Back to resultsA Study of VERVE-101 in Patients With Familial Hypercholesterolemia and Cardiovascular Disease
Primary Purpose
Heterozygous Familial Hypercholesterolemia, Atherosclerotic Cardiovascular Disease, Hypercholesterolemia
Status
Recruiting
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
VERVE-101
Sponsored by
About this trial
This is an interventional treatment trial for Heterozygous Familial Hypercholesterolemia focused on measuring VERVE-101, Familial Hypercholesterolemia, Cardiovascular Disease, Dose Escalation, Gene Editing, Base Editing
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 due to mutation in LDLR
- Established ASCVD
Exclusion Criteria:
- Diagnosis of HeFH due to mutation in PCSK9 or APOB, homozygous FH, compound heterozygous FH, double heterozygous FH
- 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
Sites / Locations
- Clinical Study CenterRecruiting
- Clinical Study CenterRecruiting
- Clinical Study CenterRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Part A: Single Ascending Dose Escalation
Part B: Single Dose Expansion
Arm Description
Participants will receive a single dose of VERVE-101 in multiple dose-escalation cohorts.
Participants will receive a single dose of VERVE-101 selected based on the doses studied in Part A.
Outcomes
Primary Outcome Measures
Incidence of treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), and adverse events of special interest (AESIs).
Secondary Outcome Measures
Evaluation of maximum observed concentration (Cmax)
Evaluation of time to maximum observed concentration (tmax)
Evaluation of terminal elimination half-life (t1/2)
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT05398029
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
Study Type
Interventional
2. Study Status
Record Verification Date
May 2023
Overall Recruitment Status
Recruiting
Study Start Date
July 5, 2022 (Actual)
Primary Completion Date
December 2024 (Anticipated)
Study Completion Date
December 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Verve Therapeutics, Inc.
4. Oversight
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
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Heterozygous Familial Hypercholesterolemia, Atherosclerotic Cardiovascular Disease, Hypercholesterolemia
Keywords
VERVE-101, Familial Hypercholesterolemia, Cardiovascular Disease, Dose Escalation, Gene Editing, Base Editing
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Model Description
Single ascending dose escalation followed by single dose expansion.
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
44 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Part A: Single Ascending Dose Escalation
Arm Type
Experimental
Arm Description
Participants will receive a single dose of VERVE-101 in multiple dose-escalation cohorts.
Arm Title
Part B: Single Dose Expansion
Arm Type
Experimental
Arm Description
Participants will receive a single dose of VERVE-101 selected based on the doses studied in Part A.
Intervention Type
Drug
Intervention Name(s)
VERVE-101
Intervention Description
Intravenous (IV) infusion.
Primary Outcome Measure Information:
Title
Incidence of treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), and adverse events of special interest (AESIs).
Time Frame
up to Day 365
Secondary Outcome Measure Information:
Title
Evaluation of maximum observed concentration (Cmax)
Time Frame
up to Day 365
Title
Evaluation of time to maximum observed concentration (tmax)
Time Frame
up to Day 365
Title
Evaluation of terminal elimination half-life (t1/2)
Time Frame
up to Day 365
Other Pre-specified Outcome Measures:
Title
Percent and absolute change from baseline in plasma PCSK9 concentration.
Time Frame
up to Day 365
Title
Percent and absolute change from baseline in LDL-C.
Time Frame
up to Day 365
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Clinical Operations at Verve Therapeutics
Phone
781-970-6833
Email
verve101clinicaltrials@vervetx.com
Facility Information:
Facility Name
Clinical Study Center
City
Auckland
Country
New Zealand
Individual Site Status
Recruiting
Facility Name
Clinical Study Center
City
Christchurch
Country
New Zealand
Individual Site Status
Recruiting
Facility Name
Clinical Study Center
City
London
Country
United Kingdom
Individual Site Status
Recruiting
12. IPD Sharing Statement
Learn more about this trial
A Study of VERVE-101 in Patients With Familial Hypercholesterolemia and Cardiovascular Disease
We'll reach out to this number within 24 hrs