Guselkumab for Skin Ulcers

(GEORGE Trial)

Overseen By Alex G Ortega-Loayza, MD, MCR

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Oregon Health and Science University

Must be taking: Prednisone

Must not be taking: Biologics, Immunosuppressives

Disqualifiers: Infections, Cancer, Hypertension, 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: Unknown

Duration: 28 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests guselkumab, a medication, to evaluate its effectiveness in treating pyoderma gangrenosum (PG), a condition causing painful skin ulcers. Researchers aim to assess its effectiveness in both the short and long term. Participants should have at least one PG ulcer measuring 4 cm² or larger and must already be receiving wound care. This trial suits those requiring ongoing systemic treatment and who can commit to regular study visits. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications for pyoderma gangrenosum (PG) before starting the study drug, with specific 'washout' periods (time without taking certain medications) ranging from 2 to 12 weeks depending on the medication. However, you can continue taking medications for other conditions, except for Methotrexate and Leflunomide, which cannot be taken together.

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

Research has shown that guselkumab is generally safe for people. It is approved for treating moderate-to-severe plaque psoriasis, indicating its safety for that condition. In studies on pyoderma gangrenosum (PG), a rare skin disorder, reports have indicated significant healing. In one case, the ulcer nearly disappeared within three months, with over 95% of the skin healing.

Although specific safety data for PG is limited, the approval for other conditions provides some reassurance about its safety. This study is in an early phase, so researchers are still learning about its safety and effectiveness for PG. Participants should discuss potential risks and benefits with their healthcare provider before joining the trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for pyoderma gangrenosum?

Unlike the standard treatments for skin ulcers, like immunosuppressants and topical steroids, Guselkumab targets a specific part of the immune system known as interleukin-23 (IL-23). This makes it unique because it directly interferes with the inflammatory process that contributes to skin ulcers, potentially offering a more targeted approach. Researchers are excited about Guselkumab because it has shown promise in other inflammatory conditions, suggesting it might provide better results or fewer side effects than existing therapies. Plus, its dosing schedule of every four weeks could be more convenient for patients compared to daily or more frequent treatments.

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

Research has shown that guselkumab, which participants in this trial will receive, may help treat pyoderma gangrenosum (PG), a painful skin condition. In some cases, patients experienced major improvements, with ulcers nearly disappearing in three months and 95% of the affected skin healing. Other reports indicate that guselkumab worked well when standard treatments, like corticosteroids, failed. Some patients fully healed after just a few doses. These findings suggest that guselkumab could be an effective option for managing PG. ^{1 2 4 6 7}

Who Is on the Research Team?

Alex G Ortega-Loayza, MD, MCR

Principal Investigator

Oregon Health and Science University, Department of Dermatology

Are You a Good Fit for This Trial?

This trial is for adults with Pyoderma Gangrenosum (PG), a rare skin condition that causes painful ulcers. Participants should have an active PG ulcer and be in generally stable health to join the study.

Inclusion Criteria

Willingness to comply with study procedures/requirements

I am eligible for systemic therapy and have been on a stable dose of 20 mg/day of prednisone for at least two weeks.

I receive wound care at least weekly.

Exclusion Criteria

Participant has known allergies, hypersensitivity, or intolerance to guselkumab or its excipients

Individuals who are pregnant, lactating or breastfeeding

History of chronic or recurrent infections, or active, untreated, acute infection, or immunocompromised to an extent that participation in the study would pose an unacceptable risk to the subject based on the investigator's clinical assessment

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive guselkumab 100 mg every 4 weeks for 28 weeks and a stable dose of prednisone daily

28 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Guselkumab

Trial Overview The trial is testing Guselkumab, a medication, to see how effective it is at treating PG. It's an open-label study, meaning everyone knows they're getting the drug, and it looks at results after 6 weeks, then again at 16 and 32 weeks.

How Is the Trial Designed?

Group I: Guselkumab for PG Experimental Treatment 1 Intervention

Subjects with PG will be treated with 100 mg every 4 weeks of guselkumab for 28 weeks in addition to starting stable dose (at least 2 weeks) of prednisone at 20 mg daily. Prednisone will be tapered based on a pre-established algorithm assessed by investigator.

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

Approved in United States as Tremfya for:

• Moderate to severe plaque psoriasis
• Psoriatic arthritis
• Moderately to severely active ulcerative colitis

Approved in European Union as Tremfya for:

• Moderate to severe plaque psoriasis
• Psoriatic arthritis
• Moderately to severely active ulcerative colitis

Who Is Running the Clinical Trial?

Oregon Health and Science University

Lead Sponsor

Trials

1,024

Recruited

7,420,000+

Janssen Scientific Affairs, LLC

Industry Sponsor

Trials

165

Recruited

579,000+

Joaquin Duato

Janssen Scientific Affairs, LLC

Chief Executive Officer since 2022

MBA from ESADE, Master of International Management from Thunderbird School of Global Management

Dr. Jijo James, MD

Janssen Scientific Affairs, LLC

Chief Medical Officer since 2014

MD from St. Johns Medical College, MPH from Columbia University

Ohio State University

Collaborator

Trials

891

Recruited

2,659,000+

Published Research Related to This Trial

In a study involving 5 patients with neurotrophic keratopathy, treatment with topical recombinant human nerve growth factor cenegermin 0.02% led to significant healing of corneal ulcers and improved corneal sensitivity after 8 weeks of use, with no adverse events reported.

Cenegermin is recommended as an effective treatment for advanced neurotrophic keratopathy, particularly when used alongside conventional therapies, as it promotes corneal healing and helps maintain corneal surface health without the need for surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neurotrophic Keratopathy Treated with Topical Recombinant Human Nerve Growth Factor (Cenegermin): Case Series Study with Long-Term Follow-Up. García-Delpech, S., Udaondo, P., Fernández-Santodomingo, AS., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06563323

Guselkumab in the Treatment of Adults With Pyoderma ... This is a Phase II study that will be open label and include a total of 17 patients who will receive the investigational product. PG will be defined by the ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7810910/

Guselkumab as a treatment option for recalcitrant ... Within 3 months, the ulcer was virtually non-existent. Re-epithelialization was notable over 95%of the original ulcer. The response was found to be durable, ...

3. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/full/10.1002/jvc2.522

Successful treatment of pyoderma gangrenosum with ... We report two successful cases of off-label treatment for PG, using guselkumab, after unsuccessful treatments with standard regimens of corticosteroids.

4. sciencedirect.com sciencedirect.com/science/article/pii/S235251262100895X

Modified dose of guselkumab for treatment of pyoderma ... She achieved complete healing after 4 doses of guselkumab (Fig 1, C). Fig 2, A, B displays the timeline of the patient's presentation, diagnosis, and treatment ...

5. synapse.patsnap.com synapse.patsnap.com/article/what-clinical-trials-have-been-conducted-for-guselkumab

What clinical trials have been conducted for Guselkumab? These trials have confirmed that guselkumab is well tolerated and effective in younger populations, with dosing regimens adapted from adult ...

6. jaadcasereports.org jaadcasereports.org/article/S2352-5126(21)00895-X/fulltext

Modified dose of guselkumab for treatment of pyoderma ... We report a case of recalcitrant PG treated with guselkumab (an IL-23 inhibitor) at a dose modified from that approved for other inflammatory conditions.

7. sciencedirect.com sciencedirect.com/science/article/pii/S0022202X24028926/pdf

The Clinical and Molecular Response of Pyoderma ... We present the results of a proof-of-concept open-label clinical trial of IL-23p19 antagonism with tildrakizumab in pyoderma gangrenosum. Gene expression ...