Comparison of GSK Measles-mumps-rubella-varicella (MMRV) Vaccine Versus PriorixTM

Study Overview
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Brief Summary
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The purpose of this study is to assess non-inferiority of two different vaccination regimens using GSK Biological's MMRV vaccine (two doses at 9 and 15 months) or Priorix™ (9 months) and one dose of MMRV vaccine (15 months) to the current standard of care which is Priorix™ administered at 9 months of age followed by concomitant administration of Priorix™ with Varilrix™ at 15 months of age in a measles endemic environment such as India.

Official Title
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A Phase IIIb, Open, Randomised, Multicentre, Primary Study in Healthy Children, to Establish the Non-inferiority of GlaxoSmithKline (GSK) Biologicals' MeMuRu-OKA Vaccine (Administered at 9 and 15 Months of Age) Versus Priorix™ (9 Months of Age) and Priorix™ Co-administered With Varilrix™ at 15 Months of Age (Comparator) and Also to Evaluate the Non-inferiority of Priorix™ (9 Months of Age) and MeMuRu-OKA Vaccine (15 Months of Age) Versus the Comparator, All Administered Subcutaneously as Two-dose Primary Vaccination Course

Conditions
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Varicella, Rubella, Mumps, Measles

Intervention / Treatment
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* Biological: GSK Biological's investigational MMRV vaccine 208136
* Biological: Priorix™
* Biological: Varilrix™


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 should be enrolled in the study. Male or female subjects between and including 9 and 10 months of age at the time of the first vaccination. Written informed consent obtained from the the parent or guardian of the subject. Healthy subjects as established by medical history and clinical examination before entering into the study. Exclusion Criteria: Use of any investigational or non-registered product other than the study vaccines within 30 days preceding the first dose of study vaccine, or planned use during the study period. Chronic administration of immunosuppressants or other immune-modifying drugs within six months prior to the first vaccine dose. Planned administration/administration of a vaccine not foreseen by the study protocol starting 30 days prior to administration of any dose of the study vaccine, up to 42 days after the vaccine dose with the exception of hepatitis A vaccine and oral poliovirus vaccine . Concurrently participating 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-registered product. Previous vaccination against measles, mumps, rubella and varicella. History of measles, mumps, rubella and/or varicella diseases. Known exposure to measles, mumps, rubella and/or varicella within 30 days prior to the start of the study. Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination. 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 neomycin. Major congenital defects or serious chronic illness. History of any neurologic disorders or seizures. Acute disease at the time of enrolment. Axillary temperature > 37.5°C (99.5°F) / Rectal temperature > 38°C (100.4°F). Administration of immunoglobulins and/or any blood products during the six months before entering the study or planned administration during the study period. Presence of a susceptible high-risk person in the same household during the study period.

Ages Eligible for Study
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Minimum Age: 9 Months
Maximum Age: 10 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Priorix-Tetra Group<br>Subjects received 2 doses of Priorix-Tetra® vaccine, 1 at Day 0 and 1 at Month 6, administered subcutaneously in the left anterolateral thigh. | Biological: GSK Biological's investigational MMRV vaccine 208136<br>* Subcutaneous injection<br>|
| Experimental: Priorix/ Priorix-Tetra Group<br>Subjects received 1 dose of Priorix™ vaccine at Day 0 and 1 dose of Priorix-Tetra® vaccine at Month 6, both administered subcutaneously in the left anterolateral thigh. | Biological: GSK Biological's investigational MMRV vaccine 208136<br>* Subcutaneous injection<br>Biological: Priorix™<br>* Subcutaneous injection<br>|
| Active Comparator: Control Group<br>Subjects received 1 dose of Priorix™ vaccine at Day 0 and 1 dose of Priorix™ vaccine co-administered with Varilirix™ vaccine at Month 6, administered subcutaneously in the left and right anterolateral thigh. | Biological: Priorix™<br>* Subcutaneous injection<br>Biological: Varilrix™<br>* Subcutaneous injection<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 | Seroconversion was defined as the appearance of antibodies [i.e. concentration/titre greater than or equal to (≥) the cut-off value] in the serum of subjects seronegative before vaccination. The cut-off values for seroconversion were 150 milli-international units per milliliter (mIU/mL), 231 units per milliliter (U/mL), 4 international units per milliliter (IU/mL) and for immunoglobulin G (IgG) varicella antibodies 1:4 dilution for measles, mumps, rubella and varicella, respectively. | At 42 - 56 days after the second vaccination dose at week 30 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Seroconverted Subjects for Measles, Mumps, Rubella and Varicella Antibodies | Seroconversion was defined as the appearance of antibodies (i.e. concentration/titre ≥ the cut-off value) in the serum of subjects seronegative before vaccination. The cut-off values for seroconversion were 150 mIU/mL, 231 U/mL, 4 IU/mL and for IgG varicella antibodies 1:4 dilution for measles, mumps, rubella and varicella, respectively. | Approximately 42 to 56 days after the first vaccine dose at week 6 | 
| Antibody Concentrations Against Measles, Mumps, Rubella and Varicella Viruses | Antibody concentrations were summarized by geometric mean concentrations (GMCs) with their 95% confidence intervals (CIs). | At 42 - 56 days after the first (at Week 6) and second (at Week 30) vaccination dose | 
| 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. | During the 4-day (Days 0-3) post-vaccination period following each dose (Dose 1 and Dose 2) | 
| Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms | Assessed solicited general symptoms were meningism and parotid gland swelling. Any = occurrence of the symptom regardless of intensity grade or relationship to vaccination. Grade 3 meningism and parotid gland swelling = meningism/parotid gland swelling which prevented normal everyday activities. Related = symptom assessed by the investigator as related to the vaccination. | During the 43-day (Days 0-42) post-vaccination period following each dose (Dose 1 and Dose 2) | 
| Number of Subjects Reporting Any, Grade 3 and Related Fever | Any fever was defined as fever ≥ 38.0°C and grade 3 fever was defined as fever > 39.5°C after vaccination. Related fever was defined as fever assessed by the investigator as related to the vaccination. | During the 43-day (Days 0-42) post-vaccination period following each dose (Dose 1 and Dose 2) | 
| Number of Subjects Reporting Any, Grade 3 and Related Rash | Any rash was defined as incidence of a rash regardless of intensity grade or relationship to vaccination and grade 3 rash greater than (>) 150 lesions. Related rash was defined as rash assessed by the investigator as causally related to the vaccination | During the 43-day (Days 0-42) post-vaccination period following each dose (Dose 1 and Dose 2) | 
| Number of Subjects Reporting Any Unsolicited Adverse Event | An unsolicited Adverse Event (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 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. | Within 43-day (Days 0-42) after the first and second vaccination dose | 
| Number of Subjects With Serious Adverse Events (SAEs) | Serious adverse events (SAEs) assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization, result in disability/incapacity or congenital anomaly/birth defect in the offspring of a study subject. | From the first study dose up to study end (Month 0 to Month 7.5 approximately) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Measles, Mumps, Immunogenicity, Vaccines, Safety, Rubella, Combined Vaccine, Varicella Vaccine, Children, Humans