CS-121 base editing of APOC3 to lower triglycerides in children and adolescents with hyperchylomicronemia

A Prospective, Single-center, Open-label, Single-arm Clinical Study to Evaluate the Safety and Efficacy of CS-121, an In Vivo Base Editing Therapy Delivered by Lipid Nanoparticles Targeting APOC3, in Children and Adolescents With Hyperchylomicronemia

This trial will test a one-time in vivo base editing therapy (CS-121) delivered by lipid nanoparticles to lower APOC3 and reduce triglycerides in children and adolescents aged 4–18 with severe hyperchylomicronemia.

Quick facts

• Phase: Early Phase 1
• Study type: Interventional
• Enrollment: 15 (estimated)
• Ages: 4 Years to 18 Years
• Sex: All
• Sponsor: Shanghai Jiao Tong University School of Medicine (Academic / other)
• Locations: 1 site (Shanghai, Shanghai Municipality)
• Trial ID: NCT07371767 on ClinicalTrials.gov

What this trial studies

CS-121 is an investigational in vivo base editing therapy delivered to the liver via lipid nanoparticles that introduces precise edits in the APOC3 gene to mimic protective loss-of-function variants. This open-label, single-arm, dose-escalation early-phase study will enroll participants aged 4 to under 18 with severe hypertriglyceridemia and genetically or clinically confirmed familial chylomicronemia. The trial focuses on safety, tolerability, PK/PD, and preliminary efficacy, with the primary aim of identifying an optimal biological dose rather than a maximum tolerated dose. Preclinical work in mice and non-human primates showed dose-dependent APOC3 editing, lowered ApoC3 protein and triglyceride levels, and acceptable safety, supporting first-in-human pediatric evaluation.

Who should consider this trial

Good fit: Ideal candidates are children and adolescents aged 4–17 with severe hypertriglyceridemia (TG ≥ 500 mg/dL) and confirmed or clinically persistent familial chylomicronemia who have inadequate triglyceride control despite standard care.

Not a fit: Patients without genetically driven familial chylomicronemia, those with only mild or secondary hypertriglyceridemia, pregnant individuals, or those currently in other interventional trials are unlikely to benefit or be eligible.

Why it matters

Potential benefit: If successful, CS-121 could substantially lower ApoC3 and triglycerides, lowering pancreatitis risk and potentially reducing the need for lifelong lipid-lowering therapies.

How similar studies have performed: Early human trials of LNP-delivered genome editors (for example NTLA-2001 targeting TTR) have shown meaningful target protein reductions and acceptable short-term safety, but APOC3 base editing in pediatric hyperchylomicronemia is a novel application.

Eligibility criteria

Inclusion Criteria:

* Male or female participants aged 4 years ≤ age \< 18 years.
* Severe hypertriglyceridemia (sHTG), defined as a triglyceride (TG) level ≥ 500 mg/dL.
* Confirmed diagnosis of genetically inherited FCS via genetic testing, or clinically diagnosed FCS plus persistent chylomicronemia.
* Failure to achieve adequate TG control, For participants under 8 years of age, the investigator determine at their discretion whether prior lipidlowering therapy has been administered.
* Participants aged 6 years and above must sign the informed consent form themselves; for participants under 18 years of age, their parent/legal guardian must sign the informed consent form. (Participants under 6 years of age are exempt from signing the written informed consent form).
* Female participants of childbearing potential must have a negative result on serum pregnancy testing.

Exclusion Criteria:

* Currently participating in other interventional clinical studies, or having an insufficient washout period of less than 5 half-lives or 30 days (whichever is longer) since the last administration of other investigational drugs.
* Used antisense oligonucleotide (ASO)-based or small interfering RNA (siRNA)-based lipid-lowering drugs targeting APOC3 within 3 months prior to study drug administration.
* History of acute pancreatitis within 1 month before dosing.
* Patients who underwent major surgery within 3 months prior to study drug administration and are judged by the investigator as unsuitable for receiving the study drug, due to potential intolerance to adverse events such as cytokine release storm.
* ALT or AST ≥2 × ULN
* Total bilirubin ≥1.5 × ULN
* eGFR \<30 mL/min/1.73 m²
* Random urine albumin-to-creatinine ratio (UACR) \>30 mg/g, or urine protein is ≥ 2+
* HbA1c ≥9%
* Coagulation function abnormalities judged by the investigator as unsuitable for CS-121 administration.
* Positive results for HBsAg, dual positivity for HCV antibody and RNA, positive for HIV, or positive for Treponema pallidum infection.
* Known major organ diseases, mental disorders, Cushing's syndrome, hypothyroidism, history of lymphoproliferative disorders, or malignant tumors in any organ system, which are judged by the investigator as unsuitable for study participation due to potential intolerance to adverse events such as cytokine Release-Storm.
* Concomitant medications/treatments judged by the investigator to affect lipid metabolism, liver and kidney function, coagulation function, or interfere with the efficacy evaluation of the study drug.
* Patients of childbearing potential who are planning pregnancy, breastfeeding, or have fertility plans.
* History of hypersensitivity to any study drug, its excipients, or drugs of similar chemical classes.
* Other medical conditions or comorbidities that, in the investigator's opinion, may interfere with study compliance or data interpretation.

Where this trial is running

Shanghai, Shanghai Municipality

• Shanghai Children's Medical Center — Shanghai, Shanghai Municipality, China (Recruiting)

Study contacts

• Study coordinator: Guoying Chang, PhD

Conditions Hyperchylomicronemia; Acute Pancreatitis; Apolipoprotein C3; In Vivo Base Editing; Lipid Nanoparticles; Gene Editing Therapy; Children and Adolescents