Clinical Trial Results:
Chronic non bacterial osteomyelitis treated with pamidronat in a randomised placebo controlled trial
Summary
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EudraCT number |
2015-002038-36 |
Trial protocol |
DK |
Global end of trial date |
30 Oct 2019
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Results information
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Results version number |
v1(current) |
This version publication date |
29 May 2020
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First version publication date |
29 May 2020
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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 |
48438
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT02594878 | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
Aarhus University Hospital, Denmark
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Sponsor organisation address |
Palle Juul-Jensens Boukevard 99, Aarhus, Denmark, 8200
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Public contact |
Caroline Marie Andreasen, Aarhus University Hospital, Department of Rheumatology, +45 7846 4252, carand@rm.dk
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Scientific contact |
Caroline Marie Andreasen, Aarhus University Hospital, Department of Rheumatology, +45 7846 4252, carand@rm.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 |
30 Oct 2019
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
30 Oct 2019
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Global end of trial reached? |
Yes
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Global end of trial date |
30 Oct 2019
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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 |
In a randomized double blind placebo controlled design in patients with chronic non bacterial osteomyelitis to investigate whether it is possible by treating with pamidronat to achieve a
1. Reduction of the inflammatory activity in the osteomyelytic boneproces measured by whole body MRIafter 9 months
2. Healing of the inflammatory activity in the osteomyelytic boneproces measured by whole body MRI after 9 months
Full length article has been accepted for publication Scandinavian Journal of Rheumatology, Accepted January 2020.
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Protection of trial subjects |
Clinical evaluation and blood samples included laboratory screening for inflammation, renal and liver functional parameters
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Background therapy |
Placebo (NaCl) | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
01 Oct 2015
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
Yes
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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 |
Denmark: 14
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Worldwide total number of subjects |
14
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EEA total number of subjects |
14
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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) |
1
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
13
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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 |
Fifty-six patients were approached of whom 23 adults and one child/family provided written consent and were assessed for eligibility. Randomisation was performed in 13 of 23 adults. One child completed the study but was excluded from the analyses for methodological reasons. | |||||||||||||||
Pre-assignment
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Screening details |
- | |||||||||||||||
Pre-assignment period milestones
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Number of subjects started |
14 | |||||||||||||||
Number of subjects completed |
14 | |||||||||||||||
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 |
Double blind | |||||||||||||||
Roles blinded |
Subject, Investigator, Monitor, Data analyst | |||||||||||||||
Blinding implementation details |
The hospital pharmacy performed the randomization. Pamidronate or placebo were identically packed at the hospital pharmacy.
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Pamidronate | |||||||||||||||
Arm description |
Pamifos 3mg/ml, Medac, Hamburg, Germany | |||||||||||||||
Arm type |
Active comparator | |||||||||||||||
Investigational medicinal product name |
Pamifos 3mg/ml, Medac, Hamburg, Germany
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
pamidronate 1 mg pamidronate kg/day, max 60 mg, first dose first series 0.5 mg/kg, administered for three consecutive days at baseline, week 12 and week 24.
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Arm title
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Sodium chloride | |||||||||||||||
Arm description |
sodium chloride 9g/l | |||||||||||||||
Arm type |
Placebo | |||||||||||||||
Investigational medicinal product name |
Sodium chloride 9g/l
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
intravenous sodium chloride 9g/l
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Baseline characteristics reporting groups
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Reporting group title |
Overall trial
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Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Subject analysis sets
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Subject analysis set title |
Data analysis
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Subject analysis set type |
Full analysis | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
Randomisation was performed in 14. One patient in the pamidronate group dropped out of the study for personal reasons after the first pamidronate cycle. One child completed the study but was excluded from the analyses for methodological reasons. Analysis were performed in placebo (n=6) and IMP (pamidronatedinatrium) (n=6)
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End points reporting groups
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Reporting group title |
Pamidronate
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Reporting group description |
Pamifos 3mg/ml, Medac, Hamburg, Germany | ||
Reporting group title |
Sodium chloride
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Reporting group description |
sodium chloride 9g/l | ||
Subject analysis set title |
Data analysis
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Subject analysis set type |
Full analysis | ||
Subject analysis set description |
Randomisation was performed in 14. One patient in the pamidronate group dropped out of the study for personal reasons after the first pamidronate cycle. One child completed the study but was excluded from the analyses for methodological reasons. Analysis were performed in placebo (n=6) and IMP (pamidronatedinatrium) (n=6)
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End point title |
Endpoints listed in table attached | ||||||||||||||||
End point description |
Primary endpoint:
Changes in disease activity score of the anterior chest wall assessed by whole body magnetic resonance imaging
Secondary endpoint:
Changes in disease chronicity score of the anterior chest wall assessed by whole body magnetic resonance imaging
Changes in disease chronicity score of the anterior chest wall assessed by computered tomography
Changes in diseaseactivity score of the spine assessed by whole body magnetic resonance imaging
Changes in disease chronicity score of the spine assessed by whole body magnetic resonance imaging
Changes in VAS pain
Changes in VAS global
Changes in biomarkers of boneresorption, boneformation and inflammation
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End point type |
Primary
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End point timeframe |
Baseline and week 36
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Attachments |
Results CNOPAM |
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Notes [1] - See reuslts attached |
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Statistical analysis title |
See results attached | ||||||||||||||||
Comparison groups |
Pamidronate v Sodium chloride v Data analysis
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Number of subjects included in analysis |
24
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Analysis specification |
Post-hoc
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Analysis type |
non-inferiority | ||||||||||||||||
P-value |
< 0.05 | ||||||||||||||||
Method |
t-test, 2-sided | ||||||||||||||||
Parameter type |
Median difference (final values) | ||||||||||||||||
Confidence interval |
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95% | ||||||||||||||||
sides |
2-sided
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lower limit |
- | ||||||||||||||||
upper limit |
- | ||||||||||||||||
Variability estimate |
Standard deviation
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Adverse events information
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Timeframe for reporting adverse events |
Assessment of AE was performed at week 1,4,12,24 and week 36 and if an extra visit was acquired.
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Adverse event reporting additional description |
Reporting of all adverse event follows The European Commission and Danish law: ”Guidelines on medical devices. Clinical investigations: Serious adverse event reporting” MEDDEV 2.7/3.
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Assessment type |
Systematic | ||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
MEDDEV 2.7 | ||||||||||||||||
Dictionary version |
3
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Reporting groups
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Reporting group title |
Adverse events
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Reporting group description |
Non- serious adverse events were reported in the pamidronate group/placebo group were: gastrointestinal symptoms (n=1/2), aching joints (n=2/1), flu-like symptoms (n=3/1), headache (n=5/1), mild hypophosphatemia (n=1/0), mild hypocalcaemia (n=1/0) and phlebitis in cubitalis vein (n=1/1). Adverse events were mainly seen following the first treatment cycle. | ||||||||||||||||
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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. | |||
Due to recruitment challenges, only 12 adults and one child completed the study and because of inadequate sample size the study was a posteriori converted to a pilot study. The child was excluded from analyses for methodological reasons. |