Clinical Trial Results:
Effects of bosentan in a HOMogenEous population of SSc subjects with an early or active SSc nailfold capillaroscopic pattern (HOME II)
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Summary
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EudraCT number |
2011-005303-32 |
Trial protocol |
NL |
Global end of trial date |
03 Jun 2014
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Results information
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Results version number |
v1(current) |
This version publication date |
04 Nov 2018
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First version publication date |
04 Nov 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 |
AC-052-438
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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 |
Actelion Pharmaceuticals Nederland bv
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Sponsor organisation address |
Beneluxlaan 2b, Woerden, Netherlands, 3446 GR
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Public contact |
Medical Director, Actelion Pharmaceuticals Nederland bv, sjansen8@its.jnj.com
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Scientific contact |
Medical Director, Actelion Pharmaceuticals Nederland bv, sjansen8@its.jnj.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 |
02 Mar 2015
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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 |
03 Jun 2014
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Was the trial ended prematurely? |
Yes
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General information about the trial
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Main objective of the trial |
Evaluate the effect of bosentan on the blood flow in the hands from baseline to 12 weeks, measured by laser Doppler imaging, in SSc subjects with an early or active SSc pattern, measured with nailfold capillaroscopy (NFM), with ongoing digital ulcer disease and a history of DU disease in the past 2 years.
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Protection of trial subjects |
The clinical trial was designed and conducted in accordance with the ICH Harmonized Tripartite Guidelines for GCP, with applicable local regulations, including the European Directive 2001/20/EC, 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 |
21 Mar 2012
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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 |
Netherlands: 44
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Worldwide total number of subjects |
44
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EEA total number of subjects |
44
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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) |
38
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From 65 to 84 years |
6
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85 years and over |
0
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Recruitment
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Recruitment details |
Among the 55 screened patients, 44 were enrolled in the study. | ||||||||||||||||
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Pre-assignment
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Screening details |
Fifty-five patients with systemic sclerosis (SSc) and a history of digital ulcers (DU) in the past two years were screened by nailfold capillaroscopy (NFM) from seven sites in the Netherlands | ||||||||||||||||
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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 |
Not applicable
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Blinding used |
Not blinded | ||||||||||||||||
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Arms
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Arm title
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Bosentan | ||||||||||||||||
Arm description |
All participants received bosentan for 3 months. They received 62.5 mg b.i.d of bosentan for the first 4 weeks followed by 125 mg b.i.d.during the next 8 weeks. Then they could continue to receive bosentan based on the clinical decision of the health care professional. | ||||||||||||||||
Arm type |
Experimental | ||||||||||||||||
Investigational medicinal product name |
Bosentan
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Investigational medicinal product code |
ACT-050088
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Other name |
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Pharmaceutical forms |
Film-coated tablet
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Routes of administration |
Oral use
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Dosage and administration details |
tablets containing 62.5 mg or 125 mg of bosentan
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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 trial | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Bosentan
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Reporting group description |
All participants received bosentan for 3 months. They received 62.5 mg b.i.d of bosentan for the first 4 weeks followed by 125 mg b.i.d.during the next 8 weeks. Then they could continue to receive bosentan based on the clinical decision of the health care professional. | ||
Subject analysis set title |
Baseline efficacy data
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Subject analysis set type |
Intention-to-treat | ||
Subject analysis set description |
The baseline values of efficacy variables were used to assess the effects of bosentan on blood flow
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Subject analysis set title |
12-week efficacy data
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Subject analysis set type |
Intention-to-treat | ||
Subject analysis set description |
The values of efficacy variables at week 12 were compared to the baseline values for each subject because each subject was considered as his or her own control
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End point title |
Change from baseline to week 12 in blood flow in the whole hand | ||||||||||||
End point description |
Blood flow in the hands was measured by laser Doppler Imaging at baseline and after 12 weeks of treatment with bosentan.
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End point type |
Primary
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End point timeframe |
Baseline and Week 12
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Statistical analysis title |
Change from baseline to Week 12 in hand blood flow | ||||||||||||
Statistical analysis description |
Change from baseline in hand blood flow was evaluated with a mixed model analysis
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Comparison groups |
12-week efficacy data v Baseline efficacy data
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Number of subjects included in analysis |
88
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Analysis specification |
Pre-specified
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Analysis type |
superiority [1] | ||||||||||||
P-value |
= 0.052 | ||||||||||||
Method |
ANCOVA | ||||||||||||
Confidence interval |
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95% | ||||||||||||
sides |
2-sided
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lower limit |
-0.066 | ||||||||||||
upper limit |
12.265 | ||||||||||||
| Notes [1] - Each subject was considered as his/her own control (data at Week 12 were compared to baseline values for each subject). The blood flow of the hand was expected to be stable in time. |
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End point title |
Change from baseline to week 12 in blood flow in fingertips (ROI1) | ||||||||||||
End point description |
A change in blood flow was measured by laser Doppler Imaging in different regions of interest of the hand (ROI), including the fingertips (ROI1)
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End point type |
Secondary
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End point timeframe |
Baseline and Week 12
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Change from baseline to week 12 in blood flow in fingers (ROI2) | ||||||||||||
End point description |
A change in blood flow was measured by laser Doppler Imaging in different regions of interest of the hand (ROI), including the fingers, excluding the tips (ROI2)
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End point type |
Secondary
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End point timeframe |
Baseline and Week 12
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Change from baseline to week 12 in blood flow in the palms of the hands (ROI3) | ||||||||||||
End point description |
A change in blood flow was measured by laser Doppler Imaging in different regions of interest of the hand (ROI), including the palms of the hands (ROI3).
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End point type |
Secondary
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End point timeframe |
Baseline and Week 12
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Change from baseline to week 12 in blood flow in the whole hand of patients who never received iloprost | ||||||||||||
End point description |
Blood flow in the hands measured by laser Doppler Imaging was analyzed separately for subjects with no history of iloprost use.
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End point type |
Secondary
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End point timeframe |
Baseline and Week 12
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Change from baseline to week 12 in ROI1 blood flow of patients who never received iloprost | ||||||||||||
End point description |
ROI1 (fingertips) Blood flow measured by laser Doppler Imaging was analyzed separately for subjects with no history of iloprost use.
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End point type |
Secondary
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End point timeframe |
Baseline and Week 12
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Change from baseline to week 12 in ROI2 blood flow of patients who never received iloprost | ||||||||||||
End point description |
ROI2 (fingers, excluding tips) blood flow measured by laser Doppler Imaging was analyzed separately for subjects with no history of iloprost use.
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End point type |
Secondary
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End point timeframe |
Baseline and Week 12
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Change from baseline to week 12 in ROI3 blood flow of patients who never received iloprost | ||||||||||||
End point description |
ROI3 (hand palms) blood flow measured by laser Doppler Imaging was analyzed separately for subjects with no history of iloprost use.
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End point type |
Secondary
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End point timeframe |
Baseline and Week 12
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Change from baseline to week 12 in number of digital ulcers and pitting scars | |||||||||||||||
End point description |
Photos were made of the hands of all patients using a digital camera to detect the presence of DUs or pitting scars.
The sum of all DUs and pitting scars in all patients were reported at baseline and after 12 weeks of treatment with bosentan.
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End point type |
Secondary
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End point timeframe |
Baseline and Week 12
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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 |
From study drug initiation up to 52 weeks of treatment (whole study period)
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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 |
21.0
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Reporting groups
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Reporting group title |
Bosentan
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Reporting group description |
43 Participants took at least one dose of bosentan, with 18 of them still on treatment at Week 52. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 0% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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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22 May 2012 |
The main reason was to increase the time window of visit at Week 12 from +/- 5 days to +/- 7 days. |
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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. | |||
| Due to slow recruitment the study was prematurely terminated and the long term effects of bosentan on vasculopathy and other secondary endpoints could not be assessed. | |||
