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Oleogel-S10 in Wound Healing of Split-Thickness Skin Graft Donor Sites (BSG-12) (BSG-12)

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ClinicalTrials.gov Identifier: NCT01807650
Recruitment Status : Completed
First Posted : March 8, 2013
Results First Posted : July 19, 2018
Last Update Posted : July 19, 2018
Sponsor:
Information provided by (Responsible Party):
Amryt Pharma ( Birken AG )

Tracking Information
First Submitted Date  ICMJE March 5, 2013
First Posted Date  ICMJE March 8, 2013
Results First Submitted Date  ICMJE July 18, 2016
Results First Posted Date  ICMJE July 19, 2018
Last Update Posted Date July 19, 2018
Study Start Date  ICMJE March 2013
Actual Primary Completion Date September 2013   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 17, 2018)
Intra-individual Difference in Time to Wound Closure [ Time Frame: 2 to 4 weeks ]
Intra-individual difference in time to wound closure between wound halves, either treated with Oleogel-S10 and non-adhesive wound dressing or treated with non-adhesive wound dressing only. 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. Difference in time to wound closure was calculated for every individual participant as [time taken for wound half treated with Oleogel-S10 to close] - [time taken for wound half treated with non-adhesive wound dressing to close], i.e., results below 0 indicate earlier wound closure of Oleogel-S10 treatment. The overall mean difference in time to wound closure was calculated based on all mean differences in time to wound closure of individual participants. Hence, primary outcome data derived from mean difference in time to wound closure by participant.
Original Primary Outcome Measures  ICMJE
 (submitted: March 7, 2013)
Intra-individual Difference in Time to Wound Closure [ Time Frame: 2-4 weeks ]
Intra-individual difference in time to wound closure between wound halves, either treated with Oleogel-S10 and non-adhesive wound dressing or treated with non-adhesive wound dressing alone
Change History Complete list of historical versions of study NCT01807650 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: July 17, 2018)
  • Time From Surgery Until Wound Closure is Achieved [ Time Frame: 2 to 4 weeks ]
    Time from surgery until wound closure is achieved, separately for wound halves treated with Oleogel-S10 and non-adhesive wound dressing vs. non-adhesive wound dressing only. While outcome measure 1 (intra-individual difference in time to wound closure) was calculated based on mean intra-individual difference in time to wound closure in 110 participants with missing values replaced by a value of 0, for outcome measure 2 missing values were not replaced. For 2 of the 110 wounds data were missing, thus the reported values are calculated from 108 STSG donor site wound halves by intervention (Oleogel-S10 and non-adhesive wound dressing vs. non-adhesive wound dressing only).
  • Percentage of Participants With Earlier Healing [ Time Frame: 2 to 4 weeks ]
    Percentage of participants with earlier healing of wound area treated with Oleogel-S10 and non-adhesive wound dressing compared to non-adhesive wound dressing only
  • Percentage of Participants With Wound Closure at Different Time Points [ Time Frame: 2 to 4 weeks ]
    For separate time points (Day 7, Day 10, Day 14, Day 18, Day 21, and Day 28), the frequencies of wound areas which have reached wound closure were calculated.
  • Percentage of Wound Epithelialization at Different Time Points as Assessed by the Investigator [ Time Frame: 2 to 4 weeks ]
    A study team member assessed the progress of wound healing by treatment regimen and noted the degree of epithelialization (expressed in percent of the original wound size) at wound dressing changes on Day 7, Day 10, Day 14, Day 18, Day 21, and Day 28.
  • Likert Scale Rating of Efficacy [ Time Frame: 2 to 4 weeks ]
    Participants and investigators were asked to grade the efficacy of Oleogel-S10 and non-adhesive wound dressing versus non-adhesive wound dressing only on a 5-point Likert scale (treatment with Oleogel-S10 is much more effective, treatment with Oleogel-S10 is more effective, both treatments have the same efficacy, non-adhesive wound dressing only is more effective, non-adhesive wound dressing only is much more effective).
  • Cosmetic Outcome at 3 and 12 Months After Surgery, Respectively [ Time Frame: 3 months and 12 months ]
    Blinded photographic evaluation which wound half resembles more closely the surrounding skin with regard to texture, redness, growth of hair, and pigmentation.
  • Likert Scale Rating of Tolerability [ Time Frame: 2 to 4 weeks ]
    Participants and investigators were asked to evaluate the tolerability of Oleogel-S10 and non-adhesive wound dressing versus non-adhesive wound dressing only (standard of care) on a 5-point Likert scale (treatment with Oleogel-S10 is much better tolerated, treatment with Oleogel-S10 is better tolerated, both treatments are equally well tolerated, non-adhesive wound dressing only is better tolerated, non-adhesive wound dressing only is much better tolerated).
  • Pharmacokinetic (PK) Data (Number of Plasma Samples With Measurable Betulin Concentration) [ Time Frame: up to 4 weeks ]
    Systemic presence/concentration of betulin in blood plasma samples. Plasma samples were collected in weekly intervals and at the end of treatment (when wound closure was achieved or at Day 28). Samples were analysed in a central laboratory with a validated LC-MS/MS method with a lower limit of quantification (LLOQ) of 1 ng/mL.
  • Pharmacokinetic (PK) Data (Plasma Betulin Concentration) [ Time Frame: up to 4 weeks ]
    Systemic presence/concentration of betulin in blood plasma samples - values for the number of samples with measurable values in samples above the lower limit of quantification (LLOQ) of 1 ng/mL
  • Frequency of Adverse Events [ Time Frame: Day 0 (start of treatment) until end of treatment (Day 28 or earlier if full wound closure was achieved earlier). ]
  • Severity of Adverse Events [ Time Frame: Day 0 (start of treatment) until end of treatment (Day 28 or earlier if full wound closure was achieved earlier). ]
    Adverse Events were graded according to the National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events (CTCAE) as being mild (NCI CTCAE Grade 1), moderate (NCI CTCAE Grade 2), severe (NCI CTCAE Grade 3), life-threatening (NCI CTCAE Grade 4) or death (NCI CTCAE Grade 5).
  • Adverse Events by Relationship to Study Medication [ Time Frame: Day 0 (start of treatment) until end of treatment (Day 28 or earlier if full wound closure was achieved earlier). ]
    Adverse events were assessed as being 'unlikely', 'possibly' or 'probably' related to study medication, 'not related' to study medication or the relationship to study medication was rated as 'unknown'.
Original Secondary Outcome Measures  ICMJE
 (submitted: March 7, 2013)
  • Time From Surgery Until Wound Closure is Achieved [ Time Frame: 2-4 weeks ]
    Time from surgery until wound closure is achieved, separately for wound halves treated with Oleogel-S10 and non-adhesive wound dressing vs. non-adhesive wound dressing alone
  • Percentage of patients with earlier healing [ Time Frame: 2-4 weeks ]
    Percentage of patients with earlier healing of wound area treated with Oleogel-S10 and non-adhesive wound dressing compared to non-adhesive wound dressing alone
  • Percentage of patients with wound closure at different time points [ Time Frame: 2-4 weeks ]
  • Percentage of Wound Epithelialization at Different Time Points as Assessed by the Investigator [ Time Frame: 2-4 weeks ]
  • Likert Scale Rating of Efficacy [ Time Frame: 2-4 weeks ]
    By direct comparison of the separate simultaneous treatments for the two wound halves, patients and investigators, respectively, are asked to grade the efficacy of Oleogel-S10 Versus Standard of Care on a questionnaire with a 5-point graded visual analogue scale
  • Cosmetic outcome after 3 and 12 months after surgery [ Time Frame: 3 months and 12 months ]
    Blinded photographic evaluation which wound half resembles more closely the surrounding skin with regard to texture, redness, growth of hair, and pigmentation.
  • Likert scale rating of tolerance [ Time Frame: 2-4 weeks ]
    By direct comparison of the separate simultaneous treatments for the two wound halves, patients and investigators, respectively, are asked to provide their opinion on the tolerance of Oleogel-S10 Versus Standard of Care on a questionnaire with a 5-point graded visual analogue scale
  • PK data (betulin concentration in blood) [ Time Frame: 2-4 weeks ]
    Systemic presence/concentration of betulin in blood plasma samples
  • Adverse events (frequency, severity, relation to study medication) [ Time Frame: assessed during treatment period (expected duration 2-4 weeks) and 3-months follow-up visit ]
    Assessment of adverse events
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Oleogel-S10 in Wound Healing of Split-Thickness Skin Graft Donor Sites (BSG-12)
Official Title  ICMJE Open, Blindly Evaluated, Prospective, Controlled, Randomized, Multicenter Phase III Clinical Trial to Compare Intra-individually the Efficacy and Tolerance of Oleogel-S10 Versus Standard of Care in Accelerating the Wound Healing of Split-Thickness Skin Graft Donor Sites
Brief Summary The main purpose of this phase III clinical trial was to show safety and efficacy of Oleogel-S10 in accelerating the wound healing of Split-Thickness Skin Graft (STSG) donor sites.
Detailed Description

Oleogel-S10 has shown efficacy and was well tolerated in previous clinical trials in participants with skin lesions. Especially the results in a previous study with STSG donor sites suggested that Oleogel-S10 should be efficacious and safe in the treatment of superficial wounds.

The present phase III clinical trial in STSG donor sites was initiated to demonstrate wound healing progress, i.e., the time to healing and the grade of epithelialization of the wound.

In this study, STSG donor sites were separated into 2 wound halves. Randomly assigned, 1 wound half was treated with Oleogel-S10 and non-adhesive wound dressing, the other wound half with non-adhesive wound dressing only (standard of care).

Wound healing progress was documented by photos which were assessed by expert reviewers blinded to the treatment of the wound halves.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Single (Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Wounds
Intervention  ICMJE
  • Drug: Oleogel-S10, non-adhesive wound dressing
    1 cm or 100 mg Oleogel-S10 per cm2 wound area (corresponds to thickness of approximately 1 mm or 0.04 inch) every 3 to 4 days until 95% epithelialization of the wound or end of treatment at Day 28
    Other Name: Episalvan®
  • Device: Non-adhesive wound dressing only
    Soft silicone faced polyurethane foam dressing such as Mepilex® only every 3 to 4 days until 95% epithelialization of the wound or end of treatment at Day 28
    Other Name: Mepilex®
Study Arms  ICMJE
  • Experimental: Oleogel-S10, non-adhesive wound dressing
    A split-thickness skin graft (STSG) donor site wound >15cm2 in size was divided in 2 halves. One half was randomized to Oleogel-S10 treatment and non-adhesive wound dressing (intra-individual comparison). Oleogel-S10 was administered (1 cm or 100 mg per cm2 wound area corresponding to thickness of about 1 mm or 0.04 inch) every 3 to 4 days until 95% epithelialization of the wound or end of treatment at Day 28.
    Intervention: Drug: Oleogel-S10, non-adhesive wound dressing
  • Non-adhesive wound dressing only
    A STSG donor site wound >15cm2 in size was divided in 2 halves. One half was randomized to treatment with non-adhesive wound dressing only (intra-individual comparison). Non-adhesive wound dressings are standard of care (SOC) in the treatment of STSG donor sites. Wound dressings were changed every 3 to 4 days.
    Intervention: Device: Non-adhesive wound dressing only
Publications * Barret JP, Podmelle F, Lipový B, Rennekampff HO, Schumann H, Schwieger-Briel A, Zahn TR, Metelmann HR; BSH-12 and BSG-12 study groups. Accelerated re-epithelialization of partial-thickness skin wounds by a topical betulin gel: Results of a randomized phase III clinical trials program. Burns. 2017 Sep;43(6):1284-1294. doi: 10.1016/j.burns.2017.03.005. Epub 2017 Apr 8.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: April 2, 2015)
112
Original Estimated Enrollment  ICMJE
 (submitted: March 7, 2013)
105
Actual Study Completion Date  ICMJE September 2014
Actual Primary Completion Date September 2013   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Participants at least 18 years old who have provided written informed consent
  • Presenting a split-thickness skin graft donor site wound with a minimum size of 15 cm2 and with a minimum width of 3 cm.
  • Participant was able to understand the Informed Consent Form (ICF) provided and was prepared to comply with all study requirements, including the following: Visiting the trial site for wound dressing change and photo documentation every third or fourth day until both wound halves were closed (but no longer than 28 days after surgery).
  • Willing to perform all necessary wound dressing changes at the trial site. Also the participant needed to agree to return to site for 3 and 12 months follow-up visits.
  • Women of childbearing potential who were in the period between menarche and menopause needed to apply a highly effective method of birth control (failure rate less than 1% per year when used consistently and correctly (e.g., implants, injectables, combined oral contraceptives, some intrauterine contraceptive devices [IUDs], sexual abstinence, or a vasectomized partner). Birth control method needed to have been applied for at least 1 monthly cycle prior to first administration of study drug, be maintained during the study treatment phase and continued for at least 30 days after the last administration of study drug. Sexually active, non-vasectomized men needed to use a barrier method (condoms) during the treatment phase of this clinical trial.

Exclusion Criteria:

  • Diseases or conditions that could, in the opinion of the Investigator, interfere with the assessment of safety or efficacy.
  • A skin disorder that was chronic or currently active and which the Investigator considered would adversely affect the healing of the acute wounds or involved the areas to be examined in this trial.
  • A history of clinically significant hypersensitivity to any of the drugs, surgical dressings or excipients to be used in this trial.
  • Known multiple allergic disorders.
  • Taking, or have taken, any investigational drugs within 3 months prior to the screening visit.
  • Pregnant or breast feeding women were not allowed to participate in the study.
  • Inappropriate to participate in the study, for any reason, in the opinion of the investigator.
  • Mental incapacity or language barriers precluding adequate understanding the ICF or co-operation or willingness to follow study procedures.
  • Previous participation in this study.
  • Employee at the investigational site, relative or spouse of the investigator.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE France,   Greece,   Latvia,   Spain
Removed Location Countries Russian Federation
 
Administrative Information
NCT Number  ICMJE NCT01807650
Other Study ID Numbers  ICMJE BSG-12
2012-003390-26 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Amryt Pharma ( Birken AG )
Study Sponsor  ICMJE Birken AG
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Juan Pedro Barret Nerin, MD Hospital Universitari Vall d´Hebron, Barcelona, Spain
PRS Account Amryt Pharma
Verification Date July 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP