Clinical Trial Results:
A phase III, single group, open study to assess the immunogenicity, safety and reactogenicity of GlaxoSmithKline (GSK) Biologicals’ 10-valent pneumococcal conjugate vaccine in Mexico when co-administered with GSK Biologicals’ Infanrix hexa (DTPa-HBV-IPV/Hib) vaccine as a 3-dose primary immunization course at 2, 4 and 6 months of age and GSK Biologicals’ Rotarix vaccine (HRV) as a 2-dose primary immunization course at 2 and 4 months of age.
Summary
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EudraCT number |
2015-001510-10 |
Trial protocol |
Outside EU/EEA |
Global end of trial date |
31 Mar 2008
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Results information
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Results version number |
v2(current) |
This version publication date |
05 Apr 2023
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First version publication date |
31 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 |
109661
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT00489554 | ||
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 |
13 Aug 2008
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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 |
31 Mar 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 compare the immunogenicity of GSK Biologicals’ 10-valent pneumococcal conjugate vaccine in Mexico, one month post dose III, when co-administered with GSK Biologicals’ Infanrix hexa and GSK Biologicals’ Rotarix vaccines, to the immune responses as observed in the pivotal non-inferiority, lot-to-lot consistency study 10PN-PD-DIT-001 in Europe.
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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. The subject’s parents/guardians were instructed to contact the investigator immediately should their child manifest any signs or symptoms they perceived as serious. Subjects were followed up for any safety event from the time the subject consented to participate in the study until she/he was discharged.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
03 Jul 2007
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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 |
Mexico: 230
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Worldwide total number of subjects |
230
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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) |
230
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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 |
230 subjects were enrolled in the study, all of whom were vaccinated. Study duration was of approximately 5 months (from Day 0, day of 1st vaccination, up to Month 5). | ||||||||||||||
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 (Day 0 to Month 5) (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||||||
Arms
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Arm title
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Synflorix Vaccine Group | ||||||||||||||
Arm description |
Subjects receiving Synflorix vaccine co-administered with DTPa-HBV-IPV/Hib (Infanrix hexa) vaccine at 2-4-6 months of age, and co-administered with HRV (Rotarix) vaccine at 2-4 months of age. 10Pn-PD-DIT and DTPa-HBV-IPV/Hib vaccines were administered intramuscularly in the thigh, on the right and left side, respectively. HRV vaccine was administered orally. | ||||||||||||||
Arm type |
Experimental | ||||||||||||||
Investigational medicinal product name |
Synflorix
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Investigational medicinal product code |
10Pn-PD-DiT
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Other name |
Pneumococcal conjugate vaccine GSK1024850A; 10Pn
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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 |
Intramuscular injection, 3 doses administered in the right thigh.
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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 |
Intramuscular injection, 3 doses administered in the left thigh.
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Investigational medicinal product name |
Rotarix
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Investigational medicinal product code |
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Other name |
HRV
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Pharmaceutical forms |
Powder and solvent for oral solution
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Routes of administration |
Oral use
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Dosage and administration details |
Oral, 2 doses.
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Baseline characteristics reporting groups
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Reporting group title |
Synflorix Vaccine Group
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Reporting group description |
Subjects receiving Synflorix vaccine co-administered with DTPa-HBV-IPV/Hib (Infanrix hexa) vaccine at 2-4-6 months of age, and co-administered with HRV (Rotarix) vaccine at 2-4 months of age. 10Pn-PD-DIT and DTPa-HBV-IPV/Hib vaccines were administered intramuscularly in the thigh, on the right and left side, respectively. HRV vaccine was administered orally. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Synflorix Vaccine Group
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Reporting group description |
Subjects receiving Synflorix vaccine co-administered with DTPa-HBV-IPV/Hib (Infanrix hexa) vaccine at 2-4-6 months of age, and co-administered with HRV (Rotarix) vaccine at 2-4 months of age. 10Pn-PD-DIT and DTPa-HBV-IPV/Hib vaccines were administered intramuscularly in the thigh, on the right and left side, respectively. HRV vaccine was administered orally. | ||
Subject analysis set title |
10Pn-001 Group
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Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
This group consisted in a pooling of the subjects receiving the 10Pn vaccine in study 10PN-PD-DIT-001 (105553) (EuDRA CT number: 2005-003300-11). These subjects received in this 10PN-PD-DIT-001 study a 3-dose primary vaccination course of 10Pn vaccine at 2, 3 and 4 months of age (3 different lots)co-administered with DTPa-HBV-IPV/Hib (Infanrix hexa), except for the second dose in France which was co-administered with Infanrix-IPV/Hib vaccine. The number of subjects in this subject analysis set is in total 1107 subjects, 230 being a placeholder value.
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End point title |
Antibody concentrations against pneumococcal vaccine serotypes [1] | ||||||||||||||||||||||||||||
End point description |
Concentrations were expressed as geometric mean concentration (GMC). The vaccine pneumococcal serotypes assessed include 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F, and 23F.
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End point type |
Primary
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End point timeframe |
One month after the administration of the 3rd vaccine dose i.e. Month 5
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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: This outcome was descriptive, focusing only on AEs; hence no statistical analyses were required. |
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No statistical analyses for this end point |
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End point title |
Antibody concentrations against Protein D [2] | ||||||||||
End point description |
Concentrations were given as geometric mean concentration (GMC) expressed as enzyme-linked immuno-sorbent assay (ELISA) units per milliliter.
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End point type |
Primary
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End point timeframe |
One month after the administration of the 3rd vaccine dose i.e. Month 5
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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: This outcome was descriptive, hence no statistical analyses were required. |
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No statistical analyses for this end point |
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End point title |
Comparison of 10PN-PD-DIT-001 study vs 10PN-PD-DIT-029 study as regards Anti-Pneumococcal Vaccine Serotype Antibody Concentrations | ||||||||||||||||||||||||||||||||||||||||||
End point description |
Antibodies assessed for this comparison endpoint were antibodies against the vaccine pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F (ANTI-1, -4, -5, -6B, -7F, -9V, -14, -18C, -19F and -23F). The seropositivity cut-off of the assay was an antibody concentration greater or equal to (>=) 0.05 µg/mL. Studies compared as regards results for antibody concentrations against 10Pn pneumococcal vaccine serotypes were studies 10PN-PD-DIT-029 (this study) and 10PN-PD-DIT-001 (105553) (EuDRA CT number: 2005-003300-11) via a comparison of 10Pn-001 Group over Synflorix Vaccine Group.
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End point type |
Primary
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End point timeframe |
One month after the administration of the 3rd vaccine dose, i.e. at Month 5
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Statistical analysis title |
10PN-PD-DIT-001 over -029 Anti-1 GMC ratio | ||||||||||||||||||||||||||||||||||||||||||
Statistical analysis description |
One month after the administration of the 3rd vaccine dose, i.e. at Month 5, ratios of geometric mean concentrations (GMCs), by enzyme-linked immunosorbent assay (ELISA), of 10Pn-001 Group over Synflorix Vaccine Group were calculated for each of the 10 pneumococcal serotypes and for protein D (PD), using an ANOVA model. This statistical analysis section concerns Anti-1 pneumococcal antibodies.
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Comparison groups |
Synflorix Vaccine Group v 10Pn-001 Group
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Number of subjects included in analysis |
1326
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Analysis specification |
Pre-specified
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Analysis type |
non-inferiority [3] | ||||||||||||||||||||||||||||||||||||||||||
Method |
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Parameter type |
GMC ratio | ||||||||||||||||||||||||||||||||||||||||||
Point estimate |
0.49
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Confidence interval |
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level |
95% | ||||||||||||||||||||||||||||||||||||||||||
sides |
2-sided
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lower limit |
0.44 | ||||||||||||||||||||||||||||||||||||||||||
upper limit |
0.55 | ||||||||||||||||||||||||||||||||||||||||||
Notes [3] - Comparability to the 10PN-PD-DIT-001 study in terms of non-inferiority was demonstrated if the upper limit of the 2-sided 95% confidence interval (CI) on the GMC ratios (GMCs from study 10PN-PD-DIT-001 over GMCs of current 10PN-PD-DIT-029 study) was below a limit of 2-fold for all of the 10 vaccine pneumococcal serotypes and for protein D (PD). |
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Statistical analysis title |
10PN-PD-DIT-001 over -029 Anti-4 GMC ratio | ||||||||||||||||||||||||||||||||||||||||||
Statistical analysis description |
One month after the administration of the 3rd vaccine dose, i.e. at Month 5, ratios of geometric mean concentrations (GMCs), by enzyme-linked immunosorbent assay (ELISA), of 10Pn-001 Group over Synflorix Vaccine Group were calculated for each of the 10 pneumococcal serotypes and for protein D (PD), using an ANOVA model. This statistical analysis section concerns Anti-4 pneumococcal antibodies.
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Comparison groups |
Synflorix Vaccine Group v 10Pn-001 Group
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Number of subjects included in analysis |
1326
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Analysis specification |
Pre-specified
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Analysis type |
non-inferiority [4] | ||||||||||||||||||||||||||||||||||||||||||
Method |
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Parameter type |
GMC ratio | ||||||||||||||||||||||||||||||||||||||||||
Point estimate |
0.48
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Confidence interval |
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level |
95% | ||||||||||||||||||||||||||||||||||||||||||
sides |
2-sided
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lower limit |
0.42 | ||||||||||||||||||||||||||||||||||||||||||
upper limit |
0.54 | ||||||||||||||||||||||||||||||||||||||||||
Notes [4] - Comparability to the 10PN-PD-DIT-001 study in terms of non-inferiority was demonstrated if the upper limit of the 2-sided 95% confidence interval (CI) on the GMC ratios (GMCs from study 10PN-PD-DIT-001 over GMCs of current 10PN-PD-DIT-029 study) was below a limit of 2-fold for all of the 10 vaccine pneumococcal serotypes and for protein D (PD). |
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Statistical analysis title |
10PN-PD-DIT-001 over -029 Anti-5 GMC ratio | ||||||||||||||||||||||||||||||||||||||||||
Statistical analysis description |
One month after the administration of the 3rd vaccine dose, i.e. at Month 5, ratios of geometric mean concentrations (GMCs), by enzyme-linked immunosorbent assay (ELISA), of 10Pn-001 Group over Synflorix Vaccine Group were calculated for each of the 10 pneumococcal serotypes and for protein D (PD), using an ANOVA model. This statistical analysis section concerns Anti-5 pneumococcal antibodies.
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Comparison groups |
Synflorix Vaccine Group v 10Pn-001 Group
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Number of subjects included in analysis |
1326
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Analysis specification |
Pre-specified
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Analysis type |
non-inferiority [5] | ||||||||||||||||||||||||||||||||||||||||||
Method |
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Parameter type |
GMC ratio | ||||||||||||||||||||||||||||||||||||||||||
Point estimate |
0.52
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Confidence interval |
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level |
95% | ||||||||||||||||||||||||||||||||||||||||||
sides |
2-sided
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lower limit |
0.47 | ||||||||||||||||||||||||||||||||||||||||||
upper limit |
0.59 | ||||||||||||||||||||||||||||||||||||||||||
Notes [5] - Comparability to the 10PN-PD-DIT-001 study in terms of non-inferiority was demonstrated if the upper limit of the 2-sided 95% confidence interval (CI) on the GMC ratios (GMCs from study 10PN-PD-DIT-001 over GMCs of current 10PN-PD-DIT-029 study) was below a limit of 2-fold for all of the 10 vaccine pneumococcal serotypes and for protein D (PD). |
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Statistical analysis title |
10PN-PD-DIT-001 over -029 Anti-6B GMC ratio | ||||||||||||||||||||||||||||||||||||||||||
Statistical analysis description |
One month after the administration of the 3rd vaccine dose, i.e. at Month 5, ratios of geometric mean concentrations (GMCs), by enzyme-linked immunosorbent assay (ELISA), of 10Pn-001 Group over Synflorix Vaccine Group were calculated for each of the 10 pneumococcal serotypes and for protein D (PD), using an ANOVA model. This statistical analysis section concerns Anti-6B pneumococcal antibodies.
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Comparison groups |
Synflorix Vaccine Group v 10Pn-001 Group
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Number of subjects included in analysis |
1326
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Analysis specification |
Pre-specified
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Analysis type |
non-inferiority [6] | ||||||||||||||||||||||||||||||||||||||||||
Method |
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Parameter type |
GMC ratio | ||||||||||||||||||||||||||||||||||||||||||
Point estimate |
0.25
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Confidence interval |
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level |
95% | ||||||||||||||||||||||||||||||||||||||||||
sides |
2-sided
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lower limit |
0.21 | ||||||||||||||||||||||||||||||||||||||||||
upper limit |
0.3 | ||||||||||||||||||||||||||||||||||||||||||
Notes [6] - Comparability to the 10PN-PD-DIT-001 study in terms of non-inferiority was demonstrated if the upper limit of the 2-sided 95% confidence interval (CI) on the GMC ratios (GMCs from study 10PN-PD-DIT-001 over GMCs of current 10PN-PD-DIT-029 study) was below a limit of 2-fold for all of the 10 vaccine pneumococcal serotypes and for protein D (PD). |
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Statistical analysis title |
10PN-PD-DIT-001 over -029 Anti-7F GMC ratio | ||||||||||||||||||||||||||||||||||||||||||
Statistical analysis description |
One month after the administration of the 3rd vaccine dose, i.e. at Month 5, ratios of geometric mean concentrations (GMCs), by enzyme-linked immunosorbent assay (ELISA), of 10Pn-001 Group over Synflorix Vaccine Group were calculated for each of the 10 pneumococcal serotypes and for protein D (PD), using an ANOVA model. This statistical analysis section concerns Anti-7F pneumococcal antibodies.
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Comparison groups |
Synflorix Vaccine Group v 10Pn-001 Group
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Number of subjects included in analysis |
1326
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Analysis specification |
Pre-specified
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Analysis type |
non-inferiority [7] | ||||||||||||||||||||||||||||||||||||||||||
Method |
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Parameter type |
GMC ratio | ||||||||||||||||||||||||||||||||||||||||||
Point estimate |
0.46
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Confidence interval |
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level |
95% | ||||||||||||||||||||||||||||||||||||||||||
sides |
2-sided
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lower limit |
0.41 | ||||||||||||||||||||||||||||||||||||||||||
upper limit |
0.52 | ||||||||||||||||||||||||||||||||||||||||||
Notes [7] - Comparability to the 10PN-PD-DIT-001 study in terms of non-inferiority was demonstrated if the upper limit of the 2-sided 95% confidence interval (CI) on the GMC ratios (GMCs from study 10PN-PD-DIT-001 over GMCs of current 10PN-PD-DIT-029 study) was below a limit of 2-fold for all of the 10 vaccine pneumococcal serotypes and for protein D (PD). |
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Statistical analysis title |
10PN-PD-DIT-001 over -029 Anti-9V GMC ratio | ||||||||||||||||||||||||||||||||||||||||||
Statistical analysis description |
One month after the administration of the 3rd vaccine dose, i.e. at Month 5, ratios of geometric mean concentrations (GMCs), by enzyme-linked immunosorbent assay (ELISA), of 10Pn-001 Group over Synflorix Vaccine Group were calculated for each of the 10 pneumococcal serotypes and for protein D (PD), using an ANOVA model. This statistical analysis section concerns Anti-9V pneumococcal antibodies.
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Comparison groups |
Synflorix Vaccine Group v 10Pn-001 Group
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Number of subjects included in analysis |
1326
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Analysis specification |
Pre-specified
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Analysis type |
non-inferiority [8] | ||||||||||||||||||||||||||||||||||||||||||
Method |
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Parameter type |
GMC ratio | ||||||||||||||||||||||||||||||||||||||||||
Point estimate |
0.35
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Confidence interval |
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level |
95% | ||||||||||||||||||||||||||||||||||||||||||
sides |
2-sided
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lower limit |
0.32 | ||||||||||||||||||||||||||||||||||||||||||
upper limit |
0.4 | ||||||||||||||||||||||||||||||||||||||||||
Notes [8] - Comparability to the 10PN-PD-DIT-001 study in terms of non-inferiority was demonstrated if the upper limit of the 2-sided 95% confidence interval (CI) on the GMC ratios (GMCs from study 10PN-PD-DIT-001 over GMCs of current 10PN-PD-DIT-029 study) was below a limit of 2-fold for all of the 10 vaccine pneumococcal serotypes and for protein D (PD). |
|||||||||||||||||||||||||||||||||||||||||||
Statistical analysis title |
10PN-PD-DIT-001 over -029 Anti-14 GMC ratio | ||||||||||||||||||||||||||||||||||||||||||
Statistical analysis description |
One month after the administration of the 3rd vaccine dose, i.e. at Month 5, ratios of geometric mean concentrations (GMCs), by enzyme-linked immunosorbent assay (ELISA), of 10Pn-001 Group over Synflorix Vaccine Group were calculated for each of the 10 pneumococcal serotypes and for protein D (PD), using an ANOVA model. This statistical analysis section concerns Anti-14 pneumococcal antibodies.
|
||||||||||||||||||||||||||||||||||||||||||
Comparison groups |
Synflorix Vaccine Group v 10Pn-001 Group
|
||||||||||||||||||||||||||||||||||||||||||
Number of subjects included in analysis |
1326
|
||||||||||||||||||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||||||||||||||||||||
Analysis type |
non-inferiority [9] | ||||||||||||||||||||||||||||||||||||||||||
Method |
|||||||||||||||||||||||||||||||||||||||||||
Parameter type |
GMC ratio | ||||||||||||||||||||||||||||||||||||||||||
Point estimate |
0.55
|
||||||||||||||||||||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||||||||||||||||||||
lower limit |
0.48 | ||||||||||||||||||||||||||||||||||||||||||
upper limit |
0.63 | ||||||||||||||||||||||||||||||||||||||||||
Notes [9] - Comparability to the 10PN-PD-DIT-001 study in terms of non-inferiority was demonstrated if the upper limit of the 2-sided 95% confidence interval (CI) on the GMC ratios (GMCs from study 10PN-PD-DIT-001 over GMCs of current 10PN-PD-DIT-029 study) was below a limit of 2-fold for all of the 10 vaccine pneumococcal serotypes and for protein D (PD). |
|||||||||||||||||||||||||||||||||||||||||||
Statistical analysis title |
10PN-PD-DIT-001 over -029 Anti-18C GMC ratio | ||||||||||||||||||||||||||||||||||||||||||
Statistical analysis description |
One month after the administration of the 3rd vaccine dose, i.e. at Month 5, ratios of geometric mean concentrations (GMCs), by enzyme-linked immunosorbent assay (ELISA), of 10Pn-001 Group over Synflorix Vaccine Group were calculated for each of the 10 pneumococcal serotypes and for protein D (PD), using an ANOVA model. This statistical analysis section concerns Anti-18C pneumococcal antibodies.
|
||||||||||||||||||||||||||||||||||||||||||
Comparison groups |
Synflorix Vaccine Group v 10Pn-001 Group
|
||||||||||||||||||||||||||||||||||||||||||
Number of subjects included in analysis |
1326
|
||||||||||||||||||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||||||||||||||||||||
Analysis type |
non-inferiority [10] | ||||||||||||||||||||||||||||||||||||||||||
Method |
|||||||||||||||||||||||||||||||||||||||||||
Parameter type |
GMC ratio | ||||||||||||||||||||||||||||||||||||||||||
Point estimate |
0.27
|
||||||||||||||||||||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||||||||||||||||||||
lower limit |
0.24 | ||||||||||||||||||||||||||||||||||||||||||
upper limit |
0.32 | ||||||||||||||||||||||||||||||||||||||||||
Notes [10] - Comparability to the 10PN-PD-DIT-001 study in terms of non-inferiority was demonstrated if the upper limit of the 2-sided 95% confidence interval (CI) on the GMC ratios (GMCs from study 10PN-PD-DIT-001 over GMCs of current 10PN-PD-DIT-029 study) was below a limit of 2-fold for all of the 10 vaccine pneumococcal serotypes and for protein D (PD). |
|||||||||||||||||||||||||||||||||||||||||||
Statistical analysis title |
10PN-PD-DIT-001 over -029 Anti-19F GMC ratio | ||||||||||||||||||||||||||||||||||||||||||
Statistical analysis description |
One month after the administration of the 3rd vaccine dose, i.e. at Month 5, ratios of geometric mean concentrations (GMCs), by enzyme-linked immunosorbent assay (ELISA), of 10Pn-001 Group over Synflorix Vaccine Group were calculated for each of the 10 pneumococcal serotypes and for protein D (PD), using an ANOVA model. This statistical analysis section concerns Anti-19F pneumococcal antibodies.
|
||||||||||||||||||||||||||||||||||||||||||
Comparison groups |
Synflorix Vaccine Group v 10Pn-001 Group
|
||||||||||||||||||||||||||||||||||||||||||
Number of subjects included in analysis |
1326
|
||||||||||||||||||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||||||||||||||||||||
Analysis type |
non-inferiority [11] | ||||||||||||||||||||||||||||||||||||||||||
Method |
|||||||||||||||||||||||||||||||||||||||||||
Parameter type |
GMC ratio | ||||||||||||||||||||||||||||||||||||||||||
Point estimate |
0.34
|
||||||||||||||||||||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||||||||||||||||||||
lower limit |
0.28 | ||||||||||||||||||||||||||||||||||||||||||
upper limit |
0.4 | ||||||||||||||||||||||||||||||||||||||||||
Notes [11] - Comparability to the 10PN-PD-DIT-001 study in terms of non-inferiority was demonstrated if the upper limit of the 2-sided 95% confidence interval (CI) on the GMC ratios (GMCs from study 10PN-PD-DIT-001 over GMCs of current 10PN-PD-DIT-029 study) was below a limit of 2-fold for all of the 10 vaccine pneumococcal serotypes and for protein D (PD). |
|||||||||||||||||||||||||||||||||||||||||||
Statistical analysis title |
10PN-PD-DIT-001 over -029 Anti-23F GMC ratio | ||||||||||||||||||||||||||||||||||||||||||
Statistical analysis description |
One month after the administration of the 3rd vaccine dose, i.e. at Month 5, ratios of geometric mean concentrations (GMCs), by enzyme-linked immunosorbent assay (ELISA), of 10Pn-001 Group over Synflorix Vaccine Group were calculated for each of the 10 pneumococcal serotypes and for protein D (PD), using an ANOVA model. This statistical analysis section concerns Anti-23F pneumococcal antibodies.
|
||||||||||||||||||||||||||||||||||||||||||
Comparison groups |
Synflorix Vaccine Group v 10Pn-001 Group
|
||||||||||||||||||||||||||||||||||||||||||
Number of subjects included in analysis |
1326
|
||||||||||||||||||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||||||||||||||||||||
Analysis type |
non-inferiority [12] | ||||||||||||||||||||||||||||||||||||||||||
Method |
|||||||||||||||||||||||||||||||||||||||||||
Parameter type |
GMC ratio | ||||||||||||||||||||||||||||||||||||||||||
Point estimate |
0.27
|
||||||||||||||||||||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||||||||||||||||||||
lower limit |
0.22 | ||||||||||||||||||||||||||||||||||||||||||
upper limit |
0.32 | ||||||||||||||||||||||||||||||||||||||||||
Notes [12] - Comparability to the 10PN-PD-DIT-001 study in terms of non-inferiority was demonstrated if the upper limit of the 2-sided 95% confidence interval (CI) on the GMC ratios (GMCs from study 10PN-PD-DIT-001 over GMCs of current 10PN-PD-DIT-029 study) was below a limit of 2-fold for all of the 10 vaccine pneumococcal serotypes and for protein D (PD). |
|
||||||||||||||||
End point title |
Comparison of 10PN-PD-DIT-001 study vs 10PN-PD-DIT-029 study as regards Anti-protein D (anti-PD) antibody concentrations | |||||||||||||||
End point description |
Antibodies assessed for this comparison endpoint were antibodies against protein D (anti-PD). The seropositivity cut-off of the assay was an antibody concentration >= 100 enzyme-linked immunosorbent assay (ELISA) units per millilitre (EL.U/mL). Studies compared as regards results for Anti-PD antibody concentrations were studies 10PN-PD-DIT-029 (this study) and 10PN-PD-DIT-001 (105553) (EuDRA CT number: 2005-003300-11) via a comparison of 10Pn-001 Group over Synflorix Vaccine Group.
|
|||||||||||||||
End point type |
Primary
|
|||||||||||||||
End point timeframe |
One month after the administration of the 3rd vaccine dose, i.e. at Month 5
|
|||||||||||||||
|
||||||||||||||||
Statistical analysis title |
10PN-PD-DIT-001 over -029 Anti-PD GMC ratio | |||||||||||||||
Statistical analysis description |
One month after the administration of the 3rd vaccine dose, i.e. at Month 5, ratios of geometric mean concentrations (GMCs), by enzyme-linked immunosorbent assay (ELISA), of 10Pn-001 Group over Synflorix Vaccine Group were calculated for each of the 10 pneumococcal serotypes and for protein D (PD), using an ANOVA model. This statistical analysis section concerns Anti-PD antibodies.
|
|||||||||||||||
Comparison groups |
Synflorix Vaccine Group v 10Pn-001 Group
|
|||||||||||||||
Number of subjects included in analysis |
1314
|
|||||||||||||||
Analysis specification |
Pre-specified
|
|||||||||||||||
Analysis type |
non-inferiority [13] | |||||||||||||||
Method |
||||||||||||||||
Parameter type |
GMC ratio | |||||||||||||||
Point estimate |
0.52
|
|||||||||||||||
Confidence interval |
||||||||||||||||
level |
95% | |||||||||||||||
sides |
2-sided
|
|||||||||||||||
lower limit |
0.46 | |||||||||||||||
upper limit |
0.6 | |||||||||||||||
Notes [13] - Comparability to the 10PN-PD-DIT-001 study in terms of non-inferiority was demonstrated if the upper limit of the 2-sided 95% confidence interval (CI) on the GMC ratios (GMCs from study 10PN-PD-DIT-001 over GMCs of current 10PN-PD-DIT-029 study) was below a limit of 2-fold for all of the 10 vaccine pneumococcal serotypes and for protein D (PD). |
|
|||||||||||||||||||||||||||||
End point title |
Opsonophagocytic titer against pneumococcal vaccine serotypes | ||||||||||||||||||||||||||||
End point description |
The results were presented as the geometric mean dilution of serum (opsonic titer) able to sustain 50% killing of live pneumococci under the assay conditions. The vaccine pneumococcal serotypes assessed include 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F, and 23F.
|
||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||
End point timeframe |
One month after the administration of the 3rd vaccine dose i.e. Month 5
|
||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||
End point title |
Number of subjects with anti-pneumococcal vaccine serotypes antibody concentrations greater than or equal to 0.2 microgram per milliliter | ||||||||||||||||||||||||||
End point description |
The vaccine pneumococcal serotypes assessed include 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F, and 23F.
|
||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||
End point timeframe |
One month after the administration of the 3rd vaccine dose i.e. Month 5
|
||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Antibody concentrations against pneumococcal cross-reactive serotypes | ||||||||||||
End point description |
Antibody concentrations were expressed as Geometric Mean Concentrations against pneumococcal cross-reactive serotypes 6A and 19A.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
One month after the administration of the 3rd vaccine dose i.e. Month 5
|
||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Opsonophagocytic titer against pneumococcal cross-reactive serotypes | ||||||||||||
End point description |
The results were presented as the geometric mean dilution of serum (opsonic titer) able to sustain 50% killing of live pneumococci under the assay conditions. The cross-reactive pneumococcal serotypes assessed include 6A and 19A.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
One month after the administration of the 3rd vaccine dose i.e. Month 5
|
||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||
End point title |
Number of subjects seropositive against vaccine pneumococcal serotypes | ||||||||||||||||||||||||||
End point description |
Seropositivity was defined as anti-pneumococcal antibody concentration greater than or equal to 0.05 microgram per milliliter. The vaccine pneumococcal serotypes assessed include 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F, and 23F.
|
||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||
End point timeframe |
One month after the administration of the 3rd vaccine dose i.e. Month 5
|
||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||
End point title |
Number of subjects seropositive for opsonic titer against vaccine pneumococcal serotypes | ||||||||||||||||||||||||||
End point description |
Seropositivity was defined as an opsonic titer greater than or equal to 8. The vaccine pneumococcal serotypes assessed include 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F, and 23F.
|
||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||
End point timeframe |
One month after the administration of the 3rd vaccine dose i.e. Month 5
|
||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||
End point title |
Number of subjects seropositive against cross-reactive pneumococcal serotypes | ||||||||||
End point description |
Seropositivity was defined as anti-pneumococcal antibody concentration greater than or equal to 0.05 microgram per milliliter. The cross-reactive pneumococcal serotypes assessed include 6A and 19A.
|
||||||||||
End point type |
Secondary
|
||||||||||
End point timeframe |
One month after the administration of the 3rd vaccine dose i.e. Month 5
|
||||||||||
|
|||||||||||
No statistical analyses for this end point |
|
|||||||||||
End point title |
Number of subjects seropositive for opsonic titer against cross-reactive pneumococcal serotypes | ||||||||||
End point description |
Seropositivity was defined as anti-pneumococcal antibody opsonic titer greater than or equal to 8. The vaccine pneumococcal cross-reactive serotypes assessed include 6A and 19A.
|
||||||||||
End point type |
Secondary
|
||||||||||
End point timeframe |
One month after the administration of the 3rd vaccine dose i.e. Month 5
|
||||||||||
|
|||||||||||
No statistical analyses for this end point |
|
|||||||||
End point title |
Number of subjects seropositive for anti-Protein D antibodies | ||||||||
End point description |
Seropositivity was defined as antibody concentration greater than or equal to 100 Enzyme-Linked Immuno Sorbent Assay (ELISA) units per milliliter.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
One month after the administration of the 3rd vaccine dose i.e. Month 5
|
||||||||
|
|||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||
End point title |
Number of subjects reporting any and grade 3 solicited local Adverse Events (AEs) | ||||||||||||||||||
End point description |
Grade 3 redness and swelling was > 30 millimeter (mm) and grade 3 pain was subjects crying when limb was moved/spontaneously painful. Any was occurrence of any local symptom regardless of grade and whatever the number of injections.
|
||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||
End point timeframe |
Within 4 days following any vaccine dose
|
||||||||||||||||||
|
|||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||||||||
End point title |
Number of subjects reporting any, grade 3 and related solicited general AEs | ||||||||||||||||||||||||||||||||||||||||||
End point description |
Any fever was defined as axillary temperature ≥ 37.5 degree centigrade (°C), grade 3 fever was axillary temperature > 39.5°C. Grade 3 drowsiness, irritability, and loss of appetite was general symptom which prevented normal everyday activities. Grade 3 diarrhea was ≥ 6 looser than normal stools/day and Grade 3 vomiting was ≥ 3 episodes of vomiting/day. Related was solicited general symptom considered by the investigator to have a causal relationship to study vaccination.
|
||||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Within 4 days following any vaccine dose
|
||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||
End point title |
Number of subjects reporting any unsolicited AEs | ||||||||
End point description |
Unsolicited AE covers any AE reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
Within 31 days after any vaccine dose
|
||||||||
|
|||||||||
No statistical analyses for this end point |
|
|||||||||
End point title |
Number of subjects reporting any serious adverse events (SAEs) | ||||||||
End point description |
SAEs assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization, result in disability/incapacity or are a congenital anomaly/birth defect in the offspring of a study subject.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
Entire study period, from Day 0 up to Month 5
|
||||||||
|
|||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse events information
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Timeframe for reporting adverse events |
Serious adverse events were assessed up to month 5. Systematically assessed frequent adverse events (AEs) and non-systematically assessed frequent AEs were assessed during 4 day and 31 day post vaccination period respectively.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Assessment type |
Non-systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
11.0
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Synflorix vaccine Group
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Subjects receiving Synflorix vaccine co-administered with DTPa-HBV-IPV/Hib (Infanrix hexa) vaccine at 2-4-6 months of age, and co-administered with HRV (Rotarix) vaccine at 2-4 months of age. 10Pn-PD-DIT and DTPa-HBV-IPV/Hib vaccines were administered intramuscularly in the thigh, on the right and left side, respectively. HRV vaccine was administered orally. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|||
Substantial protocol amendments (globally) |
|||
Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
||
13 Mar 2007 |
This amendment is made in order to update specific study information; because of an updated protocol template (version 12.4); and in general to facilitate reading of the protocol. |
||
Interruptions (globally) |
|||
Were there any global interruptions to the trial? No | |||
Limitations and caveats |
|||
Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
None reported |