Uremic Pruritus
Conditions
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.
Interventions
DRUGStage I:HSK21542 0.05 μg/kg
Following the principle of dose escalation and starting from the low dose of 0.05 μg/kg to the high dose 0.80 μg/kg
DRUGStage I:HSK21542 0.15 μg/kg
Following the principle of dose escalation and starting from the low dose of 0.05 μg/kg to the high dose 0.80 μg/kg
DRUGStage I:HSK21542 0.30 μg/kg
Following the principle of dose escalation and starting from the low dose of 0.05 μg/kg to the high dose 0.80 μg/kg
DRUGStage I:HSK21542 0.80 μg/kg
Following the principle of dose escalation and starting from the low dose of 0.05 μg/kg to the high dose 0.80 μg/kg
DRUGStage II:HSK21542 0.3 μg/kg
Randomized to HSK21542 0.3 μg/kg or 0.6 μg/kg or the corresponding placebo group
DRUGStage II:HSK21542 0.6 μg/kg
Randomized to HSK21542 0.3 μg/kg or 0.6 μg/kg or the corresponding placebo group
Sponsors
Haisco Pharmaceutical Group Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
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.
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Stage I：Safety of HSK21542 injection for multiple times within one week in hemodialysis subjects | From screening up to D14 | Adverse events (AEs) and serious adverse events (SAEs)，Vital signs、Physical examination, Laboratory examination, ECG |
| Stage II：At week 12, the change in weekly average of daily Worst Itch NRS (WI-NRS) from baseline in subjects undergoing hemodialysis | 12 week | Change from baseline in average NRS score of itch at week 12 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Stage I：Maximum Concentration (Cmax) | 1 week | Maximum Concentration of HSK21542 |
| Stage I：Half-time (T1/2) | 1 week | Half-time of HSK21542 |
| Stage I：Total body clearance following intravenous administration (CL) | 1 week | Total body clearance following intravenous administration of HSK21542 |
| Stage I：Volume of distribution following intravenous administration (Vss) | 1 week | Volume of distribution following intravenous administration of HSK21542 |
| Stage I：trough concentration (Cmin) | 1 week | trough concentration of HSK21542 |
| 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 | 1 week | 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. The Skindex-16 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. The Skindex-16 has 16 questions; the total Skindex-16 score ranges from 0 to 100. A higher total score represents worse quality of life. |
| Stage I：Correlation between prolactin level and drug exposure of HSK21542 injection in hemodialysis subjects | 1 week | Detect prolactin concentration before and after administration |
| Stage II: Safety of HSK21542 injection in the treatment of moderate and severe pruritus in hemodialysis subjects for 12 weeks | 12 weeks | Adverse events (AEs) and serious adverse events (SAEs)，Vital signs、Physical examination, Laboratory examination, ECG |
| Stage II：Area under the plasma concentration versus time curve (AUC) | 12 weeks | Plasma Area Under the Concentration-time Curve of HSK21542 |
| Stage II：Time to Maximum plasma concentration (Tmax) | 12 weeks | Time to Maximum Plasma Concentration of HSK21542 |
| Stage I：Area under the plasma concentration versus time curve (AUC) | 1 week | Plasma HSK21542 Area Under the Concentration-time Curve (AUC) |
| Stage II：Half-time (T1/2) | 12 weeks | Half-time (T1/2) of HSK21542 |
| Stage II：Total body clearance following intravenous administration (CL) | 12 weeks | Total body clearance following intravenous administration of HSK21542 |
| Stage II：Volume of distribution following intravenous administration (Vss) | 12 weeks | Volume of distribution following intravenous administration of HSK21542 |
| 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 | 12 week | 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. LS means estimated percent, odds ratio and P value used logistic and Log-binomial regression model. |
| 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 | 12 week | 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. LS means estimated percent, odds ratio and P value used logistic and Log-binomial regression model. |
| Stage II：Change from baseline in Itch-related Quality of Life as Assessed by Skindex-16 and 5-D Scale Score | 12 week | The Skindex-16 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. The Skindex-16 has 16 questions; the total Skindex-16 score ranges from 0 to 100. A higher total score represents worse quality of life. 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 duration of itch/day, degree, direction (improvement/worsening), disability (impact on activities such as work), and body distribution of itch. The 5-D Itch Scale has 5 questions; the total 5-D Itch Scale score ranges from 5 to 25, with higher scores indicating worse responses. |
| 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 | 14 week | 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. |
| Stage II: Weekly mean value of the ShOWS and OOWS Score within 2 weeks after drug withdrawal after 12 weeks of administration | 14 week | According to the weekly mean of ShOWS and OOWS scores, combined with AE, comprehensively evaluate whether there is drug withdrawal reaction. |
| Stage II: Change from baseline in the level of serum IL-6，IL-31，TNF-α，and hs-CRP | 12 weeks | Evaluate the effect of HSK21542 on IL-6, IL-31, TNF- α and hs-CRP levels. |
| Stage II: Change from baseline in the level of serum iPTH | 12 weeks | Evaluate the effect of HSK21542 on iPTH levels. |
| Stage II：Maximum Concentration (Cmax) | 12 weeks | Maximum Concentration of HSK21542 |
| Stage I：Time to the peak plasma concentration (Tmax) | 1 week | Time to Maximum Plasma HSK21542 Concentration |
Countries
China
Outcome results
None listed