Clinical Trial Results:
A phase IV, uncontrolled, open-label, multi-center study in children and adolescents: Evaluation of long-term immunogenicity in subjects boosted with a new pediatric TBE vaccine (free of protein-derived stabilizer) in study V48P4E1, five years after first booster immunization
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Summary
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EudraCT number |
2014-005105-20 |
Trial protocol |
Outside EU/EEA |
Global end of trial date |
24 May 2007
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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 |
14 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 |
V48P4E3
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT00452621 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Novartis Vaccines and Diagnostics GmbH & Co. KG
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Sponsor organisation address |
Postfach 1630, Marburg, Germany, 35006
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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 |
15 Nov 2007
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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 |
24 May 2007
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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 investigate the kinetics of the immune response of subjects who participated in studies V48P4 (primary immunization), V48P4E1 (first booster immunization) and V48P4E2 (serological follow-up) with respect to antibody titers in terms of:
• percentage of subjects with titers ≥ 10
• percentage of subjects with titers ≥ 2
• geometric mean titer (GMT)
as measured by Neutralization Test (NT, in-house, Novartis Vaccines), from Day 0 as defined in protocol V48P4 to year 5 (± 90 days) after the first booster immunization with the new TBE vaccine
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Protection of trial subjects |
This study was performed with the ethical principles that have their origin in the Declaration of Helsinki, that are consistent with Good Clinical Practice (GCP) according to International Conference on Harmonisation (ICH) guidelines, the applicable regulatory requirements(s) for the country in which the study was conducted, and applicable standard operating procedures (SOPs).
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
06 Feb 2007
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Long term follow-up planned |
Yes
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Long term follow-up rationale |
Efficacy | ||
Long term follow-up duration |
5 Years | ||
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 |
Germany: 232
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Worldwide total number of subjects |
232
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EEA total number of subjects |
232
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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) |
0
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Children (2-11 years) |
121
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Adolescents (12-17 years) |
111
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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 |
18 centers in Germany | |||||||||||||||
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Pre-assignment
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Screening details |
All enrolled subjects were included in the trial The classification of the age group (Age Classification I & II) refers to the age of the subjects in Study V48P4. | |||||||||||||||
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Period 1
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Period 1 title |
Enrolled (overall period)
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Is this the baseline period? |
Yes | |||||||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | |||||||||||||||
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Arms
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Are arms mutually exclusive |
No
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Arm title
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1-2 years | |||||||||||||||
Arm description |
Subjects aged 1-2 years (Age Classification II) and who participated in studies V48P4 (primary immunization), V48P4E1 (first booster immunization) and V48P4E2 (serological follow-up) | |||||||||||||||
Arm type |
no product administered | |||||||||||||||
Investigational medicinal product name |
no product was administered in this extension study
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Suspension for injection
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Routes of administration |
Route of administration not applicable
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Dosage and administration details |
Not applicable as this study does not involve administration of product. The pharmaceutical form selected for this study is applicable only to the parent study.
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Arm title
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3-11 years | |||||||||||||||
Arm description |
Subjects aged 3-11 years (Age Classification II) and who participated in studies V48P4 (primary immunization), V48P4E1 (first booster immunization) and V48P4E2 (serological follow-up) | |||||||||||||||
Arm type |
no product administered | |||||||||||||||
Investigational medicinal product name |
No investigational medicinal product assigned in this arm
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Arm title
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1-5 years | |||||||||||||||
Arm description |
Subjects aged 1-5 years (Age Classification I) and who participated in studies V48P4 (primary immunization), V48P4E1 (first booster immunization) and V48P4E2 (serological follow-up) | |||||||||||||||
Arm type |
no product administered | |||||||||||||||
Investigational medicinal product name |
No investigational medicinal product assigned in this arm
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Arm title
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6-11 years | |||||||||||||||
Arm description |
Subjects aged 6-11 years (Age Classification I) and who participated in studies V48P4 (primary immunization), V48P4E1 (first booster immunization) and V48P4E2 (serological follow-up) | |||||||||||||||
Arm type |
no product administered | |||||||||||||||
Investigational medicinal product name |
No investigational medicinal product assigned in this arm
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Baseline characteristics reporting groups
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Reporting group title |
Enrolled
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Reporting group description |
- | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
1-2 years
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Reporting group description |
Subjects aged 1-2 years (Age Classification II) and who participated in studies V48P4 (primary immunization), V48P4E1 (first booster immunization) and V48P4E2 (serological follow-up) | ||
Reporting group title |
3-11 years
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Reporting group description |
Subjects aged 3-11 years (Age Classification II) and who participated in studies V48P4 (primary immunization), V48P4E1 (first booster immunization) and V48P4E2 (serological follow-up) | ||
Reporting group title |
1-5 years
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Reporting group description |
Subjects aged 1-5 years (Age Classification I) and who participated in studies V48P4 (primary immunization), V48P4E1 (first booster immunization) and V48P4E2 (serological follow-up) | ||
Reporting group title |
6-11 years
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Reporting group description |
Subjects aged 6-11 years (Age Classification I) and who participated in studies V48P4 (primary immunization), V48P4E1 (first booster immunization) and V48P4E2 (serological follow-up) | ||
Subject analysis set title |
Enrolled population
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Subject analysis set type |
Full analysis | ||
Subject analysis set description |
All enrolled subjects
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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 enrolled subjects:
- who participated in the studies V48P4, V48P4E1 and V48P4E2
- who provided an evaluable serum sample
Subjects who received a booster vaccination after V48P4E2 were included in the FAS and assigned to a NT titer of 2 and an ELISA below detection limit, respectively
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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 PPS:
- who were part of the PPS of study V48P4E2
- had no major protocol violation as defined prior to the analysis
Subjects who received a booster vaccination after V48P4E2 were included in the PPS and assigned to a NT titer of 2 and an ELISA below detection limit, respectively
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Subject analysis set title |
Uninfluenced Per Protocol Population (UPPS)
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Subject analysis set type |
Per protocol | ||
Subject analysis set description |
Uninfluenced Per Protocol Population (UPPS) which consisted of all those subjects in the Per Protocol Population, which had not received an additional (i.e. not study related) TBE booster in the study period of V48P4E2 or after.
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End point title |
1. Percentage of Subjects With Antibody Titers ≥2 as Measured by Neutralization Test( NT)- PPS [1] | ||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Immunogenicity was measured in terms of the Percentage of Subjects With Antibody Titers ≥2 as Measured by NT
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End point type |
Primary
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End point timeframe |
Day 0, Day 42, Booster Day 0, Booster Day 21, 3 Years after booster, 5 Years after booster
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Statistical analysis not applicable |
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||||||||||||
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End point title |
2. Percentage of Subjects With Antibody Titers ≥10 as Measured by NT- PPS [2] | ||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Immunogenicity was measured in terms of the Percentage of Subjects With Antibody Titers ≥10 as Measured by NT
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End point type |
Primary
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End point timeframe |
Day 0, Day 42, Booster Day 0, Booster Day 21, 3 Years after booster, 5 Years after booster
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| Notes [2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Statistical analysis not applicable |
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||||||||||||
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End point title |
3.Geometric Mean Antibody Titers (GMT)as Measured by NT- PPS [3] | ||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Immunogenicity was measured in terms of the Geometric Mean Antibody Titers (GMT)as Measured by NT
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End point type |
Primary
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End point timeframe |
Day 0, Day 42, Booster Day 0, Booster Day 21, 3 Years after booster, 5 Years after booster
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| Notes [3] - 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: Statistical analysis not applicable |
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||||||||||||
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End point title |
4. Ratios of Geometric Mean Antibody Titers (GMT)as Measured by NT- PPS [4] | ||||||||||||||||||||||||||||||||||||||||
End point description |
Immunogenicity was measured in terms of the Ratios of Geometric Mean Antibody Titers (GMT)as Measured by NT
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End point type |
Primary
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End point timeframe |
Day 42, Booster Day 0, Booster Day 21, 3 Years after booster, 5 Years after booster
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| 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: Statistical analysis not applicable |
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||
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End point title |
5. Percentage of Subjects With Antibody Titers ≥2 as Measured by NT -UPPS [5] | ||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Immunogenicity was measured in terms of the Percentage of Subjects With Antibody Titers ≥2 as Measured by NT
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End point type |
Primary
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End point timeframe |
Day 0, Day 42, Booster Day 0, Booster Day 21, 3 Years after booster, 5 Years after booster
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| Notes [5] - 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: Statistical analysis not applicable |
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||||||||||||
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End point title |
6. Percentage of Subjects With Antibody Titers ≥10 as Measured by NT-UPPS [6] | ||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Immunogenicity was measured in terms of the Percentage of Subjects With Antibody Titers ≥10 as Measured by NT
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End point type |
Primary
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End point timeframe |
Day 0, Day 42, Booster Day 0, Booster Day 21, 3 Years after booster, 5 Years after booster
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| Notes [6] - 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: Statistical analysis not applicable |
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||||||||||||
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End point title |
7. Geometric Mean Antibody Titers (GMT)as Measured by NT-UPPS [7] | ||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Immunogenicity was measured in terms of the Geometric Mean Antibody Titers (GMT)as Measured by NT
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End point type |
Primary
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End point timeframe |
Day 0, Day 42, Booster Day 0, Booster Day 21, 3 Years after booster, 5 Years after booster
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| Notes [7] - 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: Statistical analysis not applicable |
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||||||||||||
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End point title |
8. Ratios of Geometric Mean Antibody Titers (GMT)as Measured by NT-UPPS [8] | ||||||||||||||||||||||||||||||||||||||||
End point description |
Immunogenicity was measured in terms of the Ratios of Geometric Mean Antibody Titers (GMT)as Measured by NT
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End point type |
Primary
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End point timeframe |
Day 42, Booster Day 0, Booster Day 21, 3 Years after booster, 5 Years after booster
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| Notes [8] - 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: Statistical analysis not applicable |
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||
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Adverse events information [1]
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Timeframe for reporting adverse events |
NA
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Adverse event reporting additional description |
NA
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Assessment type |
Non-systematic | ||
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Dictionary used for adverse event reporting
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Dictionary name |
NA | ||
Dictionary version |
NA
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| Frequency threshold for reporting non-serious adverse events: 0% | |||
| Notes [1] - There are no non-serious adverse events recorded for these results. It is expected that there will be at least one non-serious adverse event reported. Justification: NA |
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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 | |||
