Recombinant Human Thymosin Beta 4 for Injection(NL005) for Acute Myocardial Infarction

A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Phase IIc Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of Recombinant Human Thymosin Beta 4 Injection (NL005) in Patients With Acute Myocardial Infarction

The goal of this phase IIc clinical trial is to learn if recombinant human thymosin beta 4 injection (NL005) works to treat heart damage in people who have had a serious type of heart attack called ST-segment elevation myocardial infarction (STEMI) and have been treated with emergency percutaneous coronary intervention (PCI, a procedure to open the blocked artery). It will also learn about the safety of NL005. The main questions it aims to answer are:

• Does NL005 lower the size of permanent heart muscle damage measured by cardiac magnetic resonance (CMR) scan 90 days after treatment?
• What medical problems do participants have when taking NL005?

Researchers will compare two different doses of NL005 to a placebo (a look-alike substance that contains no drug) to see if NL005 works better to reduce heart damage caused by the heart attack.

Participants will:

• Receive NL005 or placebo through a vein within 4 hours after the PCI procedure, then once a day for 7 days
• Stay in the hospital for the first week for monitoring, blood draws, and electrocardiograms (heart tracings)
• Have a CMR scan on Day 6 and Day 90 to measure the size of the heart injury
• Return to the hospital for checkups on Day 30 and Day 90
• Be contacted by the study team (by phone or online) 3 times during the first year and come back to the hospital on Day 360 to check long-term recovery

This multicenter, randomized, double-blind, placebo-controlled, parallel-group phase IIc study evaluates the efficacy, safety, and pharmacokinetics of recombinant human thymosin beta 4 injection (NL005) in patients with acute STEMI undergoing primary PCI. Approximately 189 participants are randomized 1:1:1 to NL005 10 µg/kg, NL005 20 µg/kg, or matching placebo.

Eligible participants have first anterior STEMI from left anterior descending artery occlusion. Full eligibility details are provided in the corresponding module.

The study includes a screening period, a 7-day inpatient treatment phase, follow-up visits at Day 30 and Day 90, and an extended follow-up period through Day 360.

Inclusion Criteria:

• Willing and able to provide written informed consent (by the participant or legally authorized representative)
• Aged 18 to 75 years old, any sex
• Diagnosis of ST-segment elevation myocardial infarction (STEMI) with electrocardiogram (ECG) meeting protocol-specified ST-elevation criteria, and scheduled to undergo primary percutaneous coronary intervention (PCI)
• OR, regardless of ECG criteria, the participant has a completely or nearly completely blocked (TIMI flow grade 0 or 1) proximal or mid left anterior descending (LAD) coronary artery as the single culprit vessel
• The blocked LAD artery has no visible collateral blood supply from other coronary arteries (Rentrop grade 0)
• Total myocardial ischemic time (time from chest pain onset to guidewire passage during PCI) meets one of the following: 1. More than 2 hours and less than 6 hours of ischemic time, with either post-PCI LAD TIMI flow grade of 2 or less, or left ventricular ejection fraction (LVEF) of 50% or lower measured by cardiac ultrasound during PCI hospitalization; 2. Between 6 and 24 hours of ischemic time (inclusive)
• Males and females of childbearing potential must agree to use adequate contraception (such as hormonal or barrier methods, or abstinence) throughout the study

Exclusion Criteria:

• Prior history of acute myocardial infarction, chronic total coronary occlusion, coronary thrombolysis, PCI, or coronary artery bypass graft surgery
• Diagnosis of severe acute heart failure (Killip class III or higher) or chronic heart failure (NYHA functional class III or higher)
• Severe, uncontrolled arrhythmia that cannot be corrected
• Presence of aortic dissection
• Severe liver or kidney dysfunction
• History of stroke within the past 6 months
• Current or past diagnosis of any malignancy
• Blood pressure that remains at or above 180 mmHg systolic and/or 110 mmHg diastolic despite adequate antihypertensive treatment
• History of clinically significant allergic reaction, especially known allergy to protein or biologic drugs
• Participation in another clinical study within 3 months before screening
• Unable to undergo cardiac magnetic resonance (CMR) imaging (e.g., due to implanted metal devices, severe claustrophobia, or other contraindications)
• Any other condition that the investigator believes makes participation unsuitable (for example, the need for urgent or planned revascularization of non-LAD coronary arteries within 3 months)