Heart Failure With Reduced Ejection FractionPhase 1SALVADOR-HFNCT06831825
Study Assessing Left Ventricular Administration of a Genetic Medicine Directing Organ Regeneration in Heart Failure
A Phase 1 study testing YAP101 (AAV9-Sav-shRNA) in people with Heart Failure With Reduced Ejection Fraction, run by Medley Therapeutics at 1 site in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 to 79 years
- Conditions the study is for
- Heart Failure With Reduced Ejection Fraction
- What is being tested?
- YAP101 (AAV9-Sav-shRNA)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 1 siteUnited States
- Study dates
- 23 Apr 2025to Jun 2027
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 79 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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;
Show all 10Show fewer
- 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.
Who cannot join
- 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;
Show all 36Show fewer
- 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;
- A contrast allergy that cannot adequately be managed by premedication;
- Received cell-based therapy from any source;
- Received any viral vector mediated gene therapy;
- Evidence of active systemic infection at time of study product delivery;
- HIV and/or active HBV, HCV or Covid-19 infection at screening or baseline;
- Presence of LV thrombus;
- Presence of a pacemaker or ICD generator with any of the following limitations/conditions:
- manufactured before the year 2000
- leads implanted < 6 weeks prior to screening
- non-transvenous epicardial leads
- subcutaneous ICDs
- any other condition that, in the judgment of device-trained staff, would deem an MRI contraindicated;
- A cardiac resynchronization therapy (CRT) device implanted < 3 months prior to consent;
- Other MRI contraindications
- Mobitz II or higher degree atrioventricular block without a functioning pacemaker within 3 months of consent;
- 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;
- Cognitive or language barriers that prohibit obtaining informed consent or any study elements;
- Participation (currently or within the previous 30 days) in a cardiac related investigational therapeutic (including stem cell and gene-based therapies) or device trial;
- Pregnancy, lactation, plans to become pregnant in the next 12 months, or is unwilling to use acceptable forms of birth control during study participation;
- Expected survival < 1 year in the judgment of the investigator;
- 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);
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Texas Heart Institute
Houston, Texas, 77030
Clinical Research Operations Specialist, 832-355-9614, gphillip@texasheart.org
Center for Clinical Research, 832-355-9405, clinicalresearch@texasheart.org
About this study
Official title: A Phase I Study of Safety and Preliminary Efficacy of YAP101 in Subjects With Ischemic Heart Failure and Reduced Ejection Fraction
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.
Read the detailed description
This Phase I, single-center, open-label, dose-escalation trial evaluates the safety, tolerability, and preliminary efficacy of YAP101 in adults with ischemic heart failure and reduced ejection fraction (HFrEF). YAP101, a novel gene therapy, delivers adeno-associated virus with a cardiomyocyte-specific promoter to express short hairpin RNAs (shRNAs) targeting Salvador 1 (SAV1), a key regulator of the Hippo signaling pathway. By transiently suppressing this pathway, YAP101 aims to induce cardiomyocyte regeneration, reduce fibrosis, and improve myocardial function.
Eligible subjects will undergo a one-time transendocardial injection of YAP101 at one of three dose levels (5.0e12, 1.0e13, or 5.0e13 viral genomes/subject) using an investigational cardiac injection catheter. Following administration, subjects will be monitored for safety and functional outcomes through a series of outpatient visits over 12 months. Primary endpoints include the incidence of dose-limiting toxicities, adverse events, and the determination of the maximum tolerated dose (MTD). Secondary endpoints include changes in cardiac function assessed via MRI, biomarkers, exercise tolerance, and quality of life metrics.
Safety will be overseen by an independent Safety Review Team (SRT), which will assess data before dose escalation. The study employs a 3+3 dose-escalation design to identify the MTD while minimizing risks. Subjects who complete the study will have the option to enroll in a long-term follow-up study for up to 5 years.
The trial addresses the significant unmet need for regenerative therapies in heart failure, leveraging preclinical evidence of efficacy and safety. YAP101 has shown promising results in animal models, improving cardiac function, reducing fibrosis, and enhancing myocardial repair without significant adverse effects.
- Being tested
- YAP101 (AAV9-Sav-shRNA)
- 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
- Medical subject headings
- Heart Failure
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
YAP101 (AAV9-Sav-shRNA)Combination product
YAP101 delivered using YAPCATH-101
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1: 5e12 vg YAP101 | Experimental | 3 to 6 subjects Receives: Combination Product: YAP101 (AAV9-Sav-shRNA) |
| Cohort 2: 1e13 vg YAP101 | Experimental | 3 to 6 subjects Receives: Combination Product: YAP101 (AAV9-Sav-shRNA) |
| Cohort 3: 5e13 vg YAP101 | Experimental | 3 to 6 subjects Receives: Combination Product: YAP101 (AAV9-Sav-shRNA) |
| Cohort 4 (Dose Level Expansion): Dose level TBD | Experimental | Up to 6 subjects Receives: Combination Product: YAP101 (AAV9-Sav-shRNA) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of the following: DLTs and AEs
Incidence of dose limiting toxicities and adverse events
Measured: 12 months
Maximum tolerated dose
Maximum tolerated dose
Measured: 12 months
Secondary outcomes (20)
Exercise tolerance by six minute walk test (6MWT)
6MWT distance change from baseline in meters
Measured: 12 months
New York Heart Association (NYHA) Classification
NYHA Classification change from baseline (lower values indicate less severe disease, scale from class I to class IV)
Measured: 12 months
Major Adverse Cardiac Events (MACE), including death, MI, revascularization with or without stroke, MACCE
Incidence
Measured: 12 months
Hospitalization for HF and/ or other exacerbation of HF (non-hospitalization)
Incidence
Measured: 12 months
Cumulative days alive and out of the hospital
Days and total days out-of-hospital as a % of total days alive post study intervention
Measured: 12 months
LVEF by cardiac MRI
Change from baseline, %
Measured: 12 months
LVEFI by cardiac MRI
Change from baseline, % per kg
Measured: 12 months
LVEDV by cardiac MRI
Change from baseline, mL
Measured: 12 months
LVEDVI by cardiac MRI
Change from baseline, mL per kg
Measured: 12 months
LVESV by cardiac MRI
Change from baseline, mL
Measured: 12 months
LVESVI by cardiac MRI
Change from baseline, mL per kg
Measured: 12 months
Premature ventricular contraction (PVC) burden
Change from baseline, %
Measured: 12 months
Atrial fibrillation (AFib) burden
Change from baseline, %
Measured: 12 months
BNP (cardiac biomarker)
Change from baseline, %
Measured: 12 months
NT-proBNP (cardiac biomarker)
Change from baseline, %
Measured: 12 months
Health related quality of life as assessed by Minnesota Living with Heart Failure Questionnaire (MLHF)
Change in Score from baseline (lower values indicate higher quality of life, scale from 0-105)
Measured: 12 months
Survival
Days
Measured: 12 months
Cardiac transplant
Incidence
Measured: 12 months
Left ventricular assist device (LVAD) implantation
Incidence
Measured: 12 months
Anti-AAV9 capsid antibodies
Change in titer from baseline
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Feb 2025
- Study start23 Apr 2025
- Primary completionDec 2026 (estimated)
- Study completionJun 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Heart Failure With Reduced Ejection FractionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 24 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Medley Therapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Alexander Postalian, MD, Principal investigator, Texas Heart Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06831825
- Sponsor's protocol ID
- YAP101-C001
- Acronym
- SALVADOR-HF
- Status last verified
- Apr 2025
- First submitted
- 23 Jan 2025
- Last updated
- 27 Apr 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Apr 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Study of Safety and Preliminary Efficacy of YAP101 in Subjects With Ischemic Heart Failure and Reduced Ejection Fraction
- ClinicalTrials.gov ID
- NCT06831825
- Acronym / sponsor ID
- SALVADOR-HF / YAP101-C001
- Keywords
- YAP101, YAP Therapeutics, YAPtx, AAV, Regenerative medicine, Cardiac regeneration, heart regeneration, gene therapy
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 24 participants (estimated)
- Lead sponsor
- Medley TherapeuticsIndustry (pharma, biotech, devices)
- Study start
- 23 Apr 2025 (actual)
- Primary completion
- Dec 2026 (estimated)
- Study completion
- Jun 2027 (estimated)
- First posted
- 18 Feb 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
This Phase I, single-center, open-label, dose-escalation trial evaluates the safety, tolerability, and preliminary efficacy of YAP101 in adults with ischemic heart failure and reduced ejection fraction (HFrEF). YAP101, a novel gene therapy, delivers adeno-associated virus with a cardiomyocyte-specific promoter to express short hairpin RNAs (shRNAs) targeting Salvador 1 (SAV1), a key regulator of the Hippo signaling pathway. By transiently suppressing this pathway, YAP101 aims to induce cardiomyocyte regeneration, reduce fibrosis, and improve myocardial function.
Eligible subjects will undergo a one-time transendocardial injection of YAP101 at one of three dose levels (5.0e12, 1.0e13, or 5.0e13 viral genomes/subject) using an investigational cardiac injection catheter. Following administration, subjects will be monitored for safety and functional outcomes through a series of outpatient visits over 12 months. Primary endpoints include the incidence of dose-limiting toxicities, adverse events, and the determination of the maximum tolerated dose (MTD). Secondary endpoints include changes in cardiac function assessed via MRI, biomarkers, exercise tolerance, and quality of life metrics.
Safety will be overseen by an independent Safety Review Team (SRT), which will assess data before dose escalation. The study employs a 3+3 dose-escalation design to identify the MTD while minimizing risks. Subjects who complete the study will have the option to enroll in a long-term follow-up study for up to 5 years.
The trial addresses the significant unmet need for regenerative therapies in heart failure, leveraging preclinical evidence of efficacy and safety. YAP101 has shown promising results in animal models, improving cardiac function, reducing fibrosis, and enhancing myocardial repair without significant adverse effects.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Cohort 1: 5e12 vg YAP101 | Experimental | Combination Product: YAP101 (AAV9-Sav-shRNA)3 to 6 subjects |
| Cohort 2: 1e13 vg YAP101 | Experimental | Combination Product: YAP101 (AAV9-Sav-shRNA)3 to 6 subjects |
| Cohort 3: 5e13 vg YAP101 | Experimental | Combination Product: YAP101 (AAV9-Sav-shRNA)3 to 6 subjects |
| Cohort 4 (Dose Level Expansion): Dose level TBD | Experimental | Combination Product: YAP101 (AAV9-Sav-shRNA)Up to 6 subjects |
Who may qualify
- Ages
- 18 to 79 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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;
Key exclusion criteria (36 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| YAP101 (AAV9-Sav-shRNA)YAP101 delivered using YAPCATH-101 | Combination product | Cohort 1: 5e12 vg YAP101, Cohort 2: 1e13 vg YAP101, Cohort 3: 5e13 vg YAP101, Cohort 4 (Dose Level Expansion): Dose level TBD |
Primary outcome
Incidence of the following: DLTs and AEs
Time frame: 12 months
Incidence of dose limiting toxicities and adverse events
Maximum tolerated dose
Time frame: 12 months
Maximum tolerated dose
20 secondary outcomes
Exercise tolerance by six minute walk test (6MWT)
Time frame: 12 months
New York Heart Association (NYHA) Classification
Time frame: 12 months
Major Adverse Cardiac Events (MACE), including death, MI, revascularization with or without stroke, MACCE
Time frame: 12 months
Hospitalization for HF and/ or other exacerbation of HF (non-hospitalization)
Time frame: 12 months
Cumulative days alive and out of the hospital
Time frame: 12 months
LVEF by cardiac MRI
Time frame: 12 months
LVEFI by cardiac MRI
Time frame: 12 months
LVEDV by cardiac MRI
Time frame: 12 months
LVEDVI by cardiac MRI
Time frame: 12 months
LVESV by cardiac MRI
Time frame: 12 months
LVESVI by cardiac MRI
Time frame: 12 months
Premature ventricular contraction (PVC) burden
Time frame: 12 months
Atrial fibrillation (AFib) burden
Time frame: 12 months
BNP (cardiac biomarker)
Time frame: 12 months
NT-proBNP (cardiac biomarker)
Time frame: 12 months
Health related quality of life as assessed by Minnesota Living with Heart Failure Questionnaire (MLHF)
Time frame: 12 months
Survival
Time frame: 12 months
Cardiac transplant
Time frame: 12 months
Left ventricular assist device (LVAD) implantation
Time frame: 12 months
Anti-AAV9 capsid antibodies
Time frame: 12 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Apr 2025.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Alexander Postalian, MD principal investigator
Texas Heart Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing YAP101 (AAV9-Sav-shRNA) in people with Heart Failure With Reduced Ejection Fraction, run by Medley Therapeutics at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 36 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 27 Apr 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Tyler H Kibbee, MBS (713-609-1928 ext. 901, info@yaptx.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of the following: DLTs and AEs (time frame: 12 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Apr 2025.