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)
- Conditions
- Dilated Cardiomyopathy
- Interventions
- Biological: Allogeneic Neonatal mesenchymal stromal cells (nMSCs)
- Registration Number
- NCT06464588
- Lead Sponsor
- Emory University
- 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.
- Detailed Description
This study is a single site open label study with 2 phases. The 2 phases will be broken into an adult group Phase 1A with group pediatric group Phase 1B. This study will enroll patients between the ages of 4 years and 30 years old. The investigators will be looking at the safety, feasibility, and maximum tolerated dose of allogeneic neonatal mesenchymal stromal cells (nMSCs) as defined by freedom from CTCAE or Grade 3 AE that is probably or definitely related to the IP throughout the duration of the study.
A minimum of 9 and a maximum of 18 patients will be enrolled into both Phase 1A adult groups and 1B pediatric groups. Phase 1A subjects will receive study products with doses defined by the study group and Phase 1B will begin after all adult subjects have completed Phase 1A infusions, FDA and a DSMC review. All pediatric subjects will receive study product dosed per body weight in the defined study group.
Allogeneic neonatal mesenchymal stromal cells (nMSCs) will be infused via IV every 30 days for a total of 3 infusions. A check-in will be scheduled the morning after each infusion for pediatric patients. There will be a baseline visit before allogeneic neonatal mesenchymal stromal cells (nMSCs) therapy is initiated, followed by a phone call 30 days after the last infusion. There will be in person visits at 3-month, 6 months, and 1 year mark. The total duration for each patient will be 14 months.
Labs will be collected at baseline, during nMSC infusions, and at in person follow up visits to assess cardiac function. Any leftover blood samples may be stored for future research by the sponsor of the study. Echocardiograms will be completed at baseline, and 3 month-, 6 month-, and 1-year visits to look at left ventricular ejection fraction and electrocardiograms will be completed to provide measures of cardiac rhythm or rhythm. Other assessments include physical exam, 6-minute walk test, Cardiac MRI, vital signs, PedsQL questionnaire for pediatrics and The Kansas City Cardiomyopathy Questionnaire for adults.
It is expected to recruit 18-36 participants through face-to-face encounters between participants and study staff during clinical encounters at Children's Healthcare of Atlanta and Emory Health care system, Clinicaltrials.gov registration, and Institutional Review Board approved advertisements to surrounding hospitals with cardiac programs. Patients will also be recruited through MyChart. If identified as eligible to participate, the study team will seek approval by the subjects' primary cardiologist and consent and/or assent with the permission of the parent or legally authorized representative, will occur in person during a baseline visit.
After allogeneic neonatal mesenchymal stromal cells (nMSCs) infusions, pediatric patients will be provided an overnight stay at Ronald McDonald House, or a hospital affiliated hotel in case of any unanticipated effects and follow up visits the next morning. This is so pediatric patients are near the hospital for such events. Adults will not be required to stay overnight for a follow-up visit. There will be financial compensation for each study visit, and patients will be reimbursed for parking.
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 36
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Adult Cohort Allogeneic Neonatal mesenchymal stromal cells (nMSCs) 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. Pediatric Cohort Allogeneic Neonatal mesenchymal stromal cells (nMSCs) 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.
- Primary Outcome Measures
Name Time Method Proportion of participants with freedom from any Common Toxicity Criteria for Adverse Events (CTCAE) Grade 3 or greater End of study, around 12 months post-intervention 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.Maximum tolerated dose (MTD) in patients with dilated cardiomyopathy End of study, around 12 months post-intervention 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.
- Secondary Outcome Measures
Name Time Method Change of left ventricular ejection fraction (LVEF) from baseline Baseline, 3-month, 6-month, and 12-month post-intervention Change of left ventricular ejection fraction (LVEF) between baseline, 3-month, 6-month, and 12-month follow-up determined by echocardiography and cardiac MRI.
Change in N-terminal pro b-type natriuretic peptide (NT-proBNP) levels from baseline Baseline, 3-month, 6-month, and 12-month post-intervention N-terminal pro b-type natriuretic peptide (NT-proBNP) levels will be collected on infusion days, and all post infusion follow up visits.
Change of 6-minute walk test (6MWT) results Baseline, 3-month, 6-month, and 12-months post-intervention A 6-minute walk test (6MWT) will be completed at baseline, 3-month, 6-month, and 1-year visits to measure functional status if the participant is developmentally appropriate. Distance in meters will be measured until the participant can either walk 6 minutes, or they become too exhausted.
Change in Kansas City Cardiomyopathy Questionnaire Baseline, 3-month, 6-month and 12-month post-intervention Change in Kansas City Cardiomyopathy Questionnaire will be recorded (≥18 years - ≤30 years). KCCQ scores are scaled from 0 to 100 and summarized in 25-point ranges, where scores represent health status as follows: 0 to 24: very poor to poor; 25 to 49: poor to fair; 50 to 74: fair to good; and 75 to 100: good to excellent.
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 quality-of-life validated survey scores in Peds Quality of Life (QOL) survey (≥4 years - \< 18 years). Total possible score ranges from 0 to 100 and higher scores indicate better QOL.
Trial Locations
- Locations (5)
Hughes Spalding Children's Hospital
🇺🇸Atlanta, Georgia, United States
Egleston Children's Hospital
🇺🇸Atlanta, Georgia, United States
Emory Children's Center
🇺🇸Atlanta, Georgia, United States
Emory University Hospital
🇺🇸Atlanta, Georgia, United States
Scottish Rite Children's Hospital
🇺🇸Atlanta, Georgia, United States