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.
A prospective, single-arm, open-label trial of deucravacitinib 6 mg daily in patients with PPP. All participants will receive deucravacitinib 6 mg daily for 24 weeks, with study visits every 4 weeks.