HLHS
Conditions
Keywords
Pediatrics
Brief summary
This study is designed to assess the safety, tolerability, and efficacy of Lomecel-B as an adjunct therapy to the standard stage II (BDCPA) surgical intervention for HLHS. Lomecel-B will be delivered via intramyocardial injections
Detailed description
This study is designed to assess the safety, tolerability, and efficacy of Lomecel-B (formerly LMSCs) as an adjunct therapy to the standard stage II (BDCPA) surgical intervention for HLHS, which is typically performed at 4 - 6 months after birth. Lomecel-B will be delivered via intramyocardial injections. A total of 30 patients will be enrolled in 2 stages with 3 Cohorts. In the first stage, 10 consecutive HLHS patients will be enrolled and treated with Lomecel-B (Cohort A). The first 3 patients will be treated no less than 5 days apart, and will be evaluated for any treatment-emergent adverse events (TE-AEs) (e.g., induced myocardial infarction or perforation). These patients will undergo full evaluation for 5 days to demonstrate safety prior to proceeding with the remainder of the cohort. After 6 months post-treatment of the last patient of Cohort A, a formal safety review will be conducted prior to proceeding to the next phase. The second stage is double-blinded, in which 20 HLHS patients will be randomized to either receive treatment with Lomecel-B (Cohort B, 10 patients), or will receive no cells and no injection (Cohort C, 10 patients).
Interventions
BIOLOGICALLongeveron Mesenchymal Stem Cells
Allogeneic bone marrow-derived mesenchymal stem cell
Sponsors
Longeveron Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Masking description
Phase 1: no masking. Phase 2: HLHS patients which will be randomized to the treatment and control arms in a 1:1 ratio
Intervention model description
Phase 1: 10 patient safety run-in: all patients treated with LMSCs during Stage II surgery. Phase 2: 20 patients randomized 1:1 to receive either LMSCs or no cells (controls) during Stage II surgery.
Eligibility
Sex/Gender
ALL
Age
1 Days to 1 Years
Healthy volunteers
No
Inclusion criteria
all patients must have HLHS (all types) requiring BDCPA surgery.
Exclusion criteria
all patients must not have any of the following. 1. Significant coronary artery sinusoids. 2. Requirement for mechanical circulatory support prior to BDCPA surgery. 3. Underlying evidence of arrhythmia requiring anti-arrhythmia therapy. 4. Need for concomitant surgery for aortic coarctation or tricuspid valve repair. 5. HLHS and restrictive or intact atrial septum. 6. Undergoing the Stage I (Norwood) procedure that does not have HLHS. 7. Serum positivity for: HIV; hepatitis B virus surface antigen (HBV BsAg); and/or viremic hepatitis C virus (HCV). 8. Parent/guardian that is unwilling or unable to comply with necessary follow-up. 9. Unsuitability for the study based on the Investigator's clinical opinion. 10. Documented chromosomal abnormalities
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety: To evaluate the safety and feasibility of intramyocardial injection of LMSCs during the Stage II (BDCPA) operation for HLHS via incidence of Treatment-Emergent Serious Adverse Events. | Evaluated through 1 year post-treatment. | The incidence of Treatment-Emergent Serious Adverse Events will be evaluated, including: sustained/symptomatic ventricular tachycardia requiring intervention with inotropic support; aggravation of heart failure; myocardial infarction; unplanned cardiovascular operation for cardiac tamponade; infection during the first month post-treatment; and death. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Efficacy: Change from baseline in right ventricular end-systolic volume. | Evaluated through 1 year post-treatment. | Used to assess cardiac function. |
| Efficacy: Change from baseline in right ventricular end-diastolic volume. | Evaluated through 1 year post-treatment. | Used to assess cardiac function. |
| Efficacy: Change from baseline in right ventricular end-diastolic diameter. | Evaluated through 1 year post-treatment. | Used to assess cardiac function. |
| Efficacy: Change from baseline tricuspid regurgitation. | Evaluated through 1 year post-treatment. | Used to assess cardiac function. Measured by serial echocardiograms and MRI. |
| Efficacy: Change from baseline in right ventricular ejection fraction (%). | Evaluated through 1 year post-treatment. | Used to assess cardiac function. |
| Efficacy: Change in height (in centimeters). | Evaluated through 1 year post-treatment. | Used to assess change in somatic growth. |
| Efficacy: Change in head circumference (in centimeters). | Evaluated through 1 year post-treatment. | Used to assess change in somatic growth. |
| Efficacy: Number of patients with Treatment-Emergent Adverse Events, and total number of occurrences of Treatment-Emergent Adverse Events, through-out participation in trial. | Evaluated through 1 year post-treatment. | Treatment-Emergent Adverse Events will be assessed via incidence of co-morbidity, which include: cardiovascular morbidity; need for transplantation; re-hospitalizations; cardiovascular mortality; and all-cause mortality. |
| Efficacy: Change in weight (in kilograms). | Evaluated through 1 year post-treatment. | Used to assess change in somatic growth. |
Countries
United States
Outcome results
None listed