Spesolimab for Pyoderma Gangrenosum

Overseen By Giselle Singer

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Icahn School of Medicine at Mount Sinai

Must not be taking: Systemic antibiotics

Disqualifiers: HIV, Hepatitis B/C, Tuberculosis, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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: 13

Duration: 16-28 weeks

20 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing spesolimab, a medicine that blocks inflammation signals, in patients with severe skin ulcers caused by pyoderma gangrenosum. These patients often suffer from pain and have no standard treatment options. Spesolimab aims to reduce inflammation and help heal their skin ulcers.

Do I need to stop my current medications for the trial?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the study team or your doctor.

Is Spesolimab safe for human use?

Spesolimab, also known as spesolimab-sbzo or SPEVIGO, has been approved in the USA for treating generalized pustular psoriasis flares in adults, indicating it has undergone safety evaluations for this condition. While specific safety data for pyoderma gangrenosum is not available, its approval for another condition suggests it has been deemed generally safe for human use. ^{1 2 3 4 5}

How is the drug Spesolimab different from other treatments for pyoderma gangrenosum?

Spesolimab is unique because it targets the interleukin-36 receptor, which is different from other treatments that often target tumor necrosis factor (TNF) or interleukin-23. This novel mechanism may offer an alternative for patients who do not respond to or cannot tolerate existing therapies. ^{1 6 7 8 9}

Research Team

Saakshi Khattri

Principal Investigator

Icahn School of Medicine at Mount Sinai

Eligibility Criteria

Adults with moderate to severe pyoderma gangrenosum, a skin ulcer condition, who haven't responded to treatments like steroids or other immune therapies. Participants must be in good health otherwise and women of childbearing age must use effective contraception.

Inclusion Criteria

My gum disease is moderate to severe, with a score over 3.

I am not pregnant, will use effective birth control, and have a negative pregnancy test.

Subject is able to adhere to the study visit schedule and other protocol requirements

Exclusion Criteria

I haven't had serious infections or needed antibiotics in the last 2 weeks.

I have or had HIV, immunodeficiency, hepatitis B or C, or tuberculosis.

I do not have any major health issues that are not under control.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive spesolimab via a 90-minute infusion every 3 or 4 weeks, with a total of 8 or 9 visits during the study

16-28 weeks

8-9 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessments of PG lesion recurrence and quality of life

16 weeks

4-6 visits (in-person)

Treatment Details

Interventions

• Spesolimab

Trial Overview The trial is testing spesolimab's effectiveness on pyoderma gangrenosum by observing changes in the body's immune response and improvement in skin ulcers.

Participant Groups

Group I: Spesolimab Experimental Treatment 1 Intervention

900 mg of spesolimab intravenously (IV)

Spesolimab is already approved in United States, European Union for the following indications:

Approved in United States as Spevigo for:

• Generalized pustular psoriasis (GPP) in adults and pediatric patients 12 years of age and older and weighing at least 40 kg

Approved in European Union as Spevigo for:

• Generalized pustular psoriasis (GPP) flares in adults

Who Is Running the Clinical Trial?

Icahn School of Medicine at Mount Sinai

Lead Sponsor

Trials

933

Recruited

579,000+

Boehringer Ingelheim

Industry Sponsor

Trials

2,566

Recruited

16,150,000+

Findings from Research

Oral systemic treatments for pyoderma gangrenosum (PG), like cyclosporine and steroids, only achieve complete remission in about 50% of patients and can have significant side effects.

The case of a patient with peristomal PG showed a positive response to risankizumab, an anti-interleukin 23 monoclonal antibody, suggesting it could be a promising and safer treatment option that needs further research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Peristomal Pyoderma Gangrenosum Responding to Risankizumab. Weigelt, MA., Kirsner, RS.[2023]

In a study of 52 patients with pyoderma gangrenosum, biologics, particularly TNFα antagonists like infliximab and adalimumab, showed a higher effectiveness with complete remission or improvement in 63.6% to 57.1% of cases, compared to only 48.8% for corticosteroids and 20% for cyclosporine A.

Biologics and intravenous immunoglobulins (IVIGs) were found to be well-tolerated, with lower rates of adverse events (18.5% for biologics and 20% for IVIGs) compared to 40% for cyclosporine A, suggesting they are safer alternatives for treating pyoderma gangrenosum.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biologics and immunoglobulins in the treatment of pyoderma gangrenosum - analysis of 52 patients. Herberger, K., Dissemond, J., Brüggestrat, S., et al.[2019]

In a 26-week study involving 22 Japanese patients with pyoderma gangrenosum, adalimumab led to a significant reduction in ulcer size, with 54.5% of patients achieving complete skin re-epithelialization by week 26.

Adalimumab was generally well tolerated, although 18 patients experienced adverse events, primarily infections, indicating that while effective, monitoring for side effects is important.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An update on adalimumab for pyoderma gangrenosum. Yamamoto, T.[2021]

Tofacitinib, an immunosuppressive agent, showed promising results in treating pyoderma gangrenosum (PG) in a small group of 10 patients who had previously failed an average of four other treatments.

In this study, 40% of patients experienced complete healing of their ulcers, while 60% showed significant clinical improvement, suggesting that tofacitinib could be an effective steroid-sparing option for refractory PG.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tofacitinib for the treatment of refractory pyoderma gangrenosum. Orfaly, VE., Kovalenko, I., Tolkachjov, SN., et al.[2021]

Spesolimab, an interleukin-36 receptor antagonist, was approved in September 2022 in the USA specifically for treating flares of generalized pustular psoriasis (GPP) in adults.

The approval of spesolimab marks a significant milestone in the development of treatments for immune-mediated disorders, highlighting its potential efficacy in managing GPP flares.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Spesolimab: First Approval. Blair, HA.[2022]

In a case study of a 27-year-old woman with severe Crohn's disease and refractory Pyoderma gangrenosum (PG), the combination of certolizumab pegol with systemic steroids and tacrolimus led to complete healing of PG after previous treatments failed.

Certolizumab pegol may serve as an effective alternative therapy for PG in patients who cannot tolerate or do not respond to other anti-TNF therapies, highlighting its potential role in managing this challenging condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Certolizumab pegol - A new therapeutic option for refractory disseminated pyoderma gangrenosum associated with Crohn's disease. Hurabielle, C., Schneider, P., Baudry, C., et al.[2018]

New diagnostic criteria for pyoderma gangrenosum have been proposed to help speed up diagnosis and treatment, which is crucial to reduce complications and improve patient outcomes.

For treatment, local immunosuppressive therapies are recommended for mild cases, while severe cases may require systemic glucocorticoids, ciclosporin, or TNF-alpha inhibitors, with other biologics also being explored.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Pyoderma gangrenosum]. Burian, EA., Karlsmark, T., Fogh, K., et al.[2021]

A 46-year-old patient with severe pyoderma gangrenosum related to Crohn's disease showed significant improvement after receiving infliximab, a medication that targets tumor necrosis factor-alpha, administered intravenously at 5 mg/kg.

The patient's abdominal symptoms and skin lesions improved markedly after the first dose, and they have remained in remission on a maintenance regimen, suggesting that infliximab is an effective treatment for both Crohn's disease and associated skin conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Favorable response to infliximab treatment in a patient with active Crohn disease and pyoderma gangrenosum. Triantafillidis, JK., Cheracakis, P., Sklavaina, M., et al.[2015]

Glucocorticoids are the first-line treatment for pyoderma gangrenosum (PG), but recent evidence suggests that biologics, such as TNF-α inhibitors and IL-1 inhibitors, are emerging as effective alternatives.

The article reviews various treatment options for PG, including local therapies and systemic medications, aiming to guide clinicians in managing this rare and complex skin condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Current situation and the latest progress in the treatment of pyoderma gangrenosum]. Li, Y., Wang, YY., Xing, K., et al.[2022]

References

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

Peristomal Pyoderma Gangrenosum Responding to Risankizumab. [2023]

2. Germany pubmed.ncbi.nlm.nih.gov

Biologics and immunoglobulins in the treatment of pyoderma gangrenosum - analysis of 52 patients. [2019]

3. Spain pubmed.ncbi.nlm.nih.gov

An update on adalimumab for pyoderma gangrenosum. [2021]

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

Tofacitinib for the treatment of refractory pyoderma gangrenosum. [2021]

5. New Zealand pubmed.ncbi.nlm.nih.gov

Spesolimab: First Approval. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Certolizumab pegol - A new therapeutic option for refractory disseminated pyoderma gangrenosum associated with Crohn's disease. [2018]

7. Denmark pubmed.ncbi.nlm.nih.gov

[Pyoderma gangrenosum]. [2021]

8. England pubmed.ncbi.nlm.nih.gov

Favorable response to infliximab treatment in a patient with active Crohn disease and pyoderma gangrenosum. [2015]

9. China pubmed.ncbi.nlm.nih.gov

[Current situation and the latest progress in the treatment of pyoderma gangrenosum]. [2022]