DIACEREIN for Generalized epidermolysis bullosa simplex

Inclusion criteria

• {"criterion_text":"-Patient is at least 6 months old at Visit 2 (Day 1/Baseline A)."}
• {"criterion_text":"-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."}
• {"criterion_text":"-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"}
• {"criterion_text":"-Patient with ≥ 3% BSA of EBS lesions excluding palms and soles at Visit 2 (Day 1/Baseline A)."}
• {"criterion_text":"-Patient’s EBS lesions within the Treatment Area have an IGA score of ≥3 at Visit 2 (Day 1/Baseline A)."}
• {"criterion_text":"-Patient/caregiver agrees to follow study medication application instructions."}
• {"criterion_text":"-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."}
• {"criterion_text":"-Patient (and caregiver/legal guardian) is willing and able to comply with all study visits and all the protocol requirements, including completing questionnaires."}
• {"criterion_text":"-Patient (and caregiver/legal guardian) is able to provide written informed consent; assent based on age."}
• {"criterion_text":"-Female patient of childbearing potential must have a negative pregnancy test prior to randomization."}

Exclusion criteria

• {"criterion_text":"-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."}
• {"criterion_text":"-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)."}
• {"criterion_text":"-Patient has a history of allergy or hypersensitivity to any component of study medications, including diacerein or rhein."}
• {"criterion_text":"-Patient is pregnant or breastfeeding/lactating."}
• {"criterion_text":"-Patient has a planned or anticipated major surgical procedure or other activity that would interfere with their ability to comply with protocol requirements."}
• {"criterion_text":"-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."}
• {"criterion_text":"-Patient has used any diacerein-containing product within 6 months prior to Visit 2 (Day 1/Baseline A)."}
• {"criterion_text":"-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)"}
• {"criterion_text":"-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."}
• {"criterion_text":"-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)."}
• {"criterion_text":"-Patient is treated with protocol-excluded topical therapies other than steroids, within 2 weeks prior to Visit 2 (Day 1/Baseline A) that might influence the assessment of the Treatment Area throughout the study period."}
• {"criterion_text":"-Patient has been treated with topical steroids on the EBS lesions within 2 weeks or systemic steroids within 4 weeks, prior to Visit 2 (Day 1/Baseline A). (Note: inhaled and ophthalmic products containing steroids are allowed.)"}
• {"criterion_text":"-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 weeks prior to Visit 2 (Day 1/Baseline A)"}

Primary endpoints

• {"endpoint_text":"-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).","definition_or_measurement_approach":"Proportion of patients achieving IGA treatment success in the Treatment Area defined as IGA score 0 or 1 with ≥2-point reduction from Baseline A (Visit 2/Day 1) to Week 8 (Visit 5/EOT)."}

Secondary endpoints

• {"endpoint_text":"-Efficacy Endpoints: Change in % BSA of EBS lesion in the Treatment Area from Baseline A (Visit 2/Day 1) to Week 8 (Visit 5/EOT).","definition_or_measurement_approach":"Change in percent body surface area (% BSA) of EBS lesions in the Treatment Area measured from Baseline A to Week 8."}
• {"endpoint_text":"-Efficacy Endpoints: Change in pain intensity scores from Baseline A (Visit 2/Day 1) to Week 8 (Visit 5/EOT).","definition_or_measurement_approach":"Change in patient-reported pain intensity scores from Baseline A to Week 8."}
• {"endpoint_text":"-Efficacy Endpoints: Change in pruritus intensity scores from Baseline A (Visit 2/Day 1) to Week 8 (Visit 5/EOT).","definition_or_measurement_approach":"Change in patient-reported pruritus intensity scores from Baseline A to Week 8."}
• {"endpoint_text":"-Efficacy Endpoints: Change in the QOLEB from Baseline A (Visit 2/Day 1) to Week 8 (Visit 5/EOT).","definition_or_measurement_approach":"Change in Quality of Life in Epidermolysis Bullosa (QOLEB) score from Baseline A to Week 8."}
• {"endpoint_text":"-Efficacy Endpoints: Change in EBDASI score (skin activity) from Baseline A (Visit 2/Day 1) to Week 8 (Visit 5/EOT).","definition_or_measurement_approach":"Change in EBDASI (skin activity) score from Baseline A to Week 8."}
• {"endpoint_text":"-Safety Endpoints: Incidence and proportion of patients with AEs, including treatment emergent adverse events (TEAEs), and serious adverse events and relationship to the study medication.","definition_or_measurement_approach":"Incidence and proportion of patients experiencing AEs, TEAEs and serious adverse events, and assessment of relationship to study medication over the study period."}
• {"endpoint_text":"-Safety Endpoints: Incidence and proportion of patients with mild, moderate, and severe AEs","definition_or_measurement_approach":"Incidence and proportion categorized by severity (mild, moderate, severe) of adverse events."}
• {"endpoint_text":"-Safety Endpoints: Change from Baseline A (Visit 2/Day 1) in clinical laboratory results in hematology, biochemistry, and urinalysis. (If the tests are omitted at Baseline A at the discretion of the investigator, the closest data during the screening period can serve as baseline.)","definition_or_measurement_approach":"Change from Baseline A in laboratory parameters (hematology, biochemistry, urinalysis); nearest screening data may be used if baseline tests omitted."}
• {"endpoint_text":"-Safety Endpoints: Change from Baseline A (Visit 2/Day 1) in vital signs, physical examination, and ECG parameters.(If the tests are omitted at Baseline A at the discretion of the investigator, the closest data during the screening period can serve as baseline.)","definition_or_measurement_approach":"Change from Baseline A in vital signs, physical exam and ECG parameters; nearest screening data may be used if baseline omitted."}

Methods

• Country-specific recruitment arrangements documents uploaded (K1 recruitment arrangements files for BE, IE, PL, IT, FR, AT, GR, ES).
• Patient advertisement / recruitment material (documents titled 'Other subject information_Patient advertisement' and recruitment material_advertisement present in multiple MSC dossiers).

Austria

Earliest CTIS Part Ii Submission Date

01-04-2024

Latest Decision Or Authorization Date

09-07-2025

Processing Time Days

464

Number Of Sites

1

Number Of Participants

10

Belgium

Earliest CTIS Part Ii Submission Date

09-07-2024

Latest Decision Or Authorization Date

07-07-2025

Processing Time Days

363

Number Of Sites

1

Number Of Participants

4

Ireland

Earliest CTIS Part Ii Submission Date

25-07-2024

Latest Decision Or Authorization Date

14-07-2025

Processing Time Days

354

Number Of Sites

1

Number Of Participants

3

Poland

Earliest CTIS Part Ii Submission Date

11-04-2024

Latest Decision Or Authorization Date

14-07-2025

Processing Time Days

459

Number Of Sites

3

Number Of Participants

10

Italy

Earliest CTIS Part Ii Submission Date

05-04-2024

Latest Decision Or Authorization Date

09-07-2025

Processing Time Days

460

Number Of Sites

5

Number Of Participants

30

France

Earliest CTIS Part Ii Submission Date

04-07-2024

Latest Decision Or Authorization Date

08-07-2025

Processing Time Days

369

Number Of Sites

1

Number Of Participants

3

Greece

Earliest CTIS Part Ii Submission Date

12-11-2024

Latest Decision Or Authorization Date

22-10-2025

Processing Time Days

344

Number Of Sites

2

Number Of Participants

4

Spain

Earliest CTIS Part Ii Submission Date

04-12-2024

Latest Decision Or Authorization Date

10-04-2026

Processing Time Days

492

Number Of Sites

1

Number Of Participants

8

Primary sponsor

Full Name

Twi Biotechnology Inc.

Organisation Type

Pharmaceutical company

Country Of Registered Address

Taiwan