Chicken-pox Illness (Varicella Virus Disease), Chickenpox
Conditions
Keywords
Immunogenicity, Varicella, Safety, Human serum albumin, Healthy children, 12 to 23 months
Brief summary
The purpose of this study is to evaluate the safety and immunogenicity of 2 formulations of GSK Biologicals' varicella vaccines given as a 2-dose course in the second year of life.
Detailed description
GSK Biologicals has removed human serum albumin (a stabilizer) from its varicella vaccine to minimize as much as possible the use of animal or human-derived products in the production of vaccines. The study is intended to provide information on the safety and immunogenicity of GlaxoSmithKline (GSK) Biologicals' candidate varicella vaccine formulated without human serum albumin (HSA) in contrast to Varilrix™ (GSK) which contains HSA when both are used in a two-dose schedule, with the first and second doses given approximately 42 days apart in the second year of life. The immunogenicity sub-cohort will be comprised of approximately 400 subjects, representing approximately 100 subjects enrolled in each of the participating countries. Rationale for amendment 1: Sites in the UK can perform home visits. For subjects participating through home visits, the subject's parent(s) / Legally Acceptable Representative(s) \[LAR(s)\] will be requested to sign a Recruitment/Randomisation agreement to provide personal information and to agree to have their child randomised before providing written consent to participate in the study (to be provided at the 1st home visit).
Interventions
BIOLOGICALVarilrix HSA-free
2 doses will be administered, one at Day 0 and the other at Day 42
BIOLOGICALVarilrix™
2 doses will be administered, one at Day 0 and the other at Day 42
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
12 Months to 23 Months
Healthy volunteers
Yes
Inclusion criteria
* Subjects' parent(s)/ LAR(s) who, in the opinion of the investigator, can and will comply with the requirements of the protocol. * A male or female between, and including, 12 and 23 months of age (i.e. 12 months to a day before 24 months) at the time of the first study vaccination. * Written informed consent obtained from the parent(s)/LAR(s) of the subject prior to performing any study specific procedure. * Subjects in stable health as determined by investigator's clinical examination and assessment of subject's medical history. * Subjects must have had prior administration of a dose of measles, mumps and rubella (MMR) vaccine at least 30 days (Day -31 or earlier) prior to study vaccination at Day 0.
Exclusion criteria
* Child in care. * Use of any investigational or non-registered product other than the study vaccines during the period starting 30 days before the day of study vaccination (i.e., 30 days prior to Visit 1/Day 0) or planned use during the entire study period. * Concurrently participating in another clinical study, in which the child has been or will be exposed to an investigational or a non-investigational product. * Chronic administration (defined as 14 or more consecutive days) of immunosuppressants, or other immune-modifying drugs during the period starting 180 days prior to the first vaccine dose or any planned administration of immunosuppressive and immune-modifying drugs during the entire study. * For corticosteroids, this will mean prednisone ≥0.5 mg/kg/day or equivalent. * Inhaled and topical steroids are allowed. * Planned administration/ administration of a live viral vaccine not foreseen by the study protocol during the period starting 30 days prior to study vaccination at Visit 1/Day 0 until study end. Non study live viral vaccines can be administered at Visit 3 (Day 84) after completion of study procedures. * Planned administration/ administration of an inactivated vaccine not foreseen by the study protocol during the period starting 7 days prior to each vaccination (at Visit 1/Day 0 and Visit 2/Day 42) and ending 14 days after each vaccination. Outside of this period, non-study inactivated vaccines can be administered as per standard of care. * Administration of immunoglobulins and/or any blood products during the period starting 180 days prior to the first vaccine dose or planned administration from the date of first study vaccination through the entire study. * History of varicella or zoster. * Known exposure to varicella/zoster during the period starting within 30 days prior to first study vaccination. * Previous vaccination against varicella. * Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination (no laboratory testing required). * Subjects with blood dyscrasias, leukemia, and lymphomas of any type. * A family history of congenital or hereditary immunodeficiency * History of allergic disease or reactions likely to be exacerbated by any component of the vaccines, including hypersensitivity to neomycin or latex. * Major congenital defects or serious chronic illness. * Acute disease and/or fever at the time of enrolment. * Fever is defined as temperature ≥38. 0°C/100.4°F by any age appropriate route. * Subjects with a minor illness without fever may be enrolled at the discretion of the investigator. * Active untreated tuberculosis based on medical history. * Any other condition which, in the opinion of the investigator, prevents the child from participating in the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects Reporting Fever | 15-days (Days 0-14) post Dose 1 of varicella vaccination | Fever was defined as axillary temperature above (\>) 39.0 °C (\> 102.2°F) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Evaluation of Immune Response to Varicella Vaccine With Respect to Anti Varicella Zoster Virus (Anti-VZV) Antibody Concentrations (Immuno-sub Cohort) | At Day 42 and Day 84 post vaccination | Anti-VZY antibody concentrations were expressed in terms of Geometric Mean Concentrations (GMCs) |
| Number of Subjects With a Seroresponse to VZV (Immuno Sub Cohort) | At Day 42 and Day 84 post vaccination | For VZV, seroresponse was defined as, post-vaccination anti-VZV antibody concentration ≥ 50 mIU/mL among subjects who were seronegative (antibody concentration below (\< ) 25 mIU/mL) before vaccination |
| Number of Subjects Reporting Solicited Local Symptoms | 4-day post vaccination period following Dose 1 (Day 0) and Dose 2 (Day 42) | Solicited local symptoms assessed were pain, injection site redness and swelling. Any = occurrence of the specified solicited local symptom regardless of its intensity. Grade 3 pain = subject crying when limb was moved or as spontaneously painful. Grade 3 redness and swelling = above (\>) 20 mm |
| Number of Subjects Reporting Fever | 15 days post each dose of varicella vaccination | Fever was defined as axillary temperature greater than or equal to (≥) 38.0°C (≥ 100.4°F) |
| Number of Subjects Reporting Febrile Convulsions | 43-day post vaccination period following Dose 1 (Day 0) and Dose 2 (Day 42) | Any febrile convulsion = occurrence of the specified solicited general symptom regardless of its intensity. Grade 3 febrile convulsion = febrile convulsion which prevented normal, everyday activities. Related febrile convulsion = assessed by the investigator as causally related to study vaccination |
| Number of Subjects Reporting Unsolicited Adverse Events (AEs) | 43-day post vaccination period following Dose 1 (Day 0) and Dose 2 (Day 42) | Unsolicited AE covers any AE 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 = occurrence of any unsolicited symptom regardless of intensity grade or relation to vaccination |
| Number of Subjects Reporting Serious Adverse Events (SAEs) | From Day 0 through the end of study (Day 84) | SAEs assessed included medical occurrences that resulted in death, were life threatening, required hospitalisation or prolongation of hospitalisation or resulted in disability/incapacity. Any SAE = occurrence of SAE regardless of intensity grade or relation to vaccination |
| Number of Subjects Reporting Rash | 43-day post vaccination period following Dose 1 (Day 0) and Dose 2 (Day 42) | Any rash = occurrence of the specified solicited general symptom regardless of its intensity. Grade 3 rash = rash which prevented normal, everyday activities. Related rash = assessed by the investigator as causally related to study vaccination |
Countries
Estonia, Germany, Mexico, Thailand, United Kingdom
Participant flow
Pre-assignment details
Five vaccinated subjects for whom the data could not be used due to invalid informed consent were excluded.
Participants by arm
| Arm | Count |
|---|---|
| VAR_HSA_F Group 2 doses of Varilrix HSA-free vaccine, one at Visit 1 (Day 0) and the other at Visit 2 (Day 42), were given to the subjects in this group. The vaccine was administered subcutaneously in the triceps region of the left arm | 615 |
| VAR Group 2 doses of Varilrix™ vaccine, one at Visit 1 (Day 0) and the other at Visit 2 (Day 42), were given to the subjects in this group. The vaccine was administered subcutaneously in the triceps region of the left arm | 616 |
| Total | 1,231 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 2 | 0 |
| Overall Study | Protocol Violation | 0 | 1 |
| Overall Study | Unable To Arrange Visit 3 | 1 | 0 |
| Overall Study | Violation Of Procedures GSK | 0 | 1 |
| Overall Study | Withdrawal by Subject | 3 | 7 |
Baseline characteristics
| Characteristic | VAR_HSA_F Group | VAR Group | Total |
|---|---|---|---|
| Age, Continuous | 16.7 Months STANDARD_DEVIATION 3.3 | 16.9 Months STANDARD_DEVIATION 3.4 | 16.8 Months STANDARD_DEVIATION 3.3 |
| Race/Ethnicity, Customized African Heritage / African American | 3 Participants | 1 Participants | 4 Participants |
| Race/Ethnicity, Customized Asian - Central/South Asian Heritage | 2 Participants | 2 Participants | 4 Participants |
| Race/Ethnicity, Customized Asian - East Asian Heritage | 3 Participants | 2 Participants | 5 Participants |
| Race/Ethnicity, Customized Asian - South East Asian Heritage | 133 Participants | 135 Participants | 268 Participants |
| Race/Ethnicity, Customized Other | 94 Participants | 94 Participants | 188 Participants |
| Race/Ethnicity, Customized White - Arabic / North African Heritage | 1 Participants | 1 Participants | 2 Participants |
| Race/Ethnicity, Customized White - Caucasian / European Heritage | 379 Participants | 381 Participants | 760 Participants |
| Sex: Female, Male Female | 318 Participants | 312 Participants | 630 Participants |
| Sex: Female, Male Male | 297 Participants | 304 Participants | 601 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 615 | 0 / 616 |
| other Total, other adverse events | 489 / 615 | 491 / 616 |
| serious Total, serious adverse events | 13 / 615 | 15 / 616 |
Outcome results
Primary
Number of Subjects Reporting Fever
Fever was defined as axillary temperature above (\>) 39.0 °C (\> 102.2°F)
Time frame: 15-days (Days 0-14) post Dose 1 of varicella vaccination
Population: Analysis was performed on the Total Vaccinated cohort which included all vaccinated subjects with administration of either Varilrix HSA-free or Varilrix™vaccine documented. Number of participants analysed corresponds to the subjects in the Total Vaccinated cohort with documented dose 15-days (Days 0-14) post Dose 1 of varicella vaccination
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| VAR_HSA_F Group | Number of Subjects Reporting Fever | 24 Subjects |
| VAR Group | Number of Subjects Reporting Fever | 32 Subjects |
Comparison: Non-inferiority of Varilrix HSA-free vaccine to Varilrix™ vaccine in terms of percentage of subjects reporting fever \> 39.0°C (\> 102.2°F) within 15-days (Days 0-14) after Dose 1 (VAR\_HSA\_F Group minus VAR Group)95% CI: [-3.72, 1.08]
Secondary
Evaluation of Immune Response to Varicella Vaccine With Respect to Anti Varicella Zoster Virus (Anti-VZV) Antibody Concentrations (Immuno-sub Cohort)
Anti-VZY antibody concentrations were expressed in terms of Geometric Mean Concentrations (GMCs)
Time frame: At Day 42 and Day 84 post vaccination
Population: Immunogenicity analyses were performed on the According-to-protocol (ATP) cohort for immunogenicity. Immune response (in terms of GMC) was assessed in sub cohort of the ATP cohort for immunogenicity for each group (immuno sub cohort) who had blood taken and tested for anti-varicella antibodies at Day 0, Day 42, and Day 84
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| VAR_HSA_F Group | Evaluation of Immune Response to Varicella Vaccine With Respect to Anti Varicella Zoster Virus (Anti-VZV) Antibody Concentrations (Immuno-sub Cohort) | Post Dose 1 blood sample at Day 42 | 139.9 mIU/mL |
| VAR_HSA_F Group | Evaluation of Immune Response to Varicella Vaccine With Respect to Anti Varicella Zoster Virus (Anti-VZV) Antibody Concentrations (Immuno-sub Cohort) | Post Dose 2 blood sample at Day 84 | 931.8 mIU/mL |
| VAR Group | Evaluation of Immune Response to Varicella Vaccine With Respect to Anti Varicella Zoster Virus (Anti-VZV) Antibody Concentrations (Immuno-sub Cohort) | Post Dose 1 blood sample at Day 42 | 146.0 mIU/mL |
| VAR Group | Evaluation of Immune Response to Varicella Vaccine With Respect to Anti Varicella Zoster Virus (Anti-VZV) Antibody Concentrations (Immuno-sub Cohort) | Post Dose 2 blood sample at Day 84 | 1102.4 mIU/mL |
Secondary
Number of Subjects Reporting Febrile Convulsions
Any febrile convulsion = occurrence of the specified solicited general symptom regardless of its intensity. Grade 3 febrile convulsion = febrile convulsion which prevented normal, everyday activities. Related febrile convulsion = assessed by the investigator as causally related to study vaccination
Time frame: 43-day post vaccination period following Dose 1 (Day 0) and Dose 2 (Day 42)
Population: Analysis was performed on the Total Vaccinated cohort. Number of participants analysed corresponds to the subjects in the Total Vaccinated cohort with at least one documented dose 43 days following each vaccination and across doses for each of the 2 groups (VAR\_HSA\_F Group and VAR Group)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| VAR_HSA_F Group | Number of Subjects Reporting Febrile Convulsions | Febrile convulsion, Dose 1 : Grade 3 | 0 Subjects |
| VAR_HSA_F Group | Number of Subjects Reporting Febrile Convulsions | Febrile convulsion, Dose 2 : Related | 0 Subjects |
| VAR_HSA_F Group | Number of Subjects Reporting Febrile Convulsions | Febrile convulsion, Dose 2 : Any | 0 Subjects |
| VAR_HSA_F Group | Number of Subjects Reporting Febrile Convulsions | Febrile convulsion, Across Doses : Any | 1 Subjects |
| VAR_HSA_F Group | Number of Subjects Reporting Febrile Convulsions | Febrile convulsion, Dose 1 : Related | 0 Subjects |
| VAR_HSA_F Group | Number of Subjects Reporting Febrile Convulsions | Febrile convulsion, Across Doses : Grade 3 | 0 Subjects |
| VAR_HSA_F Group | Number of Subjects Reporting Febrile Convulsions | Febrile convulsion, Dose 2 : Grade 3 | 0 Subjects |
| VAR_HSA_F Group | Number of Subjects Reporting Febrile Convulsions | Febrile convulsion, Across Doses : Related | 0 Subjects |
| VAR_HSA_F Group | Number of Subjects Reporting Febrile Convulsions | Febrile convulsion, Dose 1 : Any | 1 Subjects |
| VAR Group | Number of Subjects Reporting Febrile Convulsions | Febrile convulsion, Across Doses : Related | 0 Subjects |
| VAR Group | Number of Subjects Reporting Febrile Convulsions | Febrile convulsion, Dose 1 : Any | 1 Subjects |
| VAR Group | Number of Subjects Reporting Febrile Convulsions | Febrile convulsion, Dose 1 : Grade 3 | 1 Subjects |
| VAR Group | Number of Subjects Reporting Febrile Convulsions | Febrile convulsion, Dose 1 : Related | 0 Subjects |
| VAR Group | Number of Subjects Reporting Febrile Convulsions | Febrile convulsion, Dose 2 : Any | 1 Subjects |
| VAR Group | Number of Subjects Reporting Febrile Convulsions | Febrile convulsion, Dose 2 : Grade 3 | 0 Subjects |
| VAR Group | Number of Subjects Reporting Febrile Convulsions | Febrile convulsion, Dose 2 : Related | 0 Subjects |
| VAR Group | Number of Subjects Reporting Febrile Convulsions | Febrile convulsion, Across Doses : Any | 2 Subjects |
| VAR Group | Number of Subjects Reporting Febrile Convulsions | Febrile convulsion, Across Doses : Grade 3 | 1 Subjects |
Secondary
Number of Subjects Reporting Fever
Any fever (≥ 38°C) = occurrence of any fever regardless of its intensity grade or relationship to vaccination. Grade 3 fever = temperature \> 39.5°C. Related fever = assessed by the investigator as causally related to study vaccination
Time frame: 43-day post vaccination period following Dose 1 (Day 0) and Dose 2 (Day 42)
Population: Analysis was performed on the Total Vaccinated cohort. Number of participants analysed corresponds to the subjects in the Total Vaccinated cohort with the documented dose 43 days following each vaccination and across doses for each of the 2 groups (VAR\_HSA\_F Group and VAR Group)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| VAR_HSA_F Group | Number of Subjects Reporting Fever | Fever (Axillary), Dose 1 : > 39.5 °C | 40 Subjects |
| VAR_HSA_F Group | Number of Subjects Reporting Fever | Fever (Axillary), Dose 2 : Related | 51 Subjects |
| VAR_HSA_F Group | Number of Subjects Reporting Fever | Fever (Axillary), Dose 2 : ≥ 38 °C | 172 Subjects |
| VAR_HSA_F Group | Number of Subjects Reporting Fever | Fever (Axillary), Across Doses : ≥ 38 °C | 301 Subjects |
| VAR_HSA_F Group | Number of Subjects Reporting Fever | Fever (Axillary), Dose 1 : Related | 72 Subjects |
| VAR_HSA_F Group | Number of Subjects Reporting Fever | Fever (Axillary), Across Doses : > 39.5 °C | 57 Subjects |
| VAR_HSA_F Group | Number of Subjects Reporting Fever | Fever (Axillary), Dose 2 : > 39.5 °C | 23 Subjects |
| VAR_HSA_F Group | Number of Subjects Reporting Fever | Fever (Axillary), Across Doses : Related | 111 Subjects |
| VAR_HSA_F Group | Number of Subjects Reporting Fever | Fever (Axillary), Dose 1 : ≥ 38 °C | 205 Subjects |
| VAR Group | Number of Subjects Reporting Fever | Fever (Axillary), Across Doses : Related | 95 Subjects |
| VAR Group | Number of Subjects Reporting Fever | Fever (Axillary), Dose 1 : ≥ 38 °C | 188 Subjects |
| VAR Group | Number of Subjects Reporting Fever | Fever (Axillary), Dose 1 : > 39.5 °C | 27 Subjects |
| VAR Group | Number of Subjects Reporting Fever | Fever (Axillary), Dose 1 : Related | 51 Subjects |
| VAR Group | Number of Subjects Reporting Fever | Fever (Axillary), Dose 2 : ≥ 38 °C | 177 Subjects |
| VAR Group | Number of Subjects Reporting Fever | Fever (Axillary), Dose 2 : > 39.5 °C | 31 Subjects |
| VAR Group | Number of Subjects Reporting Fever | Fever (Axillary), Dose 2 : Related | 57 Subjects |
| VAR Group | Number of Subjects Reporting Fever | Fever (Axillary), Across Doses : ≥ 38 °C | 290 Subjects |
| VAR Group | Number of Subjects Reporting Fever | Fever (Axillary), Across Doses : > 39.5 °C | 53 Subjects |
Secondary
Number of Subjects Reporting Fever
Fever was defined as axillary temperature greater than or equal to (≥) 38.0°C (≥ 100.4°F)
Time frame: 15 days post each dose of varicella vaccination
Population: Analysis was performed on the Total Vaccinated cohort. Number of participants analysed corresponds to the subjects in the Total Vaccinated cohort with documented dose 15-days post each dose of varicella vaccination for each of the 2 groups (VAR\_HSA\_F Group and VAR Group)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| VAR_HSA_F Group | Number of Subjects Reporting Fever | Fever ≥ 38 °C following Dose 1 | 83 Subjects |
| VAR_HSA_F Group | Number of Subjects Reporting Fever | Fever ≥ 38 °C following Dose 2 | 83 Subjects |
| VAR Group | Number of Subjects Reporting Fever | Fever ≥ 38 °C following Dose 1 | 92 Subjects |
| VAR Group | Number of Subjects Reporting Fever | Fever ≥ 38 °C following Dose 2 | 86 Subjects |
Secondary
Number of Subjects Reporting Rash
Any rash = occurrence of the specified solicited general symptom regardless of its intensity. Grade 3 rash = rash which prevented normal, everyday activities. Related rash = assessed by the investigator as causally related to study vaccination
Time frame: 43-day post vaccination period following Dose 1 (Day 0) and Dose 2 (Day 42)
Population: Analysis was performed on the Total Vaccinated cohort. Number of participants analysed corresponds to the subjects in the Total Vaccinated cohort with at least one documented dose 43 days following each vaccination and across doses for each of the 2 groups (VAR\_HSA\_F Group and VAR Group)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| VAR_HSA_F Group | Number of Subjects Reporting Rash | Any, Across Doses : Related | 28 Subjects |
| VAR_HSA_F Group | Number of Subjects Reporting Rash | Any, Dose 1 : Localised or generalised | 89 Subjects |
| VAR_HSA_F Group | Number of Subjects Reporting Rash | Any, Dose 1 : With fever | 32 Subjects |
| VAR_HSA_F Group | Number of Subjects Reporting Rash | Any, Dose 1 : Varicella like | 7 Subjects |
| VAR_HSA_F Group | Number of Subjects Reporting Rash | Any, Dose 1 : Grade 3 | 2 Subjects |
| VAR_HSA_F Group | Number of Subjects Reporting Rash | Any, Dose 1 : Related | 16 Subjects |
| VAR_HSA_F Group | Number of Subjects Reporting Rash | Localised, Dose 1 : Any | 65 Subjects |
| VAR_HSA_F Group | Number of Subjects Reporting Rash | Localised, Dose 1 : Administration site | 4 Subjects |
| VAR_HSA_F Group | Number of Subjects Reporting Rash | Localised, Dose 1 : Other site | 63 Subjects |
| VAR_HSA_F Group | Number of Subjects Reporting Rash | Localised, Dose 1 : With fever | 18 Subjects |
| VAR_HSA_F Group | Number of Subjects Reporting Rash | Localised, Dose 1 : Varicella like | 5 Subjects |
| VAR_HSA_F Group | Number of Subjects Reporting Rash | Localised, Dose 1 : Grade 3 | 2 Subjects |
| VAR_HSA_F Group | Number of Subjects Reporting Rash | Localised, Dose 1 : Related | 11 Subjects |
| VAR_HSA_F Group | Number of Subjects Reporting Rash | Generalised, Dose 1 : Any | 29 Subjects |
| VAR_HSA_F Group | Number of Subjects Reporting Rash | Generalised, Dose 1 : With fever | 14 Subjects |
| VAR_HSA_F Group | Number of Subjects Reporting Rash | Generalised, Dose 1 : Varicella like | 2 Subjects |
| VAR_HSA_F Group | Number of Subjects Reporting Rash | Generalised, Dose 1 : Grade 3 | 0 Subjects |
| VAR_HSA_F Group | Number of Subjects Reporting Rash | Generalised, Dose 1 : Related | 5 Subjects |
| VAR_HSA_F Group | Number of Subjects Reporting Rash | Any, Dose 2 : Localised or generalised | 76 Subjects |
| VAR_HSA_F Group | Number of Subjects Reporting Rash | Any, Dose 2 : With fever | 27 Subjects |
| VAR_HSA_F Group | Number of Subjects Reporting Rash | Any, Dose 2 : Varicella like | 4 Subjects |
| VAR_HSA_F Group | Number of Subjects Reporting Rash | Any, Dose 2 : Grade 3 | 2 Subjects |
| VAR_HSA_F Group | Number of Subjects Reporting Rash | Any, Dose 2 : Related | 15 Subjects |
| VAR_HSA_F Group | Number of Subjects Reporting Rash | Localised, Dose 2 : Any | 52 Subjects |
| VAR_HSA_F Group | Number of Subjects Reporting Rash | Localised, Dose 2 : Administration site | 1 Subjects |
| VAR_HSA_F Group | Number of Subjects Reporting Rash | Localised, Dose 2 : Other site | 51 Subjects |
| VAR_HSA_F Group | Number of Subjects Reporting Rash | Localised, Dose 2 : With fever | 16 Subjects |
| VAR_HSA_F Group | Number of Subjects Reporting Rash | Localised, Dose 2 : Varicella like | 3 Subjects |
| VAR_HSA_F Group | Number of Subjects Reporting Rash | Localised, Dose 2 : Grade 3 | 1 Subjects |
| VAR_HSA_F Group | Number of Subjects Reporting Rash | Localised, Dose 2 : Related | 12 Subjects |
| VAR_HSA_F Group | Number of Subjects Reporting Rash | Generalised, Dose 2 : Any | 25 Subjects |
| VAR_HSA_F Group | Number of Subjects Reporting Rash | Generalised, Dose 2 : With fever | 11 Subjects |
| VAR_HSA_F Group | Number of Subjects Reporting Rash | Generalised, Dose 2 : Varicella like | 1 Subjects |
| VAR_HSA_F Group | Number of Subjects Reporting Rash | Generalised, Dose 2 : Grade 3 | 1 Subjects |
| VAR_HSA_F Group | Number of Subjects Reporting Rash | Generalised, Dose 2 : Related | 3 Subjects |
| VAR_HSA_F Group | Number of Subjects Reporting Rash | Any, Across Doses : Localised or generalised | 144 Subjects |
| VAR_HSA_F Group | Number of Subjects Reporting Rash | Any, Across Doses : With fever | 55 Subjects |
| VAR_HSA_F Group | Number of Subjects Reporting Rash | Any, Across Doses : Varicella like | 11 Subjects |
| VAR_HSA_F Group | Number of Subjects Reporting Rash | Any, Across Doses : Grade 3 | 4 Subjects |
| VAR_HSA_F Group | Number of Subjects Reporting Rash | Localised, Across Doses : Related | 20 Subjects |
| VAR_HSA_F Group | Number of Subjects Reporting Rash | Localised, Across Doses : Any | 106 Subjects |
| VAR_HSA_F Group | Number of Subjects Reporting Rash | Localised, Across Doses : Administration site | 5 Subjects |
| VAR_HSA_F Group | Number of Subjects Reporting Rash | Localised, Across Doses : Other site | 103 Subjects |
| VAR_HSA_F Group | Number of Subjects Reporting Rash | Localised, Across Doses : With fever | 32 Subjects |
| VAR_HSA_F Group | Number of Subjects Reporting Rash | Localised, Across Doses : Varicella like | 8 Subjects |
| VAR_HSA_F Group | Number of Subjects Reporting Rash | Localised, Across Doses : Grade 3 | 3 Subjects |
| VAR_HSA_F Group | Number of Subjects Reporting Rash | Generalised, Across Doses : Any | 49 Subjects |
| VAR_HSA_F Group | Number of Subjects Reporting Rash | Generalised, Across Doses : With fever | 24 Subjects |
| VAR_HSA_F Group | Number of Subjects Reporting Rash | Generalised, Across Doses : Varicella like | 3 Subjects |
| VAR_HSA_F Group | Number of Subjects Reporting Rash | Generalised, Across Doses : Grade 3 | 1 Subjects |
| VAR_HSA_F Group | Number of Subjects Reporting Rash | Generalised, Across Doses : Related | 8 Subjects |
| VAR Group | Number of Subjects Reporting Rash | Localised, Across Doses : Grade 3 | 2 Subjects |
| VAR Group | Number of Subjects Reporting Rash | Localised, Dose 2 : With fever | 23 Subjects |
| VAR Group | Number of Subjects Reporting Rash | Any, Dose 1 : Localised or generalised | 104 Subjects |
| VAR Group | Number of Subjects Reporting Rash | Any, Across Doses : Related | 37 Subjects |
| VAR Group | Number of Subjects Reporting Rash | Any, Dose 1 : With fever | 27 Subjects |
| VAR Group | Number of Subjects Reporting Rash | Localised, Dose 2 : Varicella like | 2 Subjects |
| VAR Group | Number of Subjects Reporting Rash | Any, Dose 1 : Varicella like | 9 Subjects |
| VAR Group | Number of Subjects Reporting Rash | Localised, Across Doses : Related | 21 Subjects |
| VAR Group | Number of Subjects Reporting Rash | Any, Dose 1 : Grade 3 | 4 Subjects |
| VAR Group | Number of Subjects Reporting Rash | Localised, Dose 2 : Grade 3 | 1 Subjects |
| VAR Group | Number of Subjects Reporting Rash | Any, Dose 1 : Related | 23 Subjects |
| VAR Group | Number of Subjects Reporting Rash | Localised, Across Doses : Any | 112 Subjects |
| VAR Group | Number of Subjects Reporting Rash | Localised, Dose 1 : Any | 74 Subjects |
| VAR Group | Number of Subjects Reporting Rash | Localised, Dose 2 : Related | 9 Subjects |
| VAR Group | Number of Subjects Reporting Rash | Localised, Dose 1 : Administration site | 2 Subjects |
| VAR Group | Number of Subjects Reporting Rash | Generalised, Across Doses : Varicella like | 9 Subjects |
| VAR Group | Number of Subjects Reporting Rash | Localised, Dose 1 : Other site | 72 Subjects |
| VAR Group | Number of Subjects Reporting Rash | Generalised, Dose 2 : Any | 26 Subjects |
| VAR Group | Number of Subjects Reporting Rash | Localised, Dose 1 : With fever | 12 Subjects |
| VAR Group | Number of Subjects Reporting Rash | Localised, Across Doses : Administration site | 6 Subjects |
| VAR Group | Number of Subjects Reporting Rash | Localised, Dose 1 : Varicella like | 4 Subjects |
| VAR Group | Number of Subjects Reporting Rash | Generalised, Dose 2 : With fever | 12 Subjects |
| VAR Group | Number of Subjects Reporting Rash | Localised, Dose 1 : Grade 3 | 1 Subjects |
| VAR Group | Number of Subjects Reporting Rash | Generalised, Across Doses : Any | 57 Subjects |
| VAR Group | Number of Subjects Reporting Rash | Localised, Dose 1 : Related | 13 Subjects |
| VAR Group | Number of Subjects Reporting Rash | Generalised, Dose 2 : Varicella like | 3 Subjects |
| VAR Group | Number of Subjects Reporting Rash | Generalised, Dose 1 : Any | 35 Subjects |
| VAR Group | Number of Subjects Reporting Rash | Localised, Across Doses : Other site | 107 Subjects |
| VAR Group | Number of Subjects Reporting Rash | Generalised, Dose 1 : With fever | 15 Subjects |
| VAR Group | Number of Subjects Reporting Rash | Generalised, Dose 2 : Grade 3 | 4 Subjects |
| VAR Group | Number of Subjects Reporting Rash | Generalised, Dose 1 : Varicella like | 6 Subjects |
| VAR Group | Number of Subjects Reporting Rash | Generalised, Across Doses : Related | 19 Subjects |
| VAR Group | Number of Subjects Reporting Rash | Generalised, Dose 1 : Grade 3 | 3 Subjects |
| VAR Group | Number of Subjects Reporting Rash | Generalised, Dose 2 : Related | 8 Subjects |
| VAR Group | Number of Subjects Reporting Rash | Generalised, Dose 1 : Related | 11 Subjects |
| VAR Group | Number of Subjects Reporting Rash | Localised, Across Doses : With fever | 34 Subjects |
| VAR Group | Number of Subjects Reporting Rash | Any, Dose 2 : Localised or generalised | 78 Subjects |
| VAR Group | Number of Subjects Reporting Rash | Any, Across Doses : Localised or generalised | 152 Subjects |
| VAR Group | Number of Subjects Reporting Rash | Any, Dose 2 : With fever | 34 Subjects |
| VAR Group | Number of Subjects Reporting Rash | Generalised, Across Doses : With fever | 27 Subjects |
| VAR Group | Number of Subjects Reporting Rash | Any, Dose 2 : Varicella like | 5 Subjects |
| VAR Group | Number of Subjects Reporting Rash | Any, Across Doses : With fever | 59 Subjects |
| VAR Group | Number of Subjects Reporting Rash | Any, Dose 2 : Grade 3 | 5 Subjects |
| VAR Group | Number of Subjects Reporting Rash | Localised, Across Doses : Varicella like | 6 Subjects |
| VAR Group | Number of Subjects Reporting Rash | Any, Dose 2 : Related | 16 Subjects |
| VAR Group | Number of Subjects Reporting Rash | Any, Across Doses : Varicella like | 14 Subjects |
| VAR Group | Number of Subjects Reporting Rash | Localised, Dose 2 : Any | 57 Subjects |
| VAR Group | Number of Subjects Reporting Rash | Generalised, Across Doses : Grade 3 | 7 Subjects |
| VAR Group | Number of Subjects Reporting Rash | Localised, Dose 2 : Administration site | 4 Subjects |
| VAR Group | Number of Subjects Reporting Rash | Any, Across Doses : Grade 3 | 9 Subjects |
| VAR Group | Number of Subjects Reporting Rash | Localised, Dose 2 : Other site | 53 Subjects |
Secondary
Number of Subjects Reporting Serious Adverse Events (SAEs)
SAEs assessed included medical occurrences that resulted in death, were life threatening, required hospitalisation or prolongation of hospitalisation or resulted in disability/incapacity. Any SAE = occurrence of SAE regardless of intensity grade or relation to vaccination
Time frame: From Day 0 through the end of study (Day 84)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| VAR_HSA_F Group | Number of Subjects Reporting Serious Adverse Events (SAEs) | 13 Subjects |
| VAR Group | Number of Subjects Reporting Serious Adverse Events (SAEs) | 15 Subjects |
Secondary
Number of Subjects Reporting Solicited Local Symptoms
Solicited local symptoms assessed were pain, injection site redness and swelling. Any = occurrence of the specified solicited local symptom regardless of its intensity. Grade 3 pain = subject crying when limb was moved or as spontaneously painful. Grade 3 redness and swelling = above (\>) 20 mm
Time frame: 4-day post vaccination period following Dose 1 (Day 0) and Dose 2 (Day 42)
Population: Analysis was performed on the Total Vaccinated cohort. Number of participants analysed corresponds to the subjects in the Total Vaccinated cohort with at least one documented dose 4 days following each vaccination and across doses for each of the 2 groups (VAR\_HSA\_F Group and VAR Group)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| VAR_HSA_F Group | Number of Subjects Reporting Solicited Local Symptoms | Any Pain, Dose 1 | 75 Subjects |
| VAR_HSA_F Group | Number of Subjects Reporting Solicited Local Symptoms | Grade 3 Pain, Dose 1 | 2 Subjects |
| VAR_HSA_F Group | Number of Subjects Reporting Solicited Local Symptoms | Any Redness, Dose 1 | 149 Subjects |
| VAR_HSA_F Group | Number of Subjects Reporting Solicited Local Symptoms | Grade 3 Redness, Dose 1 | 3 Subjects |
| VAR_HSA_F Group | Number of Subjects Reporting Solicited Local Symptoms | Any Swelling, Dose 1 | 43 Subjects |
| VAR_HSA_F Group | Number of Subjects Reporting Solicited Local Symptoms | Grade 3 Swelling, Dose 1 | 2 Subjects |
| VAR_HSA_F Group | Number of Subjects Reporting Solicited Local Symptoms | Any Pain, Dose 2 | 63 Subjects |
| VAR_HSA_F Group | Number of Subjects Reporting Solicited Local Symptoms | Grade 3 Pain, Dose 2 | 1 Subjects |
| VAR_HSA_F Group | Number of Subjects Reporting Solicited Local Symptoms | Any Redness, Dose 2 | 168 Subjects |
| VAR_HSA_F Group | Number of Subjects Reporting Solicited Local Symptoms | Grade 3 Redness, Dose 2 | 10 Subjects |
| VAR_HSA_F Group | Number of Subjects Reporting Solicited Local Symptoms | Any Swelling, Dose 2 | 69 Subjects |
| VAR_HSA_F Group | Number of Subjects Reporting Solicited Local Symptoms | Grade 3 Swelling, Dose 2 | 1 Subjects |
| VAR_HSA_F Group | Number of Subjects Reporting Solicited Local Symptoms | Any Pain, Across Doses | 101 Subjects |
| VAR_HSA_F Group | Number of Subjects Reporting Solicited Local Symptoms | Grade 3 Pain, Across Doses | 3 Subjects |
| VAR_HSA_F Group | Number of Subjects Reporting Solicited Local Symptoms | Any Redness, Across Doses | 224 Subjects |
| VAR_HSA_F Group | Number of Subjects Reporting Solicited Local Symptoms | Grade 3 Redness, Across Doses | 13 Subjects |
| VAR_HSA_F Group | Number of Subjects Reporting Solicited Local Symptoms | Any Swelling, Across Doses | 92 Subjects |
| VAR_HSA_F Group | Number of Subjects Reporting Solicited Local Symptoms | Grade 3 Swelling, Across Doses | 3 Subjects |
| VAR Group | Number of Subjects Reporting Solicited Local Symptoms | Grade 3 Pain, Across Doses | 5 Subjects |
| VAR Group | Number of Subjects Reporting Solicited Local Symptoms | Any Pain, Dose 1 | 86 Subjects |
| VAR Group | Number of Subjects Reporting Solicited Local Symptoms | Grade 3 Redness, Dose 2 | 8 Subjects |
| VAR Group | Number of Subjects Reporting Solicited Local Symptoms | Grade 3 Pain, Dose 1 | 4 Subjects |
| VAR Group | Number of Subjects Reporting Solicited Local Symptoms | Grade 3 Swelling, Across Doses | 4 Subjects |
| VAR Group | Number of Subjects Reporting Solicited Local Symptoms | Any Redness, Dose 1 | 150 Subjects |
| VAR Group | Number of Subjects Reporting Solicited Local Symptoms | Any Swelling, Dose 2 | 71 Subjects |
| VAR Group | Number of Subjects Reporting Solicited Local Symptoms | Grade 3 Redness, Dose 1 | 2 Subjects |
| VAR Group | Number of Subjects Reporting Solicited Local Symptoms | Any Redness, Across Doses | 234 Subjects |
| VAR Group | Number of Subjects Reporting Solicited Local Symptoms | Any Swelling, Dose 1 | 42 Subjects |
| VAR Group | Number of Subjects Reporting Solicited Local Symptoms | Grade 3 Swelling, Dose 2 | 4 Subjects |
| VAR Group | Number of Subjects Reporting Solicited Local Symptoms | Grade 3 Swelling, Dose 1 | 1 Subjects |
| VAR Group | Number of Subjects Reporting Solicited Local Symptoms | Any Swelling, Across Doses | 94 Subjects |
| VAR Group | Number of Subjects Reporting Solicited Local Symptoms | Any Pain, Dose 2 | 80 Subjects |
| VAR Group | Number of Subjects Reporting Solicited Local Symptoms | Any Pain, Across Doses | 126 Subjects |
| VAR Group | Number of Subjects Reporting Solicited Local Symptoms | Grade 3 Pain, Dose 2 | 1 Subjects |
| VAR Group | Number of Subjects Reporting Solicited Local Symptoms | Grade 3 Redness, Across Doses | 10 Subjects |
| VAR Group | Number of Subjects Reporting Solicited Local Symptoms | Any Redness, Dose 2 | 185 Subjects |
Secondary
Number of Subjects Reporting Unsolicited Adverse Events (AEs)
Unsolicited AE covers any AE 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 = occurrence of any unsolicited symptom regardless of intensity grade or relation to vaccination
Time frame: 43-day post vaccination period following Dose 1 (Day 0) and Dose 2 (Day 42)
Population: Analysis was performed on the Total Vaccinated cohort. Number of participants analysed corresponds to the subjects in the Total Vaccinated cohort with the administered dose 43 days following each vaccination and across doses for each of the 2 groups (VAR\_HSA\_F Group and VAR Group)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| VAR_HSA_F Group | Number of Subjects Reporting Unsolicited Adverse Events (AEs) | Post Dose 1 | 270 Subjects |
| VAR_HSA_F Group | Number of Subjects Reporting Unsolicited Adverse Events (AEs) | Post Dose 2 | 223 Subjects |
| VAR Group | Number of Subjects Reporting Unsolicited Adverse Events (AEs) | Post Dose 1 | 282 Subjects |
| VAR Group | Number of Subjects Reporting Unsolicited Adverse Events (AEs) | Post Dose 2 | 220 Subjects |
Secondary
Number of Subjects With a Seroresponse to VZV (Immuno Sub Cohort)
For VZV, seroresponse was defined as, post-vaccination anti-VZV antibody concentration ≥ 50 mIU/mL among subjects who were seronegative (antibody concentration below (\< ) 25 mIU/mL) before vaccination
Time frame: At Day 42 and Day 84 post vaccination
Population: Immunogenicity analyses were performed on the According-to-protocol (ATP) cohort for immunogenicity. Seropositivity was assessed in sub cohort of the ATP cohort for immunogenicity for each group (immuno sub cohort) who had blood taken and tested for anti-varicella antibodies at Day 0, Day 42, and Day 84
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| VAR_HSA_F Group | Number of Subjects With a Seroresponse to VZV (Immuno Sub Cohort) | ≥ 25 mIU/mL (At Day 42) | 184 Subjects |
| VAR_HSA_F Group | Number of Subjects With a Seroresponse to VZV (Immuno Sub Cohort) | ≥ 50 mIU/mL (At Day 42) | 174 Subjects |
| VAR_HSA_F Group | Number of Subjects With a Seroresponse to VZV (Immuno Sub Cohort) | ≥ 25 mIU/mL (At Day 84) | 180 Subjects |
| VAR_HSA_F Group | Number of Subjects With a Seroresponse to VZV (Immuno Sub Cohort) | ≥ 50 mIU/mL (At Day 84) | 180 Subjects |
| VAR Group | Number of Subjects With a Seroresponse to VZV (Immuno Sub Cohort) | ≥ 50 mIU/mL (At Day 84) | 173 Subjects |
| VAR Group | Number of Subjects With a Seroresponse to VZV (Immuno Sub Cohort) | ≥ 25 mIU/mL (At Day 42) | 168 Subjects |
| VAR Group | Number of Subjects With a Seroresponse to VZV (Immuno Sub Cohort) | ≥ 25 mIU/mL (At Day 84) | 173 Subjects |
| VAR Group | Number of Subjects With a Seroresponse to VZV (Immuno Sub Cohort) | ≥ 50 mIU/mL (At Day 42) | 166 Subjects |