White Matter InjuryPhase 1WRAPNCT07688746
Neonatal White Matter Injury Trial (WRAP)
A Phase 1 study testing Clemastine fumarate in people with White Matter Injury and Brain Injury, Fetus and Neonate, run by Bridget LaMonica Ostrem, M.D., Ph.D. at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 3 to 20 weeks
- Conditions the study is for
- White Matter Injury, Brain Injury, Fetus and Neonate, Neonatal Brain Injury
- What is being tested?
- Clemastine fumarate
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 1 siteUnited States
- Study dates
- 26 Jul 2026to 1 Jul 2031
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 3 to 20 weeks
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Lena Odell, BA contact
United States1 site, 1 recruiting
- Recruiting
University of California, San Francisco
San Francisco, California, 94158
Audrey Hernando, 415-502-2425, audrey.hernando@ucsf.edu
Bridget Ostrem, MD, PhD
About this study
Official title: An Open-label, Dose-escalation, Phase I/Ib Clinical Trial to Assess the Safety and Pharmacokinetics of Clemastine in Preterm Neonates With White Matter Injury (WRAP)
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.
Read the detailed description
Preterm white matter injury (WMI) is the most common type of brain injury in premature infants and is associated with adverse neurological outcomes, including motor and cognitive disability and seizures. Preterm WMI involves an arrest of differentiation in the oligodendroglial cell lineage and a failure of normal developmental myelination. No therapies exist that directly promote brain repair and myelination or can be given at the time that preterm WMI has been identified and is likely most amenable to treatment. The lack of available treatments inherently limits the possibility for functional recovery in affected infants. Clemastine is an antihistamine and antimuscarinic agent that was identified in a high-throughput screen of FDA-approved compounds that significantly promote myelination in vitro. Clemastine was subsequently shown to promote myelination and improve functional recovery in multiple animal models of WMI, including preterm WMI, and induces remyelination in adult patients with multiple sclerosis. Clemastine is therefore an ideal potential candidate treatment for preterm WMI. The investigators will be conducting a Phase I/Ib open label dose-escalation and dose expansion study to test the safety and pharmacokinetics of oral clemastine treatment in neonates with preterm WMI.
- Conditions
- White Matter Injury, Brain Injury, Fetus and Neonate, Neonatal Brain Injury, Periventricular Leukomalacia, Periventricular White Matter Abnormalities
- Being tested
- Clemastine fumarate
- Keywords
- infant, neonate, brain injury, clemastine, white matter injury, prematurity, neuroprotection
- Medical subject headings
- Brain Injuries, Leukomalacia, Periventricular, Premature Birth
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Clemastine fumarateDrug
Clemastine fumarate oral suspension
| Study group | Role | What they receive |
|---|---|---|
| Dose level 1 | Experimental | Dose level 1 (0.01 mg/kg/day) Receives: Drug: Clemastine fumarate |
| Dose level 2 | Experimental | Dose level 2 (0.03 mg/kg/day) Receives: Drug: Clemastine fumarate |
| Dose level 3 | Experimental | Dose level 3 (0.05 mg/kg/day) Receives: Drug: Clemastine fumarate |
| Dose level 4 | Experimental | Not described Receives: Drug: Clemastine fumarate |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
Measured: From study drug administration through 30 days after the last dose
Pharmacokinetics of Clemastine in Preterm Neonates
Oral clearance (CL/F)
Measured: From day 1 through day 15
Pharmacokinetics of Clemastine in Preterm Neonates
Area under the plasma concentration-time curve from over a 24 hour period (AUC24)
Measured: From day 1 through day 15
Pharmacokinetics of Clemastine in Preterm Neonates
Average concentration (Cavg)
Measured: From day 1 through day 15
Pharmacokinetics of Clemastine in Preterm Neonates
Observed concentration at 24 hours post-dose (C24h)
Measured: From day 1 through day 15
Pharmacokinetics of Clemastine in Preterm Neonates
Maximum observed plasma concentration (Cmax)
Measured: From day 1 through day 15
Pharmacokinetics of Clemastine in Preterm Neonates
Time of the maximum observed concentration in plasma (Tmax)
Measured: From day 1 through day 15
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Jul 2026
- Study start26 Jul 2026
- Primary completion1 Apr 2028 (estimated)
- Study completion1 Jul 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for White Matter InjuryStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Model description
- 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.
- Masking
- None (open label)
- Enrolment
- 24 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Bridget LaMonica Ostrem, M.D., Ph.D.
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Neurological Disorders and Stroke (NINDS)
- Responsible party
- Sponsor-investigator, Bridget LaMonica Ostrem, M.D., Ph.D., University of California, San Francisco
- Investigators
- Bridget Ostrem, MD, PhD, Principal investigator, University of California, San Francisco
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07688746
- Sponsor's protocol ID
- 26-45933
- Other IDs
- 1DP2NS148743-01
- Acronym
- WRAP
- Status last verified
- Jul 2026
- First submitted
- 9 Jun 2026
- Last updated
- 28 Jul 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-label, Dose-escalation, Phase I/Ib Clinical Trial to Assess the Safety and Pharmacokinetics of Clemastine in Preterm Neonates With White Matter Injury (WRAP)
- ClinicalTrials.gov ID
- NCT07688746
- Acronym / sponsor ID
- WRAP / 26-45933
- Conditions
- White Matter Injury, Brain Injury, Fetus and Neonate, Neonatal Brain Injury, Periventricular Leukomalacia, Periventricular White Matter Abnormalities
- Keywords
- infant, neonate, brain injury, clemastine, white matter injury, prematurity, neuroprotection
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 24 participants (estimated)
- Lead sponsor
- Bridget LaMonica Ostrem, M.D., Ph.D.University, hospital or other
- Collaborators
- National Institute of Neurological Disorders and Stroke (NINDS)
- Study start
- 26 Jul 2026 (actual)
- Primary completion
- 1 Apr 2028 (estimated)
- Study completion
- 1 Jul 2031 (estimated)
- First posted
- 7 Jul 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Preterm white matter injury (WMI) is the most common type of brain injury in premature infants and is associated with adverse neurological outcomes, including motor and cognitive disability and seizures. Preterm WMI involves an arrest of differentiation in the oligodendroglial cell lineage and a failure of normal developmental myelination. No therapies exist that directly promote brain repair and myelination or can be given at the time that preterm WMI has been identified and is likely most amenable to treatment. The lack of available treatments inherently limits the possibility for functional recovery in affected infants. Clemastine is an antihistamine and antimuscarinic agent that was identified in a high-throughput screen of FDA-approved compounds that significantly promote myelination in vitro. Clemastine was subsequently shown to promote myelination and improve functional recovery in multiple animal models of WMI, including preterm WMI, and induces remyelination in adult patients with multiple sclerosis. Clemastine is therefore an ideal potential candidate treatment for preterm WMI. The investigators will be conducting a Phase I/Ib open label dose-escalation and dose expansion study to test the safety and pharmacokinetics of oral clemastine treatment in neonates with preterm WMI.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 4
- Model description
- 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.
| Arm | Type | Receives |
|---|---|---|
| Dose level 1 | Experimental | Drug: Clemastine fumarateDose level 1 (0.01 mg/kg/day) |
| Dose level 2 | Experimental | Drug: Clemastine fumarateDose level 2 (0.03 mg/kg/day) |
| Dose level 3 | Experimental | Drug: Clemastine fumarateDose level 3 (0.05 mg/kg/day) |
| Dose level 4 | Experimental | Drug: Clemastine fumarate |
Who may qualify
- Ages
- 3 to 20 weeks
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (6 listed)
- 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:
- Currently hospitalized in a participating intensive care nursery.
Key exclusion criteria (13 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Clemastine fumarateClemastine fumarate oral suspension | Drug | Dose level 1, Dose level 2, Dose level 3, Dose level 4 |
Primary outcome
Number of subjects who experience dose limiting toxicity
Time frame: From study drug administration through 30 days after the last dose
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.
7 secondary outcomes
Number of patients who experience any adverse events related to the study drug
Time frame: From study drug administration through 30 days after the last dose
Pharmacokinetics of Clemastine in Preterm Neonates
Time frame: From day 1 through day 15
Pharmacokinetics of Clemastine in Preterm Neonates
Time frame: From day 1 through day 15
Pharmacokinetics of Clemastine in Preterm Neonates
Time frame: From day 1 through day 15
Pharmacokinetics of Clemastine in Preterm Neonates
Time frame: From day 1 through day 15
Pharmacokinetics of Clemastine in Preterm Neonates
Time frame: From day 1 through day 15
Pharmacokinetics of Clemastine in Preterm Neonates
Time frame: From day 1 through day 15
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Jul 2026.
- Individual participant dataSharing planned: No
Related trials for White Matter Injury
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Anakinra Pilot 2 - A Study to Optimise Dose and Route of Administration of Anakinra in Preterm Infants
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Lena Odell, BA contact
Bridget Ostrem, MD, PhD principal investigator
University of California, San Francisco
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Clemastine fumarate in people with White Matter Injury and Brain Injury, Fetus and Neonate, run by Bridget LaMonica Ostrem, M.D., Ph.D. at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 28 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Audrey Hernando, BS (415-502-2425, audrey.hernando@ucsf.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of subjects who experience dose limiting toxicity (time frame: From study drug administration through 30 days after the last dose). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Jul 2026.