Clinical Trial Results:
Open, Blindly Evaluated, Prospective, Controlled, Randomised, Multicentre Phase III Clinical Trial to Compare Intra-individually the Efficacy and Tolerance of Oleogel-S10 versus Standard of Care in Accelerating the Healing of Grade 2a Partial-Thickness Burn Wounds
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Summary
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EudraCT number |
2012-000362-38 |
Trial protocol |
DE SE GB |
Global end of trial date |
04 Jul 2014
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Results information
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Results version number |
v1(current) |
This version publication date |
20 Jun 2016
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First version publication date |
14 Aug 2015
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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 |
BBW-11
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT01657292 | ||
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 |
Head of pharmaceutical development, Birken AG, T.Zahn@birken.eu
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Scientific contact |
Head of pharmaceutical development, Birken AG, T.Zahn@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 |
07 Apr 2015
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
04 Jul 2014
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Global end of trial reached? |
Yes
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Global end of trial date |
04 Jul 2014
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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 efficacy and tolerance of Oleogel-S10 with fatty gauze as wound dressing versus standard of care (defined as Octenilin wound gel) with fatty gauze as wound dressing in accelerating the healing of Grade 2a burns.
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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 Conference 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 |
Fatty gauze wound dressing. | ||
Evidence for comparator |
Octenilin wound gel, an antiseptic octenidine formulated as hydrogel, was used as reference because it represents a standard of care for treating patients with burn injuries. | ||
Actual start date of recruitment |
31 Aug 2012
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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 |
Sweden: 3
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Country: Number of subjects enrolled |
United Kingdom: 28
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Country: Number of subjects enrolled |
Germany: 31
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Country: Number of subjects enrolled |
Switzerland: 4
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Worldwide total number of subjects |
66
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EEA total number of subjects |
62
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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) |
60
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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 |
Study participants were enrolled from 31-Aug-2012 to 10-Jul-2013, in 10 clinical centres in 4 countries: Germany (4 centres), Uk (3 centres), Sweden (2 centres), and Switzerland (1 centre). | ||||||||||||||||||||||||
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Pre-assignment
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Screening details |
During screening the following was performed: check for inclusion/exclusion criteria, concomitant medication, pregnancy, demographics, medical history and signing informed consent form. 66 subjects were screened of which 5 violated eligibilty criteria and thus 61 subjects were treated. | ||||||||||||||||||||||||
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Pre-assignment period milestones
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Number of subjects started |
66 | ||||||||||||||||||||||||
Number of subjects completed |
61 | ||||||||||||||||||||||||
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Pre-assignment subject non-completion reasons
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Reason: Number of subjects |
Violation of eligibility criteria: 4 | ||||||||||||||||||||||||
Reason: Number of subjects |
Language and social reasons: 1 | ||||||||||||||||||||||||
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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 |
Randomised - controlled
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Blinding used |
Single blind | ||||||||||||||||||||||||
Roles blinded |
Assessor [1] | ||||||||||||||||||||||||
Blinding implementation details |
Treatments were intra-individually compared. Either 2 halves of 1 wound or 2 wounds of similar size and depth were used per subject. Treatment was assigned using a tamper-proof randomisation method. Treatment was open to study subjects and investigators, but assessment of efficacy was primarily based on blinded photo evaluation. Special care was taken to ensure blinding i.e. all markings were removed.
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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 | ||||||||||||||||||||||||
Arm description |
A suitable study wound was divided into 2 halves of equal size or 2 separate wounds of similar size and depth were used for evaluation. One randomly assigned wound or wound half was treated with Oleogel-S10 ointment and covered with fatty gauze. | ||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||
Investigational medicinal product name |
Oloegel-S10
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Ointment
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Routes of administration |
Topical use
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Dosage and administration details |
1 cm of ointment string Oleogel-S10 (approximately 100 mg) per cm² of wound (i.e. approximately 1 mm thick), applied at every wound dressing change (latest every second day).
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Arm title
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Octenilin | ||||||||||||||||||||||||
Arm description |
The other wound or wound half was treated with Octenilin wound gel and covered with fatty gauze. | ||||||||||||||||||||||||
Arm type |
Active comparator | ||||||||||||||||||||||||
Investigational medicinal product name |
Octenilin wound gel
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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 |
Topical use
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Dosage and administration details |
Administered at each wound dressing change (latest every second day).
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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 assessment of efficacy was primarily based on blinded photo evaluation. |
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Baseline characteristics reporting groups [1]
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Reporting group title |
Treatment period
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Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Notes [1] - The number of subjects reported to be in the baseline period is not equal to the worldwide number of subjects enrolled in the trial. It is expected that these numbers will be the same. Justification: Of the 66 subjects enrolled only wounds of 61 subjects were randomised and treated. Baseline characteristics are provided for these 61 subjects included in the safety and efficacy analyses. |
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End points reporting groups
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Reporting group title |
Oleogel-S10
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Reporting group description |
A suitable study wound was divided into 2 halves of equal size or 2 separate wounds of similar size and depth were used for evaluation. One randomly assigned wound or wound half was treated with Oleogel-S10 ointment and covered with fatty gauze. | ||
Reporting group title |
Octenilin
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Reporting group description |
The other wound or wound half was treated with Octenilin wound gel and covered with fatty gauze. | ||
Subject analysis set title |
ITT
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Subject analysis set type |
Intention-to-treat | ||
Subject analysis set description |
The ITT analysis set included all subjects who were treated at least once, i.e. who received any dose of Oleogel-S10 or Octenilin wound gel. If the application of any study medication was not certain, the subjects was included in the ITT analysis set. Patients whose wound halves were not treated with the intended (i.e. randomised) treatment regimen were excluded from the ITT analysis set.
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End point title |
Percentage of patients with earlier healing (at least 95% epithelialisation) of the wound half treated with Oloegel-S10 compared to standard of care (Octenilin wound gel), as evaluated by the majority decision of 3 independent, blinded experts | |||||||||||||||
End point description |
The blinded experts indicated for each subject whether the wounds or wound halves showed differences in time to wound closure (at least 95% epithelialisation) and, if such a difference was observed, which wound half healed faster. The majority decision of the 3 readers was used for evaluation.
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End point type |
Primary
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End point timeframe |
Photo acquired at every wound dressing change (at least every second day until full wound closure was achieved. At maximum Day 21 if wound closure was not achieved before).
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Statistical analysis title |
Primary analysis | |||||||||||||||
Statistical analysis description |
The following hypotheses were tested: H0: s0 ≤0.5 and H1: s0 >0.5 (with s0=rate of superiority of Oleogel-S10) using a 1-sided, exact binomial test with a significance level of 0.025. A total of 57 subjects were included in the analysis (intra-individual comparison). Earlier healing was shown for Oleogel-S10 treated vs Octenilin treated wound halves in 30 subjects (85.7%). Earlier healing of the Octenilin treated vs the Oleogel-S10 treated wound halves was observed in 5 subjects (14.3%).
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Comparison groups |
Oleogel-S10 v Octenilin
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Number of subjects included in analysis |
114
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Analysis specification |
Pre-specified
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Analysis type |
superiority | |||||||||||||||
P-value |
< 0.0001 [1] | |||||||||||||||
Method |
Exact binomial test | |||||||||||||||
Confidence interval |
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| Notes [1] - Based on 1-sided, exact binomial test evaluating the rate of superiority of Oleogel-S10 being >0.5. The analysis is based only on the 35 subjects for whom a difference in healing was noted. |
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Adverse events information
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Timeframe for reporting adverse events |
Day 0 (start of treatment) till end of treatment (Day 21 or earlier if full wound closure was achieved earlier, or later, if the investigator decided to change medication and/or treatment due to unsatisfying wound closure after Day 21).
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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 |
15.1
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Reporting groups
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Reporting group title |
Safety analysis set
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Reporting group description |
The SAF included all subjects who were treated at least once, i.e. who received any dose of Oleogel-S10 or Octenilin wound gel. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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? 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 | |||
