A Phase 2, Double-Blind, Randomized, 16-Week, Vehicle-Controlled, Efficacy and Safety Study of Ruxolitinib Cream Followed by an Open-Label Extension Period in Adults With Chronic Hand Eczema
- Trial ID
- 2022-502827-23-00
- Protocol
- INCB 18424-226
- Sponsor
- Incyte Corp.
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to evaluate the **efficacy** of ruxolitinib 1.5% cream compared to a vehicle cream in the treatment of participants with moderate to severe **Chronic Hand Eczema** (CHE). This is clinically relevant as it aims to determine the therapeutic potential of ruxolitinib cream in managing symptoms of CHE, which can significantly impact patients' quality of life.
Secondary objectives include:
- Further assessment of the treatment effects of ruxolitinib 1.5% cream applied twice daily in participants with CHE.
- Further evaluation of the efficacy of ruxolitinib 1.5% cream applied twice daily.
- Evaluation of participants' quality of life and other patient-reported outcomes.
- Assessment of the safety and tolerability of ruxolitinib 1.5% cream applied twice daily.
- Characterization of biomarkers associated with CHE and/or treatment.
Participants
The clinical trial involves a total of **129 participants** diagnosed with **Chronic Hand Eczema** (CHE). The study population includes both male and female subjects, aged 18 years and older, who have been experiencing CHE for at least six months prior to screening. Participants were selected based on their ability to comprehend and sign a written informed consent form, and they must have a baseline Investigator's Global Assessment (IGA) score of 3 or 4, indicating moderate to severe CHE. Additionally, participants are required to have a baseline CHE-related Itch Numeric Rating Scale (NRS) score of 4 or higher. The trial includes individuals who have been treated with at least one prescription therapy for CHE or for whom such therapy was not advisable or contraindicated. Lifestyle considerations such as willingness to avoid pregnancy or fathering children during and after the trial are also part of the selection criteria. The trial population includes vulnerable groups, ensuring a comprehensive evaluation of the treatment's efficacy across diverse demographics.
Plans and Procedures
The clinical trial is designed to evaluate the **efficacy** and safety of **ruxolitinib** cream in adults with moderate to severe **chronic hand eczema**. This is a Phase 2, double-blind, randomized, vehicle-controlled study, followed by an open-label extension period. The trial will span a total duration of 16 weeks, with an estimated end date in February 2025. Participants will be randomly assigned to receive either the active treatment, ruxolitinib cream, or a vehicle cream without the active substance, applied cutaneously. The primary endpoint is the proportion of participants achieving Investigator's Global Assessment of Chronic Hand Eczema Treatment Success (IGA-CHE-TS) at Week 16. Secondary endpoints include various measures of itch and skin pain improvement, as well as changes in quality of life scores.
The study involves several key visits, beginning with a screening visit to confirm eligibility based on criteria such as age, diagnosis duration, and baseline severity scores. Participants must have a diagnosis of chronic hand eczema for at least six months and meet specific itch and treatment history criteria. Following the screening, baseline assessments will be conducted before the first application of the study cream. Subsequent follow-up visits will occur at regular intervals to monitor efficacy and safety, with assessments including itch and skin pain scores, quality of life measures, and adverse event monitoring. The end-of-study visit will conclude the trial, with final evaluations of the primary and secondary endpoints.
Participant involvement is expected to last for the full 16-week duration of the study, with conditions for early termination including withdrawal of consent, non-compliance with study procedures, or adverse events that necessitate discontinuation. The trial is structured to ensure rigorous assessment of the treatment's impact on chronic hand eczema, with a focus on both clinical outcomes and participant safety.
Treatment
The clinical trial involves the use of **Ruxolitinib cream**, which is an investigational medication formulated as a cream. The active substance in this product is **Ruxolitinib**, a chemical compound. The cream is intended for **cutaneous use** and is applied topically. The dosage regimen specifies a maximum daily dose of 4 grams, with a total maximum dose of 896 grams over a treatment period of up to 32 weeks. The cream is manufactured by Incyte Corporation and is identified by the product code INCB018424. The primary objective of the trial is to evaluate the efficacy of Ruxolitinib 1.5% cream in treating participants with moderate to severe chronic hand eczema (CHE).
The study also includes a **Vehicle Cream**, which serves as a comparator treatment. This cream has the same formulation as the Ruxolitinib cream but does not contain the active substance. The vehicle cream is used as a placebo to assess the efficacy of the Ruxolitinib cream in a double-blind, randomized manner. The vehicle cream is also applied topically and follows the same administration schedule as the Ruxolitinib cream. This allows for a controlled comparison of the therapeutic effects of the active treatment versus the placebo.
Efficacy
The efficacy of Ruxolitinib cream in the treatment of moderate to severe **Chronic Hand Eczema (CHE)** will be assessed through a series of primary and secondary endpoints. The primary endpoint is the proportion of participants achieving Investigator's Global Assessment of Chronic Hand Eczema Treatment Success (IGA-CHE-TS) at Week 16. Secondary endpoints include the proportion of participants achieving an ITCH4 response at various timepoints, including Week 16, Week 4, Week 1 (Day 7), and Day 3. Additionally, changes from baseline in CHE-related Itch Numeric Rating Scale (NRS) scores and Skin Pain NRS scores will be evaluated at each postbaseline visit. The time to achieve a ≥4-point improvement in Itch NRS score and a ≥2-point improvement in Skin Pain NRS score from baseline will also be measured.
Further assessments will include the percentage change in Hand Eczema Severity Index (HECSI) from baseline to Week 16, Patient Global Impression of Change (PGIC) scores, and changes from baseline in Dermatology Life Quality Index (DLQI), EQ-5D-5L, Quality of Life in Hand Eczema Questionnaire (QOLHEQ), and Work Productivity and Activity Impairment Questionnaire for Chronic Hand Dermatitis (WPAI-ChHD) scores at specified weeks. The type, frequency, and severity of adverse events, as well as changes in vital signs and laboratory data for hematology and serum chemistry, will be monitored throughout the study. Efficacy parameters will be collected and analyzed at designated timepoints, including Weeks 2, 4, 8, 12, 16, 24, and 32, as well as during follow-up visits.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Ability to comprehend and willingness to sign a written ICF for the study. A signed written ICF must be obtained for inclusion, see Section 8.1.1 (of the Protocol) for additional details.
- Age ≥ 18 years at the screening visit.
- Diagnosis of CHE for at least 6 months prior to screening. Diagnosis of CHE is defined as HE lasting > 3 months or ≥ 2 recurrences within the previous 12 months.
- Screening and baseline IGA-CHE score of 3 or 4.
- Baseline CHE-related Itch NRS score ≥ 4. Baseline Itch NRS score is defined as the 7-day average of Itch NRS score directly before Day 1 (data from a minimum of 4 out of 7 days prior to Day 1 is needed).
- Have been treated with at least 1 prescription CHE therapy or if such therapy was not advisable or contraindicated.
- Willingness to avoid pregnancy or fathering children, based on specific criteria (Male participants with reproductive potential must agree to take appropriate precautions to avoid fathering children from screening through 90 days (a spermatogenesis cycle) after the last application of ruxolitinib cream and must refrain from donating sperm during this period; Female participants who are WOCBP must have a negative serum pregnancy test at screening and negative urine pregnancy test before the first application on Day 1 and must agree to take appropriate precautions to avoid pregnancy from screening through 30 days (1 menstrual cycle) after the last application of study ruxolitinib cream and must refrain from donating oocytes during this period).
Exclusion Criteria
- Known triggers for CHE (allergic or irritant, such as those identified by previous patch tests) cannot be avoided during the course of the study.
- Current treatment or treatment within 30 days or 5 half-lives (whichever is longer) before the baseline visit with another investigational medication or current enrollment in another investigational drug protocol.
- Known allergy or reaction to any of the components of the study cream.
- In the opinion of the investigator are unable or unlikely to comply with the administration schedule and study evaluations.
- Committed to a mental health institution by virtue of an order issued either by the judicial or the administrative authorities.
- Employees of the sponsor or investigator or otherwise dependents of them.
- History of (within the past 5 years) or current AD or current psoriasis.
- Concurrent conditions and history of other diseases: a. Other active skin disease or infection on the hands, including tinea manuum. In addition, foot eczema is excluded; b. Immunocompromised (eg, lymphoma, acquired immunodeficiency syndrome, or Wiskott-Aldrich syndrome); c. Chronic or acute infection requiring treatment with systemic antibiotics, antivirals, antiparasitics, antiprotozoals, or antifungals within 2 weeks before baseline; d. Active acute bacterial, fungal, or viral skin infection (eg, herpes simplex, herpes zoster, chickenpox, or impetigo) within 1 week before baseline; et al.
- Any serious illness or medical, physical, or psychiatric condition(s) that, in the investigator's opinion, would interfere with full participation in the study, including administration of study drug and attending required study visits; pose a significant risk to the participant; or interfere with interpretation of study data. Examples: a. Clinically significant or uncontrolled cardiovascular disease, including unstable angina, acute myocardial infarction, or stroke within 6 months from Day 1 of study drug application, New York Heart Association Class III or IV congestive heart failure, and arrhythmia requiring therapy or uncontrolled hypertension (blood pressure > 150/90 mm Hg) unless approved by the medical monitor/sponsor; b. Participants with or a history of malignancy in the 5 years preceding the baseline visit, except for adequately treated nonmetastatic nonmelanoma skin cancer; c. Current and/or history of arterial or venous thrombosis, including deep venous thrombosis and pulmonary embolism; d. Current and/or history of active tuberculosis or current and/or history of latent tuberculosis unless adequately treated; e. History of severe anemia, severe thrombocytopenia, or severe neutropenia.
- Particular clinical laboratory test results at screening: a. Cytopenias, defined as follows: Hemoglobin < 100 g/L (ie, 10 g/dL), Absolute neutrophil count < 1.5 × 109/L (ie, 1500/μL), Platelet count < 1 × 1011/L (ie, 100,000/μL) b. Liver function tests: AST or ALT ≥ 2.5 × ULN, Total bilirubin > 1.5 × ULN unless Gilbert syndrome; et al. (specified in the Study Protocol, section 5.2. Exclusion Criteria, page 28).
- Use of particular treatments within the indicated washout period before the baseline visit: a. 12 weeks or 5 half-lives, whichever is longer – biologic agents (eg, dupilumab). For biologic agents with washout periods longer than 12 weeks (eg, rituximab), consult the medical monitor. b. 4 weeks – systemic corticosteroids or adrenocorticotropic hormone analogs; cyclosporine, methotrexate, azathioprine, or other systemic immunosuppressive or immunomodulating agents (eg, mycophenolate or tacrolimus); or oral alitretinoin or any other systemic treatment for CHE. c. 4 weeks for any topical or systemic JAK or TYK2 inhibitor (eg, abrocitinib, baricitinib, brepocitinib, deucravacitinib, filgotinib, lestaurtinib, pacritinib, ruxolitinib, tofacitinib, upadacitinib). d. 2 weeks or 5 half-lives, whichever is longer – strong systemic CYP3A4 inhibitors. e. 2 weeks – systemic antibiotics, immunizations with live-attenuated vaccines, or sedating antihistamines unless on a long-term stable regimen (nonsedating antihistamines are permitted). f. 1 week – use of any topical treatments for CHE (other than bland emollients, eg, Aveeno® creams, ointments, sprays, and soap substitutes), such as corticosteroids, calcineurin inhibitors, topical antipruritics (eg, doxepin cream), phosphodiesterase 4 inhibitors, coal tar (shampoo), topical antibiotics or antifungals, and antibacterial cleansing body wash/soap.
- Psoralen ultraviolet A or ultraviolet B therapy for CHE within 4 weeks before baseline.
- Pregnant or lactating participants or those considering pregnancy during the period of their study participation.
- History of alcoholism or drug addiction within 1 year before screening or current alcohol or drug use that, in the opinion of the investigator, will interfere with the participant's ability to comply with the administration schedule and study assessments.
- In the EU, participants considered incapacitated (according to CTR Article 31) are excluded from the study.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Germany | Not Recruiting | 01 Oct 2023 | 20 |
 Poland | Not Recruiting | 01 Oct 2023 | 31 |
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 |
|---|---|---|---|---|---|---|
Vehicle Cream: Same formulation of cream as the Test product but without active substance. | Placebo | N/A | — | — | — | N/A |
Ruxolitinib cream | Test | CREAM | CUTANEOUS USE | 4 | 32 | PRD10399242 |