Tofacitinib Plus Imatinib in 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: Imatinib Placebo; Drug: Tofacitinib; 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:

Age ≥ 18 years at the time of screening.

Diagnosis of palmoplantar pustulosis (PPP) for at least 12 weeks prior to the screening visit.

May have a history of or concurrent plaque psoriasis.

PPPASI score ≥ 12 at both the screening and baseline visits.

PPP-IGA score ≥ 3 at both the screening and baseline visits.

Presence of pustules on the palms and/or soles at both the screening and baseline visits, defined as pustule severity ≥ 2 in at least one region (one palm or one sole) based on the PPPASI.

Must have a confirmed diagnosis of PPP by photographic adjudication.

Male and/or female participants.

Female participants must not be pregnant, not be lactating (including feeding an infant by breast pump).

Exclusion Criteria:

Significant improvement in PPP symptoms between the screening and baseline visits, defined as a reduction in PPPASI score of ≥ 5 units.

Presence of any of the following conditions: guttate psoriasis, erythrodermic psoriasis, generalized pustular psoriasis, acrodermatitis continua of Hallopeau, atopic dermatitis, dyshidrotic eczema, chronic hand eczema, or folliculitis.

Drug-induced psoriasis (e.g., first onset or current flare triggered by beta-blockers, calcium channel inhibitors, lithium preparations, or TNF inhibitors) or drug-induced pustular psoriasis (e.g., acute generalized exanthematous pustulosis, acute localized exanthematous pustulosis).

Active infection or history of infection, as follows:

Any active infection within 14 days prior to the baseline visit.

Severe infection requiring hospitalization or intravenous anti-infective treatment within 8 weeks prior to the baseline visit.

History of opportunistic infections, recurrent infections, or chronic infections that, in the investigator's opinion, would make participation in this study harmful to the participant.

Positive test results for acute or chronic hepatitis B virus (HBV), hepatitis C virus (HCV), or human immunodeficiency virus (HIV). Exclusion is defined as:

HBV positive: 1) hepatitis B surface antigen positive, or 2) anti-hepatitis B core antibody positive.

HCV positive: 1) hepatitis C antibody positive, and 2) confirmed by a confirmatory HCV test (e.g., HCV polymerase chain reaction).

Any of the following tuberculosis (TB)-related conditions:

Known active TB disease.

History of active TB involving any organ system, unless adequately treated per WHO/CDC treatment guidelines and confirmed as fully recovered by consultation with a relevant specialist.

Latent TB infection (LTBI): Participants with LTBI may be rescreened once after receiving at least 4 weeks of appropriate LTBI treatment, provided that no treatment-related hepatotoxicity is evident prior to the first dose of investigational medicinal product (ALT/AST still ≤ 3×ULN).

History of lymphoproliferative disorders (e.g., lymphoma) or current symptoms suggestive of lymphoproliferative disorders.

Current active malignancy or history of malignancy within 5 years prior to the screening visit, except for squamous cell carcinoma or basal cell carcinoma of the skin, or treated and considered cured in situ cervical cancer.

Presence of other inflammatory diseases, including but not limited to rheumatoid arthritis, hidradenitis suppurativa, inflammatory bowel disease, or systemic lupus erythematosus.

Major surgery (including joint surgery) within 8 weeks prior to the screening visit, or planned surgery during the study period.

Any systemic disease (e.g., cardiovascular, neurological, renal, hepatic, metabolic, gastrointestinal, hematological, coagulation disorders, immune system disease) that, in the investigator's opinion, is uncontrolled, unstable, or likely to progress to a clinically significant degree during the study.

Any medical or psychiatric condition (including ongoing major depression or active suicidal ideation) that, in the investigator's opinion, may impair the participant's ability to participate in the study.

History of chronic alcohol or drug abuse within 6 months prior to the screening visit, as determined by the investigator based on medical history, interview, and examination findings.

Current or prior use of IL-17A, IL-17A/F, or IL-23 inhibitors.

Receipt of any live vaccine (including attenuated vaccines) within 8 weeks prior to the baseline visit.

Vaccination not permitted during the study and within 17 weeks after the last dose of study treatment.

Laboratory abnormalities at the screening visit, including any of the following:

ALT, AST, or ALP ≥ 3×ULN.

Bilirubin > 1.5×ULN (unconjugated bilirubin > 1.5×ULN is acceptable if bilirubin is fractionated and direct bilirubin/total bilirubin ratio is < 35%).

White blood cell count < 3.0×10³/μL.

Absolute neutrophil count < 1.5×10³/μL.

Lymphocyte count < 500 cells/μL.

Hemoglobin < 8.5 g/dL.

Any other laboratory abnormality that, in the investigator's opinion, may interfere with the participant's ability to complete the study or confound the interpretation of study results.

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 11 mg QD + Imatinib placebo QD	Drug: Imatinib Placebo; Matching placebo tablet; administered orally once daily (QD); Drug: Tofacitinib; 11 mg tablet; administered orally once daily (QD)
Active Comparator: Arm 2: Imatinib Monotherapy; Imatinib 200mg QD+Tofacitinib placebo QD	Drug: Imatinib; 200 mg tablet; administered orally once daily (QD); Drug: tofacitinib Placebo; Matching placebo tablet; administered orally once daily (QD)
Experimental: Arm 3: Combination Therapy; Imatinib 200mg QD+Tofacitinib 11mg QD	Drug: Tofacitinib; 11 mg tablet; administered orally once daily (QD); Drug: Imatinib; 200 mg tablet; administered orally once daily (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, Zhejiang University, School of Medicine

Study record dates

Study Major Dates

• Study Start (Estimated): August 1, 2026
• Primary Completion (Estimated): August 1, 2028
• Study Completion (Estimated): December 30, 2030

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): August 3, 2026
• Last Update Submitted That Met QC Criteria: July 30, 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