Clinical Trial Results:
A Phase III Open Label, Multi-Center Pediatric Study in China Comparing a Booster Dose of Vaxem™ Hib to HIBERIX®
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Summary
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EudraCT number |
2014-005013-23 |
Trial protocol |
Outside EU/EEA |
Global end of trial date |
14 Dec 2009
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Results information
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Results version number |
v1(current) |
This version publication date |
11 May 2016
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First version publication date |
27 May 2015
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
M37P2E1
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT01025544 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Novartis Vaccines and Diagnostics
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Sponsor organisation address |
via Fiorentina 1, Siena, Italy, 53100
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Public contact |
Posting Director, Novartis Vaccines , RegistryContactVaccinesUS@novartis.com
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Scientific contact |
Posting Director, Novartis Vaccines , RegistryContactVaccinesUS@novartis.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
Yes
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
10 Apr 2010
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
14 Dec 2009
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
To demonstrate that a Vaxem™ Hib booster given to children aged 12–18 months is non-inferior to the comparator vaccine HIBERIX®. Non-inferiority was assessed as the percentage of subjects with anti-Polyribosyl-Ribitol-Phosphate (PRP) antibody levels ≥ 1.0 μg/mL one month after booster vaccination (i.e. long-term seroprotection rate).
To compare safety and tolerability of the booster dose of Vaxem™ Hib with the control booster dose of HIBERIX® when given to toddlers aged 12-18 months.
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Protection of trial subjects |
This clinical trial was carried out in accordance with relevant requirements of Regulation on Drug Registration and Good Clinical Practice (GCP) as well as Technical Guideline on Clinical Trial of Vaccine that were issued by the State Food and Drug Administration (SFDA), and was conducted in compliance with principles of Declaration of Helsinki. The trial was organised by Hebei Center for Disease Control (CDC). The study protocol and relevant documents were approved upon review by the Ethics Committee (EC) of Hebei CDC on August 18, 2008, and the study was conducted by qualified scientists and medical experts; the legal guardian of each subject signed a written Informed Consent Form (ICF) before initiation of the clinical trial.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
11 Sep 2009
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
China: 846
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Worldwide total number of subjects |
846
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EEA total number of subjects |
0
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
846
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
0
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
Subjects were enrolled from 2 sites in China. | |||||||||||||||
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Pre-assignment
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Screening details |
All enrolled subjects were included in the trial. | |||||||||||||||
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Period 1
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Period 1 title |
Overall study (overall period)
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Is this the baseline period? |
Yes | |||||||||||||||
Allocation method |
Non-randomised - controlled
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Blinding used |
Not blinded | |||||||||||||||
Blinding implementation details |
This was an open label study.
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Vaxem Hib | |||||||||||||||
Arm description |
Subjects who received primary vaccination with Vaxem Hib in the parent study (M37P2), received a booster dose of Vaxem Hib in this study. | |||||||||||||||
Arm type |
Experimental | |||||||||||||||
Investigational medicinal product name |
Capsular oligosaccharide of Haemophilus influenzae type b conjugated to CRM 197
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Suspension for injection in pre-filled syringe
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Routes of administration |
Intramuscular use
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Dosage and administration details |
Subjects received one injection of 0.5 mL in the deltoid region.
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Arm title
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HIBERIX | |||||||||||||||
Arm description |
Subjects who received primary vaccination with HIBERIX in the parent study (M37P2), received a booster dose of HIBERIX in this study. | |||||||||||||||
Arm type |
Active comparator | |||||||||||||||
Investigational medicinal product name |
Capsular oligosaccharide of Haemophilus influenzae type b conjugated to tetanus toxoid.
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Powder and solvent for solution for injection
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Routes of administration |
Intramuscular use
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Dosage and administration details |
Subjects received one injection of 0.5 mL in the deltoid region.
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Baseline characteristics reporting groups
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Reporting group title |
Vaxem Hib
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Reporting group description |
Subjects who received primary vaccination with Vaxem Hib in the parent study (M37P2), received a booster dose of Vaxem Hib in this study. | ||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
HIBERIX
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Reporting group description |
Subjects who received primary vaccination with HIBERIX in the parent study (M37P2), received a booster dose of HIBERIX in this study. | ||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Vaxem Hib
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Reporting group description |
Subjects who received primary vaccination with Vaxem Hib in the parent study (M37P2), received a booster dose of Vaxem Hib in this study. | ||
Reporting group title |
HIBERIX
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Reporting group description |
Subjects who received primary vaccination with HIBERIX in the parent study (M37P2), received a booster dose of HIBERIX in this study. | ||
Subject analysis set title |
Exposed Population
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Subject analysis set type |
Safety analysis | ||
Subject analysis set description |
All subjects in the enrolled population who received vaccination
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Subject analysis set title |
All Enrolled Population
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Subject analysis set type |
Intention-to-treat | ||
Subject analysis set description |
All subjects who have signed an informed consent and have been enrolled (eg, data collection).
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Subject analysis set title |
Full Analysis Set (FAS-Immunogenicity)
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Subject analysis set type |
Full analysis | ||
Subject analysis set description |
All subjects in the enrolled population who actually received a study vaccination and provided at least one evaluable serum sample before or after baseline. Baseline is defined as the time immediately before vaccination.
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Subject analysis set title |
Safety population
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Subject analysis set type |
Safety analysis | ||
Subject analysis set description |
All subjects in the exposed population who provided safety data after baseline. Baseline is defined as the time immediately before vaccination.
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Subject analysis set title |
Per Protocol Set (PPS-Immunogenicity)
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Subject analysis set type |
Per protocol | ||
Subject analysis set description |
All subjects in the FAS population who correctly received the vaccine, provided evaluable serum samples at the relevant time points (for subjects in the immunogenicity subset) and have no major protocol violation as defined prior to analysis.
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End point title |
1. Percentages of subjects achieving an anti-Polyribosil-Ribitol-Phosphate (PRP) concentration ≥ 1.0 μg/mL | |||||||||||||||
End point description |
Non-inferiority of immune response of Vaxem Hib when compared to HIBERIX was assessed in terms of percentages of subjects achieving an anti-PRP concentration ≥ 1.0 μg/mL approximately one month post booster vaccination.
Analysis was done on the Per Protocol (PP) dataset.
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End point type |
Primary
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End point timeframe |
Day 31
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Statistical analysis title |
Statistical analysis 1 | |||||||||||||||
Statistical analysis description |
Non-inferiority of immune response of Vaxem Hib when compared to HIBERIX was assessed as the between group difference in percentages of subjects achieving an anti-PRP concentration ≥ 1.0 μg/mL.
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Comparison groups |
HIBERIX v Vaxem Hib
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Number of subjects included in analysis |
543
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Analysis specification |
Pre-specified
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Analysis type |
non-inferiority [1] | |||||||||||||||
Method |
t-test, 1-sided | |||||||||||||||
Parameter type |
Difference in percentages of subjects | |||||||||||||||
Point estimate |
0
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Confidence interval |
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level |
95% | |||||||||||||||
sides |
2-sided
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lower limit |
-9999 | |||||||||||||||
upper limit |
9999 | |||||||||||||||
Variability estimate |
Standard error of the mean
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| Notes [1] - Success criterion: immune response of Vaxem Hib when compared to HIBERIX was to be considered non inferior if the lower two-sided 95% confidence limit of difference in the long-term protection rates of antibodies between the VaxemTM Hib group and the HIBERIX® group is not beyond -5% The approximation method used by the CRO in charge of the statistical analysis of the study, was not able to compute the 95% CI for the difference in proportions when values in both groups were equal to 100%. |
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End point title |
2. Percentages of subjects achieving an anti- Polyribosil-Ribitol-Phosphate (PRP) concentration ≥ 0.15 μg/mL | |||||||||||||||
End point description |
Immune response of Vaxem Hib when compared to HIBERIX was assessed in terms of percentages of subjects achieving an anti-PRP concentration ≥ 0.15 μg/mL approximately one month post booster vaccination.
Analysis was done on PP dataset.
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End point type |
Secondary
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End point timeframe |
Day 31
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| No statistical analyses for this end point | ||||||||||||||||
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End point title |
3. Anti-PRP geometric mean concentration (GMC) | |||||||||||||||
End point description |
Immune response of Vaxem Hib when compared to HIBERIX was assessed in terms of Anti-PRP GMC approximately one month post booster vaccination.
Analysis was done on PP dataset.
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End point type |
Secondary
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End point timeframe |
Day 31
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| No statistical analyses for this end point | ||||||||||||||||
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End point title |
4. Number of subjects reporting selected indicators of reactogenicity local and/or systemic reactions. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Safety and tolerability of the booster dose of Vaxem Hib when compared with the control booster dose of HIBERIX are assessed in terms of number of subjects reporting selected indicators of reactogenicity, ie, local and systemic reactions.
Analysis was done on Safety dataset.
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End point type |
Secondary
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End point timeframe |
From day 1 through 7 after vaccination.
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End point title |
5. Number of subjects reporting unsolicited adverse events (AEs) and/or serious adverse events (SAEs) | ||||||||||||||||||
End point description |
Safety and tolerability of the booster dose of Vaxem Hib when compared with the control booster dose of HIBERIX are assessed in terms of number of subjects reporting unsolicited adverse events (AEs), vaccine-related AEs and/or serious AEs (SAEs).
Analysis was done on the Safety dataset.
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End point type |
Secondary
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End point timeframe |
Throughout the entire study period.
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| No statistical analyses for this end point | |||||||||||||||||||
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Adverse events information
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Timeframe for reporting adverse events |
Selected indicators of reactogenicity were recorded from day 1 to 7 after vaccination; unsolicited AEs and SAEs were recorded throughout the entire study period.
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Adverse event reporting additional description |
Selected indicators of reactogenicity were collected by systematic assessment.
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Assessment type |
Non-systematic | |||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | |||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
12.1
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Reporting groups
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Reporting group title |
HIBERIX
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Reporting group description |
Subjects who received primary vaccination with HIBERIX in the parent study (M37P2), received a booster dose of HIBERIX in this study. | |||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Vaxem Hib
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Reporting group description |
Subjects who received primary vaccination with Vaxem Hib in the parent study (M37P2), received a booster dose of Vaxem Hib in this study. | |||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 5% | ||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? No | |||
Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
