Clinical Trial Results:
A Phase III Observer blind Single-Coordinating Center Pediatric Study in China Comparing a Booster Dose of Vaxem™ Hib to HIBERIX® When Given as Part of a Local Dosing Regimen in Infants
Summary
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EudraCT number |
2014-005135-13 |
Trial protocol |
Outside EU/EEA |
Global end of trial date |
21 Dec 2010
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Results information
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Results version number |
v1(current) |
This version publication date |
30 May 2016
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First version publication date |
09 May 2015
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Other versions |
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 |
V37_07E1
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT01226953 | ||
WHO universal trial number (UTN) |
- | ||
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 and Diagnostics, RegistryContactVaccinesUS@novartis.com
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Scientific contact |
Posting Director, Novartis Vaccines and Diagnostics, 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 |
27 May 2011
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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 |
21 Dec 2010
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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 the immune response of Vaxem™ Hib booster is non-inferior to the
immune response of comparator vaccine HIBERIX® booster as assessed by the
percentage of subjects with anti-PRP (polyribosyl-ribitol-phosphate) antibody levels
≥1.0μg/mL 30 days after booster vaccination.
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Protection of trial subjects |
This clinical study was designed, implemented and reported in accordance with the ICH Harmonized Tripartite Guidelines for Good Clinical Practice (GCP), with applicable local regulations, including the European Directive 2001/20/EC, the US CFR Title 21, Novartis codes on the protection of human rights, and with the ethical principles laid down in the Declaration of Helsinki.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
31 Oct 2010
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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: 660
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Worldwide total number of subjects |
660
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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) |
660
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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 recruited from 1 site in China. | |||||||||
Pre-assignment
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Screening details |
All enrolled subjects were included in the trial. | |||||||||
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 |
Double blind | |||||||||
Roles blinded |
Subject, Investigator, Monitor, Data analyst, Carer, Assessor | |||||||||
Arms
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Are arms mutually exclusive |
Yes
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Arm title
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VaxemHib | |||||||||
Arm description |
Subjects who received the VaxemHib vaccine in the parent study and received one booster dose of the same vaccine in this study. | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
Haemophilus influenzae type b conjugate vaccine (CRM197 Conjugate)
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Investigational medicinal product code |
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Other name |
VaxemHib
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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 |
A single dose of 0.5 mL VaxemHib was to be administered intramuscularly into the deltoid muscle.
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Arm title
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HIBERIX | |||||||||
Arm description |
Subjects who received the HIBERIX vaccine in the parent study and received one booster dose of the same vaccine in this study. | |||||||||
Arm type |
Active comparator | |||||||||
Investigational medicinal product name |
Haemophilus influenzae type b Conjugate Vaccine (Tetanus Toxoid Conjugate)
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Investigational medicinal product code |
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Other name |
HIBERIX
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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 |
A single dose of 0.5 mL HIBERIX was to be administered intramuscularly into the deltoid muscle.
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Baseline characteristics reporting groups
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Reporting group title |
VaxemHib
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Reporting group description |
Subjects who received the VaxemHib vaccine in the parent study and received one booster dose of the same vaccine in this study. | ||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
HIBERIX
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Reporting group description |
Subjects who received the HIBERIX vaccine in the parent study and received one booster dose of the same vaccine in this study. | ||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
VaxemHib
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Reporting group description |
Subjects who received the VaxemHib vaccine in the parent study and received one booster dose of the same vaccine in this study. | ||
Reporting group title |
HIBERIX
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Reporting group description |
Subjects who received the HIBERIX vaccine in the parent study and received one booster dose of the same vaccine in this study. | ||
Subject analysis set title |
All Enrolled Population, Demography
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Subject analysis set type |
Intention-to-treat | ||
Subject analysis set description |
All subjects who have signed an informed consent.
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Subject analysis set title |
Per protocol (PP) population, Immunogenicity
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Subject analysis set type |
Per protocol | ||
Subject analysis set description |
All subjects in the Full Analysis Set (FAS)/Modified Intention-to-treat (MITT) Immunogenicity population who:
- correctly receive the vaccine, and
- provide evaluable serum samples at the relevant time points, and
- have no major protocol violation as defined prior to analysis.
A major deviation is defined as a protocol deviation that is considered to have a significant impact on the immunogenicity result of the subject.
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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 provide post vaccination safety data.
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End point title |
1. Percentage of subjects achieving an anti-PRP concentration ≥1.0 μg/mL 30 days after booster vaccination. | ||||||||||||||||||
End point description |
The immune response of VaxemHib booster was assessed by the percentage of subjects with anti-PRP (polyribosyl-ribitol-phosphate) antibody levels ≥1.0μg/mL 30 days after booster vaccination.
Analysis was performed on the per protocol population.
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End point type |
Primary
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End point timeframe |
30 days after booster vaccination
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Statistical analysis title |
Statistical analysis 1 | ||||||||||||||||||
Statistical analysis description |
Non-inferiority of VaxemHib immune response following booster vaccination as compared to the immune response of comparator vaccine HIBERIX booster 30 days after vaccination.
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Comparison groups |
VaxemHib v HIBERIX
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Number of subjects included in analysis |
603
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Analysis specification |
Pre-specified
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Analysis type |
non-inferiority [1] | ||||||||||||||||||
Method |
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Parameter type |
Vaccine Group Differences | ||||||||||||||||||
Point estimate |
0
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Confidence interval |
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level |
95% | ||||||||||||||||||
sides |
2-sided
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lower limit |
-2 | ||||||||||||||||||
upper limit |
1 | ||||||||||||||||||
Notes [1] - Non-inferiority was assessed using a non-inferiority margin of -5% for the vaccine group difference in proportions of subjects achieving an anti-PRP concentration ≥1.0 μg/mL. |
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End point title |
2. Percentage of subjects achieving an anti-PRP concentration ≥0.15 μg/mL 30 days after booster vaccination | ||||||||||||||||||
End point description |
The immune response of VaxemHib booster was assessed by the percentage of subjects with anti-PRP antibody levels ≥0.15 μg/mL, 30 days after booster vaccination.
Analysis was performed on the per protocol population.
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End point type |
Secondary
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End point timeframe |
30 days after booster vaccination
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Statistical analysis title |
Statistical analysis 1 | ||||||||||||||||||
Statistical analysis description |
Non-inferiority of VaxemHib immune response following booster vaccination as compared to the immune response of comparator vaccine HIBERIX booster 30 days after vaccination.
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Comparison groups |
HIBERIX v VaxemHib
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Number of subjects included in analysis |
603
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Analysis specification |
Pre-specified
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Analysis type |
non-inferiority [2] | ||||||||||||||||||
Method |
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Parameter type |
Vaccine Group Differences | ||||||||||||||||||
Point estimate |
0
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Confidence interval |
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level |
95% | ||||||||||||||||||
sides |
2-sided
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lower limit |
-2 | ||||||||||||||||||
upper limit |
1 | ||||||||||||||||||
Notes [2] - Non-inferiority was assessed using a non-inferiority margin of -5% for the vaccine group difference in proportions of subjects achieving an anti-PRP concentration ≥0.15 μg/mL. |
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End point title |
3. Geometric mean of anti-PRP antibody concentration 30 days after booster vaccination | ||||||||||||||||||
End point description |
The immune response of VaxemHib booster was assessed by anti-PRP antibody geometric mean concentrations (GMCs), 30 days after booster vaccination.
Analysis was performed on the per protocol population.
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End point type |
Secondary
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End point timeframe |
30 days after booster vaccination
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Statistical analysis title |
Statistical analysis 1 | ||||||||||||||||||
Statistical analysis description |
Non-inferiority of VaxemHib immune response following booster vaccination as compared to the immune response of comparator vaccine HIBERIX booster
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Comparison groups |
VaxemHib v HIBERIX
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Number of subjects included in analysis |
603
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Analysis specification |
Pre-specified
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Analysis type |
non-inferiority [3] | ||||||||||||||||||
Method |
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Parameter type |
Vaccine Group Ratios | ||||||||||||||||||
Point estimate |
0.83
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Confidence interval |
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level |
95% | ||||||||||||||||||
sides |
2-sided
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lower limit |
0.7 | ||||||||||||||||||
upper limit |
1 | ||||||||||||||||||
Notes [3] - Non-inferiority was assessed using a non-inferiority margin of non-inferiority of 0.67 for the ratio of vaccine group anti-PRP GMCs |
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End point title |
4. Numbers of subjects with reported solicited local and systemic adverse events (AEs) recorded for 7 days (day 1-7) after the vaccination. | |||||||||||||||||||||||||||||||||||||||||||||
End point description |
The numbers of subjects with reported solicited local and systemic adverse events (AEs) were recorded for 7 days after the vaccination.
Analysis was performed on the safety population.
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End point type |
Secondary
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End point timeframe |
day 1-7 after the vaccination
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No statistical analyses for this end point |
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End point title |
5. Numbers of subjects with reported unsolicited adverse events (AEs) recorded for 7 days (day 1-7) after the vaccination. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
The numbers of subjects with reported unsolicited adverse events (AEs) were recorded for 7 days after the vaccination.
Analysis was performed on the safety population.
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End point type |
Secondary
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End point timeframe |
day 1-7 after the vaccination
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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 |
All adverse events were collected from day 1 to 30. Solicited local and systemic reactions were collected from day 1 to 7.
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Assessment type |
Non-systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
13.1
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Reporting groups
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Reporting group title |
VaxemHib
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Reporting group description |
Subjects who received the VaxemHib vaccine in the parent study and received one booster dose of the same vaccine. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
HIBERIX
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Reporting group description |
Subjects who received the HIBERIX vaccine in the parent study and received one booster dose of the same vaccine. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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 |