Efficacy and Safety Study of Thymosin Beta 4 in Patients With Acute Myocardial Infarction

Efficacy and Safety of Recombinant Human Thymosin β4(NL005) for Injection in Patients With Acute Myocardial Infarction: a Phase IIb Clinical Study

A multicenter randomized double-blind placebo parallel control design was used in this study. The 90 participants were randomly assigned to placebo, 0.5μg/kg dose group, and 1.0μg/kg dose group in a ratio of 1:1:1. After randomization, subjects received the trial drug or placebo intravenously within 12 hours and on days 2 to 7 after PCI. The patients were observed 90 days after PCI.

Study Overview

• Status: Completed
• Conditions: Acute Myocardial Infarction
• Intervention / Treatment: Drug: Placebo; Drug: NL005 Middle Dose; Drug: NL005 High Dose

Detailed Description

Cardiovascular magnetic resonance imaging (CMR) was performed on day 5 and day 90 after PCI to evaluate myocardial infarction size, microvascular obstruction area, left ventricular ejection fraction (LVEF), left ventricular end-systolic volume (LVESV), and left ventricular end-diastolic volume (LVEDV). Physical examination, blood routine examination, and coagulation function examination were performed before the first dose, on the 7th, 30th, and 90th day after PCI. The examination before the first dose was conducted to accept the examination results from the current onset to the first dose.Electrocardiogram (ECG) was performed before the first dose, day 2, day 7, day 30, and day 90 after PCI, and the test results from the period after PCI to the first dose were received. Vital signs were examined before the first dose, day 1 to day 7, day 30, and day 90 after PCI, and the results of the examination from the first onset to the first dose were accepted during the examination before the first dose. Blood biochemical tests were performed before the first dose, from day 2 to day 4, day 7, day 30, and day 90 after PCI. The results of the examinations from the first onset to the first dose were accepted during the examination before the first dose. High-sensitivity troponin I(hs-cTnI) or troponin I(cTnI) and amino-terminal B-type natriuretic peptide precursor (NT-proBNP) or B-type natriuretic peptide (BNP) were tested before first administration and on days 2, 3, 4, and 7 after PCI. Examination results from the time after PCI to the time before initial administration; Creatine kinase isoenzyme (CK-MB) tests were performed before the first dose, 12 hours after the first dose, day 2 (if it coincided with 12 hours after the first dose, no repeat blood collection was required), day 3, and day 4. The test results from the period after PCI to the period before the first dose were accepted. Tumor markers were detected and immunogenic blood samples were collected before the first dose and on the 30th day after PCI. The tumor markers were examined before the first dose. Urine routine examination was performed before the first dose and on the 90th day after PCI. The examination before the first dose accepted the examination results from the onset of the disease to the first dose. Drug combinations, adverse events, and cardiovascular events were recorded during the trial.

• Study Type: Interventional
• Enrollment (Actual): 90
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Beijing, China
    • Fuwai Hospital, Chinese Academy of Medical Sciences

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. The subjects or their guardians voluntarily participate in the experiment and sign the informed consent;
2. Age ≥18 years old and ≤75 years old, gender is not limited;
3. STEMI patients with proximal or/and middle occlusion of a single left anterior descending artery (TIMI grade 0-1) and PCI;
4. No coronary collateral (Rentrop grade 0);

5. meet one of the following conditions:

   • The total myocardial ischemia time before PCI was < 6 hours, and the TIMI grade after PCI was < 3
   • 6 hours ≤ Total myocardial ischemia time before PCI ≤24 hours Note: Total myocardial ischemia time =PCI wire passage time - start time of chest pain
6. All subjects (male and female) must agree to use appropriate contraceptive methods (hormonal or barrier methods, abstinence) during study participation and up to 6 months of the last dosing, and women of childbearing age must test negative for pregnancy before dosing.

Exclusion Criteria:

1. Patients with a history of myocardial infarction who have received acute coronary thrombolysis, interventional therapy, or bypass surgery; A clear diagnosis of acute heart failure (Killip grade ≥III);
2. Severe arrhythmias that cannot be corrected;
3. Aortic dissection;
4. Severe liver and kidney dysfunction or severe consumption;
5. History of major surgery or hemorrhagic stroke within six months;
6. Previous history of malignant tumors;
7. Hypertensive patients with systolic blood pressure ≥180 mmHg and/or diastolic blood pressure ≥110 mmHg after active antihypertensive treatment;
8. Clinically significant allergic reaction history, especially mannitol, drugs, protein preparations, biological products;
9. Patients who participated in other clinical studies within 3 months prior to screening;
10. Can not perform CMR examination;
11. Other conditions deemed unsuitable for inclusion by the investigators (for example, those whose coronary arteries other than the left anterior descending branch were judged by the investigators to require elective revascularization therapy at the same time or within 1 month).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Patients in this treatment group will receive placebo respective. Continuous administration for 7 days.	Drug: Placebo; 30 subjects will be randomly assigned to the placebo for 7 days
Experimental: Middle Dose; 12 hours after PCI: 0.5 ug/kg Recombinant Human Thymosin β4 （intravenous injection），Day2-Day7 after PCI：0.5 ug/kg Recombinant Human Thymosin β4 （intravenous injection）	Drug: NL005 Middle Dose; Patients in this treatment group will receive NL005 for 0.5 ug/kg respective.Continuous administration for 7 days.; Other Names: NL005（ Middle Dose）
Experimental: High Dose; 12 hours after PCI: 1.0 ug/kg Recombinant Human Thymosin β4 （intravenous injection），Day2-Day7 after PCI：1.0 ug/kg Recombinant Human Thymosin β4 （intravenous injection）	Drug: NL005 High Dose; Patients in this treatment group will receive NL005 for 1.5 ug/kg respective.Continuous administration for 7 days.; Other Names: NL005（ High Dose）

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage change of myocardial infarction area	The percentage of myocardial infarction area was defined as the percentage of CMR delayed enhancement area in the entire left ventricular myocardium as measured by plane geometry of computer-assisted enhanced myocardium.Percentage change of myocardial infarction size =D5 percentage of myocardial infarction size -D90 percentage of myocardial infarction size	Day 5、Day 90

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Myocardial mass (g)	Myocardial infarction area was defined as CMR delayed enhancement area, and myocardial mass (g) were calculated , and determined by plane geometry method of computer-aided enhanced myocardium. Myocardial infarction size change =D5 myocardial infarction size -D90 myocardial infarction size.	Day 5、Day 90
Myocardial volume (ml)	Myocardial infarction area was defined as CMR delayed enhancement area, and volume (ml) were calculated, and determined by plane geometry method of computer-aided enhanced myocardium.Myocardial infarction size change =D5 myocardial infarction size -D90 myocardial infarction size.	Day 5、Day 90
Myocardial microvessel obstruction area change value	Myocardial microvessel obstruction area change value =D5 microvessel obstruction area -D90 microvessel obstruction area	Day 5、Day 90
The change of CK-MB before and after administration	CK-MB change value = CK-MB value before administration - CK-MB value after administration	Before the first dose, 12 hours after the first dose, day 2, day 3, day 4
The area under the CK-MB curve within 4 days	CK-MB change value = CK-MB value before administration - CK-MB value after administration	Before the first dose, 12 hours after the first dose, day 2, day 3, day 4
Changes of left ventricular ejection fraction (LVEF)	Left ventricular ejection fraction (LVEF) change =D90 LVEF-D5 LVEF	Day 5、Day 90
Changes of left ventricular end-systolic volume (LVESV)	Left ventricular end-systolic volume (LVESV) change =D90 LVESV-D5 LVESV	Day 5、Day 90
Changes of left ventricular end-diastolic volume (LVEDV)	Left ventricular end-diastolic volume (LVEDV) change = D90 LVEDV-D5 LVEDV	Day 5、Day 90

Collaborators and Investigators

• Sponsor: Beijing Northland Biotech. Co., Ltd.
• Investigators: Principal Investigator: Kefei Dou, Chinese Academy of Medical Sciences, Fuwai Hospital

Study record dates

Study Major Dates

• Study Start (Actual): July 15, 2022
• Primary Completion (Actual): May 26, 2023
• Study Completion (Actual): May 29, 2023

Study Registration Dates

• First Submitted: July 20, 2023
• First Submitted That Met QC Criteria: July 31, 2023
• First Posted (Actual): August 9, 2023

Study Record Updates

• Last Update Posted (Actual): June 21, 2024
• Last Update Submitted That Met QC Criteria: June 19, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Keywords: CMR
• Additional Relevant MeSH Terms: Ischemia; Pathologic Processes; Necrosis; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Myocardial Infarction; Infarction
• Other Study ID Numbers: NL005-AMI-IIb

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No