CS-121 APOC3 Base Editing in FCS

NCT07176923 | Recruiting Early Phase 1

• 1 other identifier: CS-121-01
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

This is an open-label, single-arm, dose-escalation Phase I clinical trial to evaluate the safety, tolerability, pharmacodynamics (PD), and pharmacokinetics (PK) of CS-121, an in vivo base editing therapy delivered by lipid nanoparticles targeting APOC3, in adult participants (18-55 years) with familial chylomicronemia syndrome (FCS).

Conditions

Familial Chylomicronemia Syndrome (FCS)

Keywords

Familial Chylomicronemia Syndrome (FCS); Severe Hypertriglyceridemia; Acute Pancreatitis; Apolipoprotein C3 (APOC3); In Vivo Base Editing; Lipid Nanoparticles (LNP); Gene Editing Therapy; First-in-Human Study; Rare Metabolic Disorder

Outcome Measures

Primary Outcomes (2)

• Treatment-Emergent Adverse Events (TEAEs)

  Incidence, nature, and severity of treatment-emergent adverse events (TEAEs), including serious adverse events (SAEs), adverse events of special interest (AESIs), and abnormalities in clinical symptoms, vital signs, physical examinations, laboratory tests, and electrocardiograms (ECGs). Severity will be graded according to NCI CTCAE version 5.0.

  From the start of dosing through approximately 10 months of follow-up

• Dose-Limiting Toxicities (DLTs)

  Within 14 days after CS-121 infusion

  Number and type of dose-limiting toxicities (DLTs), defined as CTCAE grade ≥3 adverse events considered possibly, probably, or definitely related to CS-121 and persisting ≥7 days, or other adverse events/laboratory abnormalities that lead to suspension o

Secondary Outcomes (5)

• Change from Baseline in Fasting Serum Triglycerides (TG)

  Baseline through approximately 10 months after dosing

• Change from Baseline in Serum ApoC3 Protein Levels

  Baseline through approximately 10 months after dosing

• Peak Concentration (Cmax) of CS-121 Components

  From dosing through approximately 1 month after infusion.

• Time to Maximum Concentration (Tmax) of CS-121 Components

  From dosing through approximately 1 month after infusion

• Area Under the Curve (AUC) of CS-121 Components

  From dosing through approximately 1 month after infusion.

Study Arms (5)

Single Low Dose CS-121

EXPERIMENTAL

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

Biological: CS-121

Single Middle Dose CS-121

EXPERIMENTAL

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

Biological: CS-121

Single High Dose CS-121

EXPERIMENTAL

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

Biological: CS-121

Single Lower Dose 1 of CS-121

EXPERIMENTAL

Participants in this arm will receive a single lower dose 1 of CS-121.

Biological: CS-121

Single Lower Dose 2 of CS-121

EXPERIMENTAL

Participants in this arm will receive a single lower dose 2 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. In this study, participants receive a single intravenous infusion of CS-121 at escalating dose levels. The investigational product is designed to reduce ApoC3 protein expression and serum triglyceride levels in adults with familial chylomicronemia syndrome (FCS).

Single High Dose CS-121; Single Low Dose CS-121; Single Lower Dose 1 of CS-121; Single Lower Dose 2 of CS-121; Single Middle Dose CS-121

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Male or female aged 18 to 55 years (inclusive) at the time of signing informed consent.
• On regular standard therapy with good compliance, but fasting triglyceride (TG) levels have not been consistently reduced below 10 mmol/L (880 mg/dL); i.e., before screening, there must be records of at least three separate fasting TG values \>10 mmol/L (880 mg/dL), or the participant is intolerant to standard therapy.
• North American Familial Chylomicronemia Syndrome (NAFCS) score ≥45
• Able to sign informed consent and comply with the requirements and restrictions specified in the informed consent form and the protocol, such as dietary guidance and intake restrictions.
• Female participants must meet one of the following: be not of childbearing potential (e.g., documented hysterectomy, bilateral salpingectomy/sterilization, or ≥1 year postmenopausal); or, if of childbearing potential, have a negative pregnancy test at screening and be willing to use strict and effective contraception (e.g., abstinence, pharmacologic, or barrier methods) during the study. Male participants with reproductive potential must agree to use strict and effective contraception (e.g., abstinence, pharmacologic, or barrier methods) throughout the entire post-dose observation period; males without reproductive potential must provide supporting medical history (e.g., post-vasectomy).

You may not qualify if:

• Currently participating in another interventional clinical study, or last use of another investigational product with a washout period of less than 5 half-lives or 30 days (whichever is longer).
• Use of APOC3-targeted antisense oligonucleotides (ASO) or siRNA lipid-lowering agents within 6 months prior to dosing.
• History of acute pancreatitis within 3 months before dosing.
• History of acute coronary syndrome (ACS) within 6 months before dosing, such as myocardial infarction or unstable angina, or prior coronary revascularization (e.g., coronary artery bypass grafting, angioplasty, or stent implantation).
• In the investigator's judgment, receipt of major surgery within 3 months before dosing that would make the participant unsuitable for this study drug or unable to tolerate possible cytokine-release events.
• Any of the following laboratory abnormalities at screening:
• ALT or AST ≥3 × ULN Total bilirubin ≥1.5 × ULN eGFR \<30 mL/min/1.73 m² Random urine albumin-to-creatinine ratio (UACR) \>30 mg/g LDL-C \>130 mg/dL (3.4 mmol/L) HbA1c ≥9%
• Coagulation abnormalities deemed by the investigator to make CS-121 administration unsuitable.
• Positive at screening for HBsAg, HCV antibody and RNA, HIV, or Treponema pallidum (syphilis).
• Known major organ disease, psychiatric disorders, Cushing's syndrome, or malignancy that, in the investigator's judgment, would make the participant unsuitable for the study or unable to tolerate possible cytokine-release-like events.
• Concomitant medications or treatments judged by the investigator to affect lipid metabolism, hepatic or renal function, or coagulation, or to interfere with the evaluation of study drug efficacy, including but not limited to: systemic glucocorticoids, anabolic steroids, antiretroviral agents used within 4 weeks prior to dosing, plasma exchange, blood donation, or blood loss \>200 mL.
• Planning pregnancy, currently pregnant, or breastfeeding.

Sponsors & Collaborators

• CorrectSequence Therapeutics Co., Ltd: lead
• The First Affiliated Hospital of Anhui Medical University: collaborator

Study Sites (1)

The First Affiliated Hospital of Anhui Medical University

Hefei, Anhui, China

RECRUITING

MeSH Terms

Conditions

Familial hyperchylomicronemia syndrome; Hypertriglyceridemia; Pancreatitis

Condition Hierarchy (Ancestors)

Hyperlipidemias; Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Pancreatic Diseases; Digestive System Diseases

Study Officials

• YALIANG LI

  CorrectSequence Therapeutics (Shanghai) Co., Ltd

  STUDY DIRECTOR

Central Study Contacts

Yaliang Li

CONTACT

+8618621046122; yaliang.li@correctsequence.com

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: About 3-15 participants with NAFCS ≥45 and fasting triglycerides ≥10 mmol/L will be enrolled. The study follows an adaptive design with three ascending dose levels and up to two de-escalation cohorts if needed. Each cohort includes 1-3 participants; escalation proceeds after ≥14 days of safety, PK, and PD review. A single intravenous infusion of CS-121 is given, followed by 5 days of inpatient monitoring and \~10 months of follow-up to assess safety, tolerability, PK, PD, and exploratory efficacy including triglyceride reduction and pancreatitis incidence.

Study Record Dates

• First Submitted: August 30, 2025
• First Posted: September 16, 2025
• Study Start: October 15, 2025
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: February 11, 2026

Record last verified: 2026-02

Locations

CN (1)