A Study of VERVE-102 in Patients With Familial Hypercholesterolemia or Premature Coronary Artery Disease

Study Overview
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Brief Summary
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VT-10201 is an Open-label, Phase 1b, Single-ascending Dose Study That Will Evaluate the Safety of VERVE-102 Administered to Patients With Heterozygous Familial Hypercholesterolemia (HeFH) or Premature Coronary Artery Disease (CAD) Who Require Additional Lowering of LDL-C. VERVE-102 Uses Base-editing Technology Designed to Disrupt the Expression of the PCSK9 Gene in the Liver and Lower Circulating PCSK9 and LDL-C. This Study is Designed to Determine the Safety and Pharmacodynamic Profile of VERVE-102 in This Patient Population.

Official Title
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Open-label, Phase 1b, Single Ascending Dose Study to Evaluate the Safety of VERVE-102 Administered to Patients With Heterozygous Familial Hypercholesterolemia or Premature Coronary Artery Disease Who Require Additional Lowering of Low-density Lipoprotein Cholesterol

Conditions
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Heterozygous Familial Hypercholesterolemia, Premature Coronary Heart Disease

Intervention / Treatment
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* Drug: VERVE-102


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of HeFH or premature CAD Females of non-childbearing potential or males Exclusion Criteria: Homozygous familial hypercholesterolemia Active or history of chronic liver disease Current treatment with PCSK9 inhibitor or prior treatment within specified timeframe 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: 65 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.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1: Single Ascending Dose Escalation<br>Participants will receive a single dose of VERVE-102. | Drug: VERVE-102<br>* Intravenous (IV) infusion<br>|
| Experimental: Cohort 2: Single Ascending Dose Escalation<br>Participants will receive a single dose of VERVE-102. | Drug: VERVE-102<br>* Intravenous (IV) infusion<br>|
| Experimental: Cohort 3: Single Ascending Dose Escalation<br>Participants will receive a single dose of VERVE-102. | Drug: VERVE-102<br>* Intravenous (IV) infusion<br>|
| Experimental: Cohort 4: Single Ascending Dose Escalation<br>Participants will receive a single dose of VERVE-102. | Drug: VERVE-102<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) and serious adverse events (SAEs) |  | 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 | 
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Base Editing, VERVE-102, Familial Hypercholesterolemia, Coronary Artery Disease, Dose Escalation, Gene Editing