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

• Study Type: Interventional
• Enrollment (Estimated): 32
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: UCB Cares; Phone Number: 1-844-599-2273 (USA); Email: ucbcares@ucb.com
• Study Contact Backup: Name: UCB Cares; Phone Number: 001 844 599 2273; Email: UCBCares@ucb.com

Study Locations

• Australia
  • Parkville, Australia
    • Recruiting
    • Sp0968 302
  • South Brisbane, Australia
    • Recruiting
    • Sp0968 301
• Canada
  • Toronto, Canada
    • Recruiting
    • Sp0968 201
• United States
  • California
    • La Jolla, California, United States, 92037
      • Recruiting
      • Sp0968 101
    • Long Beach, California, United States, 90806
      • Recruiting
      • Sp0968 108
    • Los Angeles, California, United States, 90095
      • Recruiting
      • Sp0968 116
    • Orange, California, United States, 92868
      • Recruiting
      • Sp0968 115
    • San Diego, California, United States, 92123
      • Recruiting
      • Sp0968 190
    • San Diego, California, United States, 92123
      • Withdrawn
      • Sp0968 121
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Recruiting
      • Sp0968 118
  • Connecticut
    • Hartford, Connecticut, United States, 06106
      • Withdrawn
      • Sp0968 106
  • Florida
    • Jacksonville, Florida, United States, 32207
      • Completed
      • Sp0968 104
    • Miami, Florida, United States, 33155
      • Recruiting
      • Sp0968 107
    • Miami, Florida, United States, 33136
      • Withdrawn
      • Sp0968 114
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • Recruiting
      • Sp0968 112
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Withdrawn
      • Sp0968 103
  • New York
    • Valhalla, New York, United States, 10595
      • Recruiting
      • Sp0968 125
  • North Carolina
    • Durham, North Carolina, United States, 27705
      • Recruiting
      • Sp0968 111
  • Oregon
    • Portland, Oregon, United States, 97239
      • Completed
      • Sp0968 117
  • Tennessee
    • Nashville, Tennessee, United States, 37232-2576
      • Withdrawn
      • Sp0968 113
  • Texas
    • Austin, Texas, United States, 78723
      • Recruiting
      • Sp0968 109
  • Utah
    • Salt Lake City, Utah, United States, 84113
      • Recruiting
      • Sp0968 192
    • Salt Lake City, Utah, United States, 84132
      • Recruiting
      • Sp0968 105
  • Virginia
    • Charlottesville, Virginia, United States, 22903
      • Recruiting
      • Sp0968 102
  • Washington
    • Seattle, Washington, United States, 98105
      • Recruiting
      • Sp0968 122

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 1 year (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	Change in seizure burden measured in the Evaluation video-EEG compared with the Baseline video-EEG. Baseline seizure burden is 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.	During 2-hour Evaluation starting 1 hour after initial treatment (up to 2 hours)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Categorized percentage change in seizure burden in the Evaluation video-EEG compared with the Baseline video-EEG	The change in seizure burden will be presented in the following categories: (<-25% [worsening], -25% to <25% [no change], 25% to <50%, 50% to <80%, and ≥80%)	During 2-hour Evaluation starting 1 hour after initial treatment (up to 2 hours)
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. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study medication.	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)	Marked abnormalities are defined as abnormalities in predefined parameters based upon grade 2 toxicity lab values and neonatologist expert opinion in the neonate.	From first administration of study treatment to the End of Safety Follow-up Period (up to Day 42)
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 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	During 2-hour Evaluation starting 1 hour after initial treatment (up to 2 hours)
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: 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	During 2-hour Evaluation starting 1 hour after initial treatment (up to 2 hours)
Time to response across the 96-hour Treatment Period	Time to response is presented as median time (in hours) to the 50% reduction in study participants with severe seizure burden or 80% reduction in study participants with nonsevere seizure burden.	Across the Treatment Period (up to 96 hours)
Time to seizure freedom across the 96-hour Treatment Period	Time to seizure freedom will be analyzed as median time (in hours) to seizure freedom.	Across the Treatment Period (up to 96 hours)
Plasma/serum concentration of lacosamide (LCM)	Mean plasm/serum concentrations of lacosamide (LCM) will be presented across the Treatment Period.	Across the Treatment Period (up to 96 hours)

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 (Estimated): August 2, 2024
• Study Completion (Estimated): August 29, 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): November 21, 2023
• Last Update Submitted That Met QC Criteria: November 20, 2023
• Last Verified: November 1, 2023

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; Neurologic Manifestations; Epilepsy; Seizures; Molecular Mechanisms of Pharmacological Action; Membrane Transport Modulators; Anticonvulsants; Voltage-Gated Sodium Channel Blockers; Sodium Channel Blockers; 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