Immunogenicity & Safety Study of GSK Biologicals' 208136 Vaccine Formulated With New Measles and Rubella Working Seeds

Study Overview
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Brief Summary
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This study is undertaken to generate clinical data on GSK Biologicals' combined measles-mumps-rubella-varicella vaccine manufactured with measles and rubella obtained from newly established working seed viruses which are one passage further than the current working seed viruses. The measles-mumps-rubella-varicella vaccine manufactured with the current working seed viruses will serve as comparator. A seed lot system is a system according to which successive batches of a vaccine are derived from the same master seed virus. For routine production, a working seed lot is prepared from the master seed virus.

Official Title
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Immunogenicity & Safety Study of GSK Biologicals' 208136 Vaccine Formulated With New Measles and Rubella Working Seeds

Conditions
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Measles, Varicella, Mumps, Rubella

Intervention / Treatment
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* Biological: Priorix-Tetra (combined measles-mumps-rubella-varicella vaccine)
* Biological: GSK Biologicals' 208136, new formulation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects who the investigator believes that their parents/guardians can and will comply with the requirements of the protocol (e.g. completion of the diary cards, return for follow-up visits) should be enrolled in the study. A male or female between, and including, 11 and 21 months of age (e.g. from age 11months until the day before age 22 months) at the time of the first vaccination. Written informed consent obtained from the parent or guardian of the subject after they have been advised on the risks and benefits of the study in a language they clearly understand, and before performance of any study procedure. Free of obvious healthy problems as established by medical history and clinical examination before entering into the study. Exclusion Criteria: 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. Chronic administration (defined as more than 14 days) of immunosuppressants or other immune-modifying drugs within six months prior to the first vaccine dose. Administration of immunoglobulins and/or any blood products during the six months before entering the study or planned administration during the study period. Planned administration/ administration of a vaccine not foreseen by the study protocol within 30 days prior to until 42 days after each study vaccine dose with the exception of oral polio vaccine (OPV) which can be given at any time and routine inactivated vaccines such as pneumococcal, meningococcal or Haemophilus influenzae type b conjugate vaccines, inactivated influenza or diphtheria/tetanus containing vaccines which can be administered up to eight days before each study vaccine dose. Previous vaccination against measles, mumps, rubella and/or varicella. History of measles, mumps, rubella and/or varicella/zoster diseases. Known exposure to measles, mumps, rubella and/or varicella within 30 days prior to study start. Any confirmed or suspected immunosuppressive or immunodeficient condition, including human immunodeficiency virus (HIV) infection. A family history of congenital or hereditary immunodeficiency. History of allergic disease or reactions likely to be exacerbated by any component of the vaccine(s), including systemic hypersensitivity to neomycin. Major congenital defects or serious chronic illness. History of any neurologic disorders or seizures. Acute disease at the time of enrolment. Rectal temperature ≥38°C or axillary temperature >=37.5°C at the time of vaccination. Residence in the same household as a high risk person e.g.: New-born infants (0-4 weeks of age) Pregnant women who have a negative history of chickenpox Persons with known immunodeficiency

Ages Eligible for Study
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Minimum Age: 11 Months
Maximum Age: 21 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: Priorix-Tetra new WS Group<br>Subjects received 2 doses of Priorix-Tetra vaccine formulated with new measles and rubella working seeds at Day 0 and Week 12. | Biological: GSK Biologicals' 208136, new formulation<br>* Vaccine will be administered subcutaneously in the left upper arm (deltoid region)<br>|
| Experimental: Priorix-Tetra current WS Group<br>Subjects received 2 doses of Priorix-Tetra vaccine manufactured with current working seed virus at Day 0 and Week 12. | Biological: Priorix-Tetra (combined measles-mumps-rubella-varicella vaccine)<br>* Vaccine will be administered subcutaneously in the left upper arm (deltoid region)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects Seroconverted for Measles, Mumps, Rubella and Varicella Antibodies Greater Than or Equal to (≥) the Cut-off Value. | Seroconversion was defined as the appearance of antibodies in the serum of subjects seronegative before vaccination. The cut-off values for seroconversion was 150 milli international units per milliliter (mIU/mL), 231 units per milliliter (U/mL), 4 international units per milliliter (IU/mL) and 1:4 dilution for measles, mumps, rubella and varicella, respectively. | At 42-56 days after the first dose of study vaccine (Week 6) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects Seroconverted for Measles, Mumps, Rubella and Varicella Antibodies ≥ the Cut-off Value. | Seroconversion was defined as the appearance of antibodies in the serum of subjects seronegative before vaccination. The cut-off values for seroconversion was 150 mIU/mL, 231 U/mL, 4 IU/mL and 1:4 dilution for measles, mumps, rubella and varicella, respectively. | At 42-56 days after the second dose of study vaccine (Week 18) | 
| Antibody Titers Against Measles, Mumps, Rubella and Varicella Viruses | Antibody titers were summarized by geometric mean titers (GMTs) with their 95% confidence intervals. | At 42-56 days after the first and second dose of study vaccine(s). | 
| Number of Subjects Reporting Any and Grade 3 Solicited Local Symptoms | Assessed solicited local symptoms were pain, redness and swelling. Any = occurrence of the symptom regardless of intensity grade. Grade 3 pain = cried when limb was moved/ spontaneously painful. Grade 3 redness/ swelling = redness/ swelling spreading beyond 20 millimeters (mm) of injection site. | Within 4 days after each vaccination (Days 0-3) | 
| Number of Subjects Reporting Any and Grade 3 Solicited General Symptoms | Assessed solicited general symptoms were meningism and parotid gland swelling. Any = occurrence of the symptom regardless of intensity grade. Grade 3 meningism and parotid gland swelling = meningism/ parotid gland swelling which prevented normal everyday activities. | Within 43 days (Days 0-42) after each vaccination | 
| Number of Subjects Reporting Any, Grade 3 and Related Fever | Any fever was defined as fever greater than or equal to (≥) 38.0 Celsius degrees (°C) and grade 3 fever greater than (>) 39.5°C after vaccination. Related fever was defined as fever assessed by the investigator as related to the vaccination. | Within 43 days (Days 0-42) after each vaccination | 
| Number of Subjects Reporting Any (Local or General), Grade 3 and Related Rashes | Rash was defined as: 1) measles/ rubella rashes (macular or maculo-papular rashes): presence of macules, discolored small patches or spots of the skin, neither elevated nor depressed below the skin's surface; 2) varicella rash (maculo-papulo-vesicular): simultaneous presence of macules, papules and vesicles raised above the skin's surface; 3) other types of rash (heat rash, diaper rash etc.). Any rash = occurrence of rash regardless of intensity grade or relationship to vaccination Grade 3 rash ≥ 150 lesions and Related = rash assessed by the investigator as related to the vaccination. | Within 43 days (Days 0-42) after each vaccination | 
| Number of Subjects Reporting Any, Grade 3 and Related Unsolicited Adverse Event (AEs) | An unsolicited AE covers any untoward medical occurrence in a clinical investigation subject temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Any was defined as an adverse event (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 was reported as an unsolicited adverse event. Grade 3 was defined as an event that prevented normal activity and Related was defined as an event assessed by the investigator as causally related to the study vaccination. | Within 43 days (Days 0-42) after first vaccination dose | 
| Number of Subjects Reporting Any, Grade 3 and Related Unsolicited Adverse Event (AEs) | An unsolicited AE covers any untoward medical occurrence in a clinical investigation subject temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Any was defined as an adverse event (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 was reported as an unsolicited adverse event. Grade 3 was defined as an event that prevented normal activity and Related was defined as an event assessed by the investigator as causally related to the study vaccination. | Within 43 days (Days 86-128) after second vaccination dose | 
| Number of Subjects With Serious Adverse Events (SAEs) | Serious adverse events (SAEs) assessed included medical occurrences that resulted in death, were life threatening, required hospitalization or prolongation of existing hospitalization, resulted in disability/ incapacity or is a congenital anomaly/ birth defect in the offspring of a study subject. | From first study dose (Day 0) until study end (Week 18) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Working seed virus, Rubella, Mumps, Varicella, Combined measles-mumps-rubella-varicella vaccine, Pediatric immunization, Measles