Evaluation of the Safety and Efficacy of Hemacord HPC, Cord Blood in Subjects With Acute Ischemic Stroke
Evaluation of the Safety and Efficacy of Hemacord HPC, Cord Blood in Subjects With Acute Ischemic Stroke
This is a phase one study investigating the safety and efficacy profile of allogeneic cord
 blood hematopoietic progenitor cells (HPC, Cord Blood), when administered by intravenous
 infusion and intrathecal injection, in subjects who have sustained an acute ischemic stroke
 within the past 9 days. Treatment period consisting of 3 sessions of both intravenous
 infusion and intrathecal injection (or intravenous infusion in conjunction with mannitol for
 subjects unable to tolerate intrathecal injection). Follow-up phone calls for adverse event
 (AE) assessment will be conducted at 1 week, 1 month, and 2 months after the first
 intravenous/intrathecal treatment. A follow up clinic visit at 3 months, 6 months and 12
 months will include a neurological exam, MRI, and clinical laboratory tests/urinalysis.
The primary objective of the study is to evaluate the safety of HPC, Cord Blood (administered
 via intravenous infusion and intrathecal injection, or intravenous infusion in conjunction
 with mannitol for subjects unable to tolerate intrathecal injection) in subjects with acute
 ischemic stroke. The secondary objective is to evaluate the efficacy of HPC, Cord Blood (as
 assessed by changes in neurological tests and cerebral infarct volume as measured by
 diffusion-weighted magnetic resonance imaging (MRI)) in subjects with acute ischemic stroke.

 This is a prospective, open-label, single-center, exploratory clinical study in subjects ≥ 18
 years of age who have sustained a recent ischemic stroke. A total of 10 subjects will be
 enrolled. Subjects will be given a series of baseline neurological assessments, blood tests,
 and MRI.

 All subjects will be administered only ABO- and Rh-matched units of HPC, Cord Blood. Subjects
 will not be matched for human leukocyte antigen (HLA)-typing. For each administration of HPC,
 cord blood, the total dose (2.5 × 10^7 cells/kg; 150 × 10^7 cells) will be split for
 intrathecal injection followed immediately by intravenous infusion. HPC, Cord Blood will be
 administered via intravenous infusion and intrathecal injection, in subjects who have
 sustained an acute ischemic stroke within the past 9 days. Intravenous infusion in
 conjunction with mannitol will be used in instances where a subject is unable to tolerate
 intrathecal administration. Treatment period consisting of 3 sessions, timed 5 to 12 days
 apart. Subjects will be monitored for 6 hours post-infusion, and follow up will occur 24
 hours after each therapy session. Follow-up phone calls for adverse event (AE) assessment
 will be conducted at 1 week, 1 month, and 2 months after the first intravenous/intrathecal
 treatment. A follow up clinic visit at 2 weeks, 3 months, 6 months, and 12 months after the
 first intravenous/intrathecal treatment will include a neurological exam, MRI, and clinical
 laboratory tests/urinalysis.

 Risks of cord blood infusion include infusion-related reactions such as anaphylaxis,
 urticaria, dyspnea, hypoxia, cough, wheezing, bronchospasm, nausea, vomiting, hives, fever,
 hypertension, hypotension, bradycardia, tachycardia, rigors, chills, infection, and
 hemoglobinuria. Less likely, long-term risks include transmission of infection or Graft vs
 Host Disease.
Inclusion Criteria:

 Subjects are eligible for the study if all of the following criteria are met:

 -  Subject is ≥ 18 years old

 -  Has had a recent (within the past 9 days), acute, cortical, hemispheric, ischemic
 stroke in the MCA distribution without a midline shift as detected by MRI as a
 diffusion-weighted image (DWI) abnormality

 -  Has a persistent neurological deficit (NIHSS ≥ 7) at the time of enrollment with no
 more than a 4-point increase (worsening of score) from the screening baseline score
 compared to NIHSS baseline score at 24 hours prior to infusion.

 -  A platelet count > 100,000/µL, hemoglobin > 8 g/dL, and white blood cell count (WBC) >
 2500/µL

 -  Subjects who received tPA or underwent mechanical reperfusion may be included in the
 study

 -  Is able to provide consent to study or consent is obtained from the subject's legally
 authorized representative

 -  Subjects of childbearing potential must practice effective contraception during the
 study, and be willing to continue contraception for at least 6 months after
 intervention so that, in the opinion of the investigator, they will not become
 pregnant during the course of the study

 -  Is a good candidate for the study, in the opinion of the investigator

 -  Agrees to participate in follow-up visits

 Exclusion Criteria:

 Subjects are excluded from the study if any of the following criteria are met:

 Medical Conditions

 -  Has a medical history of neurological or orthopedic pathology with a deficit as a
 consequence that results in an mRS > 1 before stroke or has a pre-existing cognitive
 deficit

 -  Has clinically significant and/or symptomatic hemorrhage associated with stroke

 -  Has new intracranial hemorrhage, edema, or mass effect that may place the subject at
 increased risk for secondary deterioration when assessed prior to infusion

 -  Has hypotension as defined as the need for intravenous pressor support of systolic
 blood pressure < 90 mm Hg

 -  Has isolated brain stem stroke

 -  Has pure lacunar stroke

 -  Requires mechanical ventilation

 -  Requires a craniotomy

 -  Has a serious psychiatric or neurological disease that could alter evaluation on
 functional or cognitive scales

 -  Has an active systemic infection or is human immunodeficiency virus (HIV) positive or
 hepatitis C positive

 -  Has had an active malignancy within 3 years prior to the start of screening excluding
 skin cancers other than melanoma

 -  Has known coagulopathy such as Factor V Leyden, antiphospholipid syndrome (APS),
 Protein C, Protein S deficiency, sickle cell, anticardiolipin antibody, or
 phospholipid syndrome

 -  Has any concurrent illness or condition that in the opinion of the investigator might
 interfere with treatment or evaluation of safety

 -  Has a life expectancy < 6 months

 -  Has current or recent history of alcohol or drug abuse, or stroke associated with drug
 abuse

 -  Pregnant as documented by urine or blood test

 -  Renal insufficiency with estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73
 m2

 -  Hepatic insufficiency (bilirubin > 2.5 mg/dL or transaminases > 3 × the upper limit of
 normal). Subjects with Gilbert's syndrome are eligible for study enrollment if other
 liver function tests are normal, regardless of bilirubin level

 -  Uncontrolled or poorly controlled type 1 or type 2 diabetes with HbA1c > 7%

 -  Has a history of impaired hemostasis or has a prothrombin time > 14
 seconds/international normalized ratio (INR) > 1.3 second and activated partial
 thromboplastin time (aPTT) of > 70 seconds.

 -  Has a severe persistent neurological deficit (NIHSS > 24) at the time of enrollment or
 24 hours prior to infusion.

 -  Has New York Heart Association Class III or IV congestive heart failure.

 Concomitant or Prior Therapies

 -  Subjects currently receiving immunosuppressant drugs

 -  Clinical signs and symptoms of infection requiring antibiotic therapy at the time of
 enrollment that prevent adequate completion of study-related assessments as judged by
 the investigator

 -  Current therapy with anabolic steroids or appetite stimulants

 -  History of prior transfusion reaction

 -  History of intolerance or allergic response to similar biological products

 -  Known sensitivity to dimethyl sulfoxide (DMSO), Dextran 40, or plasma proteins

 -  Currently on dialysis

 -  Recipient of bone marrow or organ transplant

 -  Any previous or current treatment with angiogenic growth factors, cytokines, gene or
 stem cell therapy

 -  Subjects participating in another interventional clinical study of an investigational
 therapy within 30 days of screening

 Other

 -  Lactating women

 -  Unable to be evaluated for follow-up visits