Deucravacitinib for Nail Psoriasis

Overseen By Ralee' Bunt, MSPH

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: University of Alabama at Birmingham

Must not be taking: Strong CYP450 inducers

Disqualifiers: Uncontrolled major diseases, Psychiatric history, Substance abuse, 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: Unknown

Duration: 48 weeks

Trial Summary

What is the purpose of this trial?

. An open label proof of concept study will be conducted to assess the efficacy and safety of deucravactinib for treatment of nail psoriasis. Twenty adult patients with nail psorasis and skin disease qualifying for a systemic agent per investigator will be treated with deucravacitinib 6 mg daily. Subjects will be assessed for a total of 48 weeks. Psoriasis assessments such as the modified Nail Psoriasis Severity Index will be conducted. Photos will be used to document nail involvement. Descriptive statistical analysis will be conducted at the conclusion of the study.

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

Yes, you will need to stop taking certain medications. You must discontinue all systemic therapies for psoriasis or psoriatic arthritis at least 4 weeks before the trial, and biologics at least 2 months before. Topical therapies must be stopped 2 weeks prior, and UV therapy 2 weeks prior, with PUVA therapy stopped 4 weeks prior.

What data supports the effectiveness of the drug Deucravacitinib for nail psoriasis?

Deucravacitinib has shown effectiveness in treating moderate to severe plaque psoriasis, with over 50% of patients experiencing significant improvement in their condition during clinical trials. While specific data for nail psoriasis is not provided, its success in similar psoriasis conditions suggests potential benefits. ^{1 2 3 4 5}

Is Deucravacitinib safe for humans?

Deucravacitinib has been studied for safety in healthy subjects and patients with psoriasis, showing it is generally well-tolerated. It has been approved for use in several countries, indicating a favorable safety profile for treating moderate to severe plaque psoriasis. ^{1 2 3 6 7}

How is the drug Deucravacitinib unique for treating nail psoriasis?

Deucravacitinib is unique because it is a selective TYK2 inhibitor, which targets specific pathways involved in the inflammation process of psoriasis, potentially offering a novel approach compared to other treatments like JAK inhibitors or biologics that target different mechanisms. ^{8 9 10 11 12}

Eligibility Criteria

Adults over 18 with chronic plaque psoriasis and nail psoriasis, who are in good health aside from their skin condition. Participants must not have used systemic therapies for psoriasis or biologics within specific time frames before the study starts and be willing to have photos taken of their nails.

Inclusion Criteria

I stopped all psoriasis treatments at least 4 weeks ago, or 2 months for biologics.

I am in good health except for psoriasis or mild kidney issues.

I am 18 years old or older.

Exclusion Criteria

I have been treated with deucravacitinib before.

Other than disease under study, any clinically significant (as determined by the Investigator) cardiac, endocrinologic, pulmonary, neurologic, psychiatric, hepatic, renal, hematologic, immunologic disease, or other major disease that is currently uncontrolled

Any condition, including the presence of laboratory abnormalities, which would place the subject at unacceptable risk if he/she were to participate in the study

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 6 mg of deucravacitinib daily for the treatment of nail psoriasis

48 weeks

Regular assessments including mNAPSI and photographic documentation

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Deucravacitinib

Trial Overview The trial is testing Deucravacitinib, an oral medication, given at a dose of 6 mg daily to treat nail psoriasis. The study will follow twenty patients for 48 weeks, using assessments like the modified Nail Psoriasis Severity Index and photographs to track changes.

Participant Groups

Group I: Deucravacitinib 6 mg Daily Experimental Treatment 1 Intervention

All participants will receive 6 mg of deucravacitinib daily.

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?

University of Alabama at Birmingham

Lead Sponsor

Trials

1,677

Recruited

2,458,000+

Findings from Research

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]

Deucravacitinib, an oral medication for moderate to severe plaque psoriasis, demonstrated higher PASI 75 response rates compared to apremilast and methotrexate across all time points in a network meta-analysis of 47 randomized controlled trials.

Long-term efficacy of deucravacitinib was comparable to first-generation biologics like adalimumab and ustekinumab, making it a viable oral treatment option for patients seeking effective psoriasis management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Short-, Mid-, and Long-Term Efficacy of Deucravacitinib Versus Biologics and Nonbiologics for Plaque Psoriasis: A Network Meta-Analysis. Armstrong, AW., Warren, RB., Zhong, Y., 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 an oral small molecule that specifically inhibits TYK2, showing promising safety and efficacy for treating moderate to severe plaque psoriasis.

In phase III clinical trials, over 50% of patients taking deucravacitinib 6 mg daily achieved a significant reduction in psoriasis severity (≥75% improvement) at 16 weeks, compared to only 9-13% on placebo and 35-41% on another treatment, apremilast.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Deucravacitinib in moderate-to-severe psoriasis. Vu, A., Maloney, V., Gordon, KB.[2022]

Deucravacitinib, an oral tyrosine kinase 2 inhibitor, showed significant improvements in psoriasis symptoms and quality of life as early as Week 4 in a 12-week Phase 2 trial involving adults with moderate to severe plaque psoriasis.

Patients experienced better quality of life alongside clinical improvements, indicating that as psoriasis symptoms improved, so did their overall well-being, suggesting that deucravacitinib could be a promising new treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Deucravacitinib in Moderate to Severe Psoriasis: Clinical and Quality-of-Life Outcomes in a Phase 2 Trial. Thaçi, D., Strober, B., Gordon, KB., et al.[2022]

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 randomized, placebo-controlled trial, deucravacitinib, a selective TYK2 inhibitor, demonstrated significant clinical efficacy in treating moderate to severe psoriasis, with improvements in the Psoriasis Area and Severity Index (PASI) scores correlating with biomarker changes in the IL-23/TH17 and type I IFN pathways.

Deucravacitinib effectively normalized IL-23 and type I IFN pathway biomarkers in lesional skin, while showing selectivity by not affecting laboratory markers associated with JAK1-3 inhibition, indicating its targeted action on the TYK2 pathway.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Molecular and clinical effects of selective tyrosine kinase 2 inhibition with deucravacitinib in psoriasis. Catlett, IM., Hu, Y., Gao, L., et al.[2022]

In a pilot study of 13 patients with SAPHO syndrome, tofacitinib significantly improved nail lesions and palmoplantar psoriasis after 12 weeks, with a median reduction of 67% in Nail Psoriasis Severity Index scores and 71% in Palmoplantar Psoriasis Area and Severity Index scores.

Tofacitinib also enhanced the quality of life for patients, as indicated by a significant improvement in Dermatology Life Quality Index scores, and showed a decrease in inflammatory markers, with no severe adverse events reported during the study.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tofacitinib for the Treatment of Nail Lesions and Palmoplantar Pustulosis in Synovitis, Acne, Pustulosis, Hyperostosis, and Osteitis Syndrome. Li, C., Li, Z., Cao, Y., et al.[2021]

Tofacitinib, a new treatment for rheumatoid arthritis, shows promise in improving nail dystrophy in patients who have not responded to traditional therapies.

Nail dystrophy can be linked to autoimmune conditions like psoriasis and psoriatic arthritis, suggesting that tofacitinib may address underlying autoimmune mechanisms in these cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recovery of nail dystrophy potential new therapeutic indication of tofacitinib. Jaller, JA., Jaller, JJ., Jaller, AM., et al.[2018]

A case study showed that a patient with nail psoriasis experienced significant improvement after taking upadacitinib, a selective JAK1 inhibitor, at a dose of 15mg daily for 5 months.

The therapeutic effects of upadacitinib may be linked to its ability to target inflammatory cytokines like IL-6, IL-10, and IL-23, suggesting it could be an effective treatment option for severe nail psoriasis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Upadacitinib in nail psoriasis: a case report. Wang, N., Yang, Q., Liu, Y., et al.[2023]

In a study involving 404 patients with moderate-to-severe plaque psoriasis, guselkumab treatment led to significant improvements in nail psoriasis, with better outcomes associated with lower baseline severity and higher skin efficacy at week 16.

After stopping guselkumab treatment, patients maintained their nail psoriasis improvements longer than their skin improvements, suggesting that guselkumab may provide lasting benefits for nail health even after treatment withdrawal.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nail psoriasis dynamics during biologic treatment and withdrawal in patients with psoriasis who may be at high risk of developing psoriatic arthritis: a post hoc analysis of the VOYAGE 2 randomized trial. Tillett, W., Egeberg, A., Sonkoly, E., et al.[2023]

A consensus group of international dermatologists developed practical treatment recommendations for nail psoriasis, particularly for patients with mild skin lesions or no skin psoriasis, emphasizing tailored approaches based on the severity and type of nail involvement.

For limited nail psoriasis affecting three or fewer nails, intralesional steroid injections are recommended for cases with matrix involvement, while topical steroids and vitamin D analogues are suggested for nail bed involvement.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recommendations for the definition, evaluation, and treatment of nail psoriasis in adult patients with no or mild skin psoriasis: A dermatologist and nail expert group consensus. Rigopoulos, D., Baran, R., Chiheb, S., et al.[2019]

References

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

Deucravacitinib: First Approval. [2022]

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

Short-, Mid-, and Long-Term Efficacy of Deucravacitinib Versus Biologics and Nonbiologics for Plaque Psoriasis: A Network Meta-Analysis. [2023]

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

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

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

Deucravacitinib in moderate-to-severe psoriasis. [2022]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Deucravacitinib in Moderate to Severe Psoriasis: Clinical and Quality-of-Life Outcomes in a Phase 2 Trial. [2022]

6. Switzerland pubmed.ncbi.nlm.nih.gov

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

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

Molecular and clinical effects of selective tyrosine kinase 2 inhibition with deucravacitinib in psoriasis. [2022]

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

Tofacitinib for the Treatment of Nail Lesions and Palmoplantar Pustulosis in Synovitis, Acne, Pustulosis, Hyperostosis, and Osteitis Syndrome. [2021]

9. Germany pubmed.ncbi.nlm.nih.gov

Recovery of nail dystrophy potential new therapeutic indication of tofacitinib. [2018]

10. England pubmed.ncbi.nlm.nih.gov

Upadacitinib in nail psoriasis: a case report. [2023]

11. England pubmed.ncbi.nlm.nih.gov

Nail psoriasis dynamics during biologic treatment and withdrawal in patients with psoriasis who may be at high risk of developing psoriatic arthritis: a post hoc analysis of the VOYAGE 2 randomized trial. [2023]

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

Recommendations for the definition, evaluation, and treatment of nail psoriasis in adult patients with no or mild skin psoriasis: A dermatologist and nail expert group consensus. [2019]