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

NCT06621576 | Active Not Recruiting Early Phase 1

• 1 other identifier: HM2002-001
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

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.

Conditions

Ischaemic Heart Disease; Heart Failure

Outcome Measures

Primary Outcomes (1)

• Incidence of Adverse Events (AEs), Serious Adverse Events (SAEs) and Clinically Meaningful Changes from Baseline in Clinical Laboratory Tests, Vital Signs, and Electrocardiogram Parameters

  To assess the safety of a single 5 mg dose of HM2002 injection in treating ischemic heart failure by evaluating the incidence of adverse events (AEs) and serious adverse events (SAEs) as categorized according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0, along with clinically meaningful changes from baseline in clinical laboratory tests (including complete blood count \[CBC\], liver function tests \[LFTs\], renal function tests \[RFTs\], and coagulation function), vital signs (such as systolic and diastolic blood pressure, heart rate, respiratory rate, and body temperature), and 12-lead electrocardiogram (ECG) parameters (including heart rhythm disturbances, ST segment deviations, T wave abnormalities, and alterations in PR or QT interval).

  6 months

Secondary Outcomes (9)

• Myocardial Perfusion Changes

  Baseline, 6 months

• CMR Assessment of LVEF

  Baseline, 6 months

• NT-proBNP Level Changes

  Baseline, 1 month, 3 months, and 6 months

• Echocardiographic Assessment of Cardiac Function

  Baseline, 1 month, 3 months, and 6 months

• Perfusion Changes in Ischemic Myocardium

  Baseline, 6 months

Study Arms (1)

HM2002 Injection group

EXPERIMENTAL

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

Drug: HM2002 injection

Interventions

HM2002 injection 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.

HM2002 Injection group

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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;

You may not qualify if:

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

Sponsors & Collaborators

• Ruijin Hospital: lead
• Shanghai CirCode Biomed Co.,Ltd: collaborator
• Shanghai Bestudy Medical Technology Co., Ltd: collaborator

Study Sites (1)

Ruijin Hospital Shanghai Jiao Tong University School of Medicine

Shanghai, Shanghai Municipality, 200025, China

Location

MeSH Terms

Conditions

Coronary Artery Disease; Heart Failure

Condition Hierarchy (Ancestors)

Coronary Disease; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases

Study Officials

• Qiang Zhao, MD

  Ruijin Hospital

  PRINCIPAL INVESTIGATOR

• Yunpeng Zhu, MD

  Ruijin Hospital

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor and Director, Department of Cardiac Surgery, Vice President

Study Record Dates

• First Submitted: September 17, 2024
• First Posted: October 1, 2024
• Study Start: September 18, 2024
• Primary Completion: May 1, 2025
• Study Completion: September 1, 2025
• Last Updated: April 2, 2025

Record last verified: 2025-04

Locations

CN (1)