Cardiovascular, Dyslipidemias, Heterozygous Familial Hypercholesterolemia (HeFH), Homozygous Familial Hypercholesterolemia (HoFH), Hypercholesterolaemia, Hypertriglyceridemia, Lipid Disorder, Metabolic Disease, Mixed Hyperlipemia, Severe Hypertriglyceridemia (sHTG)
Conditions
Keywords
Refractory Dyslipidemias
Brief summary
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.
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.
Interventions
DRUGCTX310
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).
Sponsors
CRISPR Therapeutics AG
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
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/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| To evaluate the safety of CTX310 in adult subjects with dyslipidemias that are refractory to available treatments | From CTX310 infusion up to 12 months | Incidence of dose-limiting toxicities and frequency of adverse events |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| To assess the preliminary efficacy of CTX310 in adult participants with dyslipidemias that are refractory to available treatments | Over 12 months, compared to baseline | Percentage change from baseline in lipid values (LDL-C, non-HDL-C, Trigs, apoB and HDL-C) |
| To further characterize the safety of CTX310 in adult participants with dyslipidemias that are refractory to available treatments | From CTX310 infusion up to 12 months | 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. |
| To assess the pharmacokinetics (PK) of CTX310 in adult participants with dyslipidemias that are refractory to available treatments | From CTX310 infusion up to 12 months | Levels of CTX310 in blood over time |
| To assess the pharmacodynamic (PD) response of CTX310 in adult participants with dyslipidemias that are refractory to available treatments | Over 12 months, compared to baseline | Percentage change from baseline of ANGPTL3 |
Countries
Australia, New Zealand, United Kingdom, United States
Contacts
CONTACTClinical Trials
Outcome results
None listed