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

Phase 2Not Yet RecruitingNCT07586865

Beijing Northland Biotech. Co., Ltd.189 enrolled

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

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

Interventions

Recombinant Human Thymosin Beta 4 Injection (NL005)DRUG

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.

PlaceboDRUG

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.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 75 Years

Medical Language ↔ Plain English

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)

Outcomes

Primary Outcomes

Myocardial Infarct Size (absolute) at Day 90

Myocardial infarct size measured by late gadolinium enhancement cardiac magnetic resonance (LGE-CMR), expressed in absolute (grams).

Time frame: Day 90 (±7 days)

Myocardial Infarct Size (relative) at Day 90

Myocardial infarct size measured by LGE-CMR, expressed in relative (percentage of LV mass), calculated as (infarct mass / total LV mass) × 100%.

Time frame: Day 90 (±7 days)

Secondary Outcomes

Myocardial Infarct Size (absolute) at Day 6

Myocardial infarct size measured by LGE-CMR, expressed in absolute (grams).

Time frame: Day 6 (±1 day)

Myocardial Infarct Size (relative) at Day 6

Myocardial infarct size measured by LGE-CMR, expressed in relative (percentage of LV mass), calculated as (infarct mass / total LV mass) × 100%.

Time frame: Day 6 (±1 day)

Microvascular Obstruction (MVO)(absolute)

MVO measured by LGE-CMR, expressed in absolute (grams).

Time frame: Day 6 (±1 day), Day 90 (±7 days)

MVO (relative)

MVO measured by LGE-CMR, expressed in relative (percentage of LV mass), calculated as (MVO mass / total LV mass) × 100%.

Time frame: Day 6 (±1 day), Day 90 (±7 days)

Left Ventricular Ejection Fraction (LVEF)

LVEF measured by CMR.

Time frame: Day 6 (±1 day), Day 90 (±7 days)

Left Ventricular End Systolic Volume index (LVESVi)

LVESVi=left ventricular end systolic volume (LVESV)/body surface area (BSA, m²), LVESV measured by CMR.

Time frame: Day 6 (±1 day), Day 90 (±7 days)

Left Ventricular End Diastolic Volume index (LVEDVi)

LVEDVi=left ventricular end diastolic volume (LVDSV)/body surface area (BSA, m²), LVEDV measured by LGE-CMR.

Time frame: Day 6 (±1 day), Day 90 (±7 days)

LVEF at Day 90 Change from Day 6

Change from Day 6 to Day 90.

Time frame: Day 6 (±1 day), Day 90 (±7 days)

LVEDVi at Day 90 Change from Day 6

Change from Day 6 to Day 90.

Time frame: Day 6 (±1 day), Day 90 (±7 days)

LVESVi at Day 90 Change from Day 6

Change from Day 6 to Day 90.

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

Biomarkers: high-sensitivity cardiac troponin I (hs-cTnI)

Time frame: Baseline (pre-dose), Day 2/3/7/30/90

Biomarkers: creatine kinase-MB (CK-MB)

Time frame: Baseline (pre-dose), Day 2/3/7/30/90

Biomarkers: high-sensitivity C-reactive protein (hs-CRP)

Time frame: Baseline (pre-dose), Day 2/3/7/30/90

Proportion of participants with persistent MVO at Day 90.

Time frame: Day 90 (±7 days)

Number of Participants with Treatment-Emergent Adverse Events (TEAEs)

An adverse event (AE) is any untoward medical occurrence, regardless of causal relationship to study drug. A treatment-emergent adverse event (TEAE) is defined as an event that starts or worsens in severity on or after the first dose.

Time frame: First dose through Day 360

Incidence of Anti-Drug Antibodies (ADA)

Time frame: Baseline and Day 30

Peak Concentration (Cmax)

Each participant contributes a total of 4 venous blood samples during Days 1-7, with one sample drawn at each of the following post-dose time points: 3-5 minutes, 15±3 minutes, 3±15 hours, and 6±15 hours. Plasma concentrations of NL005 are measured using a validated assay. The parameter is estimated by population PK modeling, combining data from this study with data from a prior Phase I study.