Clinical trial NCT04261335: The Clinical Trial of CL2020 Cells for Neonatal Hypoxic Ischemic Encephalopathy
Official title: The Evaluation of Safety and Tolerability of CL2020 in Neonatal Hypoxic Ischemic Encephalopathy Patients With Therapeutic Hypothermia in the Dose Escalation Clinical Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Hypoxia-Ischemia, Brain
Keywords: Hypoxia-Ischemia, Brain
Infant, Newborn
Mesenchymal Stem Cells
Lead sponsor: Nagoya University
Sponsor class: OTHER
Collaborators: name: Life Science Institute, Inc.
First posted: 2020-02-07
Enrollment: 9
Sex: ALL
Minimum age (years): 4
Maximum age (years): 14
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: 3 + 3 dose escalation study design
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: Inclusion Criteria:

1. 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
2. Moderate or severe encephalopathy by a Sarnat criteria
3. Undergone therapeutic hypothermia started before six hours of birth, and done for 72 hours continuously
4. Birth weight ≥1,800 g
5. Heart rate ≥100/min, and SpO2 ≥90 %
6. Able to provide voluntary written consent after receiving adequate information about the study (consent will be obtained from an acceptable representative)

Exclusion Criteria:

1. Suspected or confirmed severe congenital abnormalities or chromosomal anomaly
2. Planned to undergo surgery or radiation therapy
3. Scheduled to take systemic corticosteroids treatment for over five days
4. Blood glucose ≥ 200 mg/dL
5. Participation in another clinical study (not exclude patients in observational studies)
6. Suspected or confirmed active and severe infection
7. Positive for HBs antigen, HCV antibody, HIV antibody, HTLV-1 antibody or syphilis serum reaction
8. History of severe hypersensitivity or anaphylactic reaction
9. Severe complications

Primary outcomes:
measure: Incidence of adverse events
timeFrame: until 12 weeks after the administration
Secondary outcomes:
measure: Incidence of composite endpoints (death, continuous respiratory support, and continuous use of vasopressors or pulmonary vasodilators)
timeFrame: at 12, 26, 38, 52, and 78 weeks after administration
measure: Mortality
timeFrame: all of the clinical trial period (up to 44 months)
measure: Overall survival
timeFrame: all of the clinical trial period (up to 44 months)
measure: Duration of continuous respiratory support
timeFrame: up to 78 weeks
measure: Duration of continuous use of vasopressors or pulmonary vasodilators
timeFrame: up to 78 weeks
measure: 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
timeFrame: 78 weeks after administration
measure: The developmental quotient in Kyoto Scale of Psychological Development 2001
timeFrame: 78 weeks after administration
measure: Presence of 1) head control, 2) roll over, 3) sitting position, 4) crawl, 5) independent gait, and 6) meaningful words
timeFrame: at 26, 38, 52, and 78weeks after administration
measure: Presence of spasticity
timeFrame: at 12, 26, 38, 52, and 78 weeks after administration
measure: Presence of epilepsy
timeFrame: until 78 weeks after administration
measure: MRI score
timeFrame: at 2, and 78 weeks after administration
measure: Gross Motor Function Classification System (GMFCS) score
timeFrame: at 78 weeks after administration
Other outcomes:
Locations:
city: Nagoya
country: Japan
facility: Nagoya University Hospital
state: Aich
Study officials:
affiliation: Department of Center for Maternal Neonatal Care, Nagoya University Hospital
name: Yoshiaki Sato, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Matsuyama N, Shimizu S, Ueda K, Suzuki T, Suzuki S, Miura R, Katayama A, Ando M, Mizuno M, Hirakawa A, Hayakawa M, Sato Y. Safety and tolerability of a multilineage-differentiating stress-enduring cell-based product in neonatal hypoxic-ischaemic encephalopathy with therapeutic hypothermia (SHIELD trial): a clinical trial protocol open-label, non-randomised, dose-escalation trial. BMJ Open. 2022 Apr 26;12(4):e057073. doi: 10.1136/bmjopen-2021-057073.