Generalized Epidermolysis Bullosa SimplexPhase 2/3EBShieldNCT06073132
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)
A Phase 2/3 study testing AC-203 in people with Generalized Epidermolysis Bullosa Simplex, run by TWi Biotechnology, Inc. at 30 sites in 18 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 6 months and older
- Conditions the study is for
- Generalized Epidermolysis Bullosa Simplex
- What is being tested?
- AC-203
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 80 participants
- Where
- 30 sitesin 18 countries
- Study dates
- 4 Apr 2024to Mar 2027
- Phase
- Phase 2/3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 6 months and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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).
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- 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.
Trial locations and contacts
30 sites in 18 countries.
30 sites in 18 countries
United States7 sites
Children's Hospital Colorado
Aurora, Colorado, 80045
Medical University of South Carolina
Charleston, South Carolina, 29425
Northwestern University - Lurie Childrens's Hospital
Chicago, Illinois, 60611
Cincinnati Childrens Hospital
Cincinnati, Ohio, 45229
Mission dermatology Center
Rancho Santa Margarita, California, 92688
Texas Dermatology and Laser Specialists
San Antonio, Texas, 78218
Stanford University
Stanford, California, 94304
Italy4 sites
Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico Milano
Milan
Università degli Studi di Modena e Reggio Emilia (UNIMORE)
Modena
Istituto Dermopatico dell'Immacolata (IDI) - Istituto di
Rome
UOS "Centro delle Dermatosi Croniche Complesse e Genodermatosi" UOC Dermatologia
Rome
Philippines3 sites
Asian Hospital
City of Muntinlupa
Iloilo Doctors Hospital
Iloilo City
Health Cube Medical Clinics
Mandaluyong
Australia2 sites
Premier Specialists
Kogarah
Sydney Children's Hospital
Randwick
China1 site
Dermatology Hospital of Southern Medical University
Guangzhou, Guangdong
Greece1 site
Hospital of Skin and Venereal Diseases of Thessaloniki
Thessaloniki
India1 site
Postgraduate Institute of Medical Education and Research (PGIMER)
Chandigarh
Malaysia1 site
Hospital Tunku Azizah (Hospital Wanita Dan Kanak-kanak Kuala Lumpur)
Kuala Lumpur
United Arab Emirates1 site
Sheikh Khalifa Medical City (SKMC)
Abu Dhabi
United Kingdom1 site
Great Ormond Street Hospital (GOSH) for Children NHS Foundation Trust - Somers Clinical Research Facility (CRF)
London
About this study
Official title: 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]
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.
Read the detailed description
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.
- Being tested
- AC-203, Vehicle
- Keywords
- Epidermolysis Bullosa Simplex, EBS
- Medical subject headings
- Epidermolysis Bullosa Simplex
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AC-203Drug
The investigational product is formulated as 1% topical ointment
VehicleDrug
Vehicle-only control study medication is the same formulation as investigational product without active ingredient
| Study group | Role | What they receive |
|---|---|---|
| Part A AC-203 | Experimental | Double-blind, AC-203 Diacerein 1% ointment, QD Receives: Drug: AC-203 |
| Part A Vehicle ointment | Placebo comparator | Double-blind, Vehicle ointment, QD Receives: Drug: Vehicle |
| Part B AC-203 | Experimental | Open-label extension phase, AC-203 Diacerein 1% ointment, QD Receives: Drug: AC-203 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
Measured: 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
The Body Surface Area (BSA) of the Assessment Area will be collected for all lesions included within the Treatment Area using the palmar method
Measured: from Baseline A (Visit 2/Day 1) to Week 8 (Visit 5/EOT)
Change in pain intensity score
Wong-Baker FACES® Pain Rating Scale will be used for patients 3 years and older.
Measured: Baseline A (Visit 2/Day 1) to Week 8 (Visit 5/EOT)
Change in pruritus intensity score
ItchyQuant will be used for patients aged 6 years and older, including adult patients
Measured: from Baseline A (Visit 2/Day 1) to Week 8 (Visit 5/EOT)
Change in EBDASI score (skin activity)
The EBDASI is a valid and reliable EB-specific outcome measurement tool to assess the overall extent of disease activity and damage in patients with various subtypes of EB, including EBS. Section I (skin), the severity of disease, including erosion/blisters/crusting etc., will be measured at 12 different skin sites.
Measured: from Baseline A (Visit 2/Day 1) to Week 8 (Visit 5/EOT).
Change in the QOLEB score
The Life Epidermolysis Bullosa (QOLEB) questionnaire is a valid and reliable, EB-specific QOL measurement tool, for the quantification of QOL in patients with various subtypes of EB, including EBS. It consists of 17 questions with four response choices from "not at all" to "constant"
Measured: from Baseline A (Visit 2/Day 1) to Week 8 (Visit 5/EOT)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Oct 2023
- Study start4 Apr 2024
- Primary completion10 Jun 2026
- Study completionMar 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Generalized Epidermolysis Bullosa SimplexStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 80 participants (estimated)
Sponsor and investigators
- Lead sponsor
- TWi Biotechnology, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06073132
- Sponsor's protocol ID
- AC-203-EBS-007
- Acronym
- EBShield
- Status last verified
- Jul 2026
- First submitted
- 12 Sep 2023
- Last updated
- 9 Jul 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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]
- ClinicalTrials.gov ID
- NCT06073132
- Acronym / sponsor ID
- EBShield / AC-203-EBS-007
- Keywords
- Epidermolysis Bullosa Simplex, EBS
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 80 participants (estimated)
- Lead sponsor
- TWi Biotechnology, Inc.Industry (pharma, biotech, devices)
- Study start
- 4 Apr 2024 (actual)
- Primary completion
- 10 Jun 2026 (actual)
- Study completion
- Mar 2027 (estimated)
- First posted
- 10 Oct 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Part A AC-203 | Experimental | Drug: AC-203Double-blind, AC-203 Diacerein 1% ointment, QD |
| Part A Vehicle ointment | Placebo comparator | Drug: VehicleDouble-blind, Vehicle ointment, QD |
| Part B AC-203 | Experimental | Drug: AC-203Open-label extension phase, AC-203 Diacerein 1% ointment, QD |
Who may qualify
- Ages
- 6 months and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (10 listed)
- 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.
Key exclusion criteria (13 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AC-203The investigational product is formulated as 1% topical ointment | Drug | Part A AC-203, Part B AC-203 |
| VehicleVehicle-only control study medication is the same formulation as investigational product without active ingredient | Drug | Part A Vehicle ointment |
Primary outcome
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
Time frame: from Baseline A (Visit 2/Day 1) to Week 8 (Visit 5/EOT)
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)
5 secondary outcomes
Change in % BSA of EBS lesions in the Treatment Area
Time frame: from Baseline A (Visit 2/Day 1) to Week 8 (Visit 5/EOT)
Change in pain intensity score
Time frame: Baseline A (Visit 2/Day 1) to Week 8 (Visit 5/EOT)
Change in pruritus intensity score
Time frame: from Baseline A (Visit 2/Day 1) to Week 8 (Visit 5/EOT)
Change in EBDASI score (skin activity)
Time frame: from Baseline A (Visit 2/Day 1) to Week 8 (Visit 5/EOT).
Change in the QOLEB score
Time frame: from Baseline A (Visit 2/Day 1) to Week 8 (Visit 5/EOT)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Jul 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
30 sites in 18 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing AC-203 in people with Generalized Epidermolysis Bullosa Simplex, run by TWi Biotechnology, Inc. at 30 sites in 18 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 9 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 30 sites in United States, Italy, Philippines, Australia, Austria and 13 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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 (time frame: from Baseline A (Visit 2/Day 1) to Week 8 (Visit 5/EOT)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Jul 2026.