RECRUITING

Study Assessing Left Ventricular Administration of a Genetic Medicine Directing Organ Regeneration in Heart Failure

Conditions

Heart Failure With Reduced Ejection Fraction YAP101 YAP Therapeutics YAPtx AAV Regenerative medicine Cardiac regeneration heart regeneration gene therapy shRNA gene silencing tissue renewal cardiac repair heart failure HFrEF HF NYHA

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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 clinical trial investigates the safety and preliminary effectiveness of YAP101, a gene therapy designed to improve heart function in adults with ischemic heart failure and reduced ejection fraction (HFrEF). Ischemic heart failure, often resulting from a prior heart attack, leads to poor heart function and quality of life. Current treatments are limited, and there is an urgent need for new therapies. YAP101 works by delivering a gene therapy using a specialized vector to heart cells, targeting a pathway involved in heart repair. By temporarily activating heart muscle regeneration, YAP101 aims to restore damaged tissue, reduce scarring, and improve the heart's pumping ability. The study will enroll participants who will receive a one-time dose of YAP101 via a minimally invasive cardiac injection. Researchers will monitor participants over 12 months to assess safety and changes in heart function, exercise tolerance, and quality of life.

Official Title

A Phase I Study of Safety and Preliminary Efficacy of YAP101 in Subjects With Ischemic Heart Failure and Reduced Ejection Fraction

Quick Facts

Study Start:2025-04-23

Study Completion:2027-06

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT06831825

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 to 79 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
1. Be ≥ 18 and \< 80 years of age; 2. Have medically stable heart failure of ischemic etiology, secondary to MI with NYHA class II or III symptoms for at least 12 months before the initiation of screening procedures; 3. Have a left ventricular ejection fraction (LVEF) ≥ 20% and ≤ 40% by cMRI at screening and baseline; 4. The subject is not a candidate for either percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG) surgery as determined by the principal investigator (or designee) in consultation with an interventional cardiologist during the screening period; 5. Be on stable, outpatient, maximally tolerated guideline directed medical therapy (GDMT) for HF for 6 weeks, unless contraindicated, and remain stable during the screening period; 6. Left ventricular (LV) end diastolic wall thickness of at least 8mm at the potential myocardial site for injection; 7. Be a candidate for cardiac catheterization; 8. Agree to protocol defined requirements for contraception; 9. Provide written informed consent.	1. Valvular heart disease including 1) mechanical or bioprosthetic heart valve; or 2) severe valvular (any valve) insufficiency/regurgitation within 12 months of consent; 2. Aortic stenosis with valve area ≤ 1.5cm2; 3. Prior heart transplant, history of LV reduction surgery, cardiomyoplasty, passive restraint device 4. Had an acute myocardial infarction within the prior 30 days before initiation of screening; 5. Unstable angina pectoris within 30 days before initiation of screening procedures; 6. Idiopathic, valvular, peri/post-partum cardiomyopathy or other cardiomyopathy of non-ischemic etiology; 7. Restrictive, obstructive, or infiltrative cardiomyopathy; pericardial constriction; amyloidosis; or uncorrected thyroid disease; 8. A history of ischemic or hemorrhagic stroke within 90 days of screening; 9. Liver dysfunction, as evidenced by enzymes (e.g., AST, ALT, alkaline phosphatase) greater than 3 times upper limit of normal; 10. A baseline eGFR \<35 mL/min/1.73m2; 11. Diabetes with poorly controlled blood glucose levels (HbA1c \> 10%); 12. A hematologic abnormality during baseline testing; 13. Coagulopathy (INR \> 1.5) not due to a reversible cause (e.g., warfarin and/or Factor Xa inhibitors); Subjects who cannot be withdrawn from anticoagulation will be excluded; 14. An underlying autoimmune disorder or current immunosuppressive therapy; 15. A contrast allergy that cannot adequately be managed by premedication; 16. Received cell-based therapy from any source; 17. Received any viral vector mediated gene therapy; 18. Evidence of active systemic infection at time of study product delivery; 19. HIV and/or active HBV, HCV or Covid-19 infection at screening or baseline; 20. Presence of LV thrombus; 21. Presence of a pacemaker or ICD generator with any of the following limitations/conditions: 1. manufactured before the year 2000 2. leads implanted \< 6 weeks prior to screening 3. non-transvenous epicardial leads 4. subcutaneous ICDs 5. any other condition that, in the judgment of device-trained staff, would deem an MRI contraindicated; 22. A cardiac resynchronization therapy (CRT) device implanted \< 3 months prior to consent; 23. Other MRI contraindications 24. Mobitz II or higher degree atrioventricular block without a functioning pacemaker within 3 months of consent; 25. A history of drug abuse or alcohol abuse, or documented medical, occupational, or legal problems arising from the use of alcohol or drugs within the past 24 months; 26. Cognitive or language barriers that prohibit obtaining informed consent or any study elements; 27. Participation (currently or within the previous 30 days) in a cardiac related investigational therapeutic (including stem cell and gene-based therapies) or device trial; 28. Pregnancy, lactation, plans to become pregnant in the next 12 months, or is unwilling to use acceptable forms of birth control during study participation; 29. Expected survival \< 1 year in the judgment of the investigator; 30. Active malignancy within the past 3 years (exceptions: localized prostate cancer, cervical or breast cancer in situ, or nonmelanoma skin cancer that has been definitively treated);

Inclusion Criteria

Exclusion Criteria

1. Be ≥ 18 and \< 80 years of age;
2. Have medically stable heart failure of ischemic etiology, secondary to MI with NYHA class II or III symptoms for at least 12 months before the initiation of screening procedures;
3. Have a left ventricular ejection fraction (LVEF) ≥ 20% and ≤ 40% by cMRI at screening and baseline;
4. The subject is not a candidate for either percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG) surgery as determined by the principal investigator (or designee) in consultation with an interventional cardiologist during the screening period;
5. Be on stable, outpatient, maximally tolerated guideline directed medical therapy (GDMT) for HF for 6 weeks, unless contraindicated, and remain stable during the screening period;
6. Left ventricular (LV) end diastolic wall thickness of at least 8mm at the potential myocardial site for injection;
7. Be a candidate for cardiac catheterization;
8. Agree to protocol defined requirements for contraception;
9. Provide written informed consent.

1. Valvular heart disease including 1) mechanical or bioprosthetic heart valve; or 2) severe valvular (any valve) insufficiency/regurgitation within 12 months of consent;
2. Aortic stenosis with valve area ≤ 1.5cm2;
3. Prior heart transplant, history of LV reduction surgery, cardiomyoplasty, passive restraint device
4. Had an acute myocardial infarction within the prior 30 days before initiation of screening;
5. Unstable angina pectoris within 30 days before initiation of screening procedures;
6. Idiopathic, valvular, peri/post-partum cardiomyopathy or other cardiomyopathy of non-ischemic etiology;
7. Restrictive, obstructive, or infiltrative cardiomyopathy; pericardial constriction; amyloidosis; or uncorrected thyroid disease;
8. A history of ischemic or hemorrhagic stroke within 90 days of screening;
9. Liver dysfunction, as evidenced by enzymes (e.g., AST, ALT, alkaline phosphatase) greater than 3 times upper limit of normal;
10. A baseline eGFR \<35 mL/min/1.73m2;
11. Diabetes with poorly controlled blood glucose levels (HbA1c \> 10%);
12. A hematologic abnormality during baseline testing;
13. Coagulopathy (INR \> 1.5) not due to a reversible cause (e.g., warfarin and/or Factor Xa inhibitors); Subjects who cannot be withdrawn from anticoagulation will be excluded;
14. An underlying autoimmune disorder or current immunosuppressive therapy;
15. A contrast allergy that cannot adequately be managed by premedication;
16. Received cell-based therapy from any source;
17. Received any viral vector mediated gene therapy;
18. Evidence of active systemic infection at time of study product delivery;
19. HIV and/or active HBV, HCV or Covid-19 infection at screening or baseline;
20. Presence of LV thrombus;
21. Presence of a pacemaker or ICD generator with any of the following limitations/conditions:
1. manufactured before the year 2000
2. leads implanted \< 6 weeks prior to screening
3. non-transvenous epicardial leads
4. subcutaneous ICDs
5. any other condition that, in the judgment of device-trained staff, would deem an MRI contraindicated;
22. A cardiac resynchronization therapy (CRT) device implanted \< 3 months prior to consent;
23. Other MRI contraindications
24. Mobitz II or higher degree atrioventricular block without a functioning pacemaker within 3 months of consent;
25. A history of drug abuse or alcohol abuse, or documented medical, occupational, or legal problems arising from the use of alcohol or drugs within the past 24 months;
26. Cognitive or language barriers that prohibit obtaining informed consent or any study elements;
27. Participation (currently or within the previous 30 days) in a cardiac related investigational therapeutic (including stem cell and gene-based therapies) or device trial;
28. Pregnancy, lactation, plans to become pregnant in the next 12 months, or is unwilling to use acceptable forms of birth control during study participation;
29. Expected survival \< 1 year in the judgment of the investigator;
30. Active malignancy within the past 3 years (exceptions: localized prostate cancer, cervical or breast cancer in situ, or nonmelanoma skin cancer that has been definitively treated);

Contacts and Locations

Study Contact

Tyler H Kibbee, MBS

CONTACT

713-609-1928

info@yaptx.com

Director of Operations

CONTACT

949-348-1188

kapgar@yaptx.com

Principal Investigator

Alexander Postalian, MD

PRINCIPAL_INVESTIGATOR

Texas Heart Institute

Study Locations (Sites)

Texas Heart Institute

Houston, Texas, 77030

United States

Collaborators and Investigators

Sponsor: YAP Therapeutics, Inc.

Alexander Postalian, MD, PRINCIPAL_INVESTIGATOR, Texas Heart Institute

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 Date2025-04-23

Study Completion Date2027-06

Study Record Updates

Study Start Date2025-04-23

Study Completion Date2027-06

Terms related to this study

Keywords Provided by Researchers

YAP101
YAP Therapeutics
YAPtx
AAV
Regenerative medicine
Cardiac regeneration
heart regeneration
gene therapy
shRNA
gene silencing
tissue renewal
cardiac repair
heart failure
HFrEF
HF
Heart failure with reduced ejection fraction
NYHA

Additional Relevant MeSH Terms

Heart Failure With Reduced Ejection Fraction