The Clinical Trial of CL2020 Cells for Neonatal Hypoxic Ischemic Encephalopathy (SHIELD)

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

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.

Study Overview

• Status: Completed
• Conditions: Hypoxia-Ischemia, Brain
• Intervention / Treatment: Biological: CL2020 cells

• Study Type: Interventional
• Enrollment (Actual): 9
• Phase: Phase 1

Contacts and Locations

Study Locations

• Japan
  • Aich
    • Nagoya, Aich, Japan, 466-8560
      • Nagoya University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 4 days to 2 weeks (Child)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CL2020 cells; Intravenous injection of CL2020 cells	Biological: CL2020 cells; 1.5 million or 15 million cells, IV on day 5 to 14 of birth

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Nagoya University
• Collaborators: Life Science Institute, Inc.
• Investigators: Principal Investigator: Yoshiaki Sato, MD, PhD, Department of Center for Maternal Neonatal Care, Nagoya University Hospital

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): March 4, 2020
• Primary Completion (Actual): September 29, 2021
• Study Completion (Actual): December 12, 2022

Study Registration Dates

• First Submitted: February 1, 2020
• First Submitted That Met QC Criteria: February 6, 2020
• First Posted (Actual): February 7, 2020

Study Record Updates

• Last Update Posted (Actual): October 3, 2023
• Last Update Submitted That Met QC Criteria: September 30, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: Infant, Newborn; Mesenchymal Stem Cells; Hypoxia-Ischemia, Brain
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Central Nervous System Diseases; Nervous System Diseases; Signs and Symptoms, Respiratory; Hypoxia, Brain; Brain Ischemia; Ischemia; Brain Diseases; Hypoxia; Hypoxia-Ischemia, Brain
• Other Study ID Numbers: CAMCR-014; jRCT2043190112 (Registry Identifier: Japan Registry of Clinical Trials)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No