Safety of HMA-CD20 in Patients With HFrEF

Exclusion Criteria

• •1. Severe primary valvular cardiopathy or valvular prosthesis (mechanical or bio-valve).
• •2. History of heart transplant surgery, cardiomyoplasty, left ventricular reduction surgery, valvuloplasty, implantation of a ventricle assist device (VAD) and surgical cardiac congenital defect correction.
• •3. Uncontrolled atrial fibrillation (HR \> 100 bpm), atrial flutter, sustained atrial fibrillation and / or significant arrhythmias such as sustained or unsustained ventricular tachychardia, bigeminy or trigeminy evidenced by Holter during the prescreening period.
• •4. Implantable cardioverter defibrillator (ICD) within the last three months.
• •5. Acute coronary syndromes that required pharmacological or mechanical reperfusion or medical treatment, within 30 days before selection.
• •6. Percutaneous coronary intervention within 30 days prior to selection.
• •7. Treatment with inotropic agents (dobutamine, milrinone, levosimendan), I.V. diuretics or vasodilators within 30 days of selection.
• •8. Pregnant women or breast feeding period without adequate prenatal care.
• •9. Untreated thyroid disease.
• •10. Patients with GFR \<30mL/min based on the cockcroft-gualt formula
• •11. Rapidly progressive glomerulonephritis, seizures or psychosis, progressive neuropathy or myopathy.
• •12. Hemoglobin: \< 8.5 mg/dL.
• •13. WBC count less than 5000/mm3
• •14. Platelets: \<100,000/mm, AST or ALT \>2.5 × upper limit of normal (ULN) unless related to primary disease.
• •15. Positive Hepatitis B or C serology (Hep B Surface antigen and Hep C antibody).
• •16. History of positive HIV.
• •17. Treatment with any investigational agent within 4 weeks of screening or 5 half-lives of the investigational drug (whichever is longer).
• •18. Recipients of an available attenuated vaccine within four weeks prior to randomization.
• •19. Previous treatment with HMA-CD20 or any immunotherapy.
• •20. History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies.
• •21. Known active bacterial, viral, fungal (excluding fungal infections of nail beds/onychomycosis), mycobacterial, or other infection (including tuberculosis or atypical mycobacterial disease) or any major episode of infection requiring hospitalization or treatment with I.V. antibiotics within four weeks of screening, or oral antibiotics within two weeks before screening.
• •22. Consistent steroid administration within the past four weeks.
• •23. Lack of peripheral venous access.
• •24. Concomitant or previous malignancies, except curatively resected non-melanoma skin carcinomas or carcinoma in situ of the cervix.
• •25. History of psychiatric disorder that would interfere with participation in this protocol, such as depression, bipolar syndrome, schizophrenia.
• •26. Patients with concomitant severe COPD or emphysema.
• •27. Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or render the patient at high risk from treatment complications.
• •28. Female participants without adequate method of contraception
• •29. Inability to comply/assist with study and follow-up procedures.
• •4.3 Elimination criteria
• •1. Progression of NYHA functional class since the initiation of the study.
• •2. BNP or troponin I elevation
• •3. New onset of pulmonary infection due to opportunistic virulent antigens (N. Jirovecci, A. Baumanni, MRSA, VRSA).
• •4. Any serious adverse event (SAE) indicative of fatal or nonfatal hepatitis, liver failure or its complications.
• •5. ALT or AST \>3x normal values with a total bilirubin ≥ 2x normal value.
• •6. WBC count \< 3000/mm3
• •7. Anaphylactic or life-threatening hypersensitivity reactions