Gene therapy to improve heart function in heart failure patients
A Phase I Study of Safety and Preliminary Efficacy of YAP101 in Subjects With Ischemic Heart Failure and Reduced Ejection Fraction
This study is testing a new gene therapy called YAP101 to see if it can help improve heart function in adults with heart failure.
Quick facts
| Phase | Phase 1 |
|---|---|
| Study type | Interventional |
| Enrollment | 24 (estimated) |
| Ages | 18 Years to 79 Years |
| Sex | All |
| Sponsor | YAP Therapeutics, Inc. Industry-sponsored |
| Locations | 1 site (Houston, Texas) |
| Trial ID | NCT06831825 on ClinicalTrials.gov |
What this trial studies
This clinical trial evaluates the safety and preliminary effectiveness of YAP101, a gene therapy aimed at enhancing heart function in adults suffering from ischemic heart failure with reduced ejection fraction (HFrEF). The therapy utilizes a specialized vector to deliver genetic material to heart cells, targeting pathways that promote heart repair and regeneration. Participants will receive a one-time injection of YAP101 and will be monitored over 12 months for safety and improvements in heart function, exercise capacity, and quality of life.
Who should consider this trial
Good fit: Ideal candidates are adults aged 18 to 80 with ischemic heart failure and reduced ejection fraction who are not candidates for surgical interventions.
Not a fit: Patients with heart failure due to non-ischemic causes or those who are candidates for surgical interventions may not benefit from this study.
Why it matters
Potential benefit: If successful, this therapy could significantly improve heart function and quality of life for patients with heart failure.
How similar studies have performed: While gene therapies for heart conditions are being explored, this specific approach using YAP101 is novel and has not been extensively tested in prior studies.
Eligibility criteria
Show full inclusion / exclusion criteria
Inclusion Criteria:
To participate, a subject MUST:
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.
Exclusion Criteria:
To participate, a subject MUST NOT HAVE:
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);
Where this trial is running
Houston, Texas
- Texas Heart Institute — Houston, Texas, United States (Recruiting)
Study contacts
- Principal investigator: Alexander Postalian, MD — Texas Heart Institute
- Study coordinator: Tyler H Kibbee, MBS
- Email: info@yaptx.com
- Phone: 713-609-1928
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.