Deucravacitinib for Rosacea

Overseen By Giselle Singer

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Icahn School of Medicine at Mount Sinai

Must not be taking: Immunosuppressives, Corticosteroids, Antibiotics, others

Disqualifiers: Skin infections, Uncontrolled diseases, 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 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 17

Duration: 8 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new medication, deucravacitinib (also known as Sotyktu or BMS-986165), to determine its effectiveness in treating moderate-to-severe papulopustular rosacea, a skin condition causing redness, bumps, and pimples. Participants will receive either the medication or a placebo (a pill with no active ingredients) for 8 weeks, followed by an additional 8 weeks where everyone receives the medication. Researchers aim to compare the medication's effects against the placebo and gather longer-term data. The trial seeks adults with at least 12 inflammatory lesions (bumps or pimples) and rosacea that noticeably affects their skin. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to developing a potential new therapy.

Do I have to stop taking my current medications for the trial?

Yes, you will need to stop taking all treatments for rosacea from screening through study completion, except for the study drug. Additionally, you must not use certain topical or oral treatments within 2 weeks of baseline and systemic immunosuppressive medications within 4 weeks of study initiation.

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

Research shows that deucravacitinib, an oral medication, is usually well-tolerated. Studies have found that at doses similar to those in this trial, most individuals experience only a few side effects. For instance, one study involving psoriasis patients found deucravacitinib safe for long-term use, with no new safety issues even after five years.

However, some individuals have reported side effects. In rare cases, deucravacitinib has worsened rosacea, the condition this trial focuses on. While the medication is generally safe, specific concerns may arise when using it for rosacea. Overall, evidence suggests that deucravacitinib is generally safe, but participants should be aware of these potential side effects. ^{1 2 3 4 5}

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

Deucravacitinib is unique because it targets the TYK2 enzyme, which plays a key role in the inflammatory process of rosacea. Most treatments for rosacea, like topical antibiotics and azelaic acid, focus on reducing bacteria and inflammation without specifically targeting the underlying immune response. Researchers are excited about deucravacitinib because it offers a novel approach by modifying the immune pathways directly, potentially leading to more effective and faster results for patients who haven't found relief with existing options.

What evidence suggests that deucravacitinib might be an effective treatment for rosacea?

Research has shown that deucravacitinib, a specific type of medication, yields promising results for treating certain skin conditions. In studies on psoriasis, this medication significantly improved outcomes compared to a placebo, with lasting effects. Although the main focus has been on psoriasis, its mechanism suggests potential benefits for other inflammatory skin conditions, such as rosacea. This trial will compare two groups: one receiving deucravacitinib and another starting with a placebo before switching to deucravacitinib. The drug targets pathways that cause inflammation, a major factor in rosacea. Early signs from similar conditions offer hope that deucravacitinib might help manage rosacea symptoms as well. ^{1 2 3 4 5}

Who Is on the Research Team?

Benjamin Ungar

Principal Investigator

Icahn School of Medicine at Mount Sinai

Are You a Good Fit for This Trial?

Adults with moderate-to-severe Papulopustular Rosacea, having an IGA score of at least 3 and a minimum of 12 inflammatory lesions. Specific inclusion or exclusion criteria are not provided but typically involve health status and other medical conditions.

Inclusion Criteria

I agree to stop all other PPR treatments for the study duration.

I have been diagnosed with PPR, have a moderate to severe rating, and more than 12 inflamed spots.

I agree not to get a live vaccine during and for 4 weeks after the study.

Exclusion Criteria

History of adverse systemic or allergic reactions to any component of the study drug

Current participation in any other study with an investigational medication

Participant who is pregnant or breast feeding or plans on becoming pregnant or breastfeeding

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 are randomized to receive 6 mg deucravacitinib or placebo once daily for 8 weeks

8 weeks

Visits at Weeks 4 and 8 (in-person)

Open-label extension

All participants receive 6 mg deucravacitinib once daily for an additional 8 weeks

8 weeks

Visits at Weeks 12 and 16 (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Deucravacitinib

Trial Overview The trial is testing Deucravacitinib, comparing it to a placebo in a double-blind study for 8 weeks. Participants will then enter an open-label phase for another 8 weeks where all receive the drug, allowing comparison between initial placebo effects and the drug's effects.

How Is the Trial Designed?

Group I: Deucravacitinib Active Control 1 Intervention

Participants receiving 6mg deucravacitinib once daily for 8 weeks. Participants previously randomized to deucravacitinib will continue to receive deucravacitinib for an additional 8 weeks until Week 16.

Group II: Placebo then Deucravacitinib Active Control 2 Interventions

Participants receiving placebo once daily for 8 weeks. At week 8, those participants originally randomized to placebo will initiate dosing with 6mg deucravacitinib once daily for 8 weeks until Week 16.

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?

Icahn School of Medicine at Mount Sinai

Lead Sponsor

Trials

933

Recruited

579,000+

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

Published Research Related to This Trial

The Rosacea Area and Severity Index (RASI) was developed to provide a more detailed evaluation of rosacea severity compared to the traditional Investigator's Global Assessment (IGA), showing a strong correlation (SCC = 0.75) between the two methods.

RASI demonstrated moderate interobserver reliability and strong intraobserver agreement, making it a practical and reliable tool for assessing rosacea severity in clinical settings and research, particularly excelling in evaluating features like rhinophyma and papules.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Validity and reliability of the Rosacea Area and Severity Index: A novel scoring system for clinical assessment of rosacea severity. Wienholtz, NKF., Thyssen, JP., Christensen, CE., et al.[2023]

Topical treatments like brimonidine, azelaic acid, and ivermectin, along with oral medications such as doxycycline and isotretinoin, have been shown to effectively improve rosacea symptoms based on high-quality evidence.

Most of these treatments do not lead to higher rates of adverse events compared to placebo, indicating they are generally safe options for patients with rosacea.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Interventions for Rosacea. van Zuuren, EJ., Fedorowicz, Z.[2018]

In a study of 21 patients with rosacea treated with the JAK inhibitor tofacitinib, 71.4% showed significant improvement in facial erythema, indicating its potential efficacy in treating this condition.

The mean change of -2.24 in the Investigator's Global Assessment score from baseline suggests that tofacitinib may effectively reduce the symptoms of rosacea, supporting its use as a treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tofacitinib for the treatment of erythematotelangiectatic and papulopustular rosacea: A retrospective case series. Sun, YH., Man, XY., Xuan, XY., et al.[2022]

Deucravacitinib is a selective inhibitor of TYK2 that operates through a unique allosteric mechanism, providing high specificity for TYK2 over JAK 1/2/3, which was confirmed through in vitro assays measuring kinase activity.

At therapeutic doses, deucravacitinib maintains effective TYK2 inhibition for 9-18 hours without affecting JAK 1/2/3, distinguishing it from other JAK inhibitors like tofacitinib, upadacitinib, and baricitinib, which show varying degrees of JAK inhibition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Selectivity Profile of the Tyrosine Kinase 2 Inhibitor Deucravacitinib Compared with Janus Kinase 1/2/3 Inhibitors. Chimalakonda, A., Burke, J., Cheng, L., et al.[2022]

This study reports the first pediatric case of a hand-foot-skin reaction caused by the oral kinase inhibitor Sorafenib, which is commonly associated with skin side effects in adults.

Topical therapy was successfully used to manage this skin reaction, allowing the child to continue their treatment with Sorafenib without interruption.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Successful topical treatment of sorafenib-induced hand-foot skin reaction in a child with hepatocellular carcinoma. Hütten, M., Lassay, L., Sachs, B., et al.[2018]

Rosacea is a common chronic inflammatory skin condition that primarily affects individuals with fair skin and a family history, with up to 60% of patients also experiencing ocular symptoms.

In Germany, several topical treatments like brimonidine, metronidazole, azelaic acid, and ivermectin are approved for rosacea, while doxycycline at a low dose is the only approved systemic treatment, with alternative off-label therapies available for resistant cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Pathogenesis, clinical picture, and current therapy of rosacea]. Gonser, LI., Gonser, CE., Schaller, M.[2018]

Imatinib mesylate (IM), a tyrosine kinase inhibitor used for cancer treatment, can cause hyperpigmented acne rosacea, a side effect not previously documented.

Sunitinib, another TKI, was associated with palmar hyperkeratosis in a patient with gastrointestinal stromal tumor, highlighting the need for awareness of skin toxicities in TKI treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acne rosacea associated imatinib mesylate in a gastrointestinal stromal tumor patient. Demirci, U., Coskun, U., Erdem, O., et al.[2018]

In a study involving five patients with severe rosacea, treatment with 13-cis retinoic acid showed significantly better results compared to standard therapies.

The therapy not only improved symptoms but also resulted in longer durations of remission for the patients, indicating its potential as an effective treatment option for severe rosacea.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Rosacea. Oral therapy with 13-cis retinoic acid]. Nikolowski, J., Plewig, G.[2013]

Rosacea is most commonly seen in Caucasian women, with a mean patient age of 50 years, and accounts for approximately 1.1 million outpatient visits annually in the U.S., primarily to dermatologists.

Topical metronidazole is the most frequently prescribed treatment for rosacea, while tetracycline is the leading systemic therapy, indicating a preference for combination treatments to manage the condition effectively.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Women commonly seek care for rosacea: dermatologists frequently provide the care. Feldman, SR., Hollar, CB., Gupta, AK., et al.[2022]

Patients treated with sorafenib, an oral multi-tyrosine kinase inhibitor, have a significantly increased risk of mucocutaneous toxicities, with hand-foot skin reactions being the most common (RR 4.33).

The study analyzed data from randomized Phase II and III trials, confirming that these toxicities occur regardless of tumor type or treatment regimen, indicating a consistent safety concern across different patient groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risk of mucocutaneous toxicities in patients with solid tumors treated with sorafenib: an updated systematic review and meta-analysis. Abdel-Rahman, O., Fouad, M.[2018]

Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) commonly cause skin-related side effects, which are usually mild, reversible, and dose-dependent, but can significantly impact patients' quality of life and treatment adherence.

A case study of a 77-year-old man revealed a rare rosaceiform rash as a side effect of erlotinib, highlighting the need for better classification of skin reactions to EGFR-TKIs to ensure timely recognition and management of all potential adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Erlotinib-induced Rosacea-like Dermatitis. Rezaković, S., Paštar, Z., Bukvić Mokos, Z., et al.[2017]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06532136

Study Details | NCT06532136 | Deucravacitinib Rosacea This will be a double-blind, randomized placebo-controlled study in which participants will be randomized 2:1 to receive 6 mg deucravacitinib or placebo ...

2. nejm.org nejm.org/doi/full/10.1056/NEJMoa1806382

Phase 2 Trial of Selective Tyrosine Kinase 2 Inhibition in ... Selective inhibition of TYK2 with the oral agent BMS-986165 at doses of 3 mg daily and higher resulted in greater clearing of psoriasis than did placebo over a ...

3. academic.oup.com academic.oup.com/ced/advance-article/doi/10.1093/ced/llaf418/8256486?searchresult=1

TYK-ed off by rosacea: an Australian case ... - Oxford Academic Deucravacitinib is an oral selective TYK2 inhibitor with demonstrated efficacy and safety for managing moderate to severe plaque psoriasis.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9120409/

Efficacy and safety of selective TYK2 inhibitor ... Both deucravacitinib doses resulted in significant improvements versus placebo (p≤0.05) in the multiplicity-controlled secondary endpoints of ...

5. news.bms.com news.bms.com/news/details/2025/New-Five-Year-Sotyktu-deucravacitinib-Data-Show-Consistent-Safety-and-Durable-Response-Rates-in-Moderate-to-Severe-Plaque-Psoriasis/default.aspx

New Five-Year Sotyktu (deucravacitinib) Data Show ... Clinical efficacy outcomes were sustained in patients who were continuously treated with Sotyktu for PASI 75 (72.1%, Year 1; 67.3%, Year 5) ...