Diacerein Ointment for Epidermolysis Bullosa

(EBShield Trial)

Recruiting at 35 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

Trial Summary

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.

What data supports the effectiveness of the drug Diacerein 1% Ointment for treating Epidermolysis Bullosa?

Research shows that Diacerein 1% Ointment significantly reduces the number of blisters in patients with Epidermolysis Bullosa Simplex, with reductions of up to 78% in some cases. The drug works by reducing inflammation and stabilizing skin cells, making it an effective and safe treatment option. ^{1 2 3 4 5}

How is the drug Diacerein 1% Ointment unique for treating epidermolysis bullosa?

Diacerein 1% Ointment is unique because it targets the inflammation and structural fragility in epidermolysis bullosa by reducing the expression of a mutated protein and inhibiting an inflammatory enzyme, which helps decrease blistering. Unlike other treatments that mainly manage symptoms, this ointment directly addresses the underlying causes of blister formation. ^{1 2 4 5 6}

What is the purpose of this trial?

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.

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

References

1. Canada pubmed.ncbi.nlm.nih.gov

Topical Diacerein Ointment for Epidermolysis Bullosa Simplex: A Review [2022]

2. England pubmed.ncbi.nlm.nih.gov

Basal pharmacokinetic parameters of topically applied diacerein in pediatric patients with generalized severe epidermolysis bullosa simplex. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Epidermolysis bullosa. Assessment of a treatment regimen. [2019]

4. England pubmed.ncbi.nlm.nih.gov

Topical diacerein for epidermolysis bullosa: a randomized controlled pilot study. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Diacerein 1% Ointment for the Treatment of Epidermolysis Bullosa Simplex: A Randomized, Controlled Trial. [2023]

6. Denmark pubmed.ncbi.nlm.nih.gov

Epidermolysis bullosa: Advances in research and treatment. [2022]