Deucravacitinib for Rosacea

Overseen by Benjamin Ungar

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Waitlist Available

Sponsor: Icahn School of Medicine at Mount Sinai

No Placebo Group

Prior Safety Data

Approved in 3 Jurisdictions

Trial Summary

What is the purpose of this trial?

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 once daily for 8 weeks, followed by an open label extension during which all participants will receive 6 mg deucravacitinib once daily for an additional 8 weeks. The open-label extension has been incorporated in order to ensure all participants receive benefit from the study, as well as to benefit from the intra-patient comparison of placebo to drug, and to provide longer-term clinical data. The study will include 33 adult participants with moderate-to-severe Papulopustular Rosacea (PPR). participants will have baseline Investigator Global Assessment (IGA) score of at least 3 and at least 12 inflammatory lesions. Beginning at Baseline/Week 0 enrolled participants will receive 6mg deucravacitinib or 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. Participants previously randomized to deucravacitinib will continue to receive deucravacitinib for an additional 8 weeks until Week 16. All participants will return for visits at Weeks 4, 8, 12 and 16 following study treatment initiation for repeat clinical assessments, medication reviews, tape-strip collection, blood and urine sample collections, and monitoring for adverse events.

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.

What data supports the idea that Deucravacitinib for Rosacea is an effective treatment?

The available research does not provide direct evidence that Deucravacitinib is effective for treating Rosacea. The studies focus on its use for other conditions like psoriasis, where it showed better results compared to a placebo and another drug called apremilast. For Rosacea, another drug, tofacitinib, showed promising results, with 71.4% of patients experiencing significant improvement. Therefore, while Deucravacitinib is effective for other conditions, there is no specific data supporting its effectiveness for Rosacea. ^{1 2 3 4 5}

What safety data exists for Deucravacitinib for Rosacea?

The provided research does not contain specific safety data for Deucravacitinib (also known as Sotyktu or BMS-986165) for Rosacea. The articles focus on skin-related side effects of other tyrosine kinase inhibitors, such as imatinib, sorafenib, and erlotinib, but do not mention Deucravacitinib. Therefore, no relevant safety data for Deucravacitinib in the context of Rosacea is available in the provided research. ^{6 7 8 9 10}

Is the drug Deucravacitinib a promising treatment for rosacea?

The information provided does not mention Deucravacitinib as a treatment for rosacea, so we cannot determine if it is promising based on the given data. ^{6 11 12 13 14}

Research Team

Benjamin Ungar

Principal Investigator

Icahn School of Medicine at Mount Sinai

Eligibility Criteria

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 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.

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

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

Treatment Details

Interventions

• Deucravacitinib (Other)

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.

Participant Groups

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 Canada for the following indications:

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+

Dr. Brendan Carr

Icahn School of Medicine at Mount Sinai

Chief Executive Officer since 2024

MD, MA, MS

Dr. Vicki LoPachin

Icahn School of Medicine at Mount Sinai

Chief Medical Officer

MD, FACP, MBA

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, 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 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]

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 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]

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]

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]

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]

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]

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]

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]

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]

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]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

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

2. 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]

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

Tofacitinib for the treatment of erythematotelangiectatic and papulopustular rosacea: A retrospective case series. [2022]

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. Switzerland pubmed.ncbi.nlm.nih.gov

Selectivity Profile of the Tyrosine Kinase 2 Inhibitor Deucravacitinib Compared with Janus Kinase 1/2/3 Inhibitors. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Acne rosacea associated imatinib mesylate in a gastrointestinal stromal tumor patient. [2018]

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

Successful topical treatment of sorafenib-induced hand-foot skin reaction in a child with hepatocellular carcinoma. [2018]

8. England pubmed.ncbi.nlm.nih.gov

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

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

Interventions for Rosacea. [2018]

10. Croatia pubmed.ncbi.nlm.nih.gov

Erlotinib-induced Rosacea-like Dermatitis. [2017]

11. Germany pubmed.ncbi.nlm.nih.gov

[Rosacea. Oral therapy with 13-cis retinoic acid]. [2013]

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

Women commonly seek care for rosacea: dermatologists frequently provide the care. [2022]

13. England 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. [2023]

14. Germany pubmed.ncbi.nlm.nih.gov

[Pathogenesis, clinical picture, and current therapy of rosacea]. [2018]