Acute Ischemic Stroke

Primary objectives To assess the safety and feasibility of two doses of human umbilical cord blood (hUCB) infusion in patients with acute ischemic stroke (AIS). Secondary objectives To evaluate the efficacy of two doses of hUCB infusion in patients with AIS.

injection

臍帶血造血幹細胞(HPC, Cord Blood, hUCB)

246

>5*10^8 TNC/bag

Primary endpoint:
• Frequency and incidence of treatment-emergent adverse events (TEAEs).
2. Secondary endpoints:
• Mean change from baseline (Day 1) in National Institutes of Health Stroke Scale
(NIHSS) scores to Day 6, 13, 34, 90, 174 and 370.
• Mean change from baseline (Day 1) in Modified Rankin Scale (mRS) scores to Day
6, 13, 34, 90, 174 and 370.
• Mean change from baseline (Day 1) in Barthel Index (BI) scores to Day 6, 13, 34,
90, 174 and 370.

1) Male or female subject ≥45 and ≤80 years of age.
2) Subject with a confirmed diagnosis of AIS and hemiplegia.
3) Subject is able to perform blood type (ABO/rhesus [Rh]/ human leukocyte
antigen [HLA]) analysis and matched within 5 days of stroke symptoms onset
and receive the first IP (i.e., hUCB)/placebo (i.e., normal saline) infusion within 9
days after stroke symptoms onset.
4) Subject with at least 2 packages of HLA-, ABO blood group-, and Rh type-matched
hUCB available for infusion.
Note: HLA-matched is defined as ≥4:6 matched pairs in HLA typing with the
available hUCB.
5) Subject with NIHSS score ranging from 6 to 18 (inclusive) at the time of
screening.
6) Subject’s brain magnetic resonance imaging (MRI) shows that the lesion(s)
located at the blood flow distribution region of the internal carotid artery,
without midline shift or hemorrhagic transformation.
7) Subjects and their partners with childbearing potential agree to use medically
accepted contraception methods.
8) Subject is willing and able to participate in all aspects of the study, including
completion of subjective evaluations, attendance at scheduled clinic visits, and
compliance with all protocol requirements as evidenced by providing a signed
informed consent (by the subject or his/her legally authorized representative).
9) Subject is ineligible to receive recombination tissue type plasminogen activator
(rt-PA) therapy or endovascular thrombectomy (EVT) for the management of
current stroke prior to screening, at the treating physician’s discretion.

1) Subject with NIHSS score changed ≥4 points with an interval of 24 hours at
screening.
2) Subject receives recombination tissue type plasminogen activator (rt-PA)
therapy or endovascular thrombectomy (EVT) for the management of current
stroke prior to screening.
3) Subject with liver or renal insufficiency, other circumstances (as follows),
acquired immune deficiency syndrome (AIDS), significant physical and medical
condition (including notifiable and rare diseases), and concurrent or underlying
disease that, according to the Investigator’s evaluation, may impact the study
assessments or put the subject’s safety at risk through participation.
Notes:
• Liver insufficiency is defined as:
▪ Alanine transaminase (ALT) >3 x upper limit of normal (ULN), or
▪ Aspartate transaminase (AST) >3 x ULN, or
▪ Total bilirubin >2.5 mg/dL.
• Renal insufficiency is defined as:
▪ Currently on dialysis, or
▪ Estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m2.
• Other circumstances which may have an impact on subject’s safety are:
▪ Absolute neutrophil count (ANC) <1,500/µL, or
▪ White blood cells (WBC) <3.6 x 103/µL, or
▪ Platelet counts <100 x 103/µL, or
▪ Hemoglobin <10 g/dL, or
▪ International normalized ratio (INR) >1.5 x ULN, or
▪ Activated partial thromboplastin time (aPTT) >1.5 x ULN.
4) Subject with known immune disease, immunodeficiency, or receives
immunosuppressive therapy/immunomodulators within 4 weeks or 5 half-lives
prior to screening, whichever is longer.
5) Subject is unable to undergo MRI assessment.
6) Subject with known hypersensitivity to dimethyl sulfoxide (DMSO), Dextran 40,
or plasma proteins.
7) Subject with pre-existing terminal illness.
8) Subject diagnosed with active-cancer or receiving chemotherapy at screening.
9) Female subject who is currently pregnant or lactating.
10) Subject is currently participating in another investigational study or has
received:
• Investigational drug within 4 weeks or 5 half-lives prior to screening,
whichever is longer, or
• Cell therapy within 1 year prior to screening.
11) Subject with the diagnosis of hemorrhagic or ischemic stroke (except for current
stroke) within 3 months prior to screening, or subject presents with poor
prognosis, outcomes (e.g., disability or weakness), or serious complications due
to previous stroke.
12) Judged by the investigator to be not suitable for study participation.