A Clinical Trial Evaluating the Efficacy and Safety of HSK21542 in Patients With Chronic Kidney Disease-Associated Pruritus

Study Overview
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Brief Summary
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This is a multi-center, randomized, double-blind, placebo-controlled study. About 310 maintenance hemodialysis patients with moderate or above chronic kidney disease-associated pruritus are planned to be enrolled. They will randomized into the treatment group (HSK21542, 0.3 μg/kg) and the control group (placebo) at a 1:1 ratio.

Official Title
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A Multi-center, Randomized, Double-blind, Placebo-controlled Phase III Clinical Study to Evaluate the Efficacy and Safety of HSK21542 Injection in Maintenance Hemodialysis Patients With Chronic Kidney Disease-associated Pruritus

Conditions
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Pruritus

Intervention / Treatment
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* Drug: HSK21542
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects who are willing to sign an informed consent form, fully understand the objectives and significance of the trial, and are willing to comply with the trial protocol before any of the study-related procedures start; Aged ≥ 18 and ≤ 75 years old, male or female; Patients with end-stage renal disease, who have received regular hemodialysis (including hemodiafiltration) 3 times per week for at least 3 months prior to screening (the judgment of regular hemodialysis is subject to the joint medical comment of the investigator and the sponsor); Dry weight at screening: 40.0-135.0 kg (inclusive); On different days of hemodialysis within 6 months prior to administration, at least two occurrences of single-pool urea clearance index (sp Kt/V) ≥ 1.2 or at least two occurrences of urea reduction ratios (URR) ≥ 65%, or one occurrence of sp Kt/V ≥ 1.2 and one occurrence of URR ≥ 65%; Having completed at least 4 assessments of the Worst Itch Numeric Rating Scale from the lead-in period through D-1 and meeting the criteria of baseline itch intensity ≥ 4 (defined as the average of all non-missing scores from the lead-in period to D-1; scores 0-10 indicates the range from no itch to the worst imaginable itch); Male subjects who agree to use condoms in sexual intercourse during the study and within 3 months after the last dose; female subjects who have been menopausal for at least one year, or who have been sterilized permanently (e.g., fallopian tube occlusion, hysterectomy, bilateral salpingectomy); or women of childbearing potential who agree to take effective contraceptive measures during the study and within 3 months after the last dose, such as oral contraceptives, condoms, and contraceptive films. Exclusion Criteria: Exclusion criteria (those who meet any of the followings are ineligible): Expecting to undergo renal transplantation and/or parathyroidectomy during the study; Having a history of allergy to opioids, such as urticaria (Note: adverse effects related to opioid use, such as constipation and nausea, are not included as the exclusion criteria in this study); Having used opioids within 7 days before screening, or being unable to avoid the use of opioids other than the investigational drug during the study; Having participated in any clinical trial of other drug or medical device within 1 month before screening (received study medication or treated by the medical device in the clinical trial); New or change of treatment received for hemoperfusion regimen within 3 months prior to screening or anticipating to adjust hemoperfusion regimen during the study; Upper extremity blood pressure in a supine position during screening: systolic blood pressure < 90 mmHg, or diastolic blood pressure < 60 mmHg, or systolic blood pressure > 180 mmHg, or diastolic blood pressure > 110 mmHg; Alanine transaminase (ALT) or AST (aspartate transaminase) > 2.5 × upper limit of normal (ULN), or total bilirubin > 2 × ULN at screening; Blood sodium > 155 mmol/L at screening; Hemoglobin < 80 g/L at screening; Positive for hepatitis B surface antigen (HBsAg), hepatitis C antibody (HCVAb), syphilis antibody, or human immunodeficiency virus (HIV) antibody at screening; Pruritus that may or must not be caused by ESRD or its complications (e.g., patients with pruritic dermatosis or cholestatic liver disease will be excluded); New or change of treatment received including antihistamines (oral, intravenous, or topical), systemic or topical corticosteroids (except for otic or ophthalmic preparations) within 7 days prior to screening or anticipating inevitable treatment regimen adjustment during the study; New or change of treatment received including gabapentin, pregabalin, calcineurin inhibitors that are within 5 half-lives prior to screening or anticipating inevitable treatment regimen adjustment during the study; New or change of medications that may affect the judgment of antipruritic efficacy, including but not limited to antipsychotics, sedative-hypnotics, selective serotonin reuptake inhibitors (SSRIs), anxiolytics, or tricyclic antidepressants within 14 days prior to screening or anticipating inevitable treatment regimen adjustment during the study; Females who are pregnant or breastfeeding; Any physiological or psychological diseases or conditions that may increase the risk of the trial, affect the subject's compliance with the protocol, or affect the subject's completion of the trial, as judged by the investigator, including but not limited to: Local pruritus limited to palms only; Pruritus during hemodialysis only; History of known or suspected abuse of or dependence on alcohol, narcotics or other drugs within 12 months before screening; Severe systolic or diastolic heart failure within 6 months prior to screening, e.g., NYHA Class IV congestive heart failure (see Appendix 7 for NYHA functional classification criteria); Severe mental illness or cognitive impairment (e.g., dementia); Any other relevant acute or chronic neurological or psychiatric condition within 3 months prior to screening that, at the discretion of the investigator, is not suitable for enrollment (e.g., encephalopathy, coma, delirium); Patients with malignancy, but excluding: curable cervical carcinoma in situ, skin basal cell or squamous cell carcinoma, or any other tumors that have been cured (no evidence of disease recurrence within 5 years).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HSK21542<br>0.3 μg/kg | Drug: HSK21542<br>* three times per week<br>|
| Experimental: Placebo<br>Placebo | Drug: Placebo<br>* three times per week<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of subjects with an improvement of ≥ 3 points from baseline in the weekly average of the daily Worst Itch Numeric Rating Scale (WI-NRS) after 12 weeks of treatment. | In the NRS score, 0-10 represents different degrees of itching, the larger the number, the more severe the itching | week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in subjects' quality of life (evaluated using the Skindex-16 scale ) after 12 weeks of treatment. | The Skindex-16 Scale is a multidimensional questionnaire which assesses itch-related quality of life over the past week. The questions cover 3 domains: symptoms, emotions, and functioning domain. A lower total score represents better quality of life. | week 12 | 
| Change from baseline in subjects' quality of life (evaluated using the 5-D itch scale) after 12 weeks of treatment. | 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. | week 12 |