Clinical Trial Results:
Multicenter, randomized, open-label, clinical study on the agreement of
Scintimun® Granulocyte and labeled 99mTc-White Blood Cells in diagnosing
infection/inflammation by immunoscintigraphy in peripheral bone and joints
with suspected osteomyelitis.
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Summary
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EudraCT number |
2006-000514-21 |
Trial protocol |
NL HU DE CZ |
Global end of trial date |
05 Jan 2008
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Results information
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Results version number |
v1(current) |
This version publication date |
16 Dec 2018
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First version publication date |
16 Dec 2018
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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 |
AG-PH3
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
CIS bio international
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Sponsor organisation address |
BP 32, GIF SUR YVETTE, France, 91192
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Public contact |
Medical information, CIS bio international, florence.chossat@curiumpharma.com
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Scientific contact |
Medical information, CIS bio international, +33 0169857108, florence.chossat@curiumpharma.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? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
24 Jun 2008
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
04 Jan 2008
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Global end of trial reached? |
Yes
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Global end of trial date |
05 Jan 2008
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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 |
The primary objective of the present study is to assess the agreement rate of Scintimun® Granulocyte and 99mTc-WBCs with regard to the diagnosis of infection/inflammation by immunoscintigraphy, based on the evaluations of three blinded and independent readers in the absence of a standard of reference (SOR) to evaluate the true status.
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Protection of trial subjects |
No specific measures put in place
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Background therapy |
- | ||
Evidence for comparator |
99mTc-hexamethyl propylene amine oxime (HMPAO) enables labelling of WBCs in vivo and does not need to perform cell isolation in vitro The patient receives both treatments (cross-over study) therefore comparison with an antibody is not possible | ||
Actual start date of recruitment |
26 Sep 2006
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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 |
Netherlands: 20
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Country: Number of subjects enrolled |
Czech Republic: 44
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Country: Number of subjects enrolled |
Germany: 2
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Country: Number of subjects enrolled |
Hungary: 42
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Country: Number of subjects enrolled |
France: 22
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Worldwide total number of subjects |
130
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EEA total number of subjects |
130
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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) |
130
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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 |
Five countries were involved. Randomisation of products injection was performed centrally. First patient first visit : 26/09/2006 Last patient last visit : 04/01/2008 | |||||||||
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Pre-assignment
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Screening details |
Patients with suspected or documented osteomyelitis in the peripheral skeleton (e.g. patients with loosening of joint prosthesis and or diabetic foot. In addition localised pain, and/or nonhealing skin ulceration, and/or fever > 37.8°C for at least 3 days, WBCs elevated, ESR elevated, suggestive RX findings. Patients with HAMA positive excluded | |||||||||
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Period 1
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Period 1 title |
overall trial (overall period)
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Is this the baseline period? |
Yes | |||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Not blinded | |||||||||
Blinding implementation details |
The study was open-label design. However the agreement rate was based on the evaluation of three blinded and independent readers in a blinded reading.
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Arms
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Are arms mutually exclusive |
No
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Arm title
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SCINTIMUN first | |||||||||
Arm description |
Multicenter, open- label, randomised, intra-individual comparison. Each patient was injected with SCINTIMUN and 99mTc-WBCs in random order with a minimum time interval of two days (a minimum of 48 hours) between the injections. In SCINTIMUN first arm, SCINTIMUN was injected first | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
besilesomab
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Investigational medicinal product code |
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Other name |
SCINTIMUN
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Pharmaceutical forms |
Kit for radiopharmaceutical preparation
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Routes of administration |
Intravenous bolus use
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Dosage and administration details |
Single administration of 800 MBq
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Investigational medicinal product name |
Exametazime
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Investigational medicinal product code |
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Other name |
CERETEC
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Pharmaceutical forms |
Kit for radiopharmaceutical preparation
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Routes of administration |
Intravenous bolus use
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Dosage and administration details |
Single administration of 330 MBq
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Arm title
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CERETEC first | |||||||||
Arm description |
Multicenter, open- label, randomised, intra-individual comparison. Each patient was injected with SCINTIMUN and 99mTc-WBCs in random order with a minimum time interval of two days (a minimum of 48 hours) between the injections. In this arm CERETEC is administered first. | |||||||||
Arm type |
Active comparator | |||||||||
Investigational medicinal product name |
hexametazime
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Investigational medicinal product code |
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Other name |
CERETEC
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Pharmaceutical forms |
Kit for radiopharmaceutical preparation
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Routes of administration |
Intravenous use
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Dosage and administration details |
Single administration of 330 MBq
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Investigational medicinal product name |
besilesomab
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Investigational medicinal product code |
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Other name |
SCINTIMUN
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Pharmaceutical forms |
Kit for radiopharmaceutical preparation
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Routes of administration |
Intravenous use
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Dosage and administration details |
800 MBq in a single injection
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Baseline characteristics reporting groups
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Reporting group title |
overall trial
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Reporting group description |
overall study population | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
SCINTIMUN first
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Reporting group description |
Multicenter, open- label, randomised, intra-individual comparison. Each patient was injected with SCINTIMUN and 99mTc-WBCs in random order with a minimum time interval of two days (a minimum of 48 hours) between the injections. In SCINTIMUN first arm, SCINTIMUN was injected first | ||
Reporting group title |
CERETEC first
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Reporting group description |
Multicenter, open- label, randomised, intra-individual comparison. Each patient was injected with SCINTIMUN and 99mTc-WBCs in random order with a minimum time interval of two days (a minimum of 48 hours) between the injections. In this arm CERETEC is administered first. | ||
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End point title |
agreement rate | |||||||||
End point description |
The primary analysis was the evaluation of the agreement rate of SCINTIMUN and 99mTc-WBCs with regard to the diagnosis of infection/inflammation by scintigraphy. The primary efficacy variable was calculated as an average across the results of the 3 blinded and independent readers
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End point type |
Primary
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End point timeframe |
overall study
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Statistical analysis title |
statistical analysis of the primary variable | |||||||||
Statistical analysis description |
The agreement rate was analysed using a modified adjusted Chi2-test to cover clustered data and multiple measurements per cluster. The limit of clinical relevance was set to 0.7. The agreement rate was supposed to be sufficient if its one-sided 97.5% confidence interval was positioned completely above 0.70.
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Comparison groups |
CERETEC first v SCINTIMUN first
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Number of subjects included in analysis |
130
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Analysis specification |
Pre-specified
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Analysis type |
non-inferiority | |||||||||
P-value |
≤ 0.025 | |||||||||
Method |
Chi-squared corrected | |||||||||
Parameter type |
Mean difference (final values) | |||||||||
Point estimate |
0.8
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Confidence interval |
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level |
95% | |||||||||
sides |
1-sided
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lower limit |
0.7 | |||||||||
upper limit |
- | |||||||||
Variability estimate |
Standard deviation
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Adverse events information
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Timeframe for reporting adverse events |
overall study
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Adverse event reporting additional description |
- Monitoring of the adverse events until Month 1,
- Measurement of vital signs before and after each injection,
- Measurement of laboratory parameters before and 24 hours after each injection, and at Month 1,
- HAMA test at Month 1 and Month 3.
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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 |
11.1
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Reporting groups
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Reporting group title |
ceretec first
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Reporting group description |
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Reporting group title |
scintimun first
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Reporting group description |
- | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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 | |||
Online references |
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| http://www.ncbi.nlm.nih.gov/pubmed/21321791 |
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