Safety and Efficacy of Diacerein 1% Ointment Topical Formulation Compared to Placebo for Subjects With Epidermolysis Bullosa Simplex (EBS)

The proposed study is an international, multicenter, randomized, double-blind,
vehicle-controlled, parallel group study to evaluate the safety and efficacy of topical
Diacerein 1% Ointment for the treatment of subjects with EBS. Subject randomization will be
stratified by genotype (KRT5 and/or KRT14 versus other genotypes) and age group (<8 and ≥8
years old). Participants will be subject to up to 6-week screening period, then be assigned
to treat EBS lesions once daily with either Diacerein 1% ointment topical formulation or
placebo control ointment for 8 weeks, followed by an 8 week follow-up period. Approximately
80 subjects are planned to be randomized to one of the 2 treatment groups in this study at
approximately 20 international investigational centers.

The primary objective of this study is 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. The secondary objectives are 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, and safety
and tolerability.

Inclusion Criteria:

- Subject is male or female at least 4 years of age at Visit 1

- 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.

- 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)

- 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 (e.g., medicated cleansers, CBD oil, MediHoney, Silvadine cream 1%, the
Investigator should consult the Medical Monitor regarding therapies not specified in
the protocol

- Subject/caregiver agrees to follow topical product application instructions during the
treatment period

- 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, for the duration of the study.

- Subject is non-pregnant, non-lactating and is not planning for pregnancy during the
study period

- 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

- Subject is willing and able to follow all study instructions and to attend all study
visits

- Subject/caregiver is able to comprehend and willing to sign an Informed Consent and/or
Assent Form.

Exclusion Criteria:

- Subject has EBS lesions to be treated that are infected (i.e., EBS lesions that
require therapy to treat an infection)

- Subject has used any diacerein containing product within 6 months prior to Visit 1

- Subject has used systemic immunotherapy or cytotoxic chemotherapy within 60 days prior
to Visit 1

- 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)

- Subject has evidence of a systemic infection or has used systemic antibiotics within 7
days prior to Visit 1

- 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.

- 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

- Subject has used any topical product containing allantoin on the EBS lesions to be
treated within 30 days prior to Visit 1

- 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)

- Subject currently has diabetes mellitus (HbA1c ≥6.5%); Note: controlled diabetes
(HbA1c < 6.5%) is also considered exclusionary

- 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 m^2) 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

- 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

- Subject has a history of sensitivity to any of the ingredients in the study
medications

- Subject has participated in an investigational drug trial/device in which
administration of an investigational study medication occurred within 30 days prior to
Visit 1.