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

Official title

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

Overview

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

Detailed description

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.

Interventions

• Drug Recombinant Human Thymosin Beta 4 Injection (NL005)
  NL005 is a sterile solution of recombinant human thymosin beta 4 formulated for intravenous injection. It is supplied as a 1.5 mg (1 mL) vial and stored at 2-8°C. For each dose, the appropriate volume is drawn to achieve 10 µg/kg or 20 µg/kg, and the total volume is adjusted to 5 mL with compatible diluent before administration.
• Drug Placebo
  The placebo is a sterile solution identical in appearance to NL005 and contains no active ingredient. It is supplied as a 1 mL vial and stored at 2-8°C. Each dose is formulated in a total volume of 5 mL and administered intravenously.

Primary outcome measures

• Myocardial Infarct Size (absolute) at Day 90 [Time frame: Day 90 (±7 days)]
• Myocardial Infarct Size (relative) at Day 90 [Time frame: Day 90 (±7 days)]

Secondary outcome measures (12)

• Myocardial Infarct Size (absolute) at Day 6 [Time frame: Day 6 (±1 day)]
• Myocardial Infarct Size (relative) at Day 6 [Time frame: Day 6 (±1 day)]
• Microvascular Obstruction (MVO)(absolute) [Time frame: Day 6 (±1 day), Day 90 (±7 days)]
• MVO (relative) [Time frame: Day 6 (±1 day), Day 90 (±7 days)]
• Left Ventricular Ejection Fraction (LVEF) [Time frame: Day 6 (±1 day), Day 90 (±7 days)]
• Left Ventricular End Systolic Volume index (LVESVi) [Time frame: Day 6 (±1 day), Day 90 (±7 days)]
• Left Ventricular End Diastolic Volume index (LVEDVi) [Time frame: Day 6 (±1 day), Day 90 (±7 days)]
• LVEF at Day 90 Change from Day 6 [Time frame: Day 6 (±1 day), Day 90 (±7 days)]
• LVEDVi at Day 90 Change from Day 6 [Time frame: Day 6 (±1 day), Day 90 (±7 days)]
• LVESVi at Day 90 Change from Day 6 [Time frame: Day 6 (±1 day), Day 90 (±7 days)]
• Biomarkers: N-terminal pro-B-type natriuretic peptide (NT-proBNP) [Time frame: Baseline (pre-dose), Day 2/3/7/30/90]
• Biomarkers: soluble ST2 (sST2) [Time frame: Baseline (pre-dose), Day 2/3/7/30/90]

Eligibility criteria

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)

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

China · 1 center

• Fuwai Hospital Chinese Academy of Medical Sciences (CAMS) — Beijing

Identifiers

NCT: NCT07586865 · NL005-AMI-IIc

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗