Safety and Immunogenicity of H1N1 Vaccines in Children Aged 6 Months to Less Than 9 Years of Age

Phase 2

Completed

Conditions: Influenza

Interventions: Biological: GSK2340273A
Biological: GSK2340274A

Registration Number: NCT00976820

Lead Sponsor: GlaxoSmithKline

Brief Summary: The purpose of this study is to characterize the safety and immune response of the H1N1 (swine) flu vaccines GSK2340274A and GSK2340273A in children 6 months to less than 9 years of age.

This Protocol Posting has been updated following the Protocol amendment 1 \& 2, September and October 2009. The sections impacted are study design, objectives and analysis methods.

Detailed Description: Collaborators: United States Department of Health and Human Services, Office of Biomedical Advanced Research and Development Authority

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 323

Inclusion Criteria

Male or female children 6 months to less than 9 years of age at the time of the first vaccination.
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.
Safety laboratory test results within the parameters specified in the protocol.
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 their parent(s)/ LAR can and will comply with the requirements of the protocol.
Female subjects of non-childbearing potential (pre-menarche) may be enrolled in the study.

Exclusion Criteria

Previous vaccination with an H1N1v-like virus vaccine or a medical history of physician-confirmed infection with an H1N1v-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.
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
Receipt of systemic glucocorticoids within 1 month prior to study enrollment, 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 3 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 4 weeks before the first dose of study vaccine, with the exception of seasonal influenza vaccine.
Planned administration of any vaccine not foreseen by the study protocol between Day 0 and the Day 42 phlebotomy, 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 any constituent of influenza vaccines; or a history of severe adverse reaction to a previous influenza vaccine.
Child in care.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
GSK2340273A/F2 Group	GSK2340273A	Subjects, aged 6 months - 9 years, male or female, received 2 doses of GSK2340273A-formulation 2 (F2) vaccine administered at a 21-day interval. The first dose was administered intramuscularly in the deltoid region of the non-dominant arm (or left arm if dominance was not yet identified) or left anterolateral thigh (for children \< 12 months of age). The second vaccine dose was administered in the deltoid region of the dominant arm (or right arm) or right anterolateral thigh (children \< 12 months of age).
Arepanrix/F1 Group	GSK2340274A	Subjects, aged 6 months - 9 years, male or female, received 2 doses of Arepanrix™-formulation 1 (F1) vaccine administered at a 21-day interval. The first dose was administered intramuscularly in the deltoid region of the non-dominant arm (or left arm if dominance was not yet identified) or left anterolateral thigh \[for children under (\<) 12 months of age\]. The second vaccine dose was administered in the deltoid region of the dominant arm (or right arm) or right anterolateral thigh (children \< 12 months of age).
Arepanrix/F2 Group	GSK2340274A	Subjects, aged 6 months - 9 years, male or female, received 2 doses of Arepanrix™-formulation 2 (F2) vaccine administered at a 21-day interval. The first dose was administered intramuscularly in the deltoid region of the non-dominant arm (or left arm if dominance was not yet identified) or left anterolateral thigh (for children \< 12 months of age). The second vaccine dose was administered in the deltoid region of the dominant arm (or right arm) or right anterolateral thigh (children \< 12 months of age).
GSK2340273A/F1 Group	GSK2340273A	Subjects, aged 6 months - 9 years, male or female, received 2 doses of GSK2340273A-formulation 1 (F1) vaccine administered at a 21-day interval. The first dose was administered intramuscularly in the deltoid region of the non-dominant arm (or left arm if dominance was not yet identified) or left anterolateral thigh (for children \< 12 months of age). The second vaccine dose was administered in the deltoid region of the dominant arm (or right arm) or right anterolateral thigh (children \< 12 months of age).

Primary Outcome Measures

Name	Time	Method
Number of Seroconverted Subjects Against Flu A/CAL/7/09 Influenza Strain - First Analysis	At Day 42	A seroconverted subject was defined as a vaccinated subject who had either a pre-vaccination reciprocal HI titer \< 10 and a post-vaccination reciprocal titer higher than or equal to (≥) 40, or a pre-vaccination reciprocal hemagglutination inhibition (HI) titer ≥ 10 and at least a 4-fold increase in post vaccination reciprocal titer against the vaccine virus.
Number of Seroconverted Subjects Against Flu A/CAL/7/09 Influenza Strain - Second Analysis	At Day 42	A seroconverted subject was defined as a vaccinated subject who had either a pre-vaccination reciprocal HI titer \< 10 and a post-vaccination reciprocal titer higher than or equal to (≥) 40, or a pre-vaccination reciprocal hemagglutination inhibition (HI) titer ≥ 10 and at least a 4-fold increase in post vaccination reciprocal titer against the vaccine virus.
Number of Seroprotected Subjects Against Flu A/CAL/7/09 Influenza Strain - Preliminary Analysis	At Day 21	A seroprotected subject was defined as a vaccinated subject with reciprocal HI titers higher than or equal to (≥) 40 against the tested virus.
Number of Seroprotected Subjects Against Flu A/CAL/7/09 Influenza Strain - First Analysis	At Day 42	A seroprotected subject was defined as a vaccinated subject with reciprocal HI titers higher than or equal to (≥) 40 against the tested virus.
Number of Seroprotected Subjects Against Flu A/CAL/7/09 Influenza Strain - Second Analysis	At Day 42	A seroprotected subject was defined as a vaccinated subject with reciprocal HI titers higher than or equal to (≥) 40 against the tested virus.
Number of Seroprotected Subjects Against Flu A/CAL/7/09 Strain - First Analysis	At Day 0	A seroprotected subject was defined as a vaccinated subject with reciprocal HI titers higher than or equal to (≥) 40 against the tested virus.
Number of Seroprotected Subjects Against Flu A/CAL/7/09 Strain - Second Analysis	At Day 0	A seroprotected subject was defined as a vaccinated subject with reciprocal HI titers higher than or equal to (≥) 40 against the tested virus.
Number of Seroconverted Subjects Against Flu A/CAL/7/09 Influenza Strain - Preliminary Analysis	At Day 21	A seroconverted subject was defined as a vaccinated subject who had either a pre-vaccination reciprocal hemagglutination inhibition (HI) titer lower than (\<) 10 and a post-vaccination reciprocal HI titer higher than or equal to (≥) 40, or a pre-vaccination reciprocal hemagglutination inhibition (HI) titer ≥ 10 and at least a 4-fold increase in post vaccination reciprocal titer against the vaccine virus.
Seroconversion Factor (SCF) for HI Antibodies Against Flu A/CAL/7/09 Influenza Strain - Preliminary Analysis	At Day 21	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.
Seroconversion Factor (SCF) for HI Antibodies Against Flu A/CAL/7/09 Influenza Strain - First Analysis	At Day 42	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.
Seroconversion Factor (SCF) for HI Antibodies Against Flu A/CAL/7/09 Influenza Strain - Second Analysis	At Day 42	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.

Secondary Outcome Measures

Name	Time	Method
Number of Seropositive Subjects for HI Antibodies - Preliminary Analysis	At Day 0 (PRE) and at Day 21	A seropositive subject was defined as a subject with antibody titers greater than or equal to (≥) 1:10. The vaccine strain assessed was Flu A/CAL/7/09.
Number of Seropositive Subjects for HI Antibodies - First Analysis	At Day 0 (PRE) and at Day 42	A seropositive subject was defined as a subject with antibody titers greater than or equal to (≥) 1:10. The vaccine strain assessed was Flu A/CAL/7/09.
Number of Seropositive Subjects for HI Antibodies - Second Analysis	At Day 0 (PRE) and at Day 42	A seropositive subject was defined as a subject with antibody titers greater than or equal to (≥) 1:10. The vaccine strain assessed was Flu A/CAL/7/09.
Number of Seropositive Subjects for HI Antibodies	At Day 0 (PRE) and at Day 182	A seropositive subject was defined as a subject with antibody titers greater than or equal to (≥) 1:10. The vaccine strain assessed was Flu A/CAL/7/09.
Titers for Serum Hemagglutination Inhibition (HI) Antibodies Against the Flu A/CAL/7/09 Influenza Strain - Preliminary Analysis	At Day 0 (PRE) and at Day 21	Titers are presented as geometric mean titers (GMTs) and measured in titers.
Titers for Serum Hemagglutination Inhibition (HI) Antibodies Against the Flu A/CAL/7/09 Influenza Strain - First Analysis	At Day 0 (PRE) and at Day 42	Titers are presented as geometric mean titers (GMTs) and measured in titers.
Titers for Serum Hemagglutination Inhibition (HI) Antibodies Against the Flu A/CAL/7/09 Influenza Strain - Second Analysis	At Day 0 (PRE) and at Day 42	Titers are presented as geometric mean titers (GMTs) and measured in titers.
Titers for Serum Hemagglutination Inhibition (HI) Antibodies Against the Flu A/CAL/7/09 Influenza Strain	At Day 0 (PRE) and at Day 182	Titers are presented as geometric mean titers (GMTs) and measured in titers.
Number of Seroconverted Subjects Against Flu A/CAL/7/09 Influenza Strain	At Day 182	A seroconverted subject was defined as a vaccinated subject who had either a pre-vaccination reciprocal hemagglutination inhibition (HI) titer lower than (\<) 10 and a post-vaccination reciprocal titer higher than or equal to (≥) 40, or a pre-vaccination reciprocal hemagglutination inhibition (HI) titer ≥ 10 and at least a 4-fold increase in post vaccination reciprocal titer against the vaccine virus.
Number of Seroprotected Subjects Against Flu A/CAL/7/09 Influenza Strain	At Day 0 (PRE) and at Day 182	A seroprotected subject was defined as a vaccinated subject with reciprocal HI titers higher than or equal to (≥) 40 against the tested virus.
Seroconversion Factor (SCF) for HI Antibodies Against Flu A/CAL/7/09 Influenza Strain	At Day 182	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.
Number of Seropositive Subjects for Neutralizing Antibodies Against Flu A/Neth/602/09 Influenza Strain	At Day 0 (PRE) and at Day 42	A seropositive subject was defined as a subject with antibody titers greater than or equal to (≥) 1:8. The vaccine strain assessed was Flu A/Neth/602/09 H1N1.
Titers for Neutralizing Antibodies Against the Flu A/Neth/602/09 Influenza Strain	At Day 0 (PRE) and at Day 42	Titers are presented as geometric mean titers (GMTs) and measured in titers.
Number of Subjects With Vaccine Responses for Neutralizing Antibody Concentrations	At Day 0 (PRE) and at Day 42	Vaccine response was defined as at least a 4-fold increase in post vaccination reciprocal titer relative to that prior to first vaccination. The vaccine strain assessed was Flu A/Neth/602/09.
Number of Subjects With Any and Grade 3 Solicited Local Symptoms - Preliminary Analysis	During the 7-day (Days 0-6) post-vaccination period	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.
Number of Subjects With Any and Grade 3 Solicited Local Symptoms - First Analysis	During the 7-day (Days 0-6) post-vaccination period following each dose and across doses	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.
Number of Subjects With Any and Grade 3 Solicited Local Symptoms - Second Analysis	During the 7-day (Days 0-6) post-vaccination period following each dose and across doses	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.
Number of Subjects Less Than 6 Years Old With Any, Grade 3 and Related Solicited General Symptoms - Preliminary Analysis	During the 7-day (Days 0-6) post-vaccination period	Assessed solicited general symptoms were drowsiness, irritability, loss of appetite and temperature \[defined as axillary temperature equal to or above (≥) 38 degrees Celsius (°C)\]. Any = occurrence of the symptom regardless of intensity grade or relationship to vaccination. Grade 3 symptom = symptom that prevented normal activity. Grade 3 loss of appetite= not eating at all. Grade 3 fever = fever ≥ 39.0 °C. Related = symptom assessed by the investigator as related to the vaccination.
Number of Subjects Aged Between 6 to Less Than 9 Years With Any, Grade 3 and Related Solicited General Symptoms - Preliminary Analysis	During the 7-day (Days 0-6) post-vaccination period	Assessed solicited general symptoms were fatigue, gastrointestinal symptoms, headache, joint pain at other location, muscle aches, shivering, sweating, temperature \[defined as axillary temperature equal to or above (≥) 38 degrees Celsius (°C)\]. 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.
Number of Subjects Less Than 6 Years Old With Any, Grade 3 and Related Solicited General Symptoms - First Analysis	During the 7-day (Days 0-6) post-vaccination period following each dose and across doses	Assessed solicited general symptoms were drowsiness, irritability, loss of appetite and temperature \[defined as axillary temperature equal to or above (≥) 38 degrees Celsius (°C)\]. 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.
Number of Subjects Aged Between 6 to Less Than 9 Years With Any, Grade 3 and Related Solicited General Symptoms - First Analysis	During the 7-day (Days 0-6) post-vaccination period following each dose and across doses	Assessed solicited general symptoms were fatigue, gastrointestinal symptoms, headache, joint pain at other location, muscle aches, and shivering, sweating, temperature \[defined as axillary temperature equal to or above (≥) 38 degrees Celsius (° C)\]. 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.
Number of Subjects Less Than 6 Years Old With Any, Grade 3 and Related Solicited General Symptoms - Second Analysis	During the 7-day (Days 0-6) post-vaccination period following each dose and across doses	Assessed solicited general symptoms were drowsiness, irritability, loss of appetite and temperature \[defined as axillary temperature equal to or above (≥) 38 degrees Celsius (°C)\]. 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.
Number of Subjects Aged Between 6 and 9 Years With Any, Grade 3 and Related Solicited General Symptoms- Second Analysis	During the 7-day (Days 0-6) post-vaccination period following each dose and across doses	Assessed solicited general symptoms were fatigue, gastrointestinal symptoms, headache, joint pain at other location, muscle aches, shivering, sweating and temperature \[defined as axillary temperature equal to or above (≥) 38 degrees Celsius (°C)\]. 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.
Number of Subjects With Haematological Laboratory Abnormalities - Preliminary Analysis	At Day 0 (PRE), at Day 7 and at Day 21	Among haematological parameters assessed were basophils \[BAS\], eosinophils \[EOS\], hematocrit \[HCT\], hemoglobin level \[HGB\], lymphocytes \[LYM\], monocytes \[MON\], neutrophils \[NEU\], platelet count \[PLC\], red blood cells \[RBC\] and white blood cells \[WBC\]. Haematological laboratory values were unknown, below, within or above the laboratory reference range defined for the specified time point and laboratory parameter.
Number of Subjects With Biochemical Laboratory Abnormalities - Preliminary Analysis	At Day 0 (PRE), at Day 7 and at Day 21	Biochemical parameters assessed for lab abnormalities were alanine aminotransferase \[ALT\], aspartate aminotransferase \[AST\], bilirubin \[BLR\], bilirubin conjugated/direct \[BCD\], creatinine \[CRE\] and blood urea nitrogen \[BUN\]. Biochemical laboratory values were unknown, below, within or above the laboratory reference range defined for the specified time point and laboratory parameter.
Number of Subjects With Haematological Laboratory Abnormalities - First Analysis	At Day 0 (PRE), at Day 7, at Day 21 and at Day 42	Among haematological parameters assessed were basophils \[BAS\], eosinophils \[EOS\], hematocrit \[HCT\], hemoglobin level \[HGB\], lymphocytes \[LYM\], monocytes \[MON\], neutrophils \[NEU\], platelet count \[PLC\], red blood cells \[RBC\] and white blood cells \[WBC\]. Haematological laboratory values were unknown, below, within or above the laboratory reference range defined for the specified time point and laboratory parameter.
Number of Subjects With Biochemical Laboratory Abnormalities - First Analysis	At Day 0 (PRE), at Day 7, at Day 21 and at Day 42	Biochemical parameters assessed for lab abnormalities were alanine aminotransferase \[ALT\], aspartate aminotransferase \[AST\], bilirubin \[BLR\], bilirubin conjugated/direct \[BCD\], creatinine \[CRE\] and blood urea nitrogen \[BUN\]. Biochemical laboratory values were unknown, below, within or above the laboratory reference range defined for the specified time point and laboratory parameter.
Number of Subjects With Haematological Laboratory Abnormalities - Second Analysis	At Day 0 (PRE), at Day 7 and at Day 21	Among haematological parameters assessed were basophils \[BAS\], eosinophils \[EOS\], hematocrit \[HCT\], hemoglobin level \[HGB\], lymphocytes \[LYM\], monocytes \[MON\], neutrophils \[NEU\], platelet count \[PLC\], red blood cells \[RBC\] and white blood cells \[WBC\], Haematological laboratory values were unknown, below, within or above the laboratory reference range defined for the specified time point and laboratory parameter.
Number of Subjects With Biochemical Laboratory Abnormalities - Second Analysis	At Day 0 (PRE), at Day 7, at Day 21 and at Day 42	Biochemical parameters assessed for lab abnormalities were alanine aminotransferase \[ALT\], aspartate aminotransferase \[AST\], bilirubin \[BLR\], bilirubin conjugated/direct \[BCD\], creatinine \[CRE\] and blood urea nitrogen \[BUN\]. Biochemical laboratory values were unknown, below, within or above the laboratory reference range defined for the specified time point and laboratory parameter.
Number of Subjects With Haematological Laboratory Abnormalities	At Day 182	Among haematological parameters assessed were basophils \[BAS\], eosinophils \[EOS\], hematocrit \[HCT\], hemoglobin level \[HGB\], lymphocytes \[LYM\], monocytes \[MON\], neutrophils \[NEU\], platelet count \[PLC\], red blood cells \[RBC\] and white blood cells \[WBC\]. Haematological laboratory values were unknown, below, within or above the laboratory reference range defined for the specified time point and laboratory parameter.
Number of Subjects With Biochemical Laboratory Abnormalities	At Day 182	Biochemical parameters assessed for lab abnormalities were alanine aminotransferase \[ALT\], aspartate aminotransferase \[AST\], bilirubin \[BLR\], bilirubin conjugated/direct \[BCD\], creatinine \[CRE\] and blood urea nitrogen \[BUN\]. Biochemical laboratory values were unknown, below, within or above the laboratory reference range defined for the specified time point and laboratory parameter.
Number of Subjects With Any Unsolicited Adverse Events (AEs) - Preliminary Analysis	Within 21 days (Days 0-20) post vaccination	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.
Number of Subjects With Any Unsolicited Adverse Events (AEs) - First Analysis	Within 42 days (Days 0-41) post vaccination	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.
Number of Subjects With Any Unsolicited Adverse Events (AEs) - Second Analysis	Within 41 days (Days 0-40) post vaccination	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.
Number of Subjects With Any Unsolicited Adverse Events (AEs)	Within 84 days (Days 0-83) post vaccination	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.
Number of Subjects With Any Medically-attended Adverse Events (MAEs) - Preliminary Analysis	Within 21 days (Days 0-20) post vaccination	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.
Number of Subjects With Any Medically-attended Adverse Events (MAEs) - First Analysis	Within 41 days (Days 0-40) post vaccination	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.
Number of Subjects With Any Medically-attended Adverse Events (MAEs) - Second Analysis	Within 42 days (Days 0-41) post vaccination	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.
Number of Subjects With Any Medically-attended Adverse Events (MAEs)	Throughout the entire study period (Day 0 - Day 385)	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.
Number of Subjects Reporting Any Potential Immune-mediated Diseases (pIMDs) - Preliminary Analysis	Within 21 days (Days 0-20) post vaccination	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.
Number of Subjects Reporting Any Potential Immune-mediated Diseases (pIMDs) - First Analysis	Within 42 days (Days 0-41) post vaccination	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.
Number of Subjects Reporting Any Potential Immune-mediated Diseases (pIMDs) - Second Analysis	Within 42 days (Days 0-41) post vaccination	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.
Number of Subjects Reporting Any Potential Immune-mediated Diseases (pIMDs)	Throughout the entire study period (Day 0 - Day 385)	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.
Number of Subjects With Serious Adverse Events (SAEs) - Preliminary Analysis	Within 21 days (Days 0-20) post vaccination	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.
Number of Subjects With Serious Adverse Events (SAEs) - First Analysis	Within 42 days (Days 0-41) post vaccination	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.
Number of Subjects With Serious Adverse Events (SAEs) - Second Analysis	Within 42 days (Day 0-41) post vaccination	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.
Number of Subjects With Serious Adverse Events (SAEs)	Throughout the entire study period (Day 0 - Day 385)	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.