Clinical trial NCT03635450: Study of hCT-MSC in Newborn Infants With Moderate or Severe HIE
Official title: A Phase I Study of hCT-MSC, an Umbilical Cord-Derived Mesenchymal Stromal Cell Product, in Newborn Infants With Moderate or Severe Hypoxic- Ischemic Neonatal Encephalopathy.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Moderate to Severe Hypoxic-ischemic Encephalopathy
Keywords: hypoxic-ischemic encephalopathy
newborn infants
therapeutic hypothermia
hCT-MSC, an Umbilical Cord Tissue-Derived Mesenchymal Stromal Cell Product
Lead sponsor: Duke University
Sponsor class: OTHER
Collaborators: name: Duke Clinical and Translational Science Institute (CTSI), part of the NIH Clinical and Translational Science Awards (CTSA)
First posted: 2018-08-17
Enrollment: 6
Sex: ALL
Minimum age (years): 0
Maximum age (years): 48
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: The first cohort of three patients will receive a single dose in the first 48 postnatal hours. If there are no safety concerns, the second cohort of three patients 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.
Primary purpose: TREATMENT

Brief summary: To determine the safety of single and repeated intravenous doses of hCT-MSC in newborn infants with HIE.

Detailed description: 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.

Eligibility criteria: 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 )

Primary outcomes:
measure: Incidence of infusion reactions
timeFrame: 24 hours after each infusion
measure: Incidence of Infections post-infusion
timeFrame: Up to 2 Weeks
Secondary outcomes:
measure: Survival
timeFrame: Up to 6 months
measure: Neurodevelopmental Assessments
timeFrame: Up to 16 postnatal months
Other outcomes:
Locations:
city: Durham
country: United States
facility: Duke University
state: North Carolina
Study officials:
affiliation: Duke University
name: Michael Cotten, MD
role: PRINCIPAL_INVESTIGATOR
References: