Diacerein Ointment for Epidermolysis Bullosa

(EBShield Trial)

Recruiting at 42 trial locations

Overseen By John C. Browning, MD

Age: Any Age

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: TWi Biotechnology, Inc.

Must not be taking: Diacerein, Systemic steroids

Disqualifiers: Psoriasis, Atopic dermatitis, Uncontrolled diabetes, others

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 5

Duration: 8 weeks

80 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new ointment called diacerein for individuals with Epidermolysis Bullosa Simplex (EBS), a condition that causes painful blisters. The goal is to determine if the ointment is safe and effective in easing symptoms. Participants will use either the diacerein ointment or a placebo (a look-alike ointment with no active ingredients) to compare results. Individuals with a confirmed diagnosis of severe or intermediate EBS who have visible skin blisters may be suitable for this trial. As a Phase 2, Phase 3 trial, this research measures the treatment's effectiveness in an initial, smaller group and represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial does not specify if you must stop all current medications, but you must report all medications you use. Some medications, like certain topical therapies and steroids, must be stopped before the trial starts.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that diacerein 1% ointment is generally safe and effective for people with epidermolysis bullosa (EBS). In earlier studies, patients experienced a significant reduction in blistering, with more than 70% improvement after six weeks of use. These studies did not report any major side effects, indicating the ointment's safety for skin use. However, some individuals might experience mild skin irritation, a common reaction to creams and ointments. Overall, the evidence suggests that diacerein 1% ointment is a promising and safe option for managing EBS symptoms. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for epidermolysis bullosa, which often focus on wound care and pain management, Diacerein 1% ointment introduces a novel approach by targeting inflammation directly. Diacerein is unique because it works by inhibiting interleukin-1 beta, a key player in the inflammatory process associated with this condition. Researchers are excited about this treatment because it offers a potential dual benefit: reducing inflammation and promoting better skin healing, which could significantly improve quality of life for patients with this challenging skin disorder.

What evidence suggests that diacerein 1% ointment might be an effective treatment for epidermolysis bullosa?

Research has shown that diacerein 1% ointment can significantly reduce blistering in people with epidermolysis bullosa simplex (EBS). One study found that patients using this ointment experienced over 70% fewer blisters after six weeks. Another study reported a 60% reduction in blisters for those using the ointment, compared to only a 15% reduction for those using a placebo. In this trial, participants will receive either the diacerein 1% ointment or a vehicle ointment as a placebo comparator. These findings suggest that diacerein 1% ointment could effectively reduce blisters in EBS. ^{1 3 4 6 7}

Are You a Good Fit for This Trial?

This trial is for patients at least 6 months old with severe or intermediate Generalized Epidermolysis Bullosa Simplex (EBS), confirmed by genetic diagnosis. They must have a specific severity of EBS lesions and be willing to follow the study's medication application instructions, report all medication use, and attend all study visits.

Inclusion Criteria

I am at least 6 months old.

I am using a highly effective birth control method.

Patient's EBS lesions within the Treatment Area have an IGA score of ≥3 at Visit 2 (Day 1/Baseline A)

Exclusion Criteria

I haven't used any skin treatments not allowed by the study in the last 2 weeks.

I haven't had a skin infection or taken antibiotics within 7 days before my first or last visit.

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)

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either the vehicle ointment or AC-203 Diacerein 1% ointment in a double-blind manner

8 weeks

5 visits (in-person)

Open-label extension

Participants receive AC-203 Diacerein 1% ointment in an open-label manner

Long-term

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Diacerein 1% Ointment

Trial Overview The trial is testing diacerein 1% ointment versus a placebo (vehicle) to see if it's effective and safe for treating generalized EBS. It includes an initial phase where neither the researchers nor participants know who gets which treatment, followed by an open-label phase where everyone knows.

How Is the Trial Designed?

Group I: Part B AC-203 Experimental Treatment 1 Intervention

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

Group II: Part A AC-203 Experimental Treatment 1 Intervention

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

Group III: Part A Vehicle ointment Placebo Group 1 Intervention

Double-blind, Vehicle ointment, QD

Diacerein 1% Ointment is already approved in United States, European Union for the following indications:

Approved in United States as Diacerein 1% Ointment for:

• Epidermolysis Bullosa Simplex (EBS)

Approved in European Union as Diacerein 1% Ointment for:

• Epidermolysis Bullosa Simplex (EBS)

Who Is Running the Clinical Trial?

TWi Biotechnology, Inc.

Lead Sponsor

Trials

10

Recruited

690+

Published Research Related to This Trial

Topical 1% diacerein has been shown to be an effective and safe non-invasive treatment for patients with generalized severe epidermolysis bullosa simplex (EBS), a condition characterized by painful blistering due to mutated K14 protein and inflammation.

Diacerein works by reducing the expression of the problematic K14 protein and inhibiting the pro-inflammatory cytokine IL-1, which contributes to the disease's symptoms, and it has received special designations from the FDA to expedite its development for pediatric use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Topical Diacerein Ointment for Epidermolysis Bullosa Simplex: A Review Limmer, AL., Nwannunu, CE., Shah, R., et al.[2022]

In a clinical phase 2/3 trial, topical application of diacerein significantly reduced blister numbers in patients with generalized severe epidermolysis bullosa simplex (EBS-gen sev), indicating its efficacy in treating this condition.

Pharmacokinetic studies showed that diacerein is effectively absorbed and metabolized to rhein in the skin, with lower systemic levels of rhein observed in patients compared to oral administration, suggesting a favorable safety profile for topical use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Basal pharmacokinetic parameters of topically applied diacerein in pediatric patients with generalized severe epidermolysis bullosa simplex. Ablinger, M., Felder, TK., Wimmer, M., et al.[2022]

In a study involving 19 patients with various types of epidermolysis bullosa, 90% of hospitalized patients showed significant improvement, with a 76% reduction in blister numbers during their stay.

While the treatment led to accelerated healing of blisters for about 50% of outpatients over 5-11 months, it had limited long-term effects on preventing new blister formation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Epidermolysis bullosa. Assessment of a treatment regimen. Haber, RM., Ramsay, CA., Boxall, LB.[2019]

In a pilot study involving five patients with epidermolysis bullosa simplex type Dowling-Meara, a topical formulation of 1% diacerein significantly reduced blistering, with a 78% reduction in one armpit compared to a 66% reduction in the other.

The effects of diacerein persisted even after stopping treatment, suggesting its potential as an effective therapy for managing blistering in this condition and warranting further confirmative studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Topical diacerein for epidermolysis bullosa: a randomized controlled pilot study. Wally, V., Kitzmueller, S., Lagler, F., et al.[2022]

In a double-blind study involving 54 patients with epidermolysis bullosa simplex (EBS), diacerein 1% ointment did not show a significant difference in efficacy compared to a vehicle ointment for reducing blistering after 8 weeks.

However, a post hoc analysis indicated that patients with severe EBS treated with diacerein had a higher rate of achieving a low Investigator’s Global Assessment score, suggesting potential benefits for this specific subgroup that warrant further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Diacerein 1% Ointment for the Treatment of Epidermolysis Bullosa Simplex: A Randomized, Controlled Trial. Teng, J., Paller, AS., Bruckner, AL., et al.[2023]

Epidermolysis bullosa (EB) is a group of rare skin disorders caused by genetic mutations, and while there is currently no cure, innovative therapies like gene, protein, and cell-based treatments are being explored at the EB House Austria.

Current clinical trials include the use of immunotherapy with an anti-PD1 monoclonal antibody for treating advanced skin cancer in EB patients, as well as topical treatments aimed at improving wound healing, highlighting the urgent need for effective therapeutic options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Epidermolysis bullosa: Advances in research and treatment. Prodinger, C., Reichelt, J., Bauer, JW., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3655927/

Topical diacerein for epidermolysis bullosa: a randomized ... The significance level was set to 5%. Results showed a statistically significant reduction of blisters within the first two weeks of P1 (t1: 100%, t2: mean left ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S0190962218301300

Diacerein orphan drug development for epidermolysis ... In this pilot study, patients achieved a reduction of blisters by more than 70% upon application of 1% diacerein cream for 6 weeks. However, blisters did not ...

3. jddonline.com jddonline.com/articles/diacerein-1-ointment-for-the-treatment-of-epidermolysis-bullosa-simplex-a-randomized-controlled-trial-S1545961623P0599X/

Diacerein 1% Ointment for the Treatment of Epidermolysis ... Diacerein 1% ointment has been shown to reduce this blistering. Objective: To evaluate the efficacy and safety of diacerein 1% ointment in the treatment of EBS.

4. clinicaltrials.gov clinicaltrials.gov/study/NCT03154333

Safety and Efficacy of Diacerein 1% Ointment for Subjects ... The purpose of this study is to compare the efficacy of diacerein 1% ointment to vehicle ointment when applied once-daily for 8 weeks in subjects with EBS.

5. epidermolysisbullosanews.com epidermolysisbullosanews.com/news/arthritis-cream-diacerein-effective-girl-hard-treat-rdeb/

Arthritis cream diacerein effective for girl with hard-to-treat ... Early data from a Phase 2 study suggested the ointment reduced skin blistering by 60% versus 15% among placebo recipients.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT03154333

Safety and Efficacy of Diacerein 1% Ointment for Subjects ... The primary objective of this study is to compare the efficacy of diacerein 1% ointment to vehicle ointment based on reduction in body surface area (BSA) of EBS ...

7. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/10.1111/1346-8138.17621

Repurposing diacerein for the treatment of chronic wounds ... These data characterize diacerein as a potential candidate for improving wound healing in RDEB through its impact on inflammatory as well as ...