The researchers are investigating a new treatment for white matter injury, which is a common type of brain injury in premature babies. The drug, clemastine, is experimental. This means that the drug is not approved by the Food and Drug Administration (FDA) for the treatment of white matter injury. The main purpose of this study is to learn whether clemastine is safe to give to infants with white matter injury. The researchers also want to understand how much clemastine gets into an infant's body when the medication is taken by mouth, and how long it stays in the body.
Born at ≤32 weeks gestational age based on prenatal ultrasound or last menstrual period (LMP).
Current age of between 35-41 weeks PMA.
Brain MRI with Grade Ib WMI or higher based on the Martinez-Biarge et al 2016 criteria.
cUS with Grade 3 or higher white matter abnormalities based on Miller et al 2003 criteria.
Known or suspected metabolic or chromosomal disorder or major congenital anomalies
Major intracranial hemorrhage within the last 1 week or intracranial hemorrhage of any age that is not controlled or continuing to cause significant mass effect or midline shift.
History of cardiac arrhythmia or current ongoing tachycardia with baseline heart rate >10% age expected norms.
Hypotension requiring ongoing vasopressor or inotropic support.
Sequential
Clemastine fumarate
DrugClemastine fumarate oral suspension
Number of subjects who experience dose limiting toxicity
The primary objective is to assess the safety of oral clemastine in preterm neonates with white matter injury (WMI) who have reached at least 35 weeks postmenstrual age (PMA), as measured by the number of subjects who experience dose limiting toxicity (DLT). PMA equals the gestational age (GA) at birth plus chronological age.
Number of patients who experience any adverse events related to the study drug
Pharmacokinetics of Clemastine in Preterm Neonates
Oral clearance (CL/F)
Pharmacokinetics of Clemastine in Preterm Neonates
Area under the plasma concentration-time curve from over a 24 hour period (AUC24)
Pharmacokinetics of Clemastine in Preterm Neonates
Average concentration (Cavg)
Auditory brainstem response (ABR) at 0-6 months corrected age (CA)
Brain magnetic resonance imaging (MRI) at 2-3 months corrected age (CA)
General Movements Assessment (GMA) at 3-5 months corrected age (CA)
Motor Optimality Score: Minimum score is 5, Maximum score is 28; higher scores mean a better outcome. Categorical Classification: Qualitative outcome categorized as normal fidgety, abnormal fidgety, or absent fidgety; normal fidgety movements represent a better outcome.
Warner Initial Developmental Evaluation of Adaptive and Functional Skills (WIDEA-FS) assessment at 18 months corrected age (CA)
Total score: : Minimum 50, Maximum 200; higher scores mean a better outcome.
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Bridget LaMonica Ostrem, M.D., Ph.D.
Lead sponsor
University of California, San Francisco
Sponsor institution
National Institute of Neurological Disorders and Stroke (NINDS)
Collaborator
