Prophylactic Antipyretic Treatment in Children Receiving Booster Dose of Pneumococcal Vaccine GSK1024850A and DTPa-HBV-IPV/Hib Vaccine (Infanrix Hexa) and Assessment of Impact of Pneumococcal Vaccination on Nasopharyngeal Carriage
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 750
- 试验地点
- 1
- 主要终点
- Number of Subjects Reported With Core Fever (Rectal Temperature) Greater Than or Equal to (≥) the Cut-off
研究概览
简要总结
The purpose of this trial is to assess if the rate of febrile reactions following the co-administration of a booster dose of pneumococcal conjugate vaccines with standard infant vaccines is lowered when paracetamol is given prophylactically and to assess the impact of pneumococcal conjugate vaccine on pneumococcal and H. influenzae nasopharyngeal carriage compared to control group receiving meningococcal conjugate vaccine (GSK134612).
This protocol posting deals with objectives & outcome measures of the booster phase. The objectives & outcome measures of the primary phase are presented in a separate protocol posting (NCT number = NCT00370318).
详细描述
The Protocol Posting has been updated in order to comply with the FDA Amendment Act, Sep 2007.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non 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 15 Months（Child）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Subjects who the investigator believes that their parents/guardians can and will comply with the requirements of the protocol should be enrolled in the study.
- •A male or female between, and including, 12-15 months of age at the time of the vaccination.
- •Written informed consent obtained from the parent or guardian of the subject.
- •Free of obvious health problems as established by medical history and clinical examination before entering into the study.
- •Subjects in the unprimed group
- •A male or female who previously participated in study 107017 and received 3 doses of pneumococcal conjugate vaccine GSK1024850A.
排除标准
- •For all subjects:
- •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 antipyretic treatment.
- •Use of any investigational or non-registered product (drug or vaccine) other than the study vaccines within one month preceding the dose of study vaccines, or planned use during the entire study period.
- •Chronic administration (defined as more than 14 days) of immunosuppressants or other immune-modifying drugs within 6 months prior to the dose of study vaccines.
- •Planned administration/administration of a vaccine not foreseen by the study protocol, during the period starting one month before the dose of study vaccines and up to one month after the dose of study vaccines.
- •History of, or intercurrent, diphtheria, tetanus, pertussis, polio, hepatitis B, Haemophilus influenzae type b disease.
- •History of allergic disease or reactions likely to be exacerbated by any component of the vaccines.
- •History of seizures (this criterion does not apply to subjects who have had a single, uncomplicated febrile convulsion in the past) or progressive neurological disease.
- •Acute disease at the time of enrolment.
- •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 within three months preceding administration of the dose of study vaccines or planned administration during the study period.
- •Subjects of which both parents have a history of atopia.
- •Subject has received systemic antibiotic therapy for acute illness within 24 hours prior to the vaccination.
- •Subject is likely to receive antipyretic treatment as a result of a concomitant illness or has been treated with paracetamol within the past 24 hours.
- •DTPa-HBV-IPV/Hib vaccine:
- •Known hypersensitivity after previous administration of diphtheria, tetanus, pertussis, polio, hepatitis B and Hib vaccines or to any component of the vaccines.
- •Encephalopathy.
- •As with other vaccines, administration of DTPa-HBV-IPV/Hib should be postponed in subjects suffering from acute mild, moderate or severe illness.
- •For subjects in the AP-AP, AP-NAP and NAP groups:
- •Administration of any pneumococcal, diphtheria, tetanus, pertussis, polio, hepatitis B and/or Haemophilus influenzae type b vaccines other than allowed and used in study
- •For subjects in the AP-AP group:
- •Subject with any contraindication to treatment with paracetamol.
- •For subjects in the unprimed group:
- •Previous vaccination with meningococcal polysaccharide vaccine of serogroup A, C, W-135 and/or Y.
- •Previous vaccination with meningococcal polysaccharide conjugate vaccine of serogroups A, C, W-135 and/or Y.
- •Planned administration of a hepatitis B vaccine not foreseen by the study protocol during the period starting one month after the dose of study vaccines and up to study end.
- •Previous vaccination with tetanus toxoid containing vaccines including T, DTP, DT, DTP-IPV, DTP-HBV-IPV and Hib-TT vaccines six months prior to study entry.
- •History of meningococcal disease due to serogroup A, C, W, or Y.
- •Administration of any pneumococcal vaccine since birth.
- •Full vaccination history since birth not available.
研究组 & 干预措施
Synflorix I Group
Subjects were vaccinated with 3 primary vaccination doses of Synflorix™ vaccine with prophylactic administration of paracetamol in study 10PN-PD-DIT-010 (107017), and received in this study at 12-15 months of age a booster dose of Synforix™ vaccine, co-administered with Infanrix™ hexa along with prophylactic antipyretic treatment.
干预措施: Pneumococcal conjugate vaccine GSK1024850A. (Biological)
Synflorix I Group
Subjects were vaccinated with 3 primary vaccination doses of Synflorix™ vaccine with prophylactic administration of paracetamol in study 10PN-PD-DIT-010 (107017), and received in this study at 12-15 months of age a booster dose of Synforix™ vaccine, co-administered with Infanrix™ hexa along with prophylactic antipyretic treatment.
干预措施: Infanrix hexa. (Biological)
Synflorix I Group
Subjects were vaccinated with 3 primary vaccination doses of Synflorix™ vaccine with prophylactic administration of paracetamol in study 10PN-PD-DIT-010 (107017), and received in this study at 12-15 months of age a booster dose of Synforix™ vaccine, co-administered with Infanrix™ hexa along with prophylactic antipyretic treatment.
干预措施: Paracetamol. (Drug)
Synflorix II Group
Subjects were vaccinated with 3 primary vaccination doses of Synforix™ vaccine without prophylactic administration of paracetamol in study 10PN-PD-DIT-010 (107017), and received in this study at 12-15 months of age a booster dose of Synforix™ vaccine, co-administered with Infanrix™ hexa without prophylactic antipyretic treatment
干预措施: Pneumococcal conjugate vaccine GSK1024850A. (Biological)
Synflorix II Group
Subjects were vaccinated with 3 primary vaccination doses of Synforix™ vaccine without prophylactic administration of paracetamol in study 10PN-PD-DIT-010 (107017), and received in this study at 12-15 months of age a booster dose of Synforix™ vaccine, co-administered with Infanrix™ hexa without prophylactic antipyretic treatment
干预措施: Infanrix hexa. (Biological)
Synflorix PRE Group
Subjects were vaccinated with 3 primary vaccination doses of Synforix™ vaccine without prophylactic administration of paracetamol in study 10PN-PD-DIT-010 (107017), and received in this study (before the implementation of the protocol amendment) at 12-15 months of age a booster dose of Synforix™ vaccine, co-administered with Infanrix™ hexa without prophylactic antipyretic treatment.
干预措施: Pneumococcal conjugate vaccine GSK1024850A. (Biological)
Synflorix PRE Group
Subjects were vaccinated with 3 primary vaccination doses of Synforix™ vaccine without prophylactic administration of paracetamol in study 10PN-PD-DIT-010 (107017), and received in this study (before the implementation of the protocol amendment) at 12-15 months of age a booster dose of Synforix™ vaccine, co-administered with Infanrix™ hexa without prophylactic antipyretic treatment.
干预措施: Infanrix hexa. (Biological)
Synflorix POST Group
Subjects were vaccinated with 3 primary vaccination doses of Synforix™ vaccine without prophylactic administration of paracetamol in study 10PN-PD-DIT-010 (107017), and received in this study (after the implementation of the protocol amendment) at 12-15 months of age a booster dose of Synforix™ vaccine, co-administered with Infanrix™ hexa without prophylactic antipyretic treatment.
干预措施: Pneumococcal conjugate vaccine GSK1024850A. (Biological)
Synflorix POST Group
Subjects were vaccinated with 3 primary vaccination doses of Synforix™ vaccine without prophylactic administration of paracetamol in study 10PN-PD-DIT-010 (107017), and received in this study (after the implementation of the protocol amendment) at 12-15 months of age a booster dose of Synforix™ vaccine, co-administered with Infanrix™ hexa without prophylactic antipyretic treatment.
干预措施: Infanrix hexa. (Biological)
Mencevax + Infanrix Hexa Group
Age-matched pneumococcal vaccine unprimed group receiving a single dose of Mencevax™ vaccine co-administered with Infanrix™ hexa vaccine.
干预措施: Infanrix hexa. (Biological)
Mencevax + Infanrix Hexa Group
Age-matched pneumococcal vaccine unprimed group receiving a single dose of Mencevax™ vaccine co-administered with Infanrix™ hexa vaccine.
干预措施: Meningococcal vaccine GSK134612. (Biological)
结局指标
主要结局
Number of Subjects Reported With Core Fever (Rectal Temperature) Greater Than or Equal to (≥) the Cut-off
时间窗: Within 4 days (Day 0-3) after primary vaccine dose.
The cut-off for core fever was 38.0 degrees Celsius (ºC).
次要结局
- Antibody Concentrations Against Certain Pneumococcal Serotypes ≥ the Cut Off.(Prior to booster vaccination (PRE), 1 month (M1) and 12 months (M12) post-booster vaccination)
- Antibody Concentrations Against Pneumococcal Serotypes 6A and 19A (Anti-6A and 19A)(Prior to booster vaccination (PRE), 1 month (M1) and 12 months (M12) post-booster vaccination)
- Opsonophagocytic Activity (OPA) Titers Against Pneumococcal Cross-reactive Serotypes 6A and 19A(Prior to booster vaccination (PRE), 1 month (M1) and 12 months (M12) post-booster vaccination)
- Number of Subjects Reported With Any and Grade 3 Solicited Local Symptoms.(During the 4-day (Days 0-3) post-primary vaccination period)
- Number of Subjects Reported With Serious Adverse Events (SAEs)(Throughout the entire study period (Month 0-Month 12))
- Number of Subjects Reported With AEs Resulting in Rash, New Onset of Chronic Illness (NOCI), Emergency Room (ER) Visits and Non-routine Physician Office Visits.(Up to 6 months after vaccination with Mencevax™)
- Opsonophagocytic Activity (OPA) Titers Against Pneumococcal Serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F(Prior to booster vaccination (PRE), 1 month (M1) and 12 months (M12) post-booster vaccination)
- Number of Subjects Reported With Core Fever (Rectal Temperature) Greater Than (>) the Cut-off(Within 4 days (Day 0-3) after primary vaccination dose)
- Concentrations of Antibodies Against Protein D (Anti-PD)(Prior to booster vaccination (PRE), 1 month (M1) and 12 months (M12) post-booster vaccination)
- Number of Subjects With Serum Bactericidal Antibodies, Using Baby Rabbit Complement for Assay (rSBA) Titres ≥ the Cut-off Values(Prior to vaccination (PRE), 1 month (M1) and 12 months (M12) post-vaccination)
- Number of Nasopharyngeal Swabs With S.Pneumoniae (Cross-reactive Serotypes)(Prior to vaccination(Pre), 1 month post-vaccination (M1), 3 months post-vaccination (M3), 7 months post-vaccination (M7), 12 months post-vaccination (M12) and across all time points (Overall))
- Number of Subjects Reported With Unsolicited Adverse Events (AEs)(Within 31 days (Days 0-30) after primary vaccine dose.)
- Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentrations(12 month post-vaccination (M12))
- Anti-polyribosyl-ribitol Phosphate (Anti-PRP) Antibody Concentrations(1 month post-vaccination (M1))
- Number of Subjects Reported With Any, Grade 3 and Related Solicited General Symptoms(During the 4-day (Day 0-3) post-vaccination period)
- Number of Subjects With Antibody Concentrations Against Certain Pneumococcal Serotypes ≥ the Cut Off(Prior to booster vaccination (PRE), 1 month (M1) and 12 months (M12) post-booster vaccination)
- rSBA-MenA, rSBA-MenC, rSBA-MenW-135 and rSBA-MenY Titers in the Mencevax + Infanrix Hexa Group(Prior to vaccination(PRE), 1 month (M1) and 12 months (M12) post- vaccination.)
- Number of Nasopharyngeal Swabs With S.Pneumoniae (Non-vaccine and Non-cross-reactive Serotypes)(Prior to vaccination(Pre), 1 month post-vaccination (M1), 3 months post-vaccination (M3), 7 months post-vaccination (M7), 12 months post-vaccination (M12) and across all time points (Overall))
- Concentrations of Antibodies Against Diphtheria and Tetanus Toxoids (Anti-D and T).(1 month post-vaccination (M1))
- Anti-poliovirus (Anti-Polio) Type 1, 2 and 3 Titers(12 month post-vaccination (M12))
- Number of Nasopharyngeal Swabs With S.Pneumoniae (Vaccine Serotypes)(Prior to vaccination(Pre), 1 month post-vaccination (M1), 3 months post-vaccination (M3), 7 months post-vaccination (M7), 12 months post-vaccination (M12) and across all time points (Overall))
- Number of Nasopharyngeal Swabs With H. Influenzae(Prior to vaccination(Pre), 1 month post-vaccination (M1), 3 months post-vaccination (M3), 7 months post-vaccination (M7), 12 months post-vaccination (M12) and across all time points (Overall))
- Number of Subjects With New Acquisition Associated to S. Pneumoniae Detected in Nasopharyngeal Swabs(1 month post-vaccination (M1), 3 months post-vaccination (M3), 7 months post-vaccination (M7), 12 months post-vaccination (M12) and across all time points (Overall))
- Number of Subjects With New Acquisition Associated to H. Influentzae Detected in Nasopharyngeal Swabs.(1 month post-vaccination (M1), 3 months post-vaccination (M3), 7 months post-vaccination (M7), 12 months post-vaccination (M12) and across all time points (Overall))
- Number of Subjects With Anti-polysaccharide N (Anti-PS) Concentrations ≥ the Cut-off Values(Prior to vaccination(PRE), 1 month (M1) and 12 months (M12) post-vaccination)
- Geometric Mean Antibody Concentration (GMCs) for Anti-polysaccharide N (Anti-PS) Antibody Concentrations(Prior to vaccination(PRE), 1 month (M1) and 12 months (M12) post- vaccination.)
- Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentrations in the Mencevax + Infanrix Hexa Group(Prior to vaccination (Pre))
- Number of Nasopharyngeal Swabs With S. Pneumoniae and H. Influenzae(Prior to vaccination(Pre), 1 month post-vaccination (M1), 3 months post-vaccination (M3), 7 months post-vaccination (M7), 12 months post-vaccination (M12) and across all time points (Overall))
- Anti-tetanus Toxoids (Anti-T) Antibody Concentrations in the Mencevax + Infanrix Hexa Group(Prior to vaccination (Pre))
- Anti-pertussis Toxoid (Anti-PT), Anti-filamentous Haemagglutinin (Anti-FHA) and Anti-pertactin (Anti-PRN) Antibody Concentrations(1 month post-vaccination (M1))
- Anti-poliovirus (Anti-Polio) Types 1, 2 and 3 Titers(1 month post-vaccination (M1))