A Phase III, Randomized, Multinational Study, Double-blinded for the Immunogenicity and Consistency Evaluation of 3 Hib-MenCY-TT Vaccine Lots and Single-blinded and Controlled for the Evaluation of Safety and Immunogenicity of GSK Biologicals' Haemophilus Influenzae Type b and Neisseria Meningitidis Serogroups C and Y-tetanus Toxoid Conjugate Vaccine Combined (Hib-MenCY-TT) Compared to Monovalent Hib Vaccine in Healthy Infants at 2, 4, 6, and 12 to 15 Months of Age.
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 4,441
- 试验地点
- 94
- 主要终点
- Anti-Polyribosyl Ribitol Phosphate (PRP) Antibody Concentrations
研究概览
简要总结
This study evaluates the immunogenicity and consistency of 3 Hib-MenCY-TT vaccine lots and the safety and immunogenicity of Hib-MenCY-TT vaccine compared to a control group receiving licensed Hib conjugate vaccine, when each are co-administered with Pediarix® to healthy infants at 2, 4, and 6 months of age. The study will also evaluate the safety and immunogenicity of Hib-MenCY-TT vaccine compared to a control group receiving licensed Hib conjugate vaccine, when each are co-administered with M-M-R® II and Varivax® at 12 to 15 months of age.
详细描述
The subjects from this study will participate in one of three cohorts:
- US Safety and Immunogenicity (Cohort 1): All immunogenicity analyses in the primary and booster phases will be evaluated in this cohort. These subjects will also contribute to the safety analyses in the primary and booster phases.
- Safety Only (Cohort 2): Only safety objectives will be assessed in the primary and booster phases for this cohort.
- Non-US Safety and Immunogenicity (Cohort 3): Only descriptive immunogenicity results in the primary and booster phases will be reported for this cohort. These subjects will also contribute to the safety analyses in the primary and booster phases.
Treatment allocation:
Primary phase: Subjects will be randomized with balanced allocation (1:1:1:1) to 1 of the 4 treatment groups and with a stratification according to the cohort. Assignment to a cohort will be based on study site.
Booster phase: Subjects who received Hib-MenCY-TT vaccine in the primary phase will receive a booster dose of Hib-MenCY-TT vaccine. Subjects who received ActHIB in the primary phase will receive a booster dose of PedvaxHIB.
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, Investigator)
入排标准
- 年龄范围
- 6 Weeks 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 that parents/guardians can and will comply with the requirements of the protocol
- •A male or female between, and including, 6 and 12 weeks of age at the time of the first vaccination.
- •Written informed consent obtained from the parent or guardian of the subject.
- •Healthy subjects as established by medical history and clinical examination before entering into the study.
- •Born after 36 weeks gestation.
- •Infants who have not received a previous dose of hepatitis B vaccine or those who have received only 1 dose of hepatitis B vaccine administered at least 30 days prior to enrollment.
- •Infants may have received a birth dose of Bacillus Calmette-Guérin (BCG) vaccine.
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.
- •Chronic administration (defined as more than 14 days) of immunosuppressants or other immune-modifying drugs since birth.
- •Planned administration/ administration of a vaccine not foreseen by the study protocol within 30 days of the first dose of study vaccine(s). (Synagis® [palivizumab, MedImmune], Prevnar (Prevenar), rotavirus vaccine, and influenza vaccine are allowed.
- •Previous vaccination against Neisseria meningitidis, Haemophilus influenzae type b, diphtheria, tetanus, pertussis, and/or poliovirus; more than one previous dose of hepatitis B vaccine.
- •History of Neisseria meningitidis, Haemophilus influenzae type b, diphtheria, tetanus, pertussis, hepatitis B, and/or poliovirus disease.
- •Any confirmed or suspected immunosuppressive or immunodeficient condition based on medical history and physical examination (no laboratory testing is required).
- •History of allergic disease or reactions likely to be exacerbated by any component of the vaccines, including dry natural latex rubber.
- •Major congenital defects or serious chronic illness.
- •History of any neurologic disorders or seizures.
- •Acute disease at time of enrollment.
- •Administration of immunoglobulins and/or any blood products since birth or planned administration during the study period.
- •Concurrent participation 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).
- •Additional specific criteria for the US subjects in Cohort
- •In addition, for Cohorts 2 and 3, subjects should not be administered M-M-R II and Varivax if any of these criteria apply:
- •History of measles, mumps, rubella or varicella.
- •Previous vaccination against measles, mumps, rubella or varicella.
- •Hypersensitivity to any component of the vaccines, including gelatin or neomycin.
- •Patients receiving immunosuppressive therapy.
- •Individuals with blood dyscrasias, leukemia, lymphomas of any type, or other malignant neoplasms affecting the bone marrow or lymphatic systems.
- •Individuals with primary and acquired immunodeficiency states.
- •Individuals with a family history of congenital or hereditary immunodeficiency, until the immune competence of the potential vaccine recipient is demonstrated.
- •Individuals with active tuberculosis.
- •Acute disease at time of booster vaccination.
研究组 & 干预措施
Menhibrix A Group
Subjects were primed with 3 doses of Menhibrix vaccine Lot A co-administered with Pediarix and boosted with 1 dose of Menhibrix vaccine, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. Menhibrix and Pediarix vaccines were administered intramuscularly in the right or left upper thigh, respectively. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.
干预措施: Varivax (Biological)
Menhibrix B Group
Subjects were primed with 3 doses of Menhibrix vaccine Lot B co-administered with Pediarix and boosted with 1 dose of Menhibrix vaccine, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. Menhibrix and Pediarix vaccines were administered intramuscularly in the right or left upper thigh, respectively. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.
干预措施: M-M-R II (Biological)
Menhibrix A Group
Subjects were primed with 3 doses of Menhibrix vaccine Lot A co-administered with Pediarix and boosted with 1 dose of Menhibrix vaccine, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. Menhibrix and Pediarix vaccines were administered intramuscularly in the right or left upper thigh, respectively. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.
干预措施: M-M-R II (Biological)
Menhibrix Group
Subjects were primed with 3 doses of Menhibrix vaccine Lot A, B or C co-administered with Pediarix and boosted with 1 dose of Menhibrix vaccine, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. Menhibrix and Pediarix vaccines were administered intramuscularly in the right or left upper thigh, respectively. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.
干预措施: M-M-R II (Biological)
Menhibrix A Group
Subjects were primed with 3 doses of Menhibrix vaccine Lot A co-administered with Pediarix and boosted with 1 dose of Menhibrix vaccine, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. Menhibrix and Pediarix vaccines were administered intramuscularly in the right or left upper thigh, respectively. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.
干预措施: GSK Biologicals' Haemophilus influenzae type b and Neisseria meningitidis 792014 vaccine (Biological)
Menhibrix A Group
Subjects were primed with 3 doses of Menhibrix vaccine Lot A co-administered with Pediarix and boosted with 1 dose of Menhibrix vaccine, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. Menhibrix and Pediarix vaccines were administered intramuscularly in the right or left upper thigh, respectively. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.
干预措施: Pediarix (Biological)
Menhibrix A Group
Subjects were primed with 3 doses of Menhibrix vaccine Lot A co-administered with Pediarix and boosted with 1 dose of Menhibrix vaccine, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. Menhibrix and Pediarix vaccines were administered intramuscularly in the right or left upper thigh, respectively. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.
干预措施: Prevnar (Biological)
Menhibrix B Group
Subjects were primed with 3 doses of Menhibrix vaccine Lot B co-administered with Pediarix and boosted with 1 dose of Menhibrix vaccine, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. Menhibrix and Pediarix vaccines were administered intramuscularly in the right or left upper thigh, respectively. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.
干预措施: GSK Biologicals' Haemophilus influenzae type b and Neisseria meningitidis 792014 vaccine (Biological)
Menhibrix B Group
Subjects were primed with 3 doses of Menhibrix vaccine Lot B co-administered with Pediarix and boosted with 1 dose of Menhibrix vaccine, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. Menhibrix and Pediarix vaccines were administered intramuscularly in the right or left upper thigh, respectively. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.
干预措施: Pediarix (Biological)
Menhibrix B Group
Subjects were primed with 3 doses of Menhibrix vaccine Lot B co-administered with Pediarix and boosted with 1 dose of Menhibrix vaccine, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. Menhibrix and Pediarix vaccines were administered intramuscularly in the right or left upper thigh, respectively. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.
干预措施: Prevnar (Biological)
Menhibrix C Group
Subjects were primed with 3 doses of Menhibrix vaccine Lot C co-administered with Pediarix and boosted with 1 dose of Menhibrix vaccine, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. Menhibrix and Pediarix vaccines were administered intramuscularly in the right or left upper thigh, respectively. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.
干预措施: GSK Biologicals' Haemophilus influenzae type b and Neisseria meningitidis 792014 vaccine (Biological)
Menhibrix C Group
Subjects were primed with 3 doses of Menhibrix vaccine Lot C co-administered with Pediarix and boosted with 1 dose of Menhibrix vaccine, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. Menhibrix and Pediarix vaccines were administered intramuscularly in the right or left upper thigh, respectively. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.
干预措施: Pediarix (Biological)
Menhibrix C Group
Subjects were primed with 3 doses of Menhibrix vaccine Lot C co-administered with Pediarix and boosted with 1 dose of Menhibrix vaccine, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. Menhibrix and Pediarix vaccines were administered intramuscularly in the right or left upper thigh, respectively. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.
干预措施: Prevnar (Biological)
Menhibrix Group
Subjects were primed with 3 doses of Menhibrix vaccine Lot A, B or C co-administered with Pediarix and boosted with 1 dose of Menhibrix vaccine, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. Menhibrix and Pediarix vaccines were administered intramuscularly in the right or left upper thigh, respectively. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.
干预措施: GSK Biologicals' Haemophilus influenzae type b and Neisseria meningitidis 792014 vaccine (Biological)
Menhibrix Group
Subjects were primed with 3 doses of Menhibrix vaccine Lot A, B or C co-administered with Pediarix and boosted with 1 dose of Menhibrix vaccine, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. Menhibrix and Pediarix vaccines were administered intramuscularly in the right or left upper thigh, respectively. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.
干预措施: Pediarix (Biological)
Menhibrix Group
Subjects were primed with 3 doses of Menhibrix vaccine Lot A, B or C co-administered with Pediarix and boosted with 1 dose of Menhibrix vaccine, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. Menhibrix and Pediarix vaccines were administered intramuscularly in the right or left upper thigh, respectively. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.
干预措施: Prevnar (Biological)
ActHIB Group
Subjects were primed with 3 doses of ActHIB co-administered with Pediarix and boosted with 1 dose of PedvaxHIB, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. ActHIB, PedvaxHIB vaccines were administered intramuscularly in the right upper thigh and Pediarix vaccine in the left upper thigh. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.
干预措施: ActHIB (Biological)
ActHIB Group
Subjects were primed with 3 doses of ActHIB co-administered with Pediarix and boosted with 1 dose of PedvaxHIB, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. ActHIB, PedvaxHIB vaccines were administered intramuscularly in the right upper thigh and Pediarix vaccine in the left upper thigh. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.
干预措施: PedvaxHIB (Biological)
Menhibrix B Group
Subjects were primed with 3 doses of Menhibrix vaccine Lot B co-administered with Pediarix and boosted with 1 dose of Menhibrix vaccine, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. Menhibrix and Pediarix vaccines were administered intramuscularly in the right or left upper thigh, respectively. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.
干预措施: Varivax (Biological)
Menhibrix Group
Subjects were primed with 3 doses of Menhibrix vaccine Lot A, B or C co-administered with Pediarix and boosted with 1 dose of Menhibrix vaccine, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. Menhibrix and Pediarix vaccines were administered intramuscularly in the right or left upper thigh, respectively. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.
干预措施: Varivax (Biological)
Menhibrix C Group
Subjects were primed with 3 doses of Menhibrix vaccine Lot C co-administered with Pediarix and boosted with 1 dose of Menhibrix vaccine, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. Menhibrix and Pediarix vaccines were administered intramuscularly in the right or left upper thigh, respectively. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.
干预措施: M-M-R II (Biological)
Menhibrix C Group
Subjects were primed with 3 doses of Menhibrix vaccine Lot C co-administered with Pediarix and boosted with 1 dose of Menhibrix vaccine, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. Menhibrix and Pediarix vaccines were administered intramuscularly in the right or left upper thigh, respectively. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.
干预措施: Varivax (Biological)
结局指标
主要结局
Anti-Polyribosyl Ribitol Phosphate (PRP) Antibody Concentrations
时间窗: One month after primary vaccination
Concentrations are given as Geometric Mean Concentrations (GMCs) and are expressed in microgram per millilitre (µg/mL) This analysis occurred on the cohort 1: Cohort 1 was to include subjects in the US on which all immunogenicity analyses were to be based. These subjects also contributed to the safety analysis.
Number of Subjects With Anti-mumps Titer Equal to or Above 28 Estimated Dose 50 (ED50)
时间窗: 42 days after the fourth dose
The analysis was performed on initially seronegative subjects. Seronegative subjects are subjects with anti-mumps antibody titers below 28 ED50 Co-administration with MMR-II vaccine.
Number of Subjects With Anti-rubella Antibody Concentrations Equal to or Above 10 International Units Per Milli-litre (IU/mL)
时间窗: 42 days after the fourth dose
The analysis was performed on initially seronegative subjects. Seronegative subjects are subjects with anti-measles antibody concentrations below 4 IU/mL. Co-administration with MMR-II vaccine.
Neisseria Meningitidis Serogroup C (MenC) Serum Bactericidal Assay Using Human Complement (hSBA) Antibody Titers
时间窗: One month after primary vaccination
Titers were expressed as Geometric Mean Titers (GMTs) This analysis occured on the cohort 1 : Cohort 1 was to include subjects in the US on which all immunogenicity analyses were to be based. These subjects also contributed to the safety analysis.
hSBA-MenC Antibody Titers
时间窗: Prior to the fourth dose vaccination and 42 days after the fourth dose
Titers are expressed as Geometric Mean Titers (GMTs) This analysis occurred on the cohort 1: Cohort 1 was to include subjects in the US on which all immunogenicity analyses were to be based. These subjects also contributed to the safety analysis.
Number of Subjects With hSBA-MenC Titer Equal to or Above 1:8
时间窗: 42 days after the fourth dose
This analysis occurred on the cohort 1: Cohort 1 was to include subjects in the US on which all immunogenicity analyses were to be based. These subjects also contributed to the safety analysis.
Number of Subjects With Anti-measles Antibody Concentrations Equal to or Above 150 Milli-international Units Per Milli-liter (mIU/ML)
时间窗: 42 days after the fourth dose
The analysis was performed on initially seronegative subjects. Seronegative subjects are subjects with anti-measles antibody concentrations below 150 mIU/mL. Co-administration with MMR-II vaccine
Number of Subjects With Anti-varicella Titer Equal to or Above 1:5
时间窗: 42 days after the fourth dose
The analysis was performed on initially seronegative subjects. Seronegative subjects are subjects with anti-measles antibody titer below 1:5. Co-administration with Varivax vaccine.
Number of Subjects With hSBA-MenY Titer Equal to or Above 1:8
时间窗: 42 days after the fourth dose
This analysis occurred on the cohort 1: Cohort 1 was to include subjects in the US on which all immunogenicity analyses were to be based. These subjects also contributed to the safety analysis.
Number of Subjects With Anti-PRP Antibody Concentration Equal to or Above 1.0 Microgram Per Milliliter
时间窗: 42 days after the fourth dose
This analysis occurred on the cohort 1: Cohort 1 was to include subjects in the US on which all immunogenicity analyses were to be based. These subjects also contributed to the safety analysis.
Neisseria Meningitidis Serogroup Y (MenY) Serum Bactericidal Assay Using Human Complement (hSBA) Antibody Titers
时间窗: One month after primary vaccination
Titers are expressen as Geometric Mean Titers (GMTs) This analysis occurred on the cohort 1: Cohort 1 was to include subjects in the US on which all immunogenicity analyses were to be based. These subjects also contributed to the safety analysis.
hSBA-MenY Antibody Titers
时间窗: Prior to the fourth dose vaccination and 42 days after the fourth dose
Titers are expressed as Geometric Mean Titers (GMTs) This analysis occurred on the cohort 1: Cohort 1 was to include subjects in the US on which all immunogenicity analyses were to be based. These subjects also contributed to the safety analysis.
Number of Subjects With Anti-PRP Antibody Concentration Equal to or Above 1.0 Microgram Per Milliliter (µg/mL)
时间窗: One month after primary vaccination
This analysis occurred on the cohort 1: Cohort 1 was to include subjects in the US on which all immunogenicity analyses were to be based. These subjects also contributed to the safety analysis.
次要结局
- Number of Subjects With Anti-tetanus (Anti-T) and Anti-diphtheria Toxoid (Anti-D) Antibody Concentrations Equal to or Above 0.1 International Units Per Millilitre (IU/mL)(One month after primary vaccination)
- Number of Subjects With hSBA-MenC and hSBA-MenY Titers Equal to or Above the Cut-off Values(Prior to the fourth dose vaccination and one month after fourth dose vaccination)
- Anti-HBS Antibody Concentrations(One month after primary vaccination)
- Number of Subjects With Antibodies to Neisseria Meningitidis Serogroup C and Y Polysaccharide Capsule (Anti-PSC and Anti-PSY) Concentrations Equal to or Above the Cut-off Values(One month after primary vaccination)
- hSBA-MenC and hSBA-MenY Antibody Titers(Prior to the fourth dose vaccination and one month after fourth dose vaccination)
- Anti-PSC and Anti-PSY Antibodies Concentrations(One month after the primary vaccination course)
- Anti-D and Anti-T Antibody Concentrations(One month after primary vaccination)
- Number of Subjects With Anti Hepatitis B Surface Antigen (Anti-HBs) Antibody Concentrations Equal to or Above 10.0 Milli-international Units Per Millilitre (mIU/mL)(One month after primary vaccination)
- Number of Subjects With Anti-pertussis Toxoid (Anti-PT), Anti-filamentous Hemagglutinin (Anti-FHA) and Anti-pertactin (Anti-PRN) Antibody Concentrations Equal to or Above 5 ELISA Units Per Millilitre (EL.U/mL)(One month after primary vaccination)
- Anti-PT, Anti-FHA and Anti-PRN Antibody Concentrations(One month after primary vaccination)
- Anti-poliovirus Types 1, 2 and 3 Titers(One month after primary vaccination)
- Anti-PSC and Anti-PSY Antibody Concentrations(Prior to the fourth dose vaccination and 42 days after fourth dose vaccination)
- Number of Subjects Reporting New Onset of Chronic Illness(es) (NOCDs)(From the fourth dose through the end of the 6-month safety follow-up)
- Number of Subjects With Anti-poliovirus Types 1, 2 and 3 Equal to or Above 8 Estimated Dose 50 (ED50)(One month after primary vaccination)
- Number of Subjects With Anti-PRP Antibody Concentrations Equal to or Above the Cut-off Values(Prior to the fourth dose vaccination and one month after fourth dose vaccination)
- Anti-rubella Antibody Concentrations(42 days after fourth vaccination)
- Number of Subjects Reporting Increased Circumferential Swelling at the Injection Limb(s)(Within 4 days (Day 0 to Day 3) after fourth dose vaccination)
- Number of Subjects Reporting Adverse Events Resulting in Physicians (MD) Office Visits(From the fourth dose through the end of the 6-month safety follow-up)
- Number of Subjects With Anti-PRP Antibody Concentration Equal to or Above 1.0 Microgram Per Milliliter (µg/mL).(Prior to the fourth dose vaccination)
- Number of Subjects With hSBA-MenC and hSBA-MenY Antibody Titers Equal to or Above the Cut-off Values(One month after the primary vaccination course)
- Anti-varicella Antibody Titers(42 days after fourth vaccination)
- Number of Subjects Reporting General Symptoms Specific to Measles, Mumps, Rubella and Varicella Vaccination(Within 43 days (Day 0 through Day 42) after vaccination)
- Anti-mumps Antibody Titers(42 days after fourth vaccination)
- Anti-PRP Antibody Concentrations(Prior to the fourth vaccination and 42 days after fourth vaccination)
- Number of Subjects With hSBA-MenC and hSBA-MenY Antibody Concentrations Equal to or Above 1:4(Prior to the fourth dose vaccination and 42 days after fourth vaccination)
- Anti-measles Antibody Concentrations(42 days after fourth vaccination)
- Number of Subjects With Anti-rubella Antibody Concentrations Equal to or Above 4 International Units Per Millilitre (IU/mL)(42 days after fourth vaccination)
- Number of Subjects With Anti-H1N1, Anti-H3N2 and Anti-influenza-B (Anti B) Antibody Titers Equal to or Above 1:40(Prior to the fourth dose vaccination and one month after the fourth dose vaccination)
- Number of Subjects Reporting Unsolicited Adverse Events (AEs)(Within 31 days (Day 0-30) following the fourth dose)
- Number of Subjects Reporting Adverse Events Resulting in Emergency Room (ER) Visits(From the fourth dose through the end of the 6-month safety follow-up)
- Number of Subjects With Anti-PSC and Anti-PSY Antibody Concentrations Equal to or Above the Cut-off Values(Prior to the fourth dose vaccination and 42 days after fourth dose vaccination)
- Number of Subjects With Anti-PRP Antibody Concentrations Equal to or Above the Cut-off Value(One month after the primary vaccination course)
- Number of Subjects With Anti-PRP Antibody Concentrations Equal to or Above 0.15 Microgram Per Milliliter (µg/mL)(Prior to the fourth dose vaccination and 42 days after fourth vaccination)
- Number of Subjects With Anti-measles Antibody Concentrations Equal to or Above 200 Milli-international Units Per Millilitre (mIU/mL)(42 days after fourth vaccination)
- Number of Subjects With Anti-mumps Titer Equal to or Above the Cut-off Values(42 days after fourth vaccination)
- Number of Subjects Reporting Fever Above 39.5 Degrees Celsius/103.1 Degrees Fahrenheit(In the 4-day (Day0-3) follow-up period after the fourth dose)
- Number of Subjects Reporting Solicited Local and General Symptoms(Within the 4 days (Day 0-3) post-vaccination period following the fourth dose)
- Number of Subjects Reporting Serious Adverse Events (SAEs)(From the fourth dose through the end of the 6-month safety follow-up)
- Number of Subjects Reporting Rash(From the fourth dose through the end of the 6-month safety follow-up)
- Number of Subjects Reporting Adverse Events Resulting in Physicians (MD) Office Visits.(From Dose 0 through 6 months after the last primary dose or until administration of the fourth dose)
- Number of Subjects With Anti-varicella Titer Equal to or Above 1:40(42 days after fourth vaccination)
- Number of Subjects With hSBA-MenC and hSBA-MenY Antibody Titer Equal to or Above 1:8.(Prior to the fourth dose vaccination)