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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called spesolimab for individuals with moderate to severe pyoderma gangrenosum, a rare condition that causes skin ulcers. The researchers aim to determine if spesolimab can improve these ulcers and understand the immune system's response to the treatment. Participants should have at least one ulcer that hasn't improved with treatments like steroids or immune blockers. For those dealing with this condition and finding previous treatments ineffective, this trial might be suitable. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important findings.

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 there any evidence suggesting that spesolimab is likely to be safe for humans?

Research has shown that spesolimab is generally safe for individuals with conditions like pyoderma gangrenosum. Some studies have tested its safety for other skin issues and found that most side effects are mild to moderate, including headaches and injection site reactions like redness or swelling. Serious side effects were rare.

Spesolimab is currently being tested in various trials, indicating some confidence in its safety. However, as with any treatment, reactions can vary, so discussing any concerns with the study team is advisable. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Most treatments for Pyoderma Gangrenosum, like corticosteroids and immunosuppressants, work by generally dampening the immune system. But spesolimab works differently, targeting a specific part of the immune system called the interleukin-36 receptor, which plays a role in inflammatory responses. Researchers are excited about spesolimab because it offers a more targeted approach, potentially reducing inflammation with fewer side effects. Additionally, spesolimab is administered intravenously, which might provide a quicker and more direct effect compared to some oral medications.

What evidence suggests that spesolimab might be an effective treatment for pyoderma gangrenosum?

Research has shown that spesolimab, the treatment under study in this trial, may help treat pyoderma gangrenosum, a rare skin condition causing painful sores. In previous studies, some patients who received spesolimab experienced significant symptom improvement. This treatment blocks parts of the immune system that cause inflammation. One successful case report demonstrated a reduction in sore size and inflammation. These findings suggest spesolimab might be a viable option for people dealing with this challenging condition. ^{1 2 5 6 7}

Who Is on the Research Team?

Saakshi Khattri

Principal Investigator

Icahn School of Medicine at Mount Sinai

Are You a Good Fit for This Trial?

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 for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06624670

NCT06624670 | A Study to Test Whether Spesolimab ... The purpose of this study is to find out whether a medicine called spesolimab helps people with pyoderma gangrenosum (PG). The main aim is to see whether ...

2. jaad.org jaad.org/article/S0190-9622(25)01851-1/fulltext

59674 Randomized Phase 3 trial of spesolimab in patients ... Conclusions: These results will provide safety and efficacy data on spesolimab as a potential treatment for ulcerative PG. Article metrics. Related Articles.

3. clinicaltrial.be clinicaltrial.be/en/details/453227?per_page=20&only_recruiting=0&only_eligible=0&only_active=0

A Study to Test Whether Spesolimab Helps People With a ... The purpose of this study is to find out whether a medicine called spesolimab helps people with pyoderma gangrenosum (PG). The main aim is to see whether ...

4. clinicaltrials.icts.uci.edu clinicaltrials.icts.uci.edu/trial/NCT06624670

Test Whether Spesolimab Helps People With a Skin ... The purpose of this study is to find out whether a medicine called spesolimab helps people with pyoderma gangrenosum (PG).

5. frontiersin.org frontiersin.org/journals/immunology/articles/10.3389/fimmu.2025.1581996/full

Case Report: Spesolimab for pyoderma gangrenosum in ... The case highlights the successful use of Spesolimab (anti-IL36R) in treating PG and explores the potential “paradoxical phenomenon” linked to anti-IL-17 ...

6. boehringer-ingelheim.com boehringer-ingelheim.com/science-innovation/human-health-innovation/clinical-pipeline/spesolimab-bi-655130-il36r-antibody-1

Spesolimab (BI 655130): IL36R antibody Indication: Pyoderma gangrenosum. Spesolimab is a first-in class anti-IL-36 receptor antibody from Boehringer Ingelheim´s own research. It is being investigated ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT06624670?term=AREA%5BLeadSponsorName%5D(boehringer%20ingelheim)%20AND%20AREA%5BOverallStatus%5D(RECRUITING)%20AND%20AREA%5BPhase%5D(PHASE1%20OR%20PHASE2%20OR%20PHASE3%20OR%20PHASE4)&rank=8

A Study to Test Whether Spesolimab Helps People With ... The purpose of this study is to find out whether a medicine called spesolimab helps people with pyoderma gangrenosum (PG). The main aim is to see whether ...