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)

NCT ID: NCT06073132

Last Updated: 2025-11-19

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2/PHASE3

Total Enrollment

80 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-04-04

Study Completion Date

2027-01-31

Brief Summary

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The proposed Phase 2/3 trial with double-blind and open-label extension phases is an international, multicenter study designed to assess the efficacy and safety of diacerein 1% ointment in patients with generalized EBS.

Detailed Description

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Epidermolysis bullosa simplex (EBS) is a genetic skin disorder characterized by skin fragility and recurrent blister formation, primarily caused by mutations in keratins 5 and 14. EBS has 3 common subtypes based on clinical severity and manifestations: localized EBS, intermediate EBS and severe EBS. Severe EBS and intermediate EBS collectively are also known as generalized EBS due to widespread blistering.

Disruption of the keratin 5/14 filament network in basal keratinocytes is a key factor in EBS pathogenesis, compromising skin integrity. The severity of EBS is linked to the extent of keratin mutations disrupting this network, particularly resulting in keratin aggregates in severe cases. Recent studies suggest that mutated keratin proteins can trigger inflammation, exacerbating EBS. Elevated proinflammatory cytokines, like IL-1β and IL-6, are observed in EBS patients, and IFN-γ may mediate inflammation, promoting keratin aggregations. As a result, targeting inflammation is considered a potential therapeutic approach in EBS.

AC-203 (diacerein 1% ointment) is a topical formulation of diacerein, well-known for its ability to inhibit IL-1β and other proinflammatory cytokines. Moreover, diacerein and its active metabolite, rhein, have demonstrated ability in reducing keratin aggregates in keratinocytes derived from severe EBS. Taken together, with its anti-inflammatory property and ability to diminish keratin aggregation, AC-203 shows promise in reducing the clinical severity of EBS.

Conditions

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Generalized Epidermolysis Bullosa Simplex

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Part A AC-203

Double-blind, AC-203 Diacerein 1% ointment, QD

Group Type EXPERIMENTAL

AC-203

Intervention Type DRUG

The investigational product is formulated as 1% topical ointment

Part A Vehicle ointment

Double-blind, Vehicle ointment, QD

Group Type PLACEBO_COMPARATOR

Vehicle

Intervention Type DRUG

Vehicle-only control study medication is the same formulation as investigational product without active ingredient

Part B AC-203

Open-label extension phase, AC-203 Diacerein 1% ointment, QD

Group Type EXPERIMENTAL

AC-203

Intervention Type DRUG

The investigational product is formulated as 1% topical ointment

Interventions

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AC-203

The investigational product is formulated as 1% topical ointment

Intervention Type DRUG

Vehicle

Vehicle-only control study medication is the same formulation as investigational product without active ingredient

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

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

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.
Minimum Eligible Age

6 Months

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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TWi Biotechnology, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Mission dermatology Center

Rancho Santa Margarita, California, United States

Site Status RECRUITING

Stanford University

Stanford, California, United States

Site Status RECRUITING

Children's Hospital Colorado

Aurora, Colorado, United States

Site Status RECRUITING

Pediatric Skin Research, LLC

Miami, Florida, United States

Site Status RECRUITING

Northwestern University - Lurie Childrens's Hospital

Chicago, Illinois, United States

Site Status RECRUITING

Stony Brook Dermatology

Stony Brook, New York, United States

Site Status RECRUITING

Cincinnati Childrens Hospital

Cincinnati, Ohio, United States

Site Status RECRUITING

Medical University of South Carolina

Charleston, South Carolina, United States

Site Status RECRUITING

Texas Dermatology and Laser Specialists

San Antonio, Texas, United States

Site Status RECRUITING

Royal Melbourne Hospital

Melbourne, Victoria, Australia

Site Status NOT_YET_RECRUITING

Premier Specialists

Kogarah, , Australia

Site Status RECRUITING

Sydney Children's Hospital

Randwick, , Australia

Site Status RECRUITING

Universitaetsklinik fuer Dermatologie und Allergologie

Salzburg, , Austria

Site Status RECRUITING

UZ Leuven

Leuven, , Belgium

Site Status RECRUITING

Hopital Necker-Enfants Malades

Paris, , France

Site Status RECRUITING

Andreas Syggros Hospital 1st University Clinic of Skin and Venereal Diseases of Athens

Athens, , Greece

Site Status NOT_YET_RECRUITING

Hospital of Skin and Venereal Diseases of Thessaloniki

Thessaloniki, , Greece

Site Status RECRUITING

Postgraduate Institute of Medical Education and Research (PGIMER)

Chandigarh, , India

Site Status RECRUITING

Children's Health Ireland

Dublin, , Ireland

Site Status RECRUITING

Tel Aviv Sourasky Medical Center

Tel Aviv, , Israel

Site Status RECRUITING

IRCCS, AOUBO, Policlinico Sant'Orsola

Bologna, , Italy

Site Status RECRUITING

Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico Milano

Milan, , Italy

Site Status RECRUITING

Università degli Studi di Modena e Reggio Emilia (UNIMORE)

Modena, , Italy

Site Status RECRUITING

Istituto Dermopatico dell'Immacolata (IDI) - Istituto di

Rome, , Italy

Site Status RECRUITING

UOS "Centro delle Dermatosi Croniche Complesse e Genodermatosi" UOC Dermatologia

Rome, , Italy

Site Status RECRUITING

Hospital Tunku Azizah (Hospital Wanita Dan Kanak-kanak Kuala Lumpur)

Kuala Lumpur, , Malaysia

Site Status RECRUITING

Asian Hospital

City of Muntinlupa, , Philippines

Site Status RECRUITING

Iloilo Doctors Hospital

Iloilo City, , Philippines

Site Status RECRUITING

Health Cube Medical Clinics

Mandaluyong, , Philippines

Site Status RECRUITING

OT.CO Clinic Osipowicz & Turkowski

Warsaw, , Poland

Site Status RECRUITING

Gangnam Severane Hospital

Seoul, , South Korea

Site Status RECRUITING

Hospital Universitario La Paz

Madrid, , Spain

Site Status RECRUITING

National Cheng Kung University Hospital

Tainan, , Taiwan

Site Status RECRUITING

Sheikh Khalifa Medical City (SKMC)

Abu Dhabi, , United Arab Emirates

Site Status RECRUITING

Great Ormond Street Hospital (GOSH) for Children NHS Foundation Trust - Somers Clinical Research Facility (CRF)

London, , United Kingdom

Site Status RECRUITING

University Hospitals Birmingham NHS Foundation Trust (UHB)

Solihull, , United Kingdom

Site Status RECRUITING

Countries

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United States Australia Austria Belgium France Greece India Ireland Israel Italy Malaysia Philippines Poland South Korea Spain Taiwan United Arab Emirates United Kingdom

Central Contacts

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Sandy Lin, PhD

Role: CONTACT

+886-2-2657-1788

TWiB

Role: CONTACT

+886-2-2657-1788

Facility Contacts

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Shireen Guide, MD

Role: primary

Joyce Teng, MD PhD

Role: primary

Anna Bruckner, MD

Role: primary

Mercedes Gonzalez, MD

Role: primary

Amy S. Paller, MD

Role: primary

Jordan Slutsky, MD

Role: primary

Kalyani Marathe, MD, MPH

Role: primary

Lara Wine Lee, MD PhD

Role: primary

Jennifer Patterson

Role: primary

John C. Browning, MD

Role: backup

Laura Scardamaglia, MD

Role: primary

Dedee Murrell, MD

Role: primary

Artiene Tatian, MD

Role: primary

Martin Laimer, MD

Role: primary

Caroline Colmant, MD

Role: primary

Christine Bodemer, MD, PhD

Role: primary

Alexandros Stratigos, MD

Role: primary

Dimitra Kyritsi, MD

Role: primary

Rahul Mahajan, MD

Role: primary

Fiona Browne, MD

Role: primary

Mor Pavlosky, MD

Role: primary

Iria Neri, MD

Role: primary

Sophie Guez, MD

Role: primary

Cristina Magnoni, MD

Role: primary

Biagio Didona, MD

Role: primary

Andrea Diociaiuti, MD

Role: primary

Kin Fon Leong, MD

Role: primary

Emerson Vista, MD

Role: primary

Anjuli Jaen, MD

Role: primary

Mae Quizon, MD

Role: primary

Katarzyna Osipowicz, MD

Role: primary

Sang Eun Lee, MD

Role: primary

Rocio Maseda Pedrero, MD

Role: primary

Chao-Kai Hsu, MD PhD

Role: primary

Shaden Mohammad Abdel Hadi, MD

Role: primary

Anna Martinez, MD

Role: primary

Ajoy Bardhan, MD

Role: primary

Other Identifiers

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AC-203-EBS-007

Identifier Type: -

Identifier Source: org_study_id

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