A Study to Evaluate the Efficacy and Safety of Ruxolitinib Cream in Participants With Prurigo Nodularis (PN)

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to evaluate the safety and tolerability of Ruxolitinib cream in participants with Prurigo Nodularis (PN).

Detailed Description
-----------------
The study comprises of a 12 week double-blind, vehicle-controlled (DBVC) treatment period, followed by a 40 week open label extension period, and 30 day safety follow-up period During the double blind period, all PN-affected areas identified at baseline will be treated, and during the open label period, only active PN-affected areas will be treated.

Official Title
-----------------
A Phase 3, Double-Blind, Randomized, Vehicle-Controlled, Efficacy and Safety Study of Ruxolitinib Cream in Participants With Prurigo Nodularis

Conditions
-----------------
Prurigo Nodularis

Intervention / Treatment
-----------------
* Drug: Ruxolitinib Cream
* Drug: Vehicle Cream


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Clinical diagnosis of PN ≥ 3 months before screening. ≥ 6 pruriginous lesions on ≥ 2 different body areas (such as right and left leg) at screening and baseline having a treatment area <20% BSA. IGA-CPG-S score of ≥ 2 at screening and baseline. Baseline PN-related WI-NRS score ≥ 7. Willingness to avoid pregnancy or fathering children. Exclusion Criteria: Chronic pruritus due to a condition other than PN Total estimated BSA treatment area (excluding the scalp) > 20%. Neuropathic and psychogenic pruritus Active atopic dermatitis lesions within 3 months of screening and baseline. Uncontrolled thyroid function Concurrent skin or other serious or unstable medical conditions which may interfere with the evaluation of PN such as immunocompromised status, acute/chronic infections, active malignancy, history of TB, history of DVT/VTE, etc Protocol defined abnormal laboratory results. Use of any protocol-defined prohibited medication unless a washout is completed or use of medication known to cause itching. 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 (within 2 weeks before baseline Pregnant or lactating, or considering pregnancy. History of alcoholism or drug addiction within 1 year Known allergy or reaction to any of the components of the study drug. 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: Vulnerable populations according to article L.1121-6 of the French Public Health Code. Adults under legal protection or who are unable to express their consent per article L.1121-8 of the French Public Health Code. Individuals not affiliated with the social security system.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 99 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ruxolitinib 1.5% Cream<br>Participants apply ruxolitinib 1.5% cream topically to the affected areas as a thin film BID for 12 weeks during the DBVC period. Participants who have completed the treatment during DBVC period will enter the open label extension (OLE) period for up to 40 weeks. | Drug: Ruxolitinib Cream<br>* Ruxolitinib cream 1.5% twice daily (BID) during the continuous and open label treatment period.<br>* Other names: INCB018424 phosphate cream;|
| Placebo Comparator: Vehicle Cream<br>Participants apply ruxolitinib matching vehicle cream topically to the affected areas as a thin film twice daily (BID) for 12 weeks during the DBVC period. Participants who have completed the treatment during DBVC period will enter the open label extension (OLE) period for up to 40 weeks. | Drug: Vehicle Cream<br>* Ruxolitinib matching vehicle cream 1.5% twice daily (BID) during the vehicle-controlled period.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Worst-Itch Numeric Rating Scale (WI-NRS) ≥ 4-point improvement in WI-NRS score Response | Defined as achieving a ≥ 4-point improvement (reduction) in Worst Itch Numeric Rating Scale (WI-NRS) score from baseline. | Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| WI-NRS4 Response | Defined as achieving a ≥ 4-point improvement (reduction) in WI-NRS score from baseline. | Week 4 | 
| Overall Treatment Success (TS) | Defined as achieving both a WI-NRS4 response and an Investigator's Global Assessment for Stage of Chronic Prurigo Treatment Success (IGA-CPG-S-TS). | Week 12 | 
| IGA-CPG-S-TS | Defined as an IGA-CPG-S score of 0 or 1 with a ≥ 2 grade improvement from baseline | Week 12 | 
| WI-NRS4 Response | Defined as achieving a ≥ 4-point improvement (reduction) in WI-NRS score from baseline. | Day 7 | 
| Proportion of participants with WI-NRS4 at each postbaseline visit. | Defined as percentage of participants that achieve a ≥ 4-point improvement in WI-NRS score | Up to 52 weeks | 
| Change from baseline in WI-NRS score | Defined as change in Intensity of itch. Itch will be measured using an NRS used to indicate the intensity of the worst itching over the past 24 hours using a 0 to 10 numeric rating scale, where 0 represents no itching and 10 represents worst itching imaginable. | Up to 52 weeks | 
| Time to ≥ 2-point improvement from baseline in WI-NRS score | Participants rate pruritus daily on Worst Itch [pruritis] Numerical Rating Scale (0=no pruritus; 10=worst imaginable pruritus) | Up to 52 weeks | 
| Time to ≥ 4-point improvement from baseline in WI-NRS score | Defined as time taken for the participant to achieve a ≥4 improvement in NRS scale compared to baseline | Up to 52 weeks | 
| Skin pain response, defined as a ≥ 2-point improvement in Skin Pain NRS score | Itch NRS is an 11-point scale (0 to 10) where 0 is no itch and 10 is the worst itch imaginable. | Skin pain response, defined as a ≥ 2-point improvement in Skin Pain NRS score | 
| Change from baseline in Skin Pain NRS score | Itch NRS is an 11-point scale (0 to 10) where 0 is no itch and 10 is the worst itch imaginable. | Up to 52 weeks | 
| IGA-TS response, defined as achieving IGA TS at each postbaseline visit. | The IGA-CPG-s for chronic prurigo nodularis considers the number of nodules, also referred to as lesions, and uses them to determine an overall severity rating on a 5-point scale ranging from 0 (clear skin) to 4 (severe). | Up to 56 weeks | 
| IGA-CPG-A 0 or 1 response, defined as achieving an IGA score of 0 or 1 at each postbaseline visit. | The IGA-CPG-A is an overall PN severity rating on a 5-point scale ranging from 0 (clear skin) to 4 (severe disease). The IGA-CPG-A score is based on disease activity based on % of PN lesions with excoriations or crusts. | Up to 56 weeks | 
| > 75% healed lesions from baseline in PAS at each postbaseline visit. | PAS includes 5 items; descriptive of the type, predominant type, distribution, and quantity of pruriginous lesions, and disease activity in terms of percentage of pruriginous lesions with excoriations/crusts on top. | Up to 56 weeks | 
| Number of Treatment-emergent adverse events (TEAEs) | TEAE defined as any adverse event either reported for the first time or worsening of a pre-existing event after first dose of study drug. | Up to 56 weeks | 
| Change from baseline in Dermatology Life Quality Index (DLQI) score at each postbaseline visit. | The DLQI is a simple, 10-question validated questionnaire to measure how much the skin problem has affected the participant over the previous 7 days | Up to 56 weeks | 
| Change from baseline in EQ-5D-5L score at each postbaseline visit. | The EQ-5D-5L questionnaire is a standardized, validated instrument for use as a measure of health outcome | Up to 56 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Prurigo Nodularis, Skin Diseases, Dermatitis, ruxolitinib, PN, INCB18424-320, INCB18424, Prurigo