Lacosamide for Neonatal Seizures

(LENS Trial)

Recruiting at 15 trial locations

Overseen By UCB Cares

Age: < 18

Sex: Any

Trial Phase: Phase 2

Sponsor: UCB Biopharma SRL

Must be taking: Phenobarbital, Levetiracetam, Midazolam

Must not be taking: Sodium channel blockers

Disqualifiers: Metabolic disturbances, Prenatal drug use, ECG abnormality, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 96 hours

32 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you must have already received phenobarbital, levetiracetam, or midazolam before joining. You cannot be on phenytoin, lidocaine, or other sodium channel blockers.

What data supports the effectiveness of the drug Lacosamide for treating seizures?

Lacosamide has been shown to reduce seizure frequency in patients with partial-onset seizures when used alongside other anti-seizure medications, according to several clinical studies. ^{1 2 3 4 5}

Is lacosamide generally safe for humans?

Lacosamide has been used as an anti-seizure medication and is generally considered safe for humans, including during breastfeeding, with no reported adverse reactions in infants. However, clinical monitoring is recommended, and long-term effects are not fully known. ^{1 3 4 5 6}

What makes the drug lacosamide unique for treating neonatal seizures?

Lacosamide is unique because it works by enhancing the slow inactivation of voltage-gated sodium channels, which is different from many other anti-seizure medications. It is also available in both oral and intravenous forms, providing flexibility in administration. ^{1 2 3 4 7}

Research Team

UCB Cares

Principal Investigator

001 844 599 2273

Eligibility Criteria

This trial is for newborns between 34 and <46 weeks of corrected gestational age, weighing at least 2.3 kg, with uncontrolled seizures despite previous treatment with certain anti-epileptic drugs. Newborns must not have seizure causes that are correctable or related to prenatal drug issues.

Inclusion Criteria

I weigh at least 2.3 kg.

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)

I have taken phenobarbital, levetiracetam, or midazolam before.

Exclusion Criteria

You have seizures caused by your mother using drugs or going through drug withdrawal before you were born.

My seizures improve with treatment for metabolic issues or have a known treatment.

You have a heart problem that shows up on an electrocardiogram (ECG) test, according to the doctor.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive lacosamide or an active comparator for seizure management

Up to 96 hours

Evaluation

Seizure burden is evaluated using video-EEG compared with baseline

2 hours

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to Day 42

Extension

Participants may continue to receive treatment in an extension period

Treatment Details

Interventions

• Active Comparator
• Lacosamide

Trial Overview The study tests the effectiveness of Lacosamide (LCM), given intravenously or orally, against a standard care comparator in reducing neonatal seizure burden as measured by EEG in newborns whose seizures persist after initial treatments.

Participant Groups

Group I: Lacosamide Experimental Treatment 2 Interventions

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.

Group II: Active Comparator Active Control 1 Intervention

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.

Who Is Running the Clinical Trial?

UCB Biopharma SRL

Lead Sponsor

Trials

118

Recruited

23,200+

Jean-Christophe Tellier

UCB Biopharma SRL

Chief Executive Officer since 2015

MD from University of Reims Champagne-Ardenne, Rheumatology specialization from University of Paris V, Executive business programs at Harvard and INSEAD

Dr. Iris Loew-Friedrich

UCB Biopharma SRL

Chief Medical Officer since 2014

MD from University of Leuven, PhD in Medical Sciences from University of Leuven

Findings from Research

In a study of 15 inpatients with frequent partial-onset seizures and cognitive or affective disorders, intravenous lacosamide significantly reduced seizure frequency by 75% in some patients, with 11 out of 15 experiencing no seizures after 2-3 days of treatment.

Lacosamide also positively impacted the emotional well-being and quality of life in 73.4% of patients, with only mild to moderate side effects reported in 2 patients, indicating it is a well-tolerated and effective option for drug-resistant seizures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[The efficacy of intravenous lacosamide in psychiatric hospital]. Vakula, IN., Bojko, EO., Vorona, UA., et al.[2018]

Lacosamide, perampanel, and zonisamide are anti-seizure medications that can be safely used by breastfeeding mothers, as their concentrations in breast milk are relatively low compared to maternal serum levels, suggesting minimal exposure to infants.

The study found that while breastfeeding is recommended for mothers on these medications, the actual exposure to infants should be monitored through serum concentration measurements to ensure safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic monitoring of lacosamide, perampanel, and zonisamide during breastfeeding. Kacirova, I., Urinovska, R., Grundmann, M.[2023]

Lacosamide (Vimpat) is an antiepileptic drug that works through a dual mechanism: it enhances the slow inactivation of voltage-gated sodium channels and modulates the CRMP-2 protein, which is involved in neuroprotection.

Clinical studies have shown that lacosamide effectively reduces seizure frequency in patients with partial-onset seizures when used alongside other antiepileptic medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Lacosamide. A new antiepileptic drug as adjunctive therapy in patients with partial-onset seizures]. Saussele, T.[2018]

A case study of a woman with pharmacoresistant epilepsy showed that breastfeeding while on lacosamide treatment resulted in low infant blood concentrations of the drug, with no reported adverse reactions, suggesting it may be safe for breastfeeding mothers on this medication.

While some studies indicate that lacosamide can pass into breast milk, the relative infant dose is generally low, and clinical monitoring of breastfed infants is recommended to ensure their safety, especially since long-term effects are still unknown.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lacosamide use during breastfeeding: A case report and a literature review. Cercos, M., Seqat, I., Facile, A., et al.[2023]

Lacosamide (Vimpat) was approved in August 2008 by the European Commission and in October 2008 by the FDA as an adjunctive therapy for partial-onset seizures in epilepsy patients.

The approval indicates that lacosamide is considered a safe and effective option to help manage seizures when used alongside other treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lacosamide. Perucca, E., Yasothan, U., Clincke, G., et al.[2018]

In a study of 481 traumatic brain injury (TBI) patients, lacosamide and phenytoin were found to be equally effective in preventing early post-traumatic seizures, with seizure rates of 0.9% for phenytoin and 1.4% for lacosamide.

However, lacosamide demonstrated a significantly better safety profile, with only 0.5% of patients experiencing adverse drug effects (ADEs) compared to 5.2% in the phenytoin group, suggesting it may be a more tolerable option for seizure prophylaxis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lacosamide versus phenytoin for the prevention of early post traumatic seizures. Kwon, SJ., Barletta, JF., Hall, ST., et al.[2020]

Lacosamide is an effective adjunctive therapy for adults and adolescents (aged 16-18 years) with partial-onset seizures, significantly reducing seizure frequency compared to placebo in studies lasting up to 8 years.

Both oral and intravenous forms of lacosamide are generally well tolerated, with most side effects being mild to moderate, although intravenous use may cause local injection site reactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lacosamide: a review of its use as adjunctive therapy in the management of partial-onset seizures. Hoy, SM.[2021]

References

1. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[The efficacy of intravenous lacosamide in psychiatric hospital]. [2018]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Therapeutic monitoring of lacosamide, perampanel, and zonisamide during breastfeeding. [2023]

3. Germany pubmed.ncbi.nlm.nih.gov

[Lacosamide. A new antiepileptic drug as adjunctive therapy in patients with partial-onset seizures]. [2018]

4. England pubmed.ncbi.nlm.nih.gov

Lacosamide use during breastfeeding: A case report and a literature review. [2023]

5. England pubmed.ncbi.nlm.nih.gov

Lacosamide. [2018]

6. United States pubmed.ncbi.nlm.nih.gov

Lacosamide versus phenytoin for the prevention of early post traumatic seizures. [2020]

7. New Zealand pubmed.ncbi.nlm.nih.gov

Lacosamide: a review of its use as adjunctive therapy in the management of partial-onset seizures. [2021]