This is a Phase I clinical study, which is a randomized, double-blind, placebo-controlled, single-dose, dose-escalation study. The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of a single subcutaneous injection of ART101 injection in healthy adult subjects. This study is planned to include 5 dose groups, with an estimated maximum sample size of approximately 40 subjects. To reduce the safety risk to subjects, a sentinel method will be used in Dose Group 1, where 2 subjects (1 receiving the investigational drug and 1 receiving placebo) will be enrolled first, followed by 6 subjects (5 receiving the investigational drug and 1 receiving placebo). There will be at least a 7-day interval between the administration to the sentinel subjects and the other subjects in Dose Group 1. Subjects in each dose group will receive a single subcutaneous injection of ART101 injection or placebo on Day 1 after at least 8 hours of fasting. Group 1 Single subcutaneous injection 25 mg (N=6) Placebo (N=2) Group 2 Single subcutaneous injection 75 mg (N=6) Placebo (N=2) Group 3 Single subcutaneous injection 150 mg (N=6) Placebo (N=2) Group 4 Single subcutaneous injection 300 mg (N=6) Placebo (N=2) Group 5 (Optional) Single subcutaneous injection ≤600 mg (N=6) Placebo (N=2) The study procedures include a screening period, a treatment period, a follow-up period, and an early termination/study completion follow-up.
The clinical trial was conducted by the Suzhou branch of Suzhou Arnatar Therapeutics Co., Ltd in China.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
QUADRUPLE
Enrollment
40
all administered via subcutaneous injection.
Suzhou Arnatar Therapeutics Co., Ltd
Suzhou, Jiangsu, China
Beijing Friendship Hospital, Capital Medical University
Beijing, China
Assess safety of ART101 by the incidence of adverse events, adverse events of special interest and SAEs
Time frame: Up to Day 169 post first dose administration
Number of participants with abnormal laboratory values and/or adverse events that are related to treatment
Fasting serum chemistry, fasting hematology, fasting coagulation, fasting LFTs, fasting lipid panel, fasting glycemic assessment, urinalysis will be assessed.
Time frame: Up to Day 169 post first dose administration
Serum PK Parameters: Maximum Concentration (Cmax)
Time frame: Samples will be collected at 11 timepoints ,including 1 timepoint pre-dose on day 1, 8 timepoints post dosing on day 1,1 timepoint on day 2 and 1 timepoint Day 3 post dosing.
Concentration change in pharmacodynamics of ART101 by noting change from baseline of serum angiotensinogen.
Time frame: Day -2 pre dosing, day 1, day 3, Day 8, Day 15, Day 22, Day 29, Day 43, Day 57, Day 85 (~3 Months), Day 127, Day 169 (6 Months), post first dose administration.
Urine PK Parameters:Renal Clearance (Ae)
Time frame: Urine will be collected between 1 hour to 0 hour pre dosing, 0 to 6 hours, 6 to 12 hours, 12 to 24 hours, 24 to 48 hours post dosing.
Serum PK Parameters: Time for maximum concentration (Tmax)
Time frame: Samples will be collected at 11 timepoints ,including 1 timepoint pre-dose on day 1, 8 timepoints post dosing on day 1,1 timepoint on day 2 and 1 timepoint Day 3 post dosing.
Serum PK Parameters: Area under the curve (AUC)
Time frame: Samples will be collected at 11 timepoints ,including 1 timepoint pre-dose on day 1, 8 timepoints post dosing on day 1,1 timepoint on day 2 and 1 timepoint Day 3 post dosing.
Serum PK Parameters- Elimination half-life (t½)
Time frame: Samples will be collected at 11 timepoints ,including 1 timepoint pre-dose on day 1, 8 timepoints post dosing on day 1,1 timepoint on day 2 and 1 timepoint Day 3 post dosing.
Serum PK parameters: Volume of distribution (Vz/F)
Time frame: Samples will be collected at 11 timepoints ,including 1 timepoint pre-dose on day 1, 8 timepoints post dosing on day 1,1 timepoint on day 2 and 1 timepoint Day 3 post dosing.
Urine PK parameters: Fraction of drug excreted in urine (fe)
Time frame: Urine will be collected between 1 hour to 0 hour pre dosing, 0 to 6 hours, 6 to 12 hours, 12 to 24 hours, 24 to 48 hours post dosing.
Urine PK parameters: Renal Clearance (CLr)
Time frame: Urine will be collected between 1 hour to 0 hour pre dosing, 0 to 6 hours, 6 to 12 hours, 12 to 24 hours, 24 to 48 hours post dosing.
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