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

Epilepsy Clinical Trial

— LENS  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04519645
• Other study ID #: SP0968
• Secondary ID: 2020-001066-10
• Status: Recruiting
• Phase: Phase 2
• Start date: March 31, 2021
• Est. completion date: August 29, 2025

Study information

• Verified date: May 2024
• Source: UCB Pharma
• Contact: UCB Cares
• Phone: 1-844-599-2273 (USA)
• Email: UCBCares[@]ucb.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 32
• Est. completion date: August 29, 2025
• Est. primary completion date: August 4, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 28 Days

Eligibility

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

Related Conditions & MeSH terms

• Electroencephalographic Neonatal Seizures
• Epilepsy
• Seizures

Intervention

Drug:
• Lacosamide intravenous
Study participants will receive lacosamide (LCM) as an intravenous (iv) infusion during the Treatment Period.
• Lacosamide oral
Study participants may receive lacosamide (LCM) as an oral solution during the Extension Period.

Other:
• Active Comparator
Active Comparator treatment will be chosen and dosed based on StOC (per local practice and treatment guidelines).

Locations

Country	Name	City	State
Australia	Sp0968 302	Parkville
Australia	Sp0968 301	South Brisbane
Canada	Sp0968 201	Toronto
United States	Sp0968 118	Aurora	Colorado
United States	Sp0968 109	Austin	Texas
United States	Sp0968 102	Charlottesville	Virginia
United States	Sp0968 111	Durham	North Carolina
United States	Sp0968 106	Hartford	Connecticut
United States	Sp0968 112	Iowa City	Iowa
United States	Sp0968 104	Jacksonville	Florida
United States	Sp0968 101	La Jolla	California
United States	Sp0968 108	Long Beach	California
United States	Sp0968 116	Los Angeles	California
United States	Sp0968 107	Miami	Florida
United States	Sp0968 114	Miami	Florida
United States	Sp0968 113	Nashville	Tennessee
United States	Sp0968 115	Orange	California
United States	Sp0968 117	Portland	Oregon
United States	Sp0968 103	Rochester	Minnesota
United States	Sp0968 105	Salt Lake City	Utah
United States	Sp0968 192	Salt Lake City	Utah
United States	Sp0968 121	San Diego	California
United States	Sp0968 190	San Diego	California
United States	Sp0968 122	Seattle	Washington
United States	Sp0968 125	Valhalla	New York

Sponsors (1)

Lead Sponsor	Collaborator
UCB Biopharma SRL

Countries where clinical trial is conducted

United States,  Australia,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)