Monovalent H5N1 Vaccine GSK1557484A in Children 6 Months to < 18 Years of Age

Safety and Immunogenicity of Monovalent H5N1 Vaccine GSK1557484A in Children 6 Months to < 18 Years of Age

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

Study Overview

• Status: Completed
• Conditions: Influenza; Influenza Vaccines
• Intervention / Treatment: Biological: Influenza A (H5N1) Virus monovalent vaccine; Biological: Saline placebo

• Study Type: Interventional
• Enrollment (Actual): 842
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • British Columbia
    • Coquitlam, British Columbia, Canada, V3K 3P4
      • GSK Investigational Site
  • Ontario
    • Hamilton, Ontario, Canada, L8L 5G8
      • GSK Investigational Site
    • Sudbury, Ontario, Canada, P3E 1H5
      • GSK Investigational Site
  • Quebec
    • Sherbrooke, Quebec, Canada, J1J 2G2
      • GSK Investigational Site
    • Sherbrooke, Quebec, Canada, J1H 1Z1
      • GSK Investigational Site
• Thailand
  • Khon Kaen, Thailand, 40002
    • GSK Investigational Site
• United States
  • California
    • Paramount, California, United States, 90723
      • GSK Investigational Site
    • Sacramento, California, United States, 95816
      • GSK Investigational Site
  • Kansas
    • Newton, Kansas, United States, 67114
      • GSK Investigational Site
  • Kentucky
    • Bardstown, Kentucky, United States, 40004
      • GSK Investigational Site
  • Louisiana
    • Metairie, Louisiana, United States, 70006
      • GSK Investigational Site
  • Missouri
    • Saint Louis, Missouri, United States, 63141
      • GSK Investigational Site
  • Nebraska
    • Omaha, Nebraska, United States, 68134
      • GSK Investigational Site
  • Nevada
    • Henderson, Nevada, United States, 89014
      • GSK Investigational Site
  • Ohio
    • Cleveland, Ohio, United States, 44121
      • GSK Investigational Site
  • Texas
    • Fort Worth, Texas, United States, 76135
      • GSK Investigational Site
    • San Angelo, Texas, United States, 76904
      • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 months to 17 years (CHILD)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

7

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Influenza A (H5N1) adjuvanted 6-<36M Group; Subjects aged at enrolment between 3 and 36 months, 36 months excluded, received 2 doses of Influenza A (H5N1) Virus monovalent vaccine (GSK1557484A vaccine or GSK Biologicals' monovalent A/Indonesia/5/2005 (H5N1) vaccine adjuvanted) at Days 0 and 21. Influenza A (H5N1) Virus monovalent vaccine was administered intramuscularly. For children aged up to 12 months, 12 months excluded (< 12 months), Dose 1 was administered in the left anterolateral thigh and Dose 2 in the right anterolateral thigh. For children older than (>=) 12 months, Dose 1 was administered in the deltoid region of the non-dominant arm (or left arm if dominance was not yet identified) and Dose 2 in the deltoid region of the dominant arm (or right arm).	Biological: Influenza A (H5N1) Virus monovalent vaccine; All subjects will receive 2 doses administered as an intramuscular (IM) injection.
EXPERIMENTAL: Influenza A (H5N1) Virus monovalent vaccine 3-<9Y Group; Subjects aged at enrolment between 3 and 9 years, 9 years excluded, received 2 doses of Influenza A (H5N1) Virus monovalent vaccine (GSK1557484A vaccine or GSK Biologicals' monovalent A/Indonesia/5/2005 (H5N1) vaccine adjuvanted) at Days 0 and 21. Influenza A (H5N1) Virus monovalent vaccine was administered intramuscularly, Dose 1 in the deltoid region of the non-dominant arm (or left arm if dominance was not yet identified) and Dose 2 in the deltoid region of the dominant arm (or right arm).	Biological: Influenza A (H5N1) Virus monovalent vaccine; All subjects will receive 2 doses administered as an intramuscular (IM) injection.
EXPERIMENTAL: Influenza A (H5N1) Virus monovalent vaccine 9-<18Y Group; Subjects aged at enrolment between 9 and 18 years, 18 years excluded, received 2 doses of Influenza A (H5N1) Virus monovalent vaccine (GSK1557484A vaccine or GSK Biologicals' monovalent A/Indonesia/5/2005 (H5N1) vaccine adjuvanted) at Days 0 and 21. Influenza A (H5N1) Virus monovalent vaccine was administered intramuscularly, Dose 1 in the deltoid region of the non-dominant arm (or left arm if dominance was not yet identified) and Dose 2 in the deltoid region of the dominant arm (or right arm).	Biological: Influenza A (H5N1) Virus monovalent vaccine; All subjects will receive 2 doses administered as an intramuscular (IM) injection.
PLACEBO_COMPARATOR: Placebo 6-<36M Group; Subjects aged at enrolment between 3 and 36 months, 36 months excluded, received 2 doses of saline placebo at Days 0 and 21. The saline placebo was administered intramuscularly. For children aged up to 12 months, 12 months excluded (< 12 months), Dose 1 was administered in the left anterolateral thigh and Dose 2 in the right anterolateral thigh. For children older than (>=) 12 months, Dose 1 was administered in the deltoid region of the non-dominant arm (or left arm if dominance was not yet identified) and Dose 2 in the deltoid region of the dominant arm (or right arm).	Biological: Saline placebo; All subjects will receive 2 doses administered as an intramuscular (IM) injection.
PLACEBO_COMPARATOR: Placebo 3-<9Y Group; Subjects aged at enrolment between 3 and 9 years, 9 years excluded, received 2 doses of saline placebo at Days 0 and 21. The saline placebo was administered intramuscularly, Dose 1 in the deltoid region of the non-dominant arm (or left arm if dominance was not yet identified) and Dose 2 in the deltoid region of the dominant arm (or right arm).	Biological: Saline placebo; All subjects will receive 2 doses administered as an intramuscular (IM) injection.
PLACEBO_COMPARATOR: Placebo 9-<18Y Group; Subjects aged at enrolment between 9 and 18 years, 18 years excluded, received 2 doses of saline placebo at Days 0 and 21. The saline placebo was administered intramuscularly, Dose 1 in the deltoid region of the non-dominant arm (or left arm if dominance was not yet identified) and Dose 2 in the deltoid region of the dominant arm (or right arm).	Biological: Saline placebo; All subjects will receive 2 doses administered as an intramuscular (IM) injection.
EXPERIMENTAL: Placebo/Influenza A (H5N1) adjuvanted Group; Subjects in this group were those who were administered the saline placebo solution in the Blinded Phase of the study (either in the Placebo 6-<36M, Placebo 3-<9Y or Placebo 9-<18Y Group). These were subjects aged at enrolment between 6 months and 18 years, 18 years excluded, who had received 2 doses of saline placebo at Days 0 and 21 in the Blinded Phase of the study, as per described in the descriptions of the Placebo 6-<36M, Placebo 3-<9Y and Placebo 9-<18Y groups. After consenting to participating to the Unblinded Phase of the study, these subjects received in addition 2 doses of Influenza A (H5N1) Virus monovalent vaccine at Days 385 (Day U0) and Day 385 + 21 days (Day U21). Influenza A (H5N1) Virus monovalent vaccine was administered intramuscularly. Dose 1 of was administered in the deltoid region of the non-dominant arm and Dose 2 in the deltoid region of the dominant arm.	Biological: Influenza A (H5N1) Virus monovalent vaccine; All subjects will receive 2 doses administered as an intramuscular (IM) injection.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Subjects Seroprotected for Haemagglutination Inhibition (HI) Antibody Titers Against the H5N1 A/Indonesia Virus Strain.	A seroprotected subject against the a/Indonesia/5/2005 (A/INDO) virus strain was defined as a subject with H5N1 reciprocal haemagglutination inhibition (HI) antibody titers greater than or equal to (>=) the seroprotection cut-off of 1:40.	At Day 42.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Haemagglutination Inhibition (HI) Antibody Titers Against the H5N1 A/Indonesia Virus Strain.	HI antibody titers against the H5N1 A/Indonesia virus strain (A/INDO) were expressed as geometric mean titers (GMTs). The cut-off of the assay was the seropositivity cut-off of higher than or equal to (>=) 1:10.	At Days 0 and 21
Number of Subjects Seroprotected for Haemagglutination Inhibition (HI) Antibody Titers Against the H5N1 A/Indonesia Virus Strain.	A seroprotected subject against the a/Indonesia/5/2005 (A/INDO) virus strain was defined as a subject with H5N1 reciprocal haemagglutination inhibition (HI) antibody titers greater than or equal to (>=) the seroprotection cut-off of 1:40.	At Days 0 and 21
Number of Seroconverted Subjects for Haemagglutination Inhibition (HI) Antibodies Against the H5N1 A/Indonesia Virus Strain.	A subject seroconverted for HI antibodies against the H5N1 A/Indonesia virus strain (A/INDO) was defined as a vaccinee with either a pre-vaccination titer less than (<) 1:10 and a post-vaccination titer higher than or equal to (>=) 1:40, or with a pre-vaccination titer >= 1:10 and at least a 4-fold increase in post-vaccination titer. As the analyses were performed and disclosed stepwise - i.e. as soon as a study phase was completed - several releases of the CTRS (result summaries) were published. To generate an integrated Clinical Study Report, one set of domain datasets covering all analyses was used and the Adapted ATP cohort for immunogenicity has been defined. As a consequence, some of the data previously disclosed and based on ATP cohort for immunogenicity at Day 42, Day 182 and Day 385 have been replaced in this summary with data generated with the Adapted ATP cohort for immunogenicity.	At Days 21 and 42
Geometric Mean Increase (GMI) for Haemagglutination Inhibition (HI) Antibodies Against the H5N1 A/Indonesia Virus Strain.	GMI also known as the seroconversion factor (SCF) or geometric mean fold rise (GMFR) was defined as the geometric mean of the within-subject ratios of the post-vaccination reciprocal HI titre to the pre-vaccination reciprocal HI titre for the vaccine virus.	At Days 21 and 42
Haemagglutination Inhibition (HI) Antibody Titers Against the H5N1 A/Indonesia Virus Strain.	HI antibody titers against the H5N1 A/Indonesia virus strain (A/INDO) were expressed as geometric mean titers (GMTs). The cut-off of the assay was the seropositivity cut-off of higher than or equal to (>=) 1:10. Adapted ATP cohort for immunogenicity included all evaluable subjects for which Day 21 and Day 42 data were obtained from the ATP cohort for immunogenicity at Day 42; Day 182 data were obtained from the ATP cohort for immunogenicity at Day 182, and Day 385 data were obtained from the ATP cohort for immunogenicity at Day 385.	At Day 0 and Day 182.
Number of Subjects Seroprotected as Regards Haemagglutination Inhibition (HI) Antibody Titers Against the H5N1 A/Indonesia Virus Strain.	A seroprotected subject against the a/Indonesia/5/2005 (A/INDO) virus strain was defined as a subject with H5N1 reciprocal haemagglutination inhibition (HI) antibody titers greater than or equal to (>=) the seroprotection cut-off of 1:40. As the analyses were performed and disclosed stepwise - i.e. as soon as a study phase was completed - several releases of the CTRS (result summaries) were published. To generate an integrated Clinical Study Report, one set of domain datasets covering all analyses was used and the Adapted ATP cohort for immunogenicity has been defined. As a consequence, some of the data previously disclosed and based on ATP cohort for immunogenicity at Day 42, Day 182 and Day 385 have been replaced in this summary with data generated with the Adapted ATP cohort for immunogenicity.	At Day 0 and Day 182
Haemagglutination Inhibition (HI) Antibody Titers Against the H5N1 A/Indonesia Virus Strain	HI antibody titers against the H5N1 A/Indonesia virus strain (A/INDO) were expressed as geometric mean titers (GMTs). The cut-off of the assay was the seropositivity cut-off of higher than or equal to (>=) 1:10. As the analyses were performed and disclosed stepwise - i.e. as soon as a study phase was completed - several releases of the CTRS (result summaries) were published. To generate an integrated Clinical Study Report, one set of domain datasets covering all analyses was used and the Adapted ATP cohort for immunogenicity has been defined. As a consequence, some of the data previously disclosed and based on ATP cohort for immunogenicity at Day 42, Day 182 and Day 385 have been replaced in this summary with data generated with the Adapted ATP cohort for immunogenicity.	At Day 42.
Number of Seroconverted Subjects for Haemagglutination Inhibition (HI) Antibodies Against the H5N1 A/Indonesia Virus Strain.	A subject seroconverted for HI antibodies against the H5N1 A/Indonesia virus strain (A/INDO) was defined as a vaccinee with either a pre-vaccination titer less than (<) 1:10 and a post-vaccination titer higher than or equal to (>=) 1:40, or with a pre-vaccination titer >= 1:10 and at least a 4-fold increase in post-vaccination titer.	At Day 182
Geometric Mean Increase (GMI) for Haemagglutination Inhibition (HI) Antibodies Against the H5N1 A/Indonesia Virus Strain.	GMI also known as the seroconversion factor (SCF) or geometric mean fold rise (GMFR) was defined as the geometric mean of the within-subject ratios of the post-vaccination reciprocal HI titre to the pre-vaccination reciprocal HI titre for the vaccine virus.	At Day 182
Haemagglutination Inhibition (HI) Antibody Titers Against the H5N1 A/Indonesia Virus Strain.	HI antibody titers against the H5N1 A/Indonesia virus strain (A/INDO) were expressed as geometric mean titers (GMTs). The cut-off of the assay was the seropositivity cut-off of higher than or equal to (>=) 1:10. As the analyses were performed and disclosed stepwise - i.e. as soon as a study phase was completed - several releases of the CTRS (result summaries) were published. To generate an integrated Clinical Study Report, one set of domain datasets covering all analyses was used and the Adapted ATP cohort for immunogenicity has been defined. As a consequence, some of the data previously disclosed and based on ATP cohort for immunogenicity at Day 42, Day 182 and Day 385 have been replaced in this summary with data generated with the Adapted ATP cohort for immunogenicity.	At Day 0 and Day 385
Number of Subjects Seroprotected for Haemagglutination Inhibition (HI) Antibody Titers Against the H5N1 A/Indonesia Virus Strain.	A seroprotected subject against the a/Indonesia/5/2005 (A/INDO) virus strain was defined as a subject with H5N1 reciprocal haemagglutination inhibition (HI) antibody titers greater than or equal to (>=) the seroprotection cut-off of 1:40. As the analyses were performed and disclosed stepwise - i.e. as soon as a study phase was completed - several releases of the CTRS (result summaries) were published. To generate an integrated Clinical Study Report, one set of domain datasets covering all analyses was used and the Adapted ATP cohort for immunogenicity has been defined. As a consequence, some of the data previously disclosed and based on ATP cohort for immunogenicity at Day 42, Day 182 and Day 385 have been replaced in this summary with data generated with the Adapted ATP cohort for immunogenicity.	At Day 0 and Day 385
Number of Seroconverted Subjects for Haemagglutination Inhibition (HI) Antibodies Against the H5N1 A/Indonesia Virus Strain.	A subject seroconverted for HI antibodies against the H5N1 A/Indonesia virus strain (A/INDO) was defined as a vaccinee with either a pre-vaccination titer less than (<) 1:10 and a post-vaccination titer higher than or equal to (>=) 1:40, or with a pre-vaccination titer >= 1:10 and at least a 4-fold increase in post-vaccination titer.	At Day 385
Geometric Mean Increase (GMI) for Haemagglutination Inhibition (HI) Antibodies Against the H5N1 A/Indonesia Virus Strain.	GMI also known as the seroconversion factor (SCF) or geometric mean fold rise (GMFR) was defined as the geometric mean of the within-subject ratios of the post-vaccination reciprocal HI titer to the pre-vaccination reciprocal HI titer for the vaccine virus.	At Day 385.
Microneutralization (MN) Antibody Titers Against the H5N1 A/Indonesia and H5N1 A/Vietnam Virus Strains.	MN HI antibody titers against the H5N1 A/Indonesia (A/INDO) and H5N1 A/Vietnam (A/VIET) virus strains were expressed as geometric mean titers (GMTs). The cut-off of the assay was the seropositivity cut-off of higher than or equal to (>=) 1:28.	At Days 0, 42, 182 and 385
Number of Subjects Seropositive for Microneutralization (MN) Antibodies Against the H5N1 A/Indonesia Virus Strain.		At Days 0 and 42
Vaccine Response Rate (VRR) for Microneutralization (MN) Antibodies Against the H5N1 A/Indonesia and H5N1 A/Vietnam Virus Strains.	VRR for MN was defined as as the incidence rate of vaccinees with a 4-fold increase in post vaccination reciprocal titer relative to Day 0.	At Day 42
Number of Subjects Reporting Solicited Local Symptoms.	Solicited local symptoms assessed were pain, redness and swelling. "Any" was defined as any occurrence of the specified solicited local symptom reported, regardless of intensity. Grade 3 pain was defined as pain that prevented normal activity. Grade 3 redness and swelling were defined as redness/swelling above 100 millimeter (mm).	During the 7-day (Days 0-6) post-vaccination periods post Doses 1 and 2 of vaccine/placebo, across doses (Year 1)
Number of Subjects Reporting Solicited Local Symptoms.	Solicited local symptoms assessed were pain and swelling. "Any" was defined as any occurrence of the specified solicited local symptom reported, regardless of intensity. Grade 3 pain was defined as pain that prevented normal activity. Grade 3 redness and swelling were defined as redness/swelling above 100 millimeter (mm).	During the 7-day (Days U0-U6) post-vaccination periods post Doses 1 and 2 of vaccine/placebo, across doses (Year 2)
Number of Subjects of Less Than 6 Years of Age Reporting Solicited General Symptoms.	Solicited general symptoms assessed in subjects of less than 6 years of age were drowsiness, irritability/fussiness, loss of appetite and fever [axillary temperature (T) higher than or equal to (>=) 38.0 degrees Celsius (°C)]. "Any" was defined as any occurrence of the specified solicited general symptom reported, regardless of intensity or relationship to vaccination. Grade 3 was defined as a general symptom that prevented normal activity. Related was defined as a general symptom assessed by the investigator as causally related to the study vaccination. Any fever was defined as axillary temperature above 38.0 degrees Celsius (°C). Grade 3 fever was axillary temperature >= 39.0°C.	During the 7-day (Days 0-6) post-vaccination periods post Doses 1 and 2 of vaccine/placebo, across doses (Year 1)
Number of Subjects of Less Than 6 Years of Age Reporting Solicited General Symptoms.	Solicited general symptoms assessed in subjects of less than 6 years of age were drowsiness, irritability/fussiness, loss of appetite and fever [axillary temperature (T) higher than or equal to (>=) 38.0 degrees Celsius (°C)]. "Any" was defined as any occurrence of the specified solicited general symptom reported, regardless of intensity or relationship to vaccination. Grade 3 was defined as a general symptom that prevented normal activity. Related was defined as a general symptom assessed by the investigator as causally related to the study vaccination. Any fever was defined as axillary temperature above 38.0 degrees Celsius (°C). Grade 3 fever was axillary temperature >=39.0°C.	During the 7-day (Days U0-U6) post-vaccination periods post Doses 1 and 2 of vaccine/placebo, across doses (Year 2)
Number of Subjects at Least 6 Years of Age Reporting Solicited General Symptoms.	Solicited general symptoms assessed in subjects of at least 6 years of age were fatigue, gastrointestinal symptoms, headache, joint pain at other location, muscle aches, shivering, sweating and fever [axillary temperature (T) >= 38.0 degrees Celsius (°C)]. Gastrointestinal symptoms included nausea, vomiting, diaorrhea and/or abdominal pain. "Any" was defined as any occurrence of the specified solicited general symptom reported, regardless of intensity or relationship to vaccination. Grade 3 was defined as a general symptom that prevented normal activity. Related was defined as a general symptom assessed by the investigator as causally related to the study vaccination. Grade 3 fever was axillary temperature >= 39.0°C.	During the 7-day (Days 0-6) post-vaccination periods post Doses 1 and 2 of vaccine/placebo, across doses (Year 1)
Number of Subjects at Least 6 Years of Age Reporting Solicited General Symptoms.	Solicited general symptoms assessed in subjects of at least 6 years of age were fatigue, gastrointestinal symptoms, headache, joint pain at other location, muscle aches, shivering, sweating and fever [axillary temperature (T) >= 38.0 degrees Celsius (°C)]. Gastrointestinal symptoms included nausea, vomiting, diaorrhea and/or abdominal pain. "Any" was defined as any occurrence of the specified solicited general symptom reported, regardless of intensity or relationship to vaccination. Grade 3 was defined as a general symptom that prevented normal activity. Related was defined as a general symptom assessed by the investigator as causally related to the study vaccination. Grade 3 fever was axillary temperature >= 39.0°C.	During the 7-day (Days U0-U6) post-vaccination periods post Doses 1 and 2 of vaccine/placebo, across doses (Year 2)
Number of Subjects With Medically-attended Adverse Events (MAEs)	MAEs were defined as adverse events with medically-attended visits that were not routine visits for physical examination or vaccination. Any MAE was defined as atleast 1 MAE experienced.	From Day 0 up to Day 385
Number of Subjects With Medically-attended Adverse Events (MAEs)	MAEs were defined as adverse events with medically-attended visits that were not routine visits for physical examination or vaccination. Any MAE was defined as atleast 1 MAE experienced.	From Day U0 up to Day U385
Number of Subjects With Any Potential Immune-Mediated Diseases (pIMDs)	Potential immune-mediated diseases (pIMDs) were defined as a subset of adverse events that included both clearly autoimmune diseases and also other inflammatory and/or neurologic disorders which might or might not have an autoimmune aetiology. "Any pIMD" was defined as at least one pIMD experienced by the study subject.	From Day 0 up to Day 385
Number of Subjects With Any Potential Immune-Mediated Diseases (pIMDs)	Potential immune-mediated diseases (pIMDs) were defined as a subset of adverse events that included both clearly autoimmune diseases and also other inflammatory and/or neurologic disorders which might or might not have an autoimmune aetiology. "Any pIMD" was defined as at least one pIMD experienced by the study subject.	From Day U0 to Day U385
Number of Subjects Reporting Pregnancies, and Outcomes of These Reported Pregnancies		From Day 0 up to Day 385
Number of Subjects Reporting Pregnancies, and Outcomes of These Reported Pregnancies		From Day U0 to Day U385
Number of Subjects With Normal and Abnormal Biochemical Parameters Assessed With Respect to Alanine Aminotransferase (ALAT) and Aspartate Aminotransferase (ASAT)	Subjects were categorized according to their results at pre-vaccination (PRE), Day 42, Day 182 and Day 385 which were normal, above normal, below the normal ranges or unknown.	From Day 0 up to Day 385
Number of Subjects With Normal and Abnormal Biochemical Parameters Assessed With Respect to Total Bilirubin (T-BIL) and Bilirubin Conjugated/Direct (BIL-C/D)	Subjects were categorized according to their results at pre-vaccination (PRE), Day 42, Day 182 and Day 385 which were normal, above normal, below the normal ranges or unknown.	From Day 0 up to Day 385
Number of Subjects With Normal and Abnormal Biochemical Parameters Assessed With Respect to Creatinine (CREA) and Blood Urea Nitrogen (BUN)	Subjects were categorized according to their results at pre-vaccination (PRE), Day 42, Day 182 and Day 385 which were normal, above normal, below the normal ranges or unknown.	From Day 0 up to Day 385
Number of Subjects With Normal and Abnormal Haematological Parameters Assessed With Respect to Basophils (BAS) and Eosinophils (EOS)	Subjects were categorized according to their results at pre-vaccination (PRE), Day 42, Day 182 and Day 385 which were normal, above normal, below the normal ranges or unknown.	From Day 0 up to Day 385
Number of Subjects With Normal and Abnormal Haematological Parameters Assessed With Respect to Haematocrit (Hcr) and Haemoglobin (Hgb)	Subjects were categorized according to their results at pre-vaccination (PRE), Day 42, Day 182 and Day 385 which were normal, above normal, below the normal ranges or unknown.	From Day 0 up to Day 385
Number of Subjects With Normal and Abnormal Haematological Parameters Assessed With Respect to Neutrophils (NEU) and Platelets (PLA)	Subjects were categorized according to their results at pre-vaccination (PRE), Day 42, Day 182 and Day 385 which were normal, above normal, below the normal ranges or unknown.	From Day 0 up to Day 385
Number of Subjects With Normal and Abnormal Haematological Parameters Assessed With Respect to Lymphocytes (LYM) and Monocytes (MON)	Subjects were categorized according to their results at pre-vaccination (PRE), Day 42, Day 182 and Day 385 which were normal, above normal, below the normal ranges or unknown.	From Day 0 up to Day 385
Number of Subjects With Normal and Abnormal Haematological Parameters Assessed With Respect to Red and White Blood Cells (RBC and WBC)	Subjects were categorized according to their results at pre-vaccination (PRE), Day 42, Day 182 and Day 385 which were normal, above normal, below the normal ranges or unknown.	From Day 0 up to Day 385
Number of Subjects Reporting Any Unsolicited Adverse Events (AEs).	An unsolicited AE was defined as any AE (i.e. any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with use of a medicinal product, whether or not considered related to the medicinal product) 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.	During the 21-day (Days 0-20) post-vaccination period following Dose 1 of vaccine/placebo
Number of Subjects Reporting Any Unsolicited Adverse Events (AEs).	An unsolicited AE was defined as any AE (i.e. any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with use of a medicinal product, whether or not considered related to the medicinal product) 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.	During the 21-day (Days 21-41) post-vaccination period following Dose 2 of vaccine/placebo
Number of Subjects Reporting Any Unsolicited Adverse Events (AEs).	An unsolicited AE was defined as any AE (i.e. any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with use of a medicinal product, whether or not considered related to the medicinal product) 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.	During the 42-day (Days 0-41) post-vaccination period following Dose 1 of vaccine/placebo
Number of Subjects Reporting Serious Adverse Events (SAEs)	A SAE was defined as any untoward medical occurrence that: resulted in death, was life threatening, required hospitalization or prolongation of hospitalization, resulted in disability/incapacity or was a congenital anomaly/birth defect in the offspring of a study subject. Any was defined as occurrence of any symptom regardless of intensity grade or relation to vaccination and related was an event assessed by the investigator as causally related to the study vaccination.	From Day 0 up to Day 385
Number of Subjects Reporting Any Unsolicited Adverse Events (AEs).	An unsolicited AE was defined as any AE (i.e. any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with use of a medicinal product, whether or not considered related to the medicinal product) 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.	During the 21-day (Days U0-U20) post-vaccination period following Dose 1 of Influenza A (H5N1) Virus monovalent vaccine
Number of Subjects Reporting Any Unsolicited Adverse Events (AEs).	An unsolicited AE was defined as any AE (i.e. any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with use of a medicinal product, whether or not considered related to the medicinal product) 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.	During the 21-day (Days U21-U41) post-vaccination period following Dose 2 of Influenza A (H5N1) Virus monovalent vaccine
Number of Subjects Reporting Any Unsolicited Adverse Events (AEs).	An unsolicited AE was defined as any AE (i.e. any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with use of a medicinal product, whether or not considered related to the medicinal product) 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. As the study is still ongoing and data per age group are not available, results are presented for the groups pooled by vaccine/placebo administered. This outcome measure will be amended when data by age group become available.	During the 42-day (Days U0-U41) post-vaccination period following Dose 1 of Influenza A (H5N1) Virus monovalent vaccine
Number of Subjects Reporting Serious Adverse Events (SAEs)	A SAE was defined as any untoward medical occurrence that: resulted in death, was life threatening, required hospitalization or prolongation of hospitalization, resulted in disability/incapacity or was a congenital anomaly/birth defect in the offspring of a study subject. Any was defined as occurrence of any symptom regardless of intensity grade or relation to vaccination and related was an event assessed by the investigator as causally related to the study vaccination.	From Day U0 up to Day U385

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Publications and helpful links

General Publications

• 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.
• 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.

Helpful Links

• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

Study record dates

Study Major Dates

• Study Start (ACTUAL): March 7, 2011
• Primary Completion (ACTUAL): July 21, 2011
• Study Completion (ACTUAL): January 26, 2014

Study Registration Dates

• First Submitted: February 24, 2011
• First Submitted That Met QC Criteria: March 7, 2011
• First Posted (ESTIMATE): March 8, 2011

Study Record Updates

• Last Update Posted (ACTUAL): November 1, 2021
• Last Update Submitted That Met QC Criteria: October 19, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Keywords: Influenza; H5N1; Pandemic
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Orthomyxoviridae Infections; Influenza, Human; Influenza in Birds
• Other Study ID Numbers: 114464; 2012-001683-29 (EUDRACT_NUMBER)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.

Study Data/Documents

1. Dataset Specification
   Information identifier: 114464
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
2. Clinical Study Report
   Information identifier: 114464
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
3. Study Protocol
   Information identifier: 114464
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
4. Informed Consent Form
   Information identifier: 114464
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
5. Statistical Analysis Plan
   Information identifier: 114464
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
6. Individual Participant Data Set
   Information identifier: 114464
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register