Homozygous Familial Hypercholesterolemia (HoFH)
Conditions
Brief summary
Significant reduction in ANGPLT3 levels is expected to reduce plasma LDL-C and TG levels and may lead to the reduction of risk of coronary heart disease and cardiovascular events associated with hypertriglyceridemia and LDL-C in subjects with persistent dyslipidemia. In this clinical study, the efficacy and safety of VSA003, an RNAi-based therapeutic targeting ANGPTL3, will be evaluated in subjects with HoFH.
Interventions
DRUGVSA003
subcutaneous injections
DRUGPlacebo
subcutaneous injections
Sponsors
Visirna Therapeutics HK Limited
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
12 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male or female aged ≥ 12 years and weighing ≥ 40 kg at the time of ICF signature; * Patients with HoFH who meet genetic or clinical diagnosis; * Willing to follow a daily low-fat diet for the duration of the study; * Receiving stable and tolerable lipid-lowering therapy prior to LDL-C testing during the screening period; * Fasting LDL-C ≥ 2.6 mmol/L.
Exclusion criteria
* Have received or are receiving targeted ANGPTL3 treatment within 5 months or 5 half-lives, whichever is longer, prior to screening; * Fasting TG ≥ 4.5 mmol/L at screening; * Presence of uncontrolled endocrine disease affecting lipids or lipoproteins; * Weight change of more than 10% in the 4 weeks prior to randomisation; * Initiation of a new dietary plan or significant differences from previous dietary structure and habits within 4 weeks prior to screening; * Women who are pregnant (including planned pregnancies) or breastfeeding; * Refusal to limit alcohol consumption to moderate limits and below during the study period, specifically no more than 14 units per week; * Uncontrolled hypertension (blood pressure \> 160/100 mmHg at screening); * New York Heart Association (NYHA) class IV heart failure or left ventricular ejection fraction \<30% within 12 months prior to screening; * History of major surgery within 12 weeks prior to baseline, or planning to undergo major surgery during the study; * Known allergy to any component of the study drug.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Percent change from baseline in serum LDL-C at month 6 | At month 6 |
Secondary
| Measure | Time frame |
|---|---|
| Percent change and absolute change in serum ANGPTL3 levels from baseline at month 6 | At month 6 |
| Percent change and absolute change in serum LDL-C, ApoB, non-HDL-C, VLDL-C, TC and TG levels from baseline | Up to month 6, Up to month 18 |
| Percent change and absolute change in serum HDL-C, ApoC-III, ApoC-II, ApoA-I, ApoA-V and Lp[a] levels from baseline | Up to month 6, Up to month 18 |
| Percentage of patients achieving ≥30% reduction in serum LDL-C from baseline | At month 6, At month 18 |
| Percentage of patients achieving ≥50% reduction in serum LDL-C from baseline | At month 6, At month 18 |
| Number of Participants with Adverse Events | Up to month 6, Up to month 18 |
| Number of Participants with Anti-Drug Antibodies (ADAs) to VSA003 Over Time | Up to month 6, Up to month 18 |
| Correlation between VSA003 serum concentrations and QT intervals | Up to month 6, Up to month 18 |
Countries
China
Outcome results
None listed