Clinical Trial Results:
A Phase 3, Open Label, Randomized, Controlled, Multi-Center Study to Evaluate the Safety and Immunogenicity of GlaxoSmithKline Biologicals Meningococcal B Recombinant Vaccine When Administered Concomitantly With Routine Vaccines to Healthy Infants in Taiwan.
Summary
|
|
EudraCT number |
2014-005568-14 |
Trial protocol |
Outside EU/EEA |
Global end of trial date |
17 Jun 2016
|
Results information
|
|
Results version number |
v2(current) |
This version publication date |
04 Sep 2020
|
First version publication date |
08 Mar 2017
|
Other versions |
v1 |
Version creation reason |
|
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
|
|||
Trial identification
|
|||
Sponsor protocol code |
205249
|
||
Additional study identifiers
|
|||
ISRCTN number |
- | ||
US NCT number |
NCT02173704 | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
|
|||
Sponsor organisation name |
GlaxoSmithKline Biologicals
|
||
Sponsor organisation address |
Rue de l'Institut 89, Rixensart, Belgium, B-1330
|
||
Public contact |
Clinical Trials Call Center, GlaxoSmithKline Biologicals, 044 2089904466, GSKClinicalSupportHD@gsk.com
|
||
Scientific contact |
Clinical Trials Call Center, GlaxoSmithKline Biologicals, 044 2089904466, GSKClinicalSupportHD@gsk.com
|
||
Paediatric regulatory details
|
|||
Is trial part of an agreed paediatric investigation plan (PIP) |
No
|
||
Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
|
||
Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
Yes
|
||
Results analysis stage
|
|||
Analysis stage |
Final
|
||
Date of interim/final analysis |
09 Dec 2016
|
||
Is this the analysis of the primary completion data? |
Yes
|
||
Primary completion date |
25 Dec 2015
|
||
Global end of trial reached? |
Yes
|
||
Global end of trial date |
17 Jun 2016
|
||
Was the trial ended prematurely? |
No
|
||
General information about the trial
|
|||
Main objective of the trial |
1. To demonstrate the sufficiency of the immune response to Bexsero® vaccine, when administered concomitantly with routine vaccines (i.e. Infanrix- IPV+Hib®, Engerix-B® and Prevenar-13®) to healthy infants at 2, 4, 6 months of age as measured by percentage of subjects with human serum bactericidal activity (hSBA) titer ≥ 1:5 against the indicator strains H44/76, 5/99 and NZ98/254 at 1 month after the third vaccination (at 7 months of age);
2. To assess the safety of a 3-dose schedule (at 2, 4, 6 months) of GSK Biologicals Meningococcal B recombinant vaccine followed by a booster dose at 12 months when concomitantly administered with routine vaccines in healthy infants;
3. To assess serious adverse events (SAEs), medically attended adverse events (AEs), AEs leading to withdrawal throughout the entire study.
|
||
Protection of trial subjects |
The subjects were observed closely for at least 30 minutes following the administration of vaccine(s), with appropriate medical treatment readily available in case of a rare anaphylactic reaction.
|
||
Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
11 Sep 2014
|
||
Long term follow-up planned |
No
|
||
Independent data monitoring committee (IDMC) involvement? |
No
|
||
Population of trial subjects
|
|||
Number of subjects enrolled per country |
|||
Country: Number of subjects enrolled |
Taiwan: 225
|
||
Worldwide total number of subjects |
225
|
||
EEA total number of subjects |
0
|
||
Number of subjects enrolled per age group |
|||
In utero |
0
|
||
Preterm newborn - gestational age < 37 wk |
0
|
||
Newborns (0-27 days) |
0
|
||
Infants and toddlers (28 days-23 months) |
225
|
||
Children (2-11 years) |
0
|
||
Adolescents (12-17 years) |
0
|
||
Adults (18-64 years) |
0
|
||
From 65 to 84 years |
0
|
||
85 years and over |
0
|
|
||||||||||||||||||||||||||||
Recruitment
|
||||||||||||||||||||||||||||
Recruitment details |
Subjects were recruited from 2 sites in Taiwan. | |||||||||||||||||||||||||||
Pre-assignment
|
||||||||||||||||||||||||||||
Screening details |
All subjects were enrolled. | |||||||||||||||||||||||||||
Period 1
|
||||||||||||||||||||||||||||
Period 1 title |
Overall Study (overall period)
|
|||||||||||||||||||||||||||
Is this the baseline period? |
Yes | |||||||||||||||||||||||||||
Allocation method |
Randomised - controlled
|
|||||||||||||||||||||||||||
Blinding used |
Not blinded | |||||||||||||||||||||||||||
Blinding implementation details |
The study was an open-label study. Therefore, no blinding procedures were utilized.
|
|||||||||||||||||||||||||||
Arms
|
||||||||||||||||||||||||||||
Are arms mutually exclusive |
Yes
|
|||||||||||||||||||||||||||
Arm title
|
Bexsero + Routine Group | |||||||||||||||||||||||||||
Arm description |
Subjects received three doses of Bexsero® vaccine at 2, 4, 6 months followed by a booster dose at 12 months, concomitantly administered with routine vaccines (i.e. combined Infanrix-IPV+Hib® and Prevenar-13® at 2, 4, 6 months of age; Engerix-B® at 6 months of age; Priorix® and Varilrix® at 12 months of age. | |||||||||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||||||||
Investigational medicinal product name |
Bexsero®
|
|||||||||||||||||||||||||||
Investigational medicinal product code |
rMenB+OMV NZ
|
|||||||||||||||||||||||||||
Other name |
GSK Biologicals Meningococcal Recombinant B with Outer Membrane Vesicles (OMV) Vaccine
|
|||||||||||||||||||||||||||
Pharmaceutical forms |
Solution for injection in pre-filled syringe
|
|||||||||||||||||||||||||||
Routes of administration |
Intramuscular use
|
|||||||||||||||||||||||||||
Dosage and administration details |
0.5 mL dose, administered in the anterolateral area of the right or left thigh.
|
|||||||||||||||||||||||||||
Investigational medicinal product name |
Prevenar-13®
|
|||||||||||||||||||||||||||
Investigational medicinal product code |
||||||||||||||||||||||||||||
Other name |
Pfizer 13-valent pneumococcal conjugate vaccine
|
|||||||||||||||||||||||||||
Pharmaceutical forms |
Solution for injection
|
|||||||||||||||||||||||||||
Routes of administration |
Intramuscular use
|
|||||||||||||||||||||||||||
Dosage and administration details |
0.5 mL dose, administered in the anterolateral area of the right or left thigh.
|
|||||||||||||||||||||||||||
Investigational medicinal product name |
Infanrix-IPV+Hib®
|
|||||||||||||||||||||||||||
Investigational medicinal product code |
||||||||||||||||||||||||||||
Other name |
GSK Biologicals 5-in-1 DTaP-IPV-Hib vaccine
|
|||||||||||||||||||||||||||
Pharmaceutical forms |
Solution for injection
|
|||||||||||||||||||||||||||
Routes of administration |
Intramuscular use
|
|||||||||||||||||||||||||||
Dosage and administration details |
0.5 mL dose, administered in the anterolateral area of the right or left thigh.
|
|||||||||||||||||||||||||||
Investigational medicinal product name |
Engerix-B®
|
|||||||||||||||||||||||||||
Investigational medicinal product code |
||||||||||||||||||||||||||||
Other name |
GSK Biologicals Hepatitis B vaccine
|
|||||||||||||||||||||||||||
Pharmaceutical forms |
Solution for injection
|
|||||||||||||||||||||||||||
Routes of administration |
Intramuscular use
|
|||||||||||||||||||||||||||
Dosage and administration details |
0.5 mL dose, administered in the anterolateral area of the right or left thigh.
|
|||||||||||||||||||||||||||
Investigational medicinal product name |
Priorix®
|
|||||||||||||||||||||||||||
Investigational medicinal product code |
||||||||||||||||||||||||||||
Other name |
GSK Biologicals Measles, Mumps and Rubella vaccine
|
|||||||||||||||||||||||||||
Pharmaceutical forms |
Solution for injection
|
|||||||||||||||||||||||||||
Routes of administration |
Subcutaneous use
|
|||||||||||||||||||||||||||
Dosage and administration details |
0.5 mL dose, administered in the anterolateral area of the right or left thigh.
|
|||||||||||||||||||||||||||
Investigational medicinal product name |
Varilrix®
|
|||||||||||||||||||||||||||
Investigational medicinal product code |
||||||||||||||||||||||||||||
Other name |
GSK Biologicals Varicella vaccine
|
|||||||||||||||||||||||||||
Pharmaceutical forms |
Solution for injection
|
|||||||||||||||||||||||||||
Routes of administration |
Subcutaneous use
|
|||||||||||||||||||||||||||
Dosage and administration details |
0.5 mL dose, administered in the anterolateral area of the right or left thigh.
|
|||||||||||||||||||||||||||
Arm title
|
Routine Group | |||||||||||||||||||||||||||
Arm description |
Subjects received routine vaccines Infanrix-IPV+Hib® and Prevenar-13® at 2, 4, 6 months of age; Engerix-B® vaccine at 6 months; Priorix® and Varilrix® vaccines at 12 months of age. | |||||||||||||||||||||||||||
Arm type |
Active comparator | |||||||||||||||||||||||||||
Investigational medicinal product name |
Prevenar-13®
|
|||||||||||||||||||||||||||
Investigational medicinal product code |
||||||||||||||||||||||||||||
Other name |
Pfizer 13-valent pneumococcal conjugate vaccine
|
|||||||||||||||||||||||||||
Pharmaceutical forms |
Solution for injection
|
|||||||||||||||||||||||||||
Routes of administration |
Intramuscular use
|
|||||||||||||||||||||||||||
Dosage and administration details |
0.5 mL dose, administered in the anterolateral area of the right or left thigh.
|
|||||||||||||||||||||||||||
Investigational medicinal product name |
Infanrix-IPV+Hib®
|
|||||||||||||||||||||||||||
Investigational medicinal product code |
||||||||||||||||||||||||||||
Other name |
GSK Biologicals 5-in-1 DTaP-IPV-Hib vaccine
|
|||||||||||||||||||||||||||
Pharmaceutical forms |
Solution for injection
|
|||||||||||||||||||||||||||
Routes of administration |
Intramuscular use
|
|||||||||||||||||||||||||||
Dosage and administration details |
0.5 mL dose, administered in the anterolateral area of the right or left thigh.
|
|||||||||||||||||||||||||||
Investigational medicinal product name |
Engerix-B®
|
|||||||||||||||||||||||||||
Investigational medicinal product code |
||||||||||||||||||||||||||||
Other name |
GSK Biologicals Hepatitis B vaccine
|
|||||||||||||||||||||||||||
Pharmaceutical forms |
Solution for injection
|
|||||||||||||||||||||||||||
Routes of administration |
Intramuscular use
|
|||||||||||||||||||||||||||
Dosage and administration details |
0.5 mL dose, administered in the anterolateral area of the right or left thigh.
|
|||||||||||||||||||||||||||
Investigational medicinal product name |
Priorix®
|
|||||||||||||||||||||||||||
Investigational medicinal product code |
||||||||||||||||||||||||||||
Other name |
GSK Biologicals Measles, Mumps and Rubella vaccine
|
|||||||||||||||||||||||||||
Pharmaceutical forms |
Solution for injection
|
|||||||||||||||||||||||||||
Routes of administration |
Subcutaneous use
|
|||||||||||||||||||||||||||
Dosage and administration details |
0.5 mL dose, administered in the anterolateral area of the right or left thigh.
|
|||||||||||||||||||||||||||
Investigational medicinal product name |
Varilrix®
|
|||||||||||||||||||||||||||
Investigational medicinal product code |
||||||||||||||||||||||||||||
Other name |
GSK Biologicals Varicella vaccine
|
|||||||||||||||||||||||||||
Pharmaceutical forms |
Solution for injection
|
|||||||||||||||||||||||||||
Routes of administration |
Subcutaneous use
|
|||||||||||||||||||||||||||
Dosage and administration details |
0.5 mL dose, administered in the anterolateral area of the right or left thigh.
|
|||||||||||||||||||||||||||
|
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Baseline characteristics reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Bexsero + Routine Group
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Subjects received three doses of Bexsero® vaccine at 2, 4, 6 months followed by a booster dose at 12 months, concomitantly administered with routine vaccines (i.e. combined Infanrix-IPV+Hib® and Prevenar-13® at 2, 4, 6 months of age; Engerix-B® at 6 months of age; Priorix® and Varilrix® at 12 months of age. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Routine Group
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Subjects received routine vaccines Infanrix-IPV+Hib® and Prevenar-13® at 2, 4, 6 months of age; Engerix-B® vaccine at 6 months; Priorix® and Varilrix® vaccines at 12 months of age. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|||
End points reporting groups
|
|||
Reporting group title |
Bexsero + Routine Group
|
||
Reporting group description |
Subjects received three doses of Bexsero® vaccine at 2, 4, 6 months followed by a booster dose at 12 months, concomitantly administered with routine vaccines (i.e. combined Infanrix-IPV+Hib® and Prevenar-13® at 2, 4, 6 months of age; Engerix-B® at 6 months of age; Priorix® and Varilrix® at 12 months of age. | ||
Reporting group title |
Routine Group
|
||
Reporting group description |
Subjects received routine vaccines Infanrix-IPV+Hib® and Prevenar-13® at 2, 4, 6 months of age; Engerix-B® vaccine at 6 months; Priorix® and Varilrix® vaccines at 12 months of age. |
|
|||||||||||||||||||||||||||||||||||||
End point title |
Percentage of subjects with human Serum Bactericidal Activity (hSBA) titer ≥ 1:5 against Neisseria meningitidis serogroup B strains | ||||||||||||||||||||||||||||||||||||
End point description |
Percentage of subjects with human Serum Bactericidal Activity (hSBA) titer ≥ 1:5 at one month following the third vaccination (at 7 months
of age) against the indicator strains H44/76, 5/99, NZ98/254 and strain M10713 when Bexsero® was administered concomitantly with routine vaccines (Infanrix-IPV+Hib®, Prevenar-13® and Engerix®).
The analysis was performed on the Full Analysis Set (FAS) population Day 152, which included all subjects in the Exposed set who received at least one dose of a study vaccination and provided immunogenicity data at relevant time points.
|
||||||||||||||||||||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||||||||||||||||||||
End point timeframe |
At Day 1 and one month after the third vaccination (Day 152)
|
||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||
Statistical analysis title |
Statistical analysis H44/76 strain | ||||||||||||||||||||||||||||||||||||
Statistical analysis description |
The null hypothesis associated with the primary objective is that the proportion of subjects with hSBA titers ≥ 1:5 one month after the third dose of the Bexsero® vaccine was ≤ 0.70.
Assuming the results for the three strains are independent, the power to reject the null hypothesis associated with the primary objectives to demonstrate sufficiency of response (for all three strains was 92 %).
|
||||||||||||||||||||||||||||||||||||
Comparison groups |
Bexsero + Routine Group v Routine Group
|
||||||||||||||||||||||||||||||||||||
Number of subjects included in analysis |
206
|
||||||||||||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||||||||||||||
Analysis type |
other [1] | ||||||||||||||||||||||||||||||||||||
Method |
Exact test of binomial proportion | ||||||||||||||||||||||||||||||||||||
Parameter type |
Single binomial proportion | ||||||||||||||||||||||||||||||||||||
Point estimate |
100
|
||||||||||||||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||||||||||||||
lower limit |
97.2 | ||||||||||||||||||||||||||||||||||||
upper limit |
100 | ||||||||||||||||||||||||||||||||||||
Notes [1] - The criterion for a sufficient immune response was that the lower limit of the two-sided 95% CI for the percentage of subjects with hSBA titer ≥ 1:5 should be ≥ 70%. |
|||||||||||||||||||||||||||||||||||||
Statistical analysis title |
Statistical analysis 5/99 strain | ||||||||||||||||||||||||||||||||||||
Statistical analysis description |
The power to reject the null hypothesis associated with the primary objective for the 5/99 strain was 99 %.
|
||||||||||||||||||||||||||||||||||||
Comparison groups |
Bexsero + Routine Group v Routine Group
|
||||||||||||||||||||||||||||||||||||
Number of subjects included in analysis |
206
|
||||||||||||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||||||||||||||
Analysis type |
other [2] | ||||||||||||||||||||||||||||||||||||
Method |
Exact test of binomial proportion | ||||||||||||||||||||||||||||||||||||
Parameter type |
Single binomial proportion | ||||||||||||||||||||||||||||||||||||
Point estimate |
100
|
||||||||||||||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||||||||||||||
lower limit |
97.2 | ||||||||||||||||||||||||||||||||||||
upper limit |
100 | ||||||||||||||||||||||||||||||||||||
Notes [2] - The criterion for a sufficient immune response was that the lower limit of the two-sided 95 % CI for the percentage of subjects with hSBA titer ≥ 1:5 should be ≥ 70 %. |
|||||||||||||||||||||||||||||||||||||
Statistical analysis title |
Statistical analysis NZ98/254 strain | ||||||||||||||||||||||||||||||||||||
Statistical analysis description |
The power to reject the null hypothesis associated with the primary objective for the NZ98/254 strain was 94 %.
|
||||||||||||||||||||||||||||||||||||
Comparison groups |
Bexsero + Routine Group v Routine Group
|
||||||||||||||||||||||||||||||||||||
Number of subjects included in analysis |
206
|
||||||||||||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||||||||||||||
Analysis type |
other [3] | ||||||||||||||||||||||||||||||||||||
Method |
Exact test of binomial proportion | ||||||||||||||||||||||||||||||||||||
Parameter type |
Single binomial proportion | ||||||||||||||||||||||||||||||||||||
Point estimate |
79
|
||||||||||||||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||||||||||||||
lower limit |
71.4 | ||||||||||||||||||||||||||||||||||||
upper limit |
85.8 | ||||||||||||||||||||||||||||||||||||
Notes [3] - The criterion for a sufficient immune response was that the lower limit of the two-sided 95% CI for the percentage of subjects with hSBA titer ≥ 1:5 should be ≥ 70 %. |
|
|||||||||||||||||||||||||||||||||||||
End point title |
Percentage of subjects with human Serum Bactericidal Assay (hSBA) titer ≥ 1:4 against Neisseria meningitidis serogroup B strains [4] | ||||||||||||||||||||||||||||||||||||
End point description |
Percentage of subjects with hSBA titer ≥ 1:4 at 1 month after third vaccination (at 7 months of age) against the indicator strains H44/76, 5/99, NZ98/254 and strain M10713 when Bexsero® was given concomitantly with routine vaccines (Infanrix-IPV + Hib®, Prevenar-13® and Engerix-B®).
|
||||||||||||||||||||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||||||||||||||||||||
End point timeframe |
At Day 1 and at one month after third vaccination (Day 152)
|
||||||||||||||||||||||||||||||||||||
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: The scope of this endpoint was descriptive analysis. No statistical analysis performed for this endpoint |
|||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||
End point title |
Percentage of subjects with hSBA titer ≥ 1:5 against Neisseria meningitidis serogroup B strains, when Bexsero® booster dose was administered with routine vaccines (Priorix® + Varilrix® vaccines) | ||||||||||||||||||||||||||||||||||||
End point description |
Percentage of subjects with hSBA titer ≥ 1:5 before and one month after booster vaccination, when Bexsero® booster dose was administered with routine vaccines (Priorix® + Varilrix® vaccines) as compared to when only routine vaccines were administered.
The analysis was performed on the FAS population Day 335, which included all subjects in the Exposed set who received at least one dose of a study vaccination and provided immunogenicity data at relevant time points.
|
||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||
End point timeframe |
Day 305 and Day 335
|
||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||
Statistical analysis title |
Statistical analysis H44/76 strain | ||||||||||||||||||||||||||||||||||||
Statistical analysis description |
The null hypothesis associated with the primary objective is that the proportion of subjects with hSBA titers ≥ 1:5 one month after the third dose of the Bexsero® vaccine was ≤ 0.70. Assuming the results for the three strains are independent, the power to reject the null hypothesis associated with the primary objectives to demonstrate sufficiency of response (for all three strains was 92%).
|
||||||||||||||||||||||||||||||||||||
Comparison groups |
Bexsero + Routine Group v Routine Group
|
||||||||||||||||||||||||||||||||||||
Number of subjects included in analysis |
207
|
||||||||||||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||||||||||||||
Analysis type |
other [5] | ||||||||||||||||||||||||||||||||||||
Method |
Exact test of binomial proportion | ||||||||||||||||||||||||||||||||||||
Parameter type |
Single binomial proportion | ||||||||||||||||||||||||||||||||||||
Point estimate |
99
|
||||||||||||||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||||||||||||||
lower limit |
95.7 | ||||||||||||||||||||||||||||||||||||
upper limit |
99.98 | ||||||||||||||||||||||||||||||||||||
Notes [5] - The criterion for a sufficient immune response was that the lower limit of the two-sided 95% CI for the percentage of subjects with hSBA titer ≥ 1:5 should be ≥ 70%. |
|||||||||||||||||||||||||||||||||||||
Statistical analysis title |
Statistical analysis 5/99 strain | ||||||||||||||||||||||||||||||||||||
Statistical analysis description |
The power to reject the null hypothesis associated with the secondary objective for the 5/99 strain was 99%.
|
||||||||||||||||||||||||||||||||||||
Comparison groups |
Bexsero + Routine Group v Routine Group
|
||||||||||||||||||||||||||||||||||||
Number of subjects included in analysis |
207
|
||||||||||||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||||||||||||||
Analysis type |
other [6] | ||||||||||||||||||||||||||||||||||||
Method |
Exact test for binomial proportion | ||||||||||||||||||||||||||||||||||||
Parameter type |
Single binomial proportion | ||||||||||||||||||||||||||||||||||||
Point estimate |
99
|
||||||||||||||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||||||||||||||
lower limit |
94.7 | ||||||||||||||||||||||||||||||||||||
upper limit |
99.82 | ||||||||||||||||||||||||||||||||||||
Notes [6] - The criterion for a sufficient immune response was that the lower limit of the two-sided 95% CI for the percentage of subjects with hSBA titer ≥ 1:5 should be ≥ 75%. |
|||||||||||||||||||||||||||||||||||||
Statistical analysis title |
Statistical analysis NZ98/254 strain | ||||||||||||||||||||||||||||||||||||
Statistical analysis description |
The power to reject the null hypothesis associated with the secondary objective for the NZ98/254 strain was 99%.
|
||||||||||||||||||||||||||||||||||||
Comparison groups |
Bexsero + Routine Group v Routine Group
|
||||||||||||||||||||||||||||||||||||
Number of subjects included in analysis |
207
|
||||||||||||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||||||||||||||
Analysis type |
other [7] | ||||||||||||||||||||||||||||||||||||
Method |
Exact test for binomial proportions | ||||||||||||||||||||||||||||||||||||
Parameter type |
Single binomial proportion | ||||||||||||||||||||||||||||||||||||
Point estimate |
94
|
||||||||||||||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||||||||||||||
lower limit |
88.7 | ||||||||||||||||||||||||||||||||||||
upper limit |
97.4 | ||||||||||||||||||||||||||||||||||||
Notes [7] - The criterion for a sufficient immune response was that the lower limit of the two-sided 95% CI for the percentage of subjects with hSBA titer ≥ 1:5 should be ≥ 75%. |
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
hSBA Geometric Mean Titers (GMTs) against Neisseria meningitidis serogroup B indicator strains, when Bexsero® vaccine was administered with routine vaccines | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
hSBA GMTs against the indicator strains H44/76, 5/99, NZ98/254 and strain M10713 were evaluated at baseline (2 months of age, Day 1), 1 month after the third vaccination with Bexsero® with concomitant routine vaccines (Infanrix-IPV+Hib®, Prevenar-13®, Engerix®) (7 months of age, Day 152) or prior to the booster dose of Bexsero® with routine vaccines (Priorix®, Varilrix®) (12 months of age, Day 305) and 1 month after the booster dose (13 months of age, Day 335), as compared to when only routine vaccines were administered.
The analysis was performed on the FAS population, which included all subjects in the Exposed set who received at least one dose of a study vaccination and provided immunogenicity data at relevant time points.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Day 1, Day 152, Day 305 and Day 335
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||
End point title |
hSBA Geometric Mean Ratios (GMRs) against Neisseria meningitidis serogroup B strains | ||||||||||||||||||||||||||||||||||||
End point description |
GMRs of post-vaccination versus pre-vaccination of hSBA titer against the indicator strains H44/76, 5/99, NZ98/254 and strain M10713 were evaluated at one month after the third vaccination with Bexsero® vaccine and concomitant routine vaccines (Infanrix-IPV+Hib®, Prevenar-13® and Engerix®) (Day 152), as compared to baseline (Day 1) or at one month after the administration of the booster dose of Bexsero® vaccine and routine vaccines (Priorix® and Varilrix®) (Day 335), as compared to prior to the booster dose (Day 305).
The analysis was performed on the FAS population, which included all subjects in the Exposed set who received at least one dose of a study vaccination and provided immunogenicity data at relevant time points.
|
||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||
End point timeframe |
At Day 1, Day 152, Day 305 and Day 335
|
||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Percentages of subjects with hSBA titers ≥ 1:8 against Neisseria meningitidis serogroup B, when Bexsero® vaccine was administered with routine vaccines | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Percentages of subjects with hSBA titers ≥1:8 against N.meningitidis serogroup B strains, at one month after concomitant administration of third primary dose of Bexsero® with routine vaccines (Infanrix-IPV+Hib® + Prevenar-13® + Engerix®) and at one month after concomitant administration of Bexsero® booster dose with routine vaccines (Priorix® + Varilrix®), as compared to when only routine vaccines were administered.
The analysis was performed on the FAS-3 population, which included all subjects in the Exposed set who received at least one dose of a study vaccination and who provided immunogenicity data at relevant time points.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
At Day 1, Day 152, Day 305 and Day 335
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Number of subjects reporting any solicited local adverse events (AEs) after receiving Bexsero® vaccine with routine vaccines, at 2, 4 and 6 months of age | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
The number of subjects who reported any solicited local symptoms following concomitant administration of Bexsero® vaccine with routine vaccines (Infanrix-IPV+Hib®, Prevenar-13® and Engerix-B®), as compared to when only routine vaccines were administered alone at 2, 4 and 6 months of age. Assessed solicited local symptoms were: Erythema, Induration, Swelling and Tenderness. Any = occurrence of the symptom regardless of intensity grade.
The analysis was performed on the Solicited Safety Set, which included all subjects in the Exposed population who provided post-vaccination reactogenicity data.
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
From Day 1 (6 hours) to Day 7 after each vaccination
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Number of subjects reporting any solicited systemic AEs and other solicited data after receiving Bexsero® vaccine with routine vaccines or routine vaccines alone, at 2, 4 and 6 months of age | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
The number of subjects who reported any solicited systemic AEs and other solicited data following concomitant administration of Bexsero® vaccine with routine vaccines (Infanrix-IPV+Hib®, Prevenar-13® and Engerix-B®), as compared to when only routine vaccines were administered alone at 2, 4 and 6 months of age. Assessed solicited systemic symptoms were: Change in Eating Habits, Diarrhea, Irritability, Persistent Crying, Rash, Sleepiness, Vomiting and Fever (defined as body temperature ≥ 38.0 °C). Other solicited data included: Prevention of Pain and/or Fever and Treatment of Pain and/or Fever. Any = occurrence of the symptom regardless of intensity grade.
The analysis was performed on the Solicited Safety Set, which included all subjects in the Exposed population who provided post-vaccination reactogenicity data.
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
From Day 1 (6 hours) to Day 7 after each vaccination
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Number of subjects reporting any solicited local AEs after receiving Bexsero® booster dose with routine vaccines, at 12 months of age | |||||||||||||||||||||||||||||||||||||||||||||
End point description |
The number of subjects who reported any solicited local AEs following concomitant administration of Bexsero® dose with routine vaccines (Priorix® and Varilrix®), as compared to when only routine vaccines were administered alone, at 12 months of age. Assessed solicited local symptoms were: Erythema, Induration, Swelling and Tenderness. Any = occurrence of the symptom regardless of intensity grade.
The analysis was performed on the Solicited Safety Set, which included all subjects in the Exposed population who provided post-vaccination reactogenicity data.
|
|||||||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
From Day 1 to Day 7 after booster vaccination
|
|||||||||||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||||||||
End point title |
Number of subjects reporting any solicited systemic AEs and other solicited data after receiving Bexsero® booster dose with routine vaccines, at 12 months of age | ||||||||||||||||||||||||||||||||||||||||||
End point description |
The number of subjects who reported any solicited systemic AEs and other solicited data following concomitant administration of Bexsero® booster dose with routine vaccines (Priorix® and Varilrix®), as compared to when only routine vaccines were administered alone at 12 months of age. Assessed solicited systemic AEs were: Change in Eating Habits, Diarrhea, Irritability, Persistent Crying, Rash, Sleepiness, Vomiting, Fever (defined as body temperature ≥ 38.0 °C) and Lymphadenopathy. Other solicited data included: Prevention of Pain and/or Fever and Treatment of Pain and/or Fever. Any = occurrence of the symptom regardless of intensity grade.
The analysis was performed on the Solicited Safety Set, which included all subjects in the Exposed population who provided post-vaccination reactogenicity data.
|
||||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
From Day 1 (6 hours) to Day 7 after vaccination
|
||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||
End point title |
Number of subjects reporting any and Grade 3 solicited systemic AEs after receiving Priorix® and Varilrix® routine vaccines at 12 months of age | ||||||||||||||||||||||||
End point description |
The number of subjects who reported any and Grade 3 solicited systemic AEs after the administration of Varilrix® and Priorix® vaccines (with and without Bexsero® vaccine) at 12 months of age. Solicited systemic AEs assessed were Rash, Lymphadenopathy and Fever (body temperature ≥ 38.0°C). The symptoms were collected for an extended period of 28 days following Varilrix® and Priorix® vaccinations. Any = occurrence of the symptom regardless of intensity grade. Grade 3 symptom = symptom that prevented normal activity. Grade 3 fever = body temperature ≥ 40.0°C.
The analysis was performed on the Safety Set (solicited AEs), which included all subjects in the Exposed population who provided post-vaccination reactogenicity data.
|
||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||
End point timeframe |
From Day 1 through Day 28 after Priorix® and Varilrix® vaccinations
|
||||||||||||||||||||||||
|
|||||||||||||||||||||||||
No statistical analyses for this end point |
|
||||||||||||||||||||||||||||||||||
End point title |
Number of subjects reporting unsolicited AEs after receiving Bexsero® vaccination with routine vaccines | |||||||||||||||||||||||||||||||||
End point description |
The number of subjects who reported any unsolicited AEs following concomitant administration of Bexsero® vaccine with routine vaccines (Infanrix-IPV + Hib®, Prevenar-13®, Engerix-B®, Priorix® and Varilrix®), as compared to when only routine vaccines were administered alone.
An unsolicited AE covers 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 and 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. Any was defined as the occurrence of any unsolicited AE regardless of intensity grade or relation to vaccination. Possibly or probably related AE = AE assessed by the investigator as related to the vaccination.
The analysis was performed on the Safety Set (Unsolicited AEs).
|
|||||||||||||||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||||||||||||||
End point timeframe |
From Day 1 to Day 7 after each vaccination
|
|||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
||||||||||||||||||||||||||||
End point title |
Number of subjects reporting serious adverse events (SAEs), medically attended AEs (MAEs), AEs leading to withdrawal, hospitalization and death | |||||||||||||||||||||||||||
End point description |
Number of subjects who reported SAEs, medically attended AEs, AEs leading to withdrawal from the study, AEs leading to hospitalization and AEs leading to death, following concomitant administration of Bexsero® vaccine with routine vaccines (Infanrix-IPV + Hib®, Prevenar-13®, Engerix-B®, Priorix® and Varilrix®), as compared to when only routine vaccines were administered alone.
SAEs assessed include medical occurrences that result in death, are life-threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity. Possibly or probably related SAE = SAE assessed by the investigator as related to the vaccination. Medically attended AEs were defined as events for which the subject received medical attention defined as hospitalization, an emergency room visit, or a visit to or from medical personnel (medical doctor) for any reason.
The analysis was performed on the Safety Set (Unsolicited AEs).
|
|||||||||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||||||||
End point timeframe |
Throughout the whole study period (from Day 1 to Day 335)
|
|||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Number of subjects reporting Grade 3 solicited local AEs after receiving Bexsero® vaccine with routine vaccines, at 2, 4 and 6 months of age | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
The number of subjects who reported Grade 3 solicited local symptoms following concomitant administration of Bexsero® vaccine with routine vaccines (Infanrix-IPV+Hib®, Prevenar-13® and Engerix-B®), as compared to when only routine vaccines were administered alone at 2, 4 and 6 months of age. Assessed solicited local symptoms were: Erythema, Induration, Swelling and Tenderness. Grade 3 symptom = symptom that prevented normal activity.
The analysis was performed on the Solicited Safety Set, which included all subjects in the Exposed population who provided post-vaccination reactogenicity data.
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
From Day 1 (6 hours) to Day 7 after each vaccination
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Number of subjects reporting Grade 3 solicited systemic AEs after receiving Bexsero® vaccine with routine vaccines or routine vaccines alone, at 2, 4 and 6 months of age | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
The number of subjects who reported Grade 3 solicited systemic AEs following concomitant administration of Bexsero® vaccine with routine vaccines (Infanrix-IPV+Hib®, Prevenar-13® and Engerix-B®), as compared to when only routine vaccines were administered alone at 2, 4 and 6 months of age. Assessed solicited systemic symptoms were: Change in Eating Habits, Diarrhea, Irritability, Persistent Crying, Rash, Sleepiness, Vomiting and Fever. Grade 3 symptom = symptom that prevented normal activity. Grade 3 Fever = body temperature ≥ 40.0 °C. Medically attended fever = any fever for which a medical visit was sought.
The analysis was performed on the Solicited Safety Set, which included all subjects in the Exposed population who provided post-vaccination reactogenicity data.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
From Day 1 (6 hours) to Day 7 after each vaccination
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Number of subjects reporting Grade 3 solicited local AEs after receiving Bexsero® booster dose with routine vaccines, at 12 months of age | |||||||||||||||||||||||||||||||||||||||||||||
End point description |
The number of subjects who reported solicited local AEs following concomitant administration of Bexsero® dose with routine vaccines (Priorix® and Varilrix®), as compared to when only routine vaccines were administered alone, at 12 months of age. Assessed solicited local symptoms were: Erythema, Induration, Swelling and Tenderness. Grade 3 symptom = symptom that prevented normal activity.
The analysis was performed on the Solicited Safety Set, which included all subjects in the Exposed population who provided post-vaccination reactogenicity data.
|
|||||||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
From Day 1 to Day 7 after booster vaccination
|
|||||||||||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||
End point title |
Number of subjects reporting Grade 3 solicited systemic AEs after receiving Bexsero® booster dose with routine vaccines, at 12 months of age | ||||||||||||||||||||||||||||||||||||
End point description |
The number of subjects who reported Grade 3 solicited systemic AEs following concomitant administration of Bexsero® booster dose with routine vaccines (Priorix® and Varilrix®), as compared to when only routine vaccines were administered alone at 12 months of age. Assessed solicited systemic AEs were: Change in Eating Habits, Diarrhea, Irritability, Persistent Crying, Rash, Sleepiness, Vomiting and Fever. Grade 3 symptom = symptom that prevented normal activity. Grade 3 Fever = body temperature ≥ 40.0°C. Medically attended fever: any fever for which a medical visit was sought.
The analysis was performed on the Solicited Safety Set, which included all subjects in the Exposed population who provided post-vaccination reactogenicity data.
|
||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||
End point timeframe |
From Day 1 (6 hours) to Day 7 after booster vaccination
|
||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse events information
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Timeframe for reporting adverse events |
Solicited local and systemic symptoms: from Day 1 to Day 7 after each vaccination; Unsolicited AEs and SAEs: throughout the study period (from Day 1 to Day 335).
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Assessment type |
Systematic | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary name |
MedDRA | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
19.0
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting groups
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Bexsero + Routine Group
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Subjects received three doses of Bexsero® vaccine at 2, 4, 6 months followed by a booster dose at 12 months, concomitantly administered with routine vaccines (i.e. combined Infanrix-IPV+Hib® and Prevenar-13® at 2, 4, 6 months of age; Engerix-B® at 6 months of age; Priorix® and Varilrix® at 12 months of age. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Routine Group
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Subjects received routine vaccines Infanrix-IPV+Hib® and Prevenar-13® at 2, 4, 6 months of age; Engerix-B® vaccine at 6 months; Priorix® and Varilrix® vaccines at 12 months of age. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Notes [1] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal. Justification: The analysis was performed on the Exposed population, only on subjects with their symptom sheets completed. [2] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal. Justification: The analysis was performed on the Exposed population, only on subjects with their symptom sheets completed. [3] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal. Justification: The analysis was performed on the Exposed population, only on subjects with their symptom sheets completed. [4] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal. Justification: The analysis was performed on the Exposed population, only on subjects with their symptom sheets completed. [5] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal. Justification: The analysis was performed on the Exposed population, only on subjects with their symptom sheets completed. [6] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal. Justification: The analysis was performed on the Exposed population, only on subjects with their symptom sheets completed. [7] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal. Justification: The analysis was performed on the Exposed population, only on subjects with their symptom sheets completed. [8] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal. Justification: The analysis was performed on the Exposed population, only on subjects with their symptom sheets completed. [9] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal. Justification: The analysis was performed on the Exposed population, only on subjects with their symptom sheets completed. [10] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal. Justification: The analysis was performed on the Exposed population, only on subjects with their symptom sheets completed. [11] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal. Justification: The analysis was performed on the Exposed population, only on subjects with their symptom sheets completed. [12] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal. Justification: The analysis was performed on the Exposed population, only on subjects with their symptom sheets completed. [13] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal. Justification: The analysis was performed on the Exposed population, only on subjects with their symptom sheets completed. [14] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal. Justification: The analysis was performed on the Exposed population, only on subjects with their symptom sheets completed. [15] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal. Justification: The analysis was performed on the Exposed population, only on subjects with their symptom sheets completed. [16] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal. Justification: The analysis was performed on the Exposed population, only on subjects with their symptom sheets completed. [17] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal. Justification: The analysis was performed on the Exposed population, only on subjects with their symptom sheets completed. [18] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal. Justification: The analysis was performed on the Exposed population, only on subjects with their symptom sheets completed. [19] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal. Justification: The analysis was performed on the Exposed population, only on subjects with their symptom sheets completed. [20] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal. Justification: The analysis was performed on the Exposed population, only on subjects with their symptom sheets completed. [21] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal. Justification: The analysis was performed on the Exposed population, only on subjects with their symptom sheets completed. [22] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal. Justification: The analysis was performed on the Exposed population, only on subjects with their symptom sheets completed. [23] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal. Justification: The analysis was performed on the Exposed population, only on subjects with their symptom sheets completed. [24] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal. Justification: The analysis was performed on the Exposed population, only on subjects with their symptom sheets completed. [25] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal. Justification: The analysis was performed on the Exposed population, only on subjects with their symptom sheets completed. [26] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal. Justification: The analysis was performed on the Exposed population, only on subjects with their symptom sheets completed. |
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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 |
||
11 Jul 2013 |
- Correction of omission;
- Presentation of each commercially available routine vaccines has been changed into “as commercially available”;
- A fourth dose of Prevenar-13 was included in the schedule treatment to complete the recommended dose schedule;
- Other Secondary endpoints were added: The percentage of subjects with SBA titers ≥ 1:8 at baseline, one month after the third vaccination, at 12 months of age (prior to the booster dose) and at 13 months of age (one month after the booster dose) for each of the three indicator strains (H44/76, 5/99, NZ98/254) and strain M10713. |
||
05 Nov 2013 |
- Exclusion criteria were modified;
- Randomization method and stratification factors were clarified;
- MMR and Varicella vaccines way of administration was better defined;
- Timeframe for solicited data collection was corrected;
- Description of statistical analysis for primary endpoint was modified. |
||
08 Jul 2014 |
- Change of the legal entity responsible for the trial to Novartis Pharma Services AG;
- The name of the serology manual was changed and protocol was updated with the new manual’s title;
- Section 3.9 ”End of Study” was added to the protocol;
- Exclusion criteria were modified to avoid extra clinic visit to the subjects;
- Criteria for delay of vaccination and/or blood sampling was changed to avoid extra clinic visit to the subjects;
- The extension of the period of observation for adverse events was better specified;
- Blood pressure measurement was removed from the list of physical examination to be performed at clinical visit because it is not a routine practice in Taiwan to measure blood pressure of young children. |
||
14 Oct 2014 |
- Inclusion criteria added;
- The enrolment process was better specified in that the screening number assigned has to be assigned by the Investigator;
- Correction of typo. |
||
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 |