The Clinical Trial of CL2020 Cells for Neonatal Hypoxic Ischemic Encephalopathy

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety and the tolerability of CL2020 cells in hypoxic ischemic encephalopathy neonates with hypothermia therapy. In addition, we will evaluate the efficacy of CL2020 cells for infant development.

Official Title
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The Evaluation of Safety and Tolerability of CL2020 in Neonatal Hypoxic Ischemic Encephalopathy Patients With Therapeutic Hypothermia in the Dose Escalation Clinical Trial

Conditions
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Hypoxia-Ischemia, Brain

Intervention / Treatment
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* Biological: CL2020 cells


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: At least 36 weeks gestation, and either one of the following criteria (i.-iii.) i. Apgar score ≤5 at 10 minutes ii. Continued resuscitation for at least 10 minutes iii. pH <7.0 or base deficit ≥16 mmol/L in any blood sample obtained within 60 min of birth Moderate or severe encephalopathy by a Sarnat criteria Undergone therapeutic hypothermia started before six hours of birth, and done for 72 hours continuously Birth weight ≥1,800 g Heart rate ≥100/min, and SpO2 ≥90 % Able to provide voluntary written consent after receiving adequate information about the study (consent will be obtained from an acceptable representative) Exclusion Criteria: Suspected or confirmed severe congenital abnormalities or chromosomal anomaly Planned to undergo surgery or radiation therapy Scheduled to take systemic corticosteroids treatment for over five days Blood glucose ≥ 200 mg/dL Participation in another clinical study (not exclude patients in observational studies) Suspected or confirmed active and severe infection Positive for HBs antigen, HCV antibody, HIV antibody, HTLV-1 antibody or syphilis serum reaction History of severe hypersensitivity or anaphylactic reaction Severe complications

Ages Eligible for Study
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Minimum Age: 4 Days
Maximum Age: 14 Days

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: 3 + 3 dose escalation study design
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CL2020 cells<br>Intravenous injection of CL2020 cells | Biological: CL2020 cells<br>* 1.5 million or 15 million cells, IV on day 5 to 14 of birth<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of adverse events | Any adverse events are summarized. | until 12 weeks after the administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of composite endpoints (death, continuous respiratory support, and continuous use of vasopressors or pulmonary vasodilators) | Incidence of composite endpoints is summarized. | at 12, 26, 38, 52, and 78 weeks after administration | 
| Mortality | Mortality is summarized. | all of the clinical trial period (up to 44 months) | 
| Overall survival | Overall survival is summarized. | all of the clinical trial period (up to 44 months) | 
| Duration of continuous respiratory support | Duration of continuous respiratory support is summarized. | up to 78 weeks | 
| Duration of continuous use of vasopressors or pulmonary vasodilators | Duration of continuous use of vasopressors or pulmonary vasodilators is summarized. | up to 78 weeks | 
| The composite score of cognitive scale, language scale, motor scale, social-emotional scale, and adaptive behavior scale in Bayley Scales of Infant and Toddler Development Third edition | Each composite scores are summarized. The higher scores mean a better outcome. | 78 weeks after administration | 
| The developmental quotient in Kyoto Scale of Psychological Development 2001 | The developmental quotient is summarized. The higher scores mean a better outcome. | 78 weeks after administration | 
| Presence of 1) head control, 2) roll over, 3) sitting position, 4) crawl, 5) independent gait, and 6) meaningful words | Presence of each event is summarized. | at 26, 38, 52, and 78weeks after administration | 
| Presence of spasticity | Presence of spasticity is summarized. Spasticity is the condition as below: increased muscle tone, or increased deep tendon reflex. | at 12, 26, 38, 52, and 78 weeks after administration | 
| Presence of epilepsy | Presence of spasticity is summarized. The definition of epilepsy is the condition based on the International League Against Epilepsy. | until 78 weeks after administration | 
| MRI score | MRI score is summarized. The scoring system is based on the report of Barkovich AJ, et al. (AJNR Am J Neuroradiol. 1998 ;19(1):143-9.) . The higher scores mean a worse outcome. | at 2, and 78 weeks after administration | 
| Gross Motor Function Classification System (GMFCS) score | GMFCS score is summarized. The gross motor function can be categorized into 5 different level. The higher scores mean a worse outcome. | at 78 weeks after administration | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hypoxia-Ischemia, Brain, Infant, Newborn, Mesenchymal Stem Cells