CS-121 APOC3 Base Editing in Children and Adolescents With Hyperchylomicronemia

NCT07371767 | Recruiting Early Phase 1

• 1 other identifier: CS-121-02
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

This is 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 (4-18 years) With Hyperchylomicronemia

Conditions

Hyperchylomicronemia

Keywords

Acute Pancreatitis; Apolipoprotein C3 (APOC3); In Vivo Base Editing; Lipid Nanoparticles (LNP); Gene Editing Therapy; Children and Adolescents

Outcome Measures

Primary Outcomes (2)

• Dose-limiting toxicities (DLTs)

  Within 14 days post CS-121 dosing

• The incidence and severity of treatment-emergent adverse events (TEAEs)

  from screening to 10 months post last dosing

Secondary Outcomes (3)

• Changes in serum triglyceride (TG) levels

  From baseline to 10 months post last dosing

• Changes in serum ApoC3 levels from baseline

  From baseline to 10 months post last dosing

• Concentrations of the active components of CS-121 (sgRNA and mRNA)

  From baseline to 1 month post last dosing

Study Arms (3)

Low Dose CS-121

EXPERIMENTAL

Participants in this arm will receive low dose of CS-121

Biological: CS-121

Middle Dose CS-121

EXPERIMENTAL

Participants in this arm will receive middle dose of CS-121

Biological: CS-121

High Dose CS-121

EXPERIMENTAL

Participants in this arm will receive high dose of CS-121

Biological: CS-121

Interventions

CS-121 BIOLOGICAL

CS-121 is a in vivo base editing therapy formulated in lipid nanoparticles for targeted editing of the APOC3 gene in hepatocytes.

High Dose CS-121; Low Dose CS-121; Middle Dose CS-121

Eligibility Criteria

• Age: 4 Years - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Shanghai Jiao Tong University School of Medicine: lead
• CorrectSequence Therapeutics Co., Ltd: collaborator

Study Sites (1)

Shanghai Children's Medical Center

Shanghai, Shanghai Municipality, China

RECRUITING

MeSH Terms

Conditions

Hyperlipoproteinemia Type I; Pancreatitis

Condition Hierarchy (Ancestors)

Lipid Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Hyperlipoproteinemias; Hyperlipidemias; Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Pancreatic Diseases; Digestive System Diseases

Central Study Contacts

Guoying Chang, PhD

CONTACT

86+15000394881; changguoying@126.com

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: chief physician

Study Record Dates

• First Submitted: January 19, 2026
• First Posted: January 28, 2026
• Study Start: January 26, 2026
• Primary Completion (Estimated): October 31, 2027
• Study Completion (Estimated): January 31, 2041
• Last Updated: January 28, 2026

Record last verified: 2026-01

Locations

CN (1)