First-in-Human Pilot Study of Epicardial Circular RNA-HM2002 Injection in CABG for Ischemic Heart Failure

Prior treatment

• need for concurrent cardiac or non-cardiac interventional or surgical procedures other than CABG (e.g., valve surgery, ventricular wall tumor surgery, peripheral arterial stenting or surgery)
• patients with prior systemic or cardiac therapy with similar nucleic acid medications

Other illness

• a known history of drug abuse or drug allergy

Lab values

• subjects with the following concomitant symptoms or diseases:
  • ECHO-confirmed LVEF ≤ 20%;
  • History of malignant arrhythmias (including multiple ventricular pre-systole, premature ventricular dystocia, tricyclic rhythm, or ventricular tachycardia) manifesting symptomatically or requiring treatment (CTCAE grade 3);
  • atrial fibrillation (including paroxysmal atrial fibrillation);
  • Long QT syndrome;
  • Estimated glomerular filtration rate (eGFR) ≤ 30 mL/min/1.73 m2; f. Serum gammaglutamyl (GGT) ≤ 1.5 mL/min/1.73 m2
  • Serum alanine aminotransferase (ALT) or aminotransferase (AST) \> 3 x upper limit normal (ULN) and total bilirubin (TBIL) \> 2 x ULN or more;
  • Severe coagulation disorders, bleeding disorders, etc;
  • history of active human immunodeficiency virus (HIV), active hepatitis C virus (HCV), or active hepatitis B virus (HBV); active HIV, HCV, and HBV infections are defined as:
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  • HIV antibody positive;
  • Anti-HCV antibody and positive for HCV RNA;
  • HBsAg positive and HBV DNA ≥1000 cps/ml (or 200 IU/ml); i. current malignancy, or a history of malignancy.

Other

• Subjects meeting any of the following criteria will be excluded from this study:
• pregnant or lactating women or those who are not using effective contraception;
• other circumstances judged by the investigator to be inappropriate, such as the investigator's judgment that the subject may be exposed to substantial safety risks, or interference with the results of the study, or lack of participation in completing this trial in accordance with the study protocol.

• Subjects must meet all of the following inclusion criteria:
• be ≥18 and ≤80 years of age at the time of signing the informative and be of either sex;
• have ischemic heart failure (IHF) with left ventricular ejection fraction (LVEF) ≤50% by echocardiography (ECHO), New York Heart Association (NYHA) cardiac function class 3-4, and be proposed to undergo elective coronary artery bypass grafting (CABG);
• voluntarily sign the informed consent form and fully understand the content, process and possible adverse reactions of the trial. Be able to complete the study according to the requirements of the trial protocol and have good compliance;