A Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of Lacosamide in Neonates With Repeated Electroencephalographic Neonatal Seizures (LENS)

A Multicenter, Open-Label, Randomized, Active Comparator Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of Lacosamide in Neonates With Repeated Electroencephalographic Neonatal Seizures

The purpose of the study is to evaluate the efficacy of lacosamide (LCM) versus an Active Comparator chosen based on standard of care (StOC) in severe and nonsevere seizure burden (defined as total minutes of electroencephalographic neonatal seizures (ENS) per hour) in neonates with seizures that are not adequately controlled with previous anti-epileptic drug (AED) treatment.

Study Overview

• Status: Terminated
• Conditions: Epilepsy; Electroencephalographic Neonatal Seizures
• Intervention / Treatment: Drug: Lacosamide intravenous; Drug: Lacosamide oral; Other: Active Comparator

• Study Type: Interventional
• Enrollment (Actual): 29
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • Parkville, Australia
    • Sp0968 302
  • South Brisbane, Australia
    • Sp0968 301
• Canada
  • Toronto, Canada
    • Sp0968 201
• United States
  • California
    • La Jolla, California, United States, 92037
      • Sp0968 101
    • Long Beach, California, United States, 90806
      • Sp0968 108
    • Los Angeles, California, United States, 90095
      • Sp0968 116
    • San Diego, California, United States, 92123
      • Sp0968 190
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Sp0968 118
  • Florida
    • Jacksonville, Florida, United States, 32207
      • Sp0968 104
    • Miami, Florida, United States, 33155
      • Sp0968 107
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • Sp0968 112
  • New York
    • Valhalla, New York, United States, 10595
      • Sp0968 125
  • Oregon
    • Portland, Oregon, United States, 97239
      • Sp0968 117
  • Texas
    • Austin, Texas, United States, 78723
      • Sp0968 109
  • Utah
    • Salt Lake City, Utah, United States, 84113
      • Sp0968 192
    • Salt Lake City, Utah, United States, 84132
      • Sp0968 105
  • Virginia
    • Charlottesville, Virginia, United States, 22903
      • Sp0968 102
  • Washington
    • Seattle, Washington, United States, 98105
      • Sp0968 122

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 3 years (Child)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Participant must be ≥34 weeks of corrected gestational age (CGA), <46 weeks of CGA, and <28 days of postnatal age (PNA)
• Participants who have confirmation on video-electroencephalogram (EEG) of ≥2 minutes of cumulative electroencephalographic neonatal seizures (ENS) or ≥3 identifiable ENS prior to entering the Treatment Period
• Participants must have received either phenobarbital (PB), levetiracetam (LEV), or midazolam (MDZ) (in any combination) before entering the study
• Participant weighs at least 2.3 kg at the time of enrollment Informed consent
• An Independent Ethics Committee (IEC)-approved written informed consent form (ICF) is signed and dated by the participant's parent(s) or legal representative(s)

Exclusion Criteria:

• Participant with seizures responding to correction of metabolic disturbances (hypoglycemia, hypomagnesemia, or hypocalcemia) or with seizures for which a targeted, known treatment is available
• Participant has seizures related to prenatal maternal drug use or drug withdrawal
• Participant has a clinically relevant electrocardiogram (ECG) abnormality, in the opinion of the investigator
• Participant receiving treatment with phenytoin (PHT), lidocaine (LDC), or other sodium channel blockers at any time

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Lacosamide; Study participants randomized to this arm will receive lacosamide (LCM) as an intravenous infusion in the Treatment Period and may continue to receive lacosamide in the Extension Period. Participants should be switched to oral dosing of LCM as soon as medically possible during the Extension Period.	Drug: Lacosamide intravenous; Study participants will receive lacosamide (LCM) as an intravenous (iv) infusion during the Treatment Period.; Other Names: LCM; Drug: Lacosamide oral; Study participants may receive lacosamide (LCM) as an oral solution during the Extension Period.; Other Names: LCM
Active Comparator: Active Comparator; Study participants randomized to this arm will receive Active Comparator chosen based on standard of care (StOC) in the Clinical Practice in the Treatment Period and may continue to receive in the Extension Period.	Other: Active Comparator; Active Comparator treatment will be chosen and dosed based on StOC (per local practice and treatment guidelines).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Seizure Burden Measured in the Evaluation Video-electroencephalogram (Video-EEG) Compared With the Baseline Video-EEG	Baseline seizure burden was defined as seizure burden measured on the continuous video-EEG (total electroencephalographic neonatal seizures (ENS) in minutes per hour) during a period of up to 2 hours immediately prior to the first administration of study drug. An ENS was defined as an EEG seizure lasting for at least 10 seconds on video-EEG. The seizure burden in the Evaluation Period was calculated as the total duration of seizures between 1 and 3 hours after the first dose of study medication divided by the duration of interpretable video-EEG available in the same period. Change in seizure burden measured in the Evaluation video-EEG compared with the Baseline video-EEG was analyzed such that a positive value indicates a reduction in seizure burden from baseline.	During 2-hour Evaluation starting 1 hour after initial treatment (up to 2 hours), compared to Baseline

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Responders in the Evaluation Video-EEG Compared With the Baseline Video-EEG	A responder is defined as a study participant who achieved the following reduction in seizure burden without need for rescue medication, compared with the seizure burden measured during the Baseline Period immediately prior to the study medication administration, evaluated for a 2-hour period starting 1 hour after the start of initial treatment: - At least 80% reduction of seizure burden in participants who were categorized by the Investigator as having non-severe seizure burden during Baseline OR - At least 50% reduction of seizure burden in participants who were categorized by the Investigator as having severe seizure burden during Baseline.	During 2-hour Evaluation starting 1 hour after initial treatment (up to 2 hours), compared to Baseline
Percentage of Participants With at Least 80% Reduction in Seizure Burden in the Evaluation a Video-EEG Compared With the Baseline Video-EEG	A responder is defined as a study participant who achieved the following reduction in seizure burden without need for rescue medication, compared with the seizure burden measured during the Baseline Period immediately prior to investigational medicinal product (IMP) administration, evaluated for a 2-hour period starting 1 hour after the start of initial treatment: A reduction in seizure burden from Baseline of >=80% regardless of baseline seizure severity. Percentage of Participants With at least 80% Reduction in Seizure Burden in the Evaluation (starting 1 hour after treatment) of a Video-EEG Compared with the Baseline Video-EEG were reported.	During 2-hour Evaluation starting 1 hour after initial treatment (up to 2 hours), compared to Baseline
Time to Response Across the 48-hour Treatment Period Compared With the Baseline Video-EEG	Time to response where response was defined as a reduction in seizure burden from Baseline of at least 80% in participants with non-severe seizure burden, and of at least 50% for participants with severe seizure burden. Time to response was censored at the date/time the participant received rescue medication or stopped video-EEG monitoring, or otherwise at the end of the 48-hour period.	Across the first 48 hours of Treatment Period, compared to Baseline
Time to Seizure Freedom Across the First 48-hour Treatment Period Compared With the Baseline Video-EEG	Seizure freedom was defined as 0 minutes of seizures in a 1-hour period (or 2-hour period for the 3-hour time point) and was analyzed across the 48 hours. The time to seizure freedom was measured in hours, defined as the first time point when the response criterion was met minus the date and time of the first dose of randomized study medication administration. Time to seizure freedom was censored at the time of receiving rescue medication, stopping video-EEG monitoring or otherwise at 48 hours after first dose.	Across the first 48 hours of Treatment Period, compared to Baseline
Absolute Change in Seizure Burden Across the First 48-hours of the Treatment Period Measured by Continuous Video-EEG Compared With the Baseline Video-EEG	Baseline seizure burden was calculated as total duration of seizures (in minutes) between -2 hour and 0 hours before first dose of study medication divided by total duration of interpretable video-EEG (in hours) in the same period. Seizure burden for 8, 16, 24, 32, 40 and 48 hour time points was calculated as total duration of seizures in the hour prior to time point divided by duration of interpretable video-EEG available in same period. If <30 minutes of interpretable video-EEG were available in the 1 hour prior to the time point, response was calculated based on seizure burden for most recent 30 minutes of interpretable video-EEG in the 2 hours (for 8 and 16 hour points) or 4 hours (for 24, 32, 40 and 48 hour points) prior to time point. The 30 minutes of video-EEG did not need to be continuous. Absolute reduction in seizure burden for these time points was calculated as seizure burden in Baseline Period minus seizure burden at that time point.	Treatment Period: 7-8 hours, 15-16 hours, 23-24 hours, 31-32 hours, 39-40 hours, 47-48 hours, compared to Baseline
Percent Change in Seizure Burden Across the First 48-hours of the Treatment Period Measured by Continuous Video-EEG Compared With the Baseline Video-EEG	The percent change in seizure burden for the 8, 16, 24, 32, 40 and 48 hour time points was calculated as the seizure burden at Baseline minus the seizure burden at the respective time point, divided by the seizure burden in the Baseline Period, multiplied by 100. Percent change in seizure burden was analyzed such that a positive value indicates a reduction in seizure burden from baseline.	Treatment Period: 7-8 hours, 15-16 hours, 23-24 hours, 31-32 hours, 39-40 hours, 47-48 hours, compared to Baseline
Percentage of Responders at the End of the First 48-hours of the Treatment Period	A responder is defined as a study participant who achieved the following reduction in seizure burden without need for rescue medication, compared with the seizure burden measured during the Baseline Period immediately prior to investigational medicinal product (IMP) administration, evaluated for a 2-hour period starting 1 hour after the start of initial treatment: At least 80% reduction of seizure burden in participants who were categorized as having nonsevere seizure burden during Baseline OR At least 50% reduction of seizure burden in participants who had at least one 30-minute period of severe seizure burden during Baseline. The denominator for the percentages was based on the number of participants with video- EEG data available at the 48 hour time point.	Across the first 48 hours of Treatment Period
Percentage of Study Participants Who Are Seizure-free (100% Reduction in Seizure Burden From Baseline) at 24 Hours After Start of the Treatment Period, Categorized by Study Participants With Non Severe or Severe Seizure Burden at Baseline	Seizure free was defined as 100% reduction in seizure burden or having no seizures in the assessment period (23 to 24 hours after first dose) from Baseline. For the study participants with severe seizure burden at Baseline (as determined by the Investigator), the numerator was defined as the number of participants with severe seizure burden at Baseline who had no seizures between 23 and 24 hours after the start of the Treatment Period. The denominator for the percentages was based on the number of participants with video-EEG data available at the 24 hour time point. Here, N='overall number of participants analyzed' and n='number analyzed' in categories.	24 hours after the start of Treatment Period, compared to Baseline
Categorized Percentage of Participants With Change in Seizure Burden in the Evaluation Video-EEG Compared With the Baseline Video-EEG	Baseline seizure burden was calculated as total duration of seizures (in minutes) between -2 and 0 hours before the first dose of study medication divided by total duration of interpretable video-EEG (in hours) in same period. Seizure burden in Evaluation Period was calculated as total duration of seizures between 1 and 3 hours after first dose of study medication divided by duration of interpretable video-EEG available in same period. Percent change in seizure burden for Evaluation period was calculated as seizure burden at Baseline minus seizure burden at respective time point, divided by seizure burden in Baseline Period, multiplied by 100. Participants classified in one of following categories based on their percent reduction from Baseline to Evaluation Period: < -25% (worsening), -25% to <25% (no change), 25% to <50%, 50% to <80%, and >=80%. Percent change in seizure burden was analyzed and categorized such that positive value indicates reduction in seizure burden from baseline.	During 2-hour Evaluation starting 1 hour after initial treatment (up to 2 hours), compared to Baseline
Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) as Reported by the Investigator	An adverse event (AE) is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study medication, whether or not considered related to the study medication. TEAEs are defined as AEs which have onset on or after the start date and time of initial study medication administration.	From first administration of study treatment to the End of Safety Follow-up Period (up to Day 42)
Percentage of Participants With Treatment-emergent Marked Abnormalities in 12-lead Electrocardiogram (ECG)	The ECG treatment-emergent marked abnormalities values are based on grade 2 toxicity based on abnormal values or clinical experience based on investigator's discretion. Participants randomized to Lacosamide and enrolled under this version of the protocol have planned assessments at Screening, 1-6 hours, 48, and 96 hours only. For participants randomized to Active Comparator treatment, only the Screening assessment was applicable.	Active Comparator: Screening; Lacosamide: Screening, 1-6 hours, 48 and 96 hours
Serum Concentration of Lacosamide	Serum concentrations of lacosamide were measured and concentration data were summarized. PK sparse sampling was performed.	Day 1: 30-90 minutes and 6 - 8 hours after start of first infusion, 30 - 90 minutes and 6 - 8 hours after start of second or third infusion, Days 2, 3 and 4

Collaborators and Investigators

• Sponsor: UCB Biopharma SRL
• Investigators: Study Director: UCB Cares, 001 844 599 2273

Study record dates

Study Major Dates

• Study Start (Actual): March 31, 2021
• Primary Completion (Actual): August 6, 2024
• Study Completion (Actual): October 31, 2024

Study Registration Dates

• First Submitted: July 31, 2020
• First Submitted That Met QC Criteria: August 19, 2020
• First Posted (Actual): August 20, 2020

Study Record Updates

• Last Update Posted (Estimated): October 3, 2025
• Last Update Submitted That Met QC Criteria: September 16, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: pediatric; epilepsy; lacosamide; LCM; Vimpat; electroencephalographic neonatal seizures; neonatal study participants; video-EEG
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Epilepsy; Organic Chemicals; Acids, Acyclic; Carboxylic Acids; Amides; Acetamides; Acetates; Lacosamide
• Other Study ID Numbers: SP0968; 2020-001066-10 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Data from this trial may be requested by qualified researchers six months after product approval in the US and/or Europe, or global development is discontinued, and 18 months after trial completion. Investigators may request access to anonymized individual patient-level data and redacted trial documents which may include: analysis-ready datasets, study protocol, annotated case report form, statistical analysis plan, dataset specifications, and clinical study report. Prior to use of the data, proposals need to be approved by an independent review panel at www.Vivli.org and a signed data sharing agreement will need to be executed. All documents are available in English only, for a prespecified time, typically 12 months, on a password protected portal. This plan may change if the risk of re-identifying trial participants is determined to be too high after the trial is completed; in this case and to protect participants, individual patient-level data would not be made available.
• IPD Sharing Time Frame: Data from this trial may be requested by qualified researchers six months after product approval in the US and/or Europe or global development is discontinued, and 18 months after trial completion.
• IPD Sharing Access Criteria: Qualified researchers may request access to anonymized IPD and redacted study documents which may include: raw datasets, analysis-ready datasets, study protocol, blank case report form, annotated case report form, statistical analysis plan, dataset specifications, and clinical study report. Prior to use of the data, proposals need to be approved by an independent review panel at www.Vivli.org and a signed data sharing agreement will need to be executed.All documents are available in English only, for a pre-specified time, typically 12 months, on a password protected portal.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No