A Phase III Randomized Controlled Trial Evaluating the Efficacy and Safety of Tofacitinib Combined With Imatinib in Patients With Moderate-to-Severe Palmoplantar Pustulosis

Phase 3Not Yet RecruitingNCT07530367

Second Affiliated Hospital, School of Medicine, Zhejiang University135 enrolled

Overview

Palmoplantar pustulosis (PPP) is a rare, chronic inflammatory skin disease primarily affecting the palms and soles. Currently, no treatment is specifically approved for PPP globally. This study aims to evaluate the efficacy and safety of tofacitinib combined with imatinib in patients with moderate-to-severe PPP.

This is a Phase III, randomized, double-blind, three-arm parallel-controlled trial. A total of 135 patients will be randomly assigned to one of three groups: tofacitinib monotherapy, imatinib monotherapy, or combination therapy. The primary endpoint is the proportion of patients achieving PPPASI 90 response at Week 16.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

135

Conditions

Palmoplantar Pustulosis (PPP)

Interventions

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: \- Participants aged ≥ 18 years. Diagnosis of PPP for at least 12 weeks prior to screening. PPPASI ≥ 12 at screening and baseline. PPP-IGA ≥ 3 at screening and baseline. Presence of pustules on palms and/or soles at screening and baseline. Confirmed diagnosis of PPP by photographic adjudication. Exclusion Criteria: * Significant improvement of PPP symptoms between screening and baseline (PPPASI decrease ≥ 5). Presence of other forms of psoriasis or inflammatory skin diseases. Active infection or history of serious infection within specified timeframes. Positive for hepatitis B, hepatitis C, or HIV. Active or latent tuberculosis. History of malignancy within 5 years (except certain skin cancers). Laboratory abnormalities meeting exclusion criteria (e.g., ALT/AST ≥ 3×ULN, ANC \< 1.5×10³/μL, etc.).

Outcomes

Primary Outcomes

Proportion of Participants Achieving PPPASI 90 Response at Week 16

PPPASI 90 response is defined as at least 90% improvement from baseline in the Palmoplantar Pustulosis Area and Severity Index (PPPASI) score. Participants who discontinue study treatment or receive prohibited concomitant therapy prior to Week 16 will be considered non-responders.

Time frame: 16 weeks

Secondary Outcomes

Proportion of Participants Achieving PPPASI 100 Response at Week 16

PPPASI 100 response is defined as complete clearance (100% improvement from baseline) in the Palmoplantar Pustulosis Area and Severity Index (PPPASI) score at Week 16.

Time frame: week 16

Proportion of Participants Achieving at Least 4-Point Improvement in Palmoplantar Pain NRS Score at Week 16

The Palmoplantar Pain Numeric Rating Scale (NRS) is an 11-point scale (0 = no pain, 10 = worst possible pain) used to assess pain intensity on the palms and soles. Response is defined as a ≥4-point improvement from baseline.

Time frame: week 16

Change from Baseline in Dermatology Life Quality Index (DLQI) Total Score at Week 16

The Dermatology Life Quality Index (DLQI) is a 10-item questionnaire that assesses the impact of skin disease on quality of life over the past week. Total score ranges from 0 to 30, with higher scores indicating greater impairment. A negative change indicates improvement.

Time frame: Week 16

Incidence of Treatment-Emergent Adverse Events (TEAEs)

Treatment-emergent adverse events are defined as any adverse event that occurs after the first dose of study treatment up to 28 days after the last dose. All TEAEs will be summarized by system organ class and preferred term.

Time frame: Baseline through end of safety follow-up (up to Week 32)

Incidence of Serious Adverse Events (SAEs)

Serious adverse events are defined as any adverse event that results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, or is a congenital anomaly/birth defect.