Clinical Trial Results:
A phase II, observer-blind follow-up study with two groups to assess the reactogenicity and immunogenicity of GlaxoSmithKline (GSK) Biologicals’ 10-valent pneumococcal conjugate vaccine (GSK1024850A), when either given as a booster dose (at 20-23 months of age) in children previously primed with three doses of the study vaccine, or when given as a two-dose catch-up immunization (at 18-21 and 20-23 months of age) in unprimed children, all previously enrolled in the 10PN-PD-DIT-005 primary vaccination study.
Summary
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EudraCT number |
2015-001449-93 |
Trial protocol |
Outside EU/EEA |
Global end of trial date |
28 Aug 2008
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Results information
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Results version number |
v2(current) |
This version publication date |
18 Apr 2021
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First version publication date |
29 Jul 2015
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Other versions |
v1 |
Version creation reason |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
110031
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT00513409 | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
GlaxoSmithKline Biologicals
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Sponsor organisation address |
Rue de l’Institut 89, Rixensart, Belgium, B-1330
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Public contact |
Clinical Trials Call Center, GlaxoSmithKline Biologicals, 44 2089904466, GSKClinicalSupportHD@gsk.com
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Scientific contact |
Clinical Trials Call Center, GlaxoSmithKline Biologicals, 44 2089904466, GSKClinicalSupportHD@gsk.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
Yes
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
16 Feb 2009
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
28 Aug 2008
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
To assess the reactogenicity of study vaccines in terms of the occurrence of adverse events with intensity grade 3
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Protection of trial subjects |
All subjects were supervised closely for at least 30 minutes following vaccination with appropriate medical treatment readily available. Vaccines were administered by qualified and trained personnel. Vaccines were administered only to eligible subjects that had no contraindications to any components of the vaccines. Subjects were followed-up from the time the subject consents to participate in the study until she/he is discharged.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
22 Aug 2007
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Long term follow-up planned |
Yes
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Long term follow-up rationale |
Safety | ||
Long term follow-up duration |
5 Months | ||
Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Chile: 163
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Worldwide total number of subjects |
163
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EEA total number of subjects |
0
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
163
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
0
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
The study included an active phase, from Month 0 to Month 3, aka one month post Dose 2 of vaccine, followed by an extended safety follow-up phase of 5 months. | ||||||||||||||||||||||||||||||
Pre-assignment
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Screening details |
During the screening the following steps occurred: check for inclusion/exclusion criteria, contraindications/precautions, medical history of the subjects and signing informed consent forms. | ||||||||||||||||||||||||||||||
Period 1
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Period 1 title |
Overall Study Period (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||||||||||||||||||
Allocation method |
Non-randomised - controlled
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Blinding used |
Single blind [1] | ||||||||||||||||||||||||||||||
Roles blinded |
Investigator, Data analyst [2] | ||||||||||||||||||||||||||||||
Blinding implementation details |
This study was conducted in an observer-blind fashion. A different person than that who performed immunogenicity & safety assessments administered study vaccines. The person responsible for preparing and administering vaccine did not have access to safety & reactogenicity information of the study.
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Synflorix Booster Group | ||||||||||||||||||||||||||||||
Arm description |
Subjectsin this group had been previously primed with Synflorix™ and Infanrix™ hexa as part of the 10PN-PD-DIT-005 primary vaccination study, received in this study one dose of Havrix™ co-administered with one dose of Infanrix™ hexa at Month 0 (Dose 1) and one dose of Synflorix™ at Month 2 (Dose 2). | ||||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||||
Investigational medicinal product name |
10-valent pneumococcal conjugate vaccine
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Investigational medicinal product code |
10Pn-PD-DiT
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Other name |
10Pn, Synforix
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Pharmaceutical forms |
Suspension for injection
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Routes of administration |
Intramuscular use
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Dosage and administration details |
One intramuscular injection Intramuscular injection, administered in the right thigh or deltoid region.
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Investigational medicinal product name |
Infanrix hexa
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Investigational medicinal product code |
DTPa-HBV-IPV/Hib
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Other name |
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Pharmaceutical forms |
Powder and suspension for suspension for injection
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Routes of administration |
Intramuscular use
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Dosage and administration details |
One intramuscular injection administered in the left thigh or deltoid region
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Investigational medicinal product name |
Havrix 720 Junior
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Investigational medicinal product code |
HAV 720
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Other name |
HAV
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Pharmaceutical forms |
Suspension for injection
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Routes of administration |
Intramuscular use
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Dosage and administration details |
One intramuscular injection administered in the right thigh or deltoid region
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Arm title
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Synflorix Catch-up Group | ||||||||||||||||||||||||||||||
Arm description |
Subjects in this group were subjects previously primed with Havrix™ and Infanrix™ hexa co-administered with Infanrix™ hexa as part of 10PN-PD-DIT-005 primary vaccination study and who received in this study a catch-up dose of Synflorix™ co-administered with Infanrix™ hexa at Month 0 (Dose 1) and one booster dose of Synflorix™ at Month 2 (Dose 2). | ||||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||||
Investigational medicinal product name |
10-valent pneumococcal conjugate vaccine
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Investigational medicinal product code |
10Pn-PD-DiT
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Other name |
10Pn, Synforix
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Pharmaceutical forms |
Suspension for injection
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Routes of administration |
Intramuscular use
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Dosage and administration details |
Two intramuscular injections administered in the right thigh or deltoid region
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Investigational medicinal product name |
Infanrix hexa
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Investigational medicinal product code |
DTPa-HBV-IPV/Hib
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Other name |
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Pharmaceutical forms |
Powder and suspension for suspension for injection
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Routes of administration |
Intramuscular use
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Dosage and administration details |
One intramuscular injection administered in the left thigh or deltoid region
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Notes [1] - The number of roles blinded appears inconsistent with a single blinded trial. It is expected that there will be one role blinded in a single blind trial. Justification: This study was conducted in an observer-blind fashion. A different person than that who performed immunogenicity & safety assessments administered study vaccines. The person responsible for preparing and administering vaccine did not have access to safety & reactogenicity information of the study. [2] - The roles blinded appear inconsistent with a simple blinded trial. Justification: This study was conducted in an observer-blind fashion. A different person than that who performed immunogenicity & safety assessments administered study vaccines. The person responsible for preparing and administering vaccine did not have access to safety & reactogenicity information of the study. |
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Baseline characteristics reporting groups
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Reporting group title |
Synflorix Booster Group
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Reporting group description |
Subjectsin this group had been previously primed with Synflorix™ and Infanrix™ hexa as part of the 10PN-PD-DIT-005 primary vaccination study, received in this study one dose of Havrix™ co-administered with one dose of Infanrix™ hexa at Month 0 (Dose 1) and one dose of Synflorix™ at Month 2 (Dose 2). | ||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Synflorix Catch-up Group
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Reporting group description |
Subjects in this group were subjects previously primed with Havrix™ and Infanrix™ hexa co-administered with Infanrix™ hexa as part of 10PN-PD-DIT-005 primary vaccination study and who received in this study a catch-up dose of Synflorix™ co-administered with Infanrix™ hexa at Month 0 (Dose 1) and one booster dose of Synflorix™ at Month 2 (Dose 2). | ||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Synflorix Booster Group
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Reporting group description |
Subjectsin this group had been previously primed with Synflorix™ and Infanrix™ hexa as part of the 10PN-PD-DIT-005 primary vaccination study, received in this study one dose of Havrix™ co-administered with one dose of Infanrix™ hexa at Month 0 (Dose 1) and one dose of Synflorix™ at Month 2 (Dose 2). | ||
Reporting group title |
Synflorix Catch-up Group
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Reporting group description |
Subjects in this group were subjects previously primed with Havrix™ and Infanrix™ hexa co-administered with Infanrix™ hexa as part of 10PN-PD-DIT-005 primary vaccination study and who received in this study a catch-up dose of Synflorix™ co-administered with Infanrix™ hexa at Month 0 (Dose 1) and one booster dose of Synflorix™ at Month 2 (Dose 2). |
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End point title |
Number of subjects reporting grade 3 symptoms (solicited and unsolicited) [1] | ||||||||||||||||||
End point description |
Grade 3 symptoms are symptoms which prevent normal, everyday activities (e.g. in a young child such symptom would prevent attendance at school/ kindergarten/ a day-care center and would cause the parents/guardians to seek medical advice).
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End point type |
Primary
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End point timeframe |
Within 4 days after the administration of any study vaccine dose
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Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: The analysis of the primary endpoint was descriptive i.e. no statistical hypothesis test was performed. |
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No statistical analyses for this end point |
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End point title |
Number of subjects reporting solicited local symptoms | ||||||||||||||||||
End point description |
Solicited local symptoms assessed include pain, redness and swelling
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End point type |
Secondary
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End point timeframe |
Within 4 days after the administration of any study vaccine dose
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No statistical analyses for this end point |
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End point title |
Number of subjects reporting solicited general symptoms | |||||||||||||||||||||
End point description |
Solicited general symptoms assessed include drowsiness, fever, irritability and loss of appetite. Fever was defined as rectal temperature ≥ 38 degrees Celsius.
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End point type |
Secondary
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End point timeframe |
Within 4 days after the administration of any study vaccine dose
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No statistical analyses for this end point |
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End point title |
Number of subjects reporting unsolicited adverse events (AEs) | ||||||||||||
End point description |
An Adverse Event is any untoward medical occurrence in a clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
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End point type |
Secondary
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End point timeframe |
Within 31 days after the administration of any study vaccine dose
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No statistical analyses for this end point |
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End point title |
Number of subjects reporting serious adverse events (SAEs) during the active phase of the study | ||||||||||||
End point description |
A serious adverse event (SAE) is any untoward medical occurrence that: results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect in the offspring of a study subject, or may evolve into one of the outcomes listed above.
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End point type |
Secondary
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End point timeframe |
Throughout the active phase of the study, from Month 0 to Month 3 (Month 0/Dose 1 administration up to 1 month after the Dose 2 of vaccine)
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No statistical analyses for this end point |
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End point title |
Number of subjects reporting serious adverse events (SAEs) throughout the entire study period | ||||||||||||
End point description |
An SAE is any untoward medical occurrence that: results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect in the offspring of a study subject, or may evolve into one of the outcomes listed above.
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End point type |
Secondary
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End point timeframe |
Throughout the entire study period (from the beginning of the booster phase up to the end of the 6-month extended safety follow-up)
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No statistical analyses for this end point |
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End point title |
Number of subjects with vaccine pneumococcal serotype antibody concentrations above the cut-off value | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Anti-pneumococcal antibody cut-off value assessed was 0.20 microgram per milliliter (μg/mL). The vaccine pneumococcal serotypes assessed include 1, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F.
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End point type |
Secondary
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End point timeframe |
Before (pre) and at Month 3, or one month after the administration of Dose 2 (post)
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No statistical analyses for this end point |
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End point title |
Number of subjects with opsonophagocytic activity against vaccine pneumococcal serotypes above the cut-off value | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Cut-off value for opsonophagocytic activity against pneumococcal antibody assessed was ≥ 8 The vaccine pneumococcal serotypes assessed include 1, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 23F.
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End point type |
Secondary
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End point timeframe |
Before (pre) and at Month 3, or one month after the administration of Dose 2 (post)
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No statistical analyses for this end point |
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End point title |
Number of subjects with anti-protein D antibody concentrations above the cut-off value | |||||||||||||||
End point description |
Anti-protein D antibody cut-off value assessed was ≥ 100 Enzyme-Linked Immuno Sorbent Assay (ELISA) unit per milliliter (EL.U/mL).
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End point type |
Secondary
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End point timeframe |
Before (pre) and at Month 3, or one month after the administration of Dose 2 (post)
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No statistical analyses for this end point |
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End point title |
Anti-hepatitis A virus antibodies concentration | ||||||||||||||||||
End point description |
Concentration of anti-hepatitis A antibodies given as geometric mean concentration (GMC) in milli-international units per milliliter (mIU/mL).
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End point type |
Secondary
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End point timeframe |
Before (pre) and at Month 3, or one month after the administration of Dose 2 (post)
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No statistical analyses for this end point |
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End point title |
Number of subjects With Anti-hepatitis A antibody concentrations above the cut-off value | |||||||||||||||
End point description |
Anti-hepatitis A antibodies cut-off value assessed was ≥ 15 mIU/mL.
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End point type |
Secondary
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End point timeframe |
Before (pre) and at Month 3, or one month after the administration of Dose 2 (post)
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No statistical analyses for this end point |
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Adverse events information
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Timeframe for reporting adverse events |
Solicited symptoms and unsolicited : 4-day (Days 0-3) and 31-day (Days 0-30) follow-up periods post vaccination(s), across doses, erspectively. SAEs : Month 0 to Month 8
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Adverse event reporting additional description |
The occurrence of reported AEs (all/related) was not available and is encoded as equal to the number of subjects affected.
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Assessment type |
Non-systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
11.1
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Reporting groups
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Reporting group title |
Synflorix booster group
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Reporting group description |
Subjectsin this group had been previously primed with Synflorix™ as part of the 10PN-PD-DIT-005 primary vaccination study, received in this study one dose of Havrix™ co-administered with one dose of Infanrix™ hexa at Month 0 (Dose 1) and one dose of Synflorix™ at Month 2 (Dose 2). | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Synflorix catch-up group
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Reporting group description |
Subjects in this group were subjects previously primed with Havrix™ co-administered with Infanrix™ hexa as part of 10PN-PD-DIT-005 primary vaccination study and who received in this study a catch-up dose of Synflorix™ co-administered with Infanrix™ hexa at Month 0 (Dose 1) and one booster dose of Synflorix™ at Month 2 (Dose 2) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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Were there any global substantial amendments to the protocol? No | |||
Interruptions (globally) |
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Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
None reported |