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An Open-label, dose-escalation, phase 1 clinical trial to determine the safety and dose of HIEstem, a treatment for neonatal intractable brain diseases

Not Applicable
Recruiting
Conditions
Certain conditions originating in the perinatal period
Registration Number
KCT0004851
Lead Sponsor
Medinno
Brief Summary

Not available

Detailed Description

Not available

Recruitment & Eligibility

Status
Recruiting
Sex
All
Target Recruitment
12
Inclusion Criteria

Hypoxic ischemic encephalopathy (HIE)
1)Not less than 35 weeks of gestational age and not less than 1,800 grams of birth weight
2)Begin of hypothermia treatment (systemic or selectively cerebral) within 6 hours after birth
3)When investigational product can be administered within 7 days (168 hours) after completion of 72-hour hypothermia treatment
4)Evidence of moderate to severe HIE
Intraventricular hemorrhage (IVH)
1)Within 14 days after diagnosis of IVH and within 28 days after birth
2)Premature neonates of 23 or more and less than 34 weeks of gestational age
3)Neonates diagnosed with intraventricular hemorrhage level 3 or 4 according to Papile’s severity classification criteria by brain ultrasound, as below

Exclusion Criteria

Hypoxic Ischemic Encephalopathy (HIE)
1)Less than 36 weeks of gestation age or less than 1,800 grams of birth weight
2)Hypothermia treatment began 6 hours after birth
3)History of or suspicious prenatal cerebral hemorrhage or intracranial infection (meningitis and encephalitis caused by bacteria, viruses, tuberculosis, parasites, etc.)
4)Genetic or congenital abnormalities that affect neurodevelopment or require various surgical treatments, i.e., severe congenital brain malformations (hydrocephalus, encephalocele, etc.), cyanotic or non-cyanotic congenital heart defects that cause heart failure, chromosomal abnormalities (Edward syndrome, Patau syndrome, Down syndrome, etc.) and severe congenital malformations (hydrops fetalis, pulmonary hypoplasia, congenital diaphragmatic hernia, congenital pulmonary cyst disease, etc.)
5)Severe congenital infectious diseases (herpes, toxoplasmosis, rubella, syphilis, AIDS, etc.)
6)Microcephaly with head circumference less than 30 cm
7)CRP > 10 mg/dl, active infection that does not respond to appropriate antibiotics, or clinically significant fulminant sepsis
8)Platelet count < 50,000/uL that is not expected to be corrected by the time of administration
9)Severe bleeding tendency that is not expected to be corrected by the time of administration
10)Expected surgery or death within 72 hours before or after administration of investigational product
11)Clinical investigators’ judgment indicating unsuitability due to parents, legal representative, or other reasons.

Intraventricular hemorrhage (IVH)
1)Suspected intraventricular hemorrhage before birth
2)History of or suspicious prenatal cerebral hemorrhage or intracranial infection (meningitis and encephalitis caused by bacteria, viruses, tuberculosis, parasites, etc.)
3)Disorders listed below, at the time of screening,
?Serious congenital brain malformations (hydrocephalus, encephalopathy, etc.)
?Cyanotic or non-cyanotic congenital heart defects that cause heart failure (patency of ductus arteriosus is excepted), chromosomal abnormalities (Edward syndrome, Patau syndrome, Down syndrome, etc.), and severe congenital malformations (hydrops fetalis, pulmonary hypoplasia, congenital diaphragmatic hernia, congenital pulmonary cyst disease, etc.)
?Severe congenital infectious disease (herpes, toxoplasmosis, rubella, syphilis, AIDS, etc.)
?CRP > 10 mg/dl, active infection that does not respond to appropriate antibiotics, or clinically significant fulminant sepsis
4)Platelet count < 50,000/uL that is not expected to be corrected by the time of administration
5)Recurrent metabolic acidosis (pH < 7.1, BE < -20) that is not expected to be corrected by the time of administration of investigational product
6)Expected surgery within 72 hours after administration of investigational product or expected surgery or death within several days after administration of investigational product
7)Patients with a history of participating in other clinical trials
8)Neonates evaluated as unsuitable to participate by clinical investigators

Study & Design

Study Type
Interventional Study
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Dose limiting toxicity (DLT) ?Death without reason within 6 hours after administration of investigational product ?Anaphylactic shock just after administration of investigational product ;New tumor lesions seen in brain ultrasound at 4 weeks and 12 weeks after the administration of the investigational drug or at 6-month MRI;Serious adverse events associated with the administration of investigational products
Secondary Outcome Measures
NameTimeMethod
ew tumor lesions seen in 2- and 5-year MRIs;adverse event
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