Oleogel-S10 in Wound Healing of Inherited Epidermolysis Bullosa (BEB-10)

• Sponsor: Birken AG (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01294241
• Collaborator: (none)
• Enrollment: 10
• Location: 1
• Arms: 2
• Duration (Months): 7
• Patients Per Site Per Month: 1.4

Study Details

Study Description

Brief Summary

The purpose of this study was to compare intra-individually the reepithelialization 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.

Condition or Disease	Intervention/Treatment	Phase
Inherited Epidermolysis Bullosa	Drug: Oleogel-S10; Device: Mepilex® soft silicone faced polyurethane foam dressing	Phase 2

Detailed Description

This study was designed as an open-label, prospective, controlled, blindly evaluated, monocentric phase II case series documentation in patients with inherited Epidermolysis bullosa (EB). The investigator either identified 1 EB wound ≥10 cm2 and ≤200 cm2 in size and divided it into 2 halves or selected 2 comparable wounds of ≥5 cm2 each. One (half of the) EB wound was treated with Oleogel-S10 and non-adhesive wound dressing. The other 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'. This was an open-label study. The investigator, the participant, 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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 10 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: Single (Outcomes Assessor)
• Masking Description: Blinded comparison of wound photo series by two independent experts
• Primary Purpose: Treatment
• Official Title: 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 Epithelialization of Skin Lesions of Patients With Epidermolysis Bullosa Hereditaria
• Study Start Date: Nov 1, 2010
• Actual Primary Completion Date: Jun 1, 2011
• Actual Study Completion Date: Jun 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Oleogel-S10 The eligible wound (half) was topically treated with Oleogel-S10 and covered with a non-adhesive wound dressing (Mepilex®) on Day 0. 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'.	Drug: Oleogel-S10; 1 cm or 125 µL or 115 mg Oleogel-S10 per cm2 wound area (corresponds to thickness of approximately 1 mm or 0.04 inch) 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'.; Other Names: Sericare® ; Device: Mepilex® soft silicone faced polyurethane foam dressing; Mepilex® soft silicone faced polyurethane foam dressing was 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'.; Other Names: Cutaneous patch
Other: Non-adhesive wound dressing Mepilex® soft silicone faced polyurethane foam dressing was used as non-active comparator. The eligible wound (half) was covered with Mepilex® as control on Day 0. 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'.	Device: Mepilex® soft silicone faced polyurethane foam dressing; Mepilex® soft silicone faced polyurethane foam dressing was 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'.; Other Names: Cutaneous patch

Outcome Measures

Primary Outcome Measures

1. Intra-individual Difference in Reepithelialization of Wound (Halves) at Day 14 in 'Recent Wounds' or Day 28 in 'Chronic Wounds' [14 days for 'recent wounds', 28 days for 'chronic wounds']

   The primary end point was the progress of reepithelialization 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®) intra-individually 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) reepithelialized faster than the other ('winner'), or whether there was no difference in reepithelialization.

Secondary Outcome Measures

1. Percentage of Wound Epithelialization at Day 7±1 [Day 7±1]

   The secondary endpoint was the intra-individual difference in median percentage of wound epithelialization at Day 7±1. Sizes of wound areas were measured using a digital wound evaluation program from the EB Center at the Department of Dermatology, University Medical Center Freiburg.

2. Percentage of Wound Epithelialization at Day 14±1 [Day 14±1]

   The secondary endpoint was the intra-individual difference in median percentage of wound epithelialization at Day 14±1. Sizes of wound areas were measured using a digital wound evaluation program from the EB Center at the Department of Dermatology, University Medical Center Freiburg.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 1 Year to 95 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Patients aged 1-95 years

2. Patient and/or his/her legal representative was informed, read and understood the patient information/informed consent form and gave written informed consent

3. Patients with inherited EB with at least 1 skin lesion between 10 cm2 and 200 cm2 (alternatively 2 comparable lesions of at least 5 cm2 each)

4. Patient and/or his/her legal representative was able and willing to follow study procedures and instructions including the following:

5. Application of Oleogel-S10 on (1 half of) the wound at every wound dressing change

6. Regular visits during the treatment period (14 days in 'recent wounds' to 28 days in 'chronic wounds')

7. Negative pregnancy test in women of childbearing potential within 7 days before start of treatment

8. Women of childbearing potential agreed to use an effective method of contraception (Pearl Index < 1, e.g. hormonal contraception including the combined oral contraceptive pill, the transdermal patch, and the contraceptive vaginal ring, intrauterine devices or sterilization) during treatment and for at least 6 months thereafter

9. Men of procreative capacity agreed to use an effective method of contraception during treatment and for at least 6 months thereafter

Exclusion Criteria:

1. Systemic treatment with steroids during the last 30 days

2. Uncontrolled diabetes mellitus or diabetic ulcers

3. Diseases or conditions that could, in the opinion of the investigator, interfere with the assessment of safety, tolerance or efficacy

4. Skin disorders adversely affecting wound healing or involving the areas eligible for study treatment

5. Hypersensitivity to the trial medication or surgical dressings to be used

6. Multiple allergic disorders

7. Administration of investigational drugs within 3 months before screening

8. Investigations or changes in management for an existing medical condition

9. Low probability to complete the study per protocol for whatever reason

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	EB Center at the Department of Dermatology, University Medical Center	Freiburg		Germany	79104

Sponsors and Collaborators

• Birken AG

Investigators

• Principal Investigator: Agnes Schwieger-Briel, MD, University Medical Center Freiburg

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Birken AG
• ClinicalTrials.gov Identifier: NCT01294241
• Other Study ID Numbers: BEB-10
• First Posted: Feb 11, 2011
• Last Update Posted: Jan 23, 2018
• Last Verified: May 1, 2017

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Birken AG: Epidermolysis bullosa; Wound healing; Epithelialization
• Additional relevant MeSH terms: Epidermolysis Bullosa

Study Results

Participant Flow

Recruitment Details	Participants were enrolled from 03 Nov 2010 to 14 Jun 2011 at 1 center (University Medical Center Freiburg) in 1 country (Germany).
Pre-assignment Detail	12 wounds in 10 participants (2 cycles of treatment in 2 participants) were treated with study medication. The reepithelialization was compared intra-individually in either 2 halves of an Epidermolysis bullosa (EB) wound ≥10 cm2 and ≤200 cm2 in size or in 2 EB wounds ≥5 cm2 in size, i.e. the total number of participants was 10 in the overall study.

Arm/Group Title	All Study Participants
Arm/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. The other wound (half) was covered with a non-adhesive wound dressing only (Mepilex®) as control (intra-individual comparison).
Period Title: Overall Study
STARTED	10
COMPLETED	10
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	All Study Participants
Arm/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. The other wound (half) was covered with a non-adhesive wound dressing only (Mepilex®) as control.
Overall Participants	10
Overall Wounds	12
Age (Count of Participants)
<=18 years	5 50%
Between 18 and 65 years	5 50%
>=65 years	0 0%
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	20
Sex: Female, Male (Count of Participants)
Female	3 30%
Male	7 70%
Region of Enrollment (participants) [Number]
Germany	10 100%

Outcome Measures

1. Primary Outcome

Title	Intra-individual Difference in Reepithelialization of Wound (Halves) at Day 14 in 'Recent Wounds' or Day 28 in 'Chronic Wounds'
Description	The primary end point was the progress of reepithelialization 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®) intra-individually 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) reepithelialized faster than the other ('winner'), or whether there was no difference in reepithelialization.
Time Frame	14 days for 'recent wounds', 28 days for 'chronic wounds'

Outcome Measure Data

Analysis Population Description

12 wounds in 10 participants (intra-individual comparison, 2 cycles of treatment in 2 participants) were evaluated by assessors that were blind to treatment. 'Undecided' wounds that were either evaluated controversially (n=2) or as being equal (n=2) were excluded from the analysis of the primary efficacy variable.

Arm/Group Title	All Study Participants
Arm/Group Description	Intra-individual comparison of two treatments: 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. The other wound (half) was covered with a non-adhesive wound dressing only (Mepilex®) as standard of care control.
Measure Participants	10
Measure Wounds	8
Faster healing of wound treated with Oleogel-S10	8
Faster healing of wound treated with dressing	0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	All Study Participants
	Comments	The intra-individual difference in reepithelialization 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
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	=0.008
	Comments	Post-hoc superiority analysis: Wounds that were either evaluated controversially (n=2) or as being equal (n=2) were excluded from the analysis of the primary efficacy variable.
	Method	Two-sided exact binomial test
	Comments

2. Secondary Outcome

Title	Percentage of Wound Epithelialization at Day 7±1
Description	The secondary endpoint was the intra-individual difference in median percentage of wound epithelialization at Day 7±1. Sizes of wound areas were measured using a digital wound evaluation program from the EB Center at the Department of Dermatology, University Medical Center Freiburg.
Time Frame	Day 7±1

Outcome Measure Data

Analysis Population Description

As 2 participants received 2 cycles of treatment each, 12 wounds were treated with study medication.

Arm/Group Title	Oleogel-S10 and Non-adhesive Wound Dressing	Non-adhesive Wound Dressing Only
Arm/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.	The other half of an EB wound ≥10 cm2 and ≤200 cm2 in size or 1 EB wound ≥5 cm2 in size was treated with non-adhesive wound Dressing only as control.
Measure Participants	10	10
Measure Wounds/wound halves	12	12
Median (Full Range) [Percentage of wound epithelialization]	69.7	57.4

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	All Study Participants
	Comments	The intra-individual difference in median percentage of wound epithelialization was tested using a two-sided Wilcoxon test.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	=0.21
	Comments	Post-hoc superiority analysis
	Method	Wilcoxon (Mann-Whitney)
	Comments

3. Secondary Outcome

Title	Percentage of Wound Epithelialization at Day 14±1
Description	The secondary endpoint was the intra-individual difference in median percentage of wound epithelialization at Day 14±1. Sizes of wound areas were measured using a digital wound evaluation program from the EB Center at the Department of Dermatology, University Medical Center Freiburg.
Time Frame	Day 14±1

Outcome Measure Data

Analysis Population Description

As 2 participants received 2 cycles of treatment each, 12 wounds were treated with study medication.

Arm/Group Title	Oleogel-S10 and Non-adhesive Wound Dressing	Non-adhesive Wound Dressing Only
Arm/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.	The other half of an EB wound ≥10 cm2 and ≤200 cm2 in size or 1 EB wound ≥5 cm2 in size was treated with non-adhesive wound Dressing only as control.
Measure Participants	10	10
Measure Wounds/wound halves	12	12
Median (Full Range) [Percentage of wound epithelialization]	87.7	79.2

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	All Study Participants
	Comments	The intra-individual difference in median percentage of wound epithelialization was tested using a two-sided Wilcoxon test.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.33
	Comments	Post-hoc superiority analysis
	Method	Wilcoxon (Mann-Whitney)
	Comments

Adverse Events

Time Frame	Adverse events were recorded from start of study treatment (Day 0) to completion of study treatment (Day 14/Day 28), i.e. for a period of up to 2 or 4 weeks.
Arm/Group Title	Safety Population
Arm/Group Description	All participants who received at least 1 dose of Oleogel-S10 were included in the safety population. All adverse events were reported for all study participants. Localized adverse events were not separately reported by intervention.
All Cause Mortality
	Safety Population
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Safety Population
	Affected / at Risk (%)	# Events
Total	0/10 (0%)
Other (Not Including Serious) Adverse Events
	Safety Population
	Affected / at Risk (%)	# Events
Total	6/10 (60%)
Infections and infestations
Flu-like syndrome	1/10 (10%)	1
Skin and subcutaneous tissue disorders
Wound area increased due to trauma/wound dressing change	5/10 (50%)	9
Wound infection	1/10 (10%)	1

Limitations/Caveats

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

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.