Phase III Efficacy and Safety Study of Oleogel-S10 in Epidermolysis Bullosa (EASE)

• ClinicalTrials.gov Identifier: NCT03068780
• Recruitment Status: Recruiting
• First Posted: March 3, 2017
• Last Update Posted: November 25, 2019
• Sponsor: Amryt Research Limited
• Information provided by (Responsible Party): Amryt Pharma ( Amryt Research Limited )

Tracking Information

• First Submitted Date: February 27, 2017
• First Posted Date: March 3, 2017
• Last Update Posted Date: November 25, 2019
• Actual Study Start Date: March 29, 2017
• Estimated Primary Completion Date: December 2019 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: July 17, 2018)

Proportion of patients with first complete closure of the EB target wound within 45 days of treatment [ Time Frame: 45±7 days ]

Proportion of patients with first complete closure of the EB target wound (defined as EB partial thickness wound of 10 cm² to 50 cm² in size aged ≥21 days and <9 months) within 45±7 days of treatment with Oleogel-S10 compared to placebo based on clinical assessment by the investigator (the wound will be rated as "closed" at first appearance of complete reepithelialisation without drainage confirmed by a second observation within the following week)

Original Primary Outcome Measures (submitted: February 27, 2017)

Proportion of patients with first complete closure of the EB target wound within 45 days of treatment [ Time Frame: 45±7 days ]

Proportion of patients with first complete closure of the EB target wound (defined as EB partial thickness wound of 10 cm² to 50 cm² in size aged ≥21 days) within 45±7 days of treatment with Oleogel-S10 compared to placebo based on clinical assessment by the investigator (the wound will be rated as "closed" at first appearance of complete reepithelialisation without drainage confirmed by a second observation within the following week)

• Change History: Complete list of historical versions of study NCT03068780 on ClinicalTrials.gov Archive Site

Current Secondary Outcome Measures (submitted: February 27, 2017)

Time to first complete closure of the EB target wound as evidenced by clinical assessment until Day 90±7. [ Time Frame: 90±7 days ]

Time to first complete closure of the EB target wound (defined as EB partial thickness wound of 10 cm² to 50 cm² in size aged ≥21 days) within 90±7 days of treatment with Oleogel-S10 compared to placebo based on clinical assessment by the investigator (the wound will be rated as "closed" at first appearance of complete reepithelialisation without drainage confirmed by a second observation within the following week)

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Phase III Efficacy and Safety Study of Oleogel-S10 in Epidermolysis Bullosa
• Official Title: Double Blind, Randomised, Vehicle Controlled, Phase III, Efficacy and Safety Study With 24-month Open-label Follow up of Oleogel-S10 in Patients With Inherited Epidermolysis Bullosa

Brief Summary

This is a Phase III, Efficacy and Safety Study of Oleogel-S10 in Participants with Inherited Epidermolysis Bullosa (EB).

EB is a rare group of genetic skin fragility disorders characterised by blistering of the skin in response to minor injury. In most cases, onset of EB is at birth or shortly after. All participants affected by any type of EB share the main characteristic of repeatedly developing painful wounds that take days to months to heal. Current treatment of EB is primarily preventative and supportive including protection from mechanical forces by avoiding rubbing, early treatment of wounds to prevent infections, and protection of the wound with adequate non-adhesive dressings to enable healing.

Oleogel-S10 was authorised in 2016 in the European Union for treatment of partial thickness wounds in adults under the brand name Episalvan®. The active pharmaceutical ingredient in Oleogel-S10 is a refined birch bark extract, quantified to 72 to 88% betulin.

This clinical study of Oleogel-S10 in patients with inherited EB has been initiated to investigate whether Oleogel-S10 is effective for treatment of EB wounds and safe in the long term use.

Oleogel-S10 will be compared to a vehicle gel placebo. The placebo is an identical looking sunflower oil gel that does not contain any active substance. The participant will receive either Oleogel-S10 or vehicle gel for a double-blind study phase of 90 days. The probability that the participant will receive Oleogel-S10 is 50%, which means that they have a 1 in 2 chance of receiving Oleogel-S10. However, in the follow-up phase of the study all participants will be treated with Oleogel S10 for a period of 24 months.

This clinical study will be performed in several countries; in total, about 250 participants are expected to participate.

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Care Provider, Investigator); Primary Purpose: Treatment
• Condition: Epidermolysis Bullosa

Intervention

• Drug: Oleogel-S10
  10% birch bark extract in 90% sunflower oil
  Other Name: Episalvan
• Drug: Placebo
  Sunflower oil gel
  Other Name: Vehicle gel

Study Arms

• Experimental: Oleogel-S10
  Intervention: Drug: Oleogel-S10
• Placebo Comparator: Placebo
  Intervention: Drug: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: April 3, 2019): 250
• Original Estimated Enrollment (submitted: February 27, 2017): 164
• Estimated Study Completion Date: February 2022
• Estimated Primary Completion Date: December 2019 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Male and female patients with the following subtypes of inherited EB: junctional EB (JEB), dystrophic EB (DEB), and Kindler syndrome aged ≥21 days,
• Patients with an EB target wound (i.e., EB partial thickness wound of 10 cm² to 50 cm² in size aged ≥21 days and <9 months),
• Patient and/or his/her legal representative has/have been informed, has/have read and understood the patient information/informed consent form, and has/have given written informed consent,
• Patient and/or his/her legal representative must be able and willing to follow study procedures and instructions.

Exclusion Criteria:

• Patient has EB simplex
• EB target wound with clinical signs of local infection,
• Use of systemic antibiotics for wound-related infections within 7 days prior to enrolment,
• Administration of systemic or topical steroids (except for inhaled, ophthalmic or topical applications, such as budesonide suspension for oesophageal strictures [e.g., Pulmicort respules® 0.25 mg/2 mL or 0.5 mg/2 mL]) within 30 days before enrolment,
• Immunosuppressive therapy or cytotoxic chemotherapy within 60 days prior to enrolment,
• Patient has undergone stem cell transplant or gene therapy for the treatment of inherited EB,
• Current and/or former malignancy including basal cell carcinomas and squamous cell carcinomas,
• Enrolment in any interventional study or treated with any investigational drug for any disease within 4 weeks prior to study entry,
• Factors present in the patient and/or his/her legal representative that could interfere with study compliance such as inability to attend scheduled study visits or compliance with home dressing changes,
• Pregnant or nursing women and women of childbearing potential including postmenarchal female adolescents not willing to use an effective form of birth control with failure rates <1% per year (e.g., implant, injectable, combined oral contraceptive, intrauterine contraceptive device, sexual abstinence, vasectomised partner) during participation in the study (and at least 3 months thereafter),
• Patient is a member of the investigational team or his/her immediate family,
• Patient lives in the same household as a study participant.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: Child, Adult, Older Adult
• Accepts Healthy Volunteers: No

Contacts

Contact: Head of Clinical Development; +35315180200; easestudy@amrytpharma.com

Contact: Medical Monitor, MD; medicalmonitor@amrytpharma.com

• Listed Location Countries: Argentina, Australia, Austria, Brazil, Chile, Colombia, Croatia, Czechia, Denmark, France, Georgia, Germany, Greece, Hong Kong, Hungary, Ireland, Israel, Italy, Romania, Russian Federation, Serbia, Singapore, Spain, Switzerland, Ukraine, United Kingdom, United States
• Removed Location Countries: Belgium

Administrative Information

• NCT Number: NCT03068780
• Other Study ID Numbers: BEB-13; 2016-002066-32 ( EudraCT Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Responsible Party: Amryt Pharma ( Amryt Research Limited )
• Study Sponsor: Amryt Research Limited
• Collaborators: Not Provided

Investigators

• Principal Investigator: Johannes S Kern, MD PhD; Melbourne Health

• PRS Account: Amryt Pharma
• Verification Date: November 2019