ACTIVE_NOT_RECRUITING

Phosphatase Inhibition by Intracoronary Gene Therapy in Subjects With Non-Ischemic NYHA Class III Heart Failure

Conditions

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

This is a Phase 2 adaptive, double-blinded, placebo-controlled, randomized, multi-center trial study to evaluate the safety and efficacy of a single dose of AB-1002, administered via antegrade intracoronary artery infusion, in males and females age \>18 years with non-ischemic cardiomyopathy and NYHA Class III symptoms of HF. Subjects will be randomized into one of three treatment groups in a 1:1:1

Official Title

A Phase 2, Adaptive, Double-blinded, Placebo Controlled, Randomized, Multi-center Trial to Evaluate the Efficacy, Safety and Tolerability of Intracoronary Infusion of AB-1002 in Adult Subjects With New York Heart Association (NYHA) Class III Heart Failure and Non-ischemic Cardiomyopathy

Quick Facts

Study Start:2023-10-20

Study Completion:2030-12-31

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:ACTIVE_NOT_RECRUITING

Study ID

NCT05598333

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
1. Subject must be age ≥18 years of age, at the time of signing the informed consent. 2. Chronic non-ischemic cardiomyopathy 3. 15% ≤ LVEF ≤ 35% by transthoracic echocardiography (TTE) at screening 4. 6MWT \>50 meters 5. Medically stable, NYHA Class III HF for a minimum of 4 weeks while on appropriate medical therapy (defined below) including, but not limited to: 1. Beta blocker therapy and ACE inhibitor or angiotensin receptor blocker (ARB) or sacubitril/valsartan combination therapy (Entresto) for ≥ 90 days prior to enrollment. 2. Cardiac resynchronization therapy (Zareba et al 2011), 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. 6. Women 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 7. Males subjects capable of fathering a child: * Must agree to use a condom and should also be advised of the benefit for a female partner to use a highly effective method of contraception as a condom may break or leak when having sexual intercourse with a woman of childbearing potential who is not currently pregnant from IP administration through 6 months after the time of IP administration * Must agree not to donate sperm for 6 months after time of receiving IP * Documented evidence of vasectomy in males for 180 days minimum prior to receiving IP is an acceptable form of contraception * Males who claim abstinence as their method of contraception are allowed, provided they agree to use barrier methods should they become sexually active from screening through 6 months after receiving IP. Males are allowed to claim abstinence as their method of contraception only when it is the preferred and usual lifestyle of the subject 8. Appropriate candidate for protocol-specified intracoronary infusion in the judgment of the infusing interventional cardiologist	9. Chronic ischemic cardiomyopathy secondary to obstructive coronary artery disease 10. Intravenous (IV) inotropic therapy, intra-aortic balloon pump (IABP) or percutaneous cardiac assist device therapy within 30 days prior to enrollment 11. Restrictive cardiomyopathy, obstructive cardiomyopathy, pericardial disease, amyloidosis, infiltrative cardiomyopathy, uncorrected thyroid disease, or dyskinetic LV aneurysm 12. Cardiac surgery or percutaneous coronary intervention (PCI) within 30 days prior to screening 13. Uncorrected Third degree heart block 14. 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 15. Prior heart transplantation, left ventricular reduction surgery (LVRS), cardiomyoplasty, passive restraint device (e.g., CorCap™ Cardiac Support Device), surgically implanted LVAD or cardiac shunt 16. Likely to receive cardiac resynchronization therapy, cardiomyoplasty, LV reduction surgery, heart transplant, conventional revascularization procedure, or valvular repair within 3 months of IP dosing in judgement of investigator. 17. Known hypersensitivity to contrast dyes (not easily controlled by antihistamines) used for angiography; history of, or likely need for, high-dose steroid pretreatment prior to contrast angiography. 18. Expected survival \< 1 year in the judgment of the investigator 19. Active or suspected infection within 48 hours prior to intra-coronary infusion as evidenced by fever or positive culture 20. Known intrinsic liver disease (e.g., cirrhosis, hepatitis A, chronic hepatitis B or hepatitis C virus infection). If serology is positive and PCR is known to be negative, subject may be eligible (confirm with medical monitor). 21. Liver function tests (alanine aminotransferase \[ALT\], aspartate aminotransferase \[AST\], alkaline phosphatase) \> 2x upper limit of normal (ULN) within 30 days prior to enrollment. 22. Chronic Kidney Disease Stage 5, dialysis dependent or eGFR\<15 within 30 days prior to enrollment 23. Bleeding diathesis or thrombocytopenia defined as platelets \<50,000 platelets/μL within 30 days prior to enrollment 24. Anemia defined as hemoglobin \<10 g/dL or transfusion dependent within 30 days prior to enrollment 25. Neutropenia defined as absolute neutrophils \<1500 mm3 within 30 days prior to enrollment 26. Known AIDS or HIV-positive status, or a previous diagnosis of immunodeficiency with an absolute neutrophil count \<1000 cells/mm3 27. Previous participation in a study of gene transfer 28. Receiving investigational intervention or participating in another clinical study within 30 days of another investigational drug administration prior to administration of AB-1002 that may impact the therapeutic potential of AB-1002. 29. Pregnancy or breastfeeding or plans to become pregnant within the next 12 months at the time of screening 30. Subjects with any other condition which in the opinion of the investigator would preclude participation in the study (including risk for non-compliance and any intercurrent conditions that pose an undue medical hazard, or which could interfere with the interpretation of the study results) 31. Malignant neoplasm within 5 years of dosing, with the exception of those with negligible risk of metastasis or death (such as adequately treated carcinoma in situs of the cervix, basal or squamous cell skin cancer, localized prostate cancer or ductal carcinoma in situ) 32. Any documented history of non-compliance with medications, illicit drug use or laboratory evidence of illicit drug use during screen period

Inclusion Criteria

Exclusion Criteria

1. Subject must be age ≥18 years of age, at the time of signing the informed consent.
2. Chronic non-ischemic cardiomyopathy
3. 15% ≤ LVEF ≤ 35% by transthoracic echocardiography (TTE) at screening
4. 6MWT \>50 meters
5. Medically stable, NYHA Class III HF for a minimum of 4 weeks while on appropriate medical therapy (defined below) including, but not limited to:
1. Beta blocker therapy and ACE inhibitor or angiotensin receptor blocker (ARB) or sacubitril/valsartan combination therapy (Entresto) for ≥ 90 days prior to enrollment.
2. Cardiac resynchronization therapy (Zareba et al 2011), 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.
6. Women 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
7. Males subjects capable of fathering a child:
* Must agree to use a condom and should also be advised of the benefit for a female partner to use a highly effective method of contraception as a condom may break or leak when having sexual intercourse with a woman of childbearing potential who is not currently pregnant from IP administration through 6 months after the time of IP administration
* Must agree not to donate sperm for 6 months after time of receiving IP
* Documented evidence of vasectomy in males for 180 days minimum prior to receiving IP is an acceptable form of contraception
* Males who claim abstinence as their method of contraception are allowed, provided they agree to use barrier methods should they become sexually active from screening through 6 months after receiving IP. Males are allowed to claim abstinence as their method of contraception only when it is the preferred and usual lifestyle of the subject
8. Appropriate candidate for protocol-specified intracoronary infusion in the judgment of the infusing interventional cardiologist

9. Chronic ischemic cardiomyopathy secondary to obstructive coronary artery disease
10. Intravenous (IV) inotropic therapy, intra-aortic balloon pump (IABP) or percutaneous cardiac assist device therapy within 30 days prior to enrollment
11. Restrictive cardiomyopathy, obstructive cardiomyopathy, pericardial disease, amyloidosis, infiltrative cardiomyopathy, uncorrected thyroid disease, or dyskinetic LV aneurysm
12. Cardiac surgery or percutaneous coronary intervention (PCI) within 30 days prior to screening
13. Uncorrected Third degree heart block
14. 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
15. Prior heart transplantation, left ventricular reduction surgery (LVRS), cardiomyoplasty, passive restraint device (e.g., CorCap™ Cardiac Support Device), surgically implanted LVAD or cardiac shunt
16. Likely to receive cardiac resynchronization therapy, cardiomyoplasty, LV reduction surgery, heart transplant, conventional revascularization procedure, or valvular repair within 3 months of IP dosing in judgement of investigator.
17. Known hypersensitivity to contrast dyes (not easily controlled by antihistamines) used for angiography; history of, or likely need for, high-dose steroid pretreatment prior to contrast angiography.
18. Expected survival \< 1 year in the judgment of the investigator
19. Active or suspected infection within 48 hours prior to intra-coronary infusion as evidenced by fever or positive culture
20. Known intrinsic liver disease (e.g., cirrhosis, hepatitis A, chronic hepatitis B or hepatitis C virus infection). If serology is positive and PCR is known to be negative, subject may be eligible (confirm with medical monitor).
21. Liver function tests (alanine aminotransferase \[ALT\], aspartate aminotransferase \[AST\], alkaline phosphatase) \> 2x upper limit of normal (ULN) within 30 days prior to enrollment.
22. Chronic Kidney Disease Stage 5, dialysis dependent or eGFR\<15 within 30 days prior to enrollment
23. Bleeding diathesis or thrombocytopenia defined as platelets \<50,000 platelets/μL within 30 days prior to enrollment
24. Anemia defined as hemoglobin \<10 g/dL or transfusion dependent within 30 days prior to enrollment
25. Neutropenia defined as absolute neutrophils \<1500 mm3 within 30 days prior to enrollment
26. Known AIDS or HIV-positive status, or a previous diagnosis of immunodeficiency with an absolute neutrophil count \<1000 cells/mm3
27. Previous participation in a study of gene transfer
28. Receiving investigational intervention or participating in another clinical study within 30 days of another investigational drug administration prior to administration of AB-1002 that may impact the therapeutic potential of AB-1002.
29. Pregnancy or breastfeeding or plans to become pregnant within the next 12 months at the time of screening
30. Subjects with any other condition which in the opinion of the investigator would preclude participation in the study (including risk for non-compliance and any intercurrent conditions that pose an undue medical hazard, or which could interfere with the interpretation of the study results)
31. Malignant neoplasm within 5 years of dosing, with the exception of those with negligible risk of metastasis or death (such as adequately treated carcinoma in situs of the cervix, basal or squamous cell skin cancer, localized prostate cancer or ductal carcinoma in situ)
32. Any documented history of non-compliance with medications, illicit drug use or laboratory evidence of illicit drug use during screen period

Contacts and Locations

Study Locations (Sites)

Cardiology P.C. Birmingham

Birmingham, Alabama, 35211

United States

University of Arizona Sarvor Heart Center

Tucson, Arizona, 85724

United States

University of California Irvine Medical Center

Irvine, California, 92697

United States

University of California San Diego

La Jolla, California, 92093

United States

University of California San Francisco

San Francisco, California, 94143

United States

Baycare Medical Group

Clearwater, Florida, 33756

United States

University of Miami

Coral Gables, Florida, 33146

United States

University of Florida

Gainesville, Florida, 32610

United States

Augusta University

Augusta, Georgia, 30912

United States

Loyola Medicine Burr Ridge

Oakbrook Terrace, Illinois, 60181

United States

University of Iowa

Iowa City, Iowa, 52242

United States

University of Kansas Medical Center (KUMC)

Kansas City, Kansas, 66160

United States

Massachusetts General Hospital

Boston, Massachusetts, 02114

United States

Brigham and Women's Hospital

Boston, Massachusetts, 02115

United States

Minneapolis Heart Institute Foundation

Minneapolis, Minnesota, 55407

United States

Mayo Clinic - Minnesota

Rochester, Minnesota, 55905

United States

Aurora Saint Luke's Health System

Kansas City, Missouri, 64111

United States

St. Louis University

St Louis, Missouri, 63117

United States

Renown Health

Reno, Nevada, 89502

United States

Morristown Medical Center - Cardiology

Morristown, New Jersey, 07962

United States

Mt. Sinai New York

New York, New York, 10029

United States

Stony Brook

Stony Brook, New York, 11794

United States

Montefiore Medical Center

The Bronx, New York, 10461

United States

Duke University

Durham, North Carolina, 27705

United States

The Christ Hospital / The Linder Center for Research

Cincinnati, Ohio, 45219

United States

University of Cincinnati

Cincinnati, Ohio, 45219

United States

MetroHealth Medical Center

Cleveland, Ohio, 44109

United States

The Ohio State University

Columbus, Ohio, 43210

United States

LVH Cardiology

Allentown, Pennsylvania, 18103

United States

Thomas Jefferson University

Philadelphia, Pennsylvania, 19107

United States

Medical University of South Carolina (MUSC) Medical Center

Charleston, South Carolina, 29425

United States

Stern Cardiovascular

Germantown, Tennessee, 38138

United States

Baylor Scott & White Advanced Heart Failure Clinic - Dallas

Dallas, Texas, 75246

United States

Baylor College of Medicine (BCM) - Baylor Heart Clinic

Houston, Texas, 77030

United States

Houston Methodist Debakey Cardiology Associates

Houston, Texas, 77030

United States

University of Washington

Seattle, Washington, 98195

United States

University of Wisconsin

Madison, Wisconsin, 53792

United States

Collaborators and Investigators

Sponsor: AskBio Inc

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2023-10-20

Study Completion Date2030-12-31

Study Record Updates

Study Start Date2023-10-20

Study Completion Date2030-12-31

Terms related to this study

Additional Relevant MeSH Terms

Congestive Heart Failure