IV donor neonatal mesenchymal stromal cells for dilated cardiomyopathy in children and young adults

A Phase 1 Open-Label Study of the Safety of Intravenous Allogeneic Neonatal Mesenchymal Cells (nMSCs) in Young Adult (1A) and Pediatric (1B) Patients With Dilated Cardiomyopathy (DCM)

We will test whether IV infusions of donor neonatal mesenchymal stromal cells can safely improve heart pumping (left ventricular ejection fraction) in children and young adults with dilated cardiomyopathy.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 36 (estimated)
• Ages: 4 Years to 30 Years
• Sex: All
• Sponsor: Emory University (Academic / other)
• Drugs / interventions: Chemotherapy
• Locations: 5 sites (Atlanta, Georgia and 4 other locations)
• Trial ID: NCT06464588 on ClinicalTrials.gov

What this trial studies

This open-label Phase 1 study at Emory gives eligible participants three intravenous infusions of allogeneic neonatal mesenchymal stromal cells spaced 30 days apart to determine safety, feasibility, and the maximum tolerated dose. Phase 1A enrolls adults 18 to <30 years and Phase 1B enrolls children 4 to <18 years after completion and review of the adult cohort, with pediatric dosing adjusted by body weight. Up to 9–18 participants across both cohorts will be followed with laboratory monitoring, echocardiography or cardiac MRI, and clinic visits at baseline, 3, 6, and 12 months with total follow-up of about 14 months. Adverse events will be recorded using CTCAE criteria and reviewed by an independent DSMC.

Who should consider this trial

Good fit: Ideal candidates are children and young adults aged 4–30 with a diagnosis of dilated cardiomyopathy, left ventricular ejection fraction ≤45% and LV dilation (end-diastolic dimension Z score >+2), who meet other protocol criteria and can attend the Atlanta site.

Not a fit: Patients without dilated cardiomyopathy, those with LVEF >45%, or those with exclusionary comorbidities or contraindications are unlikely to receive benefit from this protocol.

Why it matters

Potential benefit: If successful, this therapy could improve left ventricular function and reduce symptoms or need for advanced heart-failure treatments in young patients with DCM.

How similar studies have performed: Other mesenchymal stromal cell therapies for cardiac disease have demonstrated acceptable safety and mixed signals of functional benefit in small trials, but IV allogeneic neonatal MSCs for pediatric and young adult DCM are relatively novel.

Eligibility criteria

Inclusion Criteria

* Phase 1A: Age greater than or equal to 18 years and less than 30 years (≥18 years, \<30 years).
* Phase 1B: Age greater than or equal to 4 years and less than 18 years (≥4 years, \<18 years)
* Subjects must be able to sign their own consent for Phase 1A of the study.
* Diagnosis of dilated cardiomyopathy (DCM) defined as

  * Any Congenital Cardiac Malformation with systemic ventricular systolic dysfunction; Idiopathic Cardiomyopathy; Familial/Inherited and/or Genetic Cardiomyopathy; History of Myocarditis; Acquired (Chemotherapy, Iatrogenic, Infection, Rheumatic, Nutritional); Ischemic (e.g. Kawasaki Disease, post-operative); Left ventricular noncompaction; Coronary Artery Disease
  * Left ventricular ejection fraction less than or equal to 45% documented by two-dimensional echocardiogram or cardiac MRI within the prior six months.
  * Left ventricular dilation as defined by echocardiography left ventricular and end-diastolic dimension Z score \> +2.0
  * Biventricular physiology with systemic left ventricle
* Must receive guideline directed heart failure as defined by the American Heart Association, American College of Cardiology, and Heart Failure Society of America 118
* Have been unresponsive or poorly responsive to at least 3 months of maximum guideline directed treatments.

Exclusion Criteria

* Listed for heart transplantation (as UNOS status 1A) or hospitalized while waiting for transplant (while on inotropes or with ventricular assist device)
* Cardiovascular surgery of percutaneous intervention to palliate or correct congenital cardiovascular malformations within 3 months of the screening visit. Patients anticipated to undergo corrective heart surgery during the 12 months after entry into Part 1A/1B.
* Previous heart transplant recipient
* Unoperated primary obstructive or severe regurgitant valve (aortic, pulmonary, or tricuspid) disease, or significant systemic ventricular outflow obstruction or aortic arch obstruction.
* Severe mitral valve disease
* Restrictive or hypertrophic cardiomyopathy
* Cardiogenic shock
* Currently on extracorporeal membrane oxygenation support
* Ventricular assist device support
* Lethal, uncontrollable arrhythmia defined as an arrhythmia resulting in hemodynamic instability requiring need for defibrillation, continuous intravenous anti-arrhythmic medication or mechanical circulatory support
* Patients with persistent atrial fibrillation requiring specific pharmacotherapy
* Amyloidosis
* Ischemic dilated cardiomyopathy
* Clinical history of malignant neoplasm within 5 years (with the exception of curatively treated basal cell carcinoma, squamous cell carcinoma, or cervical carcinoma)
* Serious neurologic disorder including loss of vision, stroke, or paralysis
* High-grade pulmonary embolism requiring interventional catheter procedure or pulmonary hypertension requiring use of pulmonary vasodilators including phosphodiesterase inhibitor or nitric oxide
* High-grade renal failure \[eGFR\<45\] mL/min/1.73 m2 - serum potassium \>5.3 mmol/L
* Multiple organ failure
* Non-cardiac condition that limits life span for \<1 year
* Uncontrolled diabetes (HbA1c \>9%) at screening
* Active infection (including endocarditis) requiring pharmacotherapy
* Sepsis
* Active hemorrhagic disease (e.g., gastrointestinal bleeding, injury)
* History of cardiac transplantation
* Immune system-altering medications, or immunosuppressive therapy at the time of enrolment or within the prior 12 weeks
* Dystrophin-associated cardiomyopathy confirmed by standard cardiomyopathy panel testing
* Confirmed myocarditis at time of screening
* Elevated LFTs greater than 2 times upper limit of normal at time of consent
* Elevated WBC greater than upper limit of normal as defined by local lab at time of consent
* Presence of HLA antibodies specific for therapeutic study product
* History of noncompliance, alcohol abuse, recreational drug use, or incarceration within the last year
* Currently pregnant or breastfeeding

Where this trial is running

Atlanta, Georgia and 4 other locations

• Hughes Spalding Children's Hospital — Atlanta, Georgia, United States (Recruiting)
• Egleston Children's Hospital — Atlanta, Georgia, United States (Recruiting)
• Emory Children's Center — Atlanta, Georgia, United States (Recruiting)
• Emory University Hospital — Atlanta, Georgia, United States (Recruiting)
• Scottish Rite Children's Hospital — Atlanta, Georgia, United States (Recruiting)

Study contacts

• Principal investigator: William Mahle, MD — Emory University
• Study coordinator: William Mahle, MD

Conditions Dilated Cardiomyopathy; Neonatal Mesenchymal Cells