EDP167 dose testing for homozygous familial hypercholesterolemia

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

This trial tests whether two injections of an siRNA drug called EDP167 can lower ANGPTL3 and improve lipid levels in adults with homozygous familial hypercholesterolemia (HoFH).

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 20 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Eddingpharm (Zhuhai) Co., Ltd. (Industry-sponsored)
• Locations: 1 site (Beijing)
• Trial ID: NCT07489209 on ClinicalTrials.gov

What this trial studies

EDP167 is a GalNAc‑conjugated siRNA designed to silence hepatic ANGPTL3 and lower lipids. In this randomized Phase 2 dose-exploration trial, 20 adults with genetically or clinically confirmed HoFH will be assigned to one of two dose cohorts (200 mg or 300 mg, n=10 each) and receive injections on Day 1 and Week 12, with a 24‑week main study evaluation. Subjects who complete the main phase may enter a 6‑month extension receiving additional injections at Month 0 and Month 3 with follow-up to Month 6. The trial will monitor safety, pharmacokinetics, pharmacodynamics (including ANGPTL3, LDL‑C, triglycerides and other lipid parameters), and tolerability.

Who should consider this trial

Good fit: Adults (≥18 years) with a genetic or clinical diagnosis of HoFH, fasting LDL‑C ≥2.6 mmol/L, weight ≥40 kg, on stable lipid‑lowering therapy, and willing to use contraception and follow study procedures are ideal candidates.

Not a fit: Patients who recently received other siRNA/ASO therapies, have known allergies to the drug or its components, cannot maintain stable background therapy, or cannot comply with contraception requirements may not receive benefit from participation.

Why it matters

Potential benefit: If successful, EDP167 could offer a new way to lower ANGPTL3 and substantially reduce LDL‑C and triglycerides in patients with HoFH who have limited treatment options.

How similar studies have performed: Inhibition of ANGPTL3 has produced lipid‑lowering effects in other clinical studies, though GalNAc‑conjugated siRNA approaches in HoFH are still early-stage and not yet widely established.

Eligibility criteria

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. The pregnancy test results of Women of Childbearing Potential must be negative.
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. With a history of malignancy, unless it is believed to have been cured by adequate treatment and there is no evidence of recurrence for at least 3 years.
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.

Where this trial is running

Beijing

• Fuwai Hospital — Beijing, China (Recruiting)

Study contacts

• Principal investigator: Kefei Dou, MD — Chinese Academy of Medical Sciences, Fuwai Hospital
• Study coordinator: Wei Song

Conditions Homozygous Familial Hypercholesterolemia; Dyslipidemia; ANGPTL3; siRNA; HoFH