An International Study Evaluating the Safety and Efficacy of Diacerein 1% Ointment Topical Formulation in Subjects with Epidermolysis Bullosa Simplex (EBS)

• Register: EUCTR
• Last refreshed on: 28 February 2019
• Main ID: EUCTR2016-004427-24-NL
• Date of registration: 23/06/2017
• Prospective Registration: Yes
• Primary sponsor: Castle Creek Pharmaceuticals, LLC
• Public title: An International Study Evaluating the Safety and Efficacy of Diacerein 1% Ointment Topical Formulation in Subjects with Epidermolysis Bullosa Simplex (EBS)
• Scientific title: An International, Multicenter, Randomized, Double-Blind, Parallel-Group Phase 2 Study Evaluating the Safety and Efficacy of Diacerein 1% Ointment Topical Formulation in Subjects with Epidermolysis Bullosa Simplex (EBS) [DELIVERS Study]
• Date of first enrolment: 06/09/2017
• Target sample size: 80
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2016-004427-24
• 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): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Australia, Austria, France, Germany, Israel, Italy, Netherlands, United Kingdom, United States

Contacts

• Name: Vasiliki Iassonidou
• Affiliation: Medpace Germany GmbH

• Name: Vasiliki Iassonidou
• Affiliation: Medpace Germany GmbH

Key inclusion & exclusion criteria

Inclusion criteria:
1. Subject is male or female at least 4 years of age at Visit 1
2. Subject has a documented genetic mutation consistent with EBS. A blood or saliva sample will be collected for genetic confirmation if no documented gene mutation data is available. Gene mutations acceptable for inclusion are as follows: KRT5, KRT14, PLEC1, TGM5, PKP1, DSP, FERMT1, EXPH5, DST, KLHL24.
3. Subject has an Assessment Area of EBS lesions to be treated, that is =2% body surface area (BSA) and the EBS lesions are in one or both of the following body areas:
- Localized: plantar and/or palmar areas (plantar areas where >25% of the area has hyperkeratosis that has been present for greater than 12 weeks cannot be included as part of the Assessment Area)
- Generalized: arms, legs, torso, hands and feet (scalp, groin and areas where, in the investigator’s opinion, the study medication might become occluded cannot be included as part of the Assessment Area
4. Subject’s EBS lesions in the Assessment Area have an Investigator’s Global Assessment (IGA) score of =3
5. Subject/caregiver agrees to not use any topical therapies other than the study medication that, might influence the status of the EBS lesions during the duration of the study (e.g., medicated cleansers, CBD oil, MediHoney, Silvadine cream 1%); the Investigator should consult the Medical Monitor regarding therapies not specified in the protocol
6. Subject/caregiver agrees to follow topical product application instructions during the treatment period
7. If the subject is a woman of childbearing potential, she has a negative urine pregnancy test and agrees to use an approved effective method of birth control, as defined by this protocol (see Section 10.6), for the duration of the study.
8. Subject is non-pregnant, non-lactating and is not planning for pregnancy during the study period
9. Subject is in good general health and free of any known disease state or physical condition which, in the investigator’s opinion, might impair evaluation of the EBS lesions or which exposes the subject to an unacceptable risk by study participation
10. Subject is willing and able to follow all study instructions and to attend all study visits
11. Subject/caregiver is able to comprehend and willing to sign an Informed Consent and/or Assent Form.
Are the trial subjects under 18? yes
Number of subjects for this age range: 40
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 20
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 20

Exclusion criteria:
1. Subject has EBS lesions to be treated that are infected (i.e., EBS lesions that require therapy to treat an infection)
2. Subject has used any diacerein containing product within 6 months prior to Visit 1
3. Subject has used systemic immunotherapy or cytotoxic chemotherapy within 60 days prior to Visit 1
4. Subject has used systemic steroidal therapy or has used topical steroidal therapy on the EBS lesions to be treated within 30 days prior to Visit 2 (Note: inhaled and ophthalmic products containing steroids are allowed)
5. Subject has evidence of a systemic infection or has used systemic antibiotics within 7 days prior to Visit 1
6. Subject is currently using systemic analgesics and/or anti-histamine therapy for treatment of EBS lesions, unless on a stable regimen (i.e., the same dosing regimen) for at least 4 weeks prior to Visit 1. Note: As needed (PRN) use of acetaminophen/paracetamol or NSAIDs within the 4 weeks prior to Visit 1 are permitted provided the treatment was unrelated to EBS symptom relief.
7. Subject has used any systemic diuretics or cardiac glycosides or any systemic product that, in the opinion of the investigator, might put the subject at undue risk by study participation or interferes with the study medication application or the study assessments within 30 days prior to Visit 1
8. Subject has used any topical product containing allantoin on the EBS lesions to be treated within 30 days prior to Visit 1
9. Subject has a current malignancy, or a history of treatment for a malignancy within 2 years prior to Visit 1 (Note: does not include non-melanoma skin cancer)
10. Subject currently has diabetes mellitus (HbA1c =6.5%). Note: controlled diabetes (HbA1c < 6.5%) is also considered exclusionary
11. Subject has a history of cardiac, hepatic (ALT and or AST >2x ULN, Total bilirubin >1.5x ULN at Visit 1), or renal disease (eGFR<30 ml/min/1.73 m2) that, in the opinion of the investigator, might put the subject at undue risk by study participation or interferes with the study medication application of the study assessments
12. Subject has a non-EBS skin disease (e.g., psoriasis, atopic dermatitis, eczema, sun damage, etc.), or condition (e.g., sunburn) that, in the opinion of the investigator, might put the subject at undue risk by study participation or interferes with the study medication application or the study assessments
13. Subject has a history of sensitivity to any of the ingredients in the study medications.
14. Subject has participated in any investigational drug/device trial in which administration of an investigational study medication occurred within 30 days prior to Visit 1.


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]

Epidermolysis Bullosa Simplex (EBS)
MedDRA version: 20.0 Level: PT Classification code 10014989 Term: Epidermolysis bullosa System Organ Class: 10010331 - Congenital, familial and genetic disorders

Intervention(s)

Product Name: Diacerein
Product Code: Diacerein
Pharmaceutical Form: Ointment
INN or Proposed INN: DIACEREIN
CAS Number: 13739-02-1
Current Sponsor code: CCP-020, AC-203
Other descriptive name: Diacerein
Concentration unit: % (W/W) percent weight/weight
Concentration type: equal
Concentration number: 1-
Pharmaceutical form of the placebo: Ointment
Route of administration of the placebo: Topical use (Noncurrent)

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: Baseline (D1) and Visit 8 (D113)

Secondary Objective: To compare the effects of Diacerein 1% Ointment to Control Ointment in subjects with EBS in:
• Changes in Investigator Global Assessment (IGA) scores
• Pain
• Pruritus
• Mobility
• Safety and tolerability

Primary end point(s): The primary efficacy endpoint is based on the ITT population, and is the proportion of subjects who achieve =40% reduction in BSA of EBS lesions from Visit 2 (Week 0) to Visit 8 (Week 16).

Main Objective: To compare the efficacy of Diacerein 1% Ointment to Control Ointment based on reduction in body surface area (BSA) of EBS lesions being treated when applied once-daily for 8 weeks in subjects with EBS.

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: All except PK: Baseline (D1) and Visit 8 (D113)

PK: Visit 4 (D29); Visit 6 (D57); Visit 8 (D113)

Secondary end point(s): • The proportion of subjects achieving success on the IGA, where success is defined as at least a 2-point reduction, from Visit 2 (Week 0) to Visit 8 (Week 16).
• The proportion of subjects who achieve = 40% reduction in BSA of EBS lesions from Visit 2 (Week 0) to Visit 6 (Week 8).
• The proportion of subjects achieving success on the IGA, where success is defined as at least a 2-point reduction, from Visit 2 (Week 0) to Visit 6 (Week 8).
• The proportion of subjects with a reduction in overall pain intensity from Visit 2 (Week 0) to Visit 6 (Week 8).
• The proportion of subjects with a reduction in overall pruritus intensity from Visit 2 (Week 0) to Visit 6 (Week 8).

If the comparison for the primary endpoint is significant (two-sided p-value < 0.05), then testing will continue for the key secondary endpoints. The key secondary endpoints will be analyzed in a similar manner as the primary endpoint. To control the type I error rate for testing multiple key secondary endpoints, a fixed-sequence approach for the key secondary endpoints will be used.

Secondary ID(s)

131 384

CCP-020-301

2016-004427-24-DE

Source(s) of Monetary Support

Castle Creek Pharmaceuticals, LLC

Ethics review

Status: Approved
Approval date:
Contact: