Impact of Immediate or Delayed Prophylactic Antipyretic Treatment on the Immunogenicity, Reactogenicity and Safety of GlaxoSmithKline Biologicals' Pneumococcal Vaccine 1024850A and the Co-administered DTPa-combined Vaccines
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 850
- 试验地点
- 1
- 主要终点
- Number of Subjects With Antibody Concentrations Against Vaccine Pneumococcal Serotypes Greater Than or Equal to (≥) the Cut-off
研究概览
简要总结
The aim of the current study is to determine whether ibuprofen, given as immediate or delayed prophylactic antipyretic treatment in a standardized manner, significantly impacts the immune response in children receiving primary vaccination with GlaxoSmithKline (GSK) Biologicals' 10-valent pneumococcal conjugate vaccine, co-administered with DTPa-combined vaccines, at 3, 4 and 5 months of age.
In addition, this study will further evaluate the impact of prophylactic administration of paracetamol following primary vaccination with immediate or delayed administration or when given in an immediate manner at the time of the booster dose.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Factorial
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 12 Weeks 至 16 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) (LAR) can and will comply with the requirements of the protocol.
- •A male or female between, and including, 12 and 16 weeks (84-118 days) of age at the time of the first vaccination.
- •Written informed consent obtained from the parent(s)/LAR(s) of the subject.
- •Free of obvious health problems as established by medical history and clinical examination before entering into the study.
- •Born after a gestation period of 36 to 42 weeks inclusive.
排除标准
- •Use of any investigational or non-registered product other than the study vaccines/products within 30 days preceding the first dose of study vaccine/product, or planned use during the study period.
- •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 (.
- •Indication, other than specified in the protocol, for prophylactic or therapeutic antipyretic treatment during the study period.
- •Treatment with antipyretics in the 24 hours before study vaccination or planned administration of antipyretics in the 24 hours after study vaccination.
- •Chronic administration of immunosuppressants or other immune-modifying drugs since birth.
- •Planned administration/administration of a vaccine not foreseen by the study protocol during the period starting 30 days before each dose of study vaccine and ending 30 days after with the exception of locally recommended (pandemic) influenza vaccines, and those should be documented in the eCRF.
- •Previous vaccination against diphtheria, tetanus, pertussis, polio, hepatitis B, Haemophilus influenzae type b and/or Streptococcus pneumoniae with the exception of the vaccines where the first dose may be given within the first two weeks of life according to the national recommendations.
- •History of intercurrent diphtheria, tetanus, pertussis, polio, hepatitis B, Haemophilus influenzae type b disease.
- •History of any allergic disease or reaction likely to be exacerbated by any component of the vaccines or prophylactic antipyretic treatment, i.e. ibuprofen or paracetamol, as specified in the protocol.
- •History of any seizures or progressive neurological disease.
- •Acute disease and/or fever at the time of enrolment. The study entry should be delayed until the illness has improved.
- •Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination .
- •A family history of congenital or hereditary immunodeficiency.
- •Major congenital defects or serious chronic illness.
- •Administration of immunoglobulins and/or any blood products since birth or planned administration during entire study period.
- •Any contraindication to treatment with ibuprofen as described in the ibuprofen summary of product characteristics (SPC).
- •Any contraindication to treatment with paracetamol as described in the paracetamol SPC.
- •Body weight < 5 kg at the time of enrolment.
- •Child in care.
研究组 & 干预措施
Group DIBU
Delayed ibuprofen group: subjects receiving delayed ibuprofen treatment after each primary vaccine dose
干预措施: GSK1024850A (SynflorixTM) (Biological)
Group IIBU
Immediate ibuprofen group: subjects receiving immediate ibuprofen treatment after each primary vaccine dose
干预措施: GSK1024850A (SynflorixTM) (Biological)
Group IIBU
Immediate ibuprofen group: subjects receiving immediate ibuprofen treatment after each primary vaccine dose
干预措施: Infanrix hexa (Biological)
Group IIBU
Immediate ibuprofen group: subjects receiving immediate ibuprofen treatment after each primary vaccine dose
干预措施: Infanrix-IPV/Hib (Biological)
Group IIBU
Immediate ibuprofen group: subjects receiving immediate ibuprofen treatment after each primary vaccine dose
干预措施: Ibuprofen (Drug)
Group DIBU
Delayed ibuprofen group: subjects receiving delayed ibuprofen treatment after each primary vaccine dose
干预措施: Infanrix hexa (Biological)
Group DIBU
Delayed ibuprofen group: subjects receiving delayed ibuprofen treatment after each primary vaccine dose
干预措施: Infanrix-IPV/Hib (Biological)
Group DIBU
Delayed ibuprofen group: subjects receiving delayed ibuprofen treatment after each primary vaccine dose
干预措施: Ibuprofen (Drug)
Group NIBU
No ibuprofen group: subjects receiving no prophylactic ibuprofen treatment after each primary vaccine dose
干预措施: GSK1024850A (SynflorixTM) (Biological)
Group NIBU
No ibuprofen group: subjects receiving no prophylactic ibuprofen treatment after each primary vaccine dose
干预措施: Infanrix hexa (Biological)
Group NIBU
No ibuprofen group: subjects receiving no prophylactic ibuprofen treatment after each primary vaccine dose
干预措施: Infanrix-IPV/Hib (Biological)
Group IPARA
Immediate paracetamol group: subjects receiving immediate paracetamol treatment after each primary vaccine dose
干预措施: GSK1024850A (SynflorixTM) (Biological)
Group IPARA
Immediate paracetamol group: subjects receiving immediate paracetamol treatment after each primary vaccine dose
干预措施: Infanrix hexa (Biological)
Group IPARA
Immediate paracetamol group: subjects receiving immediate paracetamol treatment after each primary vaccine dose
干预措施: Infanrix-IPV/Hib (Biological)
Group IPARA
Immediate paracetamol group: subjects receiving immediate paracetamol treatment after each primary vaccine dose
干预措施: Paracetamol (Drug)
Group DPARA
Delayed paracetamol group: subjects receiving delayed paracetamol treatment after each primary vaccine dose
干预措施: GSK1024850A (SynflorixTM) (Biological)
Group DPARA
Delayed paracetamol group: subjects receiving delayed paracetamol treatment after each primary vaccine dose
干预措施: Infanrix hexa (Biological)
Group DPARA
Delayed paracetamol group: subjects receiving delayed paracetamol treatment after each primary vaccine dose
干预措施: Infanrix-IPV/Hib (Biological)
Group DPARA
Delayed paracetamol group: subjects receiving delayed paracetamol treatment after each primary vaccine dose
干预措施: Paracetamol (Drug)
Group NPARA
No paracetamol group: subjects receiving no prophylactic paracetamol treatment after each primary vaccine dose
干预措施: GSK1024850A (SynflorixTM) (Biological)
Group NPARA
No paracetamol group: subjects receiving no prophylactic paracetamol treatment after each primary vaccine dose
干预措施: Infanrix hexa (Biological)
Group NPARA
No paracetamol group: subjects receiving no prophylactic paracetamol treatment after each primary vaccine dose
干预措施: Infanrix-IPV/Hib (Biological)
Group IIBU-IIBU
1/3 of the subjects from the primary IIBU group receiving immediate ibuprofen treatment after booster vaccination
干预措施: GSK1024850A (SynflorixTM) (Biological)
Group IIBU-IIBU
1/3 of the subjects from the primary IIBU group receiving immediate ibuprofen treatment after booster vaccination
干预措施: Infanrix hexa (Biological)
Group IIBU-IIBU
1/3 of the subjects from the primary IIBU group receiving immediate ibuprofen treatment after booster vaccination
干预措施: Infanrix-IPV/Hib (Biological)
Group IIBU-IIBU
1/3 of the subjects from the primary IIBU group receiving immediate ibuprofen treatment after booster vaccination
干预措施: Ibuprofen (Drug)
Group IIBU-DIBU
1/3 of the subjects from the primary IIBU group receiving delayed ibuprofen treatment after booster vaccination
干预措施: GSK1024850A (SynflorixTM) (Biological)
Group IIBU-DIBU
1/3 of the subjects from the primary IIBU group receiving delayed ibuprofen treatment after booster vaccination
干预措施: Infanrix hexa (Biological)
Group IIBU-DIBU
1/3 of the subjects from the primary IIBU group receiving delayed ibuprofen treatment after booster vaccination
干预措施: Infanrix-IPV/Hib (Biological)
Group IIBU-NIBU
1/3 of the subjects from the primary IIBU group receiving no prophylactic ibuprofen treatment after booster vaccination
干预措施: GSK1024850A (SynflorixTM) (Biological)
Group IIBU-NIBU
1/3 of the subjects from the primary IIBU group receiving no prophylactic ibuprofen treatment after booster vaccination
干预措施: Infanrix hexa (Biological)
Group IIBU-NIBU
1/3 of the subjects from the primary IIBU group receiving no prophylactic ibuprofen treatment after booster vaccination
干预措施: Infanrix-IPV/Hib (Biological)
Group IIBU-NIBU
1/3 of the subjects from the primary IIBU group receiving no prophylactic ibuprofen treatment after booster vaccination
干预措施: Ibuprofen (Drug)
Group DIBU-IIBU
1/3 of the subjects from the primary DIBU group receiving immediate ibuprofen treatment after booster vaccination
干预措施: GSK1024850A (SynflorixTM) (Biological)
Group DIBU-IIBU
1/3 of the subjects from the primary DIBU group receiving immediate ibuprofen treatment after booster vaccination
干预措施: Infanrix hexa (Biological)
Group DIBU-IIBU
1/3 of the subjects from the primary DIBU group receiving immediate ibuprofen treatment after booster vaccination
干预措施: Infanrix-IPV/Hib (Biological)
Group DIBU-IIBU
1/3 of the subjects from the primary DIBU group receiving immediate ibuprofen treatment after booster vaccination
干预措施: Ibuprofen (Drug)
Group DIBU-DIBU
1/3 of the subjects from the primary DIBU group receiving delayed ibuprofen treatment after booster vaccination
干预措施: GSK1024850A (SynflorixTM) (Biological)
Group DIBU-DIBU
1/3 of the subjects from the primary DIBU group receiving delayed ibuprofen treatment after booster vaccination
干预措施: Infanrix hexa (Biological)
Group DIBU-DIBU
1/3 of the subjects from the primary DIBU group receiving delayed ibuprofen treatment after booster vaccination
干预措施: Infanrix-IPV/Hib (Biological)
Group DIBU-DIBU
1/3 of the subjects from the primary DIBU group receiving delayed ibuprofen treatment after booster vaccination
干预措施: Ibuprofen (Drug)
Group DIBU-NIBU
1/3 of the subjects from the primary DIBU group receiving no prophylactic ibuprofen treatment after booster vaccination
干预措施: GSK1024850A (SynflorixTM) (Biological)
Group DIBU-NIBU
1/3 of the subjects from the primary DIBU group receiving no prophylactic ibuprofen treatment after booster vaccination
干预措施: Infanrix hexa (Biological)
Group DIBU-NIBU
1/3 of the subjects from the primary DIBU group receiving no prophylactic ibuprofen treatment after booster vaccination
干预措施: Infanrix-IPV/Hib (Biological)
Group NIBU-IIBU
1/3 of the subjects from the primary NIBU group receiving immediate ibuprofen treatment after booster vaccination
干预措施: GSK1024850A (SynflorixTM) (Biological)
Group NIBU-IIBU
1/3 of the subjects from the primary NIBU group receiving immediate ibuprofen treatment after booster vaccination
干预措施: Infanrix hexa (Biological)
Group NIBU-IIBU
1/3 of the subjects from the primary NIBU group receiving immediate ibuprofen treatment after booster vaccination
干预措施: Infanrix-IPV/Hib (Biological)
Group NIBU-IIBU
1/3 of the subjects from the primary NIBU group receiving immediate ibuprofen treatment after booster vaccination
干预措施: Ibuprofen (Drug)
Group NIBU-DIBU
1/3 of the subjects from the primary NIBU group receiving delayed ibuprofen treatment after booster vaccination
干预措施: GSK1024850A (SynflorixTM) (Biological)
Group NIBU-DIBU
1/3 of the subjects from the primary NIBU group receiving delayed ibuprofen treatment after booster vaccination
干预措施: Infanrix hexa (Biological)
Group NIBU-DIBU
1/3 of the subjects from the primary NIBU group receiving delayed ibuprofen treatment after booster vaccination
干预措施: Infanrix-IPV/Hib (Biological)
Group NIBU-DIBU
1/3 of the subjects from the primary NIBU group receiving delayed ibuprofen treatment after booster vaccination
干预措施: Ibuprofen (Drug)
Group NIBU-NIBU
1/3 of the subjects from the primary NIBU group receiving no prophylactic ibuprofen treatment after booster vaccination
干预措施: GSK1024850A (SynflorixTM) (Biological)
Group NIBU-NIBU
1/3 of the subjects from the primary NIBU group receiving no prophylactic ibuprofen treatment after booster vaccination
干预措施: Infanrix hexa (Biological)
Group NIBU-NIBU
1/3 of the subjects from the primary NIBU group receiving no prophylactic ibuprofen treatment after booster vaccination
干预措施: Infanrix-IPV/Hib (Biological)
Group IPARA-NPARA
subjects from the primary IPARA group receiving no paracetamol treatment after booster vaccination
干预措施: GSK1024850A (SynflorixTM) (Biological)
Group IPARA-NPARA
subjects from the primary IPARA group receiving no paracetamol treatment after booster vaccination
干预措施: Infanrix hexa (Biological)
Group IPARA-NPARA
subjects from the primary IPARA group receiving no paracetamol treatment after booster vaccination
干预措施: Infanrix-IPV/Hib (Biological)
Group DPARA-IPARA
subjects from the primary DPARA group receiving immediate paracetamol treatment after booster vaccination
干预措施: GSK1024850A (SynflorixTM) (Biological)
Group DPARA-IPARA
subjects from the primary DPARA group receiving immediate paracetamol treatment after booster vaccination
干预措施: Infanrix hexa (Biological)
Group DPARA-IPARA
subjects from the primary DPARA group receiving immediate paracetamol treatment after booster vaccination
干预措施: Infanrix-IPV/Hib (Biological)
Group DPARA-IPARA
subjects from the primary DPARA group receiving immediate paracetamol treatment after booster vaccination
干预措施: Paracetamol (Drug)
Group NPARA-IPARA
subjects from the primary NPARA group receiving immediate paracetamol treatment after booster vaccination
干预措施: GSK1024850A (SynflorixTM) (Biological)
Group NPARA-IPARA
subjects from the primary NPARA group receiving immediate paracetamol treatment after booster vaccination
干预措施: Infanrix hexa (Biological)
Group NPARA-IPARA
subjects from the primary NPARA group receiving immediate paracetamol treatment after booster vaccination
干预措施: Infanrix-IPV/Hib (Biological)
Group NPARA-IPARA
subjects from the primary NPARA group receiving immediate paracetamol treatment after booster vaccination
干预措施: Paracetamol (Drug)
结局指标
主要结局
Number of Subjects With Antibody Concentrations Against Vaccine Pneumococcal Serotypes Greater Than or Equal to (≥) the Cut-off
时间窗: One month after primary immunization (At Month 3)
Antibodies 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) have been assessed by 22F-inhibition enzyme-linked immunosorbent assay (ELISA). The cut-off value of the assay was an antibody concentration greater than or equal to (≥) 0.2 micrograms per milliliter (μg/mL).
Antibody Concentrations Against Vaccine Pneumococcal Serotypes
时间窗: One month after primary immunization (At Month 3)
Anti-pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F antibody concentrations have been assessed by 22F-inhibition ELISA, presented as geometric mean concentrations (GMCs) and expressed in micrograms per milliliter (μg/mL). The seropositivity cut-off for the assay was an antibody concentration ≥ 0.05 μg/mL.
Antibody Concentrations Against Protein D (Anti-PD)
时间窗: One month after primary immunization (At Month 3)
Anti-PD antibody concentrations were presented as geometric mean concentrations (GMCs), expressed in ELISA units (EL.U) per milliliter (EL.U/mL). The seropositivity cut-off of the assay was an antibody concentration ≥ 100 EL.U/mL.
次要结局
- Antibody Concentrations Against Pertussis Toxoid (Anti-PT), Filamentous Haemagglutinin (Anti-FHA) and Pertactin (Anti-PRN)(Prior to (Month 9) and one month after booster vaccination (Month 10))
- Number of Subjects With Any Unsolicited Adverse Events (AEs)(Within 31-days (Day 0-30) following booster vaccination)
- Number of Subjects With Any and Grade 3 Solicited Local Symptoms(Within the 4-day (Days 0-3) period following booster vaccination)
- Number of Subjects With Any Serious Adverse Events (SAEs)(During the entire study period (Month 0 to 10))
- Antibody Concentrations Against Diphtheria (D) and Tetanus (T) Toxoids(One month after primary immunization (Month 3))
- Antibody Concentrations Against Diphteria (D) and Tetanus (T) Toxoids(Prior to (Month 9) and one month after booster vaccination (Month 10))
- Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms(Within the 4-day (Days 0-3) period following booster vaccination)
- Antibody Concentrations Against Vaccine Pneumococcal Serotypes(Prior to (Month 9) and one month after booster vaccination (Month 10))
- Opsonophagocytic Activity (OPA) Titers Against Vaccine Pneumococcal Serotypes(Prior to (Month 9) and one month after booster vaccination (Month 10))
- Antibody Concentrations Against Protein D (Anti-PD)(Prior to (Month 9) and one month after booster vaccination (Month 10))
- Antibody Concentrations Against Hepatitis B Surface Antigen (HBs)(One month after primary immunization (Month 3))
- Antibody Concentrations Against Hepatitis B Surface Antigen(Prior to (Month 9) and one month after booster vaccination (Month 10))
- Antibody Concentrations Against Polyribosyl-ribitol-phosphate (PRP)(Prior to (Month 9) and one month after booster vaccination (Month 10))
- Antibody Titers Against Poliovirus Type 1, 2 and 3(Prior to (Month 9) and one month after booster vaccination (Month 10))
- Antibody Concentrations Against Cross-reactive Pneumococcal Serotypes 6A and 19A(One month after primary immunization (At Month 3))