A Safety and Tolerability Trial Evaluating CTX310 in Participants With Refractory Dyslipidemias

A Phase 1 Open-label, Multicenter, First-in-human, Ascending Dose Trial Evaluating the Safety and Tolerability of a Lipid Nanoparticle Formulation of CRISPR-Guide RNA-Cas9 Nuclease (CTX310) for In Vivo Editing of the Angiopoietin-like 3 (ANGPTL3) Gene in Participants With Refractory Dyslipidemias

This is a single-arm, open-label, multicenter, ascending dose Phase 1 trial that will enroll participants 18 to 75 years of age with dyslipidemias that are refractory to available treatments.

Study Overview

• Status: Recruiting
• Conditions: Dyslipidemias; Hypercholesterolaemia; Hypertriglyceridemia; Lipid Disorder; Metabolic Disease; Cardiovascular; Homozygous Familial Hypercholesterolemia (HoFH); Severe Hypertriglyceridemia (sHTG); Mixed Hyperlipemia; Heterozygous Familial Hypercholesterolemia (HeFH)
• Intervention / Treatment: Drug: CTX310

Detailed Description

This is a phase 1, open-label, multi-center study of CTX310 in participants with refractory dyslipidemias. Subjects will receive a dose of CTX310 via intravenous (IV) infusion.

• Study Type: Interventional
• Enrollment (Estimated): 90
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Clinical Trials; Phone Number: 877-214-4634; Email: medicalaffairs@crisprtx.com

Study Locations

• Australia
  • Adelaide, Australia, 5000
    • Recruiting
    • Research Site 1
  • Brisbane, Australia, 4064
    • Not yet recruiting
    • Research Site 15
  • Brisbane, Australia
    • Not yet recruiting
    • Research Site 16
  • Camperdown, Australia, 2050
    • Not yet recruiting
    • Research Site 7
  • Heidelberg, Australia, 3084
    • Recruiting
    • Research Site 3
  • Melbourne, Australia, 3168
    • Recruiting
    • Research Site 2
• New Zealand
  • Auckland, New Zealand, 2025
    • Recruiting
    • Research Site 5
  • Christchurch, New Zealand, 8011
    • Recruiting
    • Research Site 4
• United Kingdom
  • Cambridge, United Kingdom
    • Not yet recruiting
    • Research Site 18
  • London, United Kingdom, E1 1BB
    • Not yet recruiting
    • Research Site 8
  • London, United Kingdom, SE1 1YR
    • Recruiting
    • Research Site 6
• United States
  • Florida
    • Jacksonville, Florida, United States, 32216
      • Not yet recruiting
      • Research Site 10
    • Orlando, Florida, United States, 32789
      • Recruiting
      • Research Site 17
    • Port Orange, Florida, United States, 32127
      • Recruiting
      • Research Site 11
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Not yet recruiting
      • Research Site 14
    • High Point, North Carolina, United States, 27260
      • Recruiting
      • Research Site 13
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Not yet recruiting
      • Research Site 9
  • Oregon
    • Portland, Oregon, United States, 97239
      • Not yet recruiting
      • Research Site 12

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

1. Age of ≥18 and ≤75 years at the time of signing the informed consent.
2. Able to provide written informed consent.
3. Participants diagnosed with persistent dyslipidemias defined by TG ≥150 mg/dL - and LDL-C ≥70 mg/dL in participants with ASCVD, or LDL-C ≥70 or 100mg/dL in participants with or without ASCVD respectively, or TG ≥500 mg/dL.
4. Refractory to the maximal intensity or MTD of standard of care lines of lipid-lowering therapies available through routine clinical care, for at least 12 weeks prior to screening
5. Female participants must be postmenopausal or surgically sterile.
6. All male participants and their female partners must agree to the use of an acceptable method of effective contraception for the duration of the study.

Exclusion Criteria:

1. Participants with familial chylomicronemia syndrome (FCS). Some exceptions may apply.

2. Evidence of liver disease, defined as but not limited to:

   LFTS >2 × upper limit of normal (ULN), or total bilirubin >2 × ULN, or INR >1.5 × ULN, or liver stiffness measured by liver elastography

3. Abnormal or compromised function of kidney, heart, blood or liver.
4. Acute coronary syndrome event or stroke within 24 weeks prior to Day 1. Acute pancreatitis within 12 weeks prior to Day 1.
5. Current use or use within 365 days from Day 1 of any hepatocyte-targeted small interfering RNA (except inclisiran).
6. Positive serology for HIV, hepatitis B or hepatitis C (antibody, surface antigen orNAT). Serology consistent with prior immunization will be eligible for the trial.
7. Any prior malignancy within the past 5 years, or current malignancy (exceptions for resected or removed basal cell carcinoma, squamous cell carcinoma in situ and carcinoma in situ of the cervix or breast).
8. Women of childbearing potential.

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Note: The inclusion and exclusion criteria listed represent the global protocol. Additional or modified eligibility criteria may apply in certain countries in accordance with local regulatory and ethics committee requirements and the approved country-specific protocol.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CTX310; Subjects will receive an intravenous (IV) infusion.	Drug: CTX310; CTX310 is a lipid nanoparticle (LNP) formulation of clustered regularly interspaced short palindromic repeats (CRISPR)-associated protein 9 (Cas9) components for in vivo editing of the target gene angiopoietin-like 3 (ANGPTL3).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To evaluate the safety of CTX310 in adult subjects with dyslipidemias that are refractory to available treatments	Incidence of dose-limiting toxicities and frequency of adverse events	From CTX310 infusion up to 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To assess the preliminary efficacy of CTX310 in adult participants with dyslipidemias that are refractory to available treatments	Percentage change from baseline in lipid values (LDL-C, non-HDL-C, Trigs, apoB and HDL-C)	Over 12 months, compared to baseline
To further characterize the safety of CTX310 in adult participants with dyslipidemias that are refractory to available treatments	Frequency and severity of adverse events (AE), including treatment-emergent adverse events (TEAEs) and adverse events of special interest (AESIs), clinically significant laboratory abnormalities, and clinically significant abnormal vital signs.	From CTX310 infusion up to 12 months
To assess the pharmacokinetics (PK) of CTX310 in adult participants with dyslipidemias that are refractory to available treatments	Levels of CTX310 in blood over time	From CTX310 infusion up to 12 months
To assess the pharmacodynamic (PD) response of CTX310 in adult participants with dyslipidemias that are refractory to available treatments	Percentage change from baseline of ANGPTL3	Over 12 months, compared to baseline

Collaborators and Investigators

• Sponsor: CRISPR Therapeutics AG

Study record dates

Study Major Dates

• Study Start (Actual): June 21, 2024
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): June 1, 2028

Study Registration Dates

• First Submitted: March 18, 2026
• First Submitted That Met QC Criteria: March 18, 2026
• First Posted (Actual): March 24, 2026

Study Record Updates

• Last Update Posted (Actual): May 22, 2026
• Last Update Submitted That Met QC Criteria: May 19, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Refractory Dyslipidemias
• Additional Relevant MeSH Terms: Metabolism, Inborn Errors; Genetic Diseases, Inborn; Hyperlipidemias; Lipid Metabolism, Inborn Errors; Hyperlipoproteinemias; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Nutritional and Metabolic Diseases; Hyperlipoproteinemia Type II; Homozygous Familial Hypercholesterolemia; Hypercholesterolemia; Dyslipidemias; Metabolic Diseases; Hypertriglyceridemia; Lipid Metabolism Disorders; Hyperlipoproteinemia Type V
• Other Study ID Numbers: CRSP-CVD-400

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No