A Dose-exploration Study of EDP167 in HoFH

A Multicenter, Dose-exploration, Open-label Phase II Study to Evaluate the Efficacy and Safety of EDP167 in Adult Patients With Homozygous Familial Hypercholesterolaemia

EDP167 is a double-stranded small interfering RNA (siRNA) drug targeting angiopoietin-like 3 protein (ANGPTL3), which may bring benefits for patients with dyslipidemia conditions. This is a dose exploration study in Homozygous Familial Hypercholesterolaemia (HoFH) patients to evaluate the efficacy and safety and pharmacokinetics (PK)/pharmacodynamics (PD) profiles of multiple EDP167 injections.

Study Overview

• Status: Recruiting
• Conditions: Homozygous Familial Hypercholesterolemia (HoFH)
• Intervention / Treatment: Drug: EDP167

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 N-Acetylgalactosamine (GalNAc)-conjugated siRNA therapeutic that selectively silences hepatic ANGPTL3 mRNA expression, offering a promising strategy for lipid lowering. This trial includes two phase, main study phase (including screening period and 24 weeks treatment period) and extension phase (including 6 months treatment period). In main study phase, patients with HoFH will be randomized into two dose cohorts (200mg and 300mg, 10 subjects each), receiving EDP167 injections on Day 1 and at Week 12. At Week 24 of the main study phase, subjects will be evaluated and enter the extension phase, receiving EDP167 injections at Month 0 and at Month 3. The follow-up will last till Month 6 in extension phase to evaluate the efficacy, safety, PK profile and PD effects (ANGPTL3, low-density lipoprotein cholesterol [LDL-C], triglyceride [TG], and other lipid parameters) in HoFH patients after multiple EDP167 injections.

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Wei Song; Phone Number: 86-13817957624; Email: Sophie.Song@eddingpharm.com

Study Locations

• China
  • Beijing, China
    • Recruiting
    • Fuwai Hospital
    • Contact: Ethics Committee of Fuwai Hospital; Phone Number: +86 010 88396281

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age ≥18 years old, male or female, and weight ≥40 kg.
2. Genetic diagnosis or clinical diagnosis of HoFH.
3. Fasting serum LDL-C ≥2.6 mmol/L.
4. Follow a daily low-fat diet during the study.
5. Receiving stable and tolerable lipid-lowering treatment or other drugs for chronic diseases treatments for certain periods before the study, and maintain the stable treatments throughout the study.
6. Women of childbearing potential (WOCBP) must have a negative serum pregnancy test at screening and a negative pregnancy test prior to receiving EDP167 at baseline.
7. Agree to use contraceptive measures that comply with regulations and the protocol requirements during the study, and until 6 months after the last dose.
8. Understand the study procedures, voluntarily participate, and sign the informed consent form.

Exclusion Criteria:

1. Allergic to the drug in this study, its components or similar drugs.
2. Used any antisense oligonucleotide (ASO) or small interfering nucleic acid (siRNA) drugs within 12 months prior to randomization.
3. Received treatment targeting ANGPTL3 or Apolipoprotein C3 (ApoC3), or have participated in other clinical trials within 6 months or 5 half-life (whichever longer) prior to screening.
4. Received health supplements or other medications that have been used for lipid-lowering purposes within 4 weeks prior to screening.
5. Received Lipoprotein apheresis within 8 weeks prior to screening.
6. A weight change of >10% within 4 weeks prior to randomization, or planning to undergo weight-loss surgery or weight intervention treatment during the study period.
7. Starting a new diet plan or having significant differences from the previous diet within 4 weeks prior to randomization.
8. Presence of diseases that would affect lipid or lipoprotein levels, such as nephrotic syndrome, severe liver diseases, Cushing's syndrome, hypothyroidism or hyperthyroidism, etc., which are poorly controlled, and in the opinion of the Investigator will interfere with the accurate assessment of the study results.
9. Had New York Heart Association (NYHA) grade III-IV heart failure within 12 months prior to randomization, or acute coronary syndrome or stroke within 6 months prior to randomization.
10. Performed coronary intervention within 6 months prior to randomization, or plan to perform coronary intervention during the study.
11. Have a history of major surgery within 3 months prior to screening, or plan to undergo major surgery during the study.
12. History of malignancy, unless considered cured by adequate treatment with no evidence of recurrence for ≥3 years prior to the first dose of EDP167; excluding adequately treated basal cell or squamous cell carcinoma of the skin, carcinoma in situ of the cervix, carcinoma in situ of the breast, or incidental histological findings of prostate cancer (TNM stage T1a or T1b).
13. Clinical evidence of active infections or other major or poorly controlled serious diseases, any other conditions that in the opinion of the Investigator may interfere with the study results or put the subjects at excessive risk.
14. Have a history of current existence of alcohol or drug abuse per evaluation of the investigator.
15. Uncontrolled hypertension at screening (blood pressure >160/100 mmHg).
16. Subjects with any of the following laboratory abnormalities at screening: a) fasting serum TG≥5.6 mmol/L; b) Glycosylated hemoglobin A1C (HbA1c)>8.5%; c) alanine aminotransferase (ALT) or aspartate aminotransferase (AST) or gamma-glutamyl transpeptidase (GGT)>1.5×ULN (Upper Limit Of Normal), total bilirubin (TBIL)>2×ULN; d) prothrombin time (PT) or activated partial thromboplastin time (APTT) or International Normalized Ratio (INR) clinically significant abnormal; e) Hepatitis B surface antigen (HBsAg) or antibody to hepatitis C virus (HCVAb) or human immunodeficiency virus (HIV) positive; f) estimated glomerular filtration rate (eGFR)<30 mL/min/1.73m2.
17. Donated or lost blood ≥400 mL within 3 months prior to screening.
18. Women who are pregnant, breastfeeding or planning for pregnancy.
19. Other conditions that the Investigator would consider the subject is not suitable to participate in this study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: EDP167-200mg; EDP167 200mg (N=10)	Drug: EDP167; EDP167 sc injection
Experimental: EDP167-300mg; EDP167 300mg (N=10)	Drug: EDP167; EDP167 sc injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
To evaluate the change from baseline in serum low-density lipoprotein cholesterol (LDL-C) level at week 24 of the main study phase.	Up to week 24 of the main study phase

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To evaluate the change from baseline in serum LDL-C level.		Up to month 6 of the extension phase
To evaluate the change from baseline in serum angiopioetin-like protein 3 (ANGPTL3) level.		Up to month 6 of the extension phase
To evaluate the change from baseline in serum triglyceride (TG) level.		Up to month 6 in the extension phase
To evaluate the change from baseline in serum total cholesterol (TC) level.		Up to month 6 in the extension phase
To evaluate the change from baseline in serum non-high-density lipoprotein cholesterol (non-HDL-C) level.		Up to month 6 in the extension phase
To evaluate the change from baseline in serum high-density lipoprotein cholesterol (HDL-C) level.		Up to month 6 in the extension phase
To evaluate the change from baseline in serum lipoprotein (a) [Lp (a)] level.		Up to month 6 in the extension phase
To evaluate the change from baseline in serum Apolipoprotein B (ApoB) level.		Up to month 6 in the extension phase
The proportion of subjects with serum LDL-C level <2.6mmol/L at week 24.		Up to week 24 of the main study phase
The proportion of subjects with serum LDL-C level decreased by ≥50% compared with the baseline at week 24.		Up to week 24 of the main study phase
The serum concentration of EDP167 over time.		Up to month 6 of the extension phase
To evaluate the safety and tolerability of EDP167 in subjects with HoFH.	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 month 6 of the extension phase
To evaluate the immunogenicity of EDP167.	The incidence and titer of antibodies against EDP167.	Up to month 6 of the extension phase

Collaborators and Investigators

• Sponsor: Eddingpharm (Zhuhai) Co., Ltd.
• Investigators: Principal Investigator: Kefei Dou, MD, Chinese Academy of Medical Sciences, Fuwai Hospital

Study record dates

Study Major Dates

• Study Start (Actual): February 6, 2026
• Primary Completion (Estimated): October 4, 2026
• Study Completion (Estimated): March 31, 2027

Study Registration Dates

• First Submitted: March 19, 2026
• First Submitted That Met QC Criteria: March 19, 2026
• First Posted (Actual): March 24, 2026

Study Record Updates

• Last Update Posted (Actual): May 20, 2026
• Last Update Submitted That Met QC Criteria: May 19, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Dyslipidemia; siRNA; HoFH; ANGPTL3
• Additional Relevant MeSH Terms: Metabolism, Inborn Errors; Genetic Diseases, Inborn; Metabolic Diseases; Hyperlipidemias; Lipid Metabolism Disorders; Lipid Metabolism, Inborn Errors; Hyperlipoproteinemias; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Nutritional and Metabolic Diseases; Hyperlipoproteinemia Type II; Homozygous Familial Hypercholesterolemia; Dyslipidemias
• Other Study ID Numbers: EDP167D201

Drug and device information, study documents

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