Study of hCT-MSC in Newborn Infants With Moderate or Severe HIE

The purpose of this study is to assess the safety of one and two intravenous infusions of
human umbilical cord tissue-derived mesenchymal stromal cells (hCT-MSC), the first
administered in the first 48 postnatal hours, and the second at two months postnatal age, in
term and near term infants with moderate to severe neonatal hypoxic-ischemic encephalopathy
(HIE). This is a phase I, prospective, open-label trial designed to assess the safety of one
or two intravenous doses of hCT-MSC in newborn infants with moderate to severe HIE who are
recipients of therapeutic hypothermia. Infants born at 36 0/7 weeks gestation or later who
have moderate to severe hypoxic-ischemic encephalopathy and are receiving therapeutic
hypothermia will be eligible to participate. Investigators project an accrual of 6 patients.
All infants will receive intravenous infusion(s) of hCT-MSCs. The first cohort of three
infants will receive a single dose in the first 48 postnatal hours. If there are no safety
concerns, the second cohort of three infants will receive two doses, with the first dose
given in the first 48 postnatal hours and the second dose given approximately two months
after the first dose.

The potential risks associated with infusion of MSCs include a reaction to the product (rash,
shortness of breath, wheezing, difficulty breathing, hypotension, swelling around the mouth,
throat or eyes, tachycardia, diaphoresis), transmission of infection, and HLA sensitization.
Another risk of this study is loss of confidentiality or privacy. Every effort will be made
to keep the infant's medical record confidential. The results will be summarized using
descriptive statistics and statistical testing as appropriate. Continuous secondary endpoints
will be summarized using mean, standard deviation, CV%, median, minimum, and maximum.

Inclusion Criteria:

- 36 0/7th weeks gestation or older at the time of delivery.

- Able to receive one dose of hCT-MSCs in the first 48 postnatal hours

- Willingness to return for one year assessments.

- Signs of encephalopathy within 6 hours of age

Exclusion Criteria:

- Major congenital or chromosomal abnormalities

- Severe growth restriction (birth weight <1800 g)

- Opinion by attending neonatologist that the study may interfere with clinical
treatment or safety of subject

- Moribund neonates for whom no further treatment is planned

- Infants whose mothers have unknown serologies for Hepatitis B or HIV

- Infants born to mothers are known to be HIV, Hepatitis B, Hepatitis C or who have
active syphilis or CMV infection in pregnancy

- Infants suspected of overwhelming sepsis

- ECMO initiated or likely in the first 48 hours of life

- Mother suspected to have intraamniotic infection at time of birth.

- ALL blood gases (cord and postnatal) done within the first 60 minutes had a pH > 7.15
AND base deficit < 10 mEq/L (source can be arterial, venous or capillary)

- Mother with documented Zika infection during this pregnancy

- Availability of autologous cord blood collected and usable in the randomized trial of
autologous volume- and red blood cell-reduced cord blood cells (Duke IRB Pro00066647;
clinical trials.gov link: https://clinicaltrials.gov/ct2/show/NCT02612155 )