Immunogenicity & Safety of GSK Biologicals' Inactivated Hepatitis A Vaccine (Havrix™) Co-administered With Merck & Company, Inc. Measles-Mumps-Rubella Vaccine (M-M-RII) & Merck & Co Varicella Vaccine (VARIVAX™) to Children 15 Months of Age
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 1,474
- 试验地点
- 43
- 主要终点
- Number of Subjects With Vaccine Response for Anti-rubella Antibodies in HAV+MMR+V and MMR+V→HAV Groups
研究概览
简要总结
This is a study to evaluate the immune response and safety of GSK Biologicals 2-dose inactivated hepatitis A vaccine when administered with a measles/mumps/rubella vaccine and a varicella (chickenpox) vaccine in children as young as 15 months of age.
The Protocol Posting has been updated in order to comply with the FDA Amendment Act, Sep 2007.
详细描述
An open, controlled comparison of Havrix™ administered alone or with MMR II and Varivax™. The three groups evaluated are: 1) Havrix™ alone, 2) Havrix™ + MMR II and Varivax™ and 3) MMR II and Varivax™ followed by Havrix™ one month later.
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
- None
入排标准
- 年龄范围
- 12 Months 至 13 Months（Child）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Subjects whose parents/guardians are believed by the investigator to be willing to comply with the requirements of the protocol
- •A male or female child 12 and 13 months of age at the time of entry into the Enrollment Phase
- •Written informed consent obtained from the parents or guardian of the subject,
- •Free of obvious health problems as established by medical history and history-directed physical examination before entering into the study, and
- •Parents/guardian of the subject must have a telephone or be able to be contacted by telephone
排除标准
- •Use of any investigational or non-registered drug or vaccine other than the study vaccine(s) within 42 days preceding the first dose of study vaccine, or planned use during the study period, Chronic administration (defined as more than 14 days) of immuno-suppressant or other immune-modifying drugs within six months prior to vaccination or planned administration at any time during the study period. (For corticosteroids, this will mean prednisone, or equivalent, ≥0.5 mg/kg/day. Inhaled, nasal and topical steroids are allowed.) Planned administration or administration of any vaccine not foreseen by the study protocol during the period 31 days before and 31 days after each dose of study vaccine(s).
- •Previous vaccination against hepatitis A,
- •History of hepatitis A,
- •Known exposure to hepatitis A,
- •Previous vaccination against measles, mumps, rubella and/or varicella,
- •History of measles, mumps, rubella and/or varicella,
- •Known exposure to measles, mumps, rubella and/or varicella within 30 days prior to the start of the study,
- •Planned chronic use of salicylates during the 6-week period following administration of the doses of study vaccine(s),
- •Any confirmed or suspected immunosuppressive or immunodeficient condition, including human immunodeficiency virus (HIV) infection,
- •A family history of congenital, hereditary or infectious immunodeficiency or parental risk factors for HIV infection,
- •History of allergic disease/reactions or hypersensitivity likely to be exacerbated by any component of HavrixTM, M-M-RII or VARIVAXTM, including 2-phenoxyethanol, neomycin and gelatin,
- •History of anaphylactic or anaphylactoid reactions to egg proteins,
- •History of hypersensitivity/allergic reaction to latex. Note: The tip cap and the rubber plunger of the HavrixTM needleless pre-filled syringes contain dry natural latex rubber.
- •Major congenital defects or serious chronic illness,
- •Active untreated tuberculosis,
- •History of significant blood dyscrasias
- •History of any neurologic disorder (a history of febrile seizures not associated with an underlying neurological disorder does not exclude the subject)
- •Acute disease at the time of vaccination
- •Administration of immunoglobulins and/or any blood products within three months prior to the first dose of study vaccine or planned administration at any time during the entire study period
研究组 & 干预措施
HAV+MMR+V Group
Subjects received 1 dose of Havrix®, coadministered with M-M-R®II and VARIVAX®, at Day 0 and 1 dose of Havrix® between Month 6 and Month 9
干预措施: M-M-R®II (Biological)
HAV+MMR+V Group
Subjects received 1 dose of Havrix®, coadministered with M-M-R®II and VARIVAX®, at Day 0 and 1 dose of Havrix® between Month 6 and Month 9
干预措施: VARIVAX® (Biological)
MMR+V→HAV Group
Subjects received 1 dose of M-M-R®II and VARIVAX® at Day 0 and then 2 doses of Havrix® (1 dose at Day 42 and 1 dose between Month 7.5 and Month 10.5)
干预措施: M-M-R®II (Biological)
MMR+V→HAV Group
Subjects received 1 dose of M-M-R®II and VARIVAX® at Day 0 and then 2 doses of Havrix® (1 dose at Day 42 and 1 dose between Month 7.5 and Month 10.5)
干预措施: VARIVAX® (Biological)
HAV Group
Subjects received 2 doses of Havrix® (1 dose at Day 0 and 1 dose between Month 6 and Month 9)
干预措施: Havrix® (Biological)
HAV+MMR+V Group
Subjects received 1 dose of Havrix®, coadministered with M-M-R®II and VARIVAX®, at Day 0 and 1 dose of Havrix® between Month 6 and Month 9
干预措施: Havrix® (Biological)
MMR+V→HAV Group
Subjects received 1 dose of M-M-R®II and VARIVAX® at Day 0 and then 2 doses of Havrix® (1 dose at Day 42 and 1 dose between Month 7.5 and Month 10.5)
干预措施: Havrix® (Biological)
结局指标
主要结局
Number of Subjects With Vaccine Response for Anti-rubella Antibodies in HAV+MMR+V and MMR+V→HAV Groups
时间窗: 42 days following administration of M-M-R®II and VARIVAX®
Vaccine response is defined as the appearance of antibodies with titers greater than or equal to the predefined cut-off value in the serum of subject seronegative before vaccination. Cut-off value assessed include 10 milli-international units per milliliter (mIU/mL).
Number of Subjects Seroconverted for Anti-measle, Anti-mumps and Anti-varicella Antibodies in HAV+MMR+V and MMR+V→HAV Groups
时间窗: 42 days following the administration of M-M-R®II and VARIVAX®
Seroconversion is defined as the appearance of antibodies with titers greater than or equal to the predefined cut-off value in the serum of subject seronegative before vaccination. Cut-off values assessed include 150 milli-international units per milliliter (mIU/mL) for anti-measles antibodies, 28 Effective Dose 50 (ED50) for anti-mumps antibodies and 1:5 for anti-varicella antibodies.
Anti-hepatitis A Virus (HAV) Antibody Concentrations in HAV and HAV+MMR+V Groups.
时间窗: 31 days following the second dose of Havrix®
Concentrations are given as geometric mean concentrations (GMCs) expressed as milli-international units per milliliter (mIU/mL).
Number of Subjects With Anti-hepatitis A Virus (HAV) Antibody Concentration Equal or Above the Cut-off Value in HAV and HAV+MMR+V Groups
时间窗: 31 days following the second dose of Havrix®
Anti-HAV antibody cut-off value assessed include 15 milli-international units per milliliter (mIU/mL).
次要结局
- Number of Subjects With Anti-hepatitis A Virus (HAV) Antibody Concentrations Above the Cut-off Value in MMR+V→HAV Group(31 days following the second dose of Havrix®)
- Anti-hepatitis A Virus (HAV) Antibody Concentrations in MMR+V→HAV Group(31 days following the second dose of Havrix®)
- Number of Subjects With Anti-hepatitis A Virus (HAV) Antibody Concentration Equal or Above the Cut-off Value in HAV and HAV+MMR+V Groups(42 days following the first dose of Havrix®)
- Anti-hepatitis A Virus (HAV) Antibody Concentrations in HAV and HAV+MMR+V Groups(42 days following the first dose of Havrix®)
- Number of Subjects Reporting Measles, Mumps, Rubella and Varicella Specific Solicited General Adverse Events(During the 43-day period following each dose of vaccine)
- Number of Subjects Reporting Unsolicited Adverse Events (AEs)(During the 31-day period following each dose of vaccine)
- Anti-measles, Anti-mumps, Anti-rubella and Anti-varicella Antibody Titers in HAV+MMR+V and MMR+V→HAV Groups(42 days following the administration of M-M-R®II and VARIVAX®)
- Number of Subjects With Vaccine Response to Havrix®(31 days following the second dose of Havrix®)
- Number of Subjects Reporting Serious Adverse Events (SAEs)(During the Active Phase (from Day 0 up to Day 31 after the second dose) and the Extended Safety Follow-up Phase of the study (from Day 31 after the second dose up to study end))
- Number of Subjects Reporting New Chronic Illnesses(During the Active Phase (from Day 0 up to Day 31 after the second dose) and the Extended Safety Follow-up Phase of the study (from Day 31 after the second dose up to study end))
- Number of Subjects Reporting Solicited Local Symptoms(During the 4-day period following each dose of vaccine)
- Number of Subjects Reporting Solicited General Symptoms(During the 4-day period following each dose of vaccine)
- Number of Subjects Reporting Medically Significant Events(During the Active Phase (from Day 0 up to Day 31 after the second dose) and the Extended Safety Follow-up Phase of the study (from Day 31 after the second dose up to study end))