Clinical trial NCT05710185: Deucravacitinib for the Treatment of Palmoplantar Pustulosis
Official title: Deucravacitinib for the Treatment of Palmoplantar Pustulosis
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Palmoplantar Pustulosis
Lead sponsor: Brigham and Women's Hospital
Sponsor class: OTHER
Collaborators: name: University of Pennsylvania
First posted: 2023-02-02
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: Objectives:

1. Evaluate the efficacy of deucravacitinib in adults with PPP
2. Evaluate the impact of deucravacitinib on quality of life in adults with PPP
3. 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.

Eligibility criteria: 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

Primary outcomes:
measure: Proportion of participants who achieve a ppPASI-50 response, or at least 50% improvement in ppPASI score
timeFrame: 16 weeks
Secondary outcomes:
measure: Proportion of participants who achieve a ppPASI-50 response, or at least 50% improvement in ppPASI score
timeFrame: Week 24
measure: Change from baseline in the Dermatology Quality Life Index (DLQI)
timeFrame: Week 16, Week 24
measure: Change from baseline in ppPASI
timeFrame: Week 16, Week 24
measure: Percentage of patient who achieve a Physicians Global Assessment Score of 0 or 1
timeFrame: Week 16, Week 24
measure: Change from baseline in EQ-5D VAS
timeFrame: Week 16, Week 24
measure: Change from baseline in the itch visual analogue scale (itch-VAS)
timeFrame: Week 16, Week 24
measure: Change from baseline in the pain visual analogue scale (pain-VAS)
timeFrame: Week 16, 24
Other outcomes:
Locations:
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
Study officials:
References: