Phase 3
N=23,738
COMPAS (Clinical Otitis Media & Pneumonia Study): Pneumonia & Acute Otitis Media (AOM ) Efficacy Study of the Pneumococcal Conjugate Vaccine
Infections, Streptococcal
Bottom Line
View on ClinicalTrials.gov: NCT00466947 ↗Enrolled (actual)
23,738
Serious AEs
22.1%
Results posted
Sep 2013
Primary outcome: Primary: Number of Subjects With a First Episode Reported of Bacterial Community Acquired Pneumoniae (B-CAP) — 240; 304 Subjects
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- Pneumococcal conjugate vaccine GSK1024850A (Biological); Havrix (Biological); Engerix-B (Biological); Infanrix hexa (Biological); GSK Biologicals' DTPa-IPV/Hib vaccine (Biological)
- Age
- Pediatric · 0+ yrs
- Sex
- All
- Sponsor
- GlaxoSmithKline
- Primary completion
- Aug 2010
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Subjects With a First Episode Reported of Bacterial Community Acquired Pneumoniae (B-CAP) |
240; 304 | — |
| SECONDARY Number of Subjects With Serious Adverse Events (SAEs) |
2534; 2668 | — |
| SECONDARY Number of Subjects With Any Unsolicited Adverse Event (AE), in the Panama Subset |
3530; 3518 | — |
| SECONDARY Number of Subjects With Solicited Local Symptoms Post Primary Vaccination in the Immunogenicity and Tolerability Subset |
169; 165; 118; 109; 98; 91 | — |
| SECONDARY Number of Subjects With Solicited Local Symptoms Post Booster Vaccination in the Immunogenicity and Tolerability Subset |
129; 131; 104; 98; 74; 69 | — |
| SECONDARY Number of Subjects With Solicited Local Symptoms Post Primary Vaccination in the Immunogenicity and Tolerability Subset |
169; 165; 118; 109; 98; 91 | — |
| SECONDARY Number of Subjects With Solicited Local Symptoms Post Booster Vaccination in the Immunogenicity and Tolerability Subset, for the Control Group |
81; 89; 81; 73; 70; 55 | — |
| SECONDARY Number of Subjects With Solicited General Symptoms Post Primary Vaccination in the Immunogenicity and Tolerability Subset |
236; 168; 247; 125; 289; 206 | — |
| SECONDARY Number of Subjects With Solicited General Symptoms Post Booster Vaccination in the Immunogenicity and Tolerability Subset |
74; 65; 93; 73; 121; 95 | — |
| SECONDARY Number of Subjects With a First Episode Reported of Clinically Confirmed Acute Otitis Media (AOM) (C-AOM), in the Panama Subset |
204; 239 | — |
| SECONDARY 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) |
181; 231 | — |
| SECONDARY 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 |
32; 45 | — |
| SECONDARY 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 |
6; 18 | — |
| SECONDARY 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. |
3; 4 | — |
| SECONDARY 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. |
3; 4 | — |
| SECONDARY 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 |
12; 14 | — |
| SECONDARY 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 |
12; 14 | — |
| SECONDARY 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 |
8; 7 | — |
| SECONDARY 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) |
21; 25 | — |
| SECONDARY Number of Subjects With a First Episode Reported of Community Acquired Pneumoniae (CAP) With Any Abnormal CXR With Positive Respiratory Viral Test (RVT) |
104; 112 | — |
| SECONDARY Number of Subjects With a First Episode Reported of Bacterial Community Acquired Pneumoniae (B-CAP) With Positive Respiratory Viral Test (RVT). |
35; 39 | — |
| SECONDARY Number of Subjects With a First Episode Reported of Suspected Community Acquired Pneumoniae (CAP) (S-CAP) |
2108; 2237 | — |
| SECONDARY Number of Subjects With a First Episode Reported of Community Acquired Pneumoniae (CAP) With Any Abnormal Chest X-ray (CXR) |
681; 764 | — |
| SECONDARY 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 |
425; 499; 175; 237; 85; 119 | — |
| SECONDARY 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. |
208; 256; 191; 240 | — |
| SECONDARY Number of Subjects With a First Episode Reported of Vaccine-type Invasive Pneumococcal Disease (VT-IPD). |
0; 16 | — |
| SECONDARY Number of Subjects With a First Episode Reported of a Bacteriologically Confirmed Invasive Pneumococcal Disease (Bact.-Conf. ID). |
6; 17 | — |
| SECONDARY Number of Subjects With a First Episode Reported of Pneumococcal Invasive Disease (Pneumococcal ID) |
6; 17 | — |
| SECONDARY Number of Subjects With a First Episode Reported of Invasive Pneumococcal Disease (IPD) Due to Streptococcus (S. pn.) Cross-reactive Pneumococcal Serotypes. |
2; 1 | — |
| SECONDARY 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. |
3; 0 | — |
| SECONDARY Number of Subjects With a First Episode Reported of Invasive Disease (ID) Due to Haemophilus Influenzae |
— | — |
| SECONDARY Number of Subjects With Streptococcus Pneumoniae (S. pn.) Vaccine Serotypes Identified in Nasopharyngeal Swabs, in the Carriage Subset. |
104; 123; 92; 123; 88; 109 | — |
| SECONDARY Number of Subjects With Streptococcus Pneumoniae (S. pn.) Cross-reactive Serotypes Identified in Nasopharyngeal Swabs, in the Carriage Subset. |
63; 67; 81; 63; 57; 63 | — |
| SECONDARY 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 |
99; 86; 85; 85; 83; 85 | — |
| SECONDARY Number of Subjects With H. Influenzae Strains Identified in Nasopharyngeal Swabs, in the Carriage Subset |
36; 40; 45; 44; 32; 39 | — |
| SECONDARY Number of Subjects With Acquisition of New Streptococcus Pneumoniae Strains Identified in Nasopharyngeal Swabs, in the Carriage Subset |
171; 175; 145; 165; 110; 137 | — |
| SECONDARY Number of Subjects With Acquisition of New Haemophilus Influenzae Strains Identified in Nasopharyngeal Swabs, in the Carriage Subset. |
39; 37; 27; 33; 23; 28 | — |
| SECONDARY Number of Subjects With Any Antibiotic Prescription at Least Once During the Entire Study Period, in the Carriage Subset. |
611; 626 | — |
| SECONDARY Pneumococcal Antibody Concentrations Against Pneumococcal Vaccine Serotypes, in the Immunogenicity and Tolerability Subset. |
2.51; 0.04; 3.26; 0.03; 4.20; 0.05 | — |
| SECONDARY Antibody Concentrations Against Pneumococcal Cross-reactive Serotypes 6A and 19A, in the Immunogenicity and Tolerability Subset |
0.22; 0.04; 1.14; 0.04; 0.31; 0.05 | — |
| SECONDARY Antibody Concentrations Against Pneumococcal Vaccine Serotypes, in the Immunogenicity and Tolerability Subset. |
0.35; 0.05; 3.58; 0.06; 0.65; 0.06 | — |
| SECONDARY Antibody Concentrations Against Pneumococcal Cross-reactive Serotypes 6A and 19A, in the Immunogenicity and Tolerability Subset |
0.22; 0.04; 1.14; 0.04; 0.31; 0.05 | — |
| SECONDARY Number of Subjects With Antibody Concentrations Against Pneumococcal Vaccine Serotypes >= 0.20 Micrograms Per Milliliter (µg/mL), in the Immunogenicity and Tolerability Subset |
164; 14; 219; 19; 186; 14 | — |
| SECONDARY 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 |
215; 5; 204; 18 | — |
| SECONDARY Number of Subjects With Antibody Concentrations Against Pneumococcal Vaccine Serotypes >= 0.20 Micrograms Per Milliliter (µg/mL), in the Immunogenicity and Tolerability Subset |
164; 14; 219; 19; 186; 14 | — |
| SECONDARY 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 |
119; 14; 187; 12; 129; 24 | — |
| SECONDARY 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 |
231; 87; 219; 101; 206; 95 | — |
| SECONDARY Number of Subjects With Pneumococcal Antibody Concentrations Against Serotypes 6A and 19A >= 0.05 µg/mL, in the Immunogenicity and Tolerability Subset |
210; 61; 214; 61; 196; 69 | — |
| SECONDARY 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 |
231; 87; 219; 101; 206; 95 | — |
| SECONDARY Number of Subjects With Pneumococcal Antibody Concentrations Against Serotypes 6A and 19A >= 0.05 µg/mL, in the Immunogenicity and Tolerability Subset |
210; 61; 214; 61; 196; 69 | — |
| SECONDARY 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 |
9.0; 4.6; 357.5; 4.8; 34.4; 4.6 | — |
| SECONDARY Titers for Opsonophagocytic Activity Against Cross-reactive Pneumococcal Serotypes 6A and 19A, in the Immunogenicity and Tolerability Subset |
156.9; 5.0; 18.2; 4.1 | — |
| SECONDARY 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 |
9.0; 4.6; 357.5; 4.8; 34.4; 4.6 | — |
| SECONDARY Titers for Opsonophagocytic Activity Against Pneumococcal Serotypes 6A and 19A in the Immunogenicity and Tolerability Subset |
43.8; 7.1; 277.2; 7.6; 63.9; 17.2 | — |
| SECONDARY 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 |
280; 25; 306; 15; 303; 13 | — |
| SECONDARY Number of Subjects With Titers for Opsonophagocytic Activity Against Cross-reactive Pneumococcal Serotypes 6A and 19A >= 8, in the Immunogenicity and Tolerability Subset |
232; 16; 121; 5 | — |
| SECONDARY 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 |
58; 9; 195; 14; 127; 10 | — |
| SECONDARY Number of Subjects With Titers for Opsonophagocytic Activity Against Pneumococcal Cross-reactive Serotypes 6A and 19A >= 8, in the Immunogenicity and Tolerability Subset |
99; 24; 150; 26; 104; 50 | — |
| SECONDARY Concentrations of Antibodies Against Protein D (ANTI-PD), in the Immunogenicity and Tolerability Subset |
638.6; 103.1; 2787.0; 92.4; 824.1; 94.5 | — |
| SECONDARY Concentrations of Antibodies Against Protein D (ANTI-PD), in the Immunogenicity and Tolerability Subset |
638.6; 103.1; 2787.0; 92.4; 824.1; 94.5 | — |
| SECONDARY 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 |
333; 141 | — |
| SECONDARY 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. |
223; 96; 218; 83; 198; 84 | — |
Summary
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.
Eligibility Criteria
Inclusion Criteria
- 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
Exclusion Criteria
- 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)
Data sourced from ClinicalTrials.gov (NCT00466947). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.