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

• ClinicalTrials.gov Identifier: NCT04261335
• Recruitment Status: Recruiting
• First Posted: February 7, 2020
• Last Update Posted: March 5, 2020
• Sponsor: Nagoya University
• Collaborator: Life Science Institute, Inc.
• Information provided by (Responsible Party): Yoshiaki Sato, Nagoya University

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Hypoxia-Ischemia, Brain	Biological: CL2020 cells	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 12 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Intervention Model Description: 3 + 3 dose escalation study design
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: March 4, 2020
• Estimated Primary Completion Date: December 2021
• Estimated Study Completion Date: September 2023

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Incidence of adverse events [ Time Frame: until 12 weeks after the administration ]
   Any adverse events are summarized.

Secondary Outcome Measures :

1. Incidence of composite endpoints (death, continuous respiratory support, and continuous use of vasopressors or pulmonary vasodilators) [ Time Frame: at 12, 26, 38, 52, and 78 weeks after administration ]
   Incidence of composite endpoints is summarized.
2. Mortality [ Time Frame: all of the clinical trial period (up to 44 months) ]
   Mortality is summarized.
3. Overall survival [ Time Frame: all of the clinical trial period (up to 44 months) ]
   Overall survival is summarized.
4. Duration of continuous respiratory support [ Time Frame: up to 78 weeks ]
   Duration of continuous respiratory support is summarized.
5. Duration of continuous use of vasopressors or pulmonary vasodilators [ Time Frame: up to 78 weeks ]
   Duration of continuous use of vasopressors or pulmonary vasodilators is summarized.
6. 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 [ Time Frame: 78 weeks after administration ]
   Each composite scores are summarized. The higher scores mean a better outcome.
7. The developmental quotient in Kyoto Scale of Psychological Development 2001 [ Time Frame: 78 weeks after administration ]
   The developmental quotient is summarized. The higher scores mean a better outcome.
8. Presence of 1) head control, 2) roll over, 3) sitting position, 4) crawl, 5) independent gait, and 6) meaningful words [ Time Frame: at 26, 38, 52, and 78weeks after administration ]
   Presence of each event is summarized.
9. Presence of spasticity [ Time Frame: at 12, 26, 38, 52, and 78 weeks after administration ]
   Presence of spasticity is summarized. Spasticity is the condition as below: increased muscle tone, or increased deep tendon reflex.
10. Presence of epilepsy [ Time Frame: until 78 weeks after administration ]
    Presence of spasticity is summarized. The definition of epilepsy is the condition based on the International League Against Epilepsy.
11. MRI score [ Time Frame: at 2, and 78 weeks after administration ]
    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.
12. Gross Motor Function Classification System (GMFCS) score [ Time Frame: at 78 weeks after administration ]
    GMFCS score is summarized. The gross motor function can be categorized into 5 different level. The higher scores mean a worse outcome.

Eligibility Criteria

• Ages Eligible for Study: up to 14 Days (Child)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Contacts

Contact: Yoshiaki Sato, MD, PhD; +81-52-741-2985; yoshiaki@med.nagoya-u.ac.jp

Contact: Kazuto Ueda, MD; +81-52-744-2985; ueda.kazuto@med.nagoya-u.ac.jp

Locations

Japan

Nagoya University Hospital; Recruiting

Nagoya, Aich, Japan, 466-8560

Contact: Yoshiaki Sato, MD, Ph.D +81-52-741-2985 yoshiaki@med.nagoya-u.ac.jp

Sponsors and Collaborators

Nagoya University

Life Science Institute, Inc.

Investigators

• Principal Investigator: Yoshiaki Sato, MD, PhD; Department of Center for Maternal Neonatal Care, Nagoya University Hospital

More Information

• Responsible Party: Yoshiaki Sato, MD, PhD, Associate Professor at Department of Center for Maternal Neonatal Care, Nagoya University Hospital, Nagoya University
• ClinicalTrials.gov Identifier: NCT04261335
• Other Study ID Numbers: CAMCR-014; jRCT2043190112 ( Registry Identifier: Japan Registry of Clinical Trials )
• First Posted: February 7, 2020
• Last Update Posted: March 5, 2020
• Last Verified: March 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Yoshiaki Sato, Nagoya University:

Hypoxia-Ischemia, Brain; Infant, Newborn; Mesenchymal Stem Cells

Additional relevant MeSH terms:

Brain Diseases; Brain Ischemia; Hypoxia-Ischemia, Brain; Ischemia; Hypoxia; Pathologic Processes; Signs and Symptoms, Respiratory; Central Nervous System Diseases; Nervous System Diseases; Cerebrovascular Disorders; Vascular Diseases; Cardiovascular Diseases; Hypoxia, Brain