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RECRUITINGEarly Phase 1INTERVENTIONAL

CS-121 APOC3 Base Editing in FCS

A Clinical Study to Evaluate the Safety, Tolerability, Pharmacodynamics, and Pharmacokinetics of CS-121, an In Vivo Base Editing Therapy Delivered by Lipid Nanoparticles Targeting APOC3, in Adults With Familial Chylomicronemia Syndrome

Important: This information is not medical advice. Talk to your doctor about whether a clinical trial is right for you.

About This Trial

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).

Who May Be Eligible (Plain English)

Who May Qualify: - Male or female aged 18 to 55 years (inclusive) at the time of signing willing to sign a consent form. - 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 willing to sign a consent form and comply with the requirements and restrictions specified in the willing to sign a consent form 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). Who Should NOT Join This Trial: - Currently participating in another interventional clinical study, or last use of another investigational product with a waiting period after previous treatment 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. ...See full criteria on ClinicalTrials.gov Always talk to your doctor about whether this trial is right for you.

Original Eligibility Criteria

View original clinical language
Inclusion Criteria: * 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). Exclusion Criteria: * 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.

Treatments Being Tested

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. 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).

Locations (1)

The First Affiliated Hospital of Anhui Medical University
Hefei, Anhui, China