Clinical trial NCT05598333: Phosphatase Inhibition by Intracoronary Gene Therapy in Subjects With Non-Ischemic NYHA Class III Heart Failure
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Congestive Heart Failure
Lead sponsor: AskBio Inc
Sponsor class: INDUSTRY
First posted: 2022-10-28
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Adaptive, double blinded, placebo controlled, randomized
Primary purpose: TREATMENT

Brief summary: 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

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

Eligibility criteria: 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

Primary outcomes:
measure: Cardiovascular Related Death
timeFrame: 52 weeks
measure: NYHA Classification
timeFrame: 52 weeks
measure: Left Ventricular Ejection Fraction
timeFrame: 52 weeks
measure: Peak Oxygen Update (VO2)
timeFrame: 52 weeks
measure: Six Minute Walk Test
timeFrame: 52 weeks
Secondary outcomes:
measure: Heart Failure Related Hospitalizations
timeFrame: 52 weeks
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Cardiology P.C. Birmingham
state: Alabama
city: La Jolla
country: United States
facility: University of California San Diego
state: California
city: Clearwater
country: United States
facility: Baycare Medical Group
state: Florida
city: Coral Gables
country: United States
facility: University of Miami
state: Florida
city: Gainesville
country: United States
facility: University of Florida
state: Florida
city: Augusta
country: United States
facility: Augusta University
state: Georgia
city: Oakbrook Terrace
country: United States
facility: Loyola Medicine Burr Ridge
state: Illinois
city: Iowa City
country: United States
facility: University of Iowa
state: Iowa
city: Kansas City
country: United States
facility: University of Kansas Medical Center (KUMC)
state: Kansas
city: Minneapolis
country: United States
facility: Minneapolis Heart Institute Foundation
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic - Minnesota
state: Minnesota
city: St. Louis
country: United States
facility: St. Louis University
state: Missouri
city: Reno
country: United States
facility: Renown Health
state: Nevada
city: New York
country: United States
facility: Mt. Sinai New York
state: New York
city: Stony Brook
country: United States
facility: Stony Brook
state: New York
city: Charlotte
country: United States
facility: Sanger Heart and Vascular Institute
state: North Carolina
city: Cincinnati
country: United States
facility: The Christ Hospital / The Linder Center for Research
state: Ohio
city: Cincinnati
country: United States
facility: University of Cincinnati
state: Ohio
city: Columbus
country: United States
facility: The Ohio State University
state: Ohio
city: Allentown
country: United States
facility: LVH Cardiology
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina (MUSC) Medical Center
state: South Carolina
city: Germantown
country: United States
facility: Stern Cardiovascular
state: Tennessee
city: Dallas
country: United States
facility: Baylor Scott & White Advanced Heart Failure Clinic - Dallas
state: Texas
city: Houston
country: United States
facility: Baylor College of Medicine (BCM) - Baylor Heart Clinic
state: Texas
city: Houston
country: United States
facility: Houston Methodist Debakey Cardiology Associates
state: Texas
city: Seattle
country: United States
facility: University of Washington
state: Washington
city: Madison
country: United States
facility: University of Wisconsin
state: Wisconsin
city: Graz
country: Austria
facility: Medizinische Universität Graz
city: Linz
country: Austria
facility: Kardiologie & Intensivmedizin Campus III
city: Salzburg
country: Austria
facility: SALK University Hospital
city: St.Pölten
country: Austria
facility: NÖ Landesgesundheitsagentur
city: Berlin
country: Germany
facility: Charité Universitaetsmedizin
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover (MHH)
city: Kiel
country: Germany
facility: Universitätsklinikum Schleswig-Holstein
city: Amsterdam
country: Netherlands
facility: Amsterdam UMC - Locatie AMC (Academisch Medisch Centrum)
state: North Holland
city: Nijmegen
country: Netherlands
facility: Radboud University Medical Center
city: Rotterdam
country: Netherlands
facility: Erasmus Medisch Centrum
city: Utrecht
country: Netherlands
facility: Universitair Medisch Centrum (UMC) Utrecht
city: Barcelona
country: Spain
facility: Hospital Universitario de Bellvitge
state: Catalogna
city: Pamplona
country: Spain
facility: Universidad de Navarra - Clinica Universidad de Navarra (CUN)
state: Navarra
city: Madrid
country: Spain
facility: Hospital Ramon y Cajal | Cardiology - Research Unit
city: Madrid
country: Spain
facility: Universidad Autonoma de Madrid (UAM) - Hospital Universitario La Paz (HULP)
city: Santiago De Compostela
country: Spain
facility: Complejo Hospitalario Universitario Santiago de Compostela (CHUS)
city: Valencia
country: Spain
facility: Hospital Clinico Universitario de Valencia (CHUV)
city: London
country: United Kingdom
facility: Imperial College London - National Heart & Lung Institute (NHLI) - Royal Brompton Campus
city: Manchester
country: United Kingdom
facility: Manchester Royal Infirmary
Study officials:
References: