Safety and Efficacy of Diacerein 1% Ointment for Subjects With Epidermolysis Bullosa Simplex (EBS)
Condition: Epidermolysis Bullosa Simplex
MeSH terms: Epidermolysis Bullosa; Epidermolysis Bullosa Simplex
Intervention: diacerein 1% ointment; A placebo ointment
Intervention description: diacerein 1% ointment administered topically; vehicle ointment administered topically
Intervention MeSH terms: Diacerein
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 54.0
Sex: All
Minimum age: 4 Years
Healthy volunteers: No
Keywords: Epidermolysis; bullosa; simplex; EBS

Summary:

      Epidermolysis bullosa simplex (EBS) is a rare genetic skin disease characterized by fragility
      of the skin and mucous membranes resulting in painful blisters and erosions after minor
      trauma. The purpose of this study is to compare the efficacy of diacerein 1% ointment to
      vehicle ointment when applied once-daily for 8 weeks in subjects with EBS.
    

Eligibility criteria:

        Key Inclusion Criteria:

          -  Subject is at least 4 years of age at Screening

          -  Subject has a documented genetic mutation consistent with EBS. Gene mutations
             acceptable for inclusion are as follows: KRT5, KRT14, PLEC1, TGM5, PKP1, DSP, FERMT1,
             EXPH5, DST, KLHL24.

          -  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

               -  Generalized: arms, legs, torso, hands and feet

          -  Subject's EBS lesions in the Assessment Area have an Investigator's Global Assessment
             (IGA) score of ≥3

          -  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

          -  Subject is non-pregnant as confirmed by a negative urine pregnancy screen,
             non-lactating and is not planning for pregnancy during the study period

          -  If the subject is a woman of childbearing potential, agrees to use an approved
             effective method of birth control

          -  Subject is in good general health and free of any known disease state or physical
             condition which might impair evaluation of the EBS lesions or which exposes the
             subject to an unacceptable risk by study participation

        Key Exclusion Criteria:

          -  Subject has EBS lesions to be treated that are infected

          -  Subject has used any diacerein containing product within 6 months prior to Screening

          -  Subject has used systemic immunotherapy or cytotoxic chemotherapy within 60 days prior
             to Screening

          -  Subject has used systemic steroidal therapy or has used topical steroidal therapy on
             the EBS lesions to be treated within 30 days prior to Baseline

          -  Subject has evidence of a systemic infection or has used systemic antibiotics within 7
             days prior to Screening

          -  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 Screening

          -  Subject has used any systemic diuretics or cardiac glycosides or any systemic product
             that might put the subject at undue risk

          -  Subject has used any topical product containing allantoin on the EBS lesions to be
             treated within 30 days prior to Screening

          -  Subject has a current malignancy, or a history of treatment for a malignancy within 2
             years prior to Screening

          -  Subject currently has diabetes mellitus (HbA1c ≥6.5%) or controlled diabetes (HbA1c <
             6.5%)

          -  Subject has a history of cardiac, hepatic (ALT and or AST >2x ULN, Total bilirubin
             >1.5x ULN at Screening), or renal disease (eGFR<30 ml/min/1.73 m^2)

          -  Subject has a non-EBS skin disease or condition (e.g., sunburn) that might put the
             subject at undue risk by study participation or interferes with the study medication
             application or the study assessments