INCB 18424-320: A phase 3, double-blind, randomised, vehicle-controlled, efficacy and safety study of ruxolitinib cream in participants with Prurigo Nodularis. Topical ruxolitinib evaluation in Prurigo Nodularis (TRuE-PN2)
- Trial ID
- 2022-502461-23-00
- Protocol
- INCB18424-320
- Sponsor
- Incyte Corp.
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to demonstrate the **efficacy** of ruxolitinib 1.5% cream, applied twice daily (BID), in participants with **Prurigo Nodularis** (PN). This objective is clinically relevant as it aims to establish the therapeutic potential of ruxolitinib cream in alleviating the symptoms associated with PN, a chronic skin condition characterized by intensely itchy nodules.
Secondary objectives include further demonstrating the treatment effects of ruxolitinib 1.5% cream BID in participants with PN. This will provide additional insights into the cream's effectiveness and potential benefits in managing this condition.
Participants
The clinical trial involves a total of **90 participants** diagnosed with **Prurigo Nodularis**. The study population includes both male and female subjects, aged 18 years and older, who have been clinically diagnosed with the condition for at least three months prior to screening. Participants were selected based on specific criteria, including the presence of at least six pruriginous lesions on two different body areas and a baseline WI-NRS score of 7 or higher. The trial does not specify any particular lifestyle considerations such as diet or physical activity. The study population includes individuals from a vulnerable population, indicating a need for careful ethical considerations. The trial aims to evaluate the efficacy of ruxolitinib 1.5% cream applied twice daily in this patient group.
Plans and Procedures
The clinical trial is designed as a **randomized**, **double-blind**, vehicle-controlled study to evaluate the efficacy and safety of **Ruxolitinib** cream in participants with **Prurigo Nodularis**. The trial aims to demonstrate the efficacy of Ruxolitinib 1.5% cream applied twice daily. The study is expected to commence recruitment on February 8, 2024, and conclude by April 30, 2026, with a maximum treatment period of 52 weeks. Participants will be randomly assigned to receive either the active treatment or a vehicle cream without the active substance, ensuring blinding for both participants and investigators.
The trial will include several study visits, beginning with a screening visit to confirm eligibility based on specific inclusion criteria, such as a clinical diagnosis of Prurigo Nodularis for at least three months and the presence of pruriginous lesions. Participants must also meet criteria related to age, reproductive precautions, and baseline scores on specific scales. Following the screening, eligible participants will proceed to baseline assessments before the first application of the study cream. Subsequent follow-up visits will occur at regular intervals to monitor safety, efficacy, and adherence to the treatment regimen.
The primary endpoint is the WI-NRS4 response at Week 12, defined as a ≥4-point improvement in the WI-NRS score from baseline. Secondary endpoints include the WI-NRS4 response at Week 4, Overall-TS at Week 12, and IGA-CPG-S-TS at Week 12. The end-of-study visit will assess the final outcomes and any long-term effects of the treatment. Participant involvement is expected to last up to 52 weeks, with conditions for early termination including adverse events, withdrawal of consent, or non-compliance with the study protocol.
Treatment
The clinical trial involves the use of **Ruxolitinib** cream, an experimental medication formulated as a cream for **cutaneous use**. The active substance in this formulation is Ruxolitinib, a chemical compound, with the product being developed by Incyte Corporation. The cream is administered topically at a concentration of 1.5%, with a maximum daily dose of 15 grams. The total maximum dose over the treatment period is 5460 grams. The treatment is applied twice daily (BID) for a maximum duration of 52 weeks. Participant compliance with the dosing schedule is monitored throughout the study to ensure adherence to the treatment regimen.
The study also includes a **vehicle cream** as a non-experimental treatment, serving as a placebo comparator. This vehicle cream shares the same formulation as the Ruxolitinib cream but lacks the active substance. It is also administered topically and follows the same application schedule as the experimental cream, being applied twice daily. The use of the vehicle cream allows for a controlled comparison to assess the efficacy and safety of the Ruxolitinib cream in participants with Prurigo Nodularis. Compliance with the application of the vehicle cream is similarly monitored to maintain the integrity of the study's double-blind design.
Efficacy
The efficacy of ruxolitinib cream in the treatment of **Prurigo Nodularis** will be assessed through a series of primary and secondary endpoints. The primary endpoint is the WI-NRS4 response at Week 12, defined as achieving a ≥ 4-point improvement in the WI-NRS score from baseline. Secondary endpoints include the WI-NRS4 response at Week 4, Overall-TS at Week 12, and IGA-CPG-S-TS at Week 12. The Overall-TS is defined as achieving both a WI-NRS4 response and an IGA-CPG-S TS, where IGA-CPG-S-TS is defined as an IGA-CPG-S score of 0 or 1 with a ≥ 2 grade improvement from baseline. Additionally, the WI-NRS4 response will be measured on Day 7.
These efficacy parameters will be collected and analyzed at specified timepoints, including Day 7, Week 4, and Week 12. The assessments will utilize validated scales such as the WI-NRS and IGA-CPG-S to ensure accurate and reliable measurement of symptom improvement. The trial is designed to be double-blind and vehicle-controlled, ensuring that the efficacy of the ruxolitinib cream is evaluated against a placebo (vehicle cream without active substance) under controlled conditions. The study aims to demonstrate the efficacy of ruxolitinib 1.5% cream applied twice daily in participants with Prurigo Nodularis over a treatment period of up to 52 weeks.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Ability to comprehend and willingness to sign a written ICF for the study. Note: A signed written ICF must be obtained for inclusion, see Section 8.1.1 for additional details.
- Age ≥ 18 years at the time of signing the ICF.
- Clinical diagnosis of PN ≥ 3 months before screening.
- There are ≥ 6 pruriginous lesions on ≥ 2 different body areas (such as right and left leg) at screening and baseline. Note: The total estimated BSA treatment area must be ≤ 20%.
- IGA-CPG-S score of ≥ 2 at screening and baseline.
- Baseline PN-related WI-NRS score ≥ 7. Baseline WI-NRS score is defined as the 7-day average of WI-NRS scores before Day 1 (data from a minimum of 4 out of 7 days prior to Day 1 is needed).
- Removed during Protocol Amendment 2.
- Willingness to avoid pregnancy or fathering children based on the criteria below. a. 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 study cream and must refrain from donating sperm during this period. Permitted methods in preventing pregnancy (see Appendix A) should be communicated to the participants and their understanding confirmed. b. Female participants who are WOCBP must have a negative serum pregnancy test at screening and negative urine pregnancy test before the first application of study cream 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 cream and must refrain from donating oocytes during this period. Permitted methods in preventing pregnancy (see Appendix A) should be communicated to the participants and their understanding confirmed. c. A female participant not considered to be of childbearing potential as defined in Appendix A is eligible.
Exclusion Criteria
- Acute or chronic pruritus due to a condition other than PN. (Conditions such as: scabies, insect bite, lichen simplex chronicus, psoriasis, acne, folliculitis, habitual picking, lymphomatoid papulosis, chronic actinic dermatitis, dermatitis herpetiformis, sporotrichosis, bullous disease, excoriation syndrome, venous stasis; systemic hematologic disorders [iron-deficiency anemia, polycythemia rubra vera, lymphoma, leukemia]; gastrointestinal disorders [celiac disease, gastric malignancy, obstructive biliary disease; α-1 antitrypsin deficiency]; infections [HIV, hepatitis B and C, mycobacterial]; endocrine disorders [hyperthyroidism]; psychosocial disorders [depression, anxiety], and chronic renal failure.)
- Total estimated BSA treatment area (excluding the scalp) > 20%.
- Neuropathic and psychogenic pruritus, such as but not limited to notalgia paresthetica, brachioradial pruritus, small fiber neuropathy, skin picking syndrome, or delusional parasitosis.
- Active AD lesions (signs and symptoms other than dry skin) within 6 months of screening and baseline.
- Uncontrolled hypothyroidism or hyperthyroidism at screening as determined by the investigator. Note: If the participant has a history of thyroid disease and is on treatment, the participant must be on a stable thyroid regimen for at least 6 weeks prior to Day 1.
- Concurrent conditions and history of other diseases: a. Any other concomitant skin disorder (eg, generalized erythroderma such as Netherton's syndrome), pigmentation, or extensive scarring that in the opinion of the investigator may interfere with the evaluation of pruriginous lesions or assessments of efficacy or compromise participant safety. b. Immunocompromised (eg, lymphoma, acquired immunodeficiency syndrome, 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, clinically infected AD, or impetigo) within 1 week before baseline. e. Unstable asthma or COPD requiring systemic treatment (such as intravenous steroids) or hospital admission or treatment in the emergency department within 3 months of baseline or Stable asthma or COPD requiring the dose equivalent of budesonide more than 720 µg/day (2 puffs BID of a 180-μg dose) or fluticasone more than 440 μg/day (2 puffs BID of a 110-μg dose) or other equivalent inhaled corticosteroids. f. Acute or chronic active HBV or HCV infection (see Section 8.4.5.3). Participants who have recovered or have been successfully treated with no evidence of active HBV or HCV infection and those who are immune due to HBV vaccination can enroll. g. Any underlying condition known to be associated with the clinical presentation of PN that is not under control (stable) prior to the baseline visit.
- 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 application of study cream and attending required study visits; pose a significant risk to the participant; or interfere with interpretation of study data. For example: a. Clinically significant or uncontrolled cardiovascular disease, including unstable angina, acute myocardial infarction or stroke within 6 months from Day 1, New York Heart Association Class III or IV congestive heart failure, and arrhythmia requiring therapy or uncontrolled hypertension (blood pressure > 150/90 mmHg) 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 vein 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.
- Any of the following clinical laboratory test results at screening: a. Cytopenias, defined as follows: − Hemoglobin < 100 g/L (ie, 10 g/dL) − Absolute neutrophil count < 1.5 × 10 9 /L (ie, 1500/µL) − Platelet count < 1 × 10 11 /L (ie, 100,000/µL) b. Liver function tests: − AST or ALT ≥ 2.5 × ULN − Total bilirubin > 1.5 × ULN unless Gilbert's syndrome c. Estimated glomerular filtration rate < 30 mL/min/1.73 m 2 (using the CKD-EPI 2021 Creatinine Equation). d. Positive serology test results at screening for HIV antibody. e. Any other clinically significant laboratory result that, in the opinion of the investigator, poses a significant risk to the participant.
- Use of any of the following treatments within the indicated washout period before the baseline visit: a. Five half-lives or 12 weeks, whichever is longer – biologic agents (eg, dupilumab). For biologic agents with washout periods longer than 12 weeks (eg, rituximab), consult the medical monitor. b. Current treatment or treatment within 30 days or 5 half-lives (whichever is longer) before baseline with another investigational medication or current enrollment in another investigational drug protocol. c. Four weeks for any topical or systemic JAK or TYK2 inhibitor (eg, abrocitinib, baricitinib, deucravacitinib, filgotinib, lestaurtinib, pacritinib, ruxolitinib, tofacitinib, or upadacitinib). d. Four weeks – systemic or intralesional corticosteroids or adrenocorticotropic hormone analogs, cyclosporine, methotrexate, azathioprine, or other systemic immunosuppressive or immunomodulating agents (eg, mycophenolate or tacrolimus). e. Four weeks for opioid antagonists (eg, naloxone and naltrexone). f. Four weeks for gabapentin, pregabalin, or thalidomide. g. Four weeks for the following: − Paroxetine, fluvoxamine, or other SSRIs − SNRIs − Tricyclic antidepressants h. Four weeks – recreational or medicinal use (topical, inhaled, oral, sublingual, or any other route) of cannabis or cannabinoids (eg, THC, CBD). i. Two weeks – systemic antibiotics and immunizations with live-attenuated vaccines. j. Note: Live-attenuated vaccines are prohibited during the DBVC period. COVID-19 vaccination is permitted. k. Two weeks – sedating antihistamines. l. Two weeks or 5 half-lives, whichever is longer – strong systemic CYP3A4 inhibitors. m. Two weeks – any topical treatments for PN (other than bland emollients, eg, Aveeno ® creams, ointments, sprays, and soap substitutes), such as corticosteroids, calcineurin inhibitors, topical antipruritics (eg, doxepin cream), PDE4 inhibitors, coal tar (shampoo), topical antibiotics, and antibacterial cleansing body wash/soap. n. One week – nonsedating antihistamines used for the treatment of PN.
- Current use of a medication known to cause pruritus.
- History of treatment failure (as assessed by the investigator through study participant interview) for PN or any inflammatory condition with any systemic or topical JAK inhibitors (eg, abrocitinib, baricitinib, deucravacitinib, filgotinib, lestaurtinib, pacritinib, ruxolitinib, tofacitinib, or upadacitinib).
- Psoralen and ultraviolet A or ultraviolet B therapy within 4 weeks before baseline or Ultraviolet light therapy or prolonged exposure to natural or artificial sources of ultraviolet radiation (eg, sunlight or tanning booth) within 2 weeks before baseline and/or intention to have such exposure during the study that is thought by the investigator to potentially impact the participant's PN.
- Pregnant or lactating, or considering pregnancy during 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 application schedule and study assessments.
- Removed during Protocol Amendment 1.
- Known allergy or reaction to any of the components of the study cream.
- In the opinion of the investigator, unable or unlikely to comply with the application 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.
- The following participants are excluded in France: a. Vulnerable populations according to article L.1121-6 of the French Public Health Code. b. Adults under legal protection or who are unable to express their consent per article L.1121-8 of the French Public Health Code. c. Individuals not affiliated with the social security system.
- 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 |
|---|---|---|---|
 Austria | Not Recruiting | 08 Feb 2024 | 10 |
 Bulgaria | Not Recruiting | 08 Feb 2024 | 42 |
 Denmark | Not Recruiting | 08 Feb 2024 | 5 |
 France | Not Recruiting | 08 Feb 2024 | 14 |
 Germany | Not Recruiting | 08 Feb 2024 | 12 |
 Italy | Not Recruiting | 08 Feb 2024 | 9 |
 Poland | Not Recruiting | 08 Feb 2024 | 15 |
 Spain | Not Recruiting | 08 Feb 2024 | 10 |
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 creamsame formulation of cream as the test product but without active substance | Placebo | N/A | — | — | — | N/A |
Ruxolitinib (INCB018424) cream | Test | CREAM | CUTANEOUS USE | 15 | 52 | PRD10399242 |