Back to resultsA Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of Lacosamide in Neonates With Repeated Electroencephalographic Neonatal Seizures (LENS)
Primary Purpose
Electroencephalographic Neonatal Seizures, Epilepsy
Status
Recruiting
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Lacosamide intravenous
Lacosamide oral
Active Comparator
Sponsored by
About this trial
This is an interventional treatment trial for Electroencephalographic Neonatal Seizures focused on measuring electroencephalographic neonatal seizures, epilepsy, neonatal study participants, Vimpat, lacosamide, LCM, pediatric, video-EEG
Eligibility Criteria
Inclusion Criteria:
- Participant must be at least 34 weeks of gestational age (GA)
- 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
Sites / Locations
- Sp0968 101Recruiting
- Sp0968 108Recruiting
- Sp0968 116Recruiting
- Sp0968 115Recruiting
- Sp0968 121
- Sp0968 190Recruiting
- Sp0968 118Recruiting
- Sp0968 106
- Sp0968 104
- Sp0968 114Recruiting
- Sp0968 107Recruiting
- Sp0968 112Recruiting
- Sp0968 103Recruiting
- Sp0968 125Recruiting
- Sp0968 111Recruiting
- Sp0968 117
- Sp0968 113
- Sp0968 109Recruiting
- Sp0968 192Recruiting
- Sp0968 105Recruiting
- Sp0968 102Recruiting
- Sp0968 122Recruiting
- Sp0968 302Recruiting
- Sp0968 301Recruiting
- Sp0968 201Recruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Lacosamide
Active Comparator
Arm Description
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.
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.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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
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
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.
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.
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%)
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.
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.
Plasma/serum concentration of lacosamide (LCM)
Mean plasm/serum concentrations of lacosamide (LCM) will be presented across the Treatment Period.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04519645
Brief Title
A Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of Lacosamide in Neonates With Repeated Electroencephalographic Neonatal Seizures
Acronym
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
Study Type
Interventional
2. Study Status
Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
March 31, 2021 (Actual)
Primary Completion Date
August 2, 2024 (Anticipated)
Study Completion Date
August 29, 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
UCB Biopharma SRL
4. Oversight
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
Data Monitoring Committee
Yes
5. Study Description
Brief 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Electroencephalographic Neonatal Seizures, Epilepsy
Keywords
electroencephalographic neonatal seizures, epilepsy, neonatal study participants, Vimpat, lacosamide, LCM, pediatric, video-EEG
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
Outcomes Assessor
Allocation
Randomized
Enrollment
32 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Lacosamide
Arm Type
Experimental
Arm Description
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.
Arm Title
Active Comparator
Arm Type
Active Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Lacosamide intravenous
Other Intervention Name(s)
LCM
Intervention Description
Study participants will receive lacosamide (LCM) as an intravenous (iv) infusion during the Treatment Period.
Intervention Type
Drug
Intervention Name(s)
Lacosamide oral
Other Intervention Name(s)
LCM
Intervention Description
Study participants may receive lacosamide (LCM) as an oral solution during the Extension Period.
Intervention Type
Other
Intervention Name(s)
Active Comparator
Intervention Description
Active Comparator treatment will be chosen and dosed based on StOC (per local practice and treatment guidelines).
Primary Outcome Measure Information:
Title
Change in seizure burden measured in the Evaluation video-electroencephalogram (video-EEG) compared with the Baseline video-EEG
Description
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.
Time Frame
During 2-hour Evaluation starting 1 hour after initial treatment (up to 2 hours)
Secondary Outcome Measure Information:
Title
Percentage of responders in the Evaluation video-EEG compared with the Baseline video-EEG
Description
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
Time Frame
During 2-hour Evaluation starting 1 hour after initial treatment (up to 2 hours)
Title
Percentage of participants with at least 80% reduction in seizure burden in the Evaluation a video-EEG compared with the Baseline video-EEG
Description
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
Time Frame
During 2-hour Evaluation starting 1 hour after initial treatment (up to 2 hours)
Title
Time to response across the 96-hour Treatment Period
Description
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.
Time Frame
Across the Treatment Period (up to 96 hours)
Title
Time to seizure freedom across the 96-hour Treatment Period
Description
Time to seizure freedom will be analyzed as median time (in hours) to seizure freedom.
Time Frame
Across the Treatment Period (up to 96 hours)
Title
Categorized percentage change in seizure burden in the Evaluation video-EEG compared with the Baseline video-EEG
Description
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%)
Time Frame
During 2-hour Evaluation starting 1 hour after initial treatment (up to 2 hours)
Title
Percentage of participants with treatment-emergent adverse events (TEAEs) as reported by the investigator
Description
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.
Time Frame
From first administration of study treatment to the End of Safety Follow-up Period (up to Day 42)
Title
Percentage of participants with treatment-emergent marked abnormalities in 12-lead electrocardiogram (ECG)
Description
Marked abnormalities are defined as abnormalities in predefined parameters based upon grade 2 toxicity lab values and neonatologist expert opinion in the neonate.
Time Frame
From first administration of study treatment to the End of Safety Follow-up Period (up to Day 42)
Title
Plasma/serum concentration of lacosamide (LCM)
Description
Mean plasm/serum concentrations of lacosamide (LCM) will be presented across the Treatment Period.
Time Frame
Across the Treatment Period (up to 96 hours)
10. Eligibility
Sex
All
Maximum Age & Unit of Time
28 Days
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
UCB Cares
Phone
1-844-599-2273 (USA)
Email
UCBCares@ucb.com
First Name & Middle Initial & Last Name or Official Title & Degree
UCB Cares
Phone
001 844 599 2273
Email
UCBCares@ucb.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
UCB Cares
Organizational Affiliation
001 844 599 2273
Official's Role
Study Director
Facility Information:
Facility Name
Sp0968 101
City
La Jolla
State/Province
California
ZIP/Postal Code
92037
Country
United States
Individual Site Status
Recruiting
Facility Name
Sp0968 108
City
Long Beach
State/Province
California
ZIP/Postal Code
90806
Country
United States
Individual Site Status
Recruiting
Facility Name
Sp0968 116
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Individual Site Status
Recruiting
Facility Name
Sp0968 115
City
Orange
State/Province
California
ZIP/Postal Code
92868
Country
United States
Individual Site Status
Recruiting
Facility Name
Sp0968 121
City
San Diego
State/Province
California
ZIP/Postal Code
92123
Country
United States
Individual Site Status
Withdrawn
Facility Name
Sp0968 190
City
San Diego
State/Province
California
ZIP/Postal Code
92123
Country
United States
Individual Site Status
Recruiting
Facility Name
Sp0968 118
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Individual Site Status
Recruiting
Facility Name
Sp0968 106
City
Hartford
State/Province
Connecticut
ZIP/Postal Code
06106
Country
United States
Individual Site Status
Withdrawn
Facility Name
Sp0968 104
City
Jacksonville
State/Province
Florida
ZIP/Postal Code
32207
Country
United States
Individual Site Status
Completed
Facility Name
Sp0968 114
City
Miami
State/Province
Florida
ZIP/Postal Code
33136
Country
United States
Individual Site Status
Recruiting
Facility Name
Sp0968 107
City
Miami
State/Province
Florida
ZIP/Postal Code
33155
Country
United States
Individual Site Status
Recruiting
Facility Name
Sp0968 112
City
Iowa City
State/Province
Iowa
ZIP/Postal Code
52242
Country
United States
Individual Site Status
Recruiting
Facility Name
Sp0968 103
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Individual Site Status
Recruiting
Facility Name
Sp0968 125
City
Valhalla
State/Province
New York
ZIP/Postal Code
10595
Country
United States
Individual Site Status
Recruiting
Facility Name
Sp0968 111
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27705
Country
United States
Individual Site Status
Recruiting
Facility Name
Sp0968 117
City
Portland
State/Province
Oregon
ZIP/Postal Code
97239
Country
United States
Individual Site Status
Completed
Facility Name
Sp0968 113
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232-2576
Country
United States
Individual Site Status
Withdrawn
Facility Name
Sp0968 109
City
Austin
State/Province
Texas
ZIP/Postal Code
78723
Country
United States
Individual Site Status
Recruiting
Facility Name
Sp0968 192
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84113
Country
United States
Individual Site Status
Recruiting
Facility Name
Sp0968 105
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84132
Country
United States
Individual Site Status
Recruiting
Facility Name
Sp0968 102
City
Charlottesville
State/Province
Virginia
ZIP/Postal Code
22903
Country
United States
Individual Site Status
Recruiting
Facility Name
Sp0968 122
City
Seattle
State/Province
Washington
ZIP/Postal Code
98105
Country
United States
Individual Site Status
Recruiting
Facility Name
Sp0968 302
City
Parkville
Country
Australia
Individual Site Status
Recruiting
Facility Name
Sp0968 301
City
South Brisbane
Country
Australia
Individual Site Status
Recruiting
Facility Name
Sp0968 201
City
Toronto
Country
Canada
Individual Site Status
Recruiting
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing 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 URL
https://www.Vivli.org
Learn more about this trial
A Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of Lacosamide in Neonates With Repeated Electroencephalographic Neonatal Seizures
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