Neonatal SeizurePhase 2NEOLEV3NCT05610085
A Dose Escalation Study of Levetiracetam in the Treatment of Neonatal Seizures
A Phase 2 study testing Levetiracetam Injection and Phenobarbital Sodium Injection in people with Neonatal Seizure and Neonatal Encephalopathy, run by University of California, San Diego at 6 sites in 2 countries.
Trial summary
The main purpose of this study is to determine the maximum safe tolerated dose of LEV in the treatment of neonatal seizures. Our hypothesis is that optimal dosing of Levetiracetam (LEV) to treat neonatal seizures is significantly greater than 60mg/kg. Read more about this study
- Who is it for?
- Ages Up to 1 month
- Conditions the study is for
- Neonatal Seizure, Neonatal Encephalopathy, Hypoxic-Ischemic Encephalopathy
- What is being tested?
- Levetiracetam Injection and Phenobarbital Sodium Injection
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 133 participants
- Where
- 6 sitesin 2 countries
- Study dates
- 24 Mar 2023to 31 Dec 2027
- Phase
- Phase 2
- 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 Up to 1 month
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- at risk for seizures or suspected to be having seizures;
- all seizure aetiologies except correctable metabolic abnormalities such as hypoglycaemia and hypocalcaemia;
- Term neonates (corrected gestational age between 35 and 44 weeks, postnatal age less than 28 days);
- weight > 2200g.
- Parental ability to comprehend and provide written informed consent
Who cannot join
- Cumulative seizure burden of 8 minutes/ hour or more in phases 1 and 2, Cumulative seizure burden of 20 minutes/hour or more in phase 3;
- Renal failure defined as anuria in the first 24 hours of life;
- Subjects in whom death seems imminent;
- Seizures caused by correctable metabolic abnormality, such as hypocalcaemia, hypoglycaemia.
Trial locations and contacts
6 sites in 2 countries. Contact the study team or a site near you to ask about taking part.
6 sites in 2 countries
New Zealand4 sites, 4 recruiting
- Recruiting
Auckland City Hospital
Auckland, Auckland, 1023
Cynthia Sharpe, MBChB, 021924015, cynthias@adhb.govt.nz
- Recruiting
Middlemore Hospital
Auckland, Auckland, 1050
Chris McKinlay, MBChB, +64274725099, c.mckinlay@auckland.ac.nz
Cynthia Sharpe, MBChB, +6421924015, ciasharpe@gmail.com
- Recruiting
Health New Zealand, Te Whatu Ora - Waikato Hospital
Hamilton, Waikato Region, 3204
Cynthia Sharpe, MBChB, 021924015, cynthias@adhb.govt.nz
- Recruiting
Capital and Coast District Health Board, Te Whatu Ora, Health New Zealand
Wellington, Wellington Region, 6021
Krishna Raghu, MBBS, DCH, FRACP, +64 22 309 8900, krishna.raghu@ccdhb.org.nz
Cynthia Sharpe, MBChB
United States2 sites, 1 recruiting
- Recruiting
University of Minnesota
Minneapolis, Minnesota, 55455
Brittany Faanes, MPH, 612-625-5929, grego318@umn.edu
- Completed
University of California, San Diego
San Diego, California, 92093
About this study
Official title: A Phase IIb Dose Escalation Study of Levetiracetam for the Treatment of Neonatal Seizures
The main purpose of this study is to determine the maximum safe tolerated dose of LEV in the treatment of neonatal seizures. Our hypothesis is that optimal dosing of Levetiracetam (LEV) to treat neonatal seizures is significantly greater than 60mg/kg. This study will be an open label dose-escalation, preliminary safety and efficacy study. There will be a randomized control treatment component. Infants recognized as having neonatal seizures or as being at risk of developing seizures will be recruited and started on continuous video EEG monitoring (CEEG). Eligibility will be confirmed and consent will be obtained. In the first 2 phases of the study, neurologists will identify neonates with mild-moderate seizure burden (less than 8 minutes cumulative seizure activity per hour), appropriate for study with LEV, and exclude patients with higher seizure burden where treatment with PHB is more appropriate. Phase 3 of the dose escalation will only proceed if additional efficacy of LEV has been demonstrated in phases 1 and 2. In Phase 3 we will recruit neonates with seizures of greater severity up to 20 minute seizure burden/hour. This will make the final results of study more generalizable.
If seizures are confirmed, enrolled subjects will receive 60mg/kg of LEV. Subjects whose seizures persist or recur 15 minutes after the first infusion is complete, subjects will then be randomized in the dose escalation study. Patients in the dose escalation study will be randomly assigned to receive either higher dose LEV or treatment with the control drug PHB in a 3:1 allocation ratio, stratified by site.
Funding Source- FDA OOPD
Read the detailed description
Aims/Hypotheses:
Primary Aim: To determine the recommended maximal safe dose of LEV in the setting of neonatal seizures of mild to moderate severity.
Secondary/exploratory aims:
- To study the pharmacokinetics of high dose LEV in neonates with seizures of mild to moderate severity.
- To estimate the additional efficacy of higher doses of LEV in neonates with seizures of mild to moderate severity.
- To improve technologies for the prompt detection of neonatal seizures: We will assess the latest version of Persyst's neonatal seizure detector.
Research Design
This is a Phase IIb, open label dose-escalation, preliminary safety and efficacy study. An active drug treatment control arm (PHB group) is included in the study design. This study is not designed or powered to compare high dose LEV and PHB groups, however, the randomized control group will help with interpretation of adverse events and seizure cessation efficacy seen in the high dose escalation group. This is particularly important because of the high rates of morbidity in neonates with seizures.
24-hour seizure control endpoint: cEEG reviewed by a neurophysiologist will be used for assessing 24-hour seizure control. Treatment will be considered effective in achieving 24-hour seizure control if there is a seizure burden less than 30 seconds in the 24 hours following the dose. Change in seizure burden in 2-hour post treatment period will also be assessed.
Intervention If seizure activity occurs participants will be enrolled and will receive 60mg/kg LEV.
If seizures continue babies will then be randomised to receive either:
- Additional LEV at a higher loading dose (90 mg/kg, 120 mg/kg, or 180 mg/kg (in increments) depending on the stage of the study), OR
- PHB at 20-40 mg/kg. Maintenance treatment will continue for 5 days, either IV or orally if baby is tolerating feeds.
LEV discontinuation or addition of PHB: there are multiple criteria for transition to, or addition of, PHB treatment if required for seizure control.
- Conditions
- Neonatal Seizure, Neonatal Encephalopathy, Hypoxic-Ischemic Encephalopathy, Seizure Newborn
- Being tested
- Levetiracetam Injection, Phenobarbital Sodium Injection
- Medical subject headings
- Hypoxia-Ischemia, Brain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Levetiracetam InjectionDrug
Neonates will be treated with intravenous levetiracetam 60mg/kg for first line management of seizures, and if seizures persist will be randomized to receive higher dose Levetiracetam or standard of care phenobarbital
Phenobarbital Sodium InjectionDrug
Standard of care for neonatal seizures
| Study group | Role | What they receive |
|---|---|---|
| Dose escalation with LEV | Experimental | Additional LEV at a higher dose (90 mg/kg, 120 mg/kg, or 180 mg/kg in increments depending on the stage of the study). Receives: Drug: Levetiracetam Injection |
| Standard of care Phenobarbital | Active comparator | Treatment with Phenobarbital 20mg/kg IV and if needed a further 20mg/kg totalling 40mg/kg Receives: Drug: Phenobarbital Sodium Injection |
What is being measured
The primary outcome is the main question the study is designed to answer.
The primary endpoint is the maximum safe and tolerated dose of Levetiracetam
A continual reassessment method will be used to determine the maximal safe and tolerated dose
Measured: 4 years
Secondary outcomes (7)
Levetiracetam CL
Population pharmacokinetic parameters for LEV Clearance (CL)will be calculated
Measured: 4 years
Levetiracetam Vd
Population pharmacokinetic parameters for LEV Volume of distribution (Vd) will be calculated
Measured: 4 years
Adverse event rates
Rates of adverse events seen with high dose LEV treatment will be reported and compared to rates seen in PHB control arm.
Measured: 4 years
Long-term outcome
Rates of adverse long-term outcome ( Death or Disability at 24 months) will be compared between treatment arms
Measured: 8 years
Seizure burden reduction
Number of patients with at least 50% seizure burden reduction post treatment will be compared between randomized treatment arms
Measured: 4 years
Seizure freedom rates
Number of patients who become seizure free for 24 hours post treatment will be compared between the randomized treatment groups in each stage of the study
Measured: 4 years
Estimate of efficacy of higher dose LEV
Assuming no dose limiting toxicity is demonstrated and the study proceeds to completion, 50 subjects will be treated at 120mg/kg or higher dosing level. This sample size will give satisfactory power for estimating additional efficacy of higher doses. For example, if we document an additional response rate of 15%, this sample size will provide a 95% confidence interval (0.051, 0.248) around that estimate.
Measured: 4 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Nov 2022
- Study start24 Mar 2023
- Primary completion1 Jul 2027 (estimated)
- Study completion31 Dec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Neonatal SeizureStudies of the same condition, open and under way.
- More trials run by University of California, San DiegoThe sponsor's other registered studies.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- If seizures persist or recur after 60 mg/kg LEV patients will be randomized to receive either dose escalation of levetiracetam or phenobarbital. Randomization will occur in a 3:1 ratio LEv: PHB stratified by site.
- Masking
- None (open label)
- Enrolment
- 133 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of California, San Diego
- Sponsor type
- University, hospital or other
- Collaborators
- University of Minnesota, Rady Children's Hospital, San Diego, Auckland City Hospital, University of Auckland, New Zealand, Middlemore Hospital, New Zealand, Waikato Hospital
- Responsible party
- Principal investigator, Richard H. Haas, University of California, San Diego
- Investigators
- Sonya G Wang, M.D., Principal investigator, University of MinnesotaCynthia M Sharpe, M.D., Principal investigator, Auckland City HospitalJeff J Gold, M.D. PhD, Principal investigator, University of California, San DiegoRichard H Haas, MBBChir, Study chair, University of California, San Diego
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05610085
- Sponsor's protocol ID
- FD-R-6335
- Acronym
- NEOLEV3
- Status last verified
- Oct 2026
- First submitted
- 27 Oct 2022
- Last updated
- 15 Oct 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 15 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase IIb Dose Escalation Study of Levetiracetam for the Treatment of Neonatal Seizures
- ClinicalTrials.gov ID
- NCT05610085
- Acronym / sponsor ID
- NEOLEV3 / FD-R-6335
- Conditions
- Neonatal Seizure, Neonatal Encephalopathy, Hypoxic-Ischemic Encephalopathy, Seizure Newborn
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 133 participants (estimated)
- Lead sponsor
- University of California, San DiegoUniversity, hospital or other
- Collaborators
- University of Minnesota, Rady Children's Hospital, San Diego, Auckland City Hospital, University of Auckland, New Zealand, Middlemore Hospital, New Zealand, Waikato Hospital
- Study start
- 24 Mar 2023 (actual)
- Primary completion
- 1 Jul 2027 (estimated)
- Study completion
- 31 Dec 2027 (estimated)
- First posted
- 9 Nov 2022 (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 main purpose of this study is to determine the maximum safe tolerated dose of LEV in the treatment of neonatal seizures. Our hypothesis is that optimal dosing of Levetiracetam (LEV) to treat neonatal seizures is significantly greater than 60mg/kg. This study will be an open label dose-escalation, preliminary safety and efficacy study. There will be a randomized control treatment component. Infants recognized as having neonatal seizures or as being at risk of developing seizures will be recruited and started on continuous video EEG monitoring (CEEG). Eligibility will be confirmed and consent will be obtained. In the first 2 phases of the study, neurologists will identify neonates with mild-moderate seizure burden (less than 8 minutes cumulative seizure activity per hour), appropriate for study with LEV, and exclude patients with higher seizure burden where treatment with PHB is more appropriate. Phase 3 of the dose escalation will only proceed if additional efficacy of LEV has been demonstrated in phases 1 and 2. In Phase 3 we will recruit neonates with seizures of greater severity up to 20 minute seizure burden/hour. This will make the final results of study more generalizable.
If seizures are confirmed, enrolled subjects will receive 60mg/kg of LEV. Subjects whose seizures persist or recur 15 minutes after the first infusion is complete, subjects will then be randomized in the dose escalation study. Patients in the dose escalation study will be randomly assigned to receive either higher dose LEV or treatment with the control drug PHB in a 3:1 allocation ratio, stratified by site.
Funding Source- FDA OOPD
Detailed description
Aims/Hypotheses:
Primary Aim: To determine the recommended maximal safe dose of LEV in the setting of neonatal seizures of mild to moderate severity.
Secondary/exploratory aims:
- To study the pharmacokinetics of high dose LEV in neonates with seizures of mild to moderate severity.
- To estimate the additional efficacy of higher doses of LEV in neonates with seizures of mild to moderate severity.
- To improve technologies for the prompt detection of neonatal seizures: We will assess the latest version of Persyst's neonatal seizure detector.
Research Design
This is a Phase IIb, open label dose-escalation, preliminary safety and efficacy study. An active drug treatment control arm (PHB group) is included in the study design. This study is not designed or powered to compare high dose LEV and PHB groups, however, the randomized control group will help with interpretation of adverse events and seizure cessation efficacy seen in the high dose escalation group. This is particularly important because of the high rates of morbidity in neonates with seizures.
24-hour seizure control endpoint: cEEG reviewed by a neurophysiologist will be used for assessing 24-hour seizure control. Treatment will be considered effective in achieving 24-hour seizure control if there is a seizure burden less than 30 seconds in the 24 hours following the dose. Change in seizure burden in 2-hour post treatment period will also be assessed.
Intervention If seizure activity occurs participants will be enrolled and will receive 60mg/kg LEV.
If seizures continue babies will then be randomised to receive either:
- Additional LEV at a higher loading dose (90 mg/kg, 120 mg/kg, or 180 mg/kg (in increments) depending on the stage of the study), OR
- PHB at 20-40 mg/kg. Maintenance treatment will continue for 5 days, either IV or orally if baby is tolerating feeds.
LEV discontinuation or addition of PHB: there are multiple criteria for transition to, or addition of, PHB treatment if required for seizure control.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- If seizures persist or recur after 60 mg/kg LEV patients will be randomized to receive either dose escalation of levetiracetam or phenobarbital. Randomization will occur in a 3:1 ratio LEv: PHB stratified by site.
| Arm | Type | Receives |
|---|---|---|
| Dose escalation with LEV | Experimental | Drug: Levetiracetam InjectionAdditional LEV at a higher dose (90 mg/kg, 120 mg/kg, or 180 mg/kg in increments depending on the stage of the study). |
| Standard of care Phenobarbital | Active comparator | Drug: Phenobarbital Sodium InjectionTreatment with Phenobarbital 20mg/kg IV and if needed a further 20mg/kg totalling 40mg/kg |
Who may qualify
- Ages
- Up to 1 month
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (5 listed)
- at risk for seizures or suspected to be having seizures;
- all seizure aetiologies except correctable metabolic abnormalities such as hypoglycaemia and hypocalcaemia;
- Term neonates (corrected gestational age between 35 and 44 weeks, postnatal age less than 28 days);
- weight > 2200g.
- Parental ability to comprehend and provide written informed consent
Key exclusion criteria (4 listed)
- Cumulative seizure burden of 8 minutes/ hour or more in phases 1 and 2, Cumulative seizure burden of 20 minutes/hour or more in phase 3;
- Renal failure defined as anuria in the first 24 hours of life;
- Subjects in whom death seems imminent;
- Seizures caused by correctable metabolic abnormality, such as hypocalcaemia, hypoglycaemia.
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 |
|---|---|---|
| Levetiracetam InjectionNeonates will be treated with intravenous levetiracetam 60mg/kg for first line management of seizures, and if seizures persist will be randomized to receive higher dose Levetiracetam or standard of care phenobarbital | Drug | Dose escalation with LEV |
| Phenobarbital Sodium InjectionStandard of care for neonatal seizures | Drug | Standard of care Phenobarbital |
Primary outcome
The primary endpoint is the maximum safe and tolerated dose of Levetiracetam
Time frame: 4 years
A continual reassessment method will be used to determine the maximal safe and tolerated dose
7 secondary outcomes
Levetiracetam CL
Time frame: 4 years
Levetiracetam Vd
Time frame: 4 years
Adverse event rates
Time frame: 4 years
Long-term outcome
Time frame: 8 years
Seizure burden reduction
Time frame: 4 years
Seizure freedom rates
Time frame: 4 years
Estimate of efficacy of higher dose LEV
Time frame: 4 years
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 15 Oct 2026.
- Individual participant dataSharing planned: No
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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.
Sonya G Wang, M.D. principal investigator
University of Minnesota
Cynthia M Sharpe, M.D. principal investigator
Auckland City Hospital
Jeff J Gold, M.D. PhD principal investigator
University of California, San Diego
6 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Levetiracetam Injection and Phenobarbital Sodium Injection in people with Neonatal Seizure and Neonatal Encephalopathy, run by University of California, San Diego at 6 sites in 2 countries.
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 5 inclusion and 4 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 15 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in New Zealand, 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 Sonya G Wang, M.D. (612-301-1454, sgwang@umn.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The primary endpoint is the maximum safe and tolerated dose of Levetiracetam (time frame: 4 years). 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 15 Oct 2026; AzTrials last refreshed its copy on 8 Nov 2026.