Evaluate the Efficacy and Safety of Allogeneic Umbilical Cord Mesenchymal Stem Cells As an Add-On Treatment for Acute ST-elevation Myocardial Infarction (STEMI) Patients

A Phase IIa, Dose-Escalation Followed by Randomized, Open-Label, Parallel-Group Study to Evaluate the Efficacy and Safety of Allogeneic Umbilical Cord Mesenchymal Stem Cells As an Add-On Treatment for Acute ST-elevation Myocardial Infarction (STEMI) Patients

This phase IIa study is to identify the efficacy and safety of IC(intracoronary) and IV(Intravenous) administrations of UMSC01 in patients with STEMI . This product is a new cell therapy product for treating AMI and produced by Ever Supreme Bio Technology Co., Ltd in Taiwan. The previous Phase I, open-label, single arm, single center study was conducted to evaluate the safety and to explore the efficacy of UMSC01 in subjects with STEMI via intracoronary administration followed by intravenous infusion. This first-in-human Phase I study of UMSC01 was completed on August 2nd, 2021. Among 8 subjects enrolled, no subjects experienced treatment-related TEAEs.

This is a two-stage Phase IIa, dose escalation followed by randomized, open-label, controlled with standard treatment, parallel-group study to evaluate the efficacy and safety of allogeneic umbilical cord mesenchymal stem cell, UMSC01, as an add-on treatment in subjects with STEMI. Subjects should present typical ischemic chest pain within 12 hours after symptoms onset and are diagnosed acute STEMI. Subjects should have undergone standard-of-care for STEMI, the immediate reperfusion management should include primary percutaneous coronary intervention (PCI), aspiration thrombectomy, and adjunctive antithrombotic therapy within 12 hours after the onset of symptoms. This study aims to treat eligible subjects with UMSC01 as an add-on stem cell therapy along with standard-of-care for STEMI. The investigational product (IP), UMSC01, will be applied to subjects via intracoronary (IC) infusion on the 4th - 5th day after the onset of the heart attack, followed by intravenous (IV) infusion 2 days after the IC infusion.

Inclusion Criteria:

1. Male or female subjects are aged ≥ 20, < 76 years old on date of consent

2. Presence of typical ischemic chest pain within 12 hours after symptoms onset and clinical diagnosis of acute STEMI according to the 2013 American College of Cardiology (ACC) Foundation/ American Heart Association (AHA) guideline for the Management of STEMI

3. Has undergone standard-of-care for STEMI; the immediate reperfusion management should include primary percutaneous coronary intervention (PCI), aspiration thrombectomy and adjunctive antithrombotic therapy within 12 hours after the onset of symptoms

4. Received successful acute reperfusion therapy (residual stenosis visually < 50% and thrombolysis in myocardial infarction flow ≥ 2) with placement of an intracoronary stent and having a patent infarct-related artery suitable for cell infusion to the target area of abnormal wall motion following myocardial infarction

5. Evidence of LVEF ≥ 30% and < 50% diagnosed by echocardiogram

6. Evidence of stable vital signs prior to IC infusion of UMSC01 (Day 1), defined as no clinical significance of abnormal respiration, afebrile as judged by the investigator, systolic pressure ≥ 90 mmHg and < 160 mmHg, heart rate > 50/min and < 110/min

7. Adequate pulmonary function test defined as a force expiratory volume 1 second (FEV1) > 50% predicted and peripheral artery oxygen saturation ≥ 95% at room air

8. Adequate hematopoietic function at the screening and before administration of study medication:

   • Platelets ≥ 100,000 counts/μL.
   • Hemoglobin ≥ 8 g/dL.
   • PT, APTT ≤ 1.5X upper limit of normal (ULN).

9. Has signed and dated informed consent

10. All male subjects and female subjects with child-bearing potential (between puberty and 2 years after menopause) should use appropriate contraception method(s) shown below, for at least 1 year after the last UMSC01 treatment a. Total abstinence (when this is in line with the preferred and usual lifestyle of the subject. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception) b. Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy) or tubal ligation at least six weeks before taking study treatment. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment c. Male sterilization (at least 6 months prior to screening). For female subjects on the study, the vasectomized male partner should be the sole partner for that subject d. Combination of any two of the following listed methods: (d.1+d.2 or d.1+d.3, or d.2+d.3): d.1 Use of oral, injected or implanted hormonal methods of contraception or other forms of hormonal contraception that have comparable efficacy (failure rate < 1%), for example hormone vaginal ring or transdermal hormone contraception d.2 Placement of an intrauterine device (IUD) or intrauterine system (IUS) d.3 Barrier methods of contraception: Condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal suppository

Exclusion Criteria:

1. With cardiogenic shock (defined as systolic blood pressure <80mmHg requiring vasopressors, intra-aortic balloon pump(IABP) or extracorporeal membrane oxygenation (ECMO)
2. Presence of severe aortic stenosis or regurgitation according to the recommendation of the 2020 ACC/AHA guideline for themanagement of patients with valvular heart disease
3. Presence of severe mitral stenosis or regurgitation according to the recommendation of the 2020 ACC/AHA guideline for the management of patients with valvular heart disease
4. With a need to undergo staged coronary intervention therapy or coronary artery bypass grafting (CABG) surgery
5. Under an immuno-compromised condition, with known clinically significantly autoimmune conditions, or receiving immunosuppressive treatments within 12 weeks prior to the study intervention
6. Presence of any active malignancy that required treatment within 2 years prior to Screening Visit
7. With ongoing or within the past 2 years serious medical conditions (e.g., concurrent illness), other clinically significant cardiovascular diseases, psychiatric condition (e.g., alcoholism, drug abuse), medical history, physical findings, or laboratory abnormality that in the investigators' opinion could interfere with the results of the trial or adversely affect the safety of the subject
8. With inadequate hepatic and renal function after onset of STEMI: aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≥ 4 x upper limit of normal (ULN); estimated glomerular filtration rate (eGFR) < 40 mL/min, calculated by Modification of Diet in Renal Disease equation (MDRD) 175 formula
9. With uncontrolled diabetes mellitus (blood glucose level > 200 mg/dL or HbA1c ≥ 8.5%)
10. Participation in a clinical trial of an investigational product within 3 months prior to Screening Visit
11. Known or suspected hypersensitivity or previous adverse reaction to any ingredients of study product
12. Female subject with child-bearing potential (between puberty and 2 years after menopause) who is pregnant, lactating or has positive urine pregnancy test at Screening Visit
13. Subjects not suitable to participate the trial as judged by the Investigator(s)