Baricitinib for Pyoderma Gangrenosum

Overseen By Morgan Vague, BA

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Oregon Health and Science University

Must be taking: Prednisone

Must not be taking: JAK inhibitors, Strong OAT-3 inhibitors

Disqualifiers: Malignancy, Active infection, HIV, 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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

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

Compensation: Varies

Number of Visits: Unknown

Duration: 24 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test baricitinib, a medication, to determine its effectiveness in treating pyoderma gangrenosum, a painful skin condition that causes large, open sores. Participants will take baricitinib daily alongside a stable dose of prednisone, a medication already used for this condition. The trial seeks individuals with at least one pyoderma gangrenosum ulcer measuring at least 4 cm², who have been managing their wounds weekly and are stable on prednisone. Participants must be willing to visit Oregon Health and Science University or attend remote videoconferencing visits if they live more than 30 miles away. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

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

Yes, you will need to stop taking certain medications. Participants must discontinue immunosuppressive therapies like cyclosporine and methotrexate at least 4 weeks before starting the study drug. Additionally, there are specific washout periods for biologic therapies, such as 4 weeks for drugs like infliximab and 24 weeks for rituximab.

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

Research has shown that baricitinib is generally safe. In a previous 16-week study, no new safety issues emerged, indicating good patient tolerance. Baricitinib already has approval for other health conditions, which increases confidence in its safety. While this study examines its use for pyoderma gangrenosum, existing information provides reassurance for potential participants. ^{1 2 3 4 5}

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

Unlike the standard treatments for pyoderma gangrenosum, which often rely on immunosuppressants like corticosteroids and cyclosporine, baricitinib is unique because it targets the Janus kinase (JAK) pathway. This pathway plays a key role in inflammation, and by inhibiting it, baricitinib offers a new mechanism of action that could more directly address the inflammatory processes underlying the condition. Researchers are excited about baricitinib because it may provide a more targeted approach, potentially reducing side effects associated with broader immunosuppressive therapies and improving healing times for patients.

What evidence suggests that Baricitinib might be an effective treatment for Pyoderma Gangrenosum?

Research has shown that baricitinib, a medication that blocks certain enzymes causing inflammation, holds potential for treating pyoderma gangrenosum (PG), a condition that causes painful skin ulcers. In earlier studies, baricitinib completely healed skin ulcers in two patients with PG. Another report highlighted a patient with PG unresponsive to other treatments who saw significant improvement with baricitinib. This medication reduces inflammation, a key issue in PG. These findings suggest that baricitinib could be effective for people with PG, especially those who haven't improved with other treatments. Participants in this trial will receive baricitinib alongside a stable dose of prednisone to evaluate its effectiveness in treating PG. ^{1 3 4 6 7}

Who Is on the Research Team?

Alex G Ortega-Loayza, MD, MCR

Principal Investigator

Oregon Health & Science University, Department of Dermatology

Are You a Good Fit for This Trial?

Adults aged 18-99 with Pyoderma Gangrenosum (PG) ulcers, who can travel to OHSU or do video calls for study visits. Women must use birth control or abstain; men must agree not to father children during the trial. Participants should be stable on prednisone and off other immunosuppressives for 4 weeks.

Inclusion Criteria

Willingness to comply with study procedures/requirements

I am a woman aged 18-99, not pregnant, and agree to use birth control or remain abstinent during the study.

I receive weekly wound care at home or a facility.

Exclusion Criteria

Are investigator site personnel directly affiliated with this study and/or their immediate families (spouse, parent, child, or sibling)

I have had a shingles outbreak within the last 3 months or have had recurrent or widespread shingles.

Have any other condition that precludes the subject from following and completing the protocol, in the opinion of the investigator

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 4 mg of baricitinib once daily for 24 weeks, along with a stable dose of prednisone, which is tapered based on a pre-established algorithm

24 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment, with assessments including cytokine gene expression and quality of life measures

12 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Baricitinib

Trial Overview The trial is testing Baricitinib, an oral medication, in adults with PG. It's an open-label study where everyone knows they're getting the drug. The goal is to see if it helps heal skin ulcers better than current treatments.

How Is the Trial Designed?

Group I: Baricitinib for PG Experimental Treatment 1 Intervention

Subjects with PG will be treated with 4 mg once daily of baricitinib for 24 weeks in addition to starting stable dose (at least 2 weeks) of prednisone at 30 mg daily. Prednisone will be tapered based on a pre-established algorithm assessed by investigator.

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

Approved in United States as Olumiant for:

• Rheumatoid arthritis
• Severe alopecia areata
• COVID-19

Approved in European Union as Olumiant for:

• Rheumatoid arthritis
• Severe alopecia areata
• COVID-19

Who Is Running the Clinical Trial?

Oregon Health and Science University

Lead Sponsor

Trials

1,024

Recruited

7,420,000+

Published Research Related to This Trial

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]

Pyoderma gangrenosum is a serious skin condition that often appears as ulcers and is linked to various systemic diseases, typically diagnosed through exclusion and clinical findings.

In two reported cases, chronic skin ulcers consistent with pyoderma gangrenosum completely healed after treatment with the Janus kinase inhibitor baricitinib, suggesting its potential efficacy in managing this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Successful treatment of ulcerated pyoderma gangrenosum with baricitinib, a novel JAK inhibitor. Scheinberg, M., Machado, LA., M Castro, LG., et al.[2021]

In a phase 3 trial involving 440 adults with moderate-to-severe atopic dermatitis, baricitinib (2 mg) demonstrated a significant efficacy, with 30% of patients achieving a ≥75% reduction in eczema severity at week 16 compared to only 8% in the placebo group.

Baricitinib also showed a favorable safety profile, with no new safety concerns identified over the 16-week study period, indicating it is a viable treatment option for patients who do not respond to topical therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Baricitinib in patients with moderate-to-severe atopic dermatitis: Results from a randomized monotherapy phase 3 trial in the United States and Canada (BREEZE-AD5). Simpson, EL., Forman, S., Silverberg, JI., et al.[2021]

In a study involving 1598 patients treated with baricitinib 2 mg for moderate-to-severe atopic dermatitis, the overall safety profile was confirmed, with treatment-emergent adverse events occurring in 57.9% of patients compared to 51.6% in the placebo group.

Serious adverse events were infrequent and similar between baricitinib and placebo, with no malignancies or major cardiovascular events reported during the placebo-controlled period, although longer exposure is needed to fully assess risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Extended Safety Analysis of Baricitinib 2 mg in Adult Patients with Atopic Dermatitis: An Integrated Analysis from Eight Randomized Clinical Trials. King, B., Maari, C., Lain, E., et al.[2022]

In a long-term study involving adults with moderate-to-severe atopic dermatitis, baricitinib combined with topical corticosteroids showed sustained efficacy over 68 weeks, with 26.5% of patients achieving significant improvement in their condition by Week 52.

Both 4-mg and 2-mg doses of baricitinib maintained clinically meaningful results, with higher response rates in the 2-mg group for certain measures, indicating that lower doses can also be effective in managing symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term efficacy (up to 68 weeks) of Baricitinib in combination with topical corticosteroids in adult patients with moderate-to-severe atopic dermatitis: Analysis of treatment responders, partial responders and nonresponders originating from study BREEZE-AD7. Silverberg, JI., Simpson, EL., Thyssen, JP., et al.[2023]

JAK inhibitors, including upadacitinib, baricitinib, abrocitinib, and topical ruxolitinib, have been found to have a generally favorable long-term safety profile for treating various dermatological conditions, based on a review of literature from 2000 to 2023.

The review identified 37 dermatological disorders where JAK inhibitors are supported for use, indicating their potential as effective treatment options for a wide range of skin disorders, including off-label applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-Term Safety Profile and Off-Label Use of JAK Inhibitors in Dermatological Disorders. Corbella-Bagot, L., Riquelme-McLoughlin, C., Morgado-Carrasco, D.[2023]

Baricitinib, a JAK1/JAK2 inhibitor approved for moderate-to-severe atopic dermatitis, was studied in 2636 patients over a total exposure of 4628.4 patient years, showing a low discontinuation rate due to adverse events (3.4 incidents per 100 patient years).

The safety profile of baricitinib remained consistent with previous analyses, with serious adverse events and infections occurring at rates comparable to background levels in atopic dermatitis patients, indicating no new safety concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of baricitinib for the treatment of atopic dermatitis over a median of 1.6 years and up to 3.9 years of treatment: an updated integrated analysis of eight clinical trials. Bieber, T., Katoh, N., Simpson, EL., et al.[2023]

Baricitinib, an oral JAK1/JAK2 inhibitor, has a safety profile that reflects the inherent risks of the diseases it treats, with higher rates of infections and serious adverse events observed in patients with rheumatic diseases compared to those with dermatological conditions.

In clinical studies, the incidence of major adverse cardiovascular events (MACE) with baricitinib was lower than that seen with tofacitinib and comparable to tumor necrosis factor inhibitors, indicating a favorable safety profile, especially in hospitalized COVID-19 patients treated for up to 14 days.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Review of Safety Outcomes from Clinical Trials of Baricitinib in Rheumatology, Dermatology and COVID-19. Bieber, T., Feist, E., Irvine, AD., et al.[2023]

Tofacitinib, a JAK/STAT pathway inhibitor, has shown promising results in treating pyoderma gangrenosum (PG) in three biopsy-proven cases, leading to successful outcomes without relapse during follow-up.

This treatment offers a potential new option for managing PG, which is often challenging due to its tendency to relapse and the need for prolonged steroid use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tofacitinib in pyoderma gangrenosum - A case series. Sathyanarayana, VA., Roy, D., Nagaraju, B., et al.[2023]

In a review of 148 cases of difficult-to-treat pyoderma gangrenosum (PG), it was found that the condition is more prevalent in females and those with inflammatory bowel disease, but most patients healed within a typical timeframe despite needing three or more treatments.

The study suggests that initiating biologic therapies earlier may be beneficial for PG patients, highlighting the need for standardized terminology in the field to improve treatment comparisons and outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recalcitrant Pyoderma Gangrenosum: Clinical Burden and Unmet Needs. Becker, SL., Velasco, R., Ortega-Loayza, AG.[2023]

Hospitalizations for pyoderma gangrenosum (PG) have increased from 2002 to 2012, with significant predictors including age 40-59, female sex, and multiple chronic conditions, indicating a growing healthcare burden.

Patients hospitalized for PG often face considerable risks, with over half experiencing moderate to major loss of function and a notable association with other health disorders, highlighting the need for effective management strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The inpatient burden and comorbidities of pyoderma gangrenosum in adults in the United States. Narla, S., Silverberg, JI.[2021]

JAK inhibitors, such as tofacitinib, upadacitinib, baricitinib, and abrocitinib, are highly effective for treating conditions like psoriatic arthritis and atopic dermatitis.

Despite their efficacy, JAK inhibitors are associated with increased risks of serious side effects, including venous thromboembolism and cardiovascular events, prompting the FDA to issue additional warning labels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

JAK in the [Black] Box: A Dermatology Perspective on Systemic JAK Inhibitor Safety. Elmariah, SB., Smith, JS., Merola, JF.[2022]

Baricitinib, an oral medication for moderate-to-severe atopic dermatitis, showed significant improvements in skin severity scores (EASI and SCORAD) as early as week 1 for monotherapy and week 2 for combination therapy, with effects lasting up to 16 weeks.

Patients treated with baricitinib experienced rapid and sustained improvements in quality of life, suggesting that these improvements may exceed what is reflected in traditional severity scores, indicating a potential disconnect between clinical assessments and patient experiences.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Baricitinib provides rapid and sustained improvements in absolute EASI and SCORAD outcomes in adults with moderate-to-severe atopic dermatitis. Thyssen, JP., Bieber, T., Kleyn, CE., et al.[2023]

In a Phase 3 trial with 329 patients suffering from moderate-to-severe atopic dermatitis, baricitinib (4-mg and 2-mg) combined with topical corticosteroids showed significant improvements in health-related quality of life (HRQoL) and work productivity starting as early as Week 2.

Baricitinib 4-mg maintained these improvements through Week 16, demonstrating its efficacy in reducing symptoms and enhancing overall treatment benefits compared to placebo.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of baricitinib in combination with topical steroids on atopic dermatitis symptoms, quality of life and functioning in adult patients with moderate-to-severe atopic dermatitis from the BREEZE-AD7 Phase 3 randomized trial. Wollenberg, A., Nakahara, T., Maari, C., et al.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10960974/

Use of Baricitinib in a patient with treatment-resistant ... Successful treatment of ulcerated pyoderma gangrenosum with baricitinib, a novel JAK inhibitor. J Transl Autoimmunity 2021; 4: 100099. [DOI] ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04901325?term=Baricitinib&aggFilters=status:not%20rec%20enr%20act%20com%20unk,phase:2%203&viewType=Table&rank=7

Baricitinib in the Treatment of Adults With Pyoderma ... These patients will undergo 24 weeks of baricitinib dosed daily and stable dose of prednisone dosed daily with follow-up until week 36.

3. withpower.com withpower.com/trial/phase-3-skin-diseases-8-2021-0da02

Baricitinib for Pyoderma Gangrenosum · Info for Participants Research shows that Baricitinib, a type of drug called a JAK inhibitor, helped two patients with Pyoderma Gangrenosum achieve complete remission, meaning their ...

4. s3.eu-central-1.amazonaws.com s3.eu-central-1.amazonaws.com/m-anage.com.storage.eadv/abstracts_congress_2025/61192.pdf

Abstract N°: LBA-193 Baricitinib in the Treatment of Adults ... Pyoderma gangrenosum (PG) is a rare neutrophilic dermatosis marked by chronic, painful skin ulcerations. While biologics have shown efficacy, ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8100614/

Successful treatment of ulcerated pyoderma gangrenosum ... In this research communication, we report on the first successful treatment of two PG patients with the novel JAK inhibitor, baricitinib. 1.1.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9464730/

Pyoderma Gangrenosum: An Updated Literature Review ... Treatment with systemic CS (dose 0.5–1 mg/kg/day) induces a clinical response in about 40–50% of cases [28], with widely variable complete response rates ...

7. trialx.com trialx.com/clinical-trials/listings/251107/baricitinib-in-the-treatment-of-adults-with-pyoderma-gangrenosum-pg/

Baricitinib in the Treatment of Adults With Pyoderma ... These patients will undergo 24 weeks of baricitinib dosed daily and stable dose of prednisone dosed daily with follow-up until week 36.