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

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Palmoplantar Pustulosis (PPP)
• Intervention / Treatment: Drug: Tofacitinib; Drug: Imatinib Placebo; Drug: Imatinib; Drug: tofacitinib Placebo

Detailed Description

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
• Enrollment (Estimated): 135
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Xiaoyong Man; Phone Number: +86 13600516219; Email: manxy@zju.edu.cn

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China
      • Second Affiliated Hospital, School of Medicine, Zhejiang University
      • Contact: Xibei Chen; Phone Number: +86 15088611296; Email: chenxb@zju.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Arm 1: Tofacitinib Monotherapy; Tofacitinib 5 mg BID + Imatinib placebo QD	Drug: Tofacitinib; 5 mg tablet; administered orally twice daily (BID); Drug: Imatinib Placebo; Matching placebo tablet; administered orally once daily (QD)
Active Comparator: Arm 2: Imatinib Monotherapy	Drug: Imatinib; Imatinib 400 mg QD; Drug: tofacitinib Placebo; Matching placebo tablet; administered orally twice daily (BID)
Experimental: Arm 3: Combination Therapy; Tofacitinib 5 mg BID + Imatinib 400 mg QD	Drug: Tofacitinib; 5 mg tablet; administered orally twice daily (BID); Drug: Imatinib; Imatinib 400 mg QD

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	16 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	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.	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.	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.	Baseline through end of safety follow-up (up to Week 32)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of Participants Achieving PPPASI 50/75/90/100 Response at Various Time Points	Exploratory analysis of PPPASI response rates at intermediate and follow-up time points. PPPASI response is defined as the percentage improvement from baseline in Palmoplantar Pustulosis Area and Severity Index score. Safety Issue	Weeks 2, 4, 8, 12, and 24
Change from Baseline in EQ-5D-5L Health Status Score	The EQ-5D-5L is a standardized instrument for measuring health-related quality of life. It comprises a descriptive system (5 dimensions: mobility, self-care, usual activities, pain/discomfort, anxiety/depression) and a visual analog scale (0-100).	Weeks 4, 8, 12, 16, and 24
Change from Baseline in Palmoplantar Itch NRS Score	The Palmoplantar Itch Numeric Rating Scale (NRS) is an 11-point scale (0 = no itch, 10 = worst imaginable itch) used to assess itch intensity on the palms and soles.	Weeks 2, 4, 8, 12, 16, and 24
Change from Baseline in Serum Biomarker Levels	Exploratory analysis of changes in serum biomarkers associated with palmoplantar pustulosis pathogenesis, including but not limited to IL-17, IL-22, IL-36, and stem cell factor (SCF).	Baseline and Week 16
Incidence of Adverse Events of Special Interest (AESIs)	Adverse events of special interest include: serious infections, opportunistic infections, tuberculosis, neutropenia, hypersensitivity reactions, suicidal ideation/behavior, major adverse cardiovascular events (MACE), hepatic enzyme elevation/liver function abnormalities, malignancies, and inflammatory bowel disease. Safety Issue	Baseline through end of safety follow-up (up to Week 32)

Collaborators and Investigators

• Sponsor: Second Affiliated Hospital, School of Medicine, Zhejiang University

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2026
• Primary Completion (Estimated): April 1, 2028
• Study Completion (Estimated): December 30, 2028

Study Registration Dates

• First Submitted: April 8, 2026
• First Submitted That Met QC Criteria: April 8, 2026
• First Posted (Actual): April 15, 2026

Study Record Updates

• Last Update Posted (Actual): April 15, 2026
• Last Update Submitted That Met QC Criteria: April 8, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Imatinib; Tofacitinib; Palmoplantar Pustulosis
• Additional Relevant MeSH Terms: Skin Diseases, Papulosquamous; Skin Diseases; Skin and Connective Tissue Diseases; Psoriasis; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Hydrocarbons; Hydrocarbons, Cyclic; Carboxylic Acids; Hydrocarbons, Aromatic; Amides; Pyrimidines; Benzene Derivatives; Acids, Carbocyclic; Benzoates; Benzamides; Piperazines; Imatinib Mesylate; tofacitinib
• Other Study ID Numbers: 2026-0173

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Individual participant data will not be shared.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No