Deucravacitinib for Pyoderma Gangrenosum

Overseen By Staci L Shaw

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: Dartmouth-Hitchcock Medical Center

Must not be taking: Oral steroids, Cyclosporine

Disqualifiers: Inflammatory bowel disease, HIV, others

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 123

Duration: 12 weeks

10 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing if Deucravacitinib is safe and effective for people with pyoderma gangrenosum, a skin condition. The medication works by reducing inflammation caused by certain proteins in the body.

Will I have to stop taking my current medications?

Yes, you will need to stop taking certain medications. Specifically, you must discontinue systemic therapies like biologics and immune-suppressants, with a washout period (time without taking these medications) of at least 6 months for biologics and 3 months for other immune-suppressants. However, you can continue using topical treatments and oral rescue therapy with steroids.

Is deucravacitinib safe for humans?

Deucravacitinib has been studied in humans for conditions like psoriasis, showing a favorable safety profile with no serious adverse events reported. Common side effects include upper respiratory infections, mouth ulcers, and acne, but these did not increase with longer treatment duration. ^{1 2 3 4 5}

What makes the drug deucravacitinib unique for treating pyoderma gangrenosum?

Deucravacitinib is unique because it is a first-in-class, highly selective oral inhibitor of tyrosine kinase 2 (TYK2), which works by blocking specific pathways involved in immune responses. This mechanism is different from other treatments and may offer a novel approach for conditions like pyoderma gangrenosum, where standard treatments are not well established. ^{1 2 3 4 6}

Research Team

Brian Simmons

Principal Investigator

Dartmouth-Hitchcock Medical Center

Eligibility Criteria

Adults aged 18-70 with pyoderma gangrenosum can join this trial. They must meet specific diagnostic criteria, not be pregnant or planning pregnancy, and agree to use contraception. Excluded are those with other autoimmune diseases, major illnesses, recent surgery, certain infections including TB and HIV, liver issues, blood disorders or cancer in the last 5 years.

Inclusion Criteria

I am willing and able to sign a consent form for the study.

I have not taken biologics for 6 months or other immune-suppressants for 3 months.

I agree to use effective birth control during and 30 days after the study.

Exclusion Criteria

You have been diagnosed with HIV.

I haven't had cancer or lymph diseases in the last 5 years, except for treated skin cancer.

I do not have any major illnesses or unstable conditions affecting my organs or mental health.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Deucravacitinib 6 mg tablets orally twice daily

12 weeks

Visits on Days 8, 15, 29, 57, and 85

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Follow-up visit on Day 115

Treatment Details

Interventions

• Deucravacitinib

Trial Overview The trial is testing Deucravacitinib's safety and effectiveness for treating pyoderma gangrenosum. Participants will stop other PG treatments but may use oral steroids if needed. The study requires a washout period from previous systemic therapies before starting Deucravacitinib.

Participant Groups

Group I: Deucravacitinib Experimental Treatment 1 Intervention

Participants to receive Deucravacitinib 6 mg tablets orally twice daily for 12 weeks.

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

Approved in United States as Sotyktu for:

• Moderate to severe plaque psoriasis

Approved in European Union as Sotyktu for:

• Moderate to severe plaque psoriasis

Approved in Canada as Sotyktu for:

• Moderate to severe plaque psoriasis

Who Is Running the Clinical Trial?

Dartmouth-Hitchcock Medical Center

Lead Sponsor

Trials

548

Recruited

2,545,000+

Bristol-Myers Squibb

Industry Sponsor

Trials

2,731

Recruited

4,127,000+

Headquarters

New York City, USA

Known For

Oncology & Cardiovascular

Top Products

Eliquis, Opdivo, Revlimid, Orencia

Christopher Boerner

Bristol-Myers Squibb

Chief Executive Officer since 2023

PhD in Business Administration from the Haas School of Business, University of California, Berkeley; BA in Economics and History from Washington University in St. Louis

Deepak L. Bhatt

Bristol-Myers Squibb

Chief Medical Officer since 2024

MD from Yale University; MSc in Clinical Epidemiology from the University of Pennsylvania

Findings from Research

Deucravacitinib (SOTYKTUTM) is an effective oral treatment for moderate to severe plaque psoriasis, with up to 58.4% of patients showing symptom improvement by week 16 in phase 3 trials involving 840 participants.

The drug has a favorable safety profile, with common side effects like upper respiratory infections and herpes simplex infections occurring at manageable rates, and its selectivity may enhance long-term safety compared to other treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

SOTYKTUTM (Deucravacitinib 6-mg Tablets)- A New Agent for the Management of Adult Plaque Psoriasis. Gupta, AK., Wang, T., Vincent, K., et al.[2023]

Deucravacitinib, a selective tyrosine kinase 2 inhibitor, was found to be safe and well tolerated in a study involving 40 healthy Chinese subjects, with no serious adverse events reported.

The drug showed rapid absorption and a dose-dependent increase in systemic exposure, indicating that it effectively reaches the bloodstream and maintains consistent pharmacokinetics across different doses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics and Safety of the Tyrosine Kinase 2 Inhibitor Deucravacitinib in Healthy Chinese Subjects. Jing, S., Lin, Y., Dockens, R., et al.[2023]

In a study involving 100 healthy volunteers, deucravacitinib was found to be rapidly absorbed with a half-life of 8-15 hours, showing a favorable pharmacokinetic profile and no serious adverse events, indicating good safety.

Deucravacitinib effectively inhibited key immune pathways (IL-12/IL-23 and type I IFN) in a dose-dependent manner, suggesting its potential as a therapeutic option for various immune-mediated diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-in-human study of deucravacitinib: A selective, potent, allosteric small-molecule inhibitor of tyrosine kinase 2. Catlett, IM., Aras, U., Hansen, L., et al.[2023]

In a phase 3 trial involving 66 Japanese patients with moderate to severe plaque psoriasis, deucravacitinib showed significantly higher efficacy compared to placebo and apremilast, with 78.1% of patients achieving a ≥75% reduction in PASI score at Week 16.

The safety profile of deucravacitinib was comparable to that of placebo and apremilast, with similar incidence rates of adverse events, and the most common side effect being nasopharyngitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of the selective TYK2 inhibitor, deucravacitinib, in Japanese patients with moderate to severe plaque psoriasis: Subgroup analysis of a randomized, double-blind, placebo-controlled, global phase 3 trial. Imafuku, S., Tada, Y., Hippeli, L., et al.[2023]

Deucravacitinib, an oral TYK2 inhibitor, demonstrated significant efficacy in treating moderate to severe plaque psoriasis, with 65.1% of patients achieving a PASI 75 response at week 16 across 6 clinical trials involving 2248 subjects.

The safety profile of deucravacitinib is favorable, with mild adverse events like nasopharyngitis being common, and serious adverse events occurring in only 1.35% to 9.5% of patients, making it a potentially less burdensome treatment option compared to injectable therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Deucravacitinib: The First FDA-Approved Oral TYK2 Inhibitor for Moderate to Severe Plaque Psoriasis. Truong, TM., Pathak, GN., Singal, A., et al.[2023]

Deucravacitinib is a first-in-class oral TYK2 inhibitor that works by stabilizing an inhibitory interaction within the TYK2 enzyme, which is important for treating various immune-mediated diseases.

It received its first approval in the USA on September 9, 2022, for adults with moderate-to-severe plaque psoriasis, and has since been approved in Japan for multiple forms of psoriasis, indicating its efficacy and safety in managing these conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Deucravacitinib: First Approval. Hoy, SM.[2022]

References

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

SOTYKTUTM (Deucravacitinib 6-mg Tablets)- A New Agent for the Management of Adult Plaque Psoriasis. [2023]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Pharmacokinetics and Safety of the Tyrosine Kinase 2 Inhibitor Deucravacitinib in Healthy Chinese Subjects. [2023]

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

First-in-human study of deucravacitinib: A selective, potent, allosteric small-molecule inhibitor of tyrosine kinase 2. [2023]

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

Efficacy and safety of the selective TYK2 inhibitor, deucravacitinib, in Japanese patients with moderate to severe plaque psoriasis: Subgroup analysis of a randomized, double-blind, placebo-controlled, global phase 3 trial. [2023]

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

Deucravacitinib: The First FDA-Approved Oral TYK2 Inhibitor for Moderate to Severe Plaque Psoriasis. [2023]

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

Deucravacitinib: First Approval. [2022]