Study to Evaluate the Immunogenicity and Safety of an Investigational Influenza Vaccine (H1N1) in Children

• ClinicalTrials.gov Identifier: NCT00972517
• Recruitment Status: Completed
• First Posted: September 7, 2009
• Results First Posted: September 10, 2018
• Last Update Posted: June 26, 2019
• Sponsor: GlaxoSmithKline
• Information provided by (Responsible Party): GlaxoSmithKline

Study Description

Brief Summary:

The objective of this study is to evaluate the immunogenicity and safety of GSK Biologicals' investigational vaccine GSK2340272A in children aged between 3 and 17 years.

Condition or disease	Intervention/treatment	Phase
Influenza	Biological: GSK investigational vaccine GSK2340272A	Phase 3

Detailed Description:

This Protocol Posting has been updated following Protocol amendment 1, October 2009. The impacted section are the study design section, the outcomes measures section and the intervention section.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 245 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: Safety and Immunogenicity Study of GSK Biologicals' Pandemic Influenza Candidate Vaccine (GSK2340272A) in Children Aged 3 to 17 Years
• Actual Study Start Date: September 29, 2009
• Actual Primary Completion Date: November 22, 2010
• Actual Study Completion Date: November 22, 2010

Arms and Interventions

Arm	Intervention/treatment
Experimental: Group A; Subjects receiving alternative dose of GSK23440272A vaccine	Biological: GSK investigational vaccine GSK2340272A; Three intramuscular injections

Outcome Measures

Primary Outcome Measures :

1. Humoral Immune Response in Terms of Haemagglutination Inhibition (HI) Antibody Titers Against the Flu A/California/7/2009 (H1N1) Vaccine Strain [ Time Frame: At Day 0, Day 21 and Day 42 ]
   Antibody titers were expressed as Geometric mean titers (GMTs).
2. Number of Seroconverted Subjects for HI Antibodies Against the Flu A/California/7/2009 (H1N1) Virus Strain [ Time Frame: At Day 42 ]
   A seroconverted subject was defined as a vaccinated subject with either a pre-vaccination titre less than (<) 1:10 and a post-vaccination titre greater than or equal to (≥) 1:40 or a pre-vaccination titre ≥ 1:10 and at least a 4-fold increase in post-vaccination titre. The Committee for Medicinal Products for Human Use (CHMP) criterion was fulfilled if the point estimate for SCR was greater than (>) 40% in children aged 3 to 17 years.
3. Number of Subjects Who Were Seroprotected for HI Antibodies Against the Flu A/California/7/2009 (H1N1) Virus Strain [ Time Frame: At Day 42 ]
   A seroprotected subject was defined as a vaccinated subject with a serum HI titre greater than or equal to (≥) 1:40, that usually is accepted as indicating protection. The Committee for Medicinal Products for Human Use (CHMP) criterion was fulfilled if the post-vaccination time point estimate for SPR the point estimate for SPR was greater than (>) 70% in children aged 3 to 17 years.
4. HI Antibody Geometric Mean Fold Rise (GMFR) Against the Flu A/California/7/2009 (H1N1) Virus Strain [ Time Frame: At Day 42 ]
   GMFR, also called seroconversion factor (SCF), was defined as the fold increase in serum HI GMTs post-vaccination compared to pre-vaccination. The CHMP criterion was fulfilled if the point estimate for GMFR was greater than (>) 2.5 in children aged 3 to 17 years

Secondary Outcome Measures :

1. Humoral Immune Response in Terms of Haemagglutination Inhibition (HI) Antibody Titers Against the Flu A/California/7/2009 (H1N1) Vaccine Strain [ Time Frame: At Month 6 ]
   Antibody titers were expressed as geometric mean titers (GMTs)
2. Humoral Immune Response in Terms of Haemagglutination Inhibition (HI) Antibody Titers Against the Flu A/California/7/2009 (H1N1) Vaccine Strain [ Time Frame: At Month 12 ]
   Antibody titers were expressed as geometric mean titers (GMTs)
3. Number of Seroconverted Subjects for HI Antibodies Against the Flu A/California/7/2009 (H1N1) Virus Strain [ Time Frame: At Month 6 ]
   A seroconverted subject was defined as a vaccinated subject with either a pre-vaccination titre less than (<) 1:10 and a post-vaccination titre greater than or equal to (≥) 1:40 or a pre-vaccination titre ≥ 1:10 and at least a 4-fold increase in post-vaccination titre. The Committee for Medicinal Products for Human Use (CHMP) criterion was fulfilled if the point estimate for SCR was greater than (>) 40% in children aged 3 to 17 years.
4. Number of Subjects Who Were Seroprotected for HI Antibodies Against the Flu A/California/7/2009 (H1N1) Virus Strain [ Time Frame: At Month 6 ]
   A seroprotected subject was defined as a vaccinated subject with a serum HI titre greater than or equal to (≥) 1:40, that usually is accepted as indicating protection. The Committee for Medicinal Products for Human Use (CHMP) criterion was fulfilled if the post-vaccination time point estimate for SPR the point estimate for SPR was greater than (>) 70% in children aged 3 to 17 years.
5. Number of Subjects Who Were Seroprotected for HI Antibodies Against the Flu A/California/7/2009 (H1N1) Virus Strain [ Time Frame: At Month 12 ]
   A seroprotected subject was defined as a vaccinated subject with a serum HI titre greater than or equal to (≥) 1:40, that usually is accepted as indicating protection. The Committee for Medicinal Products for Human Use (CHMP) criterion was fulfilled if the post-vaccination time point estimate for SPR the point estimate for SPR was greater than (>) 70% in children aged 3 to 17 years.
6. HI Antibody Geometric Mean Fold Rise (GMFR) Against the Flu A/California/7/2009 (H1N1) Virus Strain [ Time Frame: At Month 6 ]
   GMFR, also called seroconversion factor (SCF), was defined as the fold increase in serum HI GMTs post-vaccination compared to pre-vaccination. The CHMP criterion was fulfilled if the point estimate for GMFR was greater than (>) 2.5 in children aged 3 to 17 years
7. Humoral Immune Response in Terms of Neutralising Antibodies Against the Flu A/Netherlands/602/2009 (H1N1) Vaccine Strain [ Time Frame: At Day 0, Day 21, Day 42 and Month 6 ]
   Antibody titers were expressed as Geometric mean titers (GMTs).
8. Humoral Immune Response in Terms of Neutralising Antibodies Against the Flu A/Netherlands/602/2009 (H1N1) Vaccine Strain [ Time Frame: At Month 12 ]
   Antibody titers were expressed as Geometric mean titers (GMTs).
9. Number of Seroconverted Subjects for Neutralising Antibodies Against the Flu A/Netherlands/602/2009 (H1N1) Virus Strain [ Time Frame: At Day 21 and Day 42 ]
   A seroconverted subject was defined as a vaccinated subject with either a pre-vaccination titre less than (<) 1:10 and a post-vaccination titre greater than or equal to (≥) 1:40 or a pre-vaccination titre ≥ 1:10 and at least a 4-fold increase in post-vaccination titre. The Committee for Medicinal Products for Human Use (CHMP) criterion was fulfilled if the point estimate for SCR was greater than (>) 40% in children aged 3 to 17 years.
10. Number of Seroconverted Subjects for Neutralising Antibodies Against the Flu A/Netherlands/602/2009 (H1N1) Virus Strain [ Time Frame: At Month 6 ]
    A seroconverted subject was defined as a vaccinated subject with either a pre-vaccination titre less than (<) 1:10 and a post-vaccination titre greater than or equal to (≥) 1:40 or a pre-vaccination titre ≥ 1:10 and at least a 4-fold increase in post-vaccination titre. The Committee for Medicinal Products for Human Use (CHMP) criterion was fulfilled if the point estimate for SCR was greater than (>) 40% in children aged 3 to 17 years.
11. Number of Subjects Reporting Any and Grade 3 Solicited Local Symptoms [ Time Frame: During the 7-day (Days 0-6) post-vaccination period ]
    Solicited local symptoms assessed were pain, redness and swelling. Any was defined as any solicited local symptom reported irrespective of intensity. Grade 3 pain was defined as significant pain at rest that prevented normal everyday activities as assessed by inability to attend/do work or school or cried when limb was moved/spontaneously painful. Grade 3 redness and swelling was greater than 50 millimeters (mm) i.e. > 50mm.
12. Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms [ Time Frame: During the 7-day (Days 0-6) post-vaccination period ]
    Solicited general symptoms assessed were arthralgia, diarrhoea, drowsiness, fatigue, gastro-intestinal symptoms, headache, irritability, loss of appetite, myalgia, shivering, sweating and fever [axillary temperature above 37.5 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 above 39.0°C.
13. Number of Subjects Reporting Any Medically Attended Adverse Events (MAEs) [ Time Frame: During the entire study period (Day 0 to Month 12) ]
    MAEs were defined as adverse events with medically-attended visits that were not routine visits for physical examination or vaccination.
14. Number of Subjects Reporting Any Adverse Events of Specific Interest (AESI)/Potential Immune-mediated Diseases (pIMDs) [ Time Frame: During the entire study period (Day 0 to Month 12) ]
    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 etiology. "Any pIMD" was defined as at least one pIMD experienced by the study subject.
15. Number of Subjects Reporting Any, Grade 3 and Related Unsolicited Adverse Events (AEs). [ Time Frame: Within the 84-day after the first vaccination or from 63-day follow-up period after the second vaccination ]
    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.
16. Number of Subjects Reporting Any and Related Serious Adverse Events (SAEs) [ Time Frame: During the entire study period (Day 0 to Month 12) ]
    A serious adverse event was 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.
17. Number of Subjects With Normal and Abnormal Haematological and Biochemistry Parameters With Respect to Alanine Aminotransferase (ALAT), Aspartate Aminotransferase (ASAT), Total Bilirubin, Bilirubin Conjugated/ Direct,Creatine and Blood Urea Nitrogen(BUN) [ Time Frame: At Day 0, Day 21, Day 42 and Month 6 (M6) ]
    Subjects were categorized by age and according to their results at pre-vaccination (Day 0), Day 21, Day 42 and Month 6 which were below, within and above the normal ranges or unknown as measured by validated assay according to international standards.

Eligibility Criteria

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

Criteria

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 device.

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.

Contacts and Locations

Locations

Germany

GSK Investigational Site

Kehl, Baden-Wuerttemberg, Germany, 77694

GSK Investigational Site

Schwaebisch-Hall, Baden-Wuerttemberg, Germany, 74523

GSK Investigational Site

Stuttgart, Baden-Wuerttemberg, Germany, 70469

GSK Investigational Site

Bindlach, Bayern, Germany, 95463

GSK Investigational Site

Muenchen, Bayern, Germany, 81241

GSK Investigational Site

Noerdlingen, Bayern, Germany, 86720

GSK Investigational Site

Frankenthal, Rheinland-Pfalz, Germany, 67227

GSK Investigational Site

Worms, Rheinland-Pfalz, Germany, 67547

Sponsors and Collaborators

GlaxoSmithKline

Investigators

• Study Director: GSK Clinical Trials; GlaxoSmithKline

More Information

Additional Information:

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 Data/Documents: Informed Consent Form 

Identifier: 113638
For additional information about this study please refer to the GSK Clinical Study Register

Clinical Study Report 

Identifier: 113638
For additional information about this study please refer to the GSK Clinical Study Register

Study Protocol 

Identifier: 113638
For additional information about this study please refer to the GSK Clinical Study Register

Individual Participant Data Set 

Identifier: 113638
For additional information about this study please refer to the GSK Clinical Study Register

Dataset Specification 

Identifier: 113638
For additional information about this study please refer to the GSK Clinical Study Register

Statistical Analysis Plan 

Identifier: 113638
For additional information about this study please refer to the GSK Clinical Study Register

Annotated Case Report Form 

Identifier: 113638
For additional information about this study please refer to the GSK Clinical Study Register

Publications:

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.

Garcia-Sicilia J, Arístegui J, Omeñaca F, Carmona A, Tejedor JC, Merino JM, García-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.

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT00972517
• Other Study ID Numbers: 113638; 2009-015011-41 ( EudraCT Number )
• First Posted: September 7, 2009
• Results First Posted: September 10, 2018
• Last Update Posted: June 26, 2019
• Last Verified: June 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: IPD for this study will be made available via the Clinical Study Data Request site.
• Supporting Materials: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR)
• Time Frame: IPD is available via the Clinical Study Data Request site (click on the link provided below)
• Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.
• URL: http://clinicalstudydatarequest.com

Keywords provided by GlaxoSmithKline:

GSK Bio's influenza vaccine GSK2340272A; influenza infection

Additional relevant MeSH terms:

Influenza, Human; Respiratory Tract Infections; Infections; Orthomyxoviridae Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases