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)

Launched by EMORY UNIVERSITY · Jun 13, 2024

Keywords

ClinConnect Summary

This clinical trial is exploring the safety of a new treatment using special cells called neonatal mesenchymal stromal cells (nMSCs) for patients with a heart condition known as Dilated Cardiomyopathy (DCM). DCM can make it hard for the heart to pump blood effectively, and this study aims to find out if infusing these cells can help improve heart function in both young adults (ages 18 to 29) and children (ages 4 to 17).

To participate in the trial, individuals must have a diagnosis of DCM, with specific heart function measurements indicating their condition. They should also have been on standard heart failure treatments for at least three months without sufficient improvement. Participants will receive the nMSC treatment and will be monitored closely for any side effects or changes in their heart health. It’s important to note that the trial is not yet recruiting participants, so interested individuals should stay tuned for updates.

Gender

ALL

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