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

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

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

Study Overview

• Status: Active, not recruiting
• Conditions: Congestive Heart Failure
• Intervention / Treatment: Drug: AB-1002

Detailed Description

Subjects will be randomized into one of three treatment groups in a 1:1:1 fashion to either 7.15E13vg (n=30-50), 1.43E14 (n=30-50) or placebo group (n=30-50).

Approximately 90 to 150 subjects will be randomly assigned to study intervention Placebo

Study duration until the primary analysis at 52 week will be approximately 37 months including 25 months of recruitment and 52-week Observation Period after dosing. Once all the subjects complete the 52 weeks Observation Period, the treatment groups will be unblinded and primary analysis performed. Study participation duration: The study will last 52 weeks from dosing, with another 4 years of long-term follow-up for a total of 5 years. During the 4 year long-term follow up sites will contact subjects twice a year for two years, then once a year for the remaining two years for safety, efficacy assessments, and survival

• Study Type: Interventional
• Enrollment (Estimated): 150
• Phase: Phase 2

Contacts and Locations

Study Locations

• Austria
  • Graz, Austria, 8010
    • Medizinische Universität Graz
  • Linz, Austria, 4021
    • Kardiologie & Intensivmedizin Campus III
  • Salzburg, Austria, 5020
    • SALK University Hospital
  • Sankt Pölten, Austria
    • NÖ Landesgesundheitsagentur
• Belgium
  • Edegem, Belgium, 2650
    • UZ Antwerpen
• Bulgaria
  • Pernik, Bulgaria, 2300
    • Multiprofile Hospital for Active Treatment Sveti Georgi OOD
  • Rousse, Bulgaria, 7013
    • Specialized Hospital For Active Cardiology Treatment Medica Kor EAD
  • Sandanski, Bulgaria, 2802
    • Multiprofile Hospital for Active Treatment "South West Hospital" OOD
  • Sofia, Bulgaria, 1606
    • University Multiprofile Hospital for Active Treatment and Emergency Medicine N. I. Pirogov EAD
  • Sofia, Bulgaria, 1407
    • Acibadem City Clinic University Multiprofile Hospital for Active Treatment Tokuda EAD
  • Sofia, Bulgaria, 1797
    • University Multiprofile Hospital for Active Treatment Sofiamed OOD
  • Sofia, Bulgaria, 1309
    • Multiprofile Hospital for Active Treatment 'National Cardiology Hospital' EAD
  • Sofia, Bulgaria, 1431
    • University Multiprofile Hospital for Active Treatment 'Sveta Ekaterina' EAD
• Canada
  • Manitoba
    • Winnipeg, Manitoba, Canada, R2H2A6
      • St. Boniface Hospital
  • Newfoundland and Labrador
    • St. John's, Newfoundland and Labrador, Canada, A1B3V6
      • Memorial University Hospital
  • Ontario
    • London, Ontario, Canada, N6A5A5
      • London Health Sciences Centre
    • Toronto, Ontario, Canada, M5B1W8
      • St. Michael's Hospital
  • Quebec
    • Chicoutimi, Quebec, Canada, G7H5H6
      • CIUSSS Saguenay Lac-St-Jean
    • Montreal, Quebec, Canada, H3T1E2
      • Jewish General Hospital
    • Montreal, Quebec, Canada, H1T1C8
      • Institut de Cardiologie de Montreal
    • Montreal, Quebec, Canada, H2X3E4
      • Centre Hospitalier de l'Université de Montréal - CHUM
    • Québec, Quebec, Canada, G1R2J6
      • CHU de Québec - Université Laval
    • Québec, Quebec, Canada, G1V4G5
      • Institut Universitaire de Cardiologie et de Pneumologie de Québec - IUCPQ
• Germany
  • Berlin, Germany, 15353
    • Charite Universitaetsmedizin
  • Freiburg im Breisgau, Germany, 79106
    • Universitaetsklinikum Freiburg | Herz-Zentrum Bad Krozingen (Heart Centre Bad Krozingen)
  • Hanover, Germany, 30625
    • Medizinische Hochschule Hannover (MHH)
  • Heidelberg, Germany, 69120
    • Heidelberg University Hospital
  • Kiel, Germany, D-24105
    • Universitätsklinikum Schleswig-Holstein
  • Bavaria
    • München, Bavaria, Germany, 81675
      • Technical University of Munich (TUM)
• Hungary
  • Budapest, Hungary, H-1145
    • Budapesti Uzsoki Utcai Korhaz
  • Budapest, Hungary, 1134
    • Észak-Pesti Centrumkórház - Honvédkórház
  • Budapest, Hungary, 1122
    • Semmelweis Egyetem, Varosmajori Sziv- és Ergyogyaszati Klinika
  • Kaposvár, Hungary, 7400
    • Somogy Varmegyei Kaposi Mor Oktato Korhaz - Kardiologiai Osztaly
  • Pécs, Hungary, 7624
    • Pecsi Tudomanyegyetem Klinikai Kozpont, Szivgyogyaszati Klinika
  • Szeged, Hungary, 6725
    • Szegedi Tudományegyetem, Szent-Györgyi Albert Klinikai Központ - Belgyógyászati Klinika
• Netherlands
  • Nijmegen, Netherlands, 9101
    • Radboud University Medical Center
  • Rotterdam, Netherlands, 3015CE
    • Erasmus Medisch Centrum
  • Utrecht, Netherlands, 3508GA
    • Universitair Medisch Centrum (UMC) Utrecht
  • North Holland
    • Amsterdam, North Holland, Netherlands, 1105 AZ
      • Amsterdam UMC - Locatie AMC (Academisch Medisch Centrum)
• Poland
  • Chrzanów, Poland, 32-500
    • American Heart of Poland S.A. - MCSN, PAKS w Chrzanowie
  • Lublin, Poland, 20-049
    • 1 Wojskowy Szpital Kliniczny Z Poliklinika SPZOZ W Lublinie
  • Lublin, Poland, 20-090
    • Uniwersytecki Szpital Kliniczny (USK) Nr 4 w Lublinie
• Romania
  • Brasov, Romania
    • Spitalul Clinic Judetean De Urgenta Brasov- Sectia Cardiologie 3
  • Bucharest, Romania
    • Spitalul Universitar de Urgenta Militar Central "Dr. Carol Davila", Sectia Clinica Cardiologie I
  • Craiova, Romania
    • Spitalul Clinic Judetean De Urgenta Craiova- Sectia de Cardiologie
  • Timișoara, Romania
    • Institutul De Boli Cardiovasculare Timisoara- Clinica de Cardiologie
  • Târgu Mureş, Romania
    • Spitalul Universitar de Urgenta Bucuresti- Sectia Cardiologie 2
  • County Mures
    • Târgu Mureş, County Mures, Romania
      • Spitalul Clinic Judetean de Urgenta Targu Mures
• Spain
  • Madrid, Spain, 28034
    • Hospital Ramon y Cajal | Cardiology - Research Unit
  • Madrid, Spain, 28046
    • Universidad Autonoma de Madrid (UAM) - Hospital Universitario La Paz (HULP)
  • Santiago de Compostela, Spain, 15706
    • Complejo Hospitalario Universitario Santiago de Compostela (CHUS)
  • Valencia, Spain, 46010
    • Hospital Clinico Universitario de Valencia (CHUV)
  • Catalonia
    • Barcelona, Catalonia, Spain, 8908
      • Hospital Universitario de Bellvitge
  • Navarre
    • Pamplona, Navarre, Spain, 31008
      • Universidad de Navarra - Clínica Universidad de Navarra (CUN)
• United Kingdom
  • Cardiff, United Kingdom, CF14 4XW
    • University Hospital of Wales
  • Glasgow, United Kingdom, G81 4DY
    • NHS Golden Jubilee
  • London, United Kingdom, SW3 6LY
    • Imperial College London - National Heart & Lung Institute (NHLI) - Royal Brompton Campus
  • Manchester
    • Manchester, Manchester, United Kingdom, M13 9WL
      • Manchester Royal Infirmary
  • West Yorkshire
    • Leeds, West Yorkshire, United Kingdom, LS1 3EX
      • Leeds General Infirmary
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35211
      • Cardiology P.C. Birmingham
  • Arizona
    • Tucson, Arizona, United States, 85724
      • University of Arizona Sarvor Heart Center
  • California
    • Irvine, California, United States, 92697
      • University of California Irvine Medical Center
    • La Jolla, California, United States, 92093
      • University Of California San Diego
    • San Francisco, California, United States, 94143
      • University of California San Francisco
  • Florida
    • Clearwater, Florida, United States, 33756
      • BayCare Medical Group
    • Coral Gables, Florida, United States, 33146
      • University of Miami
    • Gainesville, Florida, United States, 32610
      • University of Florida
  • Georgia
    • Augusta, Georgia, United States, 30912
      • Augusta University
  • Illinois
    • Oakbrook Terrace, Illinois, United States, 60181
      • Loyola Medicine Burr Ridge
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • University of Kansas Medical Center (KUMC)
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Brigham and Women's Hospital
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
  • Minnesota
    • Minneapolis, Minnesota, United States, 55407
      • Minneapolis Heart Institute Foundation
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic - Minnesota
  • Missouri
    • Kansas City, Missouri, United States, 64111
      • Aurora Saint Luke's Health System
    • St Louis, Missouri, United States, 63117
      • St. Louis University
  • Nevada
    • Reno, Nevada, United States, 89502
      • Renown Health
  • New Jersey
    • Morristown, New Jersey, United States, 07962
      • Morristown Medical Center - Cardiology
  • New York
    • New York, New York, United States, 10029
      • Mt. Sinai New York
    • Stony Brook, New York, United States, 11794
      • Stony Brook
    • The Bronx, New York, United States, 10461
      • Montefiore Medical Center
  • North Carolina
    • Durham, North Carolina, United States, 27705
      • Duke University
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • University of Cincinnati
    • Cincinnati, Ohio, United States, 45219
      • The Christ Hospital / The Linder Center for Research
    • Cleveland, Ohio, United States, 44109
      • MetroHealth Medical Center
    • Columbus, Ohio, United States, 43210
      • The Ohio State University
  • Pennsylvania
    • Allentown, Pennsylvania, United States, 18103
      • LVH Cardiology
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina (MUSC) Medical Center
  • Tennessee
    • Germantown, Tennessee, United States, 38138
      • Stern Cardiovascular
  • Texas
    • Dallas, Texas, United States, 75246
      • Baylor Scott & White Advanced Heart Failure Clinic - Dallas
    • Houston, Texas, United States, 77030
      • Houston Methodist Debakey Cardiology Associates
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine (BCM) - Baylor Heart Clinic
  • Washington
    • Seattle, Washington, United States, 98195
      • University of Washington
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • University of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion 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.

      May also receive aldosterone antagonist therapy. Doses of the above medications must be stable for ≥ 30 days prior to enrollment; and

   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

   Exclusion Criteria:

   Subjects are excluded from the study if any of the following criteria apply:

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Treatment Group 3; Randomized in 1:1:1 into one of three groups. Group 3: Placebo (n=30-50)	Drug: AB-1002; Intracoronary Infusion of AB-1002 or placebo; Other Names: Gene Therapy; NAN-101
Experimental: Treatment Group 1 AB-1002; Randomized in 1:1:1 into one of three groups. Group 1: 7.15E13vg/subject (n=30-50)	Drug: AB-1002; Intracoronary Infusion of AB-1002 or placebo; Other Names: Gene Therapy; NAN-101
Experimental: Treatment Group 2 AB-1002; Randomized in 1:1:1 into one of three groups. Group 2: 1.43E14vg/subject (n=30-50)	Drug: AB-1002; Intracoronary Infusion of AB-1002 or placebo; Other Names: Gene Therapy; NAN-101

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cardiovascular Related Death		52 weeks
NYHA Classification	NYHA Classification Change from baseline	52 weeks
Left Ventricular Ejection Fraction	LVEF change from baseline	52 weeks
Six Minute Walk Test	6MWT distance change from baseline	52 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Heart Failure Related Hospitalizations	Number of hospitalizations attributed to heart failure	52 weeks

Collaborators and Investigators

• Sponsor: AskBio Inc

Study record dates

Study Major Dates

• Study Start (Actual): October 20, 2023
• Primary Completion (Estimated): October 31, 2026
• Study Completion (Estimated): December 31, 2030

Study Registration Dates

• First Submitted: October 25, 2022
• First Submitted That Met QC Criteria: October 25, 2022
• First Posted (Actual): October 28, 2022

Study Record Updates

• Last Update Posted (Estimated): December 3, 2025
• Last Update Submitted That Met QC Criteria: November 26, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Heart Diseases; Heart Failure; Investigative Techniques; Therapeutics; Biological Therapy; Genetic Techniques; Genetic Engineering; Genetic Therapy
• Other Study ID Numbers: ASK-CHF2-CS201

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: No data will be shared with researchers outside of AskBio

Drug and device information, study documents

• 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.: No