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)

NCT06464588 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: STUDY00004268
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 5

Brief Summary

This is a Phase 1 study to determine the safety and efficacy of allogeneic neonatal mesenchymal stromal cells (nMSCs) for the treatment of Dilated Cardiomyopathy. The purpose of the study is to help doctors and scientists learn if allogeneic neonatal mesenchymal stromal cells (nMSCs) infusions are a safe and effective way to improve cardiac function and left ventricular ejection fraction.

Conditions

Dilated Cardiomyopathy

Keywords

Dilated Cardiomyopathy; Neonatal Mesenchymal Cells (nMSCs)

Outcome Measures

Primary Outcomes (2)

• Proportion of participants with freedom from any Common Toxicity Criteria for Adverse Events (CTCAE) Grade 3 or greater

  Proportion of participants with freedom from any Common Toxicity Criteria for Adverse Events (CTCAE) Grade 3 or greater AE that is probably or related to the IP throughout the duration of the study will be recorded. Results can vary from 0 to 100% and higher proportion correlates with better outcome. TCAE Grade 3 is defined as severe or medically significant not immediately life-threatening; hospitalization or prolongation of hospitalization. Grade 4 and 5 AEs include composite of: death, life-threatening events, initial or prolonged hospitalization, disability of permanent damage and congenital anomaly/birth defects.

  End of study, around 12 months post-intervention

• Maximum tolerated dose (MTD) in patients with dilated cardiomyopathy

  If two patients in a dosing group have a related SAE or Dose Limiting Toxicity (DLT), then the previous dosing group will be defined as MTD.

  End of study, around 12 months post-intervention

Secondary Outcomes (5)

• Change of left ventricular ejection fraction (LVEF) from baseline

  Baseline, 3-month, 6-month, and 12-month post-intervention

• Change in N-terminal pro b-type natriuretic peptide (NT-proBNP) levels from baseline

  Baseline, 3-month, 6-month, and 12-month post-intervention

• Change of 6-minute walk test (6MWT) results

  Baseline, 3-month, 6-month, and 12-months post-intervention

• Change in quality-of-life validated survey scores in Peds Quality of Life (QOL) survey

  Baseline, 3-month, 6-month and 12-month post-intervention

• Change in Kansas City Cardiomyopathy Questionnaire

  Baseline, 3-month, 6-month and 12-month post-intervention

Study Arms (2)

Adult Cohort

EXPERIMENTAL

Adults (18-30 years) will be enrolled into all dose levels (as tolerated) of Phase 1A. Open label nMSCs will be administered intravenously in the following defined dose groups. The rate of infusion will be approximately 30- 60 minutes at 0, 15 and 30 days, with escalating dose levels: * Dose level 1: 5.0x107 nMSCs at 0, 15 and 30 days * Dose level 2: 1.0.x108 nMSCs at 0, 15 and 30 days * Dose level 3: 2.5x108 nMSCs at 0, 15 and 30 days Dose escalation will follow 3+3 study design parameters. The next dosing group will be initiated at least one month after the last subject in a particular dose level has received the last dose treatment. Once MTD has been determined, 3 additional patients will be enrolled to ensure a total of 6 patients are enrolled in MTD level for confirmation.

Biological: Allogeneic Neonatal mesenchymal stromal cells (nMSCs)

Pediatric Cohort

EXPERIMENTAL

Pediatric participants (ages 4 years-18 years) will be enrolled into dose level as determined in Phase 1B (3+3 study design; open label). nMSCs will be administered intravenously in the following defined dose groups. The rate of infusion will be approximately 30- 60 minutes at 0, 15 and 30 days, with escalating dose levels: * Dose Level 1: 0.7x106 nMSCs/kg * Dose Level 2: 1.43x106 nMSCs/kg * Dose Level 3: 2.85x106 nMSCs/kg Dose escalation will follow 3+3 study design parameters. The next dosing group will be initiated at least one month after the last subject in a particular dose level has received the last dose treatment. Once MTD has been determined, 3 additional patients will be enrolled to ensure a total of 6 patients are enrolled in MTD level for confirmation. Following intravenous delivery of nMSCs, patients will be followed at 3 months, 6 months and 1 year from the last infusion to complete all safety and efficacy assessments.

Biological: Allogeneic Neonatal mesenchymal stromal cells (nMSCs)

Interventions

Allogeneic Neonatal mesenchymal stromal cells (nMSCs) BIOLOGICAL

nMSCs will be administered intravenously in the predefined dose per each group. The rate of infusion will be approximately 30- 60 minutes at 0, 15 and 30 days, with escalating dose levels.

Also known as: nMSCs infusions

Adult Cohort; Pediatric Cohort

Eligibility Criteria

• Age: 4 Years - 30 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Emory University: lead
• The Marcus Foundation: collaborator

Study Sites (5)

Hughes Spalding Children's Hospital

Atlanta, Georgia, 30303, United States

RECRUITING

Egleston Children's Hospital

Atlanta, Georgia, 30322, United States

RECRUITING

Emory Children's Center

Atlanta, Georgia, 30322, United States

RECRUITING

Emory University Hospital

Atlanta, Georgia, 30322, United States

RECRUITING

Scottish Rite Children's Hospital

Atlanta, Georgia, 30342, United States

RECRUITING

MeSH Terms

Conditions

Cardiomyopathy, Dilated

Condition Hierarchy (Ancestors)

Cardiomegaly; Heart Diseases; Cardiovascular Diseases; Cardiomyopathies; Laminopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• William Mahle, MD

  Emory University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

William Mahle, MD

CONTACT

404-256-2593; wmahle@emory.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: June 13, 2024
• First Posted: June 18, 2024
• Study Start: July 14, 2025
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): July 1, 2027
• Last Updated: September 10, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Immediately following the publication and then for a minimum of 5 years
• Access Criteria: Proposals should be directed to mahlew@kidsheart.com and Edwin.horwitz@emory.edu. To gain access, data requestors will need to sign a data access agreement.

Locations

US (5)