EDP167 in Healthy Volunteers and Subjects With Mild Dyslipidemia

A Dose-escalation Phase I Clinical Trial to Evaluate the Safety, Tolerability, Pharmacokinetic and Pharmacodynamic of Single Dose of EDP167 Injection in Healthy Volunteers and Subjects With Mild Dyslipidemia

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.

Study Overview

• Status: Completed
• Conditions: Healthy Adult Male and Female Volunteers; Mild Dyslipidemia
• Intervention / Treatment: Drug: EDP167; Drug: Placebo

Detailed Description

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
• Enrollment (Actual): 40
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Guangzhou, China
    • Guangdong Provincial People's Hospital
  • Hangzhou, China
    • The Second Affiliated Hospital Zhejiang University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Subjects aged 18 to 60 years (inclusive) at the time of signing the informed consent form, male or female.
2. Male subjects weighing ≥50.0 kg, female subjects weighing ≥45.0 kg, and body mass index (BMI) between 18.0 and 35.0 kg/m² (inclusive).
3. Subjects with fasting serum TG ≥1.13 mmol/L and <5.6 mmol/L, and LDL-C ≥1.8 mmol/L and <4.9 mmol/L at screening.
4. Subjects with no abnormalities or only minor abnormalities judged by the investigator as clinically insignificant (excluding lipid laboratory tests) upon physical examination, vital signs, 12-lead ECG, posteroanterior and lateral chest X-rays, abdominal ultrasound, and laboratory tests at screening.
5. Subjects who have maintained a stable dietary habit for at least 4 weeks before dose administration, and have no plans to significantly change their diet or body weight during the study.
6. Female subjects of childbearing potential or male subjects with partners of childbearing potential must agree to use highly effective contraception from signing the informed consent form until 6 months after dosing and refrain from donating sperm or eggs.
7. Subjects who voluntarily sign the written informed consent form, understand the study procedures and content, are able to communicate well with the investigator, and are willing to comply with the relevant study regulations.

Exclusion Criteria:

1. Subjects with known allergy/hypersensitivity to the investigational drug, its components, or drugs of the same class.
2. Subjects with a history or current presence of serious or clinically significant diseases/abnormalities, including but not limited to cardiovascular, respiratory, endocrine, gastrointestinal, renal, hepatic, biliary, dermatologic, hematologic, immunologic, neurologic, or psychiatric diseases/abnormalities, , or any diseases (except for dyslipidemia) that the investigator considers to pose safety concerns or interfere with the pharmacokinetic evaluation.
3. Subjects who have undergone major surgery within 3 months prior to screening, or have undergone surgery that may significantly affect drug absorption, distribution, metabolism, or excretion, or who plan to undergo elective surgery during the study.
4. Subjects with any of the following laboratory abnormalities at screening: total bilirubin (TBIL), gamma-glutamyl transferase (GGT), or alkaline phosphatase (ALP) >1.5×ULN; alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >ULN.
5. Subjects with any of the following 12-lead ECG findings: QTcF >450 ms or any other clinically significant abnormal ECG result.
6. Subjects with tattoos, scars, or birthmarks on the abdomen, upper arms, or thighs that may interfere with the assessment of injection site reactions.
7. Subjects who have used any prescription drugs, over-the-counter (OTC) medications, Chinese herbal medicines, or health supplements within 14 days prior to dosing; or for whom administration occurs within 5 half-lives of any prior medication (based on the longer period); or who have used any medication known to affect lipid metabolism within 90 days prior to screening.
8. Subjects who have received any live vaccine within 4 weeks prior to screening, or who plan to receive any live vaccine during the study.
9. Subjects who have used any antisense oligonucleotide (ASO) or small interfering RNA (siRNA) therapy within 12 months prior to screening.
10. Subjects with a history of drug abuse/substance abuse, or a positive result for the specified drugs (ketamine, marijuana, morphine, MDMA, methamphetamine, cocaine) in the urine drug screen at screening.
11. Subjects who regularly consumed alcohol within 3 months prior to screening (defined as >14 units of alcohol per week; 1 unit = 360 mL of beer, or 45 mL of spirits with 40% alcohol, or 150 mL of wine), or are unwilling to abstain from alcohol during the study, or have a breath alcohol test result >0 mg/100 mL.
12. Subjects who consumed excessive amounts of tea, coffee, or caffeinated beverages (defined as >8 cups per day; 1 cup = 250 mL) within 3 months prior to screening, or consumed any such beverages within 48 hours prior to dosing, or are unwilling to abstain from them during the study.
13. Current smokers, or subjects with a positive urine nicotine test at screening, or former smokers who have quit smoking for less than 6 months.
14. Subjects with positive test results for hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCVAb), human immunodeficiency virus (HIV) antibody, or specific treponemal antibody (for syphilis) at screening.
15. Subjects with intolerance to venipuncture, difficulty in blood sampling, or a history of needle or blood syncope.
16. Subjects who have donated blood or experienced significant blood loss (≥400 mL) within 3 months prior to screening.
17. Subjects who have participated in, or are currently participating in, another clinical trial and have received the investigational product/device or placebo within 3 months prior to screening.
18. Female subjects with a positive pregnancy test at screening, or who are breastfeeding, or who plan to become pregnant during the study period.
19. Any other condition that the investigator deems inappropriate for the subject to participate in this clinical trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Quadruple

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group 1; EDP167 35mg (N=6) and Placebo (N=2)	Drug: EDP167; EDP167 sc injection; Drug: Placebo; Sterile normal saline (0.9% NaCl) sc injection
Experimental: Group 2; EDP167 100mg (N=6) and Placebo (N=2)	Drug: EDP167; EDP167 sc injection; Drug: Placebo; Sterile normal saline (0.9% NaCl) sc injection
Experimental: Group 3; EDP167 200mg (N=6) and Placebo (N=2)	Drug: EDP167; EDP167 sc injection; Drug: Placebo; Sterile normal saline (0.9% NaCl) sc injection
Experimental: Group 4; EDP167 300mg (N=6) and Placebo (N=2)	Drug: EDP167; EDP167 sc injection; Drug: Placebo; Sterile normal saline (0.9% NaCl) sc injection
Experimental: Group 5; EDP167 400mg (N=6) and Placebo (N=2)	Drug: EDP167; EDP167 sc injection; Drug: Placebo; Sterile normal saline (0.9% NaCl) sc injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Up to 85 days post-dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	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	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	Up to 48 hours post-dose
To evaluate the apparent volume of distribution (Vd) of a single subcutaneous injection of EDP167 in adult subjects.		Up to 48 hours post-dose
To evaluate the clearance (CL) of a single subcutaneous injection of EDP167 in adult subjects.		Up to 48 hours post-dose
To evaluate the elimination half-time (t1/2) of a single subcutaneous injection of EDP167 in adult subjects.		Up to 48 hours post-dose
To evaluate the pharmacodynamic characteristics (ANGPTL3) of a single subcutaneous injection of EDP167 in adult subjects.	Change from baseline in fasting serum ANGPTL3 level.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	Up to 48 hours post-dose
To evaluate the immunogenicity of EDP167.	The incidence and titer of antibodies against EDP167.	Up to 85 days post-dose

Collaborators and Investigators

• Sponsor: Eddingpharm (Zhuhai) Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2025
• Primary Completion (Actual): December 12, 2025
• Study Completion (Actual): December 12, 2025

Study Registration Dates

• First Submitted: February 2, 2026
• First Submitted That Met QC Criteria: February 9, 2026
• First Posted (Actual): February 17, 2026

Study Record Updates

• Last Update Posted (Actual): February 17, 2026
• Last Update Submitted That Met QC Criteria: February 9, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: Dyslipidemia; siRNA; ANGPTL3
• Additional Relevant MeSH Terms: Metabolic Diseases; Lipid Metabolism Disorders; Nutritional and Metabolic Diseases; Dyslipidemias
• Other Study ID Numbers: EDP167D101

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No