Early-phase Study of ART002g1 Injection in HeFH: Safety, Tolerability and Preliminary Efficacy

Shanghai Jiao Tong University

Status and phase: Not yet enrolling; Early Phase 1

Conditions: Heterozygous Familial Hypercholesterolemia

Treatments: Drug: ART002g1 Injection

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT07353398

IIT-ATMP-2026001

Details and patient eligibility

About

This study is an open-label, single ascending dose (SAD) study designed to evaluate the safety and tolerability of ART002g1 in patients with heterozygous familial hypercholesterolemia (HeFH) who require further reduction in low-density lipoprotein cholesterol (LDL-C). ART002g1 uses base editing technology, which is designed to interfere with the expression of the PCSK9 gene in the liver, thereby reducing the circulating levels of PCSK9 and LDL-C. The primary objectives of this study are to determine the safety and pharmacodynamic (PD) profiles of ART002g1 in this patient population.

Enrollment: 24 estimated patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Subjects must meet all the following criteria to be eligible for enrollment:

1. Male or female, aged 18 to 70 years (inclusive) at the time of signing the Informed Consent Form (ICF);
2. Body weight between 45 and 90 kg (inclusive) at screening;
3. Definite diagnosis of heterozygous familial hypercholesterolemia (HeFH), meeting either of the following two criteria (1) or (2):

（1) HeFH diagnosed to be caused by mutations in the LDLR, APOB, or PCSK9 gene;

(2) Meeting 2 out of the 3 following criteria for adults per the Dutch Lipid Clinical Network (DLCN) criteria:

1. Serum LDL-C ≥ 4.7 mmol/L without prior lipid-lowering treatment;
2. Cutaneous or tendinous xanthomas, or arcus cornealis (in subjects < 45 years old);
3. Presence of FH or early-onset atherosclerotic cardiovascular disease (ASCVD) in first-degree relatives.

Subjects must not be enrolled if they meet any one or more of the following exclusion criteria:

1. Diagnosis of compound heterozygous FH, double heterozygous FH, or homozygous FH (HoFH);
2. Positive for hepatitis B surface antigen (HBsAg), or positive for hepatitis B core antibody (HBcAb) with peripheral blood HBV DNA titer ≥ 1 × 10² copies/L; positive for hepatitis C virus (HCV) antibody with positive peripheral blood HCV RNA; positive for human immunodeficiency virus (HIV) antibody;
3. Any unstable systemic disease, including but not limited to: unstable angina; cerebrovascular accident or transient ischemic attack (within 6 months prior to screening); myocardial infarction (within 6 months prior to screening); history of heart failure (NYHA Class II-IV); severe arrhythmia requiring pharmacotherapy; liver, kidney, or metabolic diseases; or other unstable systemic diseases as determined by the investigator;
4. History of percutaneous transluminal coronary angioplasty (PTCA), percutaneous coronary intervention (PCI), or coronary artery bypass grafting (CABG) within 6 months prior to the first dose; or documented severe coronary artery stenosis as confirmed by coronary CT or coronary angiography within 90 days prior to randomization.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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24 participants in 3 patient groups

Experimental: ART002g1 Injection - Dose Group 1 ( Single IV Infusion)

Experimental group

Description:

Participants will receive a single dose of ART002g1.

Treatment:

Drug: ART002g1 Injection

Experimental: ART002g1 Injection - Dose Group 2 (Single IV Infusion)

Experimental group

Description:

Participants will receive a single dose of ART002g1.

Treatment:

Drug: ART002g1 Injection

Experimental: ART002g1 Injection - Extended Dose Group ( Single IV Infusion)

Experimental group

Description:

Participants will receive a single Optimal Biological Dose (OBD) of ART002g1, which is based on the results of the ascending dose escalation.

Treatment:

Drug: ART002g1 Injection