Immunogenicity and Safety of GlaxoSmithKline Biologicals' MMRV Vaccine vs. ProQuad® in Children 12-14 Months of Age

Study Overview
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Brief Summary
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The purpose of this observer blinded study is to provide information on vaccine immunogenicity and reactogenicity in comparison with the US standard of care (ProQuad®) when administered with Hepatitis A vaccine and Pneumococcal vaccine.

Official Title
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Immunogenicity of GlaxoSmithKline Biologicals' MMRV Vaccine (208136) vs. ProQuad®, When Coadministered With Hepatitis A and Pneumococcal Conjugate Vaccines to Children 12-14 Months of Age.

Conditions
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Varicella, Rubella, Mumps, Measles

Intervention / Treatment
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* Biological: Priorix-Tetra™ (MMRV vaccine 208136)
* Biological: ProQuad®
* Biological: Havrix®
* Biological: Prevnar®


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects for whom the investigator believes their parents/guardians can and will comply with the requirements of the protocol. Male or female between 12 and 14 months of age at the time of first vaccination. Written informed consent obtained from the parent/guardian of the subject. Healthy subjects as established by medical history and clinical examination before entering into the study. Have previously received 3 doses of 7-valent pneumococcal conjugate vaccine within the first year of life. Exclusion Criteria: Use of any investigational or non-registered product other than the study vaccine(s) within 30 days preceding the first dose of study vaccine, or planned use during the study period. 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-investigational product. 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 from 30 days prior to vaccination until 42 days after vaccination, except for influenza vaccine. Previous vaccination against measles, mumps, rubella and/or varicella. Previous vaccination against hepatitis A or receipt of a fourth dose of pneumococcal conjugate vaccine. History of measles, mumps, rubella and/or varicella/zoster diseases. Known exposure to measles, mumps, rubella and/or varicella/zoster 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, including human immunodeficiency virus infection. A family history of congenital or hereditary immunodeficiency. History of allergic disease or reactions likely to be exacerbated by any component of the vaccines. Major congenital defects or serious chronic illness. History of any neurologic disorders or seizures. Uncomplicated febrile convulsions are not an exclusion criterion. Residence in the same household as the following persons: New-born infants (0-4 weeks of age). Pregnant mother/women with a negative history of chickenpox disease and without recorded vaccination against chickenpox. Pregnant women at or beyond 28 weeks gestation regardless of varicella vaccination status or varicella disease history. Persons with known immunodeficiency. Acute disease at the time of enrolment. All vaccines can be administered to persons with a minor illness. Administration of polyclonal immunoglobulins and/or any blood products during the six months before entering the study or planned administration during the study period. Contra-indications to commercially available vaccines used in this study (Havrix®, Prevnar®, ProQuad®).

Ages Eligible for Study
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Minimum Age: 12 Months
Maximum Age: 14 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group A<br>Subjects received refrigerator-stored Priorix-Tetra™ (MMRV vaccine 208136 formulation A) co-administered with Havrix® and Prevnar® at Day 0 and a second dose of Havrix® at Day 180 | Biological: Priorix-Tetra™ (MMRV vaccine 208136)<br>* One subcutaneous injection.<br>Biological: Havrix®<br>* Two intramuscular injections.<br>Biological: Prevnar®<br>* One intramuscular injection.<br>|
| Experimental: Group B<br>Subjects received freezer-stored Priorix-Tetra™ (MMRV vaccine 208136 formulation B) co-administered with Havrix® and Prevnar® at Day 0 and a second dose of Havrix® at Day 180 | Biological: Priorix-Tetra™ (MMRV vaccine 208136)<br>* One subcutaneous injection.<br>Biological: Havrix®<br>* Two intramuscular injections.<br>Biological: Prevnar®<br>* One intramuscular injection.<br>|
| Active Comparator: Group C<br>Subjects received ProQuad® co-administered with Havrix® and Prevnar® at Day 0 and a second dose of Havrix® at Day 180 | Biological: ProQuad®<br>* One subcutaneous injection.<br>Biological: Havrix®<br>* Two intramuscular injections.<br>Biological: Prevnar®<br>* One intramuscular injection.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects With Seroresponse for Antibodies to Varicella Virus (VZV) | Seroresponse for antibodies to VZV is defined as the appearance post-vaccination of anti-VZV antibodies [concentration greater than or equal to the threshold of 75 milli-international units per milliliter (mIU/mL)] in the serum of subjects below the assay cut-off value of 25 mIU/mL before vaccination. | At Day 42 after vaccination | 
| Concentration of Antibodies to Varicella Virus (VZV) | Concentrations are given as Geometric Mean Concentrations (GMCs). | At Day 42 after vaccination | 
| Number of Subjects With Seroresponse for Antibodies to Mumps Virus | Seroresponse for antibodies to mumps virus is defined as the appearance post-vaccination of anti-mumps virus antibodies [titer greater than or equal to the threshold of 51 Effective Doses (ED50)] in the serum of subjects below the assay cut-off value of 24 ED50 before vaccination. | At Day 42 after vaccination | 
| Number of Subjects With Seroresponse for Antibodies to Measles Virus | Seroresponse for antibodies to measles virus is defined as the appearance post-vaccination of anti-measles virus antibodies [concentration greater than or equal to the threshold of 200 milli-international units per milliliter (mIU/mL)] in the serum of subjects below the assay cut-off value of 150 mIU/mL before vaccination. | At Day 42 after vaccination | 
| Number of Subjects With Seroresponse for Antibodies to Rubella Virus | Seroresponse for antibodies to rubella virus is defined as the appearance post-vaccination of anti-rubella virus antibodies [concentration greater than or equal to the threshold of 10 international units per milliliter (IU/mL)] in the serum of subjects below the assay cut-off value of 4 IU/mL before vaccination. | At Day 42 after vaccination | 
| Concentration of Antibodies to Hepatitis A Virus (HAV) | Concentrations are given as Geometric Mean Concentrations (GMCs). | At Day 42 after vaccination | 
| Concentration of Antibodies to S. Pneumoniae Serotypes 4, 6B, 9V, 14, 18C, 19F and 23F | Concentrations are given as Geometric Mean Concentrations (GMCs). | At Day 42 after vaccination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Antibody Titers to Mumps Virus | Data are expressed as Geometric Mean Titers (GMTs). The titer is the serum dilution giving a 50 percent reduction of the signal compared to a control without serum. | At Day 42 after vaccination | 
| Concentration of Antibodies to Measles Virus | Concentrations are given as Geometric Mean Concentrations (GMCs). | At Day 42 after vaccination | 
| Concentration of Antibodies to Rubella Virus | Concentrations are given as Geometric Mean Concentrations (GMCs). | At Day 42 after vaccination | 
| Number of Subjects With Vaccine Response to Havrix | Vaccine response to Havrix is defined as the appearance post-vaccination of anti-hepatitis A virus (anti-HAV) antibodies [concentration greater than or equal to 15 milli-international units per milliliter (mIU/mL)] in the serum of subjects seronegative before vaccination (concentration below the assay cut-off value of 15 mIU/mL) or having a 2-fold increase above the pre-vaccination concentration in subjects who were seropositive before vaccination. | At Day 42 after vaccination | 
| Number of Subjects With Concentration of Antibodies to S. Pneumoniae Serotypes 4, 6B, 9V, 14, 18C, 19F and 23F Equal or Above the Cut-off Value | Cut-off value assessed include 0.05 micrograms per milliliter (µg/mL). | At Day 42 after vaccination | 
| Number of Subjects With Concentration of Antibodies to S. Pneumoniae Serotypes 4, 6B, 9V, 14, 18C, 19F and 23F Equal or Above the Cut-off Value | Cut-off value assessed include 0.2 micrograms per milliliter (µg/mL). | At Day 42 after vaccination | 
| Number of Subjects With Concentration of Antibodies to S. Pneumoniae Serotypes 4, 6B, 9V, 14, 18C, 19F and 23F Equal or Above the Cut-off Value | Cut-off value assessed include 0.5 micrograms per milliliter (µg/mL). | At Day 42 after vaccination | 
| Number of Subjects With Concentration of Antibodies to S. Pneumoniae Serotypes 4, 6B, 9V, 14, 18C, 19F and 23F Equal or Above the Cut-off Value | Cut-off value assessed include 1.0 micrograms per milliliter (µg/mL). | At Day 42 after vaccination | 
| Number of Subjects Reporting Solicited Local Symptoms | Solicited local symptoms assessed include pain, redness and swelling. | During the 4 day follow up period following vaccination | 
| Number of Subjects Reporting Fever ≥ 38.0°C/100.4°F and > 39.5°C/103.1°F During the 15-day Follow up Period After Vaccination | Fever was measured rectally. | During the 15-day follow-up period following vaccination | 
| Number of Subjects Reporting Fever ≥ 38.0°C/100.4°F and > 39.5°C/103.1°F During the 43-day Follow-up Period After Vaccination | Fever was measured rectally. | During the 43-day follow-up period following vaccination | 
| Number of Subjects Reporting Investigator-confirmed Measles/Rubella-like Rash |  | During the 43-day follow-up period after vaccination | 
| Number of Subjects Reporting Investigator-confirmed Varicella-like Rash |  | During the 43-day follow-up period after vaccination | 
| Number of Subjects Reporting Investigator-confirmed Parotid/Salivary Gland Swelling |  | During the 43-day follow-up period after vaccination | 
| Number of Subjects Reporting Unsolicited Adverse Events and Medically-attended Adverse Events (Excluding Rash and Parotid/Salivary Gland Swelling) | Unsolicited adverse event covers any adverse event 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. Medically-attended adverse event covers any adverse event which received medical attention. Medical attention is defined as hospitalization, an emergency room visit or a visit to or from medical personnel. | During the 43-day follow-up period after vaccination | 
| Number of Subjects Reporting New Onset Chronic Illnesses and Conditions Prompting Emergency Room Visits | New onset chronic illnesses include autoimmune disorders, asthma, type I diabetes and allergies. | For approximately 6 months (Day 0-180) | 
| Number of Subjects Reporting Serious Adverse Events | Serious adverse events assessed include medical occurrences that result in death, is life threatening, require hospitalization or prolongation of hospitalization, result in disability/incapacity or are a congenital anomaly/birth defect in the offspring of a study subject. | For approximately 6 months (Day 0-180) | 

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