (SAEs)
timeFrame: Throughout the entire study period (Day 0 - Day 385)
Other outcomes:
Locations:
city: Conway
country: United States
facility: GSK Investigational Site
state: Arkansas
city: Little Rock
country: United States
facility: GSK Investigational Site
state: Arkansas
city: Frisco
country: United States
facility: GSK Investigational Site
state: California
city: Sacramento
country: United States
facility: GSK Investigational Site
state: California
city: Arkansas City
country: United States
facility: GSK Investigational Site
state: Kansas
city: Wichita
country: United States
facility: GSK Investigational Site
state: Kansas
city: Bardstown
country: United States
facility: GSK Investigational Site
state: Kentucky
city: Metairie
country: United States
facility: GSK Investigational Site
state: Louisiana
city: Saint Paul
country: United States
facility: GSK Investigational Site
state: Minnesota
city: Omaha
country: United States
facility: GSK Investigational Site
state: Nebraska
city: Cleveland
country: United States
facility: GSK Investigational Site
state: Ohio
city: Kingsport
country: United States
facility: GSK Investigational Site
state: Tennessee
city: Austin
country: United States
facility: GSK Investigational Site
state: Texas
city: Fort Worth
country: United States
facility: GSK Investigational Site
state: Texas
city: San Angelo
country: United States
facility: GSK Investigational Site
state: Texas
city: Orem
country: United States
facility: GSK Investigational Site
state: Utah
city: S. Jordan
country: United States
facility: GSK Investigational Site
state: Utah
city: Coquitlam
country: Canada
facility: GSK Investigational Site
state: British Columbia
city: Winnipeg
country: Canada
facility: GSK Investigational Site
state: Manitoba
city: Saint John's
country: Canada
facility: GSK Investigational Site
state: Newfoundland and Labrador
city: Halifax
country: Canada
facility: GSK Investigational Site
state: Nova Scotia
city: Brampton
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Hamilton
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Newmarket
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Sudbury
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Toronto
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Toronto
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Montreal
country: Canada
facility: GSK Investigational Site
state: Quebec
city: Quebec City
country: Canada
facility: GSK Investigational Site
state: Quebec
city: Sherbrooke
country: Canada
facility: GSK Investigational Site
state: Quebec
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Langley JM, Reich D, Aggarwal N, Connor D, Lebel MH, Gupta A, Garfield H, Li P, Madan A, Vaughn DW. Randomized, multicenter trial of a single dose of AS03-adjuvanted or unadjuvanted H1N1 2009 pandemic influenza vaccine in children 6 months to <9 years of age: safety and immunogenicity. Pediatr Infect Dis J. 2012 Aug;31(8):848-58. doi: 10.1097/INF.0b013e31825e6cd6.