A Study to Test GlaxoSmithKline's (GSK) Candidate Vaccine-GSK1437173A for Prevention of Shingles in Children With Kidney Transplant

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the reactogenicity, safety and immunogenicity of 2 doses of PED-HZ/su, GSK's vaccine candidate for the prevention of Herpes Zoster (HZ) in immunocompromised paediatric renal transplant recipients aged 1-17 years

Official Title
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A Reactogenicity, Safety and Immunogenicity Study of GSK's Paediatric Herpes Zoster Subunit Candidate Vaccine (PED-HZ/su) GSK143713A in Immunocompromised Paediatric Renal Transplant Recipients

Conditions
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Herpes Zoster

Intervention / Treatment
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* Biological: PED-HZ/su


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects' parent(s)/Legally Acceptable Representative(s) [LAR(s) who, in the opinion of the investigator, can and will comply, with the requirements of the protocol Written or witnessed/thumb printed informed consent obtained from the parent(s)/LAR(s) of the subject prior to performance of any study specific procedure. Written informed assent obtained from the subjects when applicable according to local requirements. A male or female between, and including, 1 and 17 years of age at the time of randomisation (Visit Day 1) Body weight ≥ 6 kg/13.23 pounds. A subject is eligible if they meet at least one of the following criteria: Documented previous VZV vaccination OR Medically verified varicella (with source documentation) OR Seropositive for VZV prior to transplantation. Subjects with renal transplant more than six months (180 days) prior randomization (Visit Day 1) Subject who has received an ABO compatible allogeneic renal transplant (allograft). Subject with stable renal function with stability defined as <20% variability between the last two creatinine measurements or based on investigator opinion after review of multiple creatinine measurements. Subject receiving maintenance immunosuppressive therapy for the prevention of allograft rejection for a minimum of one month (30 days) prior to randomization (Visit Day 1). Female subjects of childbearing potential may be enrolled in the study, if the subject has practiced adequate contraception for 30 days prior to Visit Day 1 and has agreed to continue adequate contraception during the entire treatment period and for 2 months after completion of the vaccination series Exclusion Criteria: Medical conditions Any primary kidney disease with a high incidence of recurrent primary kidney disease within the allograft Evidence of recurrent primary kidney disease within the current allograft Previous allograft loss secondary to recurrent primary kidney disease History of more than one organ transplanted (that is, kidney-liver, simultaneous double kidney or kidney-other organ(s) transplanted). Subjects with an episode of acute allograft rejection over the six months (180 days) prior to enrolment Panel Reactive Antibodies (PRA) calculated PRA (cPRA) or Calculated Reaction Frequency (cRF) score that is unknown at the time of transplant VZV serostatus unknown prior to transplant Subjects with advanced chronic kidney disease Evidence of significant proteinuria (≥ 200 g/mol creatinine) believed to be of renal origin (an example of non-renal origin is proteinuria from mucus in a reconstructed bladder) Subjects without multiple dialysis options in the event acute or chronic dialysis needed. History of unstable or progressive neurological disorder. Subjects ≤ 5 years of age with a history of one or more simple or complex febrile seizures Subjects > 5 years with history of one or more complex febrile seizures Occurrence of a varicella or HZ episode by clinical history within the 6 months (180 days) preceding Visit Day 1 Any autoimmune disease, with the following exceptions which do not constitute an exclusion criterion: IgA nephropathy Rapidly progressive glomerulonephritis Membranous glomerulonephritis Idiopathic Type I membranoproliferative glomerulonephritis Diabetes mellitus (type 1 and 2) with diabetic nephropathy Confirmed or suspected Human Immunodeficiency Virus or primary immunodeficiency disease Any other clinical condition that, in the opinion of the investigator, might pose additional risk to the subject due to participation in the study History of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccine Any condition which, in the judgement of the investigator would make intramuscular injection unsafe. Atypical Haemolytic Uraemic Syndrome. Prior/Concomitant therapy Use of any investigational or non-registered product other than the study vaccine during the period starting 30 days before Visit Day 1 (Day -29 to Day -1), or planned use during the study period. Subject in receipt of treatment for rejection during the six months (180 days) prior to enrolment. Use of anti-CD20 or other B-cell monoclonal antibody agents within 1 year of Visit Day 1 or planned administration during the duration of the study. Administration of blood products 3 months (90 days) prior to Visit Day 1 or planned administration during the duration of the study. Administration of immunoglobulins 6 months (180 days) prior to Visit Day 1 or planned administration of immunoglobulins during the duration of the study. Administration or planned administration of a vaccine within 30 days prior to Visit Day 1 up to Visit Month 2 with the exception of an inactivated or subunit influenza vaccine which may be given 8 days prior to or 14 days after Visit Day 1 and 8 days prior to or 14 days after Visit Month 1. Previous vaccination against HZ Varicella vaccination within the 6 months (180 days) preceding Visit Day 1 Planned administration during the study of an HZ or varicella vaccine (including an investigational or non-registered vaccine) other than the study vaccine Prior/Concurrent clinical study experience • Concurrent or planned participation in another clinical study, at any time during the study period, in which the subject has been or will be exposed to an investigational or a non-investigational product available locally through compassionate use programs, submitted for and pending local/country registration, approved and registered for use in other countries with well-documented Summary of Product Characteristics or Prescribing Information The name of the active component(s) of these immunosuppressants must be provided in the concomitant medication listing Other exclusions Child in care Pregnant or lactating female Female planning to become pregnant or planning to discontinue contraceptive precautions (if of childbearing potential) between one month (30 days) prior to Visit Day 1 through two months (60 days) after Visit Month 1. Evidence or high suspicion, in the opinion of the investigator, of non-compliance or non-adherence to use of induction and/or maintenance immunosuppressive therapies. Failure to fully complete the 7-day pre-vaccination diary card distributed at the Pre-vaccination visit Completion must cover the 7 days immediately prior to randomisation (Visit Day 1). Completion is defined as a minimum of 6 days completed. Subjects with less than 6 days completed may be offered a new date for Visit Day 1 and the opportunity to comply with the completion of the 7-day pre-vaccination diary card prior to the new planned Visit Day 1. Any study personnel or their immediate dependants, family, or household member.

Ages Eligible for Study
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Minimum Age: 1 Year
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PED-HZ/su 12-17 Group<br>Paediatric renal transplant recipients aged 12 to 17 years old, receiving 2 doses of the investigational vaccine (PED HZ/su) | Biological: PED-HZ/su<br>* GSK's candidate vaccine- PED-HZ/su. is administered intramuscularly in the deltoid of the non-dominant arm, on a two-dose schedule in the two investigational groups.<br>|
| No Intervention: Control 12-17 Group<br>Paediatric renal transplant recipients aged 12 to 17 years old, not receiving the investigational vaccine but being treated according to the local standard of care | |
| Experimental: PED-HZ/su 1-11 Group<br>Paediatric renal transplant recipients aged 1 to 11 years old, receiving 2 doses of the investigational vaccine (PED HZ/su). Enrolment into this group will be in a staggered manner. Following enrolment into the PED-HZ/su 12-17 group, a safety evaluation of data collected up to visit month 2 will be performed. Upon favourable outcome of the evaluation, enrolment into this group will begin. | Biological: PED-HZ/su<br>* GSK's candidate vaccine- PED-HZ/su. is administered intramuscularly in the deltoid of the non-dominant arm, on a two-dose schedule in the two investigational groups.<br>|
| No Intervention: Control 1-11 Group<br>Paediatric renal transplant recipients aged 1 to 11 years old, not receiving the investigational vaccine but being treated according to the local standard of care | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of subjects from the interventional groups, with solicited local adverse events (AEs) | Assessed solicited local AEs are pain, redness and swelling at the injection site. Pain includes tenderness. Note: GSK diary cards for collecting solicited local and general AEs/symptoms is different for subjects < 6 years and ≥ 6 years. Hence the age category of 1-11 years is further split to 1-5 years and 6-11 years. | Within 7 days after each vaccination (vaccines administered on day 1 and month 1) | 
| Number of subjects from the interventional groups, with solicited general AEs | Assessed solicited general AEs among Infants/Toddlers/Children < 6 years are: Drowsiness Fever* Irritability/Fussiness Loss of appetite Gastrointestinal (GI) symptoms** Assessed solicited general AEs among Children ≥ 6 years are: Fatigue Fever* GI symptoms** Headache Myalgia Shivering (chills) Fever is defined as temperature ≥ 38.0°C/100.4°F **GI symptoms include nausea, vomiting, diarrhoea, and/or abdominal pain Note: GSK diary cards for collecting solicited local and general AEs/symptoms is different for subjects < 6 years and ≥ 6 years. Hence the age category of 1-11 years is further split to 1-5 years and 6-11 years. | Within 7 days after each vaccination (vaccines administered on day 1 and month 1) | 
| Number of subjects from the control groups with solicited general symptoms | Assessed solicited general symptoms among Infants/Toddlers/Children < 6 years are: Drowsiness Fever* Irritability/Fussiness Loss of appetite GI symptoms** Assessed solicited general symptoms among Children ≥ 6 years are: Fatigue Fever* GI symptoms** Headache Myalgia Shivering (chills) Fever is defined as temperature ≥ 38.0°C/100.4°F **GI symptoms include nausea, vomiting, diarrhoea, and/or abdominal pain As subjects from the control group are not vaccinated, they will not complete the diary card for local solicited symptoms. | Within 7 days after Visit Day 1 | 
| Number of subjects from the control groups with solicited general symptoms | Assessed solicited general symptoms among Infants/Toddlers/Children < 6 years are: Drowsiness Fever* Irritability/Fussiness Loss of appetite GI symptoms** Assessed solicited general symptoms among Children ≥ 6 years are: Fatigue Fever* GI symptoms** Headache Myalgia Shivering (chills) Fever is defined as temperature ≥ 38.0°C/100.4°F **GI symptoms include nausea, vomiting, diarrhoea, and/or abdominal pain | Within 7 days after Visit Month 1 | 
| Number of subjects from the interventional groups with unsolicited AEs after each vaccination | An unsolicited AE is any AE reported in addition to those solicited during the clinical study. Also, any 'solicited' symptom with onset outside the specified period of follow-up for solicited symptoms is to be reported as an unsolicited adverse event. | Within 30 days after each vaccination (vaccines administered on day 1 and month 1) | 
| Number of subjects from the control groups with unsolicited symptoms | An unsolicited symptom is any symptom reported in addition to those solicited during the clinical study. Also, any 'solicited' symptom with onset outside the specified period of follow-up for solicited symptoms is to be reported as an unsolicited adverse event. | Within 30 days after Visit Day 1 | 
| Number of subjects from the control groups with unsolicited symptoms | An unsolicited symptom is any symptom reported in addition to those solicited during the clinical study. Also, any 'solicited' symptom with onset outside the specified period of follow-up for solicited symptoms is to be reported as an unsolicited adverse event. | Within 30 days after Visit Month 1 | 
| Number of subjects with serious adverse events (SAEs), potential immune mediated diseases (pIMDs) and biopsy confirmed renal allograft rejection. | An SAE is any untoward medical occurrence that results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization or results in disability/incapacity. pIMDs are sub sets of Adverse events of special interest (AESIs) that include autoimmune disease and other inflammatory and/neurological disorders of interest, which may or may not have autoimmune aetiology. The renal allograft rejections are biopsy confirmed pathophysiological changes indicative of rejection. The rejection is graded for severity and extent of histologic inflammation and injury. The reporting period for any renal allograft rejection is from Visit Day 1 to the study end (month 2). | From Visit Day 1 up to Visit Month 2 | 
| Number of subjects from the interventional groups with seizures | All seizures occurring within 30 days following study vaccination are reported. | Within 30 days after each vaccination (vaccines administered on day 1 and month 1) | 
| Number of subjects from the non-interventional groups with seizures | All seizures occurring within 30 days after visit day 1 are reported, for the control groups. | Within 30 days after Visit Day 1 | 
| Number of subjects from the non-interventional groups with seizures | All seizures occurring within 30 days of visit month 1 are reported, for the control groups | Within 30 days after Visit Month 1 | 
| Number of subjects from the interventional groups with generalized convulsive seizures | Generalized convulsive seizures are classified as follows: Level 1 of diagnostic certainty: witnessed sudden loss of consciousness AND generalized, tonic, clonic, tonic-clonic, or atonic motor manifestations Level 2 of diagnostic certainty: history of unconsciousness AND generalized, tonic, clonic, tonic-clonic, or atonic motor manifestations Level 3 of diagnostic certainty: history of unconsciousness AND other generalized motor manifestations Level 4 of diagnostic certainty: reported generalized convulsive seizure with insufficient evidence to meet the case definitions for Level 1, 2 or 3 of diagnostic certainty above Level 5 of diagnostic certainty: Not a case of generalized convulsive seizure Only levels 1 to 3 of generalized convulsive seizures will comprise the analysis for this outcome measure. | Within 7 days after each vaccination (vaccines administered on day 1 and month 1) | 
| Number of subjects from the non-interventional groups with generalized convulsive seizures | Generalized convulsive seizures are classified as follows: Level 1 of diagnostic certainty: witnessed sudden loss of consciousness AND generalized, tonic, clonic, tonic-clonic, or atonic motor manifestations Level 2 of diagnostic certainty: history of unconsciousness AND generalized, tonic, clonic, tonic-clonic, or atonic motor manifestations Level 3 of diagnostic certainty: history of unconsciousness AND other generalized motor manifestations Level 4 of diagnostic certainty: reported generalized convulsive seizure with insufficient evidence to meet the case definitions for Level 1, 2 or 3 of diagnostic certainty above Level 5 of diagnostic certainty: Not a case of generalized convulsive seizure Only levels 1 to 3 of generalized convulsive seizures will comprise the analysis for this outcome measure | Within 7 days after Visit Day 1 | 
| Number of subjects from the non-interventional groups with generalized convulsive seizures | Generalized convulsive seizures are classified as follows: Level 1 of diagnostic certainty: witnessed sudden loss of consciousness AND generalized, tonic, clonic, tonic-clonic, or atonic motor manifestations Level 2 of diagnostic certainty: history of unconsciousness AND generalized, tonic, clonic, tonic-clonic, or atonic motor manifestations Level 3 of diagnostic certainty: history of unconsciousness AND other generalized motor manifestations Level 4 of diagnostic certainty: reported generalized convulsive seizure with insufficient evidence to meet the case definitions for Level 1, 2 or 3 of diagnostic certainty above Level 5 of diagnostic certainty: Not a case of generalized convulsive seizure Only levels 1 to 3 of generalized convulsive seizures will comprise the analysis for this outcome measure | Within 7 days after Visit Month 1 | 
| Percentage of subjects with Anti-gE antibody concentrations in terms of Geometric Mean Concentrations (GMCs) | The geometric mean concentration (GMC) calculations are performed by taking the anti log of the mean of the log concentration transformations. Antibody concentrations below the cut-off of the assay will be given an arbitrary value equal to half the cut-off for GMC calculation | At Month 2 (one-month post-dose 2) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of subjects with SAEs, pIMDs and biopsy confirmed renal allograft rejections from day 1 to month 13 | An SAE is any untoward medical occurrence that results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization or results in disability/incapacity pIMDs are sub sets of Adverse events of special interest (AESIs) that include autoimmune disease and other inflammatory and/neurological disorders of interest, which may or may not have autoimmune aetiology. The renal allograft rejections are biopsy confirmed pathophysiological changes indicative of rejection. The rejection is graded for severity and extent of histologic inflammation and injury. This outcome measure is analysed during epoch 002 (day 1 to month 2) and during epoch 003 (month 2- month 13) | From Visit Day 1 up to Visit Month 13 | 
| Occurrence of Herpes Zoster cases | HZ may present classically with a unilateral, dermatomal rash that is associated with pain, pruritus, allodynia or other altered sensation. In this population, disseminated HZ may occur and present with a generalized rash with systemic symptoms such as fever. All children enrolled in the trial have a history of primary VZV infection or vaccination and in the presence of immunosuppression, disseminated HZ cannot be distinguished clinically from varicella This outcome measure is analysed during epoch 002 (day 1 to month 2) and during epoch 003 (month 2- month 13) | From Visit Day 1 until Visit Month 13 | 
| Number of subjects from the interventional pooled age group with solicited local AEs | The pooled age group includes all subjects aged 1-17 years. The assessed local AEs solicited are: Pain Redness Swelling Note: Pain includes tenderness. | Within 7 days after each vaccination (vaccines administered on day 1 and month 1) | 
| Number of subjects from the interventional pooled age group with solicited general AEs | The pooled age group includes all subjects aged 1-17 years. The assessed solicited general AEs among Infants/Toddlers/Children < 6 years are: Drowsiness Fever* Irritability/Fussiness Loss of appetite Gastrointestinal (GI) symptoms** The assessed solicited general AEs among Children ≥ 6 years are: Fatigue Fever* GI symptoms** Headache Myalgia Shivering (chills) Fever is defined as temperature ≥ 38.0°C/100.4°F **GI symptoms include nausea, vomiting, diarrhoea, and/or abdominal pain | Within 7 days after each vaccination (vaccines administered on day 1 and month 1) | 
| Number of subjects from the non-interventional pooled age group with solicited general symptoms | The pooled age group includes all subjects aged 1-17 years. The assessed solicited general symptoms among Infants/Toddlers/Children < 6 years are: Drowsiness Fever* Irritability/Fussiness Loss of appetite GI symptoms** The assessed solicited general symptoms among Children ≥ 6 years are: Fatigue Fever* GI symptoms** Headache Myalgia Shivering (chills) Fever is defined as temperature ≥ 38.0°C/100.4°F **GI symptoms include nausea, vomiting, diarrhoea, and/or abdominal pain As subjects from the control group are not vaccinated, they will not complete the diary card for local solicited symptoms. | Within 7 days after each vaccination (vaccines administered on day 1 and month 1) | 
| Number of subjects from the interventional pooled age group with unsolicited AEs after each vaccination | The pooled age group includes all subjects aged 1-17 years. An unsolicited AE is any AE reported in addition to those solicited during the clinical study. Also, any 'solicited' symptom with onset outside the specified period of follow-up for solicited symptoms is to be reported as an unsolicited adverse event. | Within 30 days after each vaccination (vaccines administered on day 1 and month 1) | 
| Number of subjects from the non-interventional pooled age group with unsolicited symptoms | The pooled age group includes all subjects aged 1-17 years. An unsolicited symptom is any symptom reported in addition to those solicited during the clinical study. Also, any 'solicited' symptom with onset outside the specified period of follow-up for solicited symptoms is to be reported as an unsolicited adverse event. | Within 30 days after each vaccination (vaccines administered on day 1 and month 1) | 
| Number of subjects from the non-interventional pooled age group with unsolicited symptoms | The pooled age group includes all subjects aged 1-17 years. An unsolicited symptom is any symptom reported in addition to those solicited during the clinical study. Also, any 'solicited' symptom with onset outside the specified period of follow-up for solicited symptoms is to be reported as an unsolicited adverse event. | Within 30 days after Visit Month 1 | 
| Number of subjects from the pooled age groups with any SAEs, pIMDs and biopsy confirmed renal allograft rejections | An SAE is any untoward medical occurrence that results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization or results in disability/incapacity pIMDs are sub sets of Adverse events of special interest (AESIs) that include autoimmune disease and other inflammatory and/neurological disorders of interest, which may or may not have autoimmune aetiology. The renal allograft rejections are biopsy confirmed pathophysiological changes indicative of rejection. The rejection is graded for severity and extent of histologic inflammation and injury. | From Visit Day 1 until Visit Month 2 | 
| Number of subjects from the pooled age groups with any SAEs, pIMDs and biopsy confirmed renal allograft rejections | An SAE is any untoward medical occurrence that results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization or results in disability/incapacity pIMDs are sub sets of Adverse events of special interest (AESIs) that include autoimmune disease and other inflammatory and/neurological disorders of interest, which may or may not have autoimmune aetiology. The renal allograft rejections are biopsy confirmed pathophysiological changes indicative of rejection. The rejection is graded for severity and extent of histologic inflammation and injury. | From Visit Day 1 until Visit Month 13 | 
| Number of subjects from the pooled age groups with HZ | HZ may present classically with a unilateral, dermatomal rash that is associated with pain, pruritus, allodynia or other altered sensation. In this population, disseminated HZ may occur and present with a generalized rash with systemic symptoms such as fever. All children enrolled in the trial have a history of primary VZV infection or vaccination and in the presence of immunosuppression, disseminated HZ cannot be distinguished clinically from varicella. This outcome measure is analysed during epoch 002 (day 1 to month 2) and during epoch 003 (month 2- month 13) | From Visit Day 1 until Visit Month 13 | 
| Number of subjects from the interventional pooled age group with seizures | The pooled age group includes all subjects aged 1-17 years. All seizures occurring within 30 days following study vaccination are reported | Within 30 days after each vaccination (vaccines administered on day 1 and month 1) | 
| Number of subjects from the non-interventional pooled age group with seizures | The pooled age group includes all subjects aged 1-17 years. All seizures occurring with 30 days after visit day 1 are reported | Within 30 days after Visit Day 1 | 
| Number of subjects from the non-interventional pooled age group with seizures | The pooled age group includes all subjects aged 1-17 years. All seizures occurring with 30 days after visit month 1 are reported | Within 30 days after each vaccination (vaccines administered on day 1 and month 1) | 
| Number of subjects from the interventional pooled age group with generalized convulsive seizures | The pooled age group includes all subjects aged 1-17 years. Generalized convulsive seizures are classified as follows: Level 1 of diagnostic certainty: witnessed sudden loss of consciousness AND generalized, tonic, clonic, tonic-clonic, or atonic motor manifestations Level 2 of diagnostic certainty: history of unconsciousness AND generalized, tonic, clonic, tonic-clonic, or atonic motor manifestations Level 3 of diagnostic certainty: history of unconsciousness AND other generalized motor manifestations Level 4 of diagnostic certainty: reported generalized convulsive seizure with insufficient evidence to meet the case definitions for Level 1, 2 or 3 of diagnostic certainty above Level 5 of diagnostic certainty: Not a case of generalized convulsive seizure Only levels 1 to 3 of generalized convulsive seizures will comprise the analysis for this outcome measure | Within 7 days after each vaccination (vaccines administered on day 1 and month 1) | 
| Number of subjects from the non-interventional pooled age group with generalized convulsive seizures | The pooled age group includes all subjects aged 1-17 years. Generalized convulsive seizures are classified as follows: Level 1 of diagnostic certainty: witnessed sudden loss of consciousness AND generalized, tonic, clonic, tonic-clonic, or atonic motor manifestations Level 2 of diagnostic certainty: history of unconsciousness AND generalized, tonic, clonic, tonic-clonic, or atonic motor manifestations Level 3 of diagnostic certainty: history of unconsciousness AND other generalized motor manifestations Level 4 of diagnostic certainty: reported generalized convulsive seizure with insufficient evidence to meet the case definitions for Level 1, 2 or 3 of diagnostic certainty above Level 5 of diagnostic certainty: Not a case of generalized convulsive seizure Only levels 1 to 3 of generalized convulsive seizures will comprise the analysis for this outcome measure | Within 7 days after each vaccination (vaccines administered on day 1 and month 1) | 
| Number of subjects from the non-interventional pooled age group with generalized convulsive seizures | The pooled age group includes all subjects aged 1-17 years. Generalized convulsive seizures are classified as follows: Level 1 of diagnostic certainty: witnessed sudden loss of consciousness AND generalized, tonic, clonic, tonic-clonic, or atonic motor manifestations Level 2 of diagnostic certainty: history of unconsciousness AND generalized, tonic, clonic, tonic-clonic, or atonic motor manifestations Level 3 of diagnostic certainty: history of unconsciousness AND other generalized motor manifestations Level 4 of diagnostic certainty: reported generalized convulsive seizure with insufficient evidence to meet the case definitions for Level 1, 2 or 3 of diagnostic certainty above Level 5 of diagnostic certainty: Not a case of generalized convulsive seizure Only levels 1 to 3 of generalized convulsive seizures will comprise the analysis for this outcome measure | Within 7 days after Visit Month 1 | 
| Vaccine Response Rate (VRR) for Anti-glycoprotein (Anti-gE) antibody concentrations | The Vaccine Response Rate for anti-gE antibodies is defined as the percentage of subjects who have at least: a 4-fold increase in the post-dose 2 anti-gE Ab concentration as compared to the pre-vaccination anti-gE Ab concentration, for subjects who are seropositive at baseline, or, a 4-fold increase in the post-dose 2 anti-gE Ab concentration as compared to the anti-gE Ab cut-off value for seropositivity, for subjects who are seronegative at baseline. This outcome measure is analysed during epoch 002 (day 1 to month 2) and during epoch 003 (month 2- month 13) | At Month 2 and Month 13 | 
| Median fold increase of anti-gE antibody concentrations | Median fold increase in antibody concentration with 95% Confidence Interval is tabulated for the interventional groups by age strata (1-11 years and 12-17 years) This outcome measure is analysed during epoch 002 (day 1 to month 2) and during epoch 003 (month 2- month 13) | At Month 2 and Month 13 | 
| Percentage of subjects with anti-gE antibody concentrations in terms of GMCs | GMC calculations are performed by taking the anti log of the mean of the log concentration transformations. Antibody concentrations below the cut-off of the assay will be given an arbitrary value equal to half the cut-off for GMC calculation | At Day 1 (pre-vaccination) and Month 13 | 
| Percentage of subjects in the interventional pooled age group, with Anti-gE antibody concentrations in terms of GMCs | GMC calculations are performed by taking the anti log of the mean of the log concentration transformations. Antibody concentrations below the cut-off of the assay will be given an arbitrary value equal to half the cut-off for GMC calculation. Median fold increase in antibody concentration with 95% Confidence Interval is to be tabulated for the interventional groups by pooled age category (1-17 years). This outcome measure is analysed during epoch 002 (day 1 to month 2) and during epoch 003 (month 2- month 13) | At Day 1, Month 2 and Month 13 |