An International, Multicenter, Randomized, Double-Blind, Parallel Group, Vehicle-Controlled, Phase 2/3 Study With Open-Label Extension Evaluating the Efficacy and Safety of Diacerein 1% Ointment for the Treatment of Generalized Epidermolysis Bullosa Simplex (EBS)

Inclusion Criteria:

1. Patient is at least 6 months old at Visit 2 (Day 1/Baseline A). (Note: Enrollment ofpatients under 4 in the EU is pending approval of the safety review for 10 patientsaged 4-12.)

2. Patients has been clinically diagnosed with severe EBS or intermediate EBS,confirmed by documented genetic diagnosis to have autosomal dominant mutations inKRT5 or KRT14 gene.

3. Patient with ≥ 3% BSA of EBS lesions excluding palms and soles at Visit 2 (Day 1/Baseline A).

4. Patient's EBS lesions within the Treatment Area have an IGA score of ≥3 at Visit 2 (Day 1/Baseline A).

5. Patient/caregiver agrees to follow study medication application instructions.

6. Patient (and caregiver/legal guardian) agrees to report use of all prescription andover-the-counter medications, including topical therapies applied to the body, e.g.,medical cleansers, bleach cleansers, bleach baths, topical antiseptics, topicaldisinfectants, etc. for the duration of the study.

7. Patient (and caregiver/legal guardian) is willing and able to comply with all studyvisits and all the protocol requirements, including completing questionnaires.

8. Patient (and caregiver/legal guardian) is able to provide written informed consent;assent based on age.

9. Female patient of childbearing potential must have a negative pregnancy test priorto randomization.

10. Female patient of childbearing potential is willing to practice highly effectivecontraception (i.e., pregnancy prevention method with a failure rate of < 1% peryear) from Screening throughout the end of the study.

Exclusion Criteria:

1. Patient has a clinically significant skin disease other than EBS (e.g., psoriasis,atopic dermatitis, eczema, sun damage, etc.), or a vascular disorder associated withcutaneous erosions/ulcerations, that may confound assessments of efficacy or safety.

2. Patient has a clinically significant underlying medical condition, psychiatriccondition (such as major depressive or psychotic disorder, severe intellectualdisability, or alcohol or drug use disorder), or requires concomitant medicationthat based on the investigator's judgement may impair evaluation of the TreatmentArea or exposes the patient to an unacceptable risk by study participation.

3. Patient has used any diacerein-containing product within 6 months prior to Visit 2 (Day 1/Baseline A).

4. Patient has had a cutaneous infection in the Treatment Area or use systemicantibiotics within 7 days prior to Visit 2 (Day 1/Baseline A).

5. Patient has uncontrolled diabetes mellitus (HbA1c ≥ 6.5%), hepatic enzymeabnormalities (alanine aminotransferase or aspartate aminotransferase >2.5 the upperlimit of normal (ULN), or total bilirubin >2.0x ULN), or renal abnormalities (estimated glomerular filtration rate [eGFR]< 30 ml/min/1.73 m2) during theScreening period.

6. Patient has a current malignancy, or a history of treatment for a malignancy within 5 years (with the exception of treated non-melanoma cutaneous malignancy e.g.,surgically resected with clear margins) prior to Visit 2 (Day 1/Baseline A).

7. Patient is treated with protocol-excluded topical therapies other than steroidswithin 2 weeks prior to Visit 2 (Day 1/Baseline A) that might influence theassessment of the Treatment Area throughout the study period.

8. Patient has been treated with topical steroids on the EBS lesions within 2 weeks orsystemic steroids within 4 weeks. prior to Visit 2 (Day 1/Baseline A). (Note:inhaled and ophthalmic products containing steroids are allowed.)

9. Patient has been treated with: (a) an approved biologic anti-inflammatory therapy (such as monoclonal antibodies that target to modulate the immune responses) and (b)other immunosuppressive/immunomodulatory therapies or chemotherapy within 8 weeksprior to Visit 2 (Day 1/Baseline A).

10. Patient has been treated with any investigational drug or device within 30 days or 5half-lives, whichever is longer, prior to Visit 2 (Day 1/Baseline A).

11. Patient has a history of allergy or hypersensitivity to any component of studymedications, including diacerein or rhein.

12. Patient is pregnant or breastfeeding/lactating.

13. Patient has a planned or anticipated major surgical procedure or other activity thatwould interfere with their ability to comply with protocol requirements.