Ischemic Heart Disease, Non-ischemic Cardiomyopathy
Conditions
Brief summary
A study to assess the safety and preliminary efficacy of serial intravenous dose of Allogeneic Mesenchymal Bone Marrow Cells in subjects with heart failure and implanted left ventricular assist devices.
Detailed description
A double-blind, placebo-controlled, single-center, randomized study to assess the safety and preliminary efficacy of a three serial intravenous doses of allogeneic mesenchymal bone marrow cells to subjects with heart failure and implanted left ventricular assist devices.
Interventions
BIOLOGICALHuman Allogeneic Mesenchymal Bone Marrow Cells (aMBMC)
Allogeneic Mesenchymal Bone Marrow Cells (aMBMC) 1.5 million cells/kg
OTHERPlacebo
1.5 mL/kg Lactated Ringer's Solution
Sponsors
Medstar Health Research Institute
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Age ≥18 years. 2. Advanced Heart Failure 3. Advanced HF defined as HF requiring LVAD implantation and deemed stable on his/her LVAD. 4. On stable medical therapy (per the discretion of the treating physician) including beta-blockers, ACE-inhibitors, angiotensin receptors blockers, angiotensin receptor neprilysin inhibitor, mineralocorticoid receptor antagonists, isosorbide, hydralazine, and mineralocorticoid receptor antagonists) and optimized pump speed for at least a month prior to randomization. 5. HS-CRP level≥2 mg/l. 6. NYHA class II-III symptoms. 7. Ability to understand and provide signed informed consent. 8. Reasonable expectation that patient will receive standard post-treatment care and attend all scheduled safety follow-up visits
Exclusion criteria
1. Women of childbearing potential. Postmenopausal women or women with permanent contraception method (defined as total hysterectomy) will not be excluded. 2. History of debilitating stroke (modified Rankin Score \> 3) within 3 months. 3. The likelihood of requirement of cardiac surgery during the study period. 4. Presence of clinically significant, uncorrected left sided valvular heart disease, active acute myocarditis, or uncontrolled hypertension defined as Persistently elevated mean arterial blood pressure (\>100 mmHg). Echocardiography within 12 months of screening. Patients can be re-evaluated, at the discretion of the investigator. 5. QTc \>550 ms (in the absence of bundle branch block, interventricular conduction delay or ventricular pacing). Electrocardiogram (ECG) within 60 days. 6. History of cardiac arrest within 3 months. 7. Hypertrophic or infiltrative cardiomyopathy. 8. Considered or listed for organ transplantation or history of organ transplantation 9. Illness other than HF with life expectancy less than 12 months. 10. Enrolled in an interventional trial or received an experimental drug or device within 30 days of randomization. 11. Left ventricular assist device implantation \>2 years prior to enrollment. 12. Biventricular assist device (Bi-VAD) support. 13. Severe COPD defined by FEV1\<1L, FEV1/FVC\<70% within 12 months if known history of COPD, otherwise FEV1\<1L, FEV1/FVC\<70% within 24 months 14. Uncontrolled seizure disorder. 15. Clinically significant hematologic, hepatic, or renal impairment as determined by screening clinical laboratory tests within the last 30 days: Liver disease = ALT or AST \> 3x normal, alkaline phosphatase or bilirubin \>2x normal Renal disease = on long term dialysis Hematologic = Unexplained persistent leukocytosis (WBC \>11 K/UL) or hemoglobin \< 8.5 gm/dl 16. Presence of any other clinically-significant medical condition, psychiatric condition, or laboratory abnormality, that in the judgment of the investigator or sponsor may affect compliance with the study protocol or pose a safety risk to the subject. 17. Inability to comply with the conditions of the protocol. 18. Acute coronary syndrome within 4 weeks (clinical diagnosis, confirmed by electrocardiographic abnormalities and elevation of troponin-I). 19. Malignancy within the previous five years, except adequately treated basal cell carcinoma, provided that it is neither infiltrating nor sclerosing, and carcinoma in situ of the cervix. 20. Active uncontrolled systemic infection. Positive blood or deep tissue cultures or clinical or imaging evidence of systemic infection despite complete course of effective antimicrobial therapy as determined by infectious diseases. Localized (non-systemic) infection is not an exclusion criterion. Patients can be re-evaluated, at the discretion of the investigator. 21. Early postpartum cardiomyopathy (within six months of diagnosis). 22. Presence of inherited or acquired immune deficiency or human immunodeficiency virus infection (HIV). Negative HIV test within the preceding 12 months is required. 23. Systemic corticosteroids, immunosuppressive drug therapy (cyclophosphamide, methotrexate, cyclosporine, tacrolimus, azathioprine, mycophenolate, sirolimus, etc.), and DNA depleting or cytotoxic drugs taken within four weeks prior to study treatment. 24. Known Porphyria. 25. Allergy to sodium citrate or any caine type of local anesthetic. 26. Patient enrolled in hospice care.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Temperature | up to 12 months post enrollment | Temperature |
| Uncontrolled Systemic Infection | up to 12 months post enrollment | Number of admission for uncontrolled systemic infection |
| All-cause Mortality | up to 12 months post enrollment | Rate of Death |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Hospitalizations Due to Right Heart Failure | day 90 | Number of hospitalizations for to right heart failure |
| NK Cell Depletion | Baseline to day 90 | percent reduction in NK cells |
| Gout Flares | Day 90 | Count of gout flares |
| 6 Minute Walk Distance Changes | Baseline and day 90 post initial infusion | 6 minute walk distance changes |
| Change in the Following Cardiac Biomarker | Baseline and day 90 post initial infusion | The change in the lab values N-Terminal Prohormone of Brain Natriuretic Peptide (NT-ProBNP) |
| Change in RV Systolic Function | Baseline and day 90 post initial infusion | Change in RV systolic function |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Human Allogeneic Mesenchymal Bone Marrow Cells (aMBMC) Three intravenous infusions of 1.5 million (aMBMC) per kg administered at approximately 2mL/min. Maximum dose as for 100kg subject or 150 million cells for any subject 100kg or more with each infusion 1 month apart.
Human Allogeneic Mesenchymal Bone Marrow Cells (aMBMC): Allogeneic Mesenchymal Bone Marrow Cells (aMBMC) 1.5 million cells/kg | 2 |
| Placebo Three intravenous infusions of 1.5 mL/kg Lactated Ringer's Solution with each infusion 1 month apart.
Placebo: 1.5 mL/kg Lactated Ringer's Solution | 2 |
| Total | 4 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 1 | 1 |
Baseline characteristics
| Characteristic | Human Allogeneic Mesenchymal Bone Marrow Cells (aMBMC) | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 1 Participants | 2 Participants | 3 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants | 0 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 2 Participants | 2 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 2 Participants | 4 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment United States | 2 Participants | 2 Participants | 4 Participants |
| Sex: Female, Male Female | 0 Participants | 1 Participants | 1 Participants |
| Sex: Female, Male Male | 2 Participants | 1 Participants | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 2 | 1 / 2 |
| other Total, other adverse events | 2 / 2 | 2 / 2 |
| serious Total, serious adverse events | 2 / 2 | 2 / 2 |
Outcome results
Primary
All-cause Mortality
Rate of Death
Time frame: up to 12 months post enrollment
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Human Allogeneic Mesenchymal Bone Marrow Cells (aMBMC) | All-cause Mortality | 1 Participants |
| Placebo | All-cause Mortality | 1 Participants |
Primary
Temperature
Temperature
Time frame: up to 12 months post enrollment
Population: Due to study termination and small sample size, no analysis was performed
Primary
Uncontrolled Systemic Infection
Number of admission for uncontrolled systemic infection
Time frame: up to 12 months post enrollment
Population: Due to study termination and small sample size, no analysis was performed
Secondary
6 Minute Walk Distance Changes
6 minute walk distance changes
Time frame: Baseline and day 90 post initial infusion
Population: Test was not performed for any subjects at 90 days, therefore no changes could be analyzed
Secondary
Change in RV Systolic Function
Change in RV systolic function
Time frame: Baseline and day 90 post initial infusion
Population: Due to study termination and small sample size, no analysis was performed
Secondary
Change in the Following Cardiac Biomarker
The change in the lab values N-Terminal Prohormone of Brain Natriuretic Peptide (NT-ProBNP)
Time frame: Baseline and day 90 post initial infusion
Population: Due to study termination and small sample size, no analysis was performed
Secondary
Gout Flares
Count of gout flares
Time frame: Day 90
Population: Due to study termination and small sample size, no analysis was performed
Secondary
Hospitalizations Due to Right Heart Failure
Number of hospitalizations for to right heart failure
Time frame: day 90
Population: Due to study termination and small sample size, no analysis was performed
Secondary
NK Cell Depletion
percent reduction in NK cells
Time frame: Baseline to day 90
Population: Due to study termination and small sample size, no analysis was performed