Efficacy of Abrocitinib for Reducing Pruritus in Adults With Prurigo Nodularis and Chronic Pruritus of Unknown Origin

Study Overview
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Brief Summary
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The primary objective is to assess the efficacy, safety, and tolerability of Abrocitinib for the treatment of Prurigo Nodularis (PN) or Chronic Pruritus of Unknown Origin (CPUO) in patients experiencing moderate to severe pruritus.

Detailed Description
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This is a trial to assess the efficacy of Abrocitinib as a therapeutic for Prurigo Nodularis (PN) and Chronic Pruritus of Unknown Origin (CPUO). The study will consist of a 4-week Screening period, a 12-week treatment period and then a 4-week follow up period. The arms will run in parallel and patients will take 200 mg oral Abrocitinib daily for the duration of the 12-week treatment period.

Official Title
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Efficacy, Safety, and Tolerability of Abrocitinib for Reducing Pruritus in Adults With Prurigo Nodularis and Chronic Pruritus of Unknown Origin

Conditions
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Prurigo Nodularis, Pruritus, Chronic Pruritus, Chronic Prurigo, Skin Diseases

Intervention / Treatment
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* Drug: Abrocitinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males or female participants between ages 18-80 years at time of signing informed consent A clinical diagnosis of prurigo nodularis, defined by the presence of at least 10 pruritic nodules on at least 2 different anatomic locations (with each arm, leg, and anterior and posterior trunk considered distinct anatomic locations) OR Subject has ongoing chronic pruritus of unknown origin, which must be present on multiple segments on the body. CPUO patients must not have known dermatologic or systemic conditions, that in the opinion of the investigator, are the cause of patient's pruritus Subject has moderate to severe pruritus, defined as average peak pruritus numeric rating scale - (PP-NRS) > 7 (range 0-10, higher score indicating greater degree of pruritus severity) in the 7 days prior to the Screening Visit. Female participants are eligible for the study if they are not pregnant, planning to become pregnant or breastfeeding during the study or not a woman of child bearing potential (WOCBP) Exclusion Criteria: Infected with hepatitis B or hepatitis C viruses. Infected with Herpes Simplex or Herpes zoster. Positive HIV serology at screening, Evidence of active or latent or inadequately treated infection with Mycobacterium tuberculosis (TB) History of lymphoproliferative disease, or active primary or recurrent malignancy History of recurrent (≥ 2) venous thromboembolism (VTE) or (DVT/PE) - deep vein thrombosis and pulmonary embolism Untreated thyroid, adrenal, or pituitary disease or nodules, or history of thyroid malignancy Have received any of the following treatment regiments specified in the timeframes outlined below: Within 6 months of first dose of study drug: Rituximab, any other B cell depleting therapies, or intravenous immunoglobulin (IVIg) Within 12 weeks of first dose of study drug: Any studies with Janus kinase (JAK) inhibitors; Cyclophosphamide (or any other cytotoxic agent), belimumab, or anifrolumab (or another anti-interferon (IFN) therapy) Within 8 weeks of first dose of study drug: Other biologics Within 6 weeks: Have been vaccinated with live or attenuated live vaccine. Within 4 weeks: Participation in other studies involving investigational drug(s) Within 4 weeks: Use of oral immune suppressants; systemic immunosuppressive therapies, neuromodulatory therapies, Phototherapy (NB UVB) or broad band phototherapy; Regular use (more than 2 visits per week) of a tanning booth/parlor. Within 1 week of first dose of study drug: Topical treatments that could affect PN; Herbal medications with unknown properties or known beneficial effects for PN.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: This is a non-randomized study with two arms conducted in parallel: an arm of 10 Prurigo Nodularis (PN) patients, and an arm of 10 Chronic pruritus of unknown origin (CPUO) patients.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Prurigo Nodularis<br>Prurigo Nodularis (PN) patients only: Study Design: Subjects meeting study criteria will undergo a 4-week washout period of other therapies that could impact pruritus through the end of the study (including antihistamines, topical steroids, systemic antipruritic therapies or immunosuppressants). | Drug: Abrocitinib<br>* During the study period, subjects will take one Abrocitinib 200 mg tablet once daily orally. Subjects will be directed to take doses of Abrocitinib at approximately the same time of day.<br>|
| Experimental: Chronic Pruritus of Unknown Origin<br>Chronic Pruritus of Unknown Origin (CPUO) patients only: Study Design: Subjects meeting study criteria will undergo a 4-week washout period of other therapies that could impact pruritus through the end of the study (including antihistamines, topical steroids, systemic antipruritic therapies or immunosuppressants). | Drug: Abrocitinib<br>* During the study period, subjects will take one Abrocitinib 200 mg tablet once daily orally. Subjects will be directed to take doses of Abrocitinib at approximately the same time of day.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change in Weekly Average Peak Pruritus Numeric Rating Scale (PP-NRS) From Baseline to Week 12 | Percent change in weekly average PP-NRS at Week 12. PP-NRS is a single self-report item on an 11-point scale (0 to10) where 0 is No itch, and 10 is the Worst itch imaginable. | Up to 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects Achieving a Reduction in Weekly Average PP-NRS From Baseline to Week 12 | Number of subjects achieving at least a 4-point reduction from baseline in weekly average PP-NRS at Week 12. The PP-NRS is a single self-report item on an 11-point scale (0 to10) where 0 is No itch, and 10 is the Worst itch imaginable. | Up to 12 weeks | 
| Itch Severity Assessed by 5-D Pruritus Scale at Baseline and Week 12 | Assess itch severity as assessed by 5-D pruritus scale. The 5-D pruritus scale scores pruritus over the past 2 weeks along 5 dimensions: duration, degree, direction, disability and distribution. Duration, degree and direction are scored from 1 to 5, with 1 indicating better control and resolution of symptoms, and 5 indicating increased intensity, severity and worsening. Disability is assessed in Leisure/Social, housework/errands, and work/school with scores ranging from N/A, and 1-5, with 1 indicating that itch never affects the activity, and 5 meaning that itch always affects this activity. The scores of each of the 5 domains are achieved separately and then summed together to obtain a total score. Scores can range between 5 no pruritus, and 25 most severe pruritus. | Baseline (week 0) and 12 weeks | 
| Quality of Life as Assessed by the Dermatology Quality of Life Index From Baseline and Week 12 | Quality of life as assessed by the Dermatology Quality of Life Index (DLQI). The DLQI is 10 questions used to assess impact of skin disease. Scores range from 0-30, with 0 corresponding to best quality of life, and 30 corresponding to worst quality of life. | Baseline (week 0) and 12 weeks | 
| Pruriginous Lesions as Assessed by the Prurigo Activity Score From Baseline and Week 12 | Pruriginous lesions as assessed by the Prurigo Activity Score (PAS). The PAS is a 7-item questionnaire that assesses the number, distribution and activity of pruriginous lesions. The score is calculated via summation of the scoring values, added up with 123 and afterwards divided by 10. This results in a range of values from 1.3 to 21.3. | Baseline (week 0) and 12 weeks | 
| Itch-scratching Behavior as Assessed by Patient Reported Outcomes Measurement Information System at Baseline and Week 12 | Itch-scratching behavior as assessed by Patient Reported Outcomes Measurement Information System (PROMIS®) Itch Questionnaire (PIQ) T-Score: Scratching. The PIQ T-Score: Scratching, is comprised of 5 questions to assess Itch-Scratching Behavior over the past 7 days. Scores for each question range from 1-5, Score range of 5-25 with scores of 1 indicating less scratching behavior and scores of 5 indicating the greatest scratching behavior. A higher PROMIS T-score represents more of the concept being measured. For negatively-worded concepts like Itch, a T-score of 60 is one SD worse than average. By comparison, an Itch T-score of 40 is one SD better than average For PROMIS, the T-scores have a mean (SD) of 50 (10) for adults in the US experiencing itch for any reason. | Baseline (week 0) and 12 weeks | 
| Number of Nodules at Baseline and Week 12 | Number of baseline prurigo nodules over time. As part of the Prurigo Activity Score, lesions are counted in a representative body region. Lesion count within the representative area at Week 0 was compared to lesion count in the representative area at Week 12. | Baseline (week 0) and 12 weeks | 
| Prurigo Nodule Severity at Baseline and Week 12 | Prurigo nodule severity using the Investigator's Global Assessment (IGA). The IGA is a physician scale assessing the number of nodules a Prurigo Nodularis (PN) patient has. Patients receive a score between 0 and 4, where 0 is clear: No prurigo nodules. Post-inflammatory hypo/hyper pigmentation may be present. Grades of 4 are severe: Abundant prurigo nodules. Marked nodule elevation. | Baseline (week 0) and 12 weeks | 
| Quality of Life as Assessed by the EuroQoL 5-Dimension at Baseline and Week 12 | Quality of life as assessed by EuroQoL 5-Dimension (EQ-5D). The 3 level version of the EQ-5D (EQ-5D-3L) assesses degree of debilitation in 5 major aspects of health: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has three possible answers. These answers equate to: No problems or Some/Moderate Problems or Severe/Extreme problems. The patient is asked to indicate their health state by ticking the box next to the most appropriate statement in each of the five dimensions. A unique health state is then defined by combining one level from each of the 5 dimensions. Each state is referred to in terms of a 5-digit code. A total of 243 possible health states codes is defined in this way. State 11111 indicates no problems on any of the five dimensions. The patient then rates how good or bad their health is on that day from a range from 0 the worst health you can imagine, to 100 the best health you can imagine. | Baseline (week 0) and 12 weeks | 
| Depression as Assessed by The Hospital Anxiety and Depression Scale at Baseline and Week 12 | Depression as assessed by The Hospital Anxiety and Depression Scale (HADS), has 7 items relating to depression. Each item scored from 0-3 with higher scores indicating higher depression. Total score range 0-21. | Baseline (week 0) and 12 weeks | 
| Anxiety as Assessed by The Hospital Anxiety and Depression Scale at Baseline and Week 12 | Anxiety as assessed by The Hospital Anxiety and Depression Scale (HADS), has 7 items relating to anxiety. Each item scored from 0-3 with higher scores indicating higher anxiety. Total score range 0-21. | Baseline (week 0) and 12 weeks | 
| Sleep Disturbance as Assessed by the SD-NRS at Baseline and Week 12 | Average sleep disturbance from Week 0 and Week 12 as assessed by (SD) NRS. The SD-NRS is an 11-point scale (0 -10) with higher scores indicating greater sleep disturbance. | Baseline (week 0) and 12 weeks | 
| Itch Intensity in Patients With Underlying Atopy at Baseline and Week 12 | Itch intensity as assessed by PP-NRS in Prurigo Nodularis patients with underlying atopy. The PP-NRS is a single self-report item on an 11-point scale (0 to10) where 0 is No itch, and 10 is the Worst itch imaginable. Atopy defined as a binary variable where patients have 2 out of 3: underlying history of atopic dermatitis, history of seasonal allergies, or asthma. | Baseline (week 0) and 12 weeks | 
| Itch Intensity in Patients Without Underlying Atopy at Baseline and Week 12 | Itch intensity as assessed by PP-NRS in Prurigo Nodularis patients without underlying atopy. The PP-NRS is a single self-report item on an 11-point scale (0 to10) where 0 is No itch, and 10 is the Worst itch imaginable. Atopy is defined as a binary variable where patients have 2 out of 3: underlying history of atopic dermatitis, history of seasonal allergies, or asthma. | Baseline (week 0) and 12 weeks | 
| Itch Intensity in CPUO Patients With High Eosinophilia at Baseline and Week 12 | Itch intensity as measured by PP-NRS in CPUO patients with high eosinophilia (greater than 500 eosinophils per micro-liter of blood). The PP-NRS is an 11-point single self-report item on a scale (0 to10) where 0 is No itch, and 10 is the Worst itch imaginable. | Baseline (week 0) and 12 weeks | 
| Cutaneous Biomarker Analysis - Gene Set Variation Analysis (GSVA), at Baseline and Week 12 | Lesional and non-lesional skin biopsies will be compared for Type 1/2/17/22 T Helper (Th) Th1/Th2/Th17/Th22 polarization before and after treatment. PN and CPUO patients had biopsies collected at Week 0 and at Week 12. PN patients had two biopsies collected: a lesional site and a non-lesional biopsy close by for comparison. The CPUO patients only had one biopsy collected at the timepoints because there are no visible lesions. CPUO will be compared from week 0 to week 12. PN will compare Lesional to non Lesional at Week 0. PN will compare Lesional to Non Lesional at Week 12. GSVA will compare gene set enrichment scores as a function of gene pathway expression which range from -1 to 1. Lower scores indicate down regulation of the gene set, and higher scores indicate up regulation. | Baseline (week 0) and 12 weeks | 
| Systemic Biomarker Analysis - Gene Set Variation Analysis (GSVA), at Baseline and Week 12 | Plasma cytokines will be analyzed for TH1/Th2/Th17/Th22 polarization before and after treatment. This outcome was posted in error. It is not appropriate to perform GSVA of plasma cytokines. It is best practice to limit GSVA to RNASeq. | Baseline and 12 weeks |