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

Sponsor

UCB Biopharma SRL (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04519645

Collaborator

(none)

Enrollment

Locations

Arms

17.1

Anticipated Duration (Months)

1.3

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Electroencephalographic Neonatal Seizures Epilepsy	Drug: Lacosamide intravenous Drug: Lacosamide oral Other: Active Comparator	Phase 2/Phase 3

Study Design

Study Type:

Interventional

Anticipated Enrollment :

32 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Single (Outcomes Assessor)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Mar 31, 2021

Anticipated Primary Completion Date :

Aug 1, 2022

Anticipated Study Completion Date :

Sep 1, 2022

Arms and Interventions

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).

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).

Outcome Measures

Primary Outcome Measures

Change in seizure burden measured in the Evaluation video-electroencephalogram (video-EEG) compared with the Baseline video-EEG [During 2-hour Evaluation starting 1 hour after initial treatment (up to 2 hours)]
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 1 hour 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 [During 2-hour Evaluation starting 1 hour after initial treatment (up to 2 hours)]
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
Percentage of participants with at least 80% reduction in seizure burden in the Evaluation a video-EEG compared with the Baseline video-EEG [During 2-hour Evaluation starting 1 hour after initial treatment (up to 2 hours)]
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
Time to response across the first 48-hours of the Treatment Period compared with the Baseline video-EEG [Across the first 48-hours of the Treatment Period (up to 48 hours)]
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 first 48-hours of the Treatment Period compared with the Baseline video-EEG [Across the first 48-hours of the Treatment Period (up to 48 hours)]
Time to seizure freedom will be analyzed as median time (in hours) to seizure freedom.
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 [Across the first 48-hours of the Treatment Period (up to 48 hours)]
Absolute change in seizure burden measured by continuous 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 1 hour immediately prior to the first administration of study drug.
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 [Across the first 48-hours of the Treatment Period (up to 48 hours)]
Percent change in seizure burden measured by continuous 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 1 hour immediately prior to the first administration of study drug.
Percentage of responders at the end of the first 48-hours of the Treatment Period [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 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
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 nonsevere or severe seizure burden at Baseline [At 24 hours after start of the Treatment Period, compared with Baseline]
For the study participants with nonsevere seizure burden at Baseline (as determined by the Investigator), the numerator is defined as the number of participants with nonsevere seizure burden at Baseline who had no seizures between 23 and 24 hours after the start of the Treatment Period. If less than 30 minutes of interpretable video-EEG are available between 23 and 24 hours after first dose then the response will be determined based on the seizure burden for the most recent 30 minutes of interpretable video-EEG between 20 and 24 hours after the start of the Treatment Period. The 30 minutes of video-EEG does not need to be continuous. If less than 30 minutes of interpretable video-EEG are available between 20 and 24 hours after first dose then seizure freedom at 24 hours will be regarded as missing. This is similarly done for severe burden.
Categorized percentage change in seizure burden in the Evaluation video-EEG compared with the Baseline video-EEG [During 2-hour Evaluation starting 1 hour after initial treatment (up to 2 hours)]
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 [From first administration of study treatment to the End of Safety Follow-up Period (up to Day 42)]
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) [From first administration of study treatment to the End of Safety Follow-up Period (up to Day 42)]
Marked abnormalities are defined as abnormalities in predefined parameters based upon grade 2 toxicity lab values and neonatologist expert opinion in the neonate.
Serum concentration of lacosamide (LCM) [Across the Treatment Period (up to 96 hours)]
Mean serum concentrations of lacosamide (LCM) will be presented across the Treatment Period.

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A to 28 Days

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Sp0968 101	La Jolla	California	United States	92037
2	Sp0968 108	Long Beach	California	United States	90806
3	Sp0968 116	Los Angeles	California	United States	90095
4	Sp0968 115	Orange	California	United States	92868
5	Sp0968 121	San Diego	California	United States	92123
6	Sp0968 190	San Diego	California	United States	92123
7	Sp0968 118	Aurora	Colorado	United States	80045
8	Sp0968 106	Hartford	Connecticut	United States	06106
9	Sp0968 104	Jacksonville	Florida	United States	32207
10	Sp0968 114	Miami	Florida	United States	33136
11	Sp0968 107	Miami	Florida	United States	33155
12	Sp0968 112	Iowa City	Iowa	United States	52242
13	Sp0968 103	Rochester	Minnesota	United States	55905
14	Sp0968 125	Valhalla	New York	United States	10595
15	Sp0968 111	Durham	North Carolina	United States	27705
16	Sp0968 117	Portland	Oregon	United States	97239
17	Sp0968 113	Nashville	Tennessee	United States	37232
18	Sp0968 109	Austin	Texas	United States	78723
19	Sp0968 192	Salt Lake City	Utah	United States	84113
20	Sp0968 105	Salt Lake City	Utah	United States	84132
21	Sp0968 102	Charlottesville	Virginia	United States	22903
22	Sp0968 122	Seattle	Washington	United States	98105
23	Sp0968 302	Parkville		Australia
24	Sp0968 301	South Brisbane		Australia
25	Sp0968 201	Toronto		Canada