AB-1002 in Patients With Class III Heart Failure

NCT04179643 | Active Not Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: NAN-CS101
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 4

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).

Conditions

Congestive Heart Failure; Heart Failure; Heart Disease, Ischemic; Cardiovascular Diseases; Heart Failure, Systolic; Heart Failure，Congestive; Heart Arrhythmia; Heart Failure, Diastolic; Heart; Complications

Outcome Measures

Primary Outcomes (2)

• Observed and change from baseline in Peak VO2

  Cardiopulmonary exercise testing using a modified Bruce protocol

  Measured at screening, month 6, 9 and month 12

• Observed and change from baseline in Echocardiographic assessment in Left Ventricular Ejection Fraction

  Echocardiography LVEF measurement

  Measured at screening, 18-24 hours post intervention, week 4, Month 3, Month 6 and Month 12

Secondary Outcomes (1)

• Observed and change from baseline in 6-minute walk test distance

  Measured at screening, Month 3, Month 6 and month 12

Study Arms (3)

3.25E13vg AB-1002

EXPERIMENTAL

Intracoronary Infusion of 3.25E13vg AB-1002 up to 6 subjects

Biological: 3 x 10e13vg AB-1002

1.08E14vg AB-1002

EXPERIMENTAL

Intracoronary Infusion of 1.08E14vg AB-1002 to 6 subjects

Biological: 3 x 10e13vg AB-1002

PLN-R14Del patients: 3.25E13vg AB-1002

EXPERIMENTAL

Intracoronary Infusion of AB-1002 at 3.25E13vg up to 6 subjects with PLN-R14Del genetic mutation

Biological: 3 x 10e13vg AB-1002

Interventions

3 x 10e13vg AB-1002 BIOLOGICAL

There are 2 components to AB-1002. The first is an active I-1 transgene (AA 1-65 with T35D), and the second is the vector, BNP116, which delivers the gene selectively to the heart after intracoronary administration.

1.08E14vg AB-1002; 3.25E13vg AB-1002; PLN-R14Del patients: 3.25E13vg AB-1002

Eligibility Criteria

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

You may qualify if:

• Age \>18 years of age
• Chronic non-ischemic cardiomyopathy
• LVEF 15% ≤ 30% by transthoracic echocardiography (TTE) within 6 months prior to enrollment
• NYHA Class III HF for a minimum of 3 months HF despite appropriate medical therapy (defined below):
• Treatment with appropriate HF therapy as tolerated, including, but not limited to:
• Beta blocker therapy and angiotensin converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) or sacubitril/valsartan combination therapy (Entresto) for ≥ 90 days prior to enrollment. May also receive aldosterone antagonist therapy. Doses of the above medications must be stable for ≥ 30 days prior to enrollment; and
• Cardiac resynchronization therapy (CRT), if clinically indicated, must have been implanted ≥ 90 days prior to enrollment. Internal cardioverter defibrillator (ICD) must be implanted, if clinically indicated ≥ 30 days prior to enrollment
• Females of childbearing potential must use at least one of the following acceptable birth control methods throughout the study and for 6 months after IP administration:
• Surgically sterile (bilateral tubal ligation, hysterectomy, bilateral oophorectomy) 6 months minimum prior to IP administration
• Intrauterine device in place for at least 90 days prior to receiving IP
• Barrier methods (diaphragm plus spermicide or condom) starting at least 30 days prior to receiving IP
• Abstinence (the subject must be willing to remain abstinent from screening to 6 months after receiving IP). Females are allowed to claim abstinence as their method of contraception only when it is the preferred and usual lifestyle of the subject
• Surgical sterilization of the partner(s) (vasectomy) for \>180 days prior to IP administration
• Hormonal contraceptives starting \> 90 days prior to IP. If hormonal contraceptives are started less than 90 days prior to receiving IP, subjects must agree to use a barrier method (diaphragm plus spermicide or condom) from screening through 90 days after initiation of hormonal contraceptives
• Males subjects capable of fathering a child:

You may not qualify if:

• 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

Sponsors & Collaborators

• AskBio Inc: lead

Study Sites (4)

Minneapolis Heart Foundation Institute

Minneapolis, Minnesota, 55407, United States

Location

The Linder Center for Education and Research at The Christ Hospital

Cincinnati, Ohio, 45219, United States

Location

The Ohio State University

Columbus, Ohio, 43210, United States

Location

University of Wisconsin at Madison

Madison, Wisconsin, 53792, United States

Location

Related Publications (1)

• Henry TD, Chung ES, Alvisi M, Sethna F, Murray DR, Traverse JH, Roessig L, Roberts L, Reddy S, Chen Y, Ozkan TG, Webb S, Mittal M, Ervin L, Sadek H, Mikhail S, Haghighi K, Jiang C, Samulski RJ, Kranias EG, Tretiakova AP, Hajjar RJ. Cardiotropic AAV gene therapy for heart failure: a phase 1 trial. Nat Med. 2025 Nov;31(11):3845-3852. doi: 10.1038/s41591-025-04011-z. Epub 2025 Oct 21.

  PMID: 41120766 DERIVED

MeSH Terms

Conditions

Heart Failure; Myocardial Ischemia; Cardiovascular Diseases; Heart Failure, Systolic; Arrhythmias, Cardiac; Heart Failure, Diastolic

Condition Hierarchy (Ancestors)

Heart Diseases; Vascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Design

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

Study Record Dates

• First Submitted: September 6, 2019
• First Posted: November 27, 2019
• Study Start: November 20, 2019
• Primary Completion: August 20, 2024
• Study Completion (Estimated): September 30, 2026
• Last Updated: April 8, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)