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

• ClinicalTrials.gov Identifier: NCT05398029
• Recruitment Status: Active, not recruiting
• First Posted: May 31, 2022
• Last Update Posted: April 8, 2024
• Sponsor: Verve Therapeutics, Inc.
• Information provided by (Responsible Party): Verve Therapeutics, Inc.

Tracking Information

• First Submitted Date: May 19, 2022
• First Posted Date: May 31, 2022
• Last Update Posted Date: April 8, 2024
• Actual Study Start Date: July 5, 2022
• Estimated Primary Completion Date: December 2024 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: May 25, 2022): Incidence of treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), and adverse events of special interest (AESIs). [ Time Frame: up to Day 365 ]
• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: May 25, 2022)

• Evaluation of maximum observed concentration (Cmax) [ Time Frame: up to Day 365 ]
• Evaluation of time to maximum observed concentration (tmax) [ Time Frame: up to Day 365 ]
• Evaluation of terminal elimination half-life (t1/2) [ Time Frame: up to Day 365 ]

• Original Secondary Outcome Measures: Same as current

Current Other Pre-specified Outcome Measures (submitted: May 25, 2022)

• Percent and absolute change from baseline in plasma PCSK9 concentration. [ Time Frame: up to Day 365 ]
• Percent and absolute change from baseline in LDL-C. [ Time Frame: up to Day 365 ]

• Original Other Pre-specified Outcome Measures: Same as current

Descriptive Information

• Brief Title: A Study of VERVE-101 in Patients With Familial Hypercholesterolemia and Cardiovascular Disease
• Official Title: 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
• 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1

Study Design

Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention Model Description:

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

Masking: None (Open Label)
Primary Purpose: Treatment

Condition

• Heterozygous Familial Hypercholesterolemia
• Atherosclerotic Cardiovascular Disease
• Hypercholesterolemia

Intervention

Drug: VERVE-101

Intravenous (IV) infusion.

Study Arms

• Experimental: Part A: Single Ascending Dose Escalation/Adaptive Design
  Participants will receive a single dose of VERVE-101 in multiple dose-escalation cohorts.
  Intervention: Drug: VERVE-101
• Experimental: Part B: Single Dose Expansion
  Participants will receive a single dose of VERVE-101 selected based on the doses studied in Part A.
  Intervention: Drug: VERVE-101

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Estimated Enrollment (submitted: May 25, 2022): 44
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: December 2024
• Estimated Primary Completion Date: December 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 75 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: New Zealand, United Kingdom

Administrative Information

• NCT Number: NCT05398029
• Other Study ID Numbers: VT-1001
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Verve Therapeutics, Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: Verve Therapeutics, Inc.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Verve Therapeutics, Inc.
• Verification Date: April 2024