Deucravacitinib for the Treatment of Palmoplantar Pustulosis

Objectives:

Evaluate the efficacy of deucravacitinib in adults with PPP
Evaluate the impact of deucravacitinib on quality of life in adults with PPP

Evaluate the safety of deucravacitinib Primary Endpoint: • Proportion of participants who achieve a ppPASI-50 response, or at least 50% improvement in ppPASI score, at 16 weeks Secondary Endpoints: • Proportion of participants who achieve at least 50% improvement in the palmoplantar pustular psoriasis area and severity index (ppPASI-50) at 24 weeks

Frequency of participants with adverse events
Change from baseline in the Dermatology Quality of Life Index
Change from baseline in ppPASI
Percentage of patients who achieved a static Physician's Global Assessment score of 0/1
Change from baseline in the EQ-5D VAS score
Change from baseline in itch VAS
Change from baseline in pain VAS Inclusion Criteria: • Adults aged 18 years of age and older
Dermatologist confirmed diagnosis of PPP for at least 6 months
Moderate-severe PPP, defined as a ppPASI > 12
Inadequate response to topical therapy and a candidate for systemic or phototherapy
Willing to discontinue current topical and/or systemic PPP treatments, except for OTC emollients Exclusion Criteria: • Participants with other immune-mediated conditions requiring concurrent systemic immunosuppressant treatments

Current/recent administration of PPP-specific medications including:

Rituximab within 6 months of the baseline visit
Biologics within 12 weeks of baseline visit
Systemic steroids, oral immunosuppressants (azathioprine, cyclosporine, methotrexate, mycophenolate mofetil, tacrolimus), oral retinoids (acitretin, isotretinoin), apremilast, or dapsone within 4 weeks of baseline visit
Phototherapy within 4 weeks of baseline visit
Prescription topical medications (including calcineurin inhibitors, crisaborole, retinoids, steroids, tar, vitamin D analogs) within 2 weeks of baseline visit
History of active infection and/or febrile illness within 7 days; or infection requiring antibiotic treatment within 30 days; or serious infection requiring hospitalization and/or IV antibiotics within 90 days

Evidence of other infection including:

Active or untreated latent tuberculosis, defined as radiographic or laboratory evidence of active TB or positive quantiferon or PPD, unless the subject has completed the recommended treatment
Human immunodeficiency virus infection (positive HIV antibody)
Active hepatitis B
Active hepatitis C

Evidence of clinically significant laboratory abnormality including:

Absolute WBC count < 3000/mm3
Platelet count < 100,000/mm3
Hemoglobin < 9.0 g/dl
ALT or AST > 3 times the upper limit of normal
History of cancer within the past 5 years, excluding treated non-melanoma skin cancer (basal cell carcinoma, squamous cell carcinoma)
Other uncontrolled chronic medical condition that may interfere with a patient's ability to participate in the clinical trial
Major surgery within 4 weeks of baseline visit
Receipt of live vaccine within 8 weeks of baseline visit
Pregnant or breastfeeding individuals
Inability to comply with any of the study procedures
Individuals who are incarcerated or compulsory detained Sample Size: A modified Simon's two-stage design will be used to maximize the safety and efficiency of this clinical trial in an orphan disease. In the first stage, 8 patients will be accrued. If 2 or fewer patients achieve a ppPASI-50 in these 8 patients, the study will be stopped. Otherwise, 10 additional patients will be accrued for a total of 18.

Analysis Plan: Descriptive statistics will be used to characterize the study population, including demographics, disease characteristics and previous treatments. For the primary outcome, the percentage of participants who achieve a ppPASI-50 response, or at least 50% improvement in ppPASI score, at 16 weeks, the response rate with a 95% CI will be calculated. For all secondary endpoints, summary and descriptive statistics will be used as appropriate , including number of observations, calculation of mean/median, standard deviation range and 95% confidence intervals.