Efficacy and Safety Evaluation of Delgocitinib Cream Versus Vehicle in Adult Patients with Mild to Severe Palmoplantar Pustulosis: A Phase 2a, Double-Blind Trial
- Trial ID
- 2024-518856-21-00
- Protocol
- LP0133-2393
- Sponsor
- Leo Pharma A/S
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to evaluate the **efficacy** of twice daily applications of delgocitinib cream 20 mg/g compared with a cream vehicle in the treatment of adult subjects with mild to severe palmoplantar pustulosis (PPP). This is clinically relevant as PPP is a chronic inflammatory skin condition that significantly impacts patients' quality of life, and effective treatments are needed to manage its symptoms.
Secondary objectives include:
- Evaluating the efficacy of delgocitinib cream compared to the cream vehicle in the treatment of adult subjects with mild to severe PPP.
- Assessing the effect of treatment with delgocitinib cream on PPP disease activity at different time points.
- Evaluating the safety and tolerability of twice daily applications of delgocitinib cream compared to the cream vehicle.
- Assessing the health-related quality of life effect of twice daily applications of delgocitinib cream compared to the cream vehicle.
Participants
The clinical trial involves a total of **65 participants** diagnosed with **mild to severe palmoplantar pustulosis** (PPP). The study population includes both male and female adults aged 18 years and above. Participants were selected based on their ability to comply with clinic visits and trial requirements, as well as a confirmed diagnosis of PPP according to the European Rare and Severe Psoriasis Expert Network (ERASPEN) criteria. The trial includes individuals with a disease duration of over six months and a Palmoplantar Pustulosis Area and Severity Index (PPPASI) of at least 8 at screening and baseline. Participants must have at least five well-demarcated fresh pustules across affected areas and have experienced inadequate response to topical corticosteroids or find them inadvisable. Women of childbearing potential are required to use an acceptable form of birth control throughout the trial. The trial population is considered vulnerable, and the selection process ensures that participants meet specific health and lifestyle criteria relevant to the study's objectives.
Plans and Procedures
The clinical trial is designed as a **randomized**, **double-blind**, controlled study to evaluate the efficacy and safety of **delgocitinib cream** 20 mg/g compared to a cream vehicle in adult subjects with mild to severe **palmoplantar pustulosis**. The trial will span a 16-week treatment period, with the primary objective being to assess the efficacy of twice-daily applications of delgocitinib cream. The primary endpoint is achieving a 75% improvement in the Palmoplantar Pustulosis Area and Severity Index (PPPASI-75) at Week 16. Secondary endpoints include achieving a PPP-PGA score of 0 or 1 with at least a 2-step improvement from baseline and a change in the overall number of fresh pustules from baseline to Week 16.
Participants will undergo a sequence of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, diagnosis, and disease severity. This visit will include a central evaluation of photographs to confirm the diagnosis of palmoplantar pustulosis. Following randomization, participants will attend regular follow-up visits to monitor treatment response and safety. The end-of-study visit will occur at the conclusion of the 16-week treatment period, where final assessments will be conducted to evaluate the primary and secondary endpoints.
The expected length of participant involvement is approximately 16 weeks, corresponding to the treatment duration. Conditions that may lead to early termination from the study include non-compliance with study procedures, withdrawal of consent, or adverse events that, in the investigator's judgment, warrant discontinuation of treatment. The trial is not categorized as low intervention and is conducted under the auspices of a phase 4 clinical trial. Participants are required to provide informed consent and meet all inclusion criteria to be eligible for participation.
Treatment
The clinical trial involves the use of **Delgocitinib cream**, which is an experimental medication formulated as a cream. The active substance in this formulation is **delgocitinib**, a chemical compound. The cream is applied cutaneously, with a concentration of 20 mg/g. Participants are instructed to apply the cream twice daily, with a maximum daily dose of 2.50 grams and a total maximum dose of 280 grams over the course of the study. The treatment period is set for 16 weeks. The cream is manufactured by LEO PHARMA A/S and is identified by the sponsor product code LP0133. Compliance with the dosing schedule is monitored throughout the trial to ensure adherence to the treatment regimen.
The study also includes a **Cream Vehicle** as a non-experimental treatment, serving as a placebo comparator. The Cream Vehicle is used to assess the efficacy and safety of the Delgocitinib cream by providing a baseline for comparison. It is applied in the same manner as the experimental cream, twice daily, and is also administered cutaneously. The Cream Vehicle does not contain any active pharmaceutical ingredients and is used to maintain the double-blind nature of the trial. Participant compliance with the application of the Cream Vehicle is similarly monitored to ensure consistency in the administration of treatments across the study population.
Efficacy
The efficacy of the investigational product, **delgocitinib cream**, will be assessed in a phase 2a, double-blind, 2-arm clinical trial. The primary endpoint for evaluating efficacy is the achievement of PPPASI-75 at Week 16. This endpoint measures a 75% improvement in the Palmoplantar Pustulosis Area and Severity Index (PPPASI) from baseline, indicating a significant reduction in disease severity. Secondary endpoints include achieving a PPP-PGA score of 0 or 1, which corresponds to clear or almost clear skin, with at least a 2-step improvement from baseline at Week 16. Additionally, the change in the overall number of fresh pustules from baseline to Week 16 will be evaluated.
Efficacy assessments will be conducted at specified timepoints, with the primary and secondary endpoints being measured at Week 16. The PPPASI and PPP-PGA scores will be determined through clinical evaluations, and the number of fresh pustules will be counted to assess changes from baseline. These assessments will be performed by trained investigators to ensure consistency and accuracy in data collection. The trial aims to provide robust data on the efficacy of delgocitinib cream in treating mild to severe palmoplantar pustulosis over a 16-week treatment period.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Signed and dated informed consent has been obtained prior to any protocol-related procedures.
- Age 18 years or above at the time of informed consent signing.
- Subject is able to comply with clinic visits and trial requirements and procedures, as assessed by the investigator.
- Diagnosis of PPP in accordance with the consensus diagnostic criteria established by the European Rare and Severe Psoriasis Expert Network (ERASPEN): primary, persistent (>3 months duration), sterile, macroscopically visible pustules on the palms and/or soles, with or without plaque psoriasis elsewhere on the body.
- Confirmed PPP by central evaluation of photographs taken at screening.
- Mild to severe PPP current condition defined by: • Disease duration of PPP of >6 months before randomisation. • PPP-PGA of at least mild severity (PPP-PGA ≥2) at screening and baseline. • Palmoplantar Pustulosis Area and Severity Index (PPPASI) ≥8 at screening and baseline.
- Presence of ≥5 well-demarcated fresh pustules (white or yellow pustules) in total across all affected areas at screening and baseline.
- Subjects with prior experiences of inadequate response with topical corticosteroids (TCS) or for whom TCS are inadvisable, as judged by the investigators.
- A woman of childbearing potential must use an acceptable form of birth control throughout the trial up until the last administration of IMP.
Exclusion Criteria
- Presence or known history of drug-induced PPP
- Presence of acrodermatitis continua of Hallopeau.
- Active dermatologic condition that could confound the diagnosis of PPP or interfere with assessment of the IMP, as assessed by the investigator
- Clinically significant infection on the palms or soles.
- Concurrent plaque psoriasis covering >5% of body surface area.
- Clinically significant infection within 4 weeks prior to baseline. Clinically significant infections are defined as: • A systemic infection. • A serious skin infection requiring parenteral (intravenous or intramuscular) antibiotics, parenteral antiviral, or parenteral antifungal medication.
- History of any known primary immunodeficiency disorder including a positive human immunodeficiency virus test at screening
- Major surgery within 8 weeks prior to screening or planned in-patient surgery or hospitalisation during the trial period
- Any documented active or suspected malignancy, or history of malignancy within 5 years prior to screening, except basal cell carcinoma of the skin, localised squamous cell carcinoma of the skin, or in situ carcinoma of the cervix appropriately treated before the baseline visit.
- Any disorder which is not stable and could: • Affect the safety of the subject throughout the trial. • Impede the subject’s ability to complete the trial.
- Any clinically significant abnormal findings occurring during the screening period and/or observed at the baseline visit that may put the subject at risk because of their participation in the trial, or can influence the subjects ability to complete the trial.
- Positive hepatitis B surface antigen and/or hepatitis B core antibody and positive hepatitis B virus DNA (subjects who have tested positive for hepatitis B core antibody are eligible if tests for hepatitis B surface antigen and hepatitis B virus DNA are negative), or positive hepatitis C virus antibody serology confirmed by hepatitis C virus RNA at screening.
- Known or suspected hypersensitivity to any component(s) of the IMP.
- Current or recent chronic alcohol or drug abuse, or any other condition associated with poor compliance as judged by the investigator.
- Women who are pregnant or lactating.
- Systemic treatment within 4 weeks prior to baseline with immunosuppressive, immunomodulating drugs, retinoids tyrosine kinase inhibitors, phosphodiesterase-4 inhibitors, or corticosteroids.
- Use of tanning beds or phototherapy on the palms or soles within 4 weeks prior to baseline.
- Use of systemic or topical janus kinase inhibitors within 4 weeks prior to baseline.
- Cutaneously applied treatment with immunomodulators or TCS on the palms or soles within 2 weeks prior to baseline.
- Use of systemic antibiotics or cutaneously applied antibiotics on the palms or soles within 2 weeks prior to baseline.
- Other transdermal or cutaneously applied therapy on the palms or soles (except for the use of subject’s own non-medicated emollients) within 1 week prior to baseline
- Cutaneously applied treatments in regions other than the palms or soles, which could interfere with clinical trial evaluations or pose a safety concern (excluding treatments for psoriasis patches or other non-exclusionary skin conditions, if needed) within 1 week prior to baseline.
- Treatment with any marketed biological therapy or investigational biologic agents: • Any cell-depleting agents including, but not limited to, rituximab: within 6 months prior to baseline, or until lymphocyte count returns to normal, whichever is longer. • Other biologics, including but not limited to, secukinumab, ustekinumab, tildrakizumab, ixekizumab, risankizumab, guselkumab, and tumour necrosis factor-alpha inhibitors: within 3 months or 5 half-lives, whichever is longer, prior to baseline.
- Treatment with any nonmarketed drug substance (that is, an agent which has not yet been made available for clinical use following registration) within the last 4 weeks prior to baseline or 5 half-lives, whichever is longer.
- Current participation in any other interventional clinical trial.
- Previously randomised in this clinical trial.
- Previously randomised in a clinical trial with delgocitinib.
- Employees of the trial site, or any other individuals directly involved with the planning or conduct of the trial, or immediate family members of such individuals.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Germany | Recruiting | 15 Aug 2025 | 30 |
 Poland | Recruiting | 15 Aug 2025 | 40 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
Cream Vehicle | Placebo | N/A | — | — | — | N/A |
Delgocitinib cream | Test | CREAM | CUTANEOUS USE | 2.50 | 16 | PRD11435696 |