A Phase II, Randomized, Observer Blind, Controlled, Multicenter Study to Assess Immunogenicity and Antibody Persistence Following Vaccination With GSK's Candidate Combined Measles, Mumps, and Rubella Vaccine (MMR) Versus M-M-R® II as a First Dose, Both Administered Subcutaneously at 12-15 Months of Age, Concomitantly With Hepatitis A Vaccine (HAV), Varicella Vaccine (VV) and Pneumococcal Conjugate Vaccine (PCV) But at Separate Sites.
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 1,259
- 试验地点
- 48
- 主要终点
- Number of Subjects With Anti-rubella Virus Antibody Concentrations Equal to or Above the Cut-off-value.
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Triple (Participant, Care Provider, Outcomes Assessor)
入排标准
- 年龄范围
- 12 Months 至 15 Months（Child）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
Priorix 1 Group
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.
干预措施: GSK Biological's investigational vaccine 209762 (Biological)
Priorix 1 Group
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.
干预措施: Varivax® (Biological)
Priorix 1 Group
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.
干预措施: Prevnar® (Biological)
Priorix 2 Group
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.
干预措施: GSK Biological's investigational vaccine 209762 (Biological)
Priorix 2 Group
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.
干预措施: Varivax® (Biological)
Priorix 2 Group
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.
干预措施: Prevnar® (Biological)
Priorix 3 Group
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.
干预措施: GSK Biological's investigational vaccine 209762 (Biological)
Priorix 3 Group
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.
干预措施: Varivax® (Biological)
Priorix 3 Group
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.
干预措施: Prevnar® (Biological)
MMR-II Group
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.
干预措施: M-M-R® II (Merck and Co) (Biological)
MMR-II Group
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.
干预措施: Varivax® (Biological)
MMR-II Group
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.
干预措施: Prevnar® (Biological)
Priorix 2 Group
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.
干预措施: Havrix® (Biological)
MMR-II Group
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.
干预措施: Havrix® (Biological)
Priorix 3 Group
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.
干预措施: Havrix® (Biological)
Priorix 1 Group
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.
干预措施: Havrix® (Biological)
结局指标
主要结局
Number of Subjects With Anti-rubella Virus Antibody Concentrations Equal to or Above the Cut-off-value.
时间窗: 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).
Number of Subjects With Anti-measles Virus Antibody Concentration Equal to or Above the Cut-off-value.
时间窗: 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.
时间窗: 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.
次要结局
- Number of Subjects Reporting Other Rash.(During the 43-day (Days 0-42) post-vaccination period)
- Number of Subjects Reporting Investigator-confirmed Parotid/Salivary Gland Swelling.(During the 43-day (Days 0-42) post-vaccination period)
- Anti-measles Virus Antibody Concentrations(At 1 year post-vaccination)
- Anti-mumps Virus Antibody Concentrations(At Day 42 after administration of a dose of Priorix vaccine.)
- Anti-S. Pneumoniae Antibody Concentrations (by Serotype).(At Day 0 before vaccination)
- Anti-varicella Antibody Concentrations.(At Day 42 after administration of a dose of Varivax vaccine.)
- Anti-hepatitis A Virus Antibody Concentrations.(At Day 42 after administration of a dose of Havrix vaccine.)
- 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.)
- 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-rubella Virus Antibody Concentrations(At 2 years post-vaccination)
- Number of Subjects Reporting Febrile Convulsions(During the 43-day (Days 0-42) post-vaccination period)
- Number of Subjects With Anti-measles Virus Antibody Concentration Equal to or Above the Cut-off-value(At 2 years post-vaccination)
- 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)
- Number of Subjects With Anti-rubella Virus Antibody Concentrations Equal to or Above the Cut-off-value.(At 2 years post-vaccination)
- Number of Subjects Reporting Fever.(During the 15-day (Days 0-14) and 43 days (Days 0-42) post-vaccination period)
- Number of Subjects With Solicited Local Symptoms.(During the 4-day (Days 0-3) post-vaccination period)
- Number of Subjects Reporting Serious Adverse Events (SAEs)(From Day 0 to Day 180 after vaccination)
- Number of Subjects With Anti-mumps Virus Antibody Titers Above the Cut-off Value (Enhanced PRN)(At 1 year post-vaccination)
- Number of Subjects With Solicited General Symptoms.(During the 15-day (Days 0-14) post-vaccination period)
- Number of Subjects Reporting Medically Attended Visit (MAEs)(During the 43-day (Days 0-42) post-vaccination period)
- Number of Subjects With Unsolicited Adverse Events (AEs).(During the 43-day (Days 0-42) post-vaccination period)
- Number of Subjects With Anti-mumps Virus Antibody Titers Above the Cut-off Value (Unenhanced PRN)(At 2 years post-vaccination)
- Number of Subjects Reporting Serious Adverse Events (SAEs).(From Day 180 to Day 730 after vaccination)
- Number of Subjects Reporting New Onset Chronic Illnesses (NOCIs).(From Day 0 to Day 180 after vaccination)
- 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)
- Anti-mumps Virus Antibody Titers (Unenhanced PRN)(At 2 years post-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 Concentrations (PPD ELISA)(At 2 years post-vaccination)
- Anti-measles Virus Antibody Concentrations(At Day 42 after administration of a dose of Priorix vaccine.)
- Anti-rubella Virus Antibody Concentrations(At Day 42 after administration of a dose of Priorix vaccine.)
- Anti-S. Pneumoniae Antibody Concentrations (by Serotype).(At Day 42 after vaccination)
- Number of Subjects With Anti-measles Virus Antibody Concentration Equal to or Above the Cut-off-value(At 1 year post-vaccination)
- Anti-measles Virus Antibody Concentrations(At 2 years post-vaccination)
- Number of Subjects With Anti-rubella Virus Antibody Concentrations Equal to or Above the Cut-off-value.(At 1 year post-vaccination)
- Anti-rubella Virus Antibody Concentrations(At 1 year post-vaccination)
- Anti-mumps Virus Antibody Titers (Unenhanced PRN)(At 1 year post-vaccination)
- Number of Subjects With Anti-mumps Virus Antibody Titers Above the Cut-off Value (Unenhanced PRN)(At 1 year post-vaccination)
- Number of Subjects With Anti-mumps Virus Antibody Concentrations Above the Cut-off Value (PPD ELISA)(At 1 year post-vaccination)