A Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of Lacosamide in Neonates With Repeated Electroencephalographic Neonatal Seizures (LENS)
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| ClinicalTrials.gov Identifier: NCT04519645 |
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Recruitment Status :
Recruiting
First Posted : August 20, 2020
Last Update Posted : October 7, 2022
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Electroencephalographic Neonatal Seizures Epilepsy | Drug: Lacosamide intravenous Drug: Lacosamide oral Other: Active Comparator | Phase 2 Phase 3 |
| Study Type : | Interventional (Clinical Trial) |
| Estimated 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 : | March 31, 2021 |
| Estimated Primary Completion Date : | August 25, 2023 |
| Estimated Study Completion Date : | September 26, 2023 |
| Arm | Intervention/treatment |
|---|---|
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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.
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Drug: Lacosamide intravenous
Study participants will receive lacosamide (LCM) as an intravenous (iv) infusion during the Treatment Period.
Other Name: LCM Drug: Lacosamide oral Study participants may receive lacosamide (LCM) as an oral solution during the Extension Period.
Other Name: LCM |
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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.
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Other: Active Comparator
Active Comparator treatment will be chosen and dosed based on StOC (per local practice and treatment guidelines). |
- Change in seizure burden measured in the Evaluation video-electroencephalogram (video-EEG) compared with the Baseline video-EEG [ Time Frame: 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.
- Percentage of responders in the Evaluation video-EEG compared with the Baseline video-EEG [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: Across the Treatment Period (up to 96 hours) ]Mean serum concentrations of lacosamide (LCM) will be presented across the Treatment Period.
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| Ages Eligible for Study: | up to 28 Days (Child) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04519645
| Contact: UCB Cares | 1-844-599-2273 (USA) | UCBCares@ucb.com | |
| Contact: UCB Cares | 001 844 599 2273 | UCBCares@ucb.com |
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| Study Director: | UCB Cares | 001 844 599 2273 |
| Responsible Party: | UCB Biopharma SRL |
| ClinicalTrials.gov Identifier: | NCT04519645 |
| Other Study ID Numbers: |
SP0968 2020-001066-10 ( EudraCT Number ) |
| First Posted: | August 20, 2020 Key Record Dates |
| Last Update Posted: | October 7, 2022 |
| Last Verified: | October 2022 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | Yes |
| 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. |
| Supporting Materials: |
Study Protocol Statistical Analysis Plan (SAP) Clinical Study Report (CSR) |
| 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. |
| 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. |
| URL: | https://vivli.org |
| 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 |
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electroencephalographic neonatal seizures epilepsy neonatal study participants Vimpat |
lacosamide LCM pediatric video-EEG |
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Epilepsy Seizures Brain Diseases Central Nervous System Diseases Nervous System Diseases Neurologic Manifestations |
Lacosamide Anticonvulsants Voltage-Gated Sodium Channel Blockers Sodium Channel Blockers Membrane Transport Modulators Molecular Mechanisms of Pharmacological Action |