EDP167 is a double-stranded small interfering RNA (siRNA) drug targeting ANGPTL3, which may bring benefits for patients with dyslipidemia conditions. This is the first in human study of EDP167 in health volunteers and subjects with mild dyslipidemia to evaluate the safety and PK/PD profiles of EDP167.
Angiopoietin-like 3 protein (ANGPTL3) is a key regulator of lipid metabolism. Clinical studies have shown that inhibition of ANGPTL3 could exert lipid-lowering effects in patients with dyslipidemia. EDP167 is a novel GalNAc-conjugated siRNA therapeutic that selectively silences hepatic ANGPTL3 mRNA expression, offering a promising strategy for lipid lowering. In this trial, subjects will be sequentially enrolled into five cohorts (35, 100, 200, 300 or 400 mg), each consists of six subjects receiving EDP167 and two receiving matching placebos. The follow-up will last for 85 days to evaluate the PK profile and PD effects (ANGPTL3, LDL-C, TG, and other lipid parameters) following a single subcutaneous injection of EDP167.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
40
Guangdong Provincial People's Hospital
Guangzhou, China
The Second Affiliated Hospital Zhejiang University School of Medicine
Hangzhou, China
To evaluate the safety and tolerability of a single subcutaneous injection of EDP167 in adult subjects.
Number of participants with adverse events and serious adverse events, with clinically significant changes in vital signs, in electrocardiogram readings, in physical examination, and in laboratory tests.
Time frame: Up to 85 days post-dose
To evaluate the plasma concentration-time area under curve (AUC) of a single subcutaneous injection of EDP167 in adult subjects.
Concentration-time area under curve (AUC) of EDP167 in plasma
Time frame: Up to 48 hours post-dose
To evaluate the time to peak concentration (Tmax) of a single subcutaneous injection of EDP167 in adult subjects.
Time to peak concentration (Tmax) of EDP167 in plasma
Time frame: Up to 48 hours post-dose
To evaluate the peak concentration (Cmax) of a single subcutaneous injection of EDP167 in adult subjects.
Peak concentration (Cmax) of EDP167 in plasma
Time frame: Up to 48 hours post-dose
To evaluate the apparent volume of distribution (Vd) of a single subcutaneous injection of EDP167 in adult subjects.
Time frame: Up to 48 hours post-dose
To evaluate the clearance (CL) of a single subcutaneous injection of EDP167 in adult subjects.
Time frame: Up to 48 hours post-dose
To evaluate the elimination half-time (t1/2) of a single subcutaneous injection of EDP167 in adult subjects.
Time frame: Up to 48 hours post-dose
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To evaluate the pharmacodynamic characteristics (ANGPTL3) of a single subcutaneous injection of EDP167 in adult subjects.
Change from baseline in fasting serum ANGPTL3 level.
Time frame: Up to 85 days post-dose
To evaluate the pharmacodynamic characteristics (TG) of a single subcutaneous injection of EDP167 in adult subjects.
Change from baseline in fasting serum TG level.
Time frame: Up to 85 days post-dose
To evaluate the pharmacodynamic characteristics (LDL-C) of a single subcutaneous injection of EDP167 in adult subjects.
Change from baseline in fasting serum LDL-C level.
Time frame: Up to 85 days post-dose
To evaluate the pharmacodynamic characteristics (TC) of a single subcutaneous injection of EDP167 in adult subjects.
Change from baseline in fasting serum TC level.
Time frame: Up to 85 days post-dose
To evaluate the pharmacodynamic characteristics (non-HDL-C) of a single subcutaneous injection of EDP167 in adult subjects.
Change from baseline in fasting serum non-HDL-C level.
Time frame: Up to 85 days post-dose
To evaluate the pharmacodynamic characteristics (VLDL-C) of a single subcutaneous injection of EDP167 in adult subjects.
Change from baseline in fasting serum VLDL-C level.
Time frame: Up to 85 days post-dose
To evaluate the pharmacodynamic characteristics (HDL-C) of a single subcutaneous injection of EDP167 in adult subjects.
Change from baseline in fasting serum HDL-C level.
Time frame: Up to 85 days post-dose
To evaluate the pharmacodynamic characteristics (Lp(a)) of a single subcutaneous injection of EDP167 in adult subjects.
Change from baseline in fasting serum Lp(a) level.
Time frame: Up to 85 days post-dose
To evaluate the pharmacodynamic characteristics (ApoB) of a single subcutaneous injection of EDP167 in adult subjects.
Change from baseline in fasting serum ApoB level.
Time frame: Up to 85 days post-dose
To evaluate the pharmacodynamic characteristics (ApoA-I) of a single subcutaneous injection of EDP167 in adult subjects.
Change from baseline in fasting serum ApoA-I level.
Time frame: Up to 85 days post-dose
The effect of EDP167 injection on QT interval evaluated by C-QT analysis.
The difference from baseline of QTcF after administration.
Time frame: Up to 48 hours post-dose
The effect of EDP167 injection on QT interval evaluated by C-QT analysis.
The correlation between drug serum concentration and QTcF.
Time frame: Up to 48 hours post-dose
To evaluate the immunogenicity of EDP167.
The incidence and titer of antibodies against EDP167.
Time frame: Up to 85 days post-dose