Immunogenicity and Safety Study of Two Formulations of GlaxoSmithKline (GSK) Biologicals' Pneumococcal Vaccine (2830929A and 2830930A) When Administered in Healthy Infants
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 953
- 试验地点
- 43
- 主要终点
- Percentage (%) of Subjects (Synflorix and 12Pn Groups) With Antibody Concentration ≥ 0.2 μg/mL for Pneumococcal Serotypes
研究概览
简要总结
The purpose of this study is to assess the immunogenicity, reactogenicity and safety of two formulations of GSK Biologicals' pneumococcal vaccine (2830929A and 2830930A) administered as 3-dose primary vaccination during the first 6 months of life followed by a booster dose in the second year of life. To comply with the routine infant immunisation program, the licensed GSK Biologicals DTPa-HBV-IPV/Hib (Infanrix hexa) vaccine will be co-administered in infants with the pneumococcal study vaccines.
详细描述
The purpose of this study is to assess the immunogenicity of the two formulations of GSK Biologicals' pneumococcal vaccine 2830929A (11-valent vaccine or 11Pn vaccine) and 2830930A (12-valent vaccine or 12Pn vaccine), when administered as 3-dose primary vaccination during the first 6 months of life followed by a booster dose in the second year of life, when compared to immune responses to the licensed vaccines Synflorix™ and Prevnar 13™, and to assess the reactogenicity and safety of these two same investigational formulations when administered according to this schedule. To comply with the routine infant immunisation program, the licensed GSK Biologicals DTPa-HBV-IPV/Hib (Infanrix hexa™) vaccine will be co-administered in infants with the pneumococcal study vaccines.
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, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 6 Weeks 至 12 Weeks（Child）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Subjects who the investigator believes that their parent(s)/Legally Acceptable Representative(s) (LARs) can and will comply with the requirements of the protocol.
- •A male or female between, and including 6 to 12 weeks (42-90 days) of age at the time of the first vaccination. In addition, the first pneumococcal and DTPa-HBV-IPV/Hib vaccination should be given in accordance with the official national recommendations for the immunisation schedule of infants.
- •Written informed consent obtained from the parents/LAR(s) of the subject.
- •Healthy subjects as established by medical history and clinical examination before entering into the study.
- •Born after a gestation period of at least 36 weeks.
排除标准
- •Child in care.
- •Use of any investigational or non-registered product 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 of immunosuppressants or other immune-modifying drugs since birth.
- •Planned administration/administration of a vaccine containing diphtheria toxoid, tetanus toxoid (except MenC-TT in Spain) or CRM197 and not foreseen by the study protocol during any time of the study period, or of any other vaccines not foreseen by the protocol in the period starting from 30 days before each dose and ending 30 days after each dose of vaccine(s), with the following exceptions:
- •Licensed influenza vaccines are always allowed, even if concomitantly administered with the study vaccines.
- •Licensed rotavirus vaccines are allowed if administered at least 7 days before or after each dose of study of vaccines.
- •Licensed MenC-TT vaccine is allowed in Spain and should be concomitantly administered with the study vaccine at around 2, 4 and 12-15 months of age.
- •In case an emergency mass vaccination for an unforeseen public health threat (e.g. a pandemic) is organised by the public health authorities, outside the routine immunization program, that vaccine can be administered at any time during the study period provided it is licensed and used according to its Summary of Product Characteristics or Prescribing Information and according to the local governmental recommendations.
- •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 .
- •Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination.
- •Family history of congenital or hereditary immunodeficiency.
- •History of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccine(s).
- •Major congenital defects or serious chronic illness, including Kawasaki's syndrome.
- •History of any neurological disorders or seizures, including conditions such as hypotensive-hyporesponsive episodes, encephalopathy and any convulsions (afebrile and febrile).
- •Acute disease and/or fever at the time of enrolment.
- •Administration of immunoglobulins and/or any blood products since birth or planned administration during study period.
- •Previous vaccination against diphtheria, tetanus, pertussis, polio, H. influenzae type b.
- •Previous vaccination against S. pneumoniae.
- •History of or intercurrent diphtheria, tetanus, pertussis, hepatitis B, polio, H. influenzae type b disease.
- •Any medical condition which might interfere with the assessment of the study objectives in the opinion of the investigator.
研究组 & 干预措施
12Pn Group
Healthy male or female subjects between, and including 6 to 12 weeks (42-90 days) of age at the time of first vaccination, received a 3-dose primary vaccination course of GSK2830930A, or 12Pn, vaccine at 2, 3 and 4 months of age, followed by a booster dose of the same vaccine at 12-15 months of age, each dose being co-administered with one dose of Infanrix hexa™. The 3 first doses of 12Pn vaccine were administered intramuscularly into the right anterolateral thigh and Infanrix hexa™ was administered intramuscularly into the left anterolateral thigh. The booster dose of 12Pn vaccine was administered intramuscularly into the right deltoid (or thigh if the deltoid muscle size was not adequate) and that of Infanrix hexa™ was administered intramuscularly into the left deltoid (or thigh if the deltoid muscle size was not adequate).
干预措施: Infanrix hexa™ (Biological)
11Pn Group
Healthy male or female subjects between, and including 6 to 12 weeks (42-90 days) of age at the time of first vaccination, received a 3-dose primary vaccination course of GSK2830929A, or 11Pn, vaccine at 2, 3 and 4 months of age, followed by a booster dose of the same vaccine at 12-15 months of age, each dose being co-administered with one dose of Infanrix hexa™. The 3 first doses of 11Pn vaccine were administered intramuscularly into the right anterolateral thigh and Infanrix hexa™ was administered intramuscularly into the left anterolateral thigh. The booster dose of 11Pn vaccine was administered intramuscularly into the right deltoid (or thigh if the deltoid muscle size was not adequate) and that of Infanrix hexa™ was administered intramuscularly into the left deltoid (or thigh if the deltoid muscle size was not adequate).
干预措施: Infanrix hexa™ (Biological)
Prevnar13 Group
Healthy male or female subjects between, and including 6 to 12 weeks (42-90 days) of age at the time of first vaccination, received a 3-dose primary vaccination course of Prevnar13™ vaccine at 2, 3 and 4 months of age, followed by a booster dose of the same vaccine at 12-15 months of age, each dose being co-administered with one dose of Infanrix hexa™. The 3 first doses of Prevnar13™ were administered intramuscularly into the right anterolateral thigh and Infanrix hexa™ was administered intramuscularly into the left anterolateral thigh. The booster dose of Prevnar13™ was administered intramuscularly into the right deltoid (or thigh if the deltoid muscle size was not adequate) and that of Infanrix hexa™ was administered intramuscularly into the left deltoid (or thigh if the deltoid muscle size was not adequate ).
干预措施: Infanrix hexa™ (Biological)
11Pn Group
Healthy male or female subjects between, and including 6 to 12 weeks (42-90 days) of age at the time of first vaccination, received a 3-dose primary vaccination course of GSK2830929A, or 11Pn, vaccine at 2, 3 and 4 months of age, followed by a booster dose of the same vaccine at 12-15 months of age, each dose being co-administered with one dose of Infanrix hexa™. The 3 first doses of 11Pn vaccine were administered intramuscularly into the right anterolateral thigh and Infanrix hexa™ was administered intramuscularly into the left anterolateral thigh. The booster dose of 11Pn vaccine was administered intramuscularly into the right deltoid (or thigh if the deltoid muscle size was not adequate) and that of Infanrix hexa™ was administered intramuscularly into the left deltoid (or thigh if the deltoid muscle size was not adequate).
干预措施: Pneumococcal conjugate vaccine GSK2830929A (Biological)
12Pn Group
Healthy male or female subjects between, and including 6 to 12 weeks (42-90 days) of age at the time of first vaccination, received a 3-dose primary vaccination course of GSK2830930A, or 12Pn, vaccine at 2, 3 and 4 months of age, followed by a booster dose of the same vaccine at 12-15 months of age, each dose being co-administered with one dose of Infanrix hexa™. The 3 first doses of 12Pn vaccine were administered intramuscularly into the right anterolateral thigh and Infanrix hexa™ was administered intramuscularly into the left anterolateral thigh. The booster dose of 12Pn vaccine was administered intramuscularly into the right deltoid (or thigh if the deltoid muscle size was not adequate) and that of Infanrix hexa™ was administered intramuscularly into the left deltoid (or thigh if the deltoid muscle size was not adequate).
干预措施: Pneumococcal conjugate vaccine GSK2830930A (Biological)
Synflorix Group
Healthy male or female subjects between, and including 6 to 12 weeks (42-90 days) of age at the time of first vaccination, received a 3-dose primary vaccination course of Synflorix™ at 2, 3 and 4 months of age, followed by a booster dose of the same vaccine at 12-15 months of age, each dose being co-administered with one dose of Infanrix hexa™. The 3 first doses of Synflorix™ were administered intramuscularly into the right anterolateral thigh and Infanrix hexa™ was administered intramuscularly into the left anterolateral thigh. The booster dose of Synflorix™ was administered intramuscularly into the right deltoid (or thigh if the deltoid muscle size was not adequate) and that of Infanrix hexa™ was administered intramuscularly into the left deltoid (or thigh if the deltoid muscle size was not adequate).
干预措施: Synflorix™ (Biological)
Prevnar13 Group
Healthy male or female subjects between, and including 6 to 12 weeks (42-90 days) of age at the time of first vaccination, received a 3-dose primary vaccination course of Prevnar13™ vaccine at 2, 3 and 4 months of age, followed by a booster dose of the same vaccine at 12-15 months of age, each dose being co-administered with one dose of Infanrix hexa™. The 3 first doses of Prevnar13™ were administered intramuscularly into the right anterolateral thigh and Infanrix hexa™ was administered intramuscularly into the left anterolateral thigh. The booster dose of Prevnar13™ was administered intramuscularly into the right deltoid (or thigh if the deltoid muscle size was not adequate) and that of Infanrix hexa™ was administered intramuscularly into the left deltoid (or thigh if the deltoid muscle size was not adequate ).
干预措施: Prevnar 13™ (Biological)
Synflorix Group
Healthy male or female subjects between, and including 6 to 12 weeks (42-90 days) of age at the time of first vaccination, received a 3-dose primary vaccination course of Synflorix™ at 2, 3 and 4 months of age, followed by a booster dose of the same vaccine at 12-15 months of age, each dose being co-administered with one dose of Infanrix hexa™. The 3 first doses of Synflorix™ were administered intramuscularly into the right anterolateral thigh and Infanrix hexa™ was administered intramuscularly into the left anterolateral thigh. The booster dose of Synflorix™ was administered intramuscularly into the right deltoid (or thigh if the deltoid muscle size was not adequate) and that of Infanrix hexa™ was administered intramuscularly into the left deltoid (or thigh if the deltoid muscle size was not adequate).
干预措施: Infanrix hexa™ (Biological)
结局指标
主要结局
Percentage (%) of Subjects (Synflorix and 12Pn Groups) With Antibody Concentration ≥ 0.2 μg/mL for Pneumococcal Serotypes
时间窗: 1 month post-dose 3 (primary phase)
N = number of subjects with post primary vaccination results available. % = percentage of subjects with ELISA pneumococcal antibody concentrations ≥ 0.2 μg/mL. Antibodies assessed for this outcome measure were those against the vaccine pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F (ANTI-1, -4, -5, -6B, -7F, -9V, -14, -18C, -19F and -23F). Antibody concentrations were measured by 22F-Inhibition enzyme-linked immunosorbent assay (ELISA).
Percentage (%) of Subjects (Prevnar13 and 12Pn Groups) With Antibody Concentration ≥ 0.2 μg/mL for Anti-6A and 19A Pneumococcal Serotypes
时间窗: 1 month post-dose 3 (primary phase)
N = number of subjects with post primary vaccination results available. % = percentage of subjects with ELISA pneumococcal antibody concentrations ≥ 0.2 μg/mL. Antibodies assessed for this outcome measure were those against the vaccine pneumococcal serotype 6A and 19A (ANTI-6A and 19A). Antibody concentrations were measured by 22F-Inhibition enzyme-linked immunosorbent assay (ELISA).
Antibody Concentrations Against Pneumococcal Serotypes During the Primary Phase of the Study
时间窗: At study Month 3, e. g. at one month post-Dose 3 of pneumococcal vaccine
Antibodies assessed for this outcome measure were those against the vaccine/cross-reactive pneumococcal serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F (ANTI-1, -3, -4, -5, -6A, -6B, -7F, -9V, -14, -18C, -19A, -19F and -23F). Antibody concentrations were measured by 22F-Inhibition enzyme-linked immunosorbent assay (ELISA), expressed as geometric mean concentrations (GMCs), in micrograms per milliliter (µg/mL). The cut-off of the assay was an antibody concentration higher than or equal to (≥) 0.05 µg/mL. Primary outcome results correspond to antibody concentrations for all serotypes presented at the exception of those for the antibodies against the cross-reactive pneumococcal serotype 3 (ANTI-3).
Percentage (%) of Subjects (Synflorix and 11Pn Groups) With Antibody Concentration ≥ 0.2 μg/mL for Pneumococcal Serotypes
时间窗: 1 month post-dose 3 (primary phase)
N = number of subjects with post primary vaccination results available. % = percentage of subjects with ELISA pneumococcal antibody concentrations ≥ 0.2 μg/mL. Antibodies assessed for this outcome measure were those against the vaccine pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F (ANTI-1, -4, -5, -6B, -7F, -9V, -14, -18C, -19F and -23F). Antibody concentrations were measured by 22F-Inhibition enzyme-linked immunosorbent assay (ELISA).
Percentage (%) of Subjects (Prevnar13 and 11Pn Groups) With Antibody Concentration ≥ 0.2 μg/mL for Anti-19A Pneumococcal Serotype
时间窗: 1 month post-dose 3 (primary phase)
N = number of subjects with post primary vaccination results available. % = percentage of subjects with ELISA pneumococcal antibody concentrations ≥ 0.2 μg/mL. Antibodies assessed for this outcome measure were those against the vaccine pneumococcal serotype 19A (ANTI-19A). Antibody concentrations were measured by 22F-Inhibition enzyme-linked immunosorbent assay (ELISA).
次要结局
- Number of Subjects With Any and Grade 3 Solicited General Symptoms and With Solicited General Symptoms With Relationship to Vaccination, During the Booster Phase of the Study(Within the 4-day (Days 0-3) period after booster vaccination)
- Number of Subjects With Any Serious Adverse Events (SAEs) During the Entire Duration of the Study(From Day 0 to Month 11)
- Titers for Opsonophagocytic Activity Against Pneumococcal Serotypes 6C During the Primary Phase of the Study(At study Month 3, e. g. at one month post-Dose 3 of pneumococcal vaccine)
- Titers for Opsonophagocytic Activity Against Pneumococcal Serotypes 19A During the Booster Phase of the Study(At study Month 11, e. g. at one month post-Booster vaccination with pneumococcal vaccine)
- Antibody Concentrations Against Pneumococcal Serotype 6C During the Primary Phase of the Study.(At study Month 3, e. g. at one month post-Dose 3 of pneumococcal vaccine)
- Titers for Opsonophagocytic Activity Against Pneumococcal Serotypes 6C During the Booster Phase of the Study(At study Month 11, e. g. at one month post-Booster vaccination with pneumococcal vaccine)
- Antibody Concentrations Against Pneumococcal Serotypes During the Booster Phase of the Study(At study Month 10 (M10) and Month 11 (M11), e.g.: prior to and at one month post booster vaccination with pneumococcal vaccine)
- Titers for Opsonophagocytic Activity Against Pneumococcal Serotypes During the Booster Phase of the Study(At study Month 11, e.g.: at one month post booster vaccination with pneumococcal vaccine)
- Titers for Opsonophagocytic Activity Against Pneumococcal Serotypes During the Primary Phase of the Study(At study Month 3, e. g. at one month post-Dose 3 of pneumococcal vaccine)
- Concentrations of Antibodies Against Protein D (Anti-PD) During the Primary Phase of the Study(At study Month 3, e. g. at one month post-Dose 3 of pneumococcal vaccine)
- Concentrations of Antibodies Against Protein D (Anti-PD) During the Booster Phase of the Study(At study Month 10 (M10) and Month 11 (M11), e.g.: prior to and at one month post booster vaccination with pneumococcal vaccine)
- Number of Subjects With Any and Grade 3 Solicited Local Symptoms During the Primary Phase(Within the 4-day (Days 0-3) post-vaccination period following each primary dose (D).)
- Number of Subjects With Any and Grade 3 Solicited General Symptoms and With Solicited General Symptoms With Relationship to Vaccination, During the Primary Phase of the Study(Within the 4-day (Days 0-3) post-vaccination period following each primary dose (D).)
- Number of Subjects With Any Unsolicited Adverse Events (AEs) During the Primary Phase of the Study(Within the 31-day (Days 0-30) period post primary vaccination, across doses)
- Number of Subjects With Any Unsolicited Adverse Events (AEs) During the Booster Phase of the Study(Within the 31-day (Days 0-30) period post booster vaccination)
- Antibody Concentrations Against Pneumococcal Serotype 6A During the Booster Phase of the Study(At study Month 10 (M10) and Month 11 (M11), e.g.: prior to and at one month post booster vaccination with pneumococcal vaccine)
- Number of Subjects With Any and Grade 3 Solicited Local Symptoms During the Booster Phase of the Study(Within the 4-day (Days 0-3) period after booster vaccination)
- Number of Subjects With Any Serious Adverse Events (SAEs)During the Primary Phase of the Study(From Month 0 to Month 3)
- Titers for Opsonophagocytic Activity Against Pneumococcal Serotypes 19A During the Primary Phase of the Study(At study Month 3, e. g. at one month post-Dose 3 of pneumococcal vaccine)
- Antibody Concentrations Against Pneumococcal Serotype 6C During the Booster Phase of the Study.(At study Month 10 (M10) and Month 11 (M11), e.g.: prior to and at one month post booster vaccination with pneumococcal vaccine)