CS-121 APOC3 Base Editing in Severe Hypertriglyceridemia

NCT07657780 | Not Yet Recruiting Early Phase 1 DMC

• 1 other identifier: CS-121-06
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

This is an open-label, single-arm, dose-escalation IIT 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 (18-65 years) with Severe Hypertriglyceridemia(sHTG).

Conditions

Severe Hypertriglyceridemia (sHTG)

Keywords

Apolipoprotein C3 (APOC3); In Vivo Base Editing; Lipid Nanoparticles (LNP); Gene Editing Therapy

Outcome Measures

Primary Outcomes (2)

• Treatment-Emergent Adverse Events (TEAEs)

  From screening to 12 months post last dosing

• Dose-Limiting Toxicities (DLTs)

  Within 14 days after CS-121 infusion

Secondary Outcomes (3)

• Change from Baseline in Fasting Serum Triglycerides (TG)

  Baseline through approximately 12 months post dosing

• Change from Baseline in Serum ApoC3 Protein Levels

  From baseline to 12 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 (5)

Single Low Dose CS-121

EXPERIMENTAL

Participants in this arm will receive a single low dose (0.5mg/kg) of CS-121.

Biological: CS-121

Single Middle Dose CS-121

EXPERIMENTAL

Participants in this arm will receive a single middle dose (0.7mg/kg) of CS-121.

Biological: CS-121

Single High Dose CS-121

EXPERIMENTAL

Participants in this arm will receive a single high dose (1.0mg/kg) of CS-121

Biological: CS-121

Single selected Lower Dose 1 of CS-121

EXPERIMENTAL

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

Biological: CS-121

Single selected Lower Dose 2 of CS-121

EXPERIMENTAL

Participants in this arm will receive a single selected 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.

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

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female participants aged 18 years ≤ age \< 65 years.
• The serum triglyceride levels of the participants failed to be effectively controlled under the standard treatment regimen (or the medication that is available and tolerable as recommended by clinical practice) and were defined as having at least 3 records of different fasting triglyceride levels ≥ 5.65 mmol/L (500 mg/dL) within 2 years..
• The screening period should include at least two different days with a TG level of ≥ 5.65 mmol/L (500 mg/dL), with an interval of at least 7 days.
• Able to sign informed consent and comply with the requirements and restrictions specified in the informed consent form and the protocol.
• 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 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.
• Requires long-term use of systemic corticosteroids and steroid drugs and cannot discontinue the medication.
• Patients who experienced acute pancreatitis within 4 weeks prior dosing.
• History of acute coronary syndrome (ACS) within 6 months before dosing, such as myocardial infarction or unstable angina, or prior coronary revascularization (such as coronary artery bypass grafting), angioplasty or stent implantation.
• In the investigator's judgment to be unsuitable for the study drug due to receipt of major surgery within 3 months before dosing.
• Any of the following laboratory abnormalities at screening:.
• ALT or AST ≥2 × ULN;
• Total bilirubin ≥2 × ULN;
• eGFR \<30 mL/min/1.73 m²
• HbA1c ≥9%;
• Absolute neutrophil count \< 1.0 × 109/L
• Hemoglobin (female)\< 100 g/L, Hemoglobin (male) \< 110 g/L
• Platelet count \< 100 × 109/L
• Coagulation function abnormalities judged by the investigator as unsuitable for CS-121 administration.

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

Location

MeSH Terms

Conditions

Hypertriglyceridemia

Condition Hierarchy (Ancestors)

Hyperlipidemias; Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Central Study Contacts

Xiaokai Li

CONTACT

+8618686610731; xiaokai.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

Study Record Dates

• First Submitted: June 15, 2026
• First Posted: June 18, 2026
• Study Start: June 15, 2026
• Primary Completion (Estimated): March 15, 2028
• Study Completion (Estimated): July 31, 2028
• Last Updated: June 18, 2026

Record last verified: 2026-06

Locations

CN (1)