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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT05610085




Registration number
NCT05610085
Ethics application status
Date submitted
27/10/2022
Date registered
9/11/2022
Date last updated
8/01/2024

Titles & IDs
Public title
A Dose Escalation Study of Levetiracetam in the Treatment of Neonatal Seizures
Scientific title
A Phase IIb Dose Escalation Study of Levetiracetam for the Treatment of Neonatal Seizures
Secondary ID [1] 0 0
FD-R-6335
Universal Trial Number (UTN)
Trial acronym
NEOLEV3
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Neonatal Seizure 0 0
Neonatal Encephalopathy 0 0
Hypoxic-Ischemic Encephalopathy 0 0
Seizure Newborn 0 0
Condition category
Condition code
Neurological 0 0 0 0
Epilepsy
Neurological 0 0 0 0
Other neurological disorders
Cardiovascular 0 0 0 0
Diseases of the vasculature and circulation including the lymphatic system

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Levetiracetam Injection
Treatment: Drugs - Phenobarbital Sodium Injection

Experimental: Dose escalation with LEV - Additional LEV at a higher dose (30 mg/kg, 60 mg/kg, or 90 mg/kg depending on the stage of the study).

Active Comparator: Standard of care Phenobarbital - Treatment with Phenobarbital 20mg/kg IV and if needed a further 20mg/kg totalling 40mg/kg


Treatment: Drugs: Levetiracetam Injection
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

Treatment: Drugs: Phenobarbital Sodium Injection
Standard of care for neonatal seizures
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
The primary endpoint is the maximum safe and tolerated dose of Levetiracetam
Timepoint [1] 0 0
4 years
Secondary outcome [1] 0 0
Levetiracetam CL
Timepoint [1] 0 0
4 years
Secondary outcome [2] 0 0
Levetiracetam Vd
Timepoint [2] 0 0
4 years
Secondary outcome [3] 0 0
Adverse event rates
Timepoint [3] 0 0
4 years
Secondary outcome [4] 0 0
Long-term outcome
Timepoint [4] 0 0
8 years
Secondary outcome [5] 0 0
Seizure burden reduction
Timepoint [5] 0 0
4 years
Secondary outcome [6] 0 0
Seizure freedom rates
Timepoint [6] 0 0
4 years
Secondary outcome [7] 0 0
Estimate of efficacy of higher dose LEV
Timepoint [7] 0 0
4 years

Eligibility
Key inclusion criteria
- 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
Minimum age
No limit
Maximum age
1 Month
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Cumulative seizure burden of 8 minutes/ hour or more in phases 1 and 2, Cumulative
seizure burden of 30 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
24/03/2023
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
31/12/2026
Actual
Sample size
Target
133
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Minnesota
Country [3] 0 0
New Zealand
State/province [3] 0 0
Auckland

Funding & Sponsors
Primary sponsor type
Other
Name
University of California, San Diego
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
University of Minnesota
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Other
Name [2] 0 0
Rady Children's Hospital, San Diego
Address [2] 0 0
Country [2] 0 0
Other collaborator category [3] 0 0
Other
Name [3] 0 0
Auckland City Hospital
Address [3] 0 0
Country [3] 0 0
Other collaborator category [4] 0 0
Other
Name [4] 0 0
University of Auckland, New Zealand
Address [4] 0 0
Country [4] 0 0
Other collaborator category [5] 0 0
Other
Name [5] 0 0
Middlemore Hospital, New Zealand
Address [5] 0 0
Country [5] 0 0

Ethics approval
Ethics application status

Summary
Brief 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. 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
30 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
Trial website
https://clinicaltrials.gov/ct2/show/NCT05610085
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Sonya G Wang, M.D.
Address 0 0
University of Minnesota
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Sonya G Wang, M.D.
Address 0 0
Country 0 0
Phone 0 0
612-301-1454
Fax 0 0
Email 0 0
sgwang@umn.edu
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT05610085