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)

NCT06073132 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: AC-203-EBS-007
• Study Type: interventional
• Target: 80
• Locations: 17 countries
• Sites: 28

Brief Summary

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.

Conditions

Generalized Epidermolysis Bullosa Simplex

Keywords

Epidermolysis Bullosa Simplex; EBS

Outcome Measures

Primary Outcomes (1)

• 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

  The static IGA is the investigator's visual clinical assessment of the average overall intensity of lesions in the designated Treatment Area at a particular time point. EBS-IGA is a 5-point scale is a 5-point scale (clear=0; almost clear=1; mild=2; moderate=3; severe=4)

  from Baseline A (Visit 2/Day 1) to Week 8 (Visit 5/EOT)

Secondary Outcomes (5)

• Change in % BSA of EBS lesions in the Treatment Area

  from Baseline A (Visit 2/Day 1) to Week 8 (Visit 5/EOT)

• Change in pain intensity score

  Baseline A (Visit 2/Day 1) to Week 8 (Visit 5/EOT)

• Change in pruritus intensity score

  from Baseline A (Visit 2/Day 1) to Week 8 (Visit 5/EOT)

• Change in EBDASI score (skin activity)

  from Baseline A (Visit 2/Day 1) to Week 8 (Visit 5/EOT).

• Change in the QOLEB score

  from Baseline A (Visit 2/Day 1) to Week 8 (Visit 5/EOT)

Study Arms (3)

Part A AC-203

EXPERIMENTAL

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

Drug: AC-203

Part A Vehicle ointment

PLACEBO COMPARATOR

Double-blind, Vehicle ointment, QD

Drug: Vehicle

Part B AC-203

EXPERIMENTAL

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

Drug: AC-203

Interventions

AC-203 DRUG

The investigational product is formulated as 1% topical ointment

Part A AC-203; Part B AC-203

Vehicle DRUG

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

Part A Vehicle ointment

Eligibility Criteria

• Age: 6 Months+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient is at least 6 months old at Visit 2 (Day 1/Baseline A).
• 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.
• Patient with ≥ 3% BSA of EBS lesions excluding palms and soles 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.
• 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.

You may not qualify if:

• 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 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).
• 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 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.
• 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.)
• 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).
• 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.

Sponsors & Collaborators

• TWi Biotechnology, Inc.: lead

Study Sites (30)

Mission dermatology Center

Rancho Santa Margarita, California, 92688, United States

Location

Stanford University

Stanford, California, 94304, United States

Location

Children's Hospital Colorado

Aurora, Colorado, 80045, United States

Location

Northwestern University - Lurie Childrens's Hospital

Chicago, Illinois, 60611, United States

Location

Cincinnati Childrens Hospital

Cincinnati, Ohio, 45229, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

Texas Dermatology and Laser Specialists

San Antonio, Texas, 78218, United States

Location

Premier Specialists

Kogarah, Australia

Location

Sydney Children's Hospital

Randwick, Australia

Location

Universitaetsklinik fuer Dermatologie und Allergologie

Salzburg, Austria

Location

UZ Leuven

Leuven, Belgium

Location

Dermatology Hospital of Southern Medical University

Guangzhou, Guangdong, China

Location

Hospital of Skin and Venereal Diseases of Thessaloniki

Thessaloniki, Greece

Location

Postgraduate Institute of Medical Education and Research (PGIMER)

Chandigarh, India

Location

Children's Health Ireland

Dublin, Ireland

Location

Tel Aviv Sourasky Medical Center

Tel Aviv, Israel

Location

Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico Milano

Milan, Italy

Location

Università degli Studi di Modena e Reggio Emilia (UNIMORE)

Modena, Italy

Location

Istituto Dermopatico dell'Immacolata (IDI) - Istituto di

Rome, Italy

Location

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

Rome, Italy

Location

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

Kuala Lumpur, Malaysia

Location

Asian Hospital

City of Muntinlupa, Philippines

Location

Iloilo Doctors Hospital

Iloilo City, Philippines

Location

Health Cube Medical Clinics

Mandaluyong, Philippines

Location

OT.CO Clinic Osipowicz & Turkowski

Warsaw, Poland

Location

Gangnam Severane Hospital

Seoul, South Korea

Location

Hospital Universitario La Paz

Madrid, Spain

Location

National Cheng Kung University Hospital

Tainan, Taiwan

Location

Sheikh Khalifa Medical City (SKMC)

Abu Dhabi, United Arab Emirates

Location

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

London, United Kingdom

Location

MeSH Terms

Conditions

Epidermolysis Bullosa Simplex

Interventions

diacerein

Condition Hierarchy (Ancestors)

Epidermolysis Bullosa; Skin Abnormalities; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Skin Diseases, Genetic; Genetic Diseases, Inborn; Skin Diseases; Skin and Connective Tissue Diseases; Skin Diseases, Vesiculobullous

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 12, 2023
• First Posted: October 10, 2023
• Study Start: April 4, 2024
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): March 1, 2027
• Last Updated: April 24, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

KR (1); GR (1); BE (1); PH (3); ES (1); GB (1); AE (1); PL (1); TW (1); IL (1); CN (1); MY (1); IN (1); IT (4); AU (1); IE (1); US (7)