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

NCT ID: NCT06621576

Last Updated: 2025-04-02

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 3 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-09-18
• Study Completion Date: 2025-09-30

Brief Summary

This exploratory, single-center, open-label clinical trial assesses the safety, tolerability, and potential efficacy of a single 5 mg dose of HM2002 injection administered via multiple-point epicardial injections for treating ischemic heart failure. Three patients aged 18-80 undergoing elective coronary artery bypass grafting (CABG) surgery will participate. Using a sentinel dosing approach, the first subject will receive HM2002, followed by a 14-day safety observation before dosing the remaining participants. If any serious adverse events or dose-limiting toxicities occur in the first subject, a Safety Review Committee will evaluate the safety data to determine whether to continue or terminate the trial.

Detailed Description

This study is a prospective, single-center, single-dose, open-label investigator-initiated exploratory clinical trial (IIT study) designed to evaluate the safety, tolerability, and potential clinical efficacy of the exploratory dose HM2002 injection administered via single-dose, multiple-point injections through the epicardium for the treatment of ischemic heart failure. The study plans to enroll three patients aged between 18 and 80 years who are scheduled to undergo elective coronary artery bypass grafting (CABG) surgery and have ischemic heart failure. Eligible patients will become study subjects after providing full written informed consent and successfully passing the inclusion and exclusion criteria screening. The exploratory dose for this trial is 5 mg HM2002 injection. The three subjects will be dosed following the sentinel dosing principle. Specifically, after the first subject completes dosing, there will be a minimum interval of 14 days (2 weeks) to confirm safety and tolerability before enrolling the remaining two subjects. If any serious adverse event (SAE) or dose-limiting toxicity (DLT) occurs in the first subject, a Safety Review Committee (SRC) meeting will be convened to review all collected safety data. The committee will then determine whether to proceed with the enrollment of subsequent subjects or terminate the trial.

Conditions

Ischaemic Heart Disease; Heart Failure

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

HM2002 Injection group

First sentinel enrollment, no DLT events followed by re-enrollment after 2 cases

Group Type: EXPERIMENTAL

HM2002 injection

Intervention Type: DRUG

Eligible subjects under general anesthesia will undergo CABG surgery. After completing the distal anastomosis, 5mg of HM2002 injection solution drawn into a 1 ml syringe will be administered via multi-point injection using an OT needle or insulin needle (preferably a 30G needle). The injections will be spaced approximately 1 cm apart, with no more than 30 injection points, into the myocardium at the edge of the MI area (with obvious infarcts) or the area of the diseased coronary artery branches (without obvious infarcts) through the epicardium.

Interventions

HM2002 injection

Eligible subjects under general anesthesia will undergo CABG surgery. After completing the distal anastomosis, 5mg of HM2002 injection solution drawn into a 1 ml syringe will be administered via multi-point injection using an OT needle or insulin needle (preferably a 30G needle). The injections will be spaced approximately 1 cm apart, with no more than 30 injection points, into the myocardium at the edge of the MI area (with obvious infarcts) or the area of the diseased coronary artery branches (without obvious infarcts) through the epicardium.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. be ≥18 and ≤80 years of age at the time of signing the informative and be of either sex;

2. 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);

3. 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;

Exclusion Criteria

Subjects meeting any of the following criteria will be excluded from this study:

1. subjects with the following concomitant symptoms or diseases:

1. ECHO-confirmed LVEF ≤ 20%;

2. 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);

3. atrial fibrillation (including paroxysmal atrial fibrillation);

4. Long QT syndrome;

5. Estimated glomerular filtration rate (eGFR) ≤ 30 mL/min/1.73 m2; f. Serum gammaglutamyl (GGT) ≤ 1.5 mL/min/1.73 m2

6. Serum alanine aminotransferase (ALT) or aminotransferase (AST) > 3 x upper limit normal (ULN) and total bilirubin (TBIL) > 2 x ULN or more;

7. Severe coagulation disorders, bleeding disorders, etc;

8. 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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1. HIV antibody positive;

2. Anti-HCV antibody and positive for HCV RNA;

3. HBsAg positive and HBV DNA ≥1000 cps/ml (or 200 IU/ml); i. current malignancy, or a history of malignancy.

2. 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)

3. patients with prior systemic or cardiac therapy with similar nucleic acid medications

4. a known history of drug abuse or drug allergy

5. pregnant or lactating women or those who are not using effective contraception;

6. 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Shanghai CirCode Biomed Co.,Ltd

INDUSTRY

Sponsor Role: collaborator

Shanghai Bestudy Medical Technology Co., Ltd

UNKNOWN

Sponsor Role: collaborator

Ruijin Hospital

OTHER

Sponsor Role: lead

Responsible Party

Qiang Zhao,MD

Professor and Director, Department of Cardiac Surgery, Vice President

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Qiang Zhao, MD

Role: PRINCIPAL_INVESTIGATOR

Ruijin Hospital

Yunpeng Zhu, MD

Role: STUDY_DIRECTOR

Ruijin Hospital

Locations

Ruijin Hospital Shanghai Jiao Tong University School of Medicine

Shanghai, Shanghai Municipality, China

Countries

China

Other Identifiers

HM2002-001

Identifier Type: -

Identifier Source: org_study_id