Phase 3 Study of Difelikefalin in Haemodialysis Chinese Adult Subjects With Moderate-to-Severe Pruritus

Study Overview
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Brief Summary
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This a multicentre study that consists of a 12-week double-blind period, and an optional 14-week open-label extension period and a 1-week follow-up period.

Detailed Description
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Total study duration for a single subject is 31 to 32 weeks with a 4-week screening period, a 12-week double-blind period, a 14-week optional open-label extension period, and a 1-week follow-up period. For subjects not participating in the open-label extension period, the total study duration is 17 weeks. Difelikefalin will be administered in the double-blind and open-label period 3 times a week at the end of each dialysis session. The total dose of the investigational product will be determined based on the subject's prescription dry body weight. The primary objective of the study is: To evaluate the efficacy of difelikefalin 0.5 μg/kg compared to placebo in reducing the intensity of itch in HD Chinese subjects with moderate-to-severe pruritus.

Official Title
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A Randomised, Double-Blind, Placebo-Controlled, Multicentre, Phase 3, Clinical Study of Difelikefalin in Haemodialysis Chinese Adult Subjects With Moderate-to-Severe Pruritus

Conditions
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Uremic Pruritus

Intervention / Treatment
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* Drug: Difelikefalin Injection
* Drug: Placebo Injection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects with chronic kidney disease (CKD) on HD 3 times weekly for ≥12 weeks prior to the informed consent procedure (including the date of informed consent) who can continue HD without changing its frequency or method. If female, is not pregnant, or nursing. If female: Is surgically sterile; or Has been amenorrhoeic for at least 1 year and is over the age of 55 years; or Has a negative serum pregnancy test within 7 days before first dose of investigational product and agrees to use acceptable contraceptive measures (e.g., hormonal contraceptives, barrier with spermicide, intrauterine device, vasectomised partner, or abstinence) from the time of informed consent until 7 days after the last dose of investigational product. If male, agrees not to donate sperm after the first dose of investigational product administration until 7 days after the last dose of investigational product, and agrees to use a condom with spermicide or abstain from heterosexual intercourse during the study until 7 days after the last dose of investigational product. Subjects with a prescription dry body weight between 40 and 100 kg, inclusive. Exclusion Criteria: Planned or anticipated to receive a kidney transplant during the study. Has localised itch restricted to the palms of the hands. Has pruritus only during the dialysis session Subjects with severe hepatic impairment (Child-Pugh Class C) or concurrent hepatic cirrhosis. Subject is receiving ongoing ultraviolet B treatment and anticipates receiving such treatment during the study. Significant systolic or diastolic heart failure (e.g., New York Heart Association Class IV congestive heart failure) Subjects with concurrent malignancy except excised basal cell or squamous cell carcinoma of the skin, or carcinoma in situ that has been excised or resected completely. Known or suspected history of alcohol, narcotic, or other drug abuse, or substance dependence within 12 months prior to screening. Severe mental illness or cognitive impairment (e.g., dementia) or other concurrent mental disorder that, in the opinion of the Investigator, would compromise the validity of study measurements. Any other relevant acute or chronic medical or neuropsychiatric condition within 3 months prior to screening (e.g., diagnosis of encephalopathy, coma, delirium). New or change of treatment received for itch including antihistamines and corticosteroids (oral, IV, or topical) within 14 days prior to screening. New or change of prescription for opioids, gabapentin, or pregabalin within 14 days prior to screening. Subject is receiving prohibited medication (e.g., nalfurafine hydrochloride, opioid antagonists)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 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
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 12-weeks double-blind period - Difelikefalin<br> | Drug: Difelikefalin Injection<br>* Participants receive Difelikefalin three times a week (0,5 micrograms/kg dry body weight). Difelikefalin is administered by intravenous bolus injection into the venous line of the dialysis circuit at the end of each dialysis.<br>|
| Placebo Comparator: 12-weeks double-blind period - Placebo<br> | Drug: Placebo Injection<br>* Participants receive Placebo three times a week (0,5 micrograms/kg dry body weight). Placebo is administered by intravenous bolus injection into the venous line of the dialysis circuit at the end of each dialysis.<br>|
| Experimental: 14-weeks optional open-label period following the double-blind period - Difelikefalin<br> | Drug: Difelikefalin Injection<br>* Participants receive Difelikefalin three times a week (0,5 micrograms/kg dry body weight). Difelikefalin is administered by intravenous bolus injection into the venous line of the dialysis circuit at the end of each dialysis.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in the weekly mean of the daily 24-hour WI-NRS score at Week 4 of the double-blind period | The degree of the most intense itching within a day will be assessed using Worst Itch Numeric Rating Scale (WI-NRS) scores. | Week 4 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of subjects achieving ≥3-point improvement from baseline with respect to the weekly mean of the daily 24-hour WI-NRS |  | Week 4 of double-blind period | 
| Proportion of subjects achieving ≥3-point improvement from baseline with respect to the weekly mean of the daily 24-hour WI-NRS |  | Week 8 of double-blind period | 
| Proportion of subjects achieving ≥3-point improvement from baseline with respect to the weekly mean of the daily 24-hour WI-NRS |  | Week 12 of double-blind period | 
| Proportion of subjects achieving ≥4-point improvement from baseline with respect to the weekly mean of the daily 24-hour WI-NRS |  | Week 4 of double-blind period | 
| Proportion of subjects achieving ≥4-point improvement from baseline with respect to the weekly mean of the daily 24-hour WI-NRS |  | Week 8 of double-blind period | 
| Proportion of subjects achieving ≥4-point improvement from baseline with respect to the weekly mean of the daily 24-hour WI-NRS |  | Week 12 of double-blind period | 
| Change from baseline in itch-related Quality of Life (QoL) at the end of Week 12 of the double-blind period, as assessed by the 5-D itch scale total score. | The 5-D itch scale is a questionnaire where patients assess the 5 dimensions of itch (degree, duration, direction, disability, and distribution). | End of double-blind period, week 12 | 
| Change from baseline in itch-related QoL at the end of Week 12 of the double-blind period, as assessed by the Skindex-10 scale total score. | The Skindex-10 scale is a questionnaire that measures QoL in relationship to the itch intensity. | End of double-blind period, week 12 | 
| Patient Global Impression of Change. | The Patient Global Impression of Change is a questionnaire that assesses the change in itch compared to the itch at the start of the study | End of double-blind period, week 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Uremic Pruritus, Chronic kidney disease-associated pruritus, CKD-aP, Difelikefalin