Tofacitinib Plus Imatinib in Moderate-to-Severe Palmoplantar Pustulosis

Official title

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

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.

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.

Interventions

• Drug Tofacitinib
  11 mg tablet; administered orally once daily (QD)
• Drug Imatinib
  200 mg tablet; administered orally once daily (QD)
• Drug tofacitinib Placebo
  Matching placebo tablet; administered orally once daily (QD)
• Drug Imatinib Placebo
  Matching placebo tablet; administered orally once daily (QD)

Primary outcome measures

• Proportion of Participants Achieving PPPASI 90 Response at Week 16 [Time frame: 16 weeks]

Secondary outcome measures (5)

• Proportion of Participants Achieving PPPASI 100 Response at Week 16 [Time frame: week 16]
• Proportion of Participants Achieving at Least 4-Point Improvement in Palmoplantar Pain NRS Score at Week 16 [Time frame: week 16]
• Change from Baseline in Dermatology Life Quality Index (DLQI) Total Score at Week 16 [Time frame: Week 16]
• Incidence of Treatment-Emergent Adverse Events (TEAEs) [Time frame: Baseline through end of safety follow-up (up to Week 32)]
• Incidence of Serious Adverse Events (SAEs) [Time frame: Baseline through end of safety follow-up (up to Week 32)]

Eligibility criteria

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

China · 1 center

• Second Affiliated Hospital, School of Medicine, Zhejiang University — Hangzhou

Identifiers

NCT: NCT07530367 · 2026-0173

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗