Study in Healthy Children (<2 Years) to Evaluate the Safety and Efficacy of GSK Biologicals' Live Attenuated Varicella Vaccine (VarilrixTM) and of GSK Biologicals' Combined Measles-Mumps-Rubella-Varicella Vaccine
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 5,803
- 试验地点
- 104
- 主要终点
- Phase A: Number of Subjects With Confirmed Varicella Case
研究概览
简要总结
An observer-blind study to evaluate GlaxoSmithKline Biologicals' live attenuated varicella vaccine and GlaxoSmithKline Biologicals' combined measles-mumps-rubella-varicella vaccine in the prevention of varicella disease in children. The Protocol Posting has been updated in order to comply with the FDA Amendment Act, Sep 2007.
详细描述
According to treatment group allocation, participants will receive study vaccines and be followed for antibody titres and occurrence of varicella disease.
This study is conducted in 2 phases. Phase A includes the vaccination period and an observation period for efficacy. The efficacy endpoints will be evaluated over at least two years after vaccination. During this period, the immunogenicity endpoints will be evaluated with respect to the immune response 43 days after vaccination and the persistence of antibodies over two years to varicella (for all subjects) and to measles, mumps and rubella (for a subset of subjects). Regarding the safety endpoints, SAEs (including any complicated varicella cases if observed) will be assessed for all subjects during the whole Phase A duration, whereas, solicited (local and general) and unsolicited adverse events will be assessed in a subset of subjects within a 43-day period after vaccination.
Phase B is an extension of Phase A. It is a long-term follow-up until Year 10 to examine the long-term efficacy of the study vaccines against clinical varicella disease as well as the long-term persistence of antibodies to varicella (for all subjects) and to measles, mumps and rubella (in a subset of subjects) after vaccination.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 11 Months 至 22 Months（Child）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Subjects for whom the investigator believes that their parents/guardians can and will comply with the requirements of the protocol for the whole duration of the study.
- •Male or female subject between 12 and 22 months of age at the time of the first vaccination.
- •Subjects free of obvious health problems, as established by medical history and physical examination before entering the study.
- •Written informed consent obtained from the parents/guardians of the subject after they have been informed on the risks and benefits of the study, in a language they clearly understand and before performance of any study procedure.
- •Subjects whose parents/guardians have direct access to telephone/mobile phone.
- •Subjects:
- •with at least one sibling (with negative history of varicella disease/vaccination) at home, or
- •attending day care center, or
- •attending childminders, i.e. someone taking care of several children, or
- •who are in contact for at least once a week with other children without a known positive history of varicella disease/vaccination, while playing in close physical contact for more than 5 minutes.
排除标准
- •Previous vaccination against measles, mumps, rubella and/or varicella.
- •History of previous measles, mumps, rubella and/or varicella/ herpes zoster diseases.
- •Known exposure to measles, mumps, rubella and/or varicella/herpes zoster within 30 days prior to the start of the study.
- •Chronic administration (defined as more than 14 days) of immunosuppressants or other immune-modifying drugs within six months prior to the first vaccine dose.
- •Administration of immunoglobulins and/or any blood products within three months prior to the first vaccine dose or planned administration during the study period.
- •Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical.
- •Family history of congenital or hereditary immunodeficiency.
- •History of allergic diseases or reactions likely to be exacerbated by any component of the vaccines, including systemic allergy to egg proteins or neomycin.
- •Major congenital defects or serious chronic illness.
- •Residence in the same household as newborns (0-4 weeks of age), pregnant women who are varicella-susceptible, persons with a known immunodeficiency or any other persons at high risk for varicella.
- •History of any neurologic disorders or seizures.
- •Use of any investigational or non-registered product (drug/vaccine other than the study vaccines) within 14 days prior to vaccination and planned use during the study period.
- •Additional exclusion criteria for subjects included in the subset:
- •- Administration of a licensed vaccine within 14 days prior to vaccination and planned use until approximately 42 days after the last study vaccine dose (Day 84) with the exception of oral polio vaccine (OPV).
研究组 & 干预措施
MMRV Group
Subjects in this group received 2 doses of Priorix-Tetra vaccine, administered subcutaneously in the deltoid region of the left arm, one at Day 0 (Visit 1) and the other at Day 42 (Visit 2).
干预措施: Priorix-tetra™ (Biological)
OKAH Group
Subjects in this group received 1 dose of Priorix at Day 0 (Visit 1) and 1 dose of Varilrix at Day 42 (Visit 2). Both vaccines were administered subcutaneously in the deltoid region of the left arm.
干预措施: Priorix™ (Biological)
OKAH Group
Subjects in this group received 1 dose of Priorix at Day 0 (Visit 1) and 1 dose of Varilrix at Day 42 (Visit 2). Both vaccines were administered subcutaneously in the deltoid region of the left arm.
干预措施: Varilrix™ (Biological)
MMR Group
Subjects in this group received 2 doses of Priorix, administered subcutaneously in the deltoid region of the left arm, one at Day 0 (Visit 1) and the other at Day 42 (Visit 2).
干预措施: Priorix™ (Biological)
结局指标
主要结局
Phase A: Number of Subjects With Confirmed Varicella Case
时间窗: From 42 days post dose 2 until the end of Phase A
Confirmed varicella case = A case that met the clinical case definition \[an illness with acute onset of diffuse, generalized maculopapulovesicular rash (i.e. spots, papules and/or vesicles) without other apparent cause\] at least in the opinion of the investigator and was confirmed by laboratory test \[Polymerase Chain Reaction (PCR) (+)\] OR a case that met the clinical definition confirmed by the Independent Data Monitoring Committee (IDMC) and was epidemiologically linked \[Epi (+)\] to a valid index case.
次要结局
- Phase B: Number of Subjects With Anti-measles Antibody Concentrations Above the Cut-off Value(At Year 4, Year 6, Year 8 and Year 10 time points)
- Phase B: Number of Subjects With Anti-mumps Antibody Concentrations Above the Cut-off Value(At Year 4, Year 6, Year 8 and Year 10 time points)
- Phase A: Number of Subjects With Seroconversion/Seroresponse to Mumps in a Subset of Subjects(At Day 0, Day 42, Day 84, Year 1 and Year 2 time points)
- Phase A: Immune Response to Rubella With Respect to Anti-rubella Antibody Concentrations in a Subset of Subjects(At Day 0, Day 42, Day 84, Year 1 and Year 2 time points)
- Phase B: Number of Subjects With Probable or Confirmed Varicella Case(From the beginning of Phase B (Year 2) up to study end (Year 10))
- Phase B: Number of Subjects With Anti-rubella Antibody Concentrations Above the Cut-off Value(At Year 4, Year 6, Year 8 and Year 10 time points)
- Phase B: Number of Subjects Reporting Serious Adverse Events (SAEs)(From the beginning of Phase B (Year 2) up to study end (Year 10))
- Phase A: Number of Subjects With Seroconversion/Seroresponse to VZV(At Day 0, Day 42, Day 84, Year 1 and Year 2 time points)
- Phase A: Number of Subjects With Moderate or Severe Confirmed Varicella Case(From 42 days post dose 2 until the end of Phase A)
- Phase A: Immune Response to Varicella Vaccine With Respect to Anti-Varicella Zoster Virus (Anti-VZV) Antibody Concentrations(At Day 0, Day 42, Day 84, Year 1 and Year 2 time points)
- Phase A: Number of Subjects With Probable or Confirmed Varicella Case(From 42 days post dose 2 until the end of Phase A)
- Phase A: Immune Response to Measles With Respect to Anti-measles Antibody Concentrations in a Subset of Subjects(At Day 0, Day 42, Day 84, Year 1 and Year 2 time points)
- Phase A: Number of Subjects With Suspected Sign of Meningism Including Febrile Convulsions(Within 43 days (Day 0-42) post-vaccination period following each dose)
- Phase A: Number of Subjects Reporting Serious Adverse Events (SAEs)(From Day 0 until the end of Phase A (Year 2))
- Phase A: Immune Response to Mumps With Respect to Anti-mumps Antibody Concentrations in a Subset of Subjects(At Day 0, Day 42, Day 84, Year 1 and Year 2 time points)
- Phase A: Number of Subjects With Seroconversion/Seroresponse to Measles in a Subset of Subjects(At Day 0, Day 42, Day 84, Year 1 and Year 2 time points)
- Phase A: Number of Subjects With Confirmed Cases of Herpes Zoster(From Day 0 until the end of Phase A (Year 2))
- Phase A: Number of Subjects Reporting Solicited Local Symptoms(4 days post-vaccination period following each dose)
- Phase A: Number of Subjects Reporting Unsolicited Adverse Events (AEs)(Within 43 days (Day 0-42) post-vaccination period following each dose)
- Phase B: Characteristics of Varicella Cases(From the beginning of Phase B (Year 2) up to study end (Year 10))
- Phase B: Immune Response to Mumps With Respect to Anti-mumps Antibody Concentrations(At Year 4, Year 6, Year 8 and Year 10 time points)
- Phase A: Number of Subjects With a Seroconversion/Seroresponse to Rubella in a Subset of Subjects(At Day 0, Day 42, Day 84, Year 1 and Year 2 time points)
- Phase A: Number of Subjects Reporting Meningism(Within 43 days (Day 0-42) post-vaccination period following each dose)
- Phase A: Number of Subjects Reporting Parotitis(Within 43 days (Day 0-42) post-vaccination period following each dose)
- Phase A: Number of Subjects Reporting Rash(Within 43 days (Day 0-42) post-vaccination period following each dose)
- Phase A: Health Economics Analysis of Factors Leading to Indirect Costs Due to Varicella Illness(During Phase A (from Day 0 up to Year 2))
- Phase B: Number of Subjects With Moderate or Severe Confirmed Varicella Case(From the beginning of Phase B (Year 2) up to study end (Year 10))
- Phase B: Health Economics Analysis of Factors Leading to Indirect Costs Due to Varicella Illness(During Phase B)
- Phase A: Number of Subjects Reporting Fever(Within 15 days (Day 0-14) post-vaccination period following each dose)
- Phase B: Number of Subjects With Confirmed Varicella Case(From the beginning of Phase B (Year 2) up to study end (Year 10))
- Phase B: Number of Subjects With Anti-VZV Antibody Concentrations Above the Cut-off Value(At Year 4, Year 6, Year 8 and Year 10 time points)
- Phase B: Immune Response to Measles With Respect to Anti-measles Antibody Concentrations(At Year 4, Year 6, Year 8 and Year 10 time points)
- Phase B: Characteristics of Zoster Cases(From 6 weeks after Dose 2 until study end (Year 10))
- Phase B: Immune Response to Varicella Vaccine With Respect to Anti-Varicella Zoster Virus (Anti-VZV) Antibody Concentrations(At Year 4, Year 6, Year 8 and Year 10 time points)
- Phase B: Immune Response to Rubella With Respect to Anti-rubella Antibody Concentrations(At Year 4, Year 6, Year 8 and Year 10 time points)
- Phase A: Number of Subjects Reporting Fever(Within 43 days (Day 0-42) post-vaccination period following each dose)