Safety and Immunogenicity Study of GSK Biologicals' Pandemic Influenza Candidate Vaccine (H1N1) (GSK2340272A)

Safety and Immunogenicity Study of GSK Biologicals' Pandemic Influenza Candidate Vaccine (GSK2340272A) in Children Aged 3 to 17 Years

This trial is designed to assess the safety and immunogenicity of a prime-boost schedule of GSK Biologicals' investigational vaccine GSK2340272A in children aged between 3 and 17 years.

Study Overview

• Status: Completed
• Conditions: Influenza
• Intervention / Treatment: Biological: Pandemic influenza vaccine GSK2340272A

• Study Type: Interventional
• Enrollment (Actual): 210
• Phase: Phase 3

Contacts and Locations

Study Locations

• Spain
  • Bilbao, Spain, 48013
    • GSK Investigational Site
  • Burgos, Spain, 09005
    • GSK Investigational Site
  • Madrid, Spain, 28046
    • GSK Investigational Site
  • Móstoles/Madrid, Spain, 28935
    • GSK Investigational Site
  • Sevilla, Spain, 41013
    • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 years to 17 years (Child)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Subjects who the investigator believes that their parent(s)/Legally Acceptable Representative(s) (LAR) can and will comply with the requirements of the protocol.
• Children, male or female, aged between 3 and 17 years at the time of the first study vaccination.
• Written informed consent obtained from the subject parent(s) or LAR(s) of the subject. Assent obtained from the subject when applicable.
• Healthy children as established by medical history and clinical examination when entering into the study.
• Parent/LAR with access to a consistent means of telephone contact, land line or mobile, but NOT a pay phone or other multiple-user.

Exclusion Criteria:

• Use of any investigational or non-registered product other than the study vaccine within 30 days preceding the first dose of the study vaccine or planned use during the study period.
• Clinically or virologically confirmed influenza infection within six months preceding the study start.
• Planned administration of any vaccine 30 days prior and 30 days after any study vaccine administration.
• Chronic administration of immunosuppressants or other immune-modifying drugs within three months prior to enrolment in this study or planned administration during the study period.
• Acute disease and/or fever at the time of enrolment
• Any confirmed or suspected immunosuppressive or immunodeficient condition based on medical history and physical examination.
• Acute or chronic, clinically-significant pulmonary, cardiovascular, hepatic or renal functional abnormality, as determined by medical history and physical examination.
• Previous administration of any H1N1 A/California-like vaccine.
• Administration of immunoglobulins and/or any blood products within the three months prior to the enrolment in this study, or planned during the study.
• If the subject is female and if she is of childbearing potential, she must practice adequate contraception for 30 days prior to vaccination, have a negative pregnancy test and continue such precautions for two months after completion of the vaccination series.
• 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.
• Known use of an analgesic or antipyretic medication within 12 hours prior to first vaccination.
• Child in Care.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group A	Biological: Pandemic influenza vaccine GSK2340272A; Two primary intramuscular (IM) injections and a booster IM injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Subjects With Haemagglutination-inhibition (HI) Antibody Concentrations Above the Cut-off Value	The seropositivity cut-off value of the assay was equal to or above (≥) 1:10 in the sera of subjects seronegative before vaccination. The flu strain assessed was A/California/7/2009 (H1N1)v-like (Flu A/CAL/7/09).	At Day 0
Number of Subjects With HI Antibody Concentrations Above the Cut-off Value	The seropositivity cut-off value of the assay was ≥ 1:10 in the sera of subjects seronegative before vaccination. The flu strain assesssed was Flu A/CAL/7/09.	At Day 42
Titers for Serum HI Antibodies	Antibody titers were presented as geometric mean titers (GMTs). The reference seropositivity cut-off value was ≥ 1:10. The flu strain assessed was Flu A/CAL/7/09.	At Day 0
Titers for Serum HI Antibodies	Antibody titers were presented as geometric mean titers (GMTs). The reference seropositivity cut-off value was ≥ 1:10. The flu strain assessed was Flu A/CAL/7/09.	At Day 42
Number of Seroconverted (SCR) Subjects in Terms of HI Antibodies	A seroconverted subject was defined as: For initially seronegative subjects [antibody titer below (<) 1:10 prior to vaccination], antibody titer ≥ 1:40 after vaccination; For initially seropositive subjects (antibody titer ≥ 1:10 prior to vaccination), at least a 4-fold increase in post-vaccination titer. The flu strain assessed was Flu A/CAL/7/09.	At Day 42
Number of Seroprotected (SPR) Subjects in Terms of HI Antibodies	Seroprotection was defined as the percentage of subjects with a serum HI titer ≥ 1:40, that usually is accepted as indicating protection. The flu strain assessed was Flu A/CAL/7/09.	At Day 42
Seroconversion Factor (SCF) for HI Antibody Titers	Seroconversion factor was defined as the fold increase in serum HI GMTs post-vaccination compared to pre-vaccination. The flu strain assessed was Flu A/CAL/7/09.	At Day 42

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Subjects With Any and Grade 3 Solicited Local Symptoms	Assessed solicited local symptoms were pain, redness and swelling. Any = occurrence of the symptom regardless of intensity grade. Grade 3 pain = pain that prevented normal activity. Grade 3 redness/swelling = redness/swelling spreading beyond 50 millimeters (mm) of injection site.	During the 7-day (Days 0-6) post-vaccination period following each dose and across doses
Number of Subjects With HI Antibody Concentrations Above the Cut-off Value	The seropositivity cut-off value of the assay was ≥ 1:10 in the sera of subjects seronegative before vaccination. The flu strain assesssed was Flu A/CAL/7/09.	At Days 0, 21, 42 and at Month 12
Titers for Serum HI Antibodies	Antibody titers were presented as geometric mean titers (GMTs). The reference seropositivity cut-off value was ≥ 1:10. The flu strain assessed was Flu A/CAL/7/09.	At Days 0, 21, 42 and at Month 12
Number of Seroconverted (SCR) Subjects in Terms of HI Antibodies	A seroconverted subject was defined as: For initially seronegative subjects [antibody titer below (<) 1:10 prior to vaccination], antibody titer ≥ 1:40 after vaccination; For initially seropositive subjects (antibody titer ≥ 1:10 prior to vaccination), at least a 4-fold increase in post-vaccination antibody titer. The flu strain assessed was Flu A/CAL/7/09.	At Days 21, 42 and at Month 12
Number of Seroprotected Subjects in Terms of HI Antibodies	Seroprotection was defined as the percentage of subjects with a serum HI titer ≥ 1:40, that usually is accepted as indicating protection. The flu strain assessed was Flu A/CAL/7/09.	At Days 0, 21, 42 and at Month 12
Seroconversion Factor (SCF) for HI Antibody Titers	Seroconversion factor was defined as the fold increase in serum HI GMTs post-vaccination compared to pre-vaccination. The flu strain assessed was Flu A/CAL/7/09.	At Days 21, 42 and at Month 12
Number of Subjects With Neutralizing Antibody Concentrations Above the Cut-off Value	The seropositivity cut-off value of the assay was ≥ 1:8 in the sera of subjects seronegative before vaccination. The flu strain assesssed was Flu A/Neth/602/09.	At Days 0, 21 and 42
Titers for Serum Neutralizing Antibodies	Antibody titers were presented as geometric mean titers (GMTs). The reference seropositivity cut-off value was ≥ 1:8. The flu strain assessed was A/Netherlands/602/2009 (H1N1)v-like (Flu A/Neth/602/09).	At Days 0, 21 and 42
Number of Subjects With Neutralizing Antibody Concentrations Above the Cut-off Value	The seropositivity cut-off value of the assay was ≥ 1:8 in the sera of subjects seronegative before vaccination. The flu strain assesssed was Flu A/Neth/602/09.	At Month 12
Titers for Serum Neutralizing Antibodies	Antibody titers were presented as geometric mean titers (GMTs). The reference seropositivity cut-off value was ≥ 1:8. The flu strain assessed was Flu A/Neth/602/09.	At Month 12
Number of Seroconverted (SCR) Subjects in Terms of H1N1 Neutralizing Antibodies	A seroconverted subject was defined as: For initially seronegative subjects, antibody titer ≥ 1:32 after vaccination; For initially seropositive subjects, at least a 4-fold increase in post-vaccination titer. The flu strain assessed was Flu A/Neth/602/09.	At Days 21 and 42
Number of Seroconverted (SCR) Subjects in Terms of H1N1 Neutralizing Antibodies	A seroconverted subject was defined as: For initially seronegative subjects, antibody titer ≥ 1:32 after vaccination; For initially seropositive subjects, at least a 4-fold increase in post-vaccination titer. The flu strain assessed was Flu A/Neth/602/09.	At Month 12
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms	Assessed solicited general symptoms were diarrhea, drowsiness, irritability, loss of appetite, shivering, sweating and fever [defined as axillary temperature equal to or above (≥) 37.5 degrees Celsius (°C)]. Any = occurrence of the symptom regardless of intensity grade. Grade 3 symptom = symptom that prevented normal activity. Grade 3 fever = fever > 39.0 °C. Related = symptom assessed by the investigator as related to the vaccination.	During the 7-day (Days 0-6) post-vaccination period following each dose and across doses
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms	Assessed solicited general symptoms were arthralgia, fatigue, gastrointestinal, headache, myalgia, shivering and fever [defined as axillary temperature equal to or above (≥) 37.5 degrees Celsius (°C)]. Any = occurrence of the symptom regardless of intensity grade. Grade 3 symptom = symptom that prevented normal activity. Grade 3 fever = fever > 39.0 °C. Related = symptom assessed by the investigator as related to the vaccination.	During the 7-day (Days 0-6) post-vaccination period following each dose and across doses
Number of Subjects With 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. Any MAE(s) = Occurrence of any MAE(s) regardless of intensity grade or relation to vaccination.	During the entire study period (from Day 0 up to Month 12)
Number of Subjects With Any Adverse Events of Specific Interest (AESIs), Including Potential Immune-mediated Disease (pIMDs)	An AESI was defined as an AE including autoimmune diseases and other mediated inflammatory disorders and assessed by the investigator as specific to the treatment administration.	During the entire study period (from Day 0 up to Month 12)
Number of Subjects With Normal or Abnormal Biochemical Levels	Among biochemical parameters assessed were alanine aminotransferase [ALAT], aspartate aminotransferase [ASAT], bilirubin [BILI], creatinine [CREA] and blood urea nitrogen [BUN]. Levels of biochemical parameters assessed in terms of normal laboratory values were - unknown, below, within and above.	At Days 0, 21 and 42
Number of Subjects With Any, Grade 3 and Related Unsolicited Adverse Events (AEs)	An unsolicited AE covers any untoward medical occurrence in a clinical investigation subject temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product and 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 the occurrence of any unsolicited AE regardless of intensity grade or relation to vaccination. Grade 3 AE = an AE which prevented normal, everyday activities. Related = AE assessed by the investigator as related to the vaccination.	During the 21-day (Days 0-20) follow-up period after the first vaccination
Number of Subjects With Any, Grade 3 and Related Unsolicited Adverse Events (AEs)	An unsolicited AE covers any untoward medical occurrence in a clinical investigation subject temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product and 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 the occurrence of any unsolicited AE regardless of intensity grade or relation to vaccination. Grade 3 AE = an AE which prevented normal, everyday activities. Related = AE assessed by the investigator as related to the vaccination.	During the 83-day (Days 0-82) follow-up period after the first vaccination and the 62-day (Days 0-61) follow-up period after the second vaccination
Number of Subjects With Serious Adverse Events (SAEs)	Serious adverse events (SAEs) assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity.	During the entire study period (from Day 0 up to Month 12)

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Publications and helpful links

General Publications

• Garcia-Sicilia J, Aristegui J, Omenaca F, Carmona A, Tejedor JC, Merino JM, Garcia-Corbeira P, Walravens K, Bambure V, Moris P, Caplanusi A, Gillard P, Dieussaert I. Safety and persistence of the humoral and cellular immune responses induced by 2 doses of an AS03-adjuvanted A(H1N1)pdm09 pandemic influenza vaccine administered to infants, children and adolescents: Two open, uncontrolled studies. Hum Vaccin Immunother. 2015;11(10):2359-69. doi: 10.1080/21645515.2015.1063754.
• Garcia-Sicilia J, Gillard P, Carmona A, Tejedor JC, Aristegui J, Merino JM, Behre U, Caplanusi A, Vaman T, Dieussaert I. Immunogenicity and safety of AS03-adjuvanted H1N1 pandemic vaccines in children and adolescents. Vaccine. 2011 Jun 10;29(26):4353-61. doi: 10.1016/j.vaccine.2011.04.011. Epub 2011 Apr 17.

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: September 10, 2009
• Primary Completion (Actual): November 27, 2010
• Study Completion (Actual): November 27, 2010

Study Registration Dates

• First Submitted: August 20, 2009
• First Submitted That Met QC Criteria: August 20, 2009
• First Posted (Estimate): August 24, 2009

Study Record Updates

• Last Update Posted (Actual): February 19, 2018
• Last Update Submitted That Met QC Criteria: July 31, 2017
• Last Verified: October 1, 2016

More Information

Terms related to this study

• Keywords: influenza infection; GSK Bio's influenza vaccine GSK2340272A
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Orthomyxoviridae Infections; Influenza, Human
• Other Study ID Numbers: 113528

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. Statistical Analysis Plan
   Information identifier: 113528
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
2. Annotated Case Report Form
   Information identifier: 113528
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
3. Informed Consent Form
   Information identifier: 113528
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
4. Clinical Study Report
   Information identifier: 113528
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
5. Individual Participant Data Set
   Information identifier: 113528
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
6. Study Protocol
   Information identifier: 113528
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
7. Dataset Specification
   Information identifier: 113528
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register