Atherosclerotic Cardiovascular Disease, Heterozygous Familial Hypercholesterolemia, Hypercholesterolemia
Conditions
Keywords
VERVE-101, Familial Hypercholesterolemia, Cardiovascular Disease, Dose Escalation, Gene Editing, Base Editing
Brief summary
VT-1001 is an open-label, phase 1b, single-ascending dose study that will evaluate the safety of VERVE-101 administered to patients with heterozygous familial hypercholesterolemia (HeFH), atherosclerotic cardiovascular disease (ASCVD), and uncontrolled hypercholesterolemia. VERVE-101 uses base-editing technology designed to disrupt the expression of the PCSK9 gene in the liver and lower circulating PCSK9 and LDL-C in patients with established ASCVD due to HeFH. This study is designed to determine the safety and pharmacodynamic profile of VERVE-101 in this patient population.
Interventions
DRUGVERVE-101
Intravenous (IV) infusion.
Sponsors
Verve Therapeutics, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Single ascending dose escalation/adaptive design followed by single dose expansion.
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Male and/or female participants 18 up to 75 years at time of signing of informed consent * Female participants not of child-bearing potential * Diagnosis of HeFH * Established ASCVD
Exclusion criteria
* Active or history of chronic liver disease * Current treatment with PCSK9 monoclonal antibody therapy * Current or past treatment with inclisiran * Clinically significant or abnormal laboratory values as defined by the protocol
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Incidence of treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), and adverse events of special interest (AESIs). | up to Day 365 |
Secondary
| Measure | Time frame |
|---|---|
| Evaluation of maximum observed concentration (Cmax) | up to Day 365 |
| Evaluation of time to maximum observed concentration (tmax) | up to Day 365 |
| Evaluation of terminal elimination half-life (t1/2) | up to Day 365 |
Other
| Measure | Time frame |
|---|---|
| Percent and absolute change from baseline in plasma PCSK9 concentration. | up to Day 365 |
| Percent and absolute change from baseline in LDL-C. | up to Day 365 |
Countries
New Zealand, United Kingdom
Outcome results
None listed