A Study Evaluating the Safety, Pharmacokinetics, and Efficacy of HSK21542 Injection in Subjects Undergoing Hemodialysis

NCT04470154 | Completed Phase 2

• 1 other identifier: HSK21542-203
• Study Type: interventional
• Target: 131
• Locations: 1 country
• Sites: 1

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

Conditions

Uremic Pruritus

Outcome Measures

Primary Outcomes (2)

• Stage I：Safety of HSK21542 injection for multiple times within one week in hemodialysis subjects

  Adverse events (AEs) and serious adverse events (SAEs)，Vital signs、Physical examination, Laboratory examination, ECG

  From screening up to D14

• Stage II：At week 12, the change in weekly average of daily Worst Itch NRS (WI-NRS) from baseline in subjects undergoing hemodialysis

  Change from baseline in average NRS score of itch at week 12

  12 week

Secondary Outcomes (23)

• Stage I：Area under the plasma concentration versus time curve (AUC)

  1 week

• Stage I：Time to the peak plasma concentration (Tmax)

  1 week

• Stage I：Maximum Concentration (Cmax)

  1 week

• Stage I：Half-time (T1/2)

  1 week

• Stage I：Total body clearance following intravenous administration (CL)

  1 week

Study Arms (6)

Stage I: 0.05 μg/kg

EXPERIMENTAL

IV HSK21542 0.05 μg/kg solution（active or placebo） administered after each dialysis session within 2h±30 min (3 times/week).

Drug: Stage I:HSK21542 0.05 μg/kg

Stage I: 0.15 μg/kg

EXPERIMENTAL

IV HSK21542 0.15 μg/kg solution（active or placebo） administered after each dialysis session within 2h±30 min (3 times/week).

Drug: Stage I:HSK21542 0.15 μg/kg

Stage I: 0.30 μg/kg

EXPERIMENTAL

IV HSK21542 0.30 μg/kg solution（active or placebo） administered after each dialysis session within 2h±30 min (3 times/week).

Drug: Stage I:HSK21542 0.30 μg/kg

Stage I: 0.80 μg/kg

EXPERIMENTAL

IV HSK21542 0.80 μg/kg solution（active or placebo） administered after each dialysis session within 2h±30 min (3 times/week).

Drug: Stage I:HSK21542 0.80 μg/kg

Stage II: 0.3 μg/kg

EXPERIMENTAL

IV HSK21542 0.3 μg/kg solution（active or placebo） administered after each dialysis session within 10 min (3 times/week).

Drug: Stage II:HSK21542 0.3 μg/kg

Stage II: 0.6 μg/kg

EXPERIMENTAL

IV HSK21542 0.3 μg/kg solution（active or placebo） administered after each dialysis session within 10 min (3 times/week).

Drug: Stage II:HSK21542 0.6 μg/kg

Interventions

Stage I:HSK21542 0.05 μg/kg DRUG

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

Stage I: 0.05 μg/kg

Stage I:HSK21542 0.15 μg/kg DRUG

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

Stage I: 0.15 μg/kg

Stage I:HSK21542 0.30 μg/kg DRUG

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

Stage I: 0.30 μg/kg

Stage I:HSK21542 0.80 μg/kg DRUG

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

Stage I: 0.80 μg/kg

Stage II:HSK21542 0.3 μg/kg DRUG

Randomized to HSK21542 0.3 μg/kg or 0.6 μg/kg or the corresponding placebo group

Stage II: 0.3 μg/kg

Stage II:HSK21542 0.6 μg/kg DRUG

Randomized to HSK21542 0.3 μg/kg or 0.6 μg/kg or the corresponding placebo group

Stage II: 0.6 μg/kg

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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;
• Aged ≥ 18 and ≤ 75 years old, male or female;
• 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);
• Patients with end-stage renal diseases who receive hemodialysis (including hemodiafiltration) 3 times in a week prior to screening for at least 3 months;
• 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;
• 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.

You may not qualify if:

• Expected to undergo kidney transplantation and/or parathyroidectomy during the study;
• Used opioids within one week before screening, or unable to avoid the use of opioids other than the investigational product during the study;
• 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);
• Used blood perfusion within 3 months before screening;
• History of medication or drug abuse;
• 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;
• Unable to comply with the standard dietary plan and unable to avoid coffee or tea during the study;
• 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;
• 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;
• Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) or total bilirubin ≥ 1.5 × upper limit of normal (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;
• Underwent major surgery (determined by the investigator as major surgery) within 3 months before screening;
• Having a total blood loss of ≥ 200mL within 1 month before screening, except for the blood loss during menstruation in females;

Sponsors & Collaborators

• Haisco Pharmaceutical Group Co., Ltd.: lead

Study Sites (1)

Guizhou Medical University Affiliated Hospital

Guiyang, Guizhou, China

Location

Related Publications (1)

• Pan M, Wang G, Zhou L, Xu Y, Yao L, Wu C, Mei C, Zhao Z, Sun D, Guan T, Chen Q, Shi M, Xu H, Zeng W, Li F, Yan R, Liu BC. Safety and effectiveness of HSK21542 for hemodialysis patients: a multiple ascending dose study. Front Pharmacol. 2023 Oct 9;14:1203642. doi: 10.3389/fphar.2023.1203642. eCollection 2023.

  PMID: 37876731 DERIVED

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: July 7, 2020
• First Posted: July 14, 2020
• Study Start: August 10, 2020
• Primary Completion: October 28, 2021
• Study Completion: October 28, 2021
• Last Updated: August 9, 2022

Record last verified: 2022-08

Locations

CN (1)