AB-1002 in Patients With Class III Heart Failure
- Conditions
- Congestive Heart FailureHeart Failure, DiastolicHeart; ComplicationsHeart Disease, IschemicHeart Failure, SystolicHeart FailureCardiovascular DiseasesHeart Failure，CongestiveHeart Arrhythmia
- Interventions
- Biological: 3 x 10e13vg NAN-101Biological: 3 x 10e13vg AB-1002
- Registration Number
- NCT04179643
- Lead Sponsor
- AskBio Inc
- Brief Summary
This is a Phase 1, prospective, multi-center, open-label, sequential dose escalation study to explore the safety, feasibility, and efficacy of a single intracoronary infusion of AB-1002 in patients with NYHA Class III heart failure. Patients with non-ischemic cardiomyopathy will be enrolled until up to 17 subjects have received infusions of investigational product. All patients will be followed until 12 months post treatment intervention, and then undergo long-term follow-up via semi-structured telephone questionnaires every 6 months for an additional 24 months (+/- 30 days).
- Detailed Description
The safety endpoints will be assessed over the 12-month follow-up period
* Adverse Events
* Clinical laboratory tests
* Vital signs
* Electrocardiograms
Efficacy Endpoints
The efficacy endpoints assessed from baseline to 6 and 12 months will include the following:
* Observed and changes from baseline in peak VO2 assessed by cardiopulmonary exercise testing
* Observed and changes from baseline in 6-minute walk test
* Observed and changes from baseline in NYHA Classification
* Total number of days alive out-of-hospital
The secondary efficacy endpoints will explore efficacy. Functional endpoints will be assessed as changes from baseline to 6 and 12 months following investigational product administration as indicated. These endpoints include:
Functional Status \& Hospitalizations
* Peak VO2 assessed by cardiopulmonary exercise testing
* 6-minute walk test
* New York Heart Association (NYHA) Classification
* Total number of days alive out-of-hospital (as well as total days out-of-hospital as a % of total days alive post study intervention)
Physiologic Assessments at 6 and 12 months compared to baseline
* Echocardiographic assessments of LVEF, LVEVD, LVEDVI, VLESV, LVEVI, SpI and GLSand degree of mitral regurgitation
* NT-proBNP level
Quality of Life at Week 8, 6 and 12 months compared to baseline
o Health related quality of life as assessed by Minnesota Living with Heart Failure Questionnaire (MLWHFQ) and Kansas City Cardiomyopathy Questionnaire
The following endpoints will also be measured over the 12 month follow-up period and long-term follow-up period (until month 36 post-intervention):
* Survival
* Cardiac transplantation
* Left ventricular assist device (LVAD) implantation
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 17
Not provided
- Chronic ischemic cardiomyopathy
- Intravenous (IV) inotropic therapy, intra-aortic balloon pump (IABP) or percutaneous cardiac assist device therapy within 30 days prior to enrollment
- Restrictive cardiomyopathy, obstructive cardiomyopathy, pericardial disease, amyloidosis, infiltrative cardiomyopathy, uncorrected thyroid disease, or dyskinetic LV aneurysm
- Cardiac surgery or percutaneous coronary intervention (PCI) within 30 days prior to enrollment
- Third degree heart block
- Clinically significant myocardial infarction (MI) in the judgment of the subject's physician (e.g., ST elevation MI [STEMI] or large non-STEMI) within 6 months prior to enrollment
- Prior heart transplantation, left ventricular reduction surgery (LVRS), cardiomyoplasty, passive restraint device (e.g., CorCap™ Cardiac Support Device), surgically implanted LVAD or cardiac shunt
- Likely to receive cardiac resynchronization therapy, cardiomyoplasty, LV reduction surgery, heart transplant, conventional revascularization procedure, or valvular repair within 3 months of IP dosing
- Known hypersensitivity to contrast dyes used for angiography; history of, or likely need for, high-dose steroid pretreatment prior to contrast angiography
- Expected survival < 1 year in the judgment of the investigator
- Active or suspected infection within 48 hours prior to enrollment as evidenced by fever or positive culture
- Known intrinsic liver disease (e.g., cirrhosis, hepatitis A, chronic hepatitis B or hepatitis C virus infection). If serology is positive and PCR is negative, subject may be eligible (confirm with medical monitor).
- Liver function tests (alanine aminotransferase [ALT], aspartate aminotransferase [AST], alkaline phosphatase) > 2x upper limit of normal (ULN) within 30 days prior to enrollment.
- Renal Failure, dialysis dependent or serum creatinine > 2.5 mg/dl within 30 days prior to enrollment
- Bleeding diathesis or thrombocytopenia defined as platelets <50,000 platelets/μL within 30 days prior to enrollment
- Anemia defined as hemoglobin <10 g/dL or transfusion dependent within 30 days prior to enrollment
- Neutropenia defined as absolute neutrophils <1500 mm3 within 30 days prior to enrollment
- Known AIDS or HIV-positive status, or a previous diagnosis of immunodeficiency with an absolute neutrophil count <1000 cells/mm3
- Previous participation in a study of gene transfer
- Receiving investigational intervention or participating in another clinical study within 30 days or within 5 half-lives of another investigational drug administration prior to administration of NAN-101 that may impact the therapeutic potential of NAN-101.
- Pregnancy or breastfeeding at the time of screening
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description 3.25E13vg AB-1002 3 x 10e13vg NAN-101 Intracoronary Infusion of 3.25E13vg AB-1002 up to 6 subjects 1.08E14vg AB-1002 3 x 10e13vg NAN-101 Intracoronary Infusion of 1.08E14vg AB-1002 to 6 subjects PLN-R14Del patients: 3.25E13vg AB-1002 3 x 10e13vg NAN-101 Intracoronary Infusion of AB-1002 at 3.25E13vg up to 6 subjects with PLN-R14Del genetic mutation 3.25E13vg AB-1002 3 x 10e13vg AB-1002 Intracoronary Infusion of 3.25E13vg AB-1002 up to 6 subjects 1.08E14vg AB-1002 3 x 10e13vg AB-1002 Intracoronary Infusion of 1.08E14vg AB-1002 to 6 subjects PLN-R14Del patients: 3.25E13vg AB-1002 3 x 10e13vg AB-1002 Intracoronary Infusion of AB-1002 at 3.25E13vg up to 6 subjects with PLN-R14Del genetic mutation
- Primary Outcome Measures
Name Time Method Observed and change from baseline in Peak VO2 Measured at screening, month 6, 9 and month 12 Cardiopulmonary exercise testing using a modified Bruce protocol
Observed and change from baseline in Echocardiographic assessment in Left Ventricular Ejection Fraction Measured at screening, 18-24 hours post intervention, week 4, Month 3, Month 6 and Month 12 Echocardiography LVEF measurement
- Secondary Outcome Measures
Name Time Method Observed and change from baseline in 6-minute walk test distance Measured at screening, Month 3, Month 6 and month 12 Analysis of Percent predicted in heart failure subjects compared to normal subjects
Trial Locations
- Locations (4)
Minneapolis Heart Foundation Institute
🇺🇸Minneapolis, Minnesota, United States
The Linder Center for Education and Research at The Christ Hospital
🇺🇸Cincinnati, Ohio, United States
The Ohio State University
🇺🇸Columbus, Ohio, United States
University of Wisconsin at Madison
🇺🇸Madison, Wisconsin, United States