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

NCT05398029 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: VT-1001
• Study Type: interventional
• Target: 13
• Locations: 2 countries
• Sites: 3

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.

Conditions

Heterozygous Familial Hypercholesterolemia; Atherosclerotic Cardiovascular Disease; Hypercholesterolemia

Keywords

VERVE-101; Familial Hypercholesterolemia; Cardiovascular Disease; Dose Escalation; Gene Editing; Base Editing

Outcome Measures

Primary Outcomes (1)

• Incidence of treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), and adverse events of special interest (AESIs).

  up to Day 365

Secondary Outcomes (3)

• 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 Outcomes (2)

• 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

Study Arms (2)

Part A: Single Ascending Dose Escalation/Adaptive Design

EXPERIMENTAL

Participants will receive a single dose of VERVE-101 in multiple dose-escalation cohorts.

Drug: VERVE-101

Part B: Single Dose Expansion

EXPERIMENTAL

Participants will receive a single dose of VERVE-101 selected based on the doses studied in Part A.

Drug: VERVE-101

Interventions

VERVE-101 DRUG

Intravenous (IV) infusion.

Part A: Single Ascending Dose Escalation/Adaptive Design; Part B: Single Dose Expansion

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Verve Therapeutics, Inc.: lead

Study Sites (3)

Clinical Study Center

Auckland, New Zealand

Location

Clinical Study Center

Christchurch, New Zealand

Location

Clinical Study Center

London, United Kingdom

Location

MeSH Terms

Conditions

Atherosclerosis; Hypercholesterolemia; Hyperlipoproteinemia Type II; Cardiovascular Diseases

Condition Hierarchy (Ancestors)

Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Hyperlipidemias; Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Lipid Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Hyperlipoproteinemias

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Single ascending dose escalation/adaptive design followed by single dose expansion.

Study Record Dates

• First Submitted: May 19, 2022
• First Posted: May 31, 2022
• Study Start: July 5, 2022
• Primary Completion: February 14, 2025
• Study Completion: February 14, 2025
• Last Updated: May 8, 2025

Record last verified: 2025-05

Locations

GB (1); NZ (2)