YAP101 Gene Therapy for Heart Failure

(SALVADOR-HF Trial)

Overseen By Director of Operations

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: YAP Therapeutics, Inc.

Must be taking: Guideline directed therapy

Must not be taking: Anticoagulants, Immunosuppressants

Disqualifiers: Valvular disease, Recent stroke, Diabetes, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 1

Duration: 1 day

24 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial requires participants to be on stable, maximally tolerated guideline-directed medical therapy for heart failure for at least 6 weeks before joining. This suggests you should continue your current heart failure medications unless advised otherwise by the study team.

What data supports the effectiveness of the YAP101 treatment for heart failure?

Research shows that targeting YAP, a protein involved in heart cell survival and growth, can help reduce heart damage and improve heart function after injury. This suggests that YAP101, which likely involves YAP, could be effective in treating heart failure by promoting heart cell survival and reducing harmful changes in the heart. ^{1 2 3 4 5}

What safety data exists for YAP101 gene therapy in humans?

Research on YAP (Yes-associated protein) suggests it plays a role in heart health, but its activation can lead to increased inflammation and fibrosis (thickening and scarring of tissue) in the heart. While YAP is important for heart cell survival and growth, its overexpression in certain heart cells can cause negative effects, indicating that careful control is needed for safety. ^{4 5 6 7 8}

How does the YAP101 treatment for heart failure differ from other treatments?

YAP101 gene therapy is unique because it targets the Yes-associated protein (YAP) to prevent fibrotic remodeling and heart failure by inhibiting fibroblast activity, which is not addressed by standard heart failure treatments. This approach focuses on reducing fibrosis and promoting cardiomyocyte survival, offering a novel mechanism compared to traditional therapies that primarily manage symptoms. ^{1 3 4 5 6}

Research Team

Alexander Postalian, MD

Principal Investigator

Texas Heart Institute

Eligibility Criteria

Adults aged 18-80 with stable heart failure due to a past heart attack, showing specific symptoms for at least a year, and having certain levels of heart pumping function can join. They must be on steady heart failure medication for 6 weeks and not eligible for other heart procedures. Candidates should have adequate heart wall thickness, be able to undergo catheterization, agree to use contraception, and provide consent.

Inclusion Criteria

My heart's left ventricle wall is thick enough for an injection.

I agree to follow the study's rules for birth control.

I have signed a consent form.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a one-time transendocardial injection of YAP101 at one of three dose levels using an investigational cardiac injection catheter

1 day

1 visit (in-person)

Monitoring

Participants are monitored for safety and functional outcomes through a series of outpatient visits

12 months

Multiple visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Long-term follow-up (optional)

Participants have the option to enroll in a long-term follow-up study for up to 5 years

Up to 5 years

Treatment Details

Interventions

• YAP101

Trial Overview The trial is testing YAP101 gene therapy in adults with ischemic heart failure. It's delivered once through a cardiac injection aiming to regenerate the damaged part of the heart muscle. The study will track safety and improvements in how well the participants' hearts work, their ability to exercise, and overall life quality over one year.

Participant Groups

Group I: Cohort 4 (Dose Level Expansion): Dose level TBD Experimental Treatment 1 Intervention

Up to 6 subjects

Group II: Cohort 3: 5e13 vg YAP101 Experimental Treatment 1 Intervention

3 to 6 subjects

Group III: Cohort 2: 1e13 vg YAP101 Experimental Treatment 1 Intervention

3 to 6 subjects

Group IV: Cohort 1: 5e12 vg YAP101 Experimental Treatment 1 Intervention

3 to 6 subjects

Who Is Running the Clinical Trial?

YAP Therapeutics, Inc.

Lead Sponsor

Trials

1

Recruited

20+

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Genetic and Pharmacological YAP Activation Induces Proliferation and Improves Survival in Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes. [2023]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Yes-Associated Protein (Yap) Is Up-Regulated in Heart Failure and Promotes Cardiac Fibroblast Proliferation. [2021]

3. United States pubmed.ncbi.nlm.nih.gov

Blockade of Fibroblast YAP Attenuates Cardiac Fibrosis and Dysfunction Through MRTF-A Inhibition. [2021]

4. United States pubmed.ncbi.nlm.nih.gov

Yes-associated protein isoform 1 (Yap1) promotes cardiomyocyte survival and growth to protect against myocardial ischemic injury. [2021]

5. England pubmed.ncbi.nlm.nih.gov

AAV-mediated YAP expression in cardiac fibroblasts promotes inflammation and increases fibrosis. [2021]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Yes-Associated Protein and Transcriptional Coactivator with PDZ-Binding Motif in Cardiovascular Diseases. [2023]

7. Netherlands pubmed.ncbi.nlm.nih.gov

Activation of Yap1/Taz signaling in ischemic heart disease and dilated cardiomyopathy. [2021]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Yes-associated protein and transcriptional coactivator with PDZ-binding motif as new targets in cardiovascular diseases. [2021]