A Study to Evaluate the Safety and Efficacy of CR845 in Chronic Kidney Disease Patients With Moderate-to-Severe Pruritus

Study Overview
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Brief Summary
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This is a multicenter, double-blind, randomized, placebo-controlled study to evaluate the safety and efficacy of 3 dose levels of oral CR845 compared to placebo in reducing the intensity of itch in chronic kidney disease (CKD) patients with moderate-to-severe pruritus. This study will consist of a Screening Period, a 7-day Run-in Period, a 12 week Treatment Period, and a Follow-up Visit (approximately 7 days after the last dose of study drug).

Detailed Description
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This study will consist of a Screening Period, a 7-day Run-in Period, a 12 week Treatment Period, and a Follow-up Visit (approximately 7 to 10 days after the last dose of study drug). Informed consent will be obtained prior to performing any study-specific procedures. Screening will occur within 7 to 28 days prior to randomization to assess eligibility. If patients continue to meet all inclusion and no exclusion criteria at the end of the 7-day Run-in Period, they will be randomized in a 1:1:1:1 ratio to receive orally once daily either placebo or CR845 tablets at doses of 0.25, 0.5 or 1 mg. Randomization will be stratified according to the patient's renal disease status: moderate CKD; severe CKD non-dialysis; severe CKD on dialysis (ie, 3 categories). A final safety Follow-up Visit will be conducted 7 to 10 days after the last dose of study drug.

Official Title
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A Multicenter, Double-blind, Randomized, Placebo-controlled Study to Evaluate the Safety and Efficacy of Oral CR845 in Chronic Kidney Disease Patients With Moderate-to-Severe Pruritus

Conditions
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Chronic Kidney Diseases, Pruritus

Intervention / Treatment
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* Drug: CR845 0.25 mg Oral Tablet
* Drug: CR845 0.5 mg Oral Tablet
* Drug: CR845 1 mg Oral Tablet
* Drug: Placebo Oral Tablet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: To be eligible for inclusion into the study, a patient must meet the following criteria: CKD patients with stage III, IV, or V (ie, moderate renal impairment with estimated glomerular filtration rate (GFR) ≥30 and <60 mL/min/1.73 m2 or severe renal impairment with estimated GFR <30 mL/min/1.73 m2). For severe CKD patients on hemodialysis, they must be receiving hemodialysis 3 times per week for at least 3 months prior to the start of screening; Prior to randomization: Has completed at least 4 Worst Itching Intensity NRS worksheets from the start of the 7-day Run-in Period; Has a mean baseline Worst Itching Intensity NRS score ≥5, defined as the average of all non-missing scores reported from the start of the 7-day Run-in Period. Exclusion Criteria: A patient will be excluded from the study if any of the following criteria are met: Patients not currently on dialysis who are likely to initiate routine dialysis during study participation; Scheduled to receive a kidney transplant during the study; New or change of treatment received for itch including antihistamines and corticosteroids (oral, intravenous [IV], or topical) within 14 days prior to screening; Received another investigational drug within 30 days prior to the start of screening or is planning to participate in another clinical study while enrolled in this study; Received ultraviolet B treatment within 30 days prior to the start of screening or anticipates receiving such treatment during the study; Participated in a previous clinical study with CR845.

Ages Eligible for Study
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Minimum Age: 18 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: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized, double-blind, placebo controlled study
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CR845 0.25 mg Oral Tablet<br>Oral CR845 0.25 mg to be taken orally once daily for 12 weeks | Drug: CR845 0.25 mg Oral Tablet<br>* CR845 0.25 mg medication taken orally 1 time/day<br>* Other names: Difelikefalin;|
| Experimental: CR845 0.5 mg Oral Tablet<br>Oral CR845 0.5 mg to be taken orally once daily for 12 weeks | Drug: CR845 0.5 mg Oral Tablet<br>* CR845 0.5 mg medication taken orally 1 time/day<br>* Other names: Difelikefalin;|
| Experimental: CR845 1 mg Oral Tablet<br>Oral CR845 1 mg to be taken orally once daily for 12 weeks | Drug: CR845 1 mg Oral Tablet<br>* CR845 1 mg medication taken orally 1 time/day<br>* Other names: Difelikefalin;|
| Placebo Comparator: Placebo Oral Tablet<br>Oral Placebo to be taken orally once daily | Drug: Placebo Oral Tablet<br>* Placebo tablet taken orally 1 time/day<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reduction of itch-intensity as assessed by the change from baseline in weekly mean of the daily 24-hour Worst Itching Intensity Numerical Rating Scale (NRS) score during Week 12 | Intensity of 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. | Baseline, Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Improvement in itch-related quality of life as assessed by the change from baseline in total Skindex-10 Scale score at the end of Week 12 | The Skindex-10 Scale is a multidimensional questionnaire which assesses itch-related quality of life over the past week. The questions cover 3 domains: disease, mood/emotional distress, and social functioning domain. A lower total score represents better quality of life. | Baseline, Week 12 | 
| Improvement in itch-related quality of life as assessed by the change from baseline in 5-D Itch Scale score at the end of Week 12 | The 5-D Itch Scale is a multidimensional questionnaire which assesses itch-related quality of life over the past 2 weeks. The questions cover five dimensions of itch including the degree, duration of itch/day, direction (improvement/worsening), disability (impact on activities such as work), and body distribution of itch. A lower total score represents better quality of life. | Baseline, Week 12 | 
| Reduction of itch intensity as assessed by the proportion of patients achieving an improvement from baseline ≥3 points with respect to the weekly mean of the daily 24-hour Worst Itching Intensity NRS score at Week 12 | Intensity of 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. | Week 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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difelikefalin, CR845, Pruritus, Chronic Itch, Itch, Itching, uremic pruritus, CKD, CKD-aP, CKD-associated pruritus, Chronic Kidney Disease, Kidney dysfunction, Generalized pruritus, Hemodialysis, Dialysis, ESRD (end stage renal disease), Kidney failure, chronic