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

NCT06831825 | Recruiting Phase 1 DMC FDA Drug FDA Device

• 1 other identifier: YAP101-C001
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Heart Failure With Reduced Ejection Fraction

Keywords

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

Outcome Measures

Primary Outcomes (2)

• Incidence of the following: DLTs and AEs

  Incidence of dose limiting toxicities and adverse events

  12 months

• Maximum tolerated dose

  Maximum tolerated dose

  12 months

Secondary Outcomes (20)

• Exercise tolerance by six minute walk test (6MWT)

  12 months

• New York Heart Association (NYHA) Classification

  12 months

• Major Adverse Cardiac Events (MACE), including death, MI, revascularization with or without stroke, MACCE

  12 months

• Hospitalization for HF and/ or other exacerbation of HF (non-hospitalization)

  12 months

• Cumulative days alive and out of the hospital

  12 months

Study Arms (4)

Cohort 1: 5e12 vg YAP101

EXPERIMENTAL

3 to 6 subjects

Combination Product: YAP101 (AAV9-Sav-shRNA)

Cohort 2: 1e13 vg YAP101

EXPERIMENTAL

3 to 6 subjects

Combination Product: YAP101 (AAV9-Sav-shRNA)

Cohort 3: 5e13 vg YAP101

EXPERIMENTAL

3 to 6 subjects

Combination Product: YAP101 (AAV9-Sav-shRNA)

Cohort 4 (Dose Level Expansion): Dose level TBD

EXPERIMENTAL

Up to 6 subjects

Combination Product: YAP101 (AAV9-Sav-shRNA)

Interventions

YAP101 (AAV9-Sav-shRNA) COMBINATION_PRODUCT

YAP101 delivered using YAPCATH-101

Cohort 1: 5e12 vg YAP101; Cohort 2: 1e13 vg YAP101; Cohort 3: 5e13 vg YAP101; Cohort 4 (Dose Level Expansion): Dose level TBD

Eligibility Criteria

• Age: 18 Years - 79 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• To participate, a subject MUST:
• Be ≥ 18 and \< 80 years of age;
• 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;
• Have a left ventricular ejection fraction (LVEF) ≥ 20% and ≤ 40% by cMRI at screening and baseline;
• 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;
• 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;
• Left ventricular (LV) end diastolic wall thickness of at least 8mm at the potential myocardial site for injection;
• Be a candidate for cardiac catheterization;
• Agree to protocol defined requirements for contraception;
• Provide written informed consent.

You may not qualify if:

• To participate, a subject MUST NOT HAVE:
• Valvular heart disease including 1) mechanical or bioprosthetic heart valve; or 2) severe valvular (any valve) insufficiency/regurgitation within 12 months of consent;
• Aortic stenosis with valve area ≤ 1.5cm2;
• Prior heart transplant, history of LV reduction surgery, cardiomyoplasty, passive restraint device
• Had an acute myocardial infarction within the prior 30 days before initiation of screening;
• Unstable angina pectoris within 30 days before initiation of screening procedures;
• Idiopathic, valvular, peri/post-partum cardiomyopathy or other cardiomyopathy of non-ischemic etiology;
• Restrictive, obstructive, or infiltrative cardiomyopathy; pericardial constriction; amyloidosis; or uncorrected thyroid disease;
• A history of ischemic or hemorrhagic stroke within 90 days of screening;
• Liver dysfunction, as evidenced by enzymes (e.g., AST, ALT, alkaline phosphatase) greater than 3 times upper limit of normal;
• A baseline eGFR \<35 mL/min/1.73m2;
• Diabetes with poorly controlled blood glucose levels (HbA1c \> 10%);
• A hematologic abnormality during baseline testing;
• 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;
• An underlying autoimmune disorder or current immunosuppressive therapy;

Sponsors & Collaborators

• YAP Therapeutics, Inc.: lead

Study Sites (1)

Texas Heart Institute

Houston, Texas, 77030, United States

RECRUITING

MeSH Terms

Conditions

Heart Failure

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Study Officials

• Alexander Postalian, MD

  Texas Heart Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Tyler H Kibbee, MBS

CONTACT

713-609-1928; info@yaptx.com

Director of Operations

CONTACT

949-348-1188; kapgar@yaptx.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 23, 2025
• First Posted: February 18, 2025
• Study Start: April 23, 2025
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): June 1, 2027
• Last Updated: April 27, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)