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)

Phase 1

• Conditions: Generalized Epidermolysis Bullosa Simplex (EBS); MedDRA version: 25.0Level: LLTClassification code: 10087382Term: Epidermolysis bullosa simplex Class: 100000004848; Therapeutic area: Diseases [C] - Skin and Connective Tissue Diseases [C17]

• Registration Number: CTIS2023-508818-42-00
• Lead Sponsor: Twi Biotechnology Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2023-12-20
• Last Update Posted: 21 August 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 87

Inclusion Criteria

Patient is at least 6 months old at Visit 2 (Day 1/Baseline A)., Female patient of childbearing potential is willing to practice highly effective contraception (i.e., pregnancy prevention method with a failure rate of < 1% per year) from Screening throughout the end of the study., Patients has been clinically diagnosed with severe EBS or intermediate EBS, confirmed by documented genetic diagnosis to have autosomal dominant mutations in KRT5 or KRT14 gene, Patients with = 5% BSA of EBS lesions excluding hands and feet at Visit 2 (Day 1/Baseline A)., Patient’s EBS lesions within the Treatment Area have an IGA score of =3 at Visit 2 (Day 1/Baseline A)., Patient/caregiver agrees to follow study medication application instructions., Patient (and caregiver/legal guardian) agrees to report use of all prescription and over-the-counter medications, including topical therapies applied to the body, e.g., medical cleansers, bleach cleansers, bleach baths, topical antiseptics, topical disinfectants, etc. for the duration of the study., Patient (and caregiver/legal guardian) is willing and able to comply with all study visits and all the protocol requirements, including completing questionnaires., Patient (and caregiver/legal guardian) is able to provide written informed consent; assent based on age., Female patient of childbearing potential must have a negative pregnancy test prior to randomization.

Exclusion Criteria

Patient has a clinically significant skin disease other than EBS (e.g., psoriasis, atopic dermatitis, eczema, sun damage, etc.), or a vascular disorder associated with cutaneous erosions/ulcerations, that may confound assessments of efficacy or safety., Patient has been treated with any investigational drug or device within 30 days or 5 half-lives, whichever is longer, prior to Visit 2 (Day 1/Baseline A)., Patient has a history of allergy or hypersensitivity to any component of study medications, including diacerein or rhein., Patient is pregnant or breastfeeding/lactating., Patient has a planned or anticipated major surgical procedure or other activity that would interfere with their ability to comply with protocol requirements., Patient has a clinically significant underlying medical condition, psychiatric condition (such as major depressive or psychotic disorder, severe intellectual disability, or alcohol or drug use disorder), or requires concomitant medication that based on the investigator’s judgement may impair evaluation of the Treatment Area or exposes the patient to an unacceptable risk by study participation., Patient has used any diacerein-containing product within 6 months prior to Visit 2 (Day 1/Baseline A)., Patient has had a cutaneous infection in the Treatment Area or use systemic antibiotics within 7 days prior to Visit 2 (Day 1/Baseline A) and prior to Visit 7 (Week 16/Baseline B)., Patient has uncontrolled diabetes mellitus (HbA1c = 6.5%), hepatic enzyme abnormalities (alanine aminotransferase or aspartate aminotransferase >2.5 the upper limit of normal (ULN), or total bilirubin >2.0x ULN), or renal abnormalities (estimated glomerular filtration rate [eGFR]< 30 ml/min/1.73 m2) during the Screening period., 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)., Patient is treated with protocol-excluded topical therapies within 2 weeks prior to Visit 2 (Day 1/Baseline A) that might influence the assessment of the Treatment Area throughout the study period., Patient has been treated with topical or systemic corticosteroids within 4 weeks and with other immunosuppressive/immunomodulatory therapies or chemotherapy within 8 weeks prior to Visit 2 (Day 1/Baseline A) and prior to Visit 7 (Week 16/Baseline B)., Patient has been treated with an approved or investigational biologic anti- inflammatory therapy (such as monoclonal antibodies that target to modulate the immune responses) within 8 weeks prior to Visit 2 (Day 1/Baseline A).

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: Primary Objective:<br><br>Part A:<br><br>To evaluate the efficacy of diacerein 1% ointment after 8 weeks of treatment in adult and pediatric patients (aged 6 months and older) with generalized EBS (severe and intermediate subtypes);Secondary Objective: Part A: To evaluate the safety of diacerein 1% ointment in adult and pediatric patients (aged 6 months and older) after 8 weeks of treatment with generalized EBS (severe and intermediate subtypes)., Part B: To evaluate the long-term safety of diacerein 1% ointment in subjects with EBS that are previously enrolled and complete Part A of the AC-203-EBS-007 study;Primary end point(s): The primary efficacy endpoint for this study is the proportion of patients achieving treatment success on the IGA of the Treatment Area, in which treatment success is defined as a score of 0 or 1 with at least a 2-point reduction from Baseline A (Visit 2/Day 1) to Week 8 (Visit 5/EOT).