Clinical Trial Results:
A phase IIa specificity trial of the diagnostic agent C-Tb, when given intradermally by the Mantoux technique to healthy volunteers previously vaccinated with BCG
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Summary
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EudraCT number |
2009-017296-17 |
Trial protocol |
GB |
Global end of trial date |
17 Oct 2011
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Results information
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Results version number |
v1(current) |
This version publication date |
17 Jul 2016
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First version publication date |
17 Jul 2016
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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 |
TESEC-03
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Additional study identifiers
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ISRCTN number |
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US NCT number |
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WHO universal trial number (UTN) |
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Sponsors
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Sponsor organisation name |
Statens Serum Institut
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Sponsor organisation address |
Artillerivej 5, Copenhagen, Denmark, 2300
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Public contact |
Toxicology and Clinical Development Unit, Statens Serum Institut, kjmo@ssi.dk
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Scientific contact |
Toxicology and Clinical Development Unit, Statens Serum Institut, kjmo@ssi.dk
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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? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
03 May 2012
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
17 Oct 2011
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Global end of trial reached? |
Yes
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Global end of trial date |
17 Oct 2011
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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 assess the specificity of the C-Tb skin test as a function of the cut-off value (i.e., the smallest size of induration measured in mm resulting in a negative outcome of the C-Tb test) when the test is administered intradermally by the Mantoux technique to healthy BCG vaccinated adults.
The present phase IIa (TESEC-03) trial in a healthy BCG vaccinated population collected data on the distribution of the induration response, if any, to C-Tb in this population. The specificity of the C-Tb test was defined as the relative frequency of subjects in a healthy population (i.e., no exposure to MTb) who have an induration response < cut-off after a C-Tb test.
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Protection of trial subjects |
Based on previous trials, 0.01 and 0.1 μg was considered safe and well tolerated.
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Background therapy |
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Evidence for comparator |
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Actual start date of recruitment |
09 May 2011
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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 |
United Kingdom: 151
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Worldwide total number of subjects |
151
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EEA total number of subjects |
151
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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) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
151
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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 |
This clinical trial was conducted at Surrey Clinical Research Centre, University of Surrey, Guildford, United Kingdom. First subject´s first visit: 09 May 2011 Last subject´s last visit: 17 October 2011 | ||||||||||
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Pre-assignment
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Screening details |
The screening visit (visit 1) took place up to 28 days before the inclusion visit (visit 2) | ||||||||||
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Period 1
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Period 1 title |
Safety set (overall period)
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Is this the baseline period? |
Yes | ||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | ||||||||||
Roles blinded |
Subject, Investigator, Monitor, Data analyst, Carer, Assessor | ||||||||||
Blinding implementation details |
C-Tb and PPD RT 23 SSI were manufactured as solutions for injection and both appeared as clear and colourless liquids. Each subject was administered 1 injection of the IMP C-Tb (0.1 μg / 0.1 mL) in one arm and 1 injection of the comparator PPD RT 23 SSI (2 T.U. / 0.1 mL) in the other arm according to split body design using a randomisation code by the Mantoux injection technique, which is the currently approved injection technique for the comparator
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Arms
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Arm title
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All subjects | ||||||||||
Arm description |
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Arm type |
Experimental | ||||||||||
Investigational medicinal product name |
C-Tb + PPD RT 23 SSI
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Injection
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Routes of administration |
Intradermal use
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Dosage and administration details |
Each subject was administered 1 injection of the IMP C-Tb (0.1 μg / 0.1 mL) in one arm and 1 injection of the comparator PPD RT 23 SSI (2 T.U. / 0.1 mL) in the other arm according to a randomisation code by use of the Mantoux injection technique, which is the currently approved injection technique for the comparator.
A disposable graduated 1 mL syringe equipped with a short-bevelled needle sized 26 gauges was used for the injection.
Stretching the skin slightly and holding the needle almost parallel to the skin with the bevelled side upwards the needle was inserted through the epidermis into the flexor surface of the right or left volar part of the forearm 5-10 cm below the elbow point. The needle was visible through the epidermis before 0.1 mL of the test solution was injected slowly intradermally.
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Baseline characteristics reporting groups
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Reporting group title |
Safety set
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Reporting group description |
- | |||||||||||||||||||||||||||||||||
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Subject analysis sets
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Subject analysis set title |
Per protocol set
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Subject analysis set type |
Per protocol | |||||||||||||||||||||||||||||||||
Subject analysis set description |
The Per Protocol set consists of all subjects who have complied with the protocol and who
have a non-missing diagnostic read out of C-Tb
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End points reporting groups
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Reporting group title |
All subjects
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Reporting group description |
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Subject analysis set title |
Per protocol set
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Subject analysis set type |
Per protocol | ||
Subject analysis set description |
The Per Protocol set consists of all subjects who have complied with the protocol and who
have a non-missing diagnostic read out of C-Tb
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End point title |
Specificity of C-Tb [1] | ||||||||||||||||||
End point description |
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End point type |
Primary
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End point timeframe |
Days 2-3 after administration of C-Tb
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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: No parametric model for the distribution was proposed,so the empirical cumulative distribution function,defined on the range from 0mm to the maximal observed diameter will constitute the main outcome of the study. For each value of d (diameter of C-Tb) in this range, an exact 95% CI for the true value of F(d) will be calculated. The estimated value of F(d) can be interpreted as the specificity of a MTb test using the value d+1 as cut-off, i.e. values above d were considered MTb test positive |
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Attachments |
Untitled (Filename: Figure for T-03 EudraCT.docx) |
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End point title |
Specificity of PPD [2] | ||||||||||||||||||
End point description |
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End point type |
Primary
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End point timeframe |
Day 2-3 after administration of PPD RT 23 SSI
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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: No parametric model for the distribution is proposed,so the empirical cumulative distribution function,defined on the range from 0mm to the maximal observed diameter will constitute the main outcome of the study. For each value of d (diameter of PPD) in this range, an exact 95% CI for the true value of F(d) will be calculated. The estimated value of F(d) can be interpreted as the specificity of a MTb test using the value d+1 as cut-off, i.e. values above d are considered MTb test positive |
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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 |
The duration of the safety follow-up period was
1. First hour after the administration of skin tests
2. 26-30 days
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
14.1
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Reporting groups
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Reporting group title |
Safety set
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Reporting group description |
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| Frequency threshold for reporting non-serious adverse events: 1% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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27 May 2011 |
Administrative changes, such as the outsourcing of the statistical reporting of the trial from Statens Serum Institut (SSI) to OnQ (CRO based in Johannesburg, SA) |
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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 | |||
Online references |
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| http://www.ncbi.nlm.nih.gov/pubmed/23691171 |
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