A Study of VERVE-101 in Patients With Familial Hypercholesterolemia and Cardiovascular Disease

Study Overview
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Brief Summary
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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.

Official Title
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Open-label, Phase 1b, Single-ascending Dose and Optional re Dosing Study to Evaluate the Safety of VERVE-101 Administered to Patients With Heterozygous Familial Hypercholesterolemia, Atherosclerotic Cardiovascular Disease, and Uncontrolled Hypercholesterolemia

Conditions
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Hypercholesterolemia, Heterozygous Familial Hypercholesterolemia, Atherosclerotic Cardiovascular Disease

Intervention / Treatment
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* Drug: VERVE-101


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: Single ascending dose escalation/adaptive design followed by single dose expansion.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part A: Single Ascending Dose Escalation/Adaptive Design<br>Participants will receive a single dose of VERVE-101 in multiple dose-escalation cohorts. | Drug: VERVE-101<br>* Intravenous (IV) infusion.<br>|
| Experimental: Part B: Single Dose Expansion<br>Participants will receive a single dose of VERVE-101 selected based on the doses studied in Part A. | Drug: VERVE-101<br>* Intravenous (IV) infusion.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 Outcome Measures

| Outcome Measure | Measure Description | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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VERVE-101, Familial Hypercholesterolemia, Cardiovascular Disease, Dose Escalation, Gene Editing, Base Editing