Clinical trial NCT01310413: Monovalent H5N1 Vaccine GSK1557484A in Children 6 Months to < 18 Years of Age
Official title: Safety and Immunogenicity of Monovalent H5N1 Vaccine GSK1557484A in Children 6 Months to < 18 Years of Age
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Influenza
Influenza Vaccines
Keywords: Influenza
H5N1
Pandemic
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2011-03-08
Enrollment: 842
Sex: ALL
Minimum age (years): 6
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: This study will assess safety and immunogenicity of GSK Biologicals' H5N1 flu candidate vaccine GSK1557484A in children 6 months to \< 18 years of age.


Eligibility criteria: Inclusion Criteria:

* A male or female child \>= 6 months and \< 18 years of age at the time of first vaccination.
* Written informed consent obtained from the subject's parent/guardian.
* Documentation of assent for children 9 to \< 18 years of age (or as deemed mandatory by local practice).
* Satisfactory baseline medical assessment by history and physical examination
* Parent/guardian and subject access to a consistent means of telephone contact, land line or mobile, but NOT a pay phone or other multiple-user device.
* Parents/guardians and subjects who the investigator believes understand the requirements of the protocol and can and will comply with them.
* Female subjects of non-childbearing potential may be enrolled in the study.
* Female subjects of childbearing potential must

  * have practiced adequate contraception for 30 days prior to vaccination, and
  * have a negative pregnancy test on the day of each vaccination, and
  * have agreed to continue adequate contraception for 2 months after completion of the vaccination series.

Exclusion Criteria:

* Medical history of physician-confirmed infection with an H5N1 virus.
* Previous vaccination at any time with an H5N1 vaccine.
* Use of any investigational or non-registered product other than the study vaccine within 30 days preceding the first dose of study vaccine/product, or planned use during the study period.
* Presence of significant acute or chronic, uncontrolled medical or psychiatric illness.
* Presence of neurological or psychiatric diagnoses which, although stable, are deemed by the investigator to render the potential subject or parent/guardian unable/unlikely to provide accurate safety reports.
* Evidence of current subject or parent/guardian substance abuse, including alcohol, by medical history.
* Presence of a temperature \>= 38.0ºC by any method, or acute symptoms greater than "mild" severity on the scheduled date of first dose.
* 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 first dose of test article or any other cytotoxic or immunosuppressive drug within 6 months prior to first dose of test article. Receipt of any immunoglobulins and/or any blood products within 3 months of first test article administration or planned administration of any of these products during the study period.
* Any significant disorder of coagulation or treatment with warfarin derivatives or heparin.
* An acute evolving neurological disorder or history of Guillain-Barré syndrome within 6 weeks of receipt of seasonal influenza vaccine.
* Administration of an inactivated seasonal influenza vaccine within 14 days, or of a live, attenuated seasonal influenza vaccine within 30 days before the first test article dose, or of any other vaccine(s) not foreseen by the study protocol within 30 days before the first test article dose.
* Planned administration of any vaccine(s) not foreseen by the study protocol through completion of the "Day 42" visit.
* Any known or suspected allergy to any constituent of influenza vaccines or history of severe reaction to any previous influenza vaccination.
* Known pregnancy, or a positive urine pregnancy test result prior to each test article dose.
* Lactating or nursing.
* Child in care.

Primary outcomes:
measure: Number of Subjects Seroprotected for Haemagglutination Inhibition (HI) Antibody Titers Against the H5N1 A/Indonesia Virus Strain.
timeFrame: At Day 42.
Secondary outcomes:
measure: Haemagglutination Inhibition (HI) Antibody Titers Against the H5N1 A/Indonesia Virus Strain.
timeFrame: At Days 0 and 21
measure: Number of Subjects Seroprotected for Haemagglutination Inhibition (HI) Antibody Titers Against the H5N1 A/Indonesia Virus Strain.
timeFrame: At Days 0 and 21
measure: Number of Seroconverted Subjects for Haemagglutination Inhibition (HI) Antibodies Against the H5N1 A/Indonesia Virus Strain.
timeFrame: At Days 21 and 42
measure: Geometric Mean Increase (GMI) for Haemagglutination Inhibition (HI) Antibodies Against the H5N1 A/Indonesia Virus Strain.
timeFrame: At Days 21 and 42
measure: Haemagglutination Inhibition (HI) Antibody Titers Against the H5N1 A/Indonesia Virus Strain.
timeFrame: At Day 0 and Day 182.
measure: Number of Subjects Seroprotected as Regards Haemagglutination Inhibition (HI) Antibody Titers Against the H5N1 A/Indonesia Virus Strain.
timeFrame: At Day 0 and Day 182
measure: Haemagglutination Inhibition (HI) Antibody Titers Against the H5N1 A/Indonesia Virus Strain
timeFrame: At Day 42.
measure: Number of Seroconverted Subjects for Haemagglutination Inhibition (HI) Antibodies Against the H5N1 A/Indonesia Virus Strain.
timeFrame: At Day 182
measure: Geometric Mean Increase (GMI) for Haemagglutination Inhibition (HI) Antibodies Against the H5N1 A/Indonesia Virus Strain.
timeFrame: At Day 182
measure: Haemagglutination Inhibition (HI) Antibody Titers Against the H5N1 A/Indonesia Virus Strain.
timeFrame: At Day 0 and Day 385
measure: Number of Subjects Seroprotected for Haemagglutination Inhibition (HI) Antibody Titers Against the H5N1 A/Indonesia Virus Strain.
timeFrame: At Day 0 and Day 385
measure: Number of Seroconverted Subjects for Haemagglutination Inhibition (HI) Antibodies Against the H5N1 A/Indonesia Virus Strain.
timeFrame: At Day 385
measure: Geometric Mean Increase (GMI) for Haemagglutination Inhibition (HI) Antibodies Against the H5N1 A/Indonesia Virus Strain.
timeFrame: At Day 385.
measure: Microneutralization (MN) Antibody Titers Against the H5N1 A/Indonesia and H5N1 A/Vietnam Virus Strains.
timeFrame: At Days 0, 42, 182 and 385
measure: Number of Subjects Seropositive for Microneutralization (MN) Antibodies Against the H5N1 A/Indonesia Virus Strain.
timeFrame: At Days 0 and 42
measure: Vaccine Response Rate (VRR) for Microneutralization (MN) Antibodies Against the H5N1 A/Indonesia and H5N1 A/Vietnam Virus Strains.
timeFrame: At Day 42
measure: Number of Subjects Reporting Solicited Local Symptoms.
timeFrame: During the 7-day (Days 0-6) post-vaccination periods post Doses 1 and 2 of vaccine/placebo, across doses (Year 1)
measure: Number of Subjects Reporting Solicited Local Symptoms.
timeFrame: During the 7-day (Days U0-U6) post-vaccination periods post Doses 1 and 2 of vaccine/placebo, across doses (Year 2)
measure: Number of Subjects of Less Than 6 Years of Age Reporting Solicited General Symptoms.
timeFrame: During the 7-day (Days 0-6) post-vaccination periods post Doses 1 and 2 of vaccine/placebo, across doses (Year 1)
measure: Number of Subjects of Less Than 6 Years of Age Reporting Solicited General Symptoms.
timeFrame: During the 7-day (Days U0-U6) post-vaccination periods post Doses 1 and 2 of vaccine/placebo, across doses (Year 2)
measure: Number of Subjects at Least 6 Years of Age Reporting Solicited General Symptoms.
timeFrame: During the 7-day (Days 0-6) post-vaccination periods post Doses 1 and 2 of vaccine/placebo, across doses (Year 1)
measure: Number of Subjects at Least 6 Years of Age Reporting Solicited General Symptoms.
timeFrame: During the 7-day (Days U0-U6) post-vaccination periods post Doses 1 and 2 of vaccine/placebo, across doses (Year 2)
measure: Number of Subjects With Medically-attended Adverse Events (MAEs)
timeFrame: From Day 0 up to Day 385
measure: Number of Subjects With Medically-attended Adverse Events (MAEs)
timeFrame: From Day U0 up to Day U385
measure: Number of Subjects With Any Potential Immune-Mediated Diseases (pIMDs)
timeFrame: From Day 0 up to Day 385
measure: Number of Subjects With Any Potential Immune-Mediated Diseases (pIMDs)
timeFrame: From Day U0 to Day U385
measure: Number of Subjects Reporting Pregnancies, and Outcomes of These Reported Pregnancies
timeFrame: From Day 0 up to Day 385
measure: Number of Subjects Reporting Pregnancies, and Outcomes of These Reported Pregnancies
timeFrame: From Day U0 to Day U385
measure: Number of Subjects With Normal and Abnormal Biochemical Parameters Assessed With Respect to Alanine Aminotransferase (ALAT) and Aspartate Aminotransferase (ASAT)
timeFrame: From Day 0 up to Day 385
measure: Number of Subjects With Normal and Abnormal Biochemical Parameters Assessed With Respect to Total Bilirubin (T-BIL) and Bilirubin Conjugated/Direct (BIL-C/D)
timeFrame: From Day 0 up to Day 385
measure: Number of Subjects With Normal and Abnormal Biochemical Parameters Assessed With Respect to Creatinine (CREA) and Blood Urea Nitrogen (BUN)
timeFrame: From Day 0 up to Day 385
measure: Number of Subjects With Normal and Abnormal Haematological Parameters Assessed With Respect to Basophils (BAS) and Eosinophils (EOS)
timeFrame: From Day 0 up to Day 385
measure: Number of Subjects With Normal and Abnormal Haematological Parameters Assessed With Respect to Haematocrit (Hcr) and Haemoglobin (Hgb)
timeFrame: From Day 0 up to Day 385
measure: Number of Subjects With Normal and Abnormal Haematological Parameters Assessed With Respect to Neutrophils (NEU) and Platelets (PLA)
timeFrame: From Day 0 up to Day 385
measure: Number of Subjects With Normal and Abnormal Haematological Parameters Assessed With Respect to Lymphocytes (LYM) and Monocytes (MON)
timeFrame: From Day 0 up to Day 385
measure: Number of Subjects With Normal and Abnormal Haematological Parameters Assessed With Respect to Red and White Blood Cells (RBC and WBC)
timeFrame: From Day 0 up to Day 385
measure: Number of Subjects Reporting Any Unsolicited Adverse Events (AEs).
timeFrame: During the 21-day (Days 0-20) post-vaccination period following Dose 1 of vaccine/placebo
measure: Number of Subjects Reporting Any Unsolicited Adverse Events (AEs).
timeFrame: During the 21-day (Days 21-41) post-vaccination period following Dose 2 of vaccine/placebo
measure: Number of Subjects Reporting Any Unsolicited Adverse Events (AEs).
timeFrame: During the 42-day (Days 0-41) post-vaccination period following Dose 1 of vaccine/placebo
measure: Number of Subjects Reporting Serious Adverse Events (SAEs)
timeFrame: From Day 0 up to Day 385
measure: Number of Subjects Reporting Any Unsolicited Adverse Events (AEs).
timeFrame: During the 21-day (Days U0-U20) post-vaccination period following Dose 1 of Influenza A (H5N1) Virus monovalent vaccine
measure: Number of Subjects Reporting Any Unsolicited Adverse Events (AEs).
timeFrame: During the 21-day (Days U21-U41) post-vaccination period following Dose 2 of Influenza A (H5N1) Virus monovalent vaccine
measure: Number of Subjects Reporting Any Unsolicited Adverse Events (AEs).
timeFrame: During the 42-day (Days U0-U41) post-vaccination period following Dose 1 of Influenza A (H5N1) Virus monovalent vaccine
measure: Number of Subjects Reporting Serious Adverse Events (SAEs)
timeFrame: From Day U0 up to Day U385
Other outcomes:
Locations:
city: Paramount
country: United States
facility: GSK Investigational Site
state: California
city: Sacramento
country: United States
facility: GSK Investigational Site
state: California
city: Newton
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 Louis
country: United States
facility: GSK Investigational Site
state: Missouri
city: Omaha
country: United States
facility: GSK Investigational Site
state: Nebraska
city: Henderson
country: United States
facility: GSK Investigational Site
state: Nevada
city: Cleveland
country: United States
facility: GSK Investigational Site
state: Ohio
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: Coquitlam
country: Canada
facility: GSK Investigational Site
state: British Columbia
city: Hamilton
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Sudbury
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Sherbrooke
country: Canada
facility: GSK Investigational Site
state: Quebec
city: Sherbrooke
country: Canada
facility: GSK Investigational Site
state: Quebec
city: Khon Kaen
country: Thailand
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Izurieta P et al. (2018) Reactogenicity and safety of AS03B-adjuvanted H5N1 influenza vaccine in children: an open-label, one-way, crossover trial. Asian Biomed (Res Rev News). 11(4):359-364.
citation: Kosalaraksa P, Jeanfreau R, Frenette L, Drame M, Madariaga M, Innis BL, Godeaux O, Izurieta P, Vaughn DW. AS03B-adjuvanted H5N1 influenza vaccine in children 6 months through 17 years of age: a phase 2/3 randomized, placebo-controlled, observer-blinded trial. J Infect Dis. 2015 Mar 1;211(5):801-10. doi: 10.1093/infdis/jiu548. Epub 2014 Oct 6.