Regression of Fibrosis & Reversal of Diastolic Dysfunction in HFpEF Patients Treated With Allogeneic CDCs

Inclusion Criteria

• ≥ 50 years old, male or female
• LVEF ≥ 50%
• Symptoms and physical findings of chronic heart failure (NYHA class II- ambulatory IV)
• Treatment with a stable, maximally-tolerated dose of diuretic(s) for a minimum of 30 days prior to randomization.
• Left atrial (LA) enlargement defined by at least one of the following: LA width (diameter) ≥ 3.8 cm or LA length ≥ 5.0 cm or LA area ≥ 20 cm2 or LA volume ≥ 55 mL or LA volume index ≥ 29 mL/m2
• BNP > 125 pg/ml for patients in NSR or > 150 pg/ml for patients in AF (BNP are BMI corrected) or resting PCWP > 15 mmHg, or exercise PCWP > 18 mmHg

Exclusion criteria-Specific to HFpEF

• Any prior echocardiographic measurement of LVEF 40 kg/m2
• Use of investigational drugs or treatments at the time of enrollment
• Systolic blood pressure > 150 mmHg but 110 beats per minute (bpm)
• Prior major organ transplant or intent to transplant (i.e., on transplant list)
• Hepatic disease as determined by any one of the following: SGOT (AST) or SGPT (ALT) values exceeding 3x the upper limit of normal (ULN), bilirubin > 1.5 mg/dl; history of chronic viral hepatitis
• Chronic Kidney Disease with eGFR 5.5 mmol/L (mEq/L)
• History or presence of any other disease with a life expectancy of < 3 years
• Non-compliance to medical regimens
• Drug or alcohol abuse within the last 12 months
• History of malignancy within the past 5 years
• Pregnant or nursing (lactating) women confirmed by a positive human chorionic gonadotropin (hCG); women of child-bearing potential (physiologically capable of becoming pregnant), unless using highly effective contraception methods during study

Exclusion criteria-Specific to CAP-1002 (not listed above)

• Diagnosis of active myocarditis
• Known hypersensitivity to contrast agents or previous H/O HIT
• Known hypersensitivity to dimethyl sulfoxide (DMSO)
• Known hypersensitivity to bovine products
• Active infection not responsive to treatment
• Active allergic reactions, connective tissue diseases or autoimmune disorders
• History of cardiac tumor or cardiac tumor demonstrated on screening
• History of previous stem cell therapy
• History of treatment with immunosuppressive agents, including chronic systemic corticosteroids, biologic agents targeting the immune system, anti-tumor and anti-neoplastic drugs or anti-VEGF within 6 months prior to enrollment (not including drug-eluting coronary stents)
• Human Immunodeficiency Virus (HIV) infection