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) [EBShield Study]

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Twi Biotechnology Inc.

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Skin and Connective Tissue Diseases [C17]

Trial duration

21 May 2024 → ongoing

Decision date (initial)

2024-04-29

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

External identifiers

EU CT number

2023-508818-42-00

ClinicalTrials.gov

NCT06073132

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

Primary Objective:

Part A:

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 objectives 2

1. 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).
2. Part B: To evaluate the long-term safety of diacerein 1% ointment in subjects with EBS that have completed Part A of the AC-203-EBS-007 study.

Conditions and MedDRA coding

Generalized Epidermolysis Bullosa Simplex (EBS)

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. Patient is at least 6 months old at Visit 2 (Day 1/Baseline A).
2. 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
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 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.
7. Patient (and caregiver/legal guardian) is willing and able to comply with all study visits 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 prior to randomization.
10. 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.

Exclusion criteria 13

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 with cutaneous erosions/ulcerations, that may confound assessments of efficacy or safety.
2. 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.
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 systemic antibiotics within 7 days prior to Visit 2 (Day 1/Baseline A)
5. 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.
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 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.
8. 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.)
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 weeks prior to Visit 2 (Day 1/Baseline A)
10. 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).
11. Patient has a history of allergy or hypersensitivity to any component of study medications, including diacerein or rhein.
12. Patient is pregnant or breastfeeding/lactating.
13. Patient has a planned or anticipated major surgical procedure or other activity that would interfere with their ability to comply with protocol requirements.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 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).

Secondary endpoints 9

1. 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).
2. Efficacy Endpoints: Change in pain intensity scores from Baseline A (Visit 2/Day 1) to Week 8 (Visit 5/EOT).
3. Efficacy Endpoints: Change in pruritus intensity scores from Baseline A (Visit 2/Day 1) to Week 8 (Visit 5/EOT).
4. Efficacy Endpoints: Change in the QOLEB from Baseline A (Visit 2/Day 1) to Week 8 (Visit 5/EOT).
5. Efficacy Endpoints: Change in EBDASI score (skin activity) from Baseline A (Visit 2/Day 1) to Week 8 (Visit 5/EOT).
6. 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.
7. Safety Endpoints: Incidence and proportion of patients with mild, moderate, and severe AEs
8. 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.)
9. 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.)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Twi Biotechnology Inc.

Sponsor organisation

Twi Biotechnology Inc.

Address

8 F, Lane 221, No 41 Gangqian Rd Lane 221 No 41 Gangqian Rd

City

Taipei

Postcode

11494

Country

Taiwan

Scientific contact point

Organisation

Twi Biotechnology Inc.

Contact name

Associate Director, Medical Research

Public contact point

Organisation

Twi Biotechnology Inc.

Contact name

Associate Director, Medical Research

Locations

8 EU/EEA countries · 15 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 156 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

16 submissions — initial application plus substantial / non-substantial modifications