Immunogenicity of GSKs' MMR Vaccine (209762) vs. M-M-R® II, When Given With Routine Vaccines at 12-15 Months of Age

Phase 2

Completed

Conditions: Mumps
Measles-Mumps-Rubella Vaccine
Rubella
Measles

Interventions: Biological: GSK Biological's investigational vaccine 209762
Biological: M-M-R® II (Merck and Co)
Biological: Varivax®
Biological: Havrix®
Biological: Prevnar®

Registration Number: NCT00861744

Lead Sponsor: GlaxoSmithKline

Brief Summary: The purpose of this study is to compare two measles, mumps and rubella conjugate vaccines (manufactured by GSK and Merck and Company ) in terms of the immune response elicited and safety with a six month follow-up after first vaccination. Additionally, antibody persistence will be assessed one and two years after administration of MMR vaccine.

The Protocol Posting has been updated following Protocol amendment 1 and 2, Oct 2009.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 1259

Inclusion Criteria

Subjects for whom the investigator believes 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.
Male or female between 12 and 15 months of age (e.g. from age 12 months until the day before age 16 months) at the time of 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 three doses of 7-valent pneumococcal conjugate vaccine within the first year of life with the third dose administered at least 30 days prior to enrolment and vaccination with study vaccines.

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.
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 (pharmaceutical product or device).
Chronic administration (defined as more than 14 days) 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 and Hib 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, varicella/zoster and hepatitis A 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 (no laboratory testing required), 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 vaccines.
Hypersensitivity to latex
Major congenital defects or serious chronic illness.
History of any neurologic disorders or seizures, including febrile seizures.
Acute disease at the time of enrolment.
Administration of polyclonal immunoglobulins and/or any blood products during the six months before entering the study or planned administration during the study period.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Priorix 1 Group	Varivax®	Subjects between 12 and 15 months of age at the time of study vaccination who received one dose of Priorix investigational vaccine (Lot 1) subcutaneously in the right upper arm. Subjects concomitantly received one dose of Havrix and Prevnar vaccines intramuscularly in the left and the right thigh, respectively and one dose of Varivax vaccine subcutaneously in the left upper arm. Subjects had previously received three doses of Prevnar vaccine within the first year of life with the third dose administered at least 30 days prior to enrollment and vaccination with study vaccines.
Priorix 1 Group	Havrix®	Subjects between 12 and 15 months of age at the time of study vaccination who received one dose of Priorix investigational vaccine (Lot 1) subcutaneously in the right upper arm. Subjects concomitantly received one dose of Havrix and Prevnar vaccines intramuscularly in the left and the right thigh, respectively and one dose of Varivax vaccine subcutaneously in the left upper arm. Subjects had previously received three doses of Prevnar vaccine within the first year of life with the third dose administered at least 30 days prior to enrollment and vaccination with study vaccines.
Priorix 2 Group	GSK Biological's investigational vaccine 209762	Subjects between 12 and 15 months of age at the time of study vaccination who received one dose of Priorix investigational vaccine (Lot 2) subcutaneously in the right upper arm. Subjects concomitantly received one dose of Havrix and Prevnar vaccines intramuscularly in the left and the right thigh, respectively and one dose of Varivax vaccine subcutaneously in the left upper arm. Subjects had previously received three doses of Prevnar vaccine within the first year of life with the third dose administered at least 30 days prior to enrollment and vaccination with study vaccines.
Priorix 2 Group	Havrix®	Subjects between 12 and 15 months of age at the time of study vaccination who received one dose of Priorix investigational vaccine (Lot 2) subcutaneously in the right upper arm. Subjects concomitantly received one dose of Havrix and Prevnar vaccines intramuscularly in the left and the right thigh, respectively and one dose of Varivax vaccine subcutaneously in the left upper arm. Subjects had previously received three doses of Prevnar vaccine within the first year of life with the third dose administered at least 30 days prior to enrollment and vaccination with study vaccines.
Priorix 1 Group	GSK Biological's investigational vaccine 209762	Subjects between 12 and 15 months of age at the time of study vaccination who received one dose of Priorix investigational vaccine (Lot 1) subcutaneously in the right upper arm. Subjects concomitantly received one dose of Havrix and Prevnar vaccines intramuscularly in the left and the right thigh, respectively and one dose of Varivax vaccine subcutaneously in the left upper arm. Subjects had previously received three doses of Prevnar vaccine within the first year of life with the third dose administered at least 30 days prior to enrollment and vaccination with study vaccines.
Priorix 1 Group	Prevnar®	Subjects between 12 and 15 months of age at the time of study vaccination who received one dose of Priorix investigational vaccine (Lot 1) subcutaneously in the right upper arm. Subjects concomitantly received one dose of Havrix and Prevnar vaccines intramuscularly in the left and the right thigh, respectively and one dose of Varivax vaccine subcutaneously in the left upper arm. Subjects had previously received three doses of Prevnar vaccine within the first year of life with the third dose administered at least 30 days prior to enrollment and vaccination with study vaccines.
Priorix 2 Group	Varivax®	Subjects between 12 and 15 months of age at the time of study vaccination who received one dose of Priorix investigational vaccine (Lot 2) subcutaneously in the right upper arm. Subjects concomitantly received one dose of Havrix and Prevnar vaccines intramuscularly in the left and the right thigh, respectively and one dose of Varivax vaccine subcutaneously in the left upper arm. Subjects had previously received three doses of Prevnar vaccine within the first year of life with the third dose administered at least 30 days prior to enrollment and vaccination with study vaccines.
Priorix 2 Group	Prevnar®	Subjects between 12 and 15 months of age at the time of study vaccination who received one dose of Priorix investigational vaccine (Lot 2) subcutaneously in the right upper arm. Subjects concomitantly received one dose of Havrix and Prevnar vaccines intramuscularly in the left and the right thigh, respectively and one dose of Varivax vaccine subcutaneously in the left upper arm. Subjects had previously received three doses of Prevnar vaccine within the first year of life with the third dose administered at least 30 days prior to enrollment and vaccination with study vaccines.
Priorix 3 Group	GSK Biological's investigational vaccine 209762	Subjects between 12 and 15 months of age at the time of study vaccination who received one dose of Priorix investigational vaccine (Lot 3) subcutaneously in the right upper arm. Subjects concomitantly received one dose of Havrix and Prevnar vaccines intramuscularly in the left and the right thigh, respectively and one dose of Varivax vaccine subcutaneously in the left upper arm. Subjects had previously received three doses of Prevnar vaccine within the first year of life with the third dose administered at least 30 days prior to enrollment and vaccination with study vaccines.
Priorix 3 Group	Varivax®	Subjects between 12 and 15 months of age at the time of study vaccination who received one dose of Priorix investigational vaccine (Lot 3) subcutaneously in the right upper arm. Subjects concomitantly received one dose of Havrix and Prevnar vaccines intramuscularly in the left and the right thigh, respectively and one dose of Varivax vaccine subcutaneously in the left upper arm. Subjects had previously received three doses of Prevnar vaccine within the first year of life with the third dose administered at least 30 days prior to enrollment and vaccination with study vaccines.
Priorix 3 Group	Havrix®	Subjects between 12 and 15 months of age at the time of study vaccination who received one dose of Priorix investigational vaccine (Lot 3) subcutaneously in the right upper arm. Subjects concomitantly received one dose of Havrix and Prevnar vaccines intramuscularly in the left and the right thigh, respectively and one dose of Varivax vaccine subcutaneously in the left upper arm. Subjects had previously received three doses of Prevnar vaccine within the first year of life with the third dose administered at least 30 days prior to enrollment and vaccination with study vaccines.
Priorix 3 Group	Prevnar®	Subjects between 12 and 15 months of age at the time of study vaccination who received one dose of Priorix investigational vaccine (Lot 3) subcutaneously in the right upper arm. Subjects concomitantly received one dose of Havrix and Prevnar vaccines intramuscularly in the left and the right thigh, respectively and one dose of Varivax vaccine subcutaneously in the left upper arm. Subjects had previously received three doses of Prevnar vaccine within the first year of life with the third dose administered at least 30 days prior to enrollment and vaccination with study vaccines.
MMR-II Group	M-M-R® II (Merck and Co)	Subjects between 12 and 15 months of age at the time of study vaccination who randomly received one dose of one of three different commercially-available lot of M-M-R II (Merck and Co.) vaccine subcutaneously in the right upper arm. Subjects concomitantly received one dose of Havrix and Prevnar vaccines intramuscularly in the left and the right thigh, respectively and one dose of Varivax vaccine subcutaneously in the left upper arm. Subjects had previously received three doses of Prevnar vaccine within the first year of life with the third dose administered at least 30 days prior to enrollment and vaccination with study vaccines.
MMR-II Group	Prevnar®	Subjects between 12 and 15 months of age at the time of study vaccination who randomly received one dose of one of three different commercially-available lot of M-M-R II (Merck and Co.) vaccine subcutaneously in the right upper arm. Subjects concomitantly received one dose of Havrix and Prevnar vaccines intramuscularly in the left and the right thigh, respectively and one dose of Varivax vaccine subcutaneously in the left upper arm. Subjects had previously received three doses of Prevnar vaccine within the first year of life with the third dose administered at least 30 days prior to enrollment and vaccination with study vaccines.
MMR-II Group	Varivax®	Subjects between 12 and 15 months of age at the time of study vaccination who randomly received one dose of one of three different commercially-available lot of M-M-R II (Merck and Co.) vaccine subcutaneously in the right upper arm. Subjects concomitantly received one dose of Havrix and Prevnar vaccines intramuscularly in the left and the right thigh, respectively and one dose of Varivax vaccine subcutaneously in the left upper arm. Subjects had previously received three doses of Prevnar vaccine within the first year of life with the third dose administered at least 30 days prior to enrollment and vaccination with study vaccines.
MMR-II Group	Havrix®	Subjects between 12 and 15 months of age at the time of study vaccination who randomly received one dose of one of three different commercially-available lot of M-M-R II (Merck and Co.) vaccine subcutaneously in the right upper arm. Subjects concomitantly received one dose of Havrix and Prevnar vaccines intramuscularly in the left and the right thigh, respectively and one dose of Varivax vaccine subcutaneously in the left upper arm. Subjects had previously received three doses of Prevnar vaccine within the first year of life with the third dose administered at least 30 days prior to enrollment and vaccination with study vaccines.

Primary Outcome Measures

Name	Time	Method
Number of Subjects With Anti-measles Virus Antibody Concentration Equal to or Above the Cut-off-value.	At Day 42 after administration of a dose of Priorix vaccine.	Anti-measles virus antibody cut-off-value assessed was ≥ 200 milli-International Units per milliliter (mIU/mL). The analysis was performed on seronegative subjects. Seronegative subjects are subjects with anti-measles virus antibody concentrations \<150 mIU/mL prior to vaccination.
Number of Subjects With Anti-mumps Virus Antibody Titer Equal to or Above the Cut-off-value.	At Day 42 after administration of a dose of Priorix vaccine.	Anti-mumps virus antibody cut-off-value assessed was ≥ 51 Estimated Dose 50 (ED50). The analysis was performed on seronegative subjects. Seronegative subjects are subjects with anti-measles virus antibody concentrations \<24 ED50 prior to vaccination.
Number of Subjects With Anti-rubella Virus Antibody Concentrations Equal to or Above the Cut-off-value.	At Day 42 after administration of a dose of Priorix vaccine.	Anti-rubella virus antibody cut-off-value assessed was ≥ 10 International Units per milliliter (IU/mL).

Secondary Outcome Measures

Name	Time	Method
Anti-S. Pneumoniae Antibody Concentrations (by Serotype).	At Day 0 before vaccination	Antibody concentrations are expressed as Geometric Mean Concentrations (GMCs) in µg/mL.
Anti-varicella Antibody Concentrations.	At Day 42 after administration of a dose of Varivax vaccine.	Antibody concentrations are expressed as Geometric Mean Titers (GMT). The analysis was performed on seronegative subjects. Seronegative subjects are subjects with antibody concentration \< 25 mIU/mL prior to vaccination.
Anti-hepatitis A Virus Antibody Concentrations.	At Day 42 after administration of a dose of Havrix vaccine.	Antibody concentrations are expressed as Geometric Mean Concentrations (GMCs) in mIU/mL. The analysis was performed on seronegative subjects. Seronegative subjects are subjects with anti-hepatitis A virus antibody concentrations \<15 mIU/mL prior to vaccination.
Number of Subjects With Anti-hepatitis A Antibody Concentrations Equal to or Above the Cut-off-value.	At Day 42 after administration of a dose of Havrix vaccine.	Anti-hepatitis A antibody cut-off-value assessed was ≥15 milli-International Units per milliliter (mIU/mL).
Number of Subjects With Anti-varicella Antibody Concentration Equal to or Above the Cut-off-value.	At Day 42 after administration of a dose of Varivax vaccine.	Anti-varicella virus antibody cut-off-value assessed was ≥ 75 milli-International Units per milliliter (mIU/mL).
Number of Subjects Reporting Other Rash.	During the 43-day (Days 0-42) post-vaccination period	Other rash = not confirmed by the investigator to be either measles/rubella-like or varicella-like in nature
Number of Subjects Reporting Investigator-confirmed Parotid/Salivary Gland Swelling.	During the 43-day (Days 0-42) post-vaccination period	Swelling with accompanying general symptoms
Anti-measles Virus Antibody Concentrations	At 1 year post-vaccination	Antibody concentrations were expressed as Geometric Mean Concentrations (GMCs) in mIU/mL. The analysis was performed on seronegative subjects. Seronegative subjects are subjects with anti-measles virus antibody concentrations \<150 mIU/mL prior to vaccination.
Anti-mumps Virus Antibody Concentrations	At Day 42 after administration of a dose of Priorix vaccine.	Antibody concentrations are expressed as Geometric Mean Titer (GMT). The analysis was performed on seronegative subjects. Seronegative subjects are subjects with antibody titer \< 24 ED50 prior to vaccination.
Anti-rubella Virus Antibody Concentrations	At 2 years post-vaccination	Antibody concentrations are expressed as Geometric Mean Concentrations (GMCs) in IU/mL. The analysis was performed on seronegative subjects. Seronegative subjects are subjects with anti-rubella virus antibody concentrations \<4 IU/mL prior to vaccination.
Number of Subjects With Anti-measles Virus Antibody Concentration Equal to or Above the Cut-off-value	At 2 years post-vaccination	Anti-measles virus antibody cut-off-value assessed was ≥ 200 milli-International Units per milliliter (mIU/mL).
Number of Subjects Reporting Investigator-confirmed Measles/Rubella-like Rash and Varicella-like Rash.	During the 43-day (Days 0-42) post-vaccination period
Anti-mumps Virus Antibody Titers (Enhanced Plaque Reduction Neutralization (PRN))	At 1 year post-vaccination	Antibody titers were expressed as Geometric Mean Titer (GMT). The analysis was performed on seronegative subjects. Seronegative subjects are subjects with antibody titer \< 24 ED50 prior to vaccination.
Number of Subjects With Anti-rubella Virus Antibody Concentrations Equal to or Above the Cut-off-value.	At 2 years post-vaccination	Anti-rubella virus antibody cut-off-value assessed was ≥ 10 International Units per milliliter (IU/mL).
Number of Subjects Reporting Fever.	During the 15-day (Days 0-14) and 43 days (Days 0-42) post-vaccination period	fever is assessed for temperature ≥38°C/100.4°F and \>39.5°C/103.1°F as measured rectally.
Number of Subjects With Solicited Local Symptoms.	During the 4-day (Days 0-3) post-vaccination period	Solicited local symptoms assessed were pain, redness and swelling.
Number of Subjects Reporting Serious Adverse Events (SAEs)	From Day 0 to Day 180 after vaccination	SAEs assessed include medical occurrences that result in death, are 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.
Number of Subjects Reporting Febrile Convulsions	During the 43-day (Days 0-42) post-vaccination period	Timing of febrile convulsions: events occured on Day 29 in the Priorix 2 Group and Day 0 in the MMR II Group. All cases of febrile convulsions were case of meningism.
Number of Subjects With Anti-mumps Virus Antibody Titers Above the Cut-off Value (Enhanced PRN)	At 1 year post-vaccination	Anti-mumps virus antibody cut-off-value assessed was ≥ 51 ED50.
Number of Subjects With Solicited General Symptoms.	During the 15-day (Days 0-14) post-vaccination period	Assessed solicited general symptoms were drowsiness, irritability and loss of appetite. Any = occurrence of the symptom regardless of intensity grade.
Number of Subjects Reporting Medically Attended Visit (MAEs)	During the 43-day (Days 0-42) post-vaccination period	MAEs were defined as events for which the subject received medical attention defined as hospitalization, an emergency room visit, or a visit to or from medical personnel (medical doctor) for any reason. Any MAE(s) = Occurrence of any MAE(s) regardless of intensity grade or relation to vaccination.
Number of Subjects Reporting New Onset Chronic Illnesses (NOCIs).	From Day 0 to Day 180 after vaccination	NOCIs included autoimmune disorders, asthma, type I diabetes, allergies.
Number of Subjects With Unsolicited Adverse Events (AEs).	During the 43-day (Days 0-42) post-vaccination period	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 and 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 = the occurrence of any unsolicited AE regardless of intensity grade or relation to vaccination.
Number of Subjects With Anti-mumps Virus Antibody Titers Above the Cut-off Value (Unenhanced PRN)	At 2 years post-vaccination	Anti-mumps virus antibody cut-off-value assessed was ≥ 4 Estimated Dose 50 (ED50).
Anti-mumps Virus Antibody Titers (Unenhanced PRN)	At 2 years post-vaccination	Antibody concentrations are expressed as Geometric Mean Titer (GMT).
Number of Subjects Reporting Serious Adverse Events (SAEs).	From Day 180 to Day 730 after vaccination	SAEs assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization, result in disability/incapacity or are congenital anomaly/birth defect in the offspring of a study subject.
Number of Subjects Reporting Conditions Prompting Emergency Room (ER) Visits.	From Day 0 to Day 180 after vaccination
Anti-mumps Virus Antibody Concentrations (Pharmaceutical Product Development (PPD) ELISA)	At 1 year post-vaccination	Antibody concentrations are expressed as Geometric Mean Concentrations (GMC) in ELISA units per milliliter (EU/mL). The analysis was performed on seronegative subjects. Seronegative subjects are subjects with anti-rubella virus antibody concentrations \<5 EU/mL prior to vaccination.
Number of Subjects With Anti-mumps Virus Antibody Concentrations Above the Cut-off Value (PPD ELISA)	At 2 years post-vaccination	Anti-mumps virus antibody cut-off-value assessed was ≥ 10 ELISA units per milliliter (EU/mL)
Anti-mumps Virus Antibody Concentrations (PPD ELISA)	At 2 years post-vaccination	Antibody concentrations are expressed as Geometric Mean Concentrations (GMC) in ELISA units per milliliter (EU/mL). The analysis was performed on seronegative subjects. Seronegative subjects are subjects with anti-rubella virus antibody concentrations \<5 EU/mL prior to vaccination.