Safety and Immune Response of Candidate H1N1 Influenza Vaccines GSK2340274A and GSK234072A in Children 3 to Less Than 10 Years Old

Study Overview
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Brief Summary
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This study is designed to characterize the safety and immunogenicity of pandemic influenza (H1N1) candidate vaccines GSK2340274A and GSK234072A in children 3 to less than 10 years old.

Official Title
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An Observer-blind Safety and Immunogenicity Study of GSK Biologicals' A/California/7/2009 (H1N1)V-like Vaccines GSK2340274A and GSK2340272A in Children 3 to Less Than 10 Years Old

Conditions
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Influenza

Intervention / Treatment
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* Biological: GSK Biologicals' GSK2340274A (two different formulations)
* Biological: GSK Biologicals' - GSK2340272A


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or pre-menarchal female children 3 to < 10 years of age at the time of the study vaccination. Less than 10 years of age implies inclusion of children who have not reached their 10th birthday as of Day 0, the day of the study 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. Subjects and/or parent(s)/LAR who the investigator believes can and will comply with the requirements of the protocol as documented by signature on the informed consent document (and, if appropriate, the informed assent document). 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 vaccination. 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 (day of study vaccination), 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. Administration of any licensed live-attenuated vaccine within 30 days before study vaccination or any licensed inactivated vaccine within 15 days before study vaccination. Planned administration of any A/California H1N1v-like vaccine other than the study vaccine between Day 0 and the Day 21 phlebotomy. Planned administration of any other vaccine not foreseen by the study protocol between Day 0 and Day 21. 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 study vaccination, 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 (A child who has been placed under the control or protection of an agency, organization, institution or entity by the courts).

Ages Eligible for Study
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Minimum Age: 3 Years
Maximum Age: 9 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AREPANRIX 1/2 GROUP<br>Healthy male or female children aged 3 to less than (<) 10 years at the time of study vaccination, who received 1 half (1/2) pediatric dose of Arepanrix™ vaccine at Day 0, administered intramuscularly in the deltoid of the non-dominant arm. | Biological: GSK Biologicals' GSK2340274A (two different formulations)<br>* Intramuscular injection<br>|
| Experimental: PANDEMRIX 1/2 GROUP<br>Healthy male or female children aged 3 to less than (<) 10 years at the time of study vaccination, who received 1 half (1/2) pediatric dose of Pandemrix™ vaccine at Day 0, administered intramuscularly in the deltoid of the non-dominant arm. | Biological: GSK Biologicals' - GSK2340272A<br>* Intramuscular injection<br>|
| Experimental: AREPANRIX GROUP<br>Healthy male or female children aged 3 to less than (<) 10 years at the time of study vaccination, who received 1 pediatric dose of Arepanrix™ vaccine at Day 0, administered intramuscularly in the deltoid of the non-dominant arm. | Biological: GSK Biologicals' GSK2340274A (two different formulations)<br>* Intramuscular injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Seroconverted Subjects for Haemagglutination Inhibition (HI) Antibodies Against Flu A/CAL/7/09 H1N1 Strain | Seroconversion rate (SCR) was defined as the proportion of subjects who had either a pre-vaccination reciprocal HI titer below (<) 10 and a post-vaccination reciprocal titre greater than or equal to (≥) 40, or a pre-vaccination reciprocal HI titer ≥ 10 and at least a 4-fold increase in post vaccination reciprocal titer against the vaccine virus. The Flu strain assessed was A/California/7/2009 (H1N1)v-like virus (Flu A/CAL/7/09), following the Committee for Medicinal Products for Human Use (CHMP) and the Center for Biologics Evaluation and Research (CBER) guidance. The CBER criterion was fulfilled if the lower 95% confidence interval (CI) for SCR was (>) 40%. The CHMP criterion was fulfilled if the point estimate for SCR was > 40%. | At Day 21 | 
| Number of Seroprotected Subjects for HI Antibodies Against Flu A/CAL/7/09 H1N1 Strain | A seroprotected subject was defined as a vaccinated subject with a serum HI titer greater than or equal to (≥) 1:40, that usually is accepted as indicating protection. The Flu strain assessed was Flu A/CAL/7/09, following the CHMP and the CBER guidance. The CBER criterion was fulfilled if the lower limit of the 95% CI for seroprotection (SPR) was > 70%. The CHMP criterion was fulfilled if the post-vaccination point estimate for SPR was > 70%. | At Day 0 | 
| Number of Seroprotected Subjects for HI Antibodies Against Flu A/CAL/7/09 H1N1 Strain | A seroprotected subject was defined as a vaccinated subject with a serum HI titer greater than or equal to (≥) 1:40, that usually is accepted as indicating protection. The Flu strain assessed was Flu A/CAL/7/09, following the CHMP and the CBER guidance. The CBER criterion was fulfilled if the lower limit of the 95% CI for seroprotection (SPR) was > 70%. The CHMP criterion was fulfilled if the post-vaccination point estimate for SPR was > 70%. | At Day 21 | 
| Geometric Mean Fold Rise (GMFR) for HI Antibodies Against Flu A/CAL/7/09 H1N1 Strain | GMFR, also called seroconversion factor (SCF), was defined as the fold increase in serum HI geometric mean titers (GMTs) post-vaccination compared to pre-vaccination. The Flu strain assessed was Flu A/CAL/7/09, following the CHMP and the CBER guidance. The CHMP criterion was fulfilled if the point estimate for GMFR was > 2.5. | At Day 21 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Seroconverted Subjects for HI Antibodies Against Flu A/CAL/7/09 H1N1 Strain | Seroconversion rate (SCR) was defined as the proportion of subjects who had either a pre-vaccination reciprocal HI titer < 10 and a post-vaccination reciprocal titer ≥ 40, or a pre-vaccination reciprocal HI titer ≥ 10 and at least a 4-fold increase in post vaccination reciprocal titer against the vaccine virus. The Flu strain assessed was Flu A/CAL/7/09, following the CHMP and the CBER guidance. The CBER criterion was fulfilled if the lower limit of the 95% CI for SCR was > 40%. The CHMP criterion was fulfilled if the post-vaccination point estimate for SCR was > 40%. | At Day 182 | 
| Number of Seroprotected Subjects for HI Antibodies Against Flu A/CAL/7/09 H1N1 Strain | A seroprotected subject was defined as a vaccinated subject with a serum HI titer greater than or equal to (≥) 1:40, that usually is accepted as indicating protection. The Flu strain assessed was Flu A/CAL/7/09, following the CHMP and the CBER guidance. The CBER criterion was fulfilled if the lower limit of the 95% CI for seroprotection (SPR) was > 70%. The CHMP criterion was fulfilled if the post-vaccination point estimate for SPR was > 70%. | At Day 0 and Day 182 | 
| Geometric Mean Fold Rise (GMFR) for HI Antibodies Against Flu A/CAL/7/09 H1N1 Strain | GMFR, also called seroconversion factor (SCF), 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, following the CHMP and the CBER guidance. The CHMP criterion was fulfilled if the post-vaccination point estimate for SCF was > 2.5. | At Day 182 | 
| Number of Subjects With HI Antibody Titers Against Flu A/CAL/7/09 H1N1 Above the Cut-off Value | The cut-off value for the humoral immune response in terms of vaccine H1N1 HI antibodies were egual to or above (≥) 1:10. The Flu strain assessed was Flu A/CAL/7/09, following the CHMP and the CBER guidance. | At Day 21 | 
| HI Antibody Titers Against Flu A/CAL/7/09 H1N1 Strain | Titers are presented as geometric mean titers (GMTs), for the seropositivity cut-off value of ≥ 1:10. The Flu strain assessed was Flu A/CAL/7/09, following the CHMP and the CBER guidance. | At Day 21 | 
| Number of Subjects With HI Antibody Titers Against Flu A/CAL/7/09 H1N1 Above the Cut-off Value | The cut-off value for the humoral immune response in terms of vaccine H1N1 HI antibodies were equal to or above (≥) 1:10. The Flu strain assessed was Flu A/CAL/7/09, following the CHMP and the CBER guidance. | At Day 182 | 
| HI Antibody Titers Against Flu A/CAL/7/09 H1N1 Strain | Titers were presented as geometric mean titers (GMTs), for the seropositivity cut-off value of ≥ 1:10. The Flu strain assessed was Flu A/CAL/7/09, following the CHMP and the CBER guidance. | At Day 182 | 
| Number of Subjects With Any and Grade 3 Solicited Local Symptoms | Assessed solicited local symptoms were pain, redness and swelling. Any = occurrence of any local symptom regardless of intensity grade. Grade 3 pain for children less than 6 years= cried when limb was moved/spontaneously painful. Grade 3 pain for children aged 6 to < 10 years= pain that prevented normal activity. Grade 3 redness/swelling = redness/swelling spreading beyond 100 millimeters (mm) of injection site. | During the 7-day (Days 0-6) post-vaccination period | 
| Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Assessed solicited general symptoms were drowsiness, irritability, loss of appetite and fever [defined as axillary temperature equal to or above 38.0 degrees Celsius (°C)]. Any = occurrence of any general symptom regardless of intensity grade or relation to vaccination. Grade 3 drowsiness= drowsiness that prevented normal activity. Grade 3 irritability= crying that could not be comforted/prevented normal activity. Grade 3 loss of appetite= not eating at all. Grade 3 fever = fever > 39.0 °C or > 40.0 °C. Related= general symptom assessed by the investigator as causally related to the vaccination. This outcome measure refers to subjects aged 3 to 5 years. | During the 7-day (Days 0-6) post-vaccination period | 
| Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Assessed solicited general symptoms were fatigue, gastrointestinal symptoms, headache, joint pain at other location, muscle aches, shivering, sweating and fever [defined as axillary temperature equal to or above 38.0 degrees Celsius (°C)]. Any = occurrence of any general symptom regardless of intensity grade or relation to vaccination. Grade 3 symptom= symptom that prevented normal activity. Grade 3 fever = fever > 39.0 °C, but ≤ 40.0 °C. Related= general symptom assessed by the investigator as causally related to the vaccination. This outcome measure refers to subjects aged 6 to 10 years. | During the 7-day (Days 0-6) post-vaccination period | 
| Number of Subjects With Medically-attended Adverse 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. Analysis of intensity and relationship to vaccination of MAEs was not performed. | Up to day 21 | 
| Number of Subjects With 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. Analysis of intensity and relationship to vaccination of MAEs was not performed. | During the entire study period (Day 0 to Day 182) | 
| Number of Subjects With Potential Immune-mediated Diseases (pIMDs) | Potential immune-mediated diseases (pIMDs) are a subset of AEs that include autoimmune diseases and other inflammatory and/or neurologic disorders of interest which may or may not have an autoimmune aetiology. | Up to Day 21 | 
| Number of Subjects With pIMDs | Potential immune-mediated diseases (pIMDs) are a subset of AEs that include autoimmune diseases and other inflammatory and/or neurologic disorders of interest which may or may not have an autoimmune aetiology. | During the entire study period (Day 0 to Day 182) | 
| Number of Subjects With 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. | Within the 21-day (Days 0-20) post-vaccination period | 
| Number of Subjects With 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. | Within the 42-day (Days 0-41) post-vaccination period | 
| 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. | Up to 21 days after vaccination | 
| Number of Subjects With Serious Adverse Events (SAEs) | 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. | During the entire study period (Day 0 to Day 182) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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H1N1, Influenza, Pandemic, GSK Bio's influenza vaccines GSK2340274A and GSK234072A