Clinical Trial Results:
Open, Prospective, Controlled Case Series Documentation to Compare Intra-individually the Efficacy and Tolerance of Sericare versus Non-adhesive Wound Dressing alone in Accelerating the Epithelialisation of Skin Lesions of Patients with Epidermolysis bullosa hereditaria
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Summary
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EudraCT number |
2010-019945-24 |
Trial protocol |
DE |
Global end of trial date |
14 Jun 2011
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Results information
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Results version number |
v1(current) |
This version publication date |
27 Oct 2016
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First version publication date |
27 Oct 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 |
BEB-10
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT01294241 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Birken AG
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Sponsor organisation address |
Streiflingsweg 11, Niefern-Oeschelbronn, Germany, 75223
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Public contact |
Clinical Development, Birken AG, +49 723397490, info@birken.eu
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Scientific contact |
Clinical Development, Birken AG, +49 723397490, info@birken.eu
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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 |
20 Oct 2011
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
14 Jun 2011
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Global end of trial reached? |
Yes
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Global end of trial date |
14 Jun 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 compare intra-individually the reepithelialisation of skin lesion(s) in inherited Epidermolysis bullosa (either 1 wound ≥10 cm2 and ≤200 cm2 in size divided in 2 equal halves or 2 comparable wounds of ≥5 cm2 each) treated with Oleogel-S10 and non-adhesive wound dressing versus non-adhesive wound dressing only.
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Protection of trial subjects |
The study was conducted in compliance with the study protocol, ethical principles originating in or derived from the Declaration of Helsinki, ethics committee informed consent regulations, and International Council on Harmonisation (ICH) Good Clinical Practice (GCP) guidelines. In addition, all national and local regulatory requirements were followed. Insurance coverage for all participating subjects was guaranteed according to applicable legal requirements. Before undergoing any study-specific procedures, subjects were informed about the nature, scope, and possible consequences of the study. The investigator was responsible for obtaining a subject's written informed consent to participate in the study.
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Background therapy |
Non-adhesive wound dressing | ||
Evidence for comparator |
Non-adhesive wound dressing is standard of care in patients with inherited Epidermolysis bullosa. | ||
Actual start date of recruitment |
03 Nov 2010
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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 |
Germany: 10
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Worldwide total number of subjects |
10
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EEA total number of subjects |
10
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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) |
3
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Adolescents (12-17 years) |
2
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Adults (18-64 years) |
5
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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 |
Subjects were enrolled from 03 Nov 2010 to 14 Jun 2011 at 1 centre (University Medical Centre Freiburg) in 1 country (Germany). | |||||||||
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Pre-assignment
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Screening details |
The investigator obtained written informed consent, checked eligibility, recorded demographic data, medical history/current medical conditions and EB subtype, performed a urine pregnancy test, did a physical examination, and identified 1 EB wound ≥10 cm2 and ≤200 cm2 in size or selected 2 comparable wounds of ≥5 cm2 each. | |||||||||
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Pre-assignment period milestones
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Number of subjects started |
10 | |||||||||
Number of subjects completed |
10 | |||||||||
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Period 1
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Period 1 title |
Treatment period (overall period)
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Is this the baseline period? |
Yes | |||||||||
Allocation method |
Non-randomised - controlled
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Blinding used |
Single blind | |||||||||
Roles blinded |
Assessor [1] | |||||||||
Blinding implementation details |
This was an open-label study. The investigator, the subject and the sponsor knew the identity of the treatment. Two independent experts were blind to treatment and assessed efficacy based on chronological series of cropped and coded photographs by wound (half) that were taken before start of treatment, during wound dressing changes and at the end of treatment on Day 14/Day 28.
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Arms
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Are arms mutually exclusive |
No
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Arm title
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Oleogel-S10 and non-adhesive wound dressing | |||||||||
Arm description |
One half of an EB wound ≥10 cm2 and ≤200 cm2 in size or 1 EB wound ≥5 cm2 in size was treated with Oleogel-S10 and non-adhesive wound dressing. | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
Oleogel-S10
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Gel
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Routes of administration |
Cutaneous use, Topical use
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Dosage and administration details |
The eligible wound (half) was topically treated with 1 cm or 125 µL or 115 mg Oleogel-S10 per cm2 wound area (corresponds to thickness of approximately 1 mm or 0.04 inches) and covered with a non-adhesive wound dressing (Mepilex®) on Day 0. Oleogel-S10 was administered at wound dressing changes about every 24 to 48 hours until discharge from hospital or until the end of treatment at Day 14 in ‘recent wounds’ or Day 28 in ‘chronic wounds’.
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Arm title
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Non-adhesive wound dressing only | |||||||||
Arm description |
Standard of care | |||||||||
Arm type |
Non-active comparator | |||||||||
Investigational medicinal product name |
Non-adhesive wound dressing
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Investigational medicinal product code |
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Other name |
Mepilex® soft silicone faced polyurethane foam dressing
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Pharmaceutical forms |
Cutaneous patch
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Routes of administration |
Topical use
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Dosage and administration details |
The eligible wound (half) was covered with a non-adhesive wound dressing only (Mepilex®) as control. Wound dressings were changed about every 24 to 48 hours until discharge from hospital or until the end of treatment at Day 14 in ‘recent wounds’ or Day 28 in ‘chronic wounds’.
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| Notes [1] - The roles blinded appear inconsistent with a simple blinded trial. Justification: Treatment was open to study subjects and investigators, but independent assessors were blind to treatment and evaluated efficacy based on chronological series of cropped and coded photographs by wound (half). |
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Baseline characteristics reporting groups
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Reporting group title |
Oleogel-S10 and non-adhesive wound dressing
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Reporting group description |
One half of an EB wound ≥10 cm2 and ≤200 cm2 in size or 1 EB wound ≥5 cm2 in size was treated with Oleogel-S10 and non-adhesive wound dressing. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Non-adhesive wound dressing only
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Reporting group description |
Standard of care | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Oleogel-S10 and non-adhesive wound dressing
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Reporting group description |
One half of an EB wound ≥10 cm2 and ≤200 cm2 in size or 1 EB wound ≥5 cm2 in size was treated with Oleogel-S10 and non-adhesive wound dressing. | ||
Reporting group title |
Non-adhesive wound dressing only
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Reporting group description |
Standard of care | ||
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End point title |
Difference (intra-individual) in reepithelialisation of wound (halves) at Day 14 in ‘recent wounds’ or Day 28 in ‘chronic wounds’ | ||||||||||||||||||
End point description |
The primary end point was the progress of reepithelialisation from baseline to either Day 14 (‘recent wounds’) or Day 28 (‘chronic wounds’) of the EB wound (half) treated with Oleogel-S10 and non-adhesive wound dressing (Mepilex®) compared to the other wound (half) covered with non-adhesive wound dressing only (intra-individual comparison). Two independent experts were blind to treatment and assessed efficacy based on chronological series of cropped and coded photographs by wound (half) that were taken before start of treatment, during wound dressing changes and at the end of treatment on Day 14/Day 28. They evaluated each series and decided whether 1 wound (half) reepithelialised faster than the other (‘winner’), or whether there was no difference in reepithelialisation.
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End point type |
Primary
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End point timeframe |
Within 14 days in ‘recent wounds’, within 28 days in ‘chronic wounds’; photographs were taken at wound dressing changes about every 24 to 48 hours until the end of treatment at Day 14 in ‘recent wounds’ or Day 28 in ‘chronic wounds’.
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| Notes [1] - As 2 subjects received 2 cycles of treatment each, 12 wounds were treated with study medication. [2] - As 2 subjects received 2 cycles of treatment each, 12 wounds were treated with study medication. |
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Statistical analysis title |
Analysis for primary endpoint | ||||||||||||||||||
Statistical analysis description |
The intra-individual difference in reepithelialisation of wound (halves) was tested using a two-sided exact binomial test. The test was performed at a significance level of 5% for the null-hypothesis of no difference δ = 0 against the hypotheses δ ≠ 0: H0: δ = 0 H1: δ ≠ 0
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Comparison groups |
Oleogel-S10 and non-adhesive wound dressing v Non-adhesive wound dressing only
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Number of subjects included in analysis |
20
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Analysis specification |
Post-hoc
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Analysis type |
superiority [3] | ||||||||||||||||||
P-value |
= 0.008 [4] | ||||||||||||||||||
Method |
Two-sided exact binomial test | ||||||||||||||||||
Confidence interval |
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| Notes [3] - 12 wounds in 10 subjects (intra-individual comparison; 2 cycles of treatment in 2 subjects) were evaluated by assessors that were blind to treatment. Wounds that were either evaluated controversially (n=2) or as being equal (n=2) were excluded from the analysis of the primary efficacy variable. [4] - Oleogel-S10 + non-adhesive wound dressing (Mepilex®) accelerated the reepithelialisation significantly (8 of 8 decided cases; p=0.008, binomial test) compared to non-adhesive wound dressing only (0 of 8 decided cases). |
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End point title |
Difference (intra-individual) in median percentage of wound epithelialisation | ||||||||||||||||||
End point description |
The secondary endpoint was the intra-individual difference in median percentage of wound epithelialisation at Day 7±1 and at Day 14±1. Sizes of wound areas were measured using a digital wound evaluation program from the EB Centre at the Department of Dermatology, University Medical Centre Freiburg.
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End point type |
Secondary
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End point timeframe |
Day 7±1, Day 14±1
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| Notes [5] - As 2 subjects received 2 cycles of treatment each, 12 wounds were treated with study medication. [6] - As 2 subjects received 2 cycles of treatment each, 12 wounds were treated with study medication. |
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Statistical analysis title |
Secondary analysis | ||||||||||||||||||
Statistical analysis description |
The intra-individual difference in median percentage of wound epithelialisation was tested using a two-sided Wilcoxon test.
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Comparison groups |
Oleogel-S10 and non-adhesive wound dressing v Non-adhesive wound dressing only
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Number of subjects included in analysis |
20
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Analysis specification |
Post-hoc
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Analysis type |
superiority [7] | ||||||||||||||||||
P-value |
= 0.21 [8] | ||||||||||||||||||
Method |
Wilcoxon (Mann-Whitney) | ||||||||||||||||||
Confidence interval |
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| Notes [7] - On Day 7±1 the median wound epithelialisation was 69.7% (min. 17.3%; max. 90.4%) in areas treated with Oleogel-S10 + non-adhesive wound dressing compared to 57.4% (min. 10.0%; max. 81.3%) in areas treated with non-adhesive wound dressing only (p=0.21, Wilcoxon-test). [8] - Day 7±1 |
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Statistical analysis title |
Secondary analysis | ||||||||||||||||||
Statistical analysis description |
The intra-individual difference in median percentage of wound epithelialisation was tested using a two-sided Wilcoxon test.
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Comparison groups |
Oleogel-S10 and non-adhesive wound dressing v Non-adhesive wound dressing only
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Number of subjects included in analysis |
20
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Analysis specification |
Post-hoc
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Analysis type |
superiority [9] | ||||||||||||||||||
P-value |
= 0.33 [10] | ||||||||||||||||||
Method |
Wilcoxon (Mann-Whitney) | ||||||||||||||||||
Confidence interval |
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| Notes [9] - On Day 14±1 the median wound epithelialisation was 87.7% (min. 2.7%; max. 100.0%) in areas treated with Oleogel-S10 + non-adhesive wound dressing compared to 79.2% (min. 0.0%; max. 98.3%) in areas treated with non-adhesive wound dressing only (p=0.33, Wilcoxon-test). [10] - Day 14±1 |
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Adverse events information
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Timeframe for reporting adverse events |
Adverse events were recorded from start of study treatment to completion of study treatment.
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Assessment type |
Non-systematic | ||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||
Dictionary version |
10.0
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Reporting groups
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Reporting group title |
Safety population
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Reporting group description |
All subjects who received at least 1 dose of Oleogel-S10 were included in the safety population. | ||||||||||||||||||||||||||||
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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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03 Mar 2011 |
Implementation of an undecided efficacy assessment (no difference in epithelialisation) and more precise definition of statistical evaluation in case of controversial assessments |
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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. | |||
| Small sample size, subjects with dystrophic Epidermolysis bullosa only, difficult wound size analysis at fixed study days due to several episodes of re-trauma in both intervention and control wounds | |||
