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

Safety and Immunogenicity Study of GSK Biologicals' Pandemic Influenza (H1N1) Candidate Vaccine (GSK2340274A) in Children Aged 10 to Less Than 18 Years

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.

Study Overview

• Status: Completed
• Conditions: Influenza
• Intervention / Treatment: Biological: GSK Biologicals' Influenza investigational vaccine GSK2340274A; Biological: Placebo (saline); Biological: GSK Biologicals' Influenza investigational vaccine GSK2340273A

• Study Type: Interventional
• Enrollment (Actual): 310
• Phase: Phase 2

Contacts and Locations

Study Locations

• Estonia
  • Tartu, Estonia, 50106
    • GSK Investigational Site
• Slovakia
  • 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
    • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 10 years to 17 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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: Placebo (saline); One dose intramuscularly; Biological: GSK Biologicals' Influenza investigational vaccine GSK2340273A; Two doses intramuscularly

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Subjects Seroconverted for HI Antibodies Against Flu A/CAL/7/09 H1N1 Strain	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	At Day 21
Number of Subjects Seroprotected for HI Antibodies Against Flu A/CAL/7/09 H1N1 Strain	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.	At Day 0 and Day 21
HI Antibody Seroconversion Factors Against Flu A/CAL/7/09 H1N1 Strain	Seroconversion factors were defined as the fold increase in serum HI GMTs post-vaccination compared to Day 0.	At Day 21

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
HI Antibody Titres Against Flu A/CAL/7/09 H1N1 Strain	Antibody titres were expressed as Geometric mean titers (GMTs).	At Day 0 and Day 42
HI Antibody Titres Against Flu A/CAL/7/09 H1N1 Strain	Antibody titres were expressed as GMTs.	At Day 0 and Day 182
HI Antibody Titres Against Flu A/CAL/7/09 H1N1 Strain	Antibody titres were expressed as Geometric mean titers (GMTs).	At Days 0, 182 and 189
Number of Subjects Seroconverted for HI Antibodies Against Flu A/CAL/7/09 H1N1 Strain	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.	At Day 42
HI Antibody Titres Against Flu A/CAL/7/09 H1N1 Strain	Antibody titers were expressed as GMTs.	At Day 0 and Day 21
Number of Subjects Seroconverted for HI Antibodies Against Flu A/CAL/7/09 H1N1 Strain	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.	At Day 182
Number of Subjects Seroconverted for HI Antibodies Against Flu A/CAL/7/09 H1N1 Strain	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.	At Day 189
Number of Subjects Seroconverted for HI Antibodies Against Flu A/CAL/7/09 H1N1 Strain	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.	At Day 189
The Number of Subjects Seroprotected for HI Antibodies Against Flu A/CAL/7/09 H1N1	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.	At Day 0 and Day 42
Number of Subjects Seroprotected to HI Antibodies Against Flu A/CAL/7/09 H1N1	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.	At Day 0 and Day 182
Number of Subjects Seroprotected to HI Antibodies Against Flu A/CAL/7/09 H1N1	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.	At Day 0, Day 182 and Day 189
Geometric Mean Fold Rise (GMFR) for HI Antibodies Against Flu A/CAL/7/09 H1N1	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.	At Day 42
GMFR for HI Antibodies Against Flu A/CAL/7/09 H1N1	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.	At Day 182
GMFR for HI Antibodies Against Flu A/CAL/7/09 H1N1 Using Day 0 as Reference Activity	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.	At Day 189
GMFR for HI Antibodies Against Flu A/CAL/7/09 H1N1 Using Day 182 as Reference Activity	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.	At Day 189
Number of Subjects Reporting Any and Grade 3 Solicited Local Adverse Events (AEs)	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.	During the 7-day (Days 0-6) post-vaccination period following each dose
Number of Subjects Reporting Any and Grade 3 Solicited Local AEs	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	During the 7-day (Days 0-6) post-vaccination period following booster dose
Number of Subjects Reporting Any, Grade 3 and Related Solicited General AEs	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.	During the 7-day (Days 0-6) post-vaccination period following each dose
Number of Subjects Reporting Any, Grade 3 and Related Solicited General AEs	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.	During the 7-day (Days 0-6) post-vaccination period following booster dose
Number of Subjects Reporting Any Medically Attended Events (MAEs)	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.	During the entire study period (Days 0-364) following the first vaccination
Number of Subjects Reporting Potential Immune-Mediated Diseases (pIMDs)	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.	During the entire study period (Days 0-364) following first vaccination
Number of Subjects With Normal and Abnormal Hematological and Biochemical Parameters Assessed With Respect to Normal Laboratory Ranges	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).	At Days 0, 21, 42, 182 and 189
Number of Subjects Reporting Any Unsolicited AEs	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.	During the 42-day (Days 0-41) follow up period after first vaccination.
Number of Subjects Reporting Any Unsolicited AEs	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.	During the 21-day (Days 0-20) follow-up period after booster vaccination.
Number of Subjects Reporting Serious Adverse Events (SAEs)	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.	During the entire study period (Day 0 to Day 364)

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Publications and helpful links

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: February 1, 2010
• Primary Completion (Actual): September 27, 2010
• Study Completion (Actual): May 10, 2011

Study Registration Dates

• First Submitted: December 17, 2009
• First Submitted That Met QC Criteria: December 17, 2009
• First Posted (Estimate): December 21, 2009

Study Record Updates

• Last Update Posted (Actual): August 17, 2018
• Last Update Submitted That Met QC Criteria: July 4, 2018
• Last Verified: November 1, 2016

More Information

Terms related to this study

• Keywords: children; Clinical trial; H1N1; pandemic influenza
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Orthomyxoviridae Infections; Influenza, Human; Physiological Effects of Drugs; Immunologic Factors; Vaccines
• Other Study ID Numbers: 113883

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. Clinical Study Report
   Information identifier: 113883
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
2. Statistical Analysis Plan
   Information identifier: 113883
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
3. Dataset Specification
   Information identifier: 113883
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
4. Informed Consent Form
   Information identifier: 113883
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
5. Study Protocol
   Information identifier: 113883
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
6. Individual Participant Data Set
   Information identifier: 113883
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register