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Study of GSK Biologicals' Pandemic Influenza (H1N1) Candidate Vaccine in Children Aged 10 to Less Than 18 Years

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT01035749
First received: December 17, 2009
Last updated: November 28, 2016
Last verified: November 2016
  Purpose
The purpose of this study is to show that vaccination with a single dose of GSK Biologicals' pandemic H1N1 vaccine results in an immune response that meets or exceeds European Medicines Agency (EMEA) Committee for Medicinal Products for Human Use (CHMP) guidance criteria for a pandemic influenza vaccine.

Condition Intervention Phase
Influenza
Biological: GSK Biologicals' Influenza investigational vaccine GSK2340274A
Biological: GSK Biologicals' Influenza investigational vaccine GSK2340273A
Biological: Placebo (saline)
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Safety and Immunogenicity Study of GSK Biologicals' Pandemic Influenza (H1N1) Candidate Vaccine (GSK2340274A) in Children Aged 10 to Less Than 18 Years

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Number of Subjects Seroconverted for HI Antibodies Against Flu A/CAL/7/09 H1N1 Strain [ Time Frame: At Day 21 ]
    Seroconversion defined as: - For initially seronegative subjects, antibody titre ≥ 1:40 after vaccination - For initially seropositive subjects, antibody titre after vaccination ≥ 4 fold the pre-vaccination antibody titre

  • Number of Subjects Seroprotected for HI Antibodies Against Flu A/CAL/7/09 H1N1 Strain [ Time Frame: At Day 0 and Day 21 ]
    A seroprotected subject was defined as a subject with a serum HI titer greater than or equal to 1:40 that usually is accepted as indicating protection.

  • HI Antibody Seroconversion Factors Against Flu A/CAL/7/09 H1N1 Strain [ Time Frame: At Day 21 ]
    Seroconversion factors were defined as the fold increase in serum HI GMTs post-vaccination compared to Day 0.


Secondary Outcome Measures:
  • HI Antibody Titres Against Flu A/CAL/7/09 H1N1 Strain [ Time Frame: At Day 0 and Day 42 ]
    Antibody titres were expressed as Geometric mean titers (GMTs).

  • HI Antibody Titres Against Flu A/CAL/7/09 H1N1 Strain [ Time Frame: At Day 0 and Day 182 ]
    Antibody titres were expressed as GMTs.

  • HI Antibody Titres Against Flu A/CAL/7/09 H1N1 Strain [ Time Frame: At Days 0, 182 and 189 ]
    Antibody titres were expressed as Geometric mean titers (GMTs).

  • Number of Subjects Seroconverted for HI Antibodies Against Flu A/CAL/7/09 H1N1 Strain [ Time Frame: At Day 42 ]
    A seroconverted subject was defined as a subject who had either a pre-vaccination titre below 1:10 and a post-vaccination titre greater than or equal to 1:40 or a pre-vaccination titre greater than or equal to 1:10 and at least a 4-fold increase in post-vaccination titre.

  • HI Antibody Titres Against Flu A/CAL/7/09 H1N1 Strain [ Time Frame: At Day 0 and Day 21 ]
    Antibody titers were expressed as GMTs.

  • Number of Subjects Seroconverted for HI Antibodies Against Flu A/CAL/7/09 H1N1 Strain [ Time Frame: At Day 182 ]
    A seroconverted subject was defined as a subject who had either a pre-vaccination titre below 1:10 and a post-vaccination titre greater than or equal to 1:40 or a pre-vaccination titre greater than or equal to 1:10 and at least a 4-fold increase in post-vaccination titre.

  • Number of Subjects Seroconverted for HI Antibodies Against Flu A/CAL/7/09 H1N1 Strain [ Time Frame: At Day 189 ]
    A seroconverted subject was defined as a subject who had either a pre-vaccination titre below 1:10 and a post-vaccination titre greater than or equal to 1:40 or a pre-vaccination titre greater than or equal to 1:10 and at least a 4-fold increase in post-vaccination titre. Day 0 was used as reference activity.

  • Number of Subjects Seroconverted for HI Antibodies Against Flu A/CAL/7/09 H1N1 Strain [ Time Frame: At Day 189 ]
    A seroconverted subject was defined as a subject who had either a pre-vaccination titer below 1:10 and a post-vaccination titer greater than or equal to 1:40 or a pre-vaccination titer greater than or equal to 1:10 and at least a 4-fold increase in post-vaccination titer. Day 182 was used as reference activity.

  • The Number of Subjects Seroprotected for HI Antibodies Against Flu A/CAL/7/09 H1N1 [ Time Frame: At Day 0 and Day 42 ]
    A seroprotected subject was defined as a subject with a serum HI titre greater than or equal to 1:40 that usually is accepted as indicating protection.

  • Number of Subjects Seroprotected to HI Antibodies Against Flu A/CAL/7/09 H1N1 [ Time Frame: At Day 0 and Day 182 ]
    A seroprotected subject was defined as a subject with a serum HI titre greater than or equal to 1:40 that usually is accepted as indicating protection.

  • Number of Subjects Seroprotected to HI Antibodies Against Flu A/CAL/7/09 H1N1 [ Time Frame: At Day 0, Day 182 and Day 189 ]
    A seroprotected subject was defined as a subject with a serum HI titer greater than or equal to 1:40 that usually is accepted as indicating protection.

  • Geometric Mean Fold Rise (GMFR) for HI Antibodies Against Flu A/CAL/7/09 H1N1 [ Time Frame: At Day 42 ]
    GMFR (also known as the seroconversion factor, SCF) 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.

  • GMFR for HI Antibodies Against Flu A/CAL/7/09 H1N1 [ Time Frame: At Day 182 ]
    GMFR (also known as the seroconversion factor, SCF) 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.

  • GMFR for HI Antibodies Against Flu A/CAL/7/09 H1N1 Using Day 0 as Reference Activity [ Time Frame: At Day 189 ]
    GMFR (also known as the seroconversion factor, SCF) 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.

  • GMFR for HI Antibodies Against Flu A/CAL/7/09 H1N1 Using Day 182 as Reference Activity [ Time Frame: At Day 189 ]
    GMFR (also known as the seroconversion factor, SCF) 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.

  • Number of Subjects Reporting Any and Grade 3 Solicited Local Adverse Events (AEs) [ Time Frame: During the 7-day (Days 0-6) post-vaccination period following each dose ]
    Any was defined as occurrence of any local symptom regardless of their intensity grade.Grade 3 redness and swelling was > 100 millimeter (mm) and grade 3 pain was defined as pain that prevented normal activity.

  • Number of Subjects Reporting Any and Grade 3 Solicited Local AEs [ Time Frame: During the 7-day (Days 0-6) post-vaccination period following booster dose ]
    Any was defined as occurrence of any local symptom regardless of their intensity grade.Grade 3 redness and swelling was > 100 millimeter (mm) and grade 3 pain was defined as pain that prevented normal activity

  • Number of Subjects Reporting Any, Grade 3 and Related Solicited General AEs [ Time Frame: During the 7-day (Days 0-6) post-vaccination period following each dose ]
    Solicited general symptoms assessed were arthralgia, fatigue, gastrointestinal, headache, myalgia, shivering, sweating and fever (Fever = axillary temperature equal to or above 38.0 degrees Celsius (°C)). Any = any solicited general symptom reported irrespective of intensity and relationship to vaccination. Related = symptoms considered by the investigator to have a causal relationship to vaccination. Grade 3 symptoms = symptoms that prevented normal activity. Grade 3 fever = axillary temperature equal to or above (≥) 39.0°C.

  • Number of Subjects Reporting Any, Grade 3 and Related Solicited General AEs [ Time Frame: During the 7-day (Days 0-6) post-vaccination period following booster dose ]
    Solicited general symptoms assessed were arthralgia, fatigue, gastrointestinal, headache, myalgia, shivering, sweating and fever (Fever = axillary temperature equal to or above 38.0 degrees Celsius (°C)). Any = any solicited general symptom reported irrespective of intensity and relationship to vaccination. Related = symptoms considered by the investigator to have a causal relationship to vaccination. Grade 3 symptoms = symptoms that prevented normal activity. Grade 3 fever = axillary temperature equal to or above (≥) 39.0°C.

  • Number of Subjects Reporting Any Medically Attended Events (MAEs) [ Time Frame: During the entire study period (Days 0-364) following the first vaccination ]
    MAEs were defined as events for which the subject received medical attention defined as hospitalization, an emergency room visit or a visit to or from medical personnel (medical doctor) for any reason.

  • Number of Subjects Reporting Potential Immune-Mediated Diseases (pIMDs) [ Time Frame: During the entire study period (Days 0-364) following first vaccination ]
    pIMDs were defined as a subset of AEs that included both clearly autoimmune diseases and also other inflammatory and/or neurologic disorders which may or may not have an autoimmune etiology.

  • Number of Subjects With Normal and Abnormal Hematological and Biochemical Parameters Assessed With Respect to Normal Laboratory Ranges [ Time Frame: At Days 0, 21, 42, 182 and 189 ]
    Subjects were categorized according to their results at pre-vaccination (PRE), Day 21, Day 42, Day 182 and Day 189 which were within normal, above normal, below the normal ranges or unknown. The laboratory parameters assessed were Alanine aminotransferase (ALAT), Aspartate aminotransferase (ASAT), Total Bilirubin, Creatinine, Hematocrit, Hemoglobin, Platelets, Blood urea nitrogen (BUN) and White blood cells (WBCs).

  • Number of Subjects Reporting Any Unsolicited AEs [ Time Frame: During the 42-day (Days 0-41) follow up period after first vaccination. ]
    Unsolicited AE covers any AE 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 any symptom regardless of intensity or relationship to vaccination.

  • Number of Subjects Reporting Any Unsolicited AEs [ Time Frame: During the 21-day (Days 0-20) follow-up period after booster vaccination. ]
    Unsolicited AE covers any AE 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 any symptom regardless of intensity or relationship to vaccination.

  • Number of Subjects Reporting Serious Adverse Events (SAEs) [ Time Frame: During the entire study period (Day 0 to Day 364) ]
    SAEs: medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization, result in disability/incapacity or are a congenital anomaly/birth defect in the offspring of a study subject.


Enrollment: 310
Study Start Date: February 2010
Study Completion Date: May 2011
Primary Completion Date: September 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: AREPANRIX-ADJUVANTED F1 2D GROUP
Subjects received 2 doses of Arepanrix ™ formulation 1 adjuvanted vaccine on Day 0 and Day 182 (booster) and one dose of saline placebo on Day 21.
Biological: GSK Biologicals' Influenza investigational vaccine GSK2340274A
One or two doses administered intramuscularly
Biological: Placebo (saline)
One dose intramuscularly
Experimental: AREPANRIX-ADJUVANTED F2 2D GROUP
Subjects received 2 doses of Arepanrix ™ formulation 2 adjuvanted vaccine on Day 0 and Day 182 (booster) and one dose of saline placebo on Day 21.
Biological: GSK Biologicals' Influenza investigational vaccine GSK2340274A
One or two doses administered intramuscularly
Biological: Placebo (saline)
One dose intramuscularly
Experimental: AREPANRIX-ADJUVANTED F2 3D GROUP
Subjects received 3 doses of Arepanrix ™ formulation 2 adjuvanted vaccine on Day 0, Day 21 and Day 182 (booster).
Biological: GSK Biologicals' Influenza investigational vaccine GSK2340274A
One or two doses administered intramuscularly
Experimental: AREPANRIX-UNADJUVANTED F2 2D GROUP
Subjects received 2 doses of Arepanrix ™ unadjuvanted vaccine on Day 0 and Day 182 (booster) and one dose of saline placebo on Day 21.
Biological: GSK Biologicals' Influenza investigational vaccine GSK2340273A
Two doses intramuscularly
Biological: Placebo (saline)
One dose intramuscularly

  Eligibility

Ages Eligible for Study:   10 Years to 17 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Male or female children 10 to < 18 years of age at the time of the first vaccination. "Less than 18 years of age" implies inclusion of adolescents who have not reached their 18th birthday as of Day 0, the day of the first vaccine dose under this protocol.
  • 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.
  • 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 they and/or their parent(s)/LAR can and will comply with the requirements of the protocol.

Exclusion Criteria:

  • Medical history of physician-confirmed infection with an A/California/7/2009 (H1N1)v-like virus.
  • Previous vaccination at any time with an A/California/7/2009 (H1N1)v-like virus vaccine.
  • 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 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 vaccine within 30 days before the first dose of study vaccine, with the exception of seasonal influenza vaccine (which may be given within 2 weeks before the first dose of study vaccine).
  • Planned administration of any A/California H1N1v-like vaccine other than the study vaccine between Day 0 and the Day 189 phlebotomy.
  • Planned administration of any other vaccine not foreseen by the study protocol between Day 0 and Day 42 after the first vaccine dose, 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 consumption of eggs; or a history of severe adverse reaction to a previous influenza vaccine.
  • Child in care.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01035749

Locations
Estonia
GSK Investigational Site
Tartu, Estonia, 50106
Slovakia
GSK Investigational Site
Cifer, Slovakia, 919 43
GSK Investigational Site
Dolny Kubin, Slovakia, 026 01
GSK Investigational Site
Dunajska Streda, Slovakia, 929 01
GSK Investigational Site
Nova Dubnica, Slovakia, 018 51
GSK Investigational Site
Nove Mesto nad Vahom, Slovakia, 915 01
GSK Investigational Site
Puchov, Slovakia, 020 01
GSK Investigational Site
Ruzomberok, Slovakia, 034 01
GSK Investigational Site
Trencin, Slovakia, 911 01
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

Additional Information:
Study Data/Documents: Clinical Study Report  This link exits the ClinicalTrials.gov site
Identifier: 113883
For additional information about this study please refer to the GSK Clinical Study Register
Statistical Analysis Plan  This link exits the ClinicalTrials.gov site
Identifier: 113883
For additional information about this study please refer to the GSK Clinical Study Register
Dataset Specification  This link exits the ClinicalTrials.gov site
Identifier: 113883
For additional information about this study please refer to the GSK Clinical Study Register
Informed Consent Form  This link exits the ClinicalTrials.gov site
Identifier: 113883
For additional information about this study please refer to the GSK Clinical Study Register
Study Protocol  This link exits the ClinicalTrials.gov site
Identifier: 113883
For additional information about this study please refer to the GSK Clinical Study Register
Individual Participant Data Set  This link exits the ClinicalTrials.gov site
Identifier: 113883
For additional information about this study please refer to the GSK Clinical Study Register

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT01035749     History of Changes
Other Study ID Numbers: 113883
Study First Received: December 17, 2009
Results First Received: November 28, 2016
Last Updated: November 28, 2016
Individual Participant Data  
Plan to Share IPD: Yes
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.

Keywords provided by GlaxoSmithKline:
pandemic influenza
Clinical trial
H1N1
children

Additional relevant MeSH terms:
Influenza, Human
Orthomyxoviridae Infections
RNA Virus Infections
Virus Diseases
Respiratory Tract Infections
Respiratory Tract Diseases
Vaccines
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on April 21, 2017