A Safety and Immune Study of 2 Types of GlaxoSmithKline's Varicella Vaccines Given as a 2-doses Course to Healthy Children 12-23 Months of Age.

Study Overview
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Brief Summary
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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
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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).

Official Title
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Safety and Immunogenicity Study of 2 Formulations of GSK Biologicals' Varicella Vaccines Given as a 2-dose Course in the Second Year of Life.

Conditions
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Chicken-pox Illness (Varicella Virus Disease), Chickenpox

Intervention / Treatment
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* Biological: Varilrix HSA-free
* Biological: Varilrix™


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 12 Months
Maximum Age: 23 Months

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: VAR_HSA_F Group<br>2 doses of Varilrix HSA-free vaccine, one at Visit 1 (Day 0) and the other at Visit 2 (Day 42), will be given to the subjects in this group. The vaccine will be administered subcutaneously in the triceps region of the left arm | Biological: Varilrix HSA-free<br>* 2 doses will be administered, one at Day 0 and the other at Day 42<br>|
| Active Comparator: VAR Group<br>2 doses of Varilrix™ vaccine, one at Visit 1 (Day 0) and the other at Visit 2 (Day 42), will be given to the subjects in this group. The vaccine will be administered subcutaneously in the triceps region of the left arm | Biological: Varilrix™<br>* 2 doses will be administered, one at Day 0 and the other at Day 42<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects Reporting Fever | Fever was defined as axillary temperature above (>) 39.0 °C (> 102.2°F) | 15-days (Days 0-14) post Dose 1 of varicella vaccination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects Reporting Fever | Fever was defined as axillary temperature greater than or equal to (≥) 38.0°C (≥ 100.4°F) | 15 days post each dose of varicella vaccination | 
| 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) | At Day 42 and Day 84 post vaccination | 
| 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 | At Day 42 and Day 84 post vaccination | 
| 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 | 4-day post vaccination period following Dose 1 (Day 0) and Dose 2 (Day 42) | 
| 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 | 43-day post vaccination period following Dose 1 (Day 0) and Dose 2 (Day 42) | 
| 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 | 43-day post vaccination period following Dose 1 (Day 0) and Dose 2 (Day 42) | 
| 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 | 43-day post vaccination period following Dose 1 (Day 0) and Dose 2 (Day 42) | 
| 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 | 43-day post vaccination period following Dose 1 (Day 0) and Dose 2 (Day 42) | 
| 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 | From Day 0 through the end of study (Day 84) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Immunogenicity, Varicella, Safety, Human serum albumin, Healthy children, 12 to 23 months