Evaluate the Safety and Explore Efficacy of Umbilical Cord Mesenchymal Stem Cells in Acute Ischemic Stroke
Evaluate the Safety and Explore Efficacy of Umbilical Cord Mesenchymal Stem Cells in Acute Ischemic Stroke
This study is a first-in-human assessment of safety of using umbilical cord mesenchymal stem
 cells (UCMSCs) in patients with Acute Ischemic Stroke via a combination of intra arterial
 (IA) and intravenous (IV) stem cell administration. The novelty of the current UMSC01
 treatment study is the dual route of administration. Since dual administration of UCMSC via
 IA and IV had never been conducted in humans, there may be unknown risks to humans not
 predicted from the preclinical studies. However, the risk to patients in this trial will be
 minimized by rigorous adherence to the eligibility criteria, use of appropriate dose and
 concentration of stem cells, standardized techniques of stem cell infusion, and intensive
 patient monitoring during and after stem cell infusion.
Each year about 700,000 people experience a new or recurrent stroke in the United
 States.Stroke is a leading cause of death, along with cancer and coronary heart disease, and
 the most common cause of physical disability in adults. Moreover, stroke causes a greater
 loss of healthy life years, as measured in disability adjusted life years, than other
 diseases.

 This product is a new cell therapy product for treating Stroke and produced by Ever Supreme
 Bio Technology Co., Ltd in Taiwan. For animal studies, UMSC01 has been demonstrated its
 effectiveness for acute myocardial infarction (AMI) and stroke. The UMSC01 has been
 demonstrated its effective effect in the animal models of stroke in the current studies. The
 acute stroke rats receiving intracerebral UMSC01 transplantation showed significantly
 improved neurological function compared to vehicle-treated control rats.
Donor-Inclusion Criteria:

 1. Pregnant women who are aged ≥ 20, <50 years old on the date of consent.

 2. Pregnant women who are willing to and has given her signed written informed consent.

 3. Pregnant women whose gestation age ≥ 34 weeks and have intact placenta.

 4. Pregnant women who have not had any complication of pregnancy.

 5. Pregnant women who are willing to provide a personal and family medical history (as
 much available) of herself and the biologic father (as much available), prior to or
 following collection of the umbilical cord.

 Donor-Exclusion Criteria:

 1. Pregnant women who have clinically severe and/or life threatening disease(s) such as
 uncontrolled diabetes mellitus (fasting sugar level > 250 mg/dL) and malignant tumor.

 2. Pregnant women who have been tested positive for the following tests within 7 days
 before or after umbilical cord acquirement:

 -  Human immunodeficiency virus-1 (HIV-I): anti- HIV-I and nucleic acid test (NAT)

 -  HIV-II

 -  Hepatitis B virus (HBV): Hepatitis B surface antigen (HBsAg), anti- Hepatitis B
 core (HBc) and NAT

 -  Hepatitis C virus (HCV): anti-HCV and NAT

 -  Cytomegalovirus (CMV)

 -  Treponema pallidum

 -  Chlamydia trachomatis

 -  Neisseria gonorrhea

 -  Human T cell leukemia virus-I/II (HTLV-I/II)

 -  West Nile virus (WNV) NAT

 3. Pregnant women are with increased risk for Creutzfeldt-Jakob disease (CJD) if you have
 received a non-synthetic dura mater transplant, human pituitary-derived growth
 hormone, or have one or more blood relatives diagnosed with CJD.

 4. Pregnant women had spent three months or more cumulatively in the United Kingdom (U.K)
 from the beginning of 1980 through the end of 1996; or had received any transfusion of
 blood or blood components in the U.K. or France between 1980 and the present; or lived
 5 years or more cumulatively in Europe.

 5. Pregnant women or her sexual partners were born or lived in certain countries in
 Africa (Cameroon, Central African Republic, Chad, Congo, Equatorial Guinea, Gabon,
 Niger, or Nigeria) after 1977 (risk factor for HIV group O).

 6. Pregnant women who have medical diagnosis of Zika virus (ZIKV) infection or residence
 in, or travel to, an area with active ZIKV transmission (according to the list from
 Centers for Disease Control and Prevention. Zika Virus: Areas with Zika) at any point
 during that pregnancy.

 7. Pregnant women who have sex at any point during that pregnancy with a male who is
 known to medical diagnosis of ZIKV infection or residence in, or travel to, an area
 with active ZIKV transmission.

 8. Pregnant women who have received blood infusion or stayed for more than 3 months in
 WNV potential countries.

 9. Pregnant women who have unexplained post-donation febrile illness with headache or
 other symptoms suggestive of WNV infection (i.e., flu-like symptoms that include fever
 with headache, eye pain, body aches, generalized weakness, new skin rash or swollen
 lymph nodes or other evidence of WNV infection) within two weeks.

 10. Pregnant women who have medical history of tuberculosis.

 11. Pregnant women who have medical history of malignant tumor.

 12. Fetuses that have found with genetic disease in prenatal checkups.

 13. Pregnant women who would like to store cord blood or umbilical cord cells, other than
 this study usage.

 14. Pregnant women who are not suitable to donate as judged by the Investigator(s).

 Subject-Inclusion Criteria:

 1. Male or female who are age ≥ 20, ≤80 years old on date of consent.

 2. Patients who have had a recent (onset within the past 36 hours) acute ischemic stroke
 in the unilateral middle cerebral artery (MCA) distribution (M1 and M2). The location
 of ischemic stroke should be diagnosed by magnetic resonance image (MRI).

 3. Patients who have National Institutes of Health Stroke Scale (NIHSS) score of 8 to 17
 with both motor arm and motor leg scores ≥ 3 (MRC scale).

 4. Patients who have Glasgow Coma Scale (GCS) score of > 8 on the date of consent.

 5. Patients who have modified Rankin Scale (mRS) of 2~4 on the date of consent and their
 mRS prior to stroke onset should be 0 or 1 (either by self-reported history or by
 family/caregiver report).

 6. Patients who have stable vital signs for at least 24 hours, defined as normal
 respiration, afebrile and mean arterial pressure ≤ 180 mmHg.

 7. Patient's random blood sugar <350 mg/dl and > 50 mg/dl and normal urea/ electrolytes.

 8. Patient has appropriated blood clotting function as assessed by the following
 laboratory requirements: PT, APTT ≤ 1.5X upper limit of normal (ULN).

 9. Patients are willing to sign informed consent or assent by the next of kin.

 10. All male patients and female patients with child-bearing potential (between puberty
 and 2 years after menopause) should use appropriate contraception method(s) shown
 below, for at least 4 weeks after UMSC01 treatment.

 1. 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).

 2. 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.

 3. 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.

 4. 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.

 Subject-Exclusion Criteria:

 1. Patients with recurring stroke attack within 6 months before this current stroke
 episode.

 2. Patients with signs of midline shift, hemorrhagic transformation or fluctuation of
 symptoms.

 3. Patients who have participated in other investigational studies and received any
 treatment within 4 weeks prior to receiving UMSC01.

 4. Patients who have immuno-compromised condition,or are with known clinically
 significantly autoimmune conditions or are receiving immunosuppressive treatments.

 5. Patients who are unable to undergo brain Single-photo Emission Computed Tomography
 (SPECT), CT, MRI and PET scans for any reason.

 6. Patients with inadequate hepatic and renal function after onset of acute ischemic
 stroke: Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) ≥ 5 x
 upper limit of normal (ULN); estimated glomerular filtration rate (eGFR) < 30 mL/min
 at screening.

 7. Patients who have medical history of malignant tumor, spinal injury or other
 clinically significant neurological diseases that will confound the evaluation of this
 study.

 8. Patients who have clinically active peripheral nephropathy, myopathy or other
 clinically significant neurological diseases that will confound the evaluation of this
 study.

 9. Patients who have a difference in NIHSS score ≥ 5 between the time beginning
 hospitalization and investigational product (IP) treatment.

 10. Patients who are diagnosed of heart failure with a New York Heart Association (NYHA)
 score of III or IV.

 11. Patients not suitable to participate the trial as judged by the investigator(s).