Cell therapy using human embryonic stem cells for heart dysfunction

A Phase I, Randomized Pilot Study of Human Embryonic Stem Cell-Derived Cardiomyocytes (hESC-CMs) in PaTients With ChrOnic Ischemic Left VentRicular Dysfunction Secondary to Myocardial Infarction (HECTOR)

This study is testing if using heart cells made from human embryonic stem cells can help people with heart problems after a heart attack feel better.

Quick facts

• Phase: PHASE1
• Study type: Interventional
• Enrollment: 18 (estimated)
• Ages: 21 Years to 80 Years
• Sex: All
• Sponsor: Stanford University (other)
• Locations: 1 site (Palo Alto, California)
• Trial ID: NCT05068674 on ClinicalTrials.gov

What this trial studies

This clinical study aims to evaluate the safety and efficacy of human embryonic stem cell-derived cardiomyocytes (hESC-CMs) in improving cardiac function in patients with chronic ischemic left ventricular dysfunction following a myocardial infarction. It is a phase I dose-escalation pilot study that will enroll approximately eighteen patients who are candidates for cardiac catheterization. The study will assess the maximum tolerated dose (MTD) of the cell therapy before proceeding to a larger phase II randomized trial.

Who should consider this trial

Good fit: Ideal candidates are adults aged 21 to 80 with chronic ischemic left ventricular dysfunction due to a prior myocardial infarction.

Not a fit: Patients with non-ischemic heart failure or those who do not meet the inclusion criteria will not benefit from this study.

Why it matters

Potential benefit: If successful, this therapy could significantly improve heart function and survival rates in patients with chronic ischemic heart conditions.

How similar studies have performed: While the use of stem cell therapies is a growing field, this specific approach using hESC-CMs is novel and has not been extensively tested in prior studies.

Eligibility criteria

Inclusion Criteria:

* Be ≥ 21 and \< 80 years of age.
* Provide written informed consent.
* Have a diagnosis of chronic ischemic left ventricular dysfunction secondary to MI as defined by previous myocardial infarction documented by an imaging study demonstrating coronary artery disease with corresponding areas of akinesis, dyskinesis, or severe hypokinesis.
* Be a candidate for cardiac catheterization within 5 to 10 weeks of screening.
* Have been treated with appropriate maximal medical therapy for heart failure or postinfarction left ventricular dysfunction. For beta-blockade, the patient must have been on a stable dose of a clinically appropriate beta-blocker for 3 months. For angiotensinconverting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) or angiotensin receptor neprilysin inhibitors (ARNIs) or have appropriate medical indication precluding use of one or both of these agents, the patient must have been on a stable dose of a clinically appropriate agent for 1 month or within no more than doubling the dose of any of ARB, ACE inhibitors, and ARNIs over the last 3 months.
* Left ventricular ejection fraction below 40%.
* Class II/III NYHA symptoms of heart failure within the 6 months prior to baseline testing.
* Hospitalization in the past 6 months or NT pro-BNP \> 1200 pg/mL, or \>1600 pg/mL if atrial fibrillation was present.
* Automated implantable cardioverter-defibrillator (AICD) in place.

Exclusion Criteria:

* Have a baseline glomerular filtration rate \< 35 ml/min/1.73 m2
* Have a known, serious radiographic contrast allergy.
* Have a prosthetic aortic valve or heart constrictive device.
* Have a documented presence of aortic stenosis (aortic stenosis graded as 1.5 cm2 or less).
* Have a documented presence of moderate to severe aortic insufficiency (echocardiographic assessment of aortic insufficiency graded as ≥+2).
* Have evidence of a life-threatening arrhythmia in the absence of a defibrillator (nonsustained ventricular tachycardia ≥ 20 consecutive beats or complete second- or third-degree heart block in the absence of a functioning pacemaker) or QTc interval \> 550 ms on screening ECG.
* AICD firing in the past 60 days prior to enrollment.
* Be eligible for or require coronary artery revascularization.
* Have a hematologic abnormality as evidenced by hematocrit \< 25%, white blood cell \< 2,500/µl, or platelet values \< 100,000/µl without another explanation.
* Have liver dysfunction, as evidenced by enzymes (AST and ALT) greater than three times the ULN.
* Have a coagulopathy (INR \> 1.3) not due to a reversible cause (i.e., Coumadin). Patients on Coumadin will be withdrawn 5 days before the procedure and confirmed to have an INR \< 1.3. Patients who cannot be withdrawn from Coumadin will be excluded from enrollment.
* Have known allergies to penicillin or streptomycin.
* Be an organ transplant recipient.
* Have a history of organ or cell transplant rejection.
* Have a clinical history of malignancy within 5 years (i.e., patients with prior malignancy must be disease-free for 5 years), except curatively-treated basal cell carcinoma, squamous cell carcinoma, or cervical carcinoma.
* Have a non-cardiac condition that limits lifespan to \< 1 year.
* Be on chronic therapy with immunosuppressant medication, such as corticosteroids or TNFα antagonists.
* Be serum-positive for HIV, hepatitis BsAg, or viremic hepatitis C.
* Be currently participating (or participated within the previous 30 days) in an investigational therapeutic or device trial.
* Be a female patient who is pregnant, nursing, or have child-bearing potential but is not using effective birth control.
* Tested positive for SARS-CoV-2 within the last 30 days

Where this trial is running

Palo Alto, California

• Stanford Hospital and Clinics — Palo Alto, California, United States (RECRUITING)

Study contacts

• Study coordinator: Joseph C. Wu, MD, PhD

Conditions: Chronic Ischemic Left Ventricular Dysfunction