COMPAS: A Phase III Study to Demonstrate Efficacy of GSK Biologicals' 10-valent Pneumococcal Vaccine (GSK1024850A) Against Community Acquired Pneumonia and Acute Otitis Media
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 23,802
- 试验地点
- 21
- 主要终点
- Number of Subjects With a First Episode Reported of Bacterial Community Acquired Pneumoniae (B-CAP)
研究概览
简要总结
This is a study in a large number of healthy children less than 3 years old to measure the efficacy of GlaxoSmithKline (GSK) Biologicals' 10-valent pneumococcal conjugate candidate vaccine (Synflorix vaccine, or GSK1024850A) to prevent cases of pneumonia (lung infection) likely caused by bacteria (Streptococcus pneumoniae and Haemophilus influenzae) or cases of otitis media (ear infection) in children under 3 years old.
详细描述
The Protocol Posting has been updated in order to comply with the FDA Amendment Act, Sep 2007. The following vaccines will be offered by the sponsor:
- Two doses of hepatitis A vaccine will be offered to all subjects to comply with national recommendations.
- NeisVac-C vaccine against Neisseria meningitis group C will be offered to all subjects in Argentina at 12 months of age.
- Varicella vaccine will be offered to all subjects in Colombia and Panama at 12 months of age.
- Two doses of Rotarix vaccine will be offered to all subjects in Colombia within the first six months of life.
In addition, all subjects will receive a dose of Hepatitis B vaccine at birth according to national recommendations and a dose of measles, mumps and rubella (MMR) vaccine at 12 to 15 months of age according to local Extended Program of Immunization (EPI) .
These vaccines will not be provided by the sponsor. The protocol posting has been updated according to the amendment of the protocol dated 25 Nov 2008. The protocol posting has been updated according to the amendment of the protocol dated 14 December 2009. The protocol posting has been updated according to the amendment of the protocol dated 09 September 2010.
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
- Double (Care Provider, Investigator)
入排标准
- 年龄范围
- 6 Weeks 至 16 Weeks（Child）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •A male or female between, and including, 6 and 16 weeks of age at the time of the first vaccination. Pre-term born infants can be included in the study starting from 8 weeks of chronological age at the time of first vaccination and up to 16 weeks of chronological age
- •Subjects should be living in the area covered by the surveillance system for community acquired pneumonia (CAP), invasive disease and acute otitis media (AOM) •Written informed consent obtained from the parent or guardian of the subject.
- •Free of any known or suspected health problems (as established by medical history and clinical examination before entering into the study), that would contraindicate the initiation of routine immunizations outside a clinical trial context.
- •Subjects for whom the investigator believes that their parents/guardians can and will comply with the requirements of the protocol
排除标准
- •Use of any investigational or non-registered drug or planned use during the study period.
- •Use or planned use of any investigational or non-registered vaccine other than the study vaccine(s).
- •Previous vaccination against diphtheria, tetanus, pertussis, Haemophilus influenzae type b, hepatitis A and/or Streptococcus. pneumoniae . Locally recommended EPI vaccines to be given at birth are allowed, but should be administered at least one month before the first dose of the study vaccine .Other locally recommended vaccines are always allowed, even if concomitantly administered with the study vaccines. •Previous or planned vaccination with a registered pneumococcal vaccine such as Prevnar is not allowed. If Prevnar immunization needs to be initiated, due to the presence of a high risk disease for pneumococcal infections for which the Prevnar vaccine is made locally available, the subject can not be enrolled in the study and should be referred to the specific Prevnar immunization program.
- •History of allergic disease or reactions likely to be exacerbated by any component of the vaccines.
- •History of any neurologic disorders or seizures.
- •Acute disease at the time of enrolment
- •For Colombia: infants with low birth weight ( less than (<) 2.500 grams)
研究组 & 干预措施
Synflorix Group
Subjects received 3 primary doses of Synflorix at 2, 4 and 6 months of age co-administered with Infanrix-hexa and booster dose of Synflorix at 15-18 months of age co-administered with Infanrix-IPV/Hib. All vaccines were administered intramuscularly in the right (Synflorix) or the left (Infanrix-hexa, Infanrix-IPV/Hib) thigh (primary dose) or deltoid (booster dose).
干预措施: Pneumococcal conjugate vaccine GSK1024850A (Biological)
Synflorix Group
Subjects received 3 primary doses of Synflorix at 2, 4 and 6 months of age co-administered with Infanrix-hexa and booster dose of Synflorix at 15-18 months of age co-administered with Infanrix-IPV/Hib. All vaccines were administered intramuscularly in the right (Synflorix) or the left (Infanrix-hexa, Infanrix-IPV/Hib) thigh (primary dose) or deltoid (booster dose).
干预措施: Havrix (Biological)
Synflorix Group
Subjects received 3 primary doses of Synflorix at 2, 4 and 6 months of age co-administered with Infanrix-hexa and booster dose of Synflorix at 15-18 months of age co-administered with Infanrix-IPV/Hib. All vaccines were administered intramuscularly in the right (Synflorix) or the left (Infanrix-hexa, Infanrix-IPV/Hib) thigh (primary dose) or deltoid (booster dose).
干预措施: GSK Biologicals' DTPa-IPV/Hib vaccine (Biological)
Control Group
Subjects received 3 doses of Engerix at 2, 4 and 6 months of age co-administered with Infanrix-IPV/Hib and 1 dose of Havrix co-administered with Infanrix-IPV/Hib at 15-18 months of age. All vaccines were administered in the right (Engerix, Havrix) or the left (Infanrix-IPV/Hib) thigh.
干预措施: Havrix (Biological)
Control Group
Subjects received 3 doses of Engerix at 2, 4 and 6 months of age co-administered with Infanrix-IPV/Hib and 1 dose of Havrix co-administered with Infanrix-IPV/Hib at 15-18 months of age. All vaccines were administered in the right (Engerix, Havrix) or the left (Infanrix-IPV/Hib) thigh.
干预措施: GSK Biologicals' DTPa-IPV/Hib vaccine (Biological)
Synflorix Group
Subjects received 3 primary doses of Synflorix at 2, 4 and 6 months of age co-administered with Infanrix-hexa and booster dose of Synflorix at 15-18 months of age co-administered with Infanrix-IPV/Hib. All vaccines were administered intramuscularly in the right (Synflorix) or the left (Infanrix-hexa, Infanrix-IPV/Hib) thigh (primary dose) or deltoid (booster dose).
干预措施: Infanrix hexa (Biological)
Control Group
Subjects received 3 doses of Engerix at 2, 4 and 6 months of age co-administered with Infanrix-IPV/Hib and 1 dose of Havrix co-administered with Infanrix-IPV/Hib at 15-18 months of age. All vaccines were administered in the right (Engerix, Havrix) or the left (Infanrix-IPV/Hib) thigh.
干预措施: Engerix-B (Biological)
结局指标
主要结局
Number of Subjects With a First Episode Reported of Bacterial Community Acquired Pneumoniae (B-CAP)
时间窗: Any time from 2 weeks after Dose 3 up to 31 August 2010
A B-CAP episode was defined as a radiologically confirmed community acquired pneumoniae (CAP) episode with either alveolar consolidation/pleural effusion on the chest X-ray (CXR) or with non-alveolar infiltrates but with C reactive protein (CRP) higher than or equal to (\>=) 40 milligrams per liter (mg/L). The results are presented for data lock point for the primary outcome analysis (31 August 2010), which was performed, as per protocol, when at least 535 first B-CAP episodes were reported from 2 weeks after the third vaccination dose. After analysis on primary outcome was performed, re-monitoring activities revealed Informed Consent Form issues for some subjects. Therefore, a sensitivity analysis excluding 144 subjects was performed. This analysis confirmed the validity of the results for primary outcome.
次要结局
- Number of Subjects With Any Unsolicited Adverse Event (AE), in the Panama Subset(Throughout the study (Month 0 to Month 22-25))
- Number of Subjects With Solicited Local Symptoms Post Booster Vaccination in the Immunogenicity and Tolerability Subset, for the Control Group(Within the 4-days (Days 0-3) follow-up period following the booster vaccine administration.)
- Number of Subjects With a First Episode Reported of Bacteriologically Confirmed Acute Otitis Media (AOM) (B-AOM) Due to Streptococcus Pneumoniae (S. pn.) Cross-reactive Serotypes, in the Panama Subset.(Any time from 2 weeks post primary vaccination Dose 3 to study end at Month 22-25)
- Number of Subjects With a First Episode Reported of Bacteriologically Confirmed Acute Otitis Media (AOM) (B-AOM) Due to Other Pneumococcal Serotypes, in the Panama Subset.(Any time from 2 weeks post primary vaccination Dose 3 to study end at Month 22-25)
- Number of Subjects With Solicited Local Symptoms Post Booster Vaccination in the Immunogenicity and Tolerability Subset(Within the 4-days (Days 0-3) follow-up period following the booster vaccine administration)
- Number of Subjects With Solicited General Symptoms Post Primary Vaccination in the Immunogenicity and Tolerability Subset(Within the 4-days (Days 0-3) follow-up period across the 3 doses of the primary study vaccine administration)
- Number of Subjects With Solicited General Symptoms Post Booster Vaccination in the Immunogenicity and Tolerability Subset(Within the 4-days (Days 0-3) follow-up period following the booster vaccine administration)
- Number of Subjects With a First Episode Reported of Community Acquired Pneumoniae (CAP) With Alveolar Consolidation or Pleural Effusion on the Chest X-ray (CXR) (C-CAP)(Any time from 2 weeks post primary vaccination Dose 3 to study end at Month 22-25)
- Number of Subjects With a First Episode Reported of Bacteriologically Confirmed Acute Otitis Media (AOM) (B-AOM) Due to Haemophilus Influenzae (H. Influenzae), in the Panama Subset(Any time from 2 weeks post primary vaccination Dose 3 to study end at Month 22-25)
- Number of Subjects With a First Episode Reported of Bacteriologically Confirmed Acute Otitis Media (AOM) (B-AOM) Due to Other AOM Pathogens, in the Panama Subset(Any time from 2 weeks post primary vaccination Dose 3 to study end at Month 22-25)
- Number of Subjects With Serious Adverse Events (SAEs)(Throughout the study (Month 0 to Month 22-25))
- Number of Subjects With a First Episode Reported of Clinically Confirmed Acute Otitis Media (AOM) (C-AOM), in the Panama Subset(Any time from 2 weeks after Dose 3 to study end at Month 22-25)
- Number of Subjects With a First Episode Reported of Bacteriologically Confirmed Acute Otitis Media (AOM) (B-AOM) Due to Any Bacterial Pathogen, in the Panama Subset(Any time from 2 weeks post primary vaccination Dose 3 to study end at Month 22-25)
- Number of Subjects With a First Episode Reported of Bacteriologically Confirmed Acute Otitis Media (AOM) (B-AOM) Due to Streptococcus Pneumoniae (S. pn.) Vaccine Serotypes, in the Panama Subset(Any time from 2 weeks post primary vaccination Dose 3 to study end at Month 22-25)
- Number of Subjects With a First Episode Reported of Bacteriologically Confirmed Acute Otitis Media (AOM) (B-AOM) Due to Non-typeable Haemophilus Influenzae (H. Influenzae), in the Panama Subset(Any time from 2 weeks post primary vaccination Dose 3 to study end at Month 22-25)
- Number of Subjects With a First Episode Reported of Community Acquired Pneumoniae (CAP) With Alveolar Consolidation or Pleural Effusion on the Chest X-ray (CXR) (C-CAP) With Positive Respiratory Viral Test (RVT)(Any time from 2 weeks post primary vaccination Dose 3 to study end at Month 22-25)
- Number of Subjects With a First Episode Reported of Community Acquired Pneumoniae (CAP) With Any Abnormal CXR With Positive Respiratory Viral Test (RVT)(Any time from 2 weeks post primary vaccination Dose 3 to study end at Month 22-25)
- Number of Subjects With a First Episode Reported of Bacterial Community Acquired Pneumoniae (B-CAP) With Positive Respiratory Viral Test (RVT).(Any time from 2 weeks post primary vaccination Dose 3 to study end at Month 22-25)
- Number of Subjects With a First Episode Reported of CAP With Either Alveolar Consolidation/Pleural Effusion on Chest X-ray (CXR) (C-CAP) or With Non-alveolar Infiltrates (NAI-CAP) But With C Reactive Protein (CRP) >= Cut-off.(Any time from 2 weeks post primary vaccination Dose 3 to study end at Month 22-25)
- Number of Subjects With a First Episode Reported of Vaccine-type Invasive Pneumococcal Disease (VT-IPD).(Any time from 2 weeks post primary vaccination Dose 3 to study end at Month 22-25)
- Number of Subjects With a First Episode Reported of Invasive Pneumococcal Disease (IPD) Due to Streptococcus (S. pn.) Cross-reactive Pneumococcal Serotypes.(Any time from 2 weeks post primary vaccination Dose 3 to study end at Month 22-25)
- Number of Subjects With a First Episode Reported of Invasive Pneumococcal Disease (IPD) Due to Pneumococcal Serotypes Other Than Streptococcus (S. pn.) Vaccine and Cross-reactive Serotypes.(Any time from 2 weeks post primary vaccination Dose 3 to study end at Month 22-25)
- Number of Subjects With a First Episode Reported of Invasive Disease (ID) Due to Haemophilus Influenzae(Any time from 2 weeks post primary vaccination Dose 3 to study end at Month 22-25)
- Number of Subjects With Streptococcus Pneumoniae (S. pn.) Serotypes Identified in Nasopharyngeal Swabs Other Than the Synflorix Vaccine and Cross-reactive Serotypes, in the Carriage Subset(At Months 5, 10-13, 13-16, 14-17, 16-19 and 22-25)
- Number of Subjects With a First Episode Reported of Suspected Community Acquired Pneumoniae (CAP) (S-CAP)(Any time from 2 weeks post primary vaccination Dose 3 to study end at Month 22-25)
- Number of Subjects With a First Episode Reported of Community Acquired Pneumoniae (CAP) With Any Abnormal Chest X-ray (CXR)(Any time from 2 weeks post primary vaccination Dose 3 to study end at Month 22-25)
- Number of Subjects With a First Episode Reported of Suspected Community Acquired Pneumoniae (CAP) (S-CAP) With C Reactive Protein (CRP) >= Cut-off, Regardless of Chest X-ray (CXR) Reading(Any time from 2 weeks post primary vaccination Dose 3 to study end at Month 22-25)
- Number of Subjects With a First Episode Reported of a Bacteriologically Confirmed Invasive Pneumococcal Disease (Bact.-Conf. ID).(Any time from 2 weeks post primary vaccination Dose 3 to study end at Month 22-25)
- Number of Subjects With a First Episode Reported of Pneumococcal Invasive Disease (Pneumococcal ID)(Any time from 2 weeks post primary vaccination Dose 3 to study end at Month 22-25)
- Number of Subjects With Streptococcus Pneumoniae (S. pn.) Vaccine Serotypes Identified in Nasopharyngeal Swabs, in the Carriage Subset.(At Months 5, 10-13, 13-16, 14-17, 16-19 and 22-25)
- Number of Subjects With Acquisition of New Streptococcus Pneumoniae Strains Identified in Nasopharyngeal Swabs, in the Carriage Subset(At Months 10-13, 13-16, 14-17, 16-19 and 22-25)
- Antibody Concentrations Against Pneumococcal Cross-reactive Serotypes 6A and 19A, in the Immunogenicity and Tolerability Subset(Before the administration of booster vaccination (PRE), and 1 month and 9 months post booster vaccination (M1 POST-BST and M9 POST-BST))
- Antibody Concentrations Against Pneumococcal Vaccine Serotypes, in the Immunogenicity and Tolerability Subset.(Before the administration of booster vaccination (PRE), and 1 month and 9 months post booster vaccination (M1 POST-BST and M9 POST-BST))
- Number of Subjects With Streptococcus Pneumoniae (S. pn.) Cross-reactive Serotypes Identified in Nasopharyngeal Swabs, in the Carriage Subset.(At Months 5, 10-13, 13-16, 14-17, 16-19 and 22-25)
- Number of Subjects With H. Influenzae Strains Identified in Nasopharyngeal Swabs, in the Carriage Subset(At Months 5, 10-13, 13-16, 14-17, 16-19 and 22-25)
- Number of Subjects With Acquisition of New Haemophilus Influenzae Strains Identified in Nasopharyngeal Swabs, in the Carriage Subset.(At Months 10-13, 13-16, 14-17, 16-19 and 22-25)
- Number of Subjects With Any Antibiotic Prescription at Least Once During the Entire Study Period, in the Carriage Subset.(Throughout the study (Month 0 to Month 22-25))
- Pneumococcal Antibody Concentrations Against Pneumococcal Vaccine Serotypes, in the Immunogenicity and Tolerability Subset.(At Month 5, one month after the third dose of primary vaccination)
- Number of Subjects With Antibody Concentrations Against Pneumococcal Vaccine Serotypes >= 0.20 Micrograms Per Milliliter (µg/mL), in the Immunogenicity and Tolerability Subset(Before the administration of booster vaccination (PRE), and 1 month and 9 months post booster vaccination (M1 POST-BST and M9 POST-BST))
- Number of Subjects With Antibody Concentrations Against Pneumococcal Cross-reactive Serotypes 6A and 19A >= 0.20 Micrograms Per Milliliter (µg/mL), in the Immunogenicity and Tolerability Subset(At Month 5, one month after the third dose of primary vaccination)
- Number of Subjects With Pneumococcal Antibody Concentrations Against Cross-reactive Serotypes 6A and 19A Higher >= 0.20 Micrograms Per Milliliter (µg/mL), in the Immunogenicity and Tolerability Subset(Before the administration of booster vaccination (PRE), and 1 month and 9 months post booster vaccination (M1 POST-BST and M9 POST-BST))
- Number of Subjects With Antibody Concentrations Against Vaccine Pneumococcal Serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F >= 0.05 Microgram Per Milliliter (µg/mL), in the Immunogenicity and Tolerability Subset(Before the administration of booster vaccination (PRE), and 1 month and 9 months post booster vaccination (M1 POST-BST and M9 POST-BST)
- Number of Subjects With Pneumococcal Antibody Concentrations Against Serotypes 6A and 19A >= 0.05 µg/mL, in the Immunogenicity and Tolerability Subset(Before the administration of booster vaccination (PRE), and 1 month and 9 months post booster vaccination (M1 POST-BST and M9 POST-BST) .)
- Titers for Opsonophagocytic Activity Against Vaccine Pneumococcal Serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F, in the Immunogenicity and Tolerability Subset(Before the administration of booster vaccination (PRE), and 1 month and 9 months post booster vaccination (M1 POST-BST and M9 POST-BST))
- Number of Subjects With Titers for Opsonophagocytic Activity Against Pneumococcal Cross-reactive Serotypes 6A and 19A >= 8, in the Immunogenicity and Tolerability Subset(Before the administration of booster vaccination (PRE), and 1 month and 9 months post booster vaccination (M1 POST-BST and M9 POST-BST).)
- Number of Subjects With Anti-protein D (ANTI-PD) Antibody Concentrations >= 100 Enzyme-linked Immunosorbent Assay Units Per Milliliter ( EL.U/mL), in the Immunogenicity and Tolerability Subset(At Month 5, one month after the third dose of primary vaccination)
- Number of Subjects With Anti-protein D (ANTI-PD) Antibody Concentrations >= 100 Enzyme-linked Immunosorbent Assay Units Per Milliliter ( EL.U/mL), in the Immunogenicity and Tolerability Subset.(Before the administration of booster vaccination (PRE), and 1 month and 9 months post booster vaccination (M1 Post-BST and M9 POST-BST)
- Titers for Opsonophagocytic Activity Against Pneumococcal Serotypes 6A and 19A in the Immunogenicity and Tolerability Subset(Before the administration of booster vaccination (PRE), and 1 month and 9 months post booster vaccination (M1 POST-BST and M9 POST-BST))
- Number of Subjects With Titers for Opsonophagocytic Activity Against Vaccine Pneumococcal Serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F => 8, in the Immunogenicity and Tolerability Subset(At Month 5, one month after the third dose of primary vaccination)
- Concentrations of Antibodies Against Protein D (ANTI-PD), in the Immunogenicity and Tolerability Subset(Before the administration of booster vaccination (PRE), and 1 month and 9 months post booster vaccination (M1 Post-BST and M9 POST-BST))
- Titers for Opsonophagocytic Activity Against Cross-reactive Pneumococcal Serotypes 6A and 19A, in the Immunogenicity and Tolerability Subset(At Month 5, one month after the third dose of primary vaccination)
- Number of Subjects With Titers for Opsonophagocytic Activity Against Cross-reactive Pneumococcal Serotypes 6A and 19A >= 8, in the Immunogenicity and Tolerability Subset(At Month 5, one month after the third dose of primary vaccination)
- Number of Subjects With Titers for Opsonophagocytic Activity Against Vaccine Pneumococcal Serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F >= 8, in the Immunogenicity and Tolerability Subset(Before the administration of booster vaccination (PRE), and 1 month and 9 months post booster vaccination (M1 POST-BST and M9 POST-BST))
- Number of Subjects With Solicited Local Symptoms Post Primary Vaccination in the Immunogenicity and Tolerability Subset(Within the 4-days (Days 0-3) follow-up period across the 3 doses of the primary study vaccine administration)