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

January 19, 2026 updated by: Xiumin Wang, PhD, Shanghai Jiao Tong University School of Medicine

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 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

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

CS-121 is an investigational, in vivo base editing therapy delivered by lipid nanoparticles (LNPs) targeting the APOC3 gene in the liver. By introducing precise base edits at specific APOC3 loci, CS-121 is intended to mimic naturally occurring protective mutations that reduce APOC3 expression, thereby restoring triglyceride clearance pathways and lowering pancreatitis risk. Preclinical studies in transgenic mouse and non-human primate models demonstrated dose-dependent APOC3 editing, reductions in serum ApoC3 protein and triglyceride levels, and acceptable safety profiles, supporting advancement into human evaluation. This open-label, single-arm, dose-escalation early exploratory trial designed to evaluate the safety, tolerability, PK/PD characteristics and preliminary efficacy of CS-121 in patients with hyperchylomicronemia. Based on the properties of gene editing therapy, the primary focus of the study is to identify the optimal biological dose (OBD) rather than the traditional maximum tolerated dose (MTD).

Study Type

Interventional

Enrollment (Estimated)

15

Phase

  • Early Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • China
    • Shanghai Municipality
      • Shanghai, Shanghai Municipality, China
        • Recruiting
        • Shanghai Children's Medical Center
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Low Dose CS-121
Participants in this arm will receive low dose of CS-121
Biological: CS-121
CS-121 is a in vivo base editing therapy formulated in lipid nanoparticles for targeted editing of the APOC3 gene in hepatocytes.
Experimental: Middle Dose CS-121
Participants in this arm will receive middle dose of CS-121
Biological: CS-121
CS-121 is a in vivo base editing therapy formulated in lipid nanoparticles for targeted editing of the APOC3 gene in hepatocytes.
Experimental: High Dose CS-121
Participants in this arm will receive high dose of CS-121
Biological: CS-121
CS-121 is a in vivo base editing therapy formulated in lipid nanoparticles for targeted editing of the APOC3 gene in hepatocytes.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Dose-limiting toxicities (DLTs)
Time Frame: Within 14 days post CS-121 dosing
Within 14 days post CS-121 dosing
The incidence and severity of treatment-emergent adverse events (TEAEs)
Time Frame: from screening to 10 months post last dosing
from screening to 10 months post last dosing

Secondary Outcome Measures

Outcome Measure
Time Frame
Changes in serum triglyceride (TG) levels
Time Frame: From baseline to 10 months post last dosing
From baseline to 10 months post last dosing
Changes in serum ApoC3 levels from baseline
Time Frame: From baseline to 10 months post last dosing
From baseline to 10 months post last dosing
Concentrations of the active components of CS-121 (sgRNA and mRNA)
Time Frame: From baseline to 1 month post last dosing
From baseline to 1 month post last dosing

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Shanghai Jiao Tong University School of Medicine

Collaborators

CorrectSequence Therapeutics Co., Ltd

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

January 26, 2026

Primary Completion (Estimated)

October 31, 2027

Study Completion (Estimated)

January 31, 2041

Study Registration Dates

First Submitted

January 19, 2026

First Submitted That Met QC Criteria

January 19, 2026

First Posted (Actual)

January 28, 2026

Study Record Updates

Last Update Posted (Actual)

January 28, 2026

Last Update Submitted That Met QC Criteria

January 19, 2026

Last Verified

January 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CS-121-02

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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