Clinical trial NCT04470154: A Study Evaluating the Safety, Pharmacokinetics, and Efficacy of HSK21542 Injection in Subjects Undergoing Hemodialysis
Official title: A Multi-center, Randomized, Double-blind, Placebo-controlled Phase II Clinical Trial Evaluating the Safety, Pharmacokinetics, and Efficacy of HSK21542 Injection in Subjects Undergoing Hemodialysis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Uremic Pruritus
Lead sponsor: Haisco Pharmaceutical Group Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2020-07-14
Enrollment: 131
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This study is a multicenter study, which is divided into two stages. The first stage is a dose escalation, randomized, double-blind, placebo-controlled study of multiple intravenous administration within one week in hemodialysis subjects. The second stage is a randomized, double-blind, placebo-controlled study of Administration for 12 weeks in hemodialysis subjects with moderate or severe pruritus.
Primary purpose: TREATMENT

Brief summary: This is a multi-center, randomized, double-blind, placebo-controlled phase II clinical trial. The main objective is to evaluate the safety, pharmacokinetics, and efficacy of HSK21542 injection in subjects undergoing hemodialysis

Detailed description: This study is a multicenter study, which is divided into two stages. The first stage is a dose escalation, randomized, double-blind, placebo-controlled study of multiple intravenous administration within one week in hemodialysis subjects. The second stage is a randomized, double-blind, placebo-controlled study of Administration for 12 weeks in hemodialysis subjects with moderate or severe pruritus. In the second stage, consist of a Screening Visit, a 7-day Run-in Period, a 12 week Double-blind Treatment Period, and a 2-week Discontinuation Period. Informed consent will be obtained prior to performing any study-specific procedures. The Screening Visit will occur within 8 to 28 days prior to randomization to assess eligibility.

Eligibility criteria: Stage1: Inclusion Criteria:

1. Subjects who are willing to sign an informed consent form, fully understand the objectives and purposes of the study, and are willing to comply with the study protocol before any of the study-related procedures start;
2. Aged ≥ 18 and ≤ 75 years old, male or female;
3. Dry weight ≥ 50.0 kg at screening, body mass index (BMI = weight (kg) / height2 \[m2\]) in the range of 16.0-30.0 kg/m\^2 (inclusive);
4. Patients with end-stage renal diseases who receive hemodialysis (including hemodiafiltration) 3 times in a week prior to screening for at least 3 months;
5. Patients with at least two occurrences of single-compartment urea clearance (sp Kt/V, see Appendix 7 for the calculation formula) ≥ 1.2, or at least two occurrences of urea reduction ratio (URR) ≥ 65%, or one occurrence of sp Kt/V ≥ 1.2 and one occurrence of URR ≥ 65% on different days of dialysis within 3 months before screening;
6. Male subjects must agree to use condoms in sexual intercourse during the study and within 3 months after the last dose; female subjects should have had menopause for at least one year, or should have had permanent sterilization (e.g., fallopian tube occlusion, hysterectomy, bilateral salpingectomy); or women of childbearing potential must 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.

Stage1: Exclusion Criteria:

1. Expected to undergo kidney transplantation and/or parathyroidectomy during the study;
2. 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);
3. Used opioids within one week before screening, or unable to avoid the use of opioids other than the investigational product during the study;
4. 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);
5. Used blood perfusion within 3 months before screening;
6. History of medication or drug abuse;
7. Average daily alcohol consumption greater than 15 g (15 g of alcohol is equivalent to 450 mL of beer or 150 mL of wine or 50 mL of light liquor) within 3 months before screening;
8. Unable to comply with the standard dietary plan and unable to avoid coffee or tea during the study;
9. Blood pressure of upper limbs in the supine position at screening: systolic blood pressure \< 90 mmHg, or diastolic blood pressure \< 60 mmHg, or systolic blood pressure \> 180 mmHg, or diastolic blood pressure \> 110 mmHg;
10. New York Heart Association (NYHA) Class ≥ III at screening; or confirmed to have abnormal ECG at screening and determined by the investigator to be inappropriate to be enrolled, including QTcF ≥ 480 ms;
11. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) or total bilirubin ≥ 1.5 × upper limit of normal (ULN) at screening;
12. Blood sodium \> 155 mmol/L at screening;
13. Hemoglobin ≤ 80 g/L at screening;
14. Positive for hepatitis B surface antigen (HBsAg), hepatitis C antibody (HCVAb), syphilis antibody, or human immunodeficiency virus (HIV) antibody at screening;
15. Underwent major surgery (determined by the investigator as major surgery) within 3 months before screening;
16. Having a total blood loss of ≥ 200mL within 1 month before screening, except for the blood loss during menstruation in females;
17. Females who are pregnant or breastfeeding;
18. 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 study physician, including but not limited to:

    1. Severe mental illness or cognitive impairment (e.g., dementia);
    2. Any other relevant acute or chronic neurological and psychiatric diseases (e.g., encephalopathy, coma, delirium) within 3 months before screening;
    3. Patients with malignant tumors (including malignant tumors that have been cured without recurrence).

Primary outcomes:
measure: Stage I：Safety of HSK21542 injection for multiple times within one week in hemodialysis subjects
timeFrame: From screening up to D14
measure: Stage II：At week 12, the change in weekly average of daily Worst Itch NRS (WI-NRS) from baseline in subjects undergoing hemodialysis
timeFrame: 12 week
Secondary outcomes:
measure: Stage I：Area under the plasma concentration versus time curve (AUC)
timeFrame: 1 week
measure: Stage I：Time to the peak plasma concentration (Tmax)
timeFrame: 1 week
measure: Stage I：Maximum Concentration (Cmax)
timeFrame: 1 week
measure: Stage I：Half-time (T1/2)
timeFrame: 1 week
measure: Stage I：Total body clearance following intravenous administration (CL)
timeFrame: 1 week
measure: Stage I：Volume of distribution following intravenous administration (Vss)
timeFrame: 1 week
measure: Stage I：trough concentration (Cmin)
timeFrame: 1 week
measure: Stage I：Change from baseline in average daily Worst Itch NRS (WI-NRS) and Itch-related Quality of Life as Assessed by Skindex-16 Scale Score
timeFrame: 1 week
measure: Stage I：Correlation between prolactin level and drug exposure of HSK21542 injection in hemodialysis subjects
timeFrame: 1 week
measure: Stage II: Safety of HSK21542 injection in the treatment of moderate and severe pruritus in hemodialysis subjects for 12 weeks
timeFrame: 12 weeks
measure: Stage II：Area under the plasma concentration versus time curve (AUC)
timeFrame: 12 weeks
measure: Stage II：Time to Maximum plasma concentration (Tmax)
timeFrame: 12 weeks
measure: Stage II：Maximum Concentration (Cmax)
timeFrame: 12 weeks
measure: Stage II：Half-time (T1/2)
timeFrame: 12 weeks
measure: Stage II：Total body clearance following intravenous administration (CL)
timeFrame: 12 weeks
measure: Stage II：Volume of distribution following intravenous administration (Vss)
timeFrame: 12 weeks
measure: Stage II: The proportion of subjects change from baseline ≥3 points with respect to the weekly mean of the daily 24-hour Worst Itching Intensity NRS Score at Week 12
timeFrame: 12 week
measure: Stage II: The proportion of subjects change from baseline ≥4 points with respect to the weekly mean of the daily 24-hour Worst Itching Intensity NRS Score at Week 12
timeFrame: 12 week
measure: Stage II：Change from baseline in Itch-related Quality of Life as Assessed by Skindex-16 and 5-D Scale Score
timeFrame: 12 week
measure: Stage II: Weekly mean value of the daily 24-hour Worst Itching Intensity NRS Score within 2 weeks after drug withdrawal after 12 weeks of administration
timeFrame: 14 week
measure: Stage II: Weekly mean value of the ShOWS and OOWS Score within 2 weeks after drug withdrawal after 12 weeks of administration
timeFrame: 14 week
measure: Stage II: Change from baseline in the level of serum IL-6，IL-31，TNF-α，and hs-CRP
timeFrame: 12 weeks
measure: Stage II: Change from baseline in the level of serum iPTH
timeFrame: 12 weeks
Other outcomes:
Locations:
city: Guiyang
country: China
facility: Guizhou Medical University Affiliated Hospital
state: Guizhou
Study officials:
References: