A Clinical Trial which compare the safety and efficacy of a wound gel, the study treatment, or a sunflower oil-based vehicle gel in patients with Inherited Epidermolysis Bullosa (EB)

• Register: EUCTR
• Last refreshed on: 3 April 2017
• Main ID: EUCTR2016-002066-32-ES
• Date of registration: 10/03/2017
• Prospective Registration: Yes
• Primary sponsor: Amryt Research Limited
• Public title: A Clinical Trial which compare the safety and efficacy of a wound gel, the study treatment, or a sunflower oil-based vehicle gel in patients with Inherited Epidermolysis Bullosa (EB)
• Scientific 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 - EASE study
• Date of first enrolment: 16/03/2017
• Target sample size: 164
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2016-002066-32
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Australia, Austria, Croatia, France, Germany, Greece, Ireland, Israel, Italy, Mexico, Spain, Switzerland, Turkey, United Kingdom, United States

Contacts

• Name: Tobias Zahn
• Affiliation: Amryt Research Limited

• Name: Tobias Zahn
• Affiliation: Amryt Research Limited

Key inclusion & exclusion criteria

Inclusion criteria:
A patient will be eligible for study participation only if all of the following criteria apply:
1. Male and female patients with any subtype of inherited EB including EBS, JEB, DEB, and Kindler syndrome age >=4 years [Note: Children <4 years of age may be included only after confirmation by the Independent Data Monitoring Committee (IDMC) upon review of the safety and bioanalytical data at the interim safety review stage].
2. Patients with an EB target wound (i.e., EB partial thickness wound of 10 cm2 to 50 cm2 in size aged >=21 days)
3. 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
4. Patient and/or his/her legal representative must be able and willing to follow study procedures and instructions
Are the trial subjects under 18? yes
Number of subjects for this age range: 82
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 82
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range 0

Exclusion criteria:
A patient will not be eligible to participate in this study if any of the following criteria apply:
1. EB target wound with clinical signs of local infection
2. Use of systemic antibiotics for wound-related infections within 7 days prior to enrolment
3. 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
4. Immunosuppressive therapy or cytotoxic chemotherapy within 60 days prior to enrolment
5. Patient has undergone stem cell transplant or gene therapy for the treatment of inherited EB
6. Current and/or former malignancy including basal cell carcinomas and squamous cell carcinomas
7. Enrolment in any interventional study or treated with any investigational drug for any disease within 4 weeks prior to study entry
8. 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
9. 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)
10.Patient is a member of the investigational team or his/her immediate family
11.Patient lives in the same household as a study participant.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Skin and Connective Tissue Diseases [C17]

Inherited Epidermolysis Bullosa
MedDRA version: 19.1 Level: PT Classification code 10014989 Term: Epidermolysis bullosa System Organ Class: 10010331 - Congenital, familial and genetic disorders

Intervention(s)

Trade Name: Episalvan gel
Product Name: Oleogel-S10
Pharmaceutical Form: Gel
INN or Proposed INN: Birch bark extract
CAS Number: 1640971-03-4
Current Sponsor code: Dry extract from betulae cortex
Other descriptive name: BIRCH BARK EXTRACT
Concentration unit: % (W/W) percent weight/weight
Concentration type: equal
Concentration number: 10-
Pharmaceutical form of the placebo: Gel
Route of administration of the placebo: Cutaneous use

Primary Outcome(s)

Primary end point(s): 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 in any subtype of inherited EB) within 45±7 days of treatment with Oleogel-S10 compared to vehicle 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)

Main Objective: The primary objective of the double-blind phase is to compare the efficacy of Oleogel-S10 (treatment arm A) with vehicle (treatment arm B) in the promotion of healing of EB partial thickness wounds. This will be assessed as evidenced by the incidence of the 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 in any subtype of inherited EB) within 45+-7 days of treatment).

Timepoint(s) of evaluation of this end point: See section E.5.1

Secondary Objective: 1/ Compare the efficacy of IMP with placebo as evidenced by several criteria described in the protocol
2/ Compare the safety of IMP with placebo as evidenced by the incidence, severity, and relatedness of AEs and based on laboratory assessments
3/ Compare the tolerability of IMP with placebo
4/ Assess betulin exposure

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: See section E.5.2

Secondary end point(s): Secondary efficacy endpoints
• Time to first complete closure of the EB target wound as evidenced by clinical assessment until D90+-7.
• Proportion of patients with first complete closure of the EB target wound within D14+-5, D30+-7, D60+-7, and D90+-7 based on clinical assessment by the investigator
• Proportion of patients with first complete closure of the EB target wound within at D7+-5, D14+-5, D30+-7, D45+-7, D60+-7, and D90+-7 based on patient assessment
• Proportion of patients with first complete closure of the EB target wound at D7+-5, D14+-5, D30+-7, D45+-7, D60+-7, and D90+-7 based on blinded evaluation of photographs
• Percentage change from baseline (D0) in EB target wound size as evidenced by blinded evaluation of photographs taken at D7+-5, D14+-5, D30+-7, D45+-7, D60+-7, and D90+-7
• Change from baseline (D0) in total body wound burden as evidenced by clinical assessment using Section I (assessment of the skin except for the anogenital region) of the ‘EB Disease Activity and Scarring Index’ (EBDASI) at D30+-7, D60+-7, and D90+-7
• Change from baseline (D0) in body surface area percentage (BSAP) of TBSA affected by EB partial thickness wounds as evidenced by clinical assessment based on the ‘Lund and Browder’ chart at D30+-7, D60+-7, and D90+-7
• The incidence and maximum severity of wound infection between baseline (D0) and D90+-7 as evidenced by AEs and/or use of topical and/or systemic antibiotics (related to wound infection)
• Change from baseline (D0) in ‘background’ pain using the ‘Face, Legs, Activity, Cry, Consolability’ (FLACC) scale in patients <4 years of age and the ‘Wong-Baker FACES® Pain Rating Scale’ in patients >=4 years of age before wound dressing changes at D7+-5, D14+-5, D30+-7, D45+-7, D60+-7, and D90+-7
• Change from baseline (D0) in ‘procedural’ pain using the FLACC scale in patients <4 years of age and the ‘Wong-Baker FACES® Pain Rating Scale’ in patients >=4 years of age after wound dressing changes at D7+-5, D14+-5, D30+-7, D45+-7, D60+-7, and D90+-7
• Change from baseline (D0) in itching using the ‘Itch Man Scale’ in patients >=4 years and up to 13 years of age and the ‘Leuven Itch Scale’ in patients >=14 years of age before wound dressing changes at D7+-5, D30+-7, D60+-7, and D90+-7
• Change from baseline in impact of wounds on sleep (in patients >=14 years of age) as measured by differences in 11-point Likert scales at D7+-5, D30+-7, D60+-7, and D90+-7
• The number of days missed from school or from work due to EB as reported by patients at D0, D14+-5, D30+-7, D45+-7, D60+-7, and D90+-7
• Evaluation of the treatment response (in patients >=14 years of age) using the Treatment Satisfaction Questionnaire for Medication (TSQM), Version 9 at D7+-5, D30+-7, D60+-7, and D90+-7
Safety endpoints
• Incidence, severity, and relatedness of AEs
• Local tolerability as judged by the investigator
• Safety laboratory data
• Systemic exposure to betulin, if consent provided

Secondary ID(s)

BEB-13

Source(s) of Monetary Support

Amryt Research Limited