Safety and Efficacy of H1N1 Vaccines in Children Aged 6 Months to Less Than 10 Years of Age

Study Overview
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Brief Summary
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The purpose of this study is to characterize the safety and efficacy of GSK Biologicals' H1N1 flu candidate vaccines GSK2340274A and GSK2340273A in children 6 months to less than 10 years of age.

Official Title
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A Study to Evaluate the Safety and Efficacy of A/California/7/2009 (H1N1)V-like Vaccines GSK2340274A and GSK2340273A in Children Aged 6 Months to Less Than 10 Years of Age

Conditions
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Influenza

Intervention / Treatment
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* Biological: GSK Biologicals' investigational vaccine GSK2340274A (alternative formulations)
* Biological: GSK Biologicals' investigational vaccine GSK2340273A (alternative formulations)
* Biological: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female children 6 months to less than 10 years of age at the time of the first 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 first vaccine dose under this protocol. Written informed consent obtained from the subject's parent(s)/legally acceptable representative(s) (LAR(s)); written informed assent obtained from the subject if appropriate pre local requirements). Stable health status as defined by absence of a health event satisfying the definition of a SAE, or a change in an ongoing drug therapy due to therapeutic failure or symptoms of drug toxicity, within 1 month prior to enrolment. Parent(s)/LAR(s) available and accessible for active surveillance contacts. Parent(s)/LAR(s) and (if age-appropriate, subjects) who, in the investigator's opinion, can and will comply with the requirements of the protocol as documented by signature on the informed consent document. Female subjects of non-childbearing potential (pre-menarche) may be enrolled in the study. Exclusion Criteria: Previous vaccination with an A/California/7/2009 (H1N1)v-like virus vaccine. Medical history of physician-confirmed infection with an A/California/7/2009 (H1N1)v-like virus. 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 (≥ 100.4ºF) 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 live attenuated vaccine within 4 weeks before the first vaccination or of any licensed inactivated vaccine within 2 weeks before the first vaccination. Planned administration of any vaccine not foreseen by the study protocol between Day 0 and Day 42. 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. Planned use of a pandemic monovalent A/California/7/2009 (H1N1)v-like virus vaccine other than the study vaccines during the study period. Planned administration of seasonal trivalent influenza vaccine during the 4 month period following Day 0. Use of any investigational or non-registered product (drug or vaccine) other than the study vaccine(s) within 30 days before the first dose of study vaccine, or planned use during the study period. Any known or suspected allergy to any constituent of influenza vaccines (including egg proteins or mercurial preservatives); 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.

Ages Eligible for Study
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Minimum Age: 6 Months
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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arepanrix 2D 6M-3Y Group<br>Subjects, male and female, aged 6 months (M) to 3 years (Y), received 2 doses (D) of the Arepanrix™ vaccine at a 21-day interval (Days 0 and 21). First doses were administered in the deltoid region of the non-dominant arm (or left arm if dominance is not yet identified) or, for children <12 months of age, in the left anterolateral thigh. Second doses were administered at a 21-day interval in the deltoid region of the dominant arm (or right arm) or, for, children <12 months of age, in the right anterolateral thigh. | Biological: GSK Biologicals' investigational vaccine GSK2340274A (alternative formulations)<br>* Intramuscular injection, one or two doses<br>* Other names: Arepanrix;|
| Experimental: Arepanrix 2D 3Y-10Y Group<br>Subjects, male and female, aged 3 years (Y) to 10 years, received 2 doses (D) of the Arepanrix™ vaccine at a 21-day interval (Days 0 and 21). First doses were administered in the deltoid region of the non-dominant arm (or left arm if dominance is not yet identified). Second doses were administered at a 21-day interval in the deltoid region of the dominant arm (or right arm). | Biological: GSK Biologicals' investigational vaccine GSK2340274A (alternative formulations)<br>* Intramuscular injection, one or two doses<br>* Other names: Arepanrix;|
| Experimental: Arepanrix 1D 6M-3Y Group<br>Subjects, male and female, aged 6 months (M) to 3 years (Y), received 1 dose (D) of the Arepanrix™ vaccine followed by 1 dose of saline placebo at a 21-day interval at a 21-day interval (Days 0 and 21). First doses were administered in the deltoid region of the non-dominant arm (or left arm if dominance is not yet identified) or, for children <12 months of age, in the left anterolateral thigh. Second doses were administered at a 21-day interval in the deltoid region of the dominant arm (or right arm) or, for, children <12 months of age, in the right anterolateral thigh. | Biological: GSK Biologicals' investigational vaccine GSK2340274A (alternative formulations)<br>* Intramuscular injection, one or two doses<br>* Other names: Arepanrix;Biological: Placebo<br>* Intramuscular injection, one dose<br>|
| Experimental: Arepanrix 1D 3Y-10Y Group<br>Subjects, male and female, aged 3 years (Y) to 10 years, received 1 dose (D) of the Arepanrix™ vaccine followed by 1 dose of saline placebo at a 21-day interval at a 21-day interval (Days 0 and 21). First doses were administered in the deltoid region of the non-dominant arm (or left arm if dominance is not yet identified). Second doses were administered at a 21-day interval in the deltoid region of the dominant arm (or right arm). | Biological: GSK Biologicals' investigational vaccine GSK2340274A (alternative formulations)<br>* Intramuscular injection, one or two doses<br>* Other names: Arepanrix;Biological: Placebo<br>* Intramuscular injection, one dose<br>|
| Experimental: GSK2340273A 6M-3Y Group<br>Subjects, male and female, aged 6 months (M) to 3 years (Y), received 2 doses (D) of the GSK2340273A vaccine at a 21-day interval (Days 0 and 21). First doses were administered in the deltoid region of the non-dominant arm (or left arm if dominance is not yet identified) or, for children <12 months of age, in the left anterolateral thigh. Second doses were administered at a 21-day interval in the deltoid region of the dominant arm (or right arm) or, for, children <12 months of age, in the right anterolateral thigh. | Biological: GSK Biologicals' investigational vaccine GSK2340273A (alternative formulations)<br>* Intramuscular injection, two doses<br>|
| Experimental: GSK2340273A 3Y-10Y Group<br>Subjects, male and female, aged 3 years (Y) to 10 years, received 2 doses (D) of the GSK2340273A vaccine at a 21-day interval (Days 0 and 21). First doses were administered in the deltoid region of the non-dominant arm (or left arm if dominance is not yet identified). Second doses were administered at a 21-day interval in the deltoid region of the dominant arm (or right arm). | Biological: GSK Biologicals' investigational vaccine GSK2340273A (alternative formulations)<br>* Intramuscular injection, two doses<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects Reporting at Least One A/California Influenza Event | The influenza virus presence was confirmed by quantitative reverse transcription polymerase chain reaction assay (RT-qPCR). | From 14 days after first vaccination until study conclusion on Day 385 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects Reporting at Least One A/California Influenza Event | The influenza virus presence was confirmed by quantitative reverse transcription polymerase chain reaction assay (RT-qPCR). | From 42 days after first vaccination until study conclusion on Day 385 | 
| Number of Subjects Reporting at Least One A/California Influenza Event | The influenza virus presence was confirmed by quantitative reverse transcription polymerase chain reaction assay (RT-qPCR). | From Day 0 until study conclusion on Day 385 | 
| Number of Subjects Reporting at Least One Culture Confirmed A/California Influenza Event | The influenza virus presence was confirmed by a positive culture. | From 14 days after first vaccination until study conclusion on Day 385 | 
| Number of Subjects Reporting at Least One Culture Confirmed A/California Influenza Event | The influenza virus presence was confirmed by a positive culture. | From 42 days after first vaccination until study conclusion on Day 385 | 
| Number of Subjects Reporting at Least One Culture Confirmed A/California Influenza Event | The influenza virus presence was confirmed by a positive culture. | From Day 0 until study conclusion on Day 385 | 
| Number of Subjects With at Least One Pneumonia Event |  | From 14 days after first vaccination until study conclusion on Day 385 | 
| Number of Subjects With at Least One Pneumonia Event |  | From 42 days after first vaccination until study conclusion on Day 385 | 
| Number of Subjects With at Least One Pneumonia Event |  | From Day 0 after first vaccination until study conclusion on Day 385 | 
| Number of Subjects With at Least One Pneumonia Event | Pneumonia was confirmed by quantitative reverse transcription polymerase chain reaction assay (RT-qPCR). | From 14 days after first vaccination until study conclusion at Day 385 | 
| Number of Subjects With at Least One Pneumonia Event | Pneumonia was confirmed by quantitative reverse transcription polymerase chain reaction assay (RT-qPCR). | From 42 days after first vaccination until study conclusion at Day 385 | 
| Number of Subjects With at Least One Pneumonia Event | Pneumonia was confirmed by quantitative reverse transcription polymerase chain reaction assay (RT-qPCR). | From Day 0 after first vaccination until study conclusion at Day 385 | 
| Number of Subjects With Protocol Specified Influenza-like Illness (ILI) Symptoms in All Reported ILI Cases | Protocol specified ILI symptoms were: fever, muscle aches all over the body, cough, sore throat, runny or stuffy nose, short of breath, headache, vomiting, diarrhea, chills and fatigue. | From Day 0 until study end at Day 385 | 
| Number of Subjects With Protocol Specified Influenza-like Illness (ILI) Symptoms in All Reported ILI Cases | Protocol specified ILI symptoms were: fever, muscle aches all over the body, cough, sore throat, runny or stuffy nose, short of breath, headache, vomiting, diarrhea, chills and fatigue. Analysis for the time frame Day 42 till Day 385 was not performed as planned per protocol. | From Day 14 until study end at Day 385 | 
| Number of Subjects With Protocol Specified ILI Symptoms in RT-qPCR-confirmed A/California Influenza Cases | Protocol specified ILI symptoms were: fever, muscle aches all over the body, cough, sore throat, runny or stuffy nose, short of breath, headache, vomiting, diarrhea, chills and fatigue. | From Day 0 until study end at Day 385 | 
| Number of Subjects With Protocol Specified ILI Symptoms in RT-qPCR-confirmed A/California Influenza Cases | Protocol specified ILI symptoms were: fever, muscle aches all over the body, cough, sore throat, runny or stuffy nose, short of breath, headache, vomiting, diarrhea, chills and fatigue. Analysis for the time frame Day 42 till Day 385 was not performed as planned per protocol. | From Day 14 until study end at Day 385 | 
| 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 100 millimeters (mm) of injection site. | During the 7-day follow-up period (Day 0 - Day 6) after each dose and across doses | 
| Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms in Children Aged 6 Months to Less Than 6 Years | Assessed solicited general symptoms were drowsiness, irritability, loss of appetite and temperature [defined as axillary temperature equal to or above (≥) 38.0 degrees Celsius (°C)]. Any = occurrence of the symptom regardless of intensity grade. Grade 3 drowsiness = drowsiness which prevented normal everyday activity. Grade 3 irritability = crying that could not be comforted/ prevented normal activity. Grade 3 loss of appetite = not eating at all. Grade 3 temperature = fever ≥ 39.0 °C. Related = symptom assessed by the investigator as related to the vaccination. | During the 7-day follow-up period (Day 0 - Day 6) after each dose and across doses | 
| Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms in Children Aged Between 6 to 10 Years | Assessed solicited general symptoms were fatigue, gastrointestinal symptoms (gastro.sympt.), headache, joint pain at other location, muscle aches, shivering, sweating and temperature [defined as axillary temperature equal to or above (≥) 38.0 degrees Celsius (°C)]. Any = Incidence of a particular symptom regardless of intensity grade or relationship to study vaccination. Grade 3 = symptom which prevented normal everyday activity. Grade 3 temperature = fever ≥ 39.0 °C. Related = symptom assessed by the investigator as related to the vaccination. | During the 7-day follow-up period (Day 0 - Day 6) after each dose and across doses | 
| Number of Subjects Reporting Any 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 385 | 
| Number of Subjects With Any 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. | Up to Day 385 | 
| Number of Subjects With Any 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. | From Day 0 to Day 42 | 
| 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 Day 385 | 
| Titers for Serum Hemagglutination Inhibition (HI) Antibodies Against Flu A/CAL/7/09 (H1N1) Influenza Strain | Titers are presented as geometric mean titers (GMTs). | At Days 0 and 42 | 
| Number of Seropositive Subjects for Hemagglutination Inhibition (HI) Antibodies Against Flu A/CAL/7/09 (H1N1) Influenza Strain | A seropositive subject was defined as a subject whose HI titers were greater than or equal to (≥) 1:10. | At Days 0 and 42 | 
| Number of Seroconverted (SCR) Subjects for Flu A/CAL/7/09 (H1N1) Influenza Strain | Seroconversion was defined as: for initially seronegative subjects, antibody titer ≥ 1:40 after vaccination; and for initially seropositive subjects, antibody titer after vaccination ≥ 4 fold the pre-vaccination antibody titer. | At Day 42 | 
| Number of Seroprotected (SPR) Subjects Against Flu A/CAL/7/09 (H1N1) Influenza Strain | A seroprotected subject was defined as a vaccinated subject with serum Hemagglutination Inhibition (HI) titer ≥ 1:40. | At Days 0 and 42 | 
| Seroconversion Factor for Hemagglutination Inhibition (HI) Antibodies Against Flu A/CAL/7/09 (H1N1) Influenza Strain | The seroconversion factor (SCF) was defined as the fold increase in serum Hemagglutination Inhibition (HI) geometric mean titers (GMTs) post-vaccination compared to Day 0. | At Day 42 | 
| Geometric Mean Antibody Titer Ratio Adjusted for Baseline Titers for Serum Hemagglutination Inhibition (HI) Antibodies Against Flu A/CAL/7/09 (H1N1) | The geometric mean titer ratio (GMT ratio) was defined as the ratio of geometric mean of the post-vaccination reciprocal HI titer between groups. The analysis was not performed for Day 182 and Day 385 as planned per protocol. | At Day 42 | 
| Titers for Serum Hemagglutination Inhibition (HI) Antibodies Against Flu A/CAL/7/09 (H1N1) | Titers are presented as geometric mean titers (GMTs). | At Days 0 and 182 | 
| Number of Seropositive Subjects for Hemagglutination Inhibition (HI) Antibodies Against Flu A/CAL/7/09 (H1N1) Influenza Strain | A seropositive subject was defined as a subject whose HI titers were greater than or equal to (≥) 1:10. | At Days 0 and 182 | 
| Number of Seroconverted (SCR) Subjects for Flu A/CAL/7/09 (H1N1) Influenza Strain | Seroconversion was defined as: for initially seronegative subjects, antibody titer ≥ 1:40 after vaccination; and for initially seropositive subjects, antibody titer after vaccination ≥ 4 fold the pre-vaccination antibody titer. | At Day 182 | 
| Number of Seroprotected (SPR) Subjects Against Flu A/CAL/7/09 (H1N1) Influenza Strain | A seroprotected subject was defined as a vaccinated subject with serum Hemagglutination Inhibition (HI) titer ≥ 1:40. | At Days 0 and 182 | 
| Seroconversion Factor for Hemagglutination Inhibition (HI) Antibodies Against Flu A/CAL/7/09 (H1N1) Influenza Strain | The seroconversion factor (SCF) was defined as the fold increase in serum Hemagglutination Inhibition (HI) geometric mean titers (GMTs) post vaccination compared to Day 0. | At Day 182 | 
| Titers for Serum Hemagglutination Inhibition (HI) Antibodies Against Flu A/CAL/7/09 (H1N1) Influenza Strain | Titers are presented as geometric mean titers (GMTs). | At Days 0 and 385 | 
| Number of Seropositive Subjects for Hemagglutination Inhibition (HI) Antibodies Against Flu A/CAL/7/09 (H1N1) Influenza Strain | A seropositive subject was defined as a subject whose HI titers was greater than or equal to (≥) 1:10. | At Days 0 and 385 | 
| Number of Seroconverted (SCR) Subjects for Flu A/CAL/7/09 (H1N1) Influenza Strain | Seroconversion was defined as: for initially seronegative subjects, antibody titer ≥ 1:40 after vaccination; and for initially seropositive subjects, antibody titer after vaccination ≥ 4 fold the pre-vaccination antibody titer. | At Day 385 | 
| Number of Seroprotected (SPR) Subjects Against Flu A/CAL/7/09 (H1N1) Influenza Strain | A seroprotected subject was defined as a vaccinated subject with serum Hemagglutination Inhibition (HI) titer ≥ 1:40. | At Days 0 and 385 | 
| Seroconversion Factor for Hemagglutination Inhibition (HI) Antibodies Against Flu A/CAL/7/09 (H1N1) Influenza Strain | The seroconversion factor (SCF) was defined as the fold increase in serum Hemagglutination Inhibition (HI) geometric mean titers (GMTs) post vaccination compared to Day 0. | At Day 385 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Influenza, H1N1, Pandemic