Health TrialsbyHealthPanel

CS-121 APOC3 Base Editing in FCS

ConditionFamilial Chylomicronemia Syndrome (FCS)
Trial statusRecruiting
Trial phaseEarly Phase 1
Trial typeInterventional
Biological sexAll
Age18-55
SponsorCorrectSequence Therapeutics Co., Ltd

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).

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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.

Disqualifiers

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).

Trial design

Design model

Sequential

Treatments tested in this trial

  • CS-121

    Biological/Vaccine

    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).

Treatment groups

15 Participants
are divided into 5 treatment groups
Group A: Single Low Dose CS-121Experimental treatment 1 intervention
Group B: Single Middle Dose CS-121Experimental treatment 1 intervention
Group C: Single High Dose CS-121Experimental treatment 1 intervention
Group D: Single Lower Dose 1 of CS-121Experimental treatment 1 intervention
Group E: Single Lower Dose 2 of CS-121Experimental treatment 1 intervention

Trial outcomes

Primary outcomes

1

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.

Time frame
From the start of dosing through approximately 10 months of follow-up
2

Dose-Limiting Toxicities (DLTs)

Within 14 days after CS-121 infusion

Time frame
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

1

Change from Baseline in Fasting Serum Triglycerides (TG)

Absolute and relative change in fasting serum triglyceride levels compared with baseline values.

Time frame
Baseline through approximately 10 months after dosing
2

Change from Baseline in Serum ApoC3 Protein Levels

Absolute and relative change in serum ApoC3 protein concentrations compared with baseline values.

Time frame
Baseline through approximately 10 months after dosing
3

Peak Concentration (Cmax) of CS-121 Components

Maximum observed concentration of CS-121 components following intravenous infusion.

Time frame
From dosing through approximately 1 month after infusion.
4

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

Time to reach maximum observed concentration of CS-121 components following intravenous infusion

Time frame
From dosing through approximately 1 month after infusion

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

CorrectSequence Therapeutics Co., Ltd

Lead sponsor

The First Affiliated Hospital of Anhui Medical University

Collaborator

Source ClinicalTrials.gov
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