Clinical Trial Results:
Immunogenicity and Safety of DTaP-IPV-HB-PRP~T Combined Vaccine
Given at 3, 5, and 12 Months of Age Concomitantly or Sequentially with
4CMenB Vaccine in Italian and Finnish Infants
Summary
|
|
EudraCT number |
2019-002585-12 |
Trial protocol |
IT FI |
Global end of trial date |
13 Dec 2023
|
Results information
|
|
Results version number |
v1(current) |
This version publication date |
01 May 2025
|
First version publication date |
01 May 2025
|
Other versions |
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 |
A3L00057
|
||
Additional study identifiers
|
|||
ISRCTN number |
- | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
U1111-1239-0365 | ||
Sponsors
|
|||
Sponsor organisation name |
Sanofi Winthrop Industrie
|
||
Sponsor organisation address |
82 Avenue Raspail, Gentilly, France, 94250
|
||
Public contact |
Trial Transparency team, Sanofi Winthrop Industrie, Contact-US@sanofi.com
|
||
Scientific contact |
Trial Transparency team, Sanofi Winthrop Industrie, Contact-US@sanofi.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 |
04 Oct 2024
|
||
Is this the analysis of the primary completion data? |
No
|
||
Global end of trial reached? |
Yes
|
||
Global end of trial date |
13 Dec 2023
|
||
Was the trial ended prematurely? |
No
|
||
General information about the trial
|
|||
Main objective of the trial |
To demonstrate the non-inferiority of the co-administration of diphtheria (D), tetanus (T), pertussis (acellular, component), hepatitis B (recombinant deoxyribonucleic acid [rDNA]), poliomyelitis (inactivated) and Haemophilus influenzae type b conjugate vaccine (adsorbed) (DTaP-IPV-HB-PRP~T combined vaccine) with 4-component meningococcal B (4CMenB) vaccine in terms of seroprotection rates for anti-hepatitis B surface antigen (HBsAg) and anti-haemophilus influenzae type b polyribosyl ribitol phosphate (Hib PRP) antibodies (Ab) compared to the sequential administration of the same vaccines.
|
||
Protection of trial subjects |
Vaccinations were performed by qualified and trained study personnel. Participants with allergy to any of the vaccine components were not vaccinated. After vaccination, participants were also kept under clinical observation for 30 minutes to ensure their safety. Appropriate medical equipment were also available on site in case of any immediate allergic reactions.
|
||
Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
14 Jan 2021
|
||
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 |
Finland: 98
|
||
Country: Number of subjects enrolled |
Italy: 299
|
||
Worldwide total number of subjects |
397
|
||
EEA total number of subjects |
397
|
||
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) |
397
|
||
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 |
The study was conducted at 11 sites in Italy and Finland. | |||||||||||||||||||||||||||
Pre-assignment
|
||||||||||||||||||||||||||||
Screening details |
A total of 397 participants were randomized in this study. | |||||||||||||||||||||||||||
Period 1
|
||||||||||||||||||||||||||||
Period 1 title |
Overall study (overall period)
|
|||||||||||||||||||||||||||
Is this the baseline period? |
Yes | |||||||||||||||||||||||||||
Allocation method |
Randomised - controlled
|
|||||||||||||||||||||||||||
Blinding used |
Not blinded | |||||||||||||||||||||||||||
Arms
|
||||||||||||||||||||||||||||
Are arms mutually exclusive |
Yes
|
|||||||||||||||||||||||||||
Arm title
|
Group 1: Co-administration | |||||||||||||||||||||||||||
Arm description |
Participants received 0.5 milliliter (mL) intramuscular (IM) injection of hexavalent DTaP-IPV-HB-PRP~T combined vaccine administered concomitantly with 0.5 mL IM injection each of pneumococcal polysaccharide conjugate (13-valent, adsorbed) (PCV13) vaccine and 4CMenB vaccine at 3, 5, and 12 months of age. | |||||||||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||||||||
Investigational medicinal product name |
DTaP-IPV-HB-PRP~T combined vaccine
|
|||||||||||||||||||||||||||
Investigational medicinal product code |
||||||||||||||||||||||||||||
Other name |
Hexyon®, Hexaxim®, Hexacima®
|
|||||||||||||||||||||||||||
Pharmaceutical forms |
Suspension for injection in pre-filled syringe
|
|||||||||||||||||||||||||||
Routes of administration |
Intramuscular use
|
|||||||||||||||||||||||||||
Dosage and administration details |
Participants received 0.5 mL IM injection of hexavalent DTaP-IPV-HB-PRP~T combined vaccine at 3, 5 and 12 months of age.
|
|||||||||||||||||||||||||||
Investigational medicinal product name |
4CMenB vaccine
|
|||||||||||||||||||||||||||
Investigational medicinal product code |
||||||||||||||||||||||||||||
Other name |
Bexsero®
|
|||||||||||||||||||||||||||
Pharmaceutical forms |
Suspension for injection in pre-filled syringe
|
|||||||||||||||||||||||||||
Routes of administration |
Intramuscular use
|
|||||||||||||||||||||||||||
Dosage and administration details |
Participants received 0.5 mL IM injection of 4CMenB vaccine at 3, 5, and 12 months of age.
|
|||||||||||||||||||||||||||
Investigational medicinal product name |
PCV13 vaccine
|
|||||||||||||||||||||||||||
Investigational medicinal product code |
||||||||||||||||||||||||||||
Other name |
Prevenar® 13
|
|||||||||||||||||||||||||||
Pharmaceutical forms |
Suspension for injection
|
|||||||||||||||||||||||||||
Routes of administration |
Intramuscular use
|
|||||||||||||||||||||||||||
Dosage and administration details |
Participants received 0.5 mL IM injection of PCV13 vaccine at 3, 5, and 12 months of age.
|
|||||||||||||||||||||||||||
Arm title
|
Group 2: Sequential administration | |||||||||||||||||||||||||||
Arm description |
Participants received 0.5 mL IM injection of hexavalent DTaP-IPV-HB-PRP~T combined vaccine administered concomitantly with 0.5 mL IM injection of PCV13 vaccine at 3, 5, and 12 months of age and a sequential administration of 0.5 mL IM injection of 4CMenB vaccine at 4, 6, and 13 months of age. | |||||||||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||||||||
Investigational medicinal product name |
DTaP-IPV-HB-PRP~T combined vaccine
|
|||||||||||||||||||||||||||
Investigational medicinal product code |
||||||||||||||||||||||||||||
Other name |
Hexyon®, Hexaxim®, Hexacima®
|
|||||||||||||||||||||||||||
Pharmaceutical forms |
Suspension for injection in pre-filled syringe
|
|||||||||||||||||||||||||||
Routes of administration |
Intramuscular use
|
|||||||||||||||||||||||||||
Dosage and administration details |
Participants received 0.5 mL IM injection of hexavalent DTaP-IPV-HB-PRP~T combined vaccine at 3, 5 and 12 months of age.
|
|||||||||||||||||||||||||||
Investigational medicinal product name |
4CMenB vaccine
|
|||||||||||||||||||||||||||
Investigational medicinal product code |
||||||||||||||||||||||||||||
Other name |
Bexsero®
|
|||||||||||||||||||||||||||
Pharmaceutical forms |
Suspension for injection in pre-filled syringe
|
|||||||||||||||||||||||||||
Routes of administration |
Intramuscular use
|
|||||||||||||||||||||||||||
Dosage and administration details |
Participants received 0.5 mL IM injection of 4CMenB vaccine at 4, 6 and 13 months of age.
|
|||||||||||||||||||||||||||
Investigational medicinal product name |
PCV13 vaccine
|
|||||||||||||||||||||||||||
Investigational medicinal product code |
||||||||||||||||||||||||||||
Other name |
Prevenar® 13
|
|||||||||||||||||||||||||||
Pharmaceutical forms |
Suspension for injection
|
|||||||||||||||||||||||||||
Routes of administration |
Intramuscular use
|
|||||||||||||||||||||||||||
Dosage and administration details |
Participants received 0.5 mL IM injection of PCV13 vaccine at 3, 5, and 12 months of age.
|
|||||||||||||||||||||||||||
|
|
|||||||||||||||||||||||||||||||||||||||||||||
Baseline characteristics reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Group 1: Co-administration
|
||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Participants received 0.5 milliliter (mL) intramuscular (IM) injection of hexavalent DTaP-IPV-HB-PRP~T combined vaccine administered concomitantly with 0.5 mL IM injection each of pneumococcal polysaccharide conjugate (13-valent, adsorbed) (PCV13) vaccine and 4CMenB vaccine at 3, 5, and 12 months of age. | ||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Group 2: Sequential administration
|
||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Participants received 0.5 mL IM injection of hexavalent DTaP-IPV-HB-PRP~T combined vaccine administered concomitantly with 0.5 mL IM injection of PCV13 vaccine at 3, 5, and 12 months of age and a sequential administration of 0.5 mL IM injection of 4CMenB vaccine at 4, 6, and 13 months of age. | ||||||||||||||||||||||||||||||||||||||||||||
|
|
|||
End points reporting groups
|
|||
Reporting group title |
Group 1: Co-administration
|
||
Reporting group description |
Participants received 0.5 milliliter (mL) intramuscular (IM) injection of hexavalent DTaP-IPV-HB-PRP~T combined vaccine administered concomitantly with 0.5 mL IM injection each of pneumococcal polysaccharide conjugate (13-valent, adsorbed) (PCV13) vaccine and 4CMenB vaccine at 3, 5, and 12 months of age. | ||
Reporting group title |
Group 2: Sequential administration
|
||
Reporting group description |
Participants received 0.5 mL IM injection of hexavalent DTaP-IPV-HB-PRP~T combined vaccine administered concomitantly with 0.5 mL IM injection of PCV13 vaccine at 3, 5, and 12 months of age and a sequential administration of 0.5 mL IM injection of 4CMenB vaccine at 4, 6, and 13 months of age. |
|
|||||||||||||
End point title |
Percentage of Participants who Achieved Anti-Hepatitis B Surface Antigen (HBsAg) Antibodies Concentration Above Predefined Threshold | ||||||||||||
End point description |
Anti-HBsAg Ab were measured by the commercially available VITROS ECi/ECiQ immunodiagnostic system using chemiluminescence detection technology. The percentage of participants with an anti-HBsAg Ab concentration >=10 milli international units per mL (mIU/mL) was assessed. Percentages are rounded off to the tenth decimal place. Analysis was performed on per protocol analysis set (PPAS) which was a subset of the full analysis set (FAS: a subset of randomized participants who received at least 1 dose of the study vaccine) that included participants who did not present with any of the protocol deviations.
|
||||||||||||
End point type |
Primary
|
||||||||||||
End point timeframe |
Day 30 post-dose 3 of DTaP-IPV-HB-PRP~T combined vaccine (Month 13)
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Difference in percentage of participants | ||||||||||||
Comparison groups |
Group 1: Co-administration v Group 2: Sequential administration
|
||||||||||||
Number of subjects included in analysis |
246
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
non-inferiority [1] | ||||||||||||
Method |
|||||||||||||
Parameter type |
Difference in percentage of participants | ||||||||||||
Point estimate |
2.1
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-2.4 | ||||||||||||
upper limit |
8.3 | ||||||||||||
Notes [1] - Non-inferiority concluded if the lower limit of 2-sided 95% confidence interval (CI) of difference between groups was greater than -10% |
|
|||||||||||||
End point title |
Percentage of Participants who Achieved Anti-polyribosyl Ribitol Phosphate (PRP) Antibodies Concentration Above Predefined Threshold | ||||||||||||
End point description |
Anti-PRP Ab were measured using a Farr-type radioimmunoassay (RIA). The percentage of participants with an anti-PRP Ab concentration >=1.0 microgram [mcg]/mL was assessed. Percentages are rounded off to the tenth decimal place. Analysis was performed on PPAS which was a subset of the FAS that included participants who did not present with any of the protocol deviations.
|
||||||||||||
End point type |
Primary
|
||||||||||||
End point timeframe |
Day 30 post-dose 3 of DTaP-IPV-HB-PRP~T combined vaccine (Month 13)
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Difference in percentage of participants | ||||||||||||
Comparison groups |
Group 1: Co-administration v Group 2: Sequential administration
|
||||||||||||
Number of subjects included in analysis |
246
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
non-inferiority [2] | ||||||||||||
Method |
|||||||||||||
Parameter type |
Difference in percentage of participants | ||||||||||||
Point estimate |
-8.3
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-15.3 | ||||||||||||
upper limit |
-0.4 | ||||||||||||
Notes [2] - Non-inferiority concluded if the lower limit of 2-sided 95% CI of difference between groups was greater than -10% |
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Percentage of Participants who Achieved Antibodies Against all Antigens of DTaP-IPV-HB-PRP~T Combined Vaccine Above Predefined Thresholds | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
The following cut-off values were considered:
• >=0.01 IU/mL, >=0.1 IU/mL, and >=1.0 IU/mL for anti-D and anti-T Ab concentrations
• >=8 (1/dilution) for anti-poliovirus 1, 2, and 3 Ab titers
• >=lower limit of quantification (LLOQ) and >=4 times (*) LLOQ for anti-pertussis (PT) and anti-filamentous hemagglutinin (FHA) Ab concentrations
• >=0.15 mcg/mL and >=1.0 mcg/mL for anti-PRP Ab concentrations
• >=10 mIU/mL and >=100 mIU/mL for anti-HBsAg Ab concentrations.
The Ab concentrations against diphtheria, pertussis, tetanus antigens were assayed using electrochemiluminescence (ECL) immunoassay method. Anti-poliovirus types 1, 2, and 3 was measured by a neutralization assay. Percentages are rounded off to the tenth decimal place. Analysis was performed on PPAS which was a subset of the FAS that included participants who did not present with any of the protocol deviations. Here ’n’= number of participants with data collected for each specified category.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Pre-dose 1 (Month 3) and Day 30 post-dose 3 of DTaP-IPV-HB-PRP~T combined vaccine (Month 13)
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Geometric Mean Concentrations (GMCs) of Antibodies Against all Antigens of the DTaP-IPV-HB-PRP~T Combined Vaccine Except Polio 1, 2 and 3 | ||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
GMCs of Abs against diphtheria, pertussis, tetanus antigens were assayed using ECL immunoassay method. GMCs of Abs against PRP were measured using a Farr-type RIA. Anti-HBsAg Ab were measured by the commercially available VITROSECi/ECiQ immunodiagnostic system using chemiluminescence detection technology. Individual Ab concentrations for D, T, PT, FHA, PRP, and HBsAg are presented. Analysis was performed on PPAS which was a subset of the FAS that included participants who did not present with any of the protocol deviations. Here ’n’= number of participants with data collected for each specified category.
|
||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Pre-dose 1 (Month 3) and Day 30 post-dose 3 of DTaP-IPV-HB-PRP~T combined vaccine (Month 13)
|
||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||
End point title |
Geometric Mean Titers (GMTs) of Antibodies Against Polio 1, 2 and 3 | ||||||||||||||||||||||||||||||
End point description |
Anti-poliovirus types 1, 2, and 3 were measured by a neutralization assay. Individual Ab titers for poliovirus types 1, 2, and 3 are presented. Analysis was performed on PPAS which was a subset of the FAS that included participants who did not present with any of the protocol deviations. Only those participants with data collected at specified timepoint are reported. Here ’n’= number of participants with data collected for each specified category.
|
||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||
End point timeframe |
Pre-dose 1 (Month 3) and Day 30 post-dose 3 of DTaP-IPV-HB-PRP~T combined vaccine (Month 13)
|
||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
||||||||||||||||||||||||||||||||||||||||
End point title |
Geometric Mean Ratio (GMRs) of Antibodies Against all Antigens of the DTaP-IPV-HB-PRP~T Combined Vaccine | |||||||||||||||||||||||||||||||||||||||
End point description |
GMR was the ratio of the individual titers post vaccination over pre-vaccination (30 days post-dose 3 over pre-dose 1). GMRs for D, T, poliovirus types 1, 2, and 3, PT, FHA, PRP, and HBsAg are presented. Analysis was performed on PPAS which was a subset of the FAS that included participants who did not present with any of the protocol deviations. Here ’n’= number of participants with data collected for each specified category.
|
|||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||||||||||||||||||||
End point timeframe |
Pre-dose 1 (Month 3) and Day 30 post-dose 3 of DTaP-IPV-HB-PRP~T combined vaccine (Month 13)
|
|||||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||
End point title |
Percentage of Participants With Seroconversion for Anti-pertussis Toxoid and Anti-filamentous Hemagglutinin Adhesion | ||||||||||||||||||
End point description |
The Ab concentrations against pertussis antigens were assayed using ECL immunoassay method. Seroconversion was defined as >=4-fold increase from pre-dose 1 to post-dose 3 Ab concentrations. Percentages are rounded off to the tenth decimal place. Analysis was performed on PPAS which was a subset of the FAS that included participants who did not present with any of the protocol deviations. Only those participants with data collected at specified timepoints are reported. Here ’n’= number of participants with data collected for each specified category.
|
||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||
End point timeframe |
From pre-dose 1 (Month 3) up to Day 30 post-dose 3 of DTaP-IPV-HB-PRP~T combined vaccine (Month 13)
|
||||||||||||||||||
|
|||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||
End point title |
Percentage of Participants With a Vaccine Response to Pertussis Toxoid and Filamentous Hemagglutinin Adhesion | ||||||||||||||||||
End point description |
The Ab concentrations against pertussis antigens were assayed using ECL immunoassay method. Vaccine response was defined as post-dose 3 Ab concentrations >=4 * LLOQ, if pre-dose 1 Ab concentrations <4 * LLOQ or post-dose 3 Ab concentration >=pre-dose 1 Ab concentration, if pre-dose 1 Ab concentrations >=4 * LLOQ. Percentages are rounded off to the tenth decimal place. Analysis was performed on PPAS which was a subset of the FAS that included participants who did not present with any of the protocol deviations. Only those participants with data collected at specified timepoints are reported. Here ’n’= number of participants with data collected for a particular category.
|
||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||
End point timeframe |
Pre-dose 1 (Month 3) and Day 30 post-dose 3 of DTaP-IPV-HB-PRP~T combined vaccine (Month 13)
|
||||||||||||||||||
|
|||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||
End point title |
Percentage of Participants With Antibodies Against 4-component Meningococcal B Vaccine Measured by Serum Bactericidal Assay Using Human Complement (hSBA) Above Predefined Threshold | ||||||||||||||||||||||||||||||
End point description |
Functional Ab activity against a panel of different nesseiria meningitidis antigens (neisseria adhesin A [NadA], factor H binding protein [fHbp] and outer membrane vesicles containing outer membrane protein [PorA P1.4]) were measured using an hSBA assay. Cut-off value was >=5 (1/dilution) Ab titers. Percentages are rounded off to the tenth decimal place. Analysis was performed on PPAS which was a subset of the FAS that included participants who did not present with any of the protocol deviations. Only those participants with data collected at specified timepoints are reported. Here ’n’= number of participants with data collected for each specified category. 99999=no participants experiencing the endpoint.
|
||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||
End point timeframe |
Pre-dose 1 (Month 3) and Day 30 post-dose 3 of 4CMenB vaccine (Month 13 for Group 1; Month 14 for Group 2)
|
||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||
End point title |
Geometric Mean Titers of Antibodies Against Antigens of the 4-component Meningococcal B Vaccine | ||||||||||||||||||||||||||||||
End point description |
Functional Ab activity against a panel of different N. meningitidis antigens (NadA, fHbp and PorA P1.4) were measured using an hSBA assay. Analysis was performed on PPAS which was a subset of the FAS that included participants who did not present with any of the protocol deviations. Only those participants with data collected at specified timepoints are reported. Here ’n’= number of participants with data collected for each specified category. -99999 and 99999=not calculated.
|
||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||
End point timeframe |
Pre-dose 1 (Month 3) and Day 30 post-dose 3 of 4CMenB vaccine (Month 13 for Group 1; Month 14 for Group 2)
|
||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
||||||||||||||||||||||
End point title |
Geometric Mean Titer Ratio (GMTRs) of Antibodies Against Antigens of the 4-component Meningococcal B Vaccine (4CMenB) | |||||||||||||||||||||
End point description |
GMTR was the ratio of the individual titers post-vaccination over pre-vaccination (Day 30 post-dose 3 over pre-dose 1). Functional Ab activity against a panel of different N. meningitidis strains (NadA, fHbp and PorA P1.4) were measured using an hSBA assay. Analysis was performed on PPAS which was a subset of the FAS that included participants who did not present with any of the protocol deviations. Only those participants with data collected at specified timepoints are reported. Here ’n’= number of participants with data collected for each specified category.
|
|||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||
End point timeframe |
Pre-dose 1 (Month 3) and Day 30 post-dose 3 of 4CMenB vaccine (Month 13 for Group 1; Month 14 for Group 2)
|
|||||||||||||||||||||
|
||||||||||||||||||||||
No statistical analyses for this end point |
|
||||||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Geometric Mean Concentrations of Antibodies Against Pneumococcal Capsular Polysaccharide (PnPS) Antigens of the Pneumococcal Polysaccharide Conjugate Vaccine (13-valent, Adsorbed) Vaccine | |||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Anti-pneumococcal Ab was assessed by pneumococcal capsular polysaccharide (PnPS) immunoglobulin G (IgG) ECL assay which is used to quantitate the amount of anti-streptococcus pneumoniae PS (serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F) Ab in human serum. Analysis was performed on PPAS which was a subset of the FAS that included participants who did not present with any of the protocol deviations. GMC for the study population was calculated. Only those participants with data collected at specified timepoint are reported. Here ’n’= number of participants with data collected for each specified category.
|
|||||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Day 30 post-dose 3 of PCV13 vaccine (Month 13)
|
|||||||||||||||||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
||||||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Percentage of Participants With a Vaccine Response to Pneumococcal Capsular Polysaccharide Antigens | |||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
The PnPS IgG ECL assay is used to quantitate the amount of anti-Streptococcus pneumoniae PS (serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F) Ab in human serum. Vaccine response was defined as Day 30 post-dose 3 Ab concentration >=0.35 mcg/mL. Percentages are rounded off to the tenth decimal place. Analysis was performed on PPAS which was a subset of the FAS that included participants who did not present with any of the protocol deviations. Only those participants with data collected at specified timepoint are reported. Here ’n’= number of participants with data collected for each specified category.
|
|||||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Day 30 post-dose 3 of PCV13 vaccine (Month 13)
|
|||||||||||||||||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
||||||||||
End point title |
Number of Participants With Immediate Unsolicited Adverse Events | |||||||||
End point description |
An AE was any untoward medical occurrence in a participant or in a clinical investigation participant administered a medicinal product and which did not necessarily have a causal relationship with this treatment. Immediate events were recorded to capture medically relevant unsolicited systemic AEs (including those related to the product administered) that occurred within the first 30 minutes after vaccination. An unsolicited AE was an observed AE that did not fulfill the conditions prelisted in the case report book (CRB) in terms of diagnosis and/or onset window post-vaccination and included both serious adverse events (SAEs) and non-serious unsolicited AEs. Analysis was performed on the safety analysis set (SafAS) which included those participants who received at least 1 dose of the study vaccine (i.e., 1 dose of the hexavalent vaccine) and had any safety data available.
|
|||||||||
End point type |
Secondary
|
|||||||||
End point timeframe |
Up to 30 minutes post each vaccination
|
|||||||||
|
||||||||||
No statistical analyses for this end point |
|
||||||||||||||||
End point title |
Number of Participants With Solicited Injection Site and Systemic Reactions | |||||||||||||||
End point description |
A solicited reaction was a "pre-listed" adverse reaction (sign or symptom) observed and reported under the conditions (nature and onset) prelisted in the protocol and CRB and were considered to be related to the product administered. An injection site reaction was an adverse reaction at and around the injection site which were commonly inflammatory reactions. Solicited injection site reactions included tenderness, erythema and swelling around the injection site. Solicited systemic reactions included fever, vomiting, abnormal crying, drowsiness, appetite loss, and irritability. Analysis was performed on SafAS which included those participants who received at least 1 dose of the study vaccine (i.e., 1 dose of the hexavalent vaccine) and had any safety data available. Only those participants with data collected at specified timepoint are reported.
|
|||||||||||||||
End point type |
Secondary
|
|||||||||||||||
End point timeframe |
Up to 7 days post each vaccination
|
|||||||||||||||
|
||||||||||||||||
No statistical analyses for this end point |
|
||||||||||
End point title |
Number of Participants With Unsolicited Non-serious Adverse Events | |||||||||
End point description |
An AE was any untoward medical occurrence in a clinical investigation participant administered a medicinal product, and which did not necessarily have a causal relationship with this treatment. An unsolicited AE was an observed AE that did not fulfill the conditions prelisted in the CRB in terms of diagnosis and/or onset window post-vaccination. Unsolicited non-serious AEs are reported. Analysis was performed on SafAS which included those participants who received at least 1 dose of the study vaccine (i.e., 1 dose of the hexavalent vaccine) and had any safety data available.
|
|||||||||
End point type |
Secondary
|
|||||||||
End point timeframe |
Up to 30 days post each vaccination
|
|||||||||
|
||||||||||
No statistical analyses for this end point |
|
||||||||||||||||
End point title |
Number of Participants With Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESIs) | |||||||||||||||
End point description |
An SAE was any untoward medical occurrence that at any dose resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, or was an important medical event. An AESI (serious or non-serious) was defined as one of scientific and medical concern specific to the Sponsor's product or program, for which ongoing monitoring and rapid communication by the Investigator to the Sponsor was appropriate. The following AE were captured as AESI throughout the study: extensive limb swelling, hypotonic hyporesponsive episode, convulsions (whether febrile or not), anaphylactic reactions, apnea, and severe neurological conditions. Analysis was performed on SafAS.
|
|||||||||||||||
End point type |
Secondary
|
|||||||||||||||
End point timeframe |
From Day 0 (Month 3) up to Month 13 for Group 1 and Month 14 for Group 2
|
|||||||||||||||
|
||||||||||||||||
No statistical analyses for this end point |
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse events information
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Timeframe for reporting adverse events |
From Day 0 (Month 3) up to Month 13 for Group 1 and Month 14 for Group 2
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse event reporting additional description |
Analysis was performed on SafAS which included those participants who received at least 1 dose of the study vaccine (i.e., 1 dose of the hexavalent vaccine) and had any safety data available.
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Assessment type |
Systematic | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary name |
MedDRA | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
26.1
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting groups
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Group 2: Sequential administration
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Participants received 0.5 mL IM injection of hexavalent DTaP-IPV-HB-PRP~T combined vaccine administered concomitantly with 0.5 mL IM injection of PCV13 vaccine at 3, 5, and 12 months of age and a sequential administration of 0.5 mL IM injection of 4CMenB vaccine at 4, 6, and 13 months of age. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Group 1: Co-administration
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Participants received 0.5 mL IM injection of hexavalent DTaP-IPV-HB-PRP~T combined vaccine administered concomitantly with 0.5 mL IM injection each of PCV13 vaccine and 4CMenB vaccine at 3, 5, and 12 months of age. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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 |
||
21 Jul 2020 |
Updated version following the Italian Medicines Agency (AIFA) feedback. |
||
29 Jan 2021 |
Update of responsible personnel list and study plan. |
||
21 Jan 2022 |
Enrollment of participants in study A3L00057 was slower than anticipated. Therefore, to limit the duration of the study, additional sites in 1 European country where the tested vaccines (Hexyon, Bexsero, Prevenar 13) were licensed (Finland) were added. |
||
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 |