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
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
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
15
CS-121 is a in vivo base editing therapy formulated in lipid nanoparticles for targeted editing of the APOC3 gene in hepatocytes.
Shanghai Children's Medical Center
Shanghai, Shanghai Municipality, China
RECRUITINGDose-limiting toxicities (DLTs)
Time frame: 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
Changes in serum triglyceride (TG) levels
Time frame: 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
Concentrations of the active components of CS-121 (sgRNA and mRNA)
Time frame: From baseline to 1 month post last dosing
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