Neonatal White Matter Injury Trial (WRAP)

NCT07688746 | Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: 26-459331DP2NS148743-01
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

White Matter Injury; Neonatal Brain Injury; Brain Injury, Fetus and Neonate; Periventricular White Matter Abnormalities; Periventricular Leukomalacia

Keywords

infant; neonate; brain injury; clemastine; white matter injury; prematurity; neuroprotection

Outcome Measures

Primary Outcomes (1)

• 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.

  From study drug administration through 30 days after the last dose

Secondary Outcomes (7)

• Number of patients who experience any adverse events related to the study drug

  From study drug administration through 30 days after the last dose

• Pharmacokinetics of Clemastine in Preterm Neonates

  From day 1 through day 15

• Pharmacokinetics of Clemastine in Preterm Neonates

  From day 1 through day 15

• Pharmacokinetics of Clemastine in Preterm Neonates

  From day 1 through day 15

• Pharmacokinetics of Clemastine in Preterm Neonates

  From day 1 through day 15

Other Outcomes (7)

• Auditory brainstem response (ABR) at 0-6 months corrected age (CA)

  0-6 months corrected age

• Brain magnetic resonance imaging (MRI) at 2-3 months corrected age (CA)

  2-3 months corrected age (CA)

• General Movements Assessment (GMA) at 3-5 months corrected age (CA)

  3-5 months corrected age (CA)

Study Arms (4)

Dose level 1

EXPERIMENTAL

Dose level 1 (0.01 mg/kg/day)

Drug: Clemastine fumarate

Dose level 2

EXPERIMENTAL

Dose level 2 (0.03 mg/kg/day)

Drug: Clemastine fumarate

Dose level 3

EXPERIMENTAL

Dose level 3 (0.05 mg/kg/day)

Drug: Clemastine fumarate

Dose level 4

EXPERIMENTAL

Drug: Clemastine fumarate

Interventions

Clemastine fumarate DRUG

Clemastine fumarate oral suspension

Dose level 1; Dose level 2; Dose level 3; Dose level 4

Eligibility Criteria

• Age: 3 Weeks - 20 Weeks
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Born at ≤32 weeks gestational age based on prenatal ultrasound or last menstrual period (LMP).
• Current age of between 35-41 weeks PMA.
• Imaging evidence of white matter injury on any scan as defined by either brain MRI or cUS criteria:
• 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.
• Currently hospitalized in a participating intensive care nursery.

You may not qualify if:

• 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.
• Not able to receive enteral medications.
• Clinically significant sedation due to critical illness or medications.
• Concomitant use of any other putative neuroprotective or myelination promoting therapy as determined by the investigator.
• Serum creatinine, aspartate aminotransferase (AST), or alanine aminotransferase (ALT) \>2x the upper limit of normal for age.
• Family history of epilepsy due to a confirmed or suspected genetic cause.
• History of confirmed seizure activity.
• If ≥36 weeks postmenstrual age, required respiratory support greater than 2L/min, noninvasive positive airway pressure, or mechanical ventilation upon reaching 36 weeks postmenstrual age due to diagnosis of moderate or severe BPD.
• If less than 36 weeks postmenstrual age, currently requiring respiratory support greater than 2L/min, noninvasive positive airway pressure, or mechanical ventilation, unless respiratory support is being given to promote lung development and not due to clinical need.
• Major medical conditions, laboratory abnormalities, or concurrent treatments that, in opinion of the investigator, may affect interpretation of study results or patient safety.

Sponsors & Collaborators

• Bridget LaMonica Ostrem, M.D., Ph.D.: lead
• National Institute of Neurological Disorders and Stroke (NINDS): collaborator

Study Sites (1)

University of California, San Francisco

San Francisco, California, 94158, United States

RECRUITING

MeSH Terms

Conditions

Brain Injuries; Leukomalacia, Periventricular; Premature Birth

Interventions

Clemastine

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Wounds and Injuries; Cerebrovascular Disorders; Encephalomalacia; Vascular Diseases; Cardiovascular Diseases; Infant, Premature, Diseases; Infant, Newborn, Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Obstetric Labor, Premature; Obstetric Labor Complications; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases

Intervention Hierarchy (Ancestors)

Pyrrolidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Bridget Ostrem, MD, PhD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Audrey Hernando, BS

CONTACT

415-502-2425; audrey.hernando@ucsf.edu

Lena Odell, BA

CONTACT

elizabeth.odell@ucsf.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Clinical Professor of Neurology

Model Details: This is an open-label dose-escalation and dose-expansion study. The Phase I component will employ a conventional "3+3" design with a minimum of three and a maximum of six patients in each of up to three dose levels (Dose level 1, 2, and 3). This is an adaptive, PK-guided trial and a fourth dose will be added if needed to reach the target exposure for the final dose.

Study Record Dates

• First Submitted: June 9, 2026
• First Posted: July 7, 2026
• Study Start: July 26, 2026
• Primary Completion (Estimated): April 1, 2028
• Study Completion (Estimated): July 1, 2031
• Last Updated: July 28, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)