Clinical Trial Results:
A Phase 4/3, Open-Label, Single-Arm, Multicenter Study to Describe the Safety and Immunogenicity of 13-valent Pneumococcal Conjugate Vaccine in Adults 50 to 65 Years of Age and in Children 6 to 17 Years of Age in India
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Summary
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EudraCT number |
2014-001174-34 |
Trial protocol |
Outside EU/EEA |
Global end of trial date |
31 Jul 2015
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Results information
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Results version number |
v1(current) |
This version publication date |
29 Dec 2016
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First version publication date |
29 Dec 2016
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Other versions |
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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 |
B1851140
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT02034877 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Pfizer, Inc.
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Sponsor organisation address |
235 E 42nd Street, New York, United States, NY 10017
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Public contact |
Pfizer ClinicalTrials.gov Call Center, Pfizer, Inc., 001 800-718-1021, ClinicalTrials.gov_Inquiries@pfizer.com
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Scientific contact |
Pfizer ClinicalTrials.gov Call Center, Pfizer, Inc., 001 800-718-1021, ClinicalTrials.gov_Inquiries@pfizer.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 |
22 Jan 2016
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
31 Jul 2015
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Global end of trial reached? |
Yes
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Global end of trial date |
31 Jul 2015
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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 describe the safety profile of 13-valent Pneumococcal Conjugate vaccine (13vPnC) in adult subjects 50 to 65 years of age. To describe the safety profile of 13vPnC in pediatric subjects 6 to 17 years of age. To describe the immune responses to the 13 pneumococcal serotypes induced by13vPnC in a subset of approximately 400 adult subjects 50 to 65 years of age. To describe the immune responses to the 13 pneumococcal serotypes induced by 13vPnC in pediatric subjects 6 to 17 years of age.
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Protection of trial subjects |
The study was in compliance with the ethical principles derived from the Declaration of Helsinki and in compliance with all International Conference on Harmonization (ICH) Good Clinical Practice (GCP) Guidelines. All the local regulatory requirements pertinent to safety of trial subjects were followed.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
10 Aug 2014
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Long term follow-up planned |
No
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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 |
India: 1199
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Worldwide total number of subjects |
1199
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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) |
0
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Children (2-11 years) |
157
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Adolescents (12-17 years) |
43
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Adults (18-64 years) |
997
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From 65 to 84 years |
2
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85 years and over |
0
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Recruitment
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Recruitment details |
- | ||||||||||||||||||
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Pre-assignment
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Screening details |
A total of 1200 (200 pediatric and 1000 adult) subjects were randomized in the study. Out of the 1000 adult subjects, 999 subjects and all 200 pediatric subject received vaccination. | ||||||||||||||||||
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Period 1
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Period 1 title |
Overall Study (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||||||||||
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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13vPnC (Pediatric Subjects) | ||||||||||||||||||
Arm description |
Pediatric subjects aged 6 to 17 years received 1 single 0.5 milliliter (mL) dose of 13vPnC intramuscularly. | ||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||
Investigational medicinal product name |
13-valent pneumococcal conjugate vaccine (13vPnC)
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Investigational medicinal product code |
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Other name |
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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 |
Pediatric subjects received 1 single 0.5 mL dose of 13vPnC intramuscularly.
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Arm title
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13vPnC (Adult Subjects) | ||||||||||||||||||
Arm description |
Adult subjects aged 50 to 65 years received 1 single 0.5 mL dose of 13vPnC intramuscularly. | ||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||
Investigational medicinal product name |
13-valent pneumococcal conjugate vaccine (13vPnC)
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Investigational medicinal product code |
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Other name |
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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 |
Adult subjects received 1 single 0.5 mL dose of 13vPnC intramuscularly.
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Baseline characteristics reporting groups
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Reporting group title |
13vPnC (Pediatric Subjects)
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Reporting group description |
Pediatric subjects aged 6 to 17 years received 1 single 0.5 milliliter (mL) dose of 13vPnC intramuscularly. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
13vPnC (Adult Subjects)
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Reporting group description |
Adult subjects aged 50 to 65 years received 1 single 0.5 mL dose of 13vPnC intramuscularly. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
13vPnC (Pediatric Subjects)
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Reporting group description |
Pediatric subjects aged 6 to 17 years received 1 single 0.5 milliliter (mL) dose of 13vPnC intramuscularly. | ||
Reporting group title |
13vPnC (Adult Subjects)
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Reporting group description |
Adult subjects aged 50 to 65 years received 1 single 0.5 mL dose of 13vPnC intramuscularly. | ||
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End point title |
Percentage of Subjects With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs) Within 1 Month After 13vPnC Vaccination [1] | |||||||||||||||
End point description |
An AE was any untoward medical occurrence in a subjects who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent were events between first dose of study drug and up to 1 month after last dose that were absent before treatment or that worsened relative to pretreatment state. Safety population included all subjects who received 1 dose of 13vPnC vaccination.
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End point type |
Primary
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End point timeframe |
Within 1 month after 13vPnC vaccination
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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: No statistical analyses was planned for this primary endpoint |
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End point title |
Serotype-Specific Pneumococcal Opsonophagocytic Activity (OPA) Geometric Mean Titer (GMT) Before 13vPnC Vaccination [2] | |||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Antibody-mediated opsonophagocytic activity against each of 13 pneumococcal serotypes(1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F)were measured using a quantitative functional OPA assay. OPA titers were expressed as reciprocal of highest serum dilution that reduces survival of pneumococci by at least 50 percent (%).For each serotype, GMTs were calculated using logarithmically transformed assay results. Confidence intervals(CIs) for GMTs were back transformations of CI based on Student t distribution for mean of logarithmically transformed assay results.Evaluable immunogenicity population:eligible subjects received 13vPnC;had blood drawn within pre-specified time-frames with at least 1 valid,determinate assay result,no major protocol violation. Only 400 adults were selected for immunogenicity analysis.Here, ‘n’=number of subjects with valid and determinate assay results for specified serotype. Number of subjects analyzed (N) signifies subjects evaluable for this endpoint.
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End point type |
Primary
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End point timeframe |
Before 13vPnC vaccination
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| Notes [2] - 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: No statistical analyses was planned for this primary endpoint |
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| No statistical analyses for this end point | ||||||||||||||||||||||||||||||||||||||||||||||||||||
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End point title |
Serotype-Specific Pneumococcal Opsonophagocytic Activity (OPA) Geometric Mean Titer (GMT) 1 Month After 13vPnC Vaccination [3] | |||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Antibody-mediated opsonophagocytic activity against each of the 13 pneumococcal serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) were measured using a quantitative functional OPA assay. OPA titers were expressed as the reciprocal of highest serum dilution that reduces survival of the pneumococci by at least 50%. For each serotype, GMTs were calculated using the logarithmically transformed assay results. CIs for GMTs were back transformations of a CI based on Student t distribution for the mean of the logarithmically transformed assay results. Evaluable immunogenicity population: eligible subjects received 13vPnC;had blood drawn within pre-specified time-frames with at least 1 valid,determinate assay result,no major protocol violation. Only 400 adults were selected for immunogenicity analysis. Here, ‘n’=number of subjects with valid and determinate assay results for specified serotype. Number of subjects analyzed (N) signifies subjects evaluable for this endpoint.
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End point type |
Primary
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End point timeframe |
1 month after 13vPnC vaccination
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| Notes [3] - 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: No statistical analyses was planned for this primary endpoint |
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| No statistical analyses for this end point | ||||||||||||||||||||||||||||||||||||||||||||||||||||
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End point title |
Geometric Mean Fold Rise (GMFR) for Serotype-Specific Pneumococcal Opsonophagocytic Activity (OPA) From Before 13vPnC Vaccination to 1 Month After 13vPnC Vaccination [4] | |||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
GMFRs for the 13 pneumococcal serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) from before 13vPnC vaccination to 1 month after 13vPnC vaccination were computed using the logarithmically transformed assay results. CIs for GMFRs were back transformations of a CI based on the Student t distribution for the mean logarithm of the mean fold rise. GMFRs were calculated using all subjects with available data from both before and after vaccination blood draws. Evaluable immunogenicity population: eligible subjects received 13vPnC;had blood drawn within pre-specified time-frames with at least 1 valid,determinate assay result,no major protocol violation. Only 400 adults were selected for immunogenicity analysis. Here, ‘n’=number of subjects with valid and determinate assay results for specified serotype. Number of subjects analyzed (N) signifies subjects evaluable for this endpoint.
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End point type |
Primary
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End point timeframe |
Before 13vPnC vaccination, 1 month after 13vPnC vaccination
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| Notes [4] - 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: No statistical analyses was planned for this primary endpoint |
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| No statistical analyses for this end point | ||||||||||||||||||||||||||||||||||||||||||||||||||||
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End point title |
Percentage of Subjects With OPA Titer Greater Than or Equal to (>=) Lower Limit of Quantitation (LLOQ) Before 13vPnC Vaccination [5] | |||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Percentage of subjects achieving serotype-specific pneumococcal OPA titer >=LLOQ, along with corresponding 95% CIs for 13 pneumococcal serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F) are presented. Exact 2-sided CIs for were calculated using Clopper and Pearson method. LLOQ in titers for each serotype was: Pn001, 18; Pn003, 12; Pn004, 21; Pn005, 29; Pn06A, 37; Pn06B, 43; Pn7F, 210 (for adult subjects); Pn7F, 113 (for pediatric subjects) Pn09V, 345 (for adult subjects); Pn09V, 141 (for pediatric subjects); Pn014, 35; Pn18C, 31; Pn19A, 18; Pn19F, 48; Pn23F, 13. Evaluable immunogenicity population: eligible subjects received 13vPnC;had blood drawn within pre-specified time-frames with at least 1 valid,determinate assay result,no major protocol violation. Only 400 adults were selected for immunogenicity analysis. Here, ‘n’=number of subjects with valid and determinate assay results for specified serotype and “N” signifies subjects evaluable for this endpoint.
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End point type |
Primary
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End point timeframe |
Before 13vPnC vaccination
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| Notes [5] - 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: No statistical analyses was planned for this primary endpoint |
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| No statistical analyses for this end point | ||||||||||||||||||||||||||||||||||||||||||||||||||||
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End point title |
Percentage of Subjects With OPA Titer Greater Than or Equal to (>=) Lower Limit of Quantitation (LLOQ) 1 Month After 13vPnC Vaccination [6] | |||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Percentage of subjects achieving serotype-specific pneumococcal OPA titer >=LLOQ, along with corresponding 95% CIs for 13 pneumococcal serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F) are presented. Exact 2-sided CIs were calculated using Clopper and Pearson method. LLOQ in titers for each serotype was: Pn001, 18; Pn003, 12; Pn004, 21; Pn005, 29; Pn06A, 37; Pn06B, 43; Pn7F, 210 (for adult subjects); Pn7F, 113 (for pediatric subjects) Pn09V, 345 (for adult subjects); Pn09V, 141 (for pediatric subjects); Pn014, 35; Pn18C, 31; Pn19A, 18; Pn19F, 48; Pn23F, 13. Evaluable immunogenicity population: eligible subjects received 13vPnC;had blood drawn within pre-specified time-frames with at least 1 valid,determinate assay result,no major protocol violation. Only 400 adults were selected for immunogenicity analysis. Here, ‘n’=number of subjects with valid and determinate assay results for specified serotype and “N” signifies subjects evaluable for this endpoint.
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End point type |
Primary
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End point timeframe |
1 month after 13vPnC vaccination
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| Notes [6] - 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: No statistical analyses was planned for this primary endpoint |
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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 |
Baseline to 1 month after 13vPnC vaccination (up to 42 days)
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Assessment type |
Non-systematic | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
17.1
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Reporting groups
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Reporting group title |
13vPnC (Adult Subjects)
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Reporting group description |
Adult subjects aged 50 to 65 years received 1 single 0.5 mL dose of 13vPnC intramuscularly. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
13vPnC (Pediatric Subjects)
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Reporting group description |
Pediatric subjects aged 6 to 17 years received 1 single 0.5 mL dose of 13vPnC intramuscularly. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 0% | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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24 Jun 2013 |
To add immunogenicity objective for the adult group and to add a pediatric cohort. |
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15 Sep 2014 |
To change the study phase to 4/3 in the study title and throughout the protocol to reflect that the extension of the indication to children and adolescents aged 6 to 17 years is under review and not yet approved. |
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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 | |||
