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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Arm 1: Tofacitinib Monotherapy | Active Comparator | Tofacitinib 5 mg BID + Imatinib placebo QD |
|
| Arm 2: Imatinib Monotherapy | Active Comparator |
| |
| Arm 3: Combination Therapy | Experimental | Tofacitinib 5 mg BID + Imatinib 400 mg QD |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Tofacitinib | Drug | 5 mg tablet; administered orally twice daily (BID) |
|
| 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 |
| 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 |
| 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 |
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:
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.).
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Xiaoyong Man | Contact | +86 13600516219 | manxy@zju.edu.cn |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Second Affiliated Hospital, School of Medicine, Zhejiang University | Hangzhou | Zhejiang | China |
Individual participant data will not be shared.
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| Imatinib | Drug | Imatinib 400 mg QD |
|
| tofacitinib Placebo | Drug | Matching placebo tablet; administered orally twice daily (BID) |
|
| Imatinib Placebo | Drug | Matching placebo tablet; administered orally once daily (QD) |
|
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) |
| 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) |
| ID | Term |
|---|---|
| D011565 | Psoriasis |
| ID | Term |
|---|---|
| D017444 | Skin Diseases, Papulosquamous |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
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| ID | Term |
|---|---|
| C479163 | tofacitinib |
| D000068877 | Imatinib Mesylate |
| ID | Term |
|---|---|
| D001549 | Benzamides |
| D000577 | Amides |
| D009930 | Organic Chemicals |
| D001565 | Benzoates |
| D000146 | Acids, Carbocyclic |
| D002264 | Carboxylic Acids |
| D001555 | Benzene Derivatives |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D010879 | Piperazines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D011743 | Pyrimidines |
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