Immunogenicity and Safety Study of GSK Biologicals' Priorix Vaccine (209762) at an End of Shelf-life Potency Compared to Merck & Co., Inc.'s Measles-mumps-rubella (MMR) Vaccine When Both Are Given on a 2-dose Schedule to Healthy Children in Their 2nd Year of Life
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 4,538
- 试验地点
- 82
- 主要终点
- Percentage of Subjects With Anti-measles Virus Antibody Concentration Equal to or Above the Cut-off-value (by Enzyme-linked Immunosorbent Assay [ELISA])
研究概览
简要总结
The purpose of this study is to evaluate end of shelf-life potency in terms of the immunogenicity and safety of GSK Biologicals' trivalent MMR vaccine, by comparing it to Merck & Co., Inc.'s MMR vaccine, which is approved for use in the United States (US).
详细描述
This trial is a Phase IIIA, randomized, observer-blind, controlled, multi-center, multi-country study with four parallel groups. This study will evaluate the immunogenicity and safety of GSK Biologicals' trivalent investigational MMR vaccine (referred to as Inv_MMR vaccine, throughout this document) in contrast to the US standard of care comparator vaccine (M-M-R II, Merck and Co., Inc., referred to as Com_MMR throughout this document) in children during their second year of life. The first dose of this two-dose study is designed to establish the end of shelf-life potency of Inv_MMR vaccine. The Inv_MMR vaccine will be given as one of two lots; one of a minimum potency, designated Inv_MMR_Min; and the other at a mid-range or medium potency designated Inv_MMR_Med to two groups. The second dose for both of these Inv_MMR groups will have a potency within the release range of the marketed vaccine. The Com_MMR vaccine will consist of two lots designated Com_MMR_L1 and Com_MMR_L2 and will be analyzed as pooled lots within the study. The first MMR vaccine dose will be co-administered with Varivax, Havrix and (in the US sub-cohort only) Prevnar 13 which are routinely administered to children of this age in the US.
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
- •Male or female child between 12 and 15 months of age at the time of vaccination.
- •The investigator believes that the parent(s) or Legally Acceptable Representative(s) (LAR(s)) of the child, can, and will comply with the requirements of the protocol.
- •Written informed consent obtained from the parent(s)/LAR(s) of the child.
- •Child is in stable health as determined by investigator's clinical examination and assessment of child's medical history.
- •For US children only:
- •Child that previously received a 3-dose series of Prevnar 13 with last dose at least 60 days prior to study entry.
排除标准
- •Child in care.
- •Use of any investigational or non-registered product other than the study vaccine(s) during the period starting 30 days before the day of study vaccination or planned use during the entire study period.
- •Concurrently participating in another clinical study, in which the child has been or will be exposed to an investigational or a non-investigational product. Chronic administration of immunosuppressants, or other immune-modifying drugs during the period starting 180 days prior to the first vaccine dose or any planned administration of immunosuppressive and immune-modifying drugs during the entire study.
- •Inhaled and topical steroids are allowed.
- •Planned administration / administration of a vaccine not foreseen by the study protocol during the period starting 30 days prior to study vaccination at Visit 1 and ending at Visit 2 (or ending at Visit 3 for the US post-dose 2 sub-cohort). Please Note:
- •Inactivated influenza (Flu) vaccine and Haemophilus influenzae type b conjugate vaccine (Hib) vaccines may be given at any time during the study, including the day of study vaccination (Flu and Hib vaccines must be administered at a different location than the study vaccine/s).
- •Any age appropriate vaccine may be given starting at Visit 2 (or starting at Visit 3 for the US post-dose 2 sub-cohort), and anytime thereafter.
- •Administration of immunoglobulins and/or any blood products during the period starting 180 days prior to study vaccination at Visit 1 or planned administration from the date of vaccination through the immunogenicity evaluation at Visit 2, or at Visit 3 for the US post-dose 2 sub-cohort.
- •History of measles, mumps, rubella, varicella/zoster and/or hepatitis A diseases.
- •Known exposure to measles, mumps, rubella and/or varicella/zoster during the period starting 30 days prior to the first study vaccination.
- •Previous vaccination against measles, mumps, rubella, hepatitis A and/or varicella virus.
- •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 hypersensitivity to neomycin, latex or gelatin.
- •Blood dyscrasias, leukemia, lymphomas of any type, or other malignant neoplasms affecting the bone marrow or lymphatic systems.
- •Acute disease at the time of enrollment. Acute disease is defined as the presence of a moderate or severe illness with or without fever. Fever is defined as temperature ≥38°C/100.4°F by any age appropriate route. All vaccines can be administered to persons with a minor illness such as diarrhea, mild upper respiratory infection without fever.
- •Active untreated tuberculosis based on medical history.
- •Any other condition which, in the opinion of the Investigator, prevents the child from participating in the study.
- •For US children only:
- •A child that previously received a fourth dose of any pneumococcal conjugate vaccine.
结局指标
主要结局
Percentage of Subjects With Anti-measles Virus Antibody Concentration Equal to or Above the Cut-off-value (by Enzyme-linked Immunosorbent Assay [ELISA])
时间窗: At Day 42
For measles virus, a seroresponse was defined as post-vaccination anti-measles virus antibody concentration equal or above \[≥\] 200 mIU/mL (ELISA) among subjects who were seronegative (antibody concentration less than \[\<\] 150 mIU/mL) before dose 1. Criteria to demonstrate an acceptable immune response of Inv_MMR_Min/Inv_MMR_Med vaccine in terms of seroresponse rate for measles virus at Day 42: The lower limit of the two-sided 97.5% CI for the seroresponse rate of Inv_MMR_Min/Inv_MMR_Med was to be ≥ 90% for antibodies to measles virus.
Percentage of Subjects With Anti-mumps Virus Antibody Concentration Equal to or Above the Cut-off-value (by ELISA)
时间窗: At Day 42
For mumps virus, a seroresponse was defined as post-vaccination anti-mumps virus antibody concentration ≥ 10 EU/mL (ELISA) among subjects who were seronegative (antibody concentration \< 5 EU/mL) before dose 1. Criteria to demonstrate an acceptable immune response of Inv_MMR_Min/Inv_MMR_Med vaccine in terms of seroresponse rate for mumps virus at Day 42: The lower limit of the two-sided 97.5% CI for the seroresponse rate of Inv_MMR_Min/Inv_MMR_Med was to be ≥ 90% for antibodies to mumps virus.
Percentage of Subjects With Anti-mumps Virus Antibody Concentration Equal to or Above the Cut-off-value (by Plaque Reduction Neutralization Test [PRNT])
时间窗: At Day 42
For mumps virus as measured by PRNT, a seroresponse was defined as post-vaccination anti-mumps virus antibody concentration ≥ 4 End point Dilution 50% (ED50) (PRNT) among subjects who were seronegative (antibody concentration \< 2.5 ED50) before dose 1.
Percentage of Subjects With Anti-rubella Virus Antibody Concentration Equal to or Above the Cut-off-value (by ELISA)
时间窗: At Day 42
For rubella virus, a seroresponse was defined as post-vaccination anti-rubella virus antibody concentration ≥ 10 IU/mL (ELISA) among subjects who were seronegative (antibody concentration \< 4 IU/mL) before dose 1. Criteria to demonstrate an acceptable immune response of Inv_MMR_Min/Inv_MMR_Med vaccine in terms of seroresponse rate for rubella virus at Day 42: The lower limit of the two-sided 97.5% CI for the seroresponse rate of Inv_MMR_Min/Inv_MMR_Med was to be ≥ 90% for antibodies to mumps virus.
Anti-measles Virus Antibody Concentrations (by ELISA)
时间窗: At Day 42
Antibody concentrations were expressed as Geometric Mean Concentrations (GMCs) in mIU/mL.
Anti-mumps Virus Antibody Concentrations (by ELISA)
时间窗: At Day 42
Antibody concentrations were expressed as GMCs in EU/mL.
Anti-mumps Virus Antibody Concentrations (by PRNT)
时间窗: At Day 42
Antibody concentrations were expressed as Geometric Mean Titers (GMTs).
Anti-rubella Virus Antibody Concentrations (by ELISA)
时间窗: At Day 42
Antibody concentrations were expressed as GMCs in IU/mL.
次要结局
- Number of Subjects Reporting Any MMR Specific Solicited General AEs Post Dose 2(During the 43-day (Days 0-42) post-vaccination period)
- Percentage of Subjects With Anti-measles Virus Antibody Concentration Equal to or Above the Cut-off-value (by ELISA)(At Day 84)
- Percentage of Subjects With Anti-mumps Virus Antibody Concentration Equal to or Above the Cut-off-value (by ELISA)(At Day 84)
- Percentage of Subjects With Anti-rubella Virus Antibody Concentration Equal to or Above the Cut-off-value (by ELISA)(At Day 84)
- Anti-measles Virus Antibody Concentrations (by ELISA)(At Day 84)
- Anti-mumps Virus Antibody Concentrations (by ELISA)(At Day 84)
- Anti-rubella Virus Antibody Concentrations (by ELISA)(At Day 84)
- Number of Subjects With Any Solicited Local Adverse Events (AEs) Post Dose 1(During the 4-day (Days 0-3) post-vaccination period)
- Number of Subjects With Any Solicited Local AEs Post Dose 2(During the 4-day (Days 0-3) post-vaccination period)
- Number of Subjects With Any Solicited General AEs Post Dose 1(During the 15-day (Days 0-14) post-vaccination period)
- Number of Subjects Reporting Any Fever Post Dose 1(During the 43-day (Days 0-42) post-vaccination period)
- Number of Subjects Reporting Any Fever Post Dose 2(During the 43-day (Days 0-42) post-vaccination period)
- Number of Subjects Reporting Any Rash Post Dose 1(During the 43-day (Days 0-42) post-vaccination period)
- Number of Subjects Reporting Any Rash Post Dose 2(During the 43-day (Days 0-42) post-vaccination period)
- Number of Subjects Reporting Any MMR Specific Solicited General AEs Post Dose 1(During the 43-day (Days 0-42) post-vaccination period)
- Number of Subjects Reporting Any Unsolicited AES Post Dose 1(During the 43-day (Days 0-42) post-vaccination period)
- Number of Subjects Reporting Any Unsolicited AES Post Dose 2(During the 43-day (Days 0-42) post-vaccination period)
- Number of Subjects Reporting Any AEs of Specific Interest(From Day 0 through the end of the study (Day 222))
- Number of Subjects Reporting Any Serious Adverse Events (SAEs)(From Day 0 through the end of the study (Day 222))