Clinical trial NCT05485818: Safety and Efficacy Study of Thymosin Beta 4 in Patients With Acute Myocardial Infarction.Infarction
Official title: Phase IIa Clinical Study of Efficacy and Safety of Injectable Recombinant Human Thymosin Beta 4 in Patients With Acute Myocardial Infarction
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Acute Myocardial Infarction
Keywords: AMI
Lead sponsor: Beijing Northland Biotech. Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2022-08-03
Enrollment: 62
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: A multicenter randomized double-blind placebo parallel control design was used in this study.60 subjects eligible for inclusion will be randomly assigned to either a low-dose (0.25ug/kg) medium-dose (0.5ug/kg) high-dose (2.0ug/kg) experimental drug group or a control group (placebo) at a ratio of 1:1:1:1.After randomization, subjects received the experimental drug or placebo once a day, intravenously, on day 2 to 7, 12 hours and 4 hours after PCI.Ninety days after PCI were observed.

Detailed description: Subjects underwent cardiovascular magnetic resonance imaging (CMR) on the 90th day after PCI, which was used to evaluate the myocardial salvage index myocardial infarction area, microvascular occlusion area, left ventricular ejection fraction (LVEF), left ventricular end-systolic volume (LVESV), and left ventricular end-diastolic volume (LVEDV).Echocardiography was performed on the 5th and the 90th day after PCI to evaluate the left indoor diameter (LV) and left atrial diameter (LA) of LVEF.

Physical examination routine blood coagulation function was performed on the 30th and 90th day after PCI in the screening period (pre-screening results were acceptable);Electrocardiogram (ECG) was performed on the 30th and the 90th day after PCI on the 2nd day after the first administration;During the screening period (results before screening are acceptable), vital signs should be measured from day 1 to day 7 after PCI (during each dose, vital signs should be measured twice on day 7, including before and after administration), on day 30 and day 90;Blood biochemical examinations were performed from day 2 to day 4, day 7, day 30, and day 90 after PCI before the first administration;Creatine kinase isoenzyme (CK-MB) hypersensitive 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 detected on day 2, day 3, day 4 and day 7 after PCI before the first administration.Tumor markers were detected and immunogenicity blood samples were collected 30 days after PCI before the first administration.Routine urinalysis was performed 90 days after PCI before the first administration;Adverse drug events and cardiovascular events were continuously recorded during the trial.

Eligibility criteria: Inclusion Criteria:

1. The subject or its legal representative will voluntarily participate in the study and sign the informed consent;
2. Age 18 and 75, regardless of gender;
3. STEMI patients with left anterior descending branch single-artery middle occlusion (TIMI grading 0\~1, see Appendix 1 for TIMI grading) and receiving PCI;
4. No obvious collateral of coronary artery (Rentrop grade 0\~1,Rentrop grade see Appendix 2);
5. Chest pain occurred for 6 hours and 12 hours before PCI;
6. TIMI grade 3 after PCI;
7. All subjects (male and female) must agree to use appropriate contraceptive methods (hormonal or barrier contraceptive methods, abstinence) during the study period and up to 6 months after the last administration, and women of childbearing age must test negative for pregnancy before administration.

Exclusion Criteria:

1. Patients who have a history of myocardial infarction or have received coronary artery acute thrombolytic interventional therapy with bypass surgery;
2. patients who received thrombolytic therapy after onset;
3. patients who were clearly diagnosed as acute heart failure (Killip grade II,Killip classification in annex 3);
4. Severe arrhythmia that cannot be corrected;
5. Aortic dissection or suspected presence;
6. Severe liver and kidney dysfunction or severe depletion, etc;
7. major surgical history or hemorrhagic stroke in half a year;
8. Has or has a history of malignancy;
9. Systolic blood pressure ≥180 mmHg and/or diastolic blood pressure ≥110 mmHg in patients with hypertension after active antihypertensive treatment;
10. Clinically, he had a significant history of allergy, especially to mannitol, drugs, protein preparations and biological products;
11. Screening of patients who participated in other clinical studies within the first 3 months;
12. Failure to perform CMR test: such as claustrophobia, renal failure (eGFR \< 30ml/min);
13. Other conditions not considered suitable for inclusion by the researcher.

Primary outcomes:
measure: Change of myocardial infarction area on Day 5 and day 90 after PCI
timeFrame: Day 5、Day 90
Secondary outcomes:
measure: Change of myocardial salvage index on Day 5 and day 90 after PCI
timeFrame: Day 5、Day 90
measure: Change of microvascular obstruction area on Day 5 and day 90 after PCI
timeFrame: Day 5、Day 90
measure: Change of LA on Day 5 and day 90 after PCI
timeFrame: Day 5、Day 90
measure: Changeof LV on Day 5 and day 90 after PCI
timeFrame: Day 5、Day 90
measure: Change of LVEF on Day 5 and day 90 after PCI
timeFrame: Day 5、Day 90
measure: Change of LVESV on Day 5 and day 90 after PCI
timeFrame: Day 5、Day 90
measure: Change of LVEDV on Day 5 and day 90 after PCI
timeFrame: Day 5、Day 90
measure: Number of participants with treatment-related adverse events as assessed by NCI-CTCAE v5.0
timeFrame: Day0、Day1、Day2、Day3、Day4、Day5、Day6、Day7、Day30、Day90
measure: Incidence of anti-drug antibody (ADA)
timeFrame: Day 0、Day 30
Other outcomes:
Locations:
city: Beijing
country: China
facility: Fuwai Hospital, Chinese Academy of Medical Sciences
Study officials:
affiliation: Chinese Academy of Medical Sciences, Fuwai Hospital
name: KeFei Dou
role: PRINCIPAL_INVESTIGATOR
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