Lacosamide for Neonatal Seizures

(LENS Trial)

No longer recruiting at 18 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called lacosamide to determine if it can better control seizures in newborns whose seizures aren't well-managed by other medications. The study compares lacosamide to a standard treatment to identify which is more effective in reducing severe and non-severe seizures. Babies who have already tried other anti-seizure drugs like phenobarbital, levetiracetam, or midazolam, but still experience seizures lasting at least two minutes, might be suitable for this trial. As a Phase 2 trial, this research measures how well lacosamide works in an initial, smaller group of newborns.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that lacosamide is approved for treating certain types of seizures in adults and older children, indicating extensive study in these groups. However, less information exists about its use in newborns. Some studies have explored lacosamide for newborns with difficult-to-treat seizures, but safety data for this age group remains limited.

This trial is in a middle stage, meaning initial safety tests in humans have been completed, but more information is needed to fully understand its safety in newborns. Lacosamide appears well-tolerated in other age groups, but researchers continue to investigate its use in infants to ensure the benefits outweigh any potential risks. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for seizures?

Unlike the standard treatment options for neonatal seizures, which often include medications like phenobarbital and phenytoin, lacosamide offers a different approach. Lacosamide is unique because it works by enhancing the slow inactivation of sodium channels in the brain, potentially providing more targeted seizure control. Researchers are excited about lacosamide because it can be administered intravenously initially and then transitioned to an oral form, which may offer more flexibility and convenience in managing seizures in newborns. This dual delivery system could mean faster stabilization and easier long-term management compared to current options.

What evidence suggests that this trial's treatments could be effective for neonatal seizures?

Research has shown that lacosamide, which participants in this trial may receive, can effectively treat seizures. It works well as an additional therapy for seizures that are difficult to manage in both adults and newborns. One study at a medical center found it safe and effective for newborns with challenging seizures, including some born prematurely. This suggests that lacosamide could help reduce seizures in newborns who haven't responded well to other treatments. Meanwhile, another group in this trial will receive an active comparator based on the standard of care. ^{2 6 7 8 9}

Who Is on the Research Team?

UCB Cares

Principal Investigator

001 844 599 2273

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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]

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]

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]

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 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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6493858/

Lacosamide and Epilepsy - PMC Findings suggest that lacosamide is an effective agent for adjunctive treatment of refractory partial‐onset seizures.

2. journals.sagepub.com journals.sagepub.com/doi/abs/10.1345/aph.1M303

Lacosamide: An Adjunctive Agent for Partial-Onset ... To review the pharmacology, pharmacokinetics, efficacy, and safety of lacosamide, a new agent for use as adjunctive treatment in partial-onset ...

3. aesnet.org aesnet.org/abstractslisting/neonatal-seizures-safety-and-efficacy-of-lacosamide-therapy-a-single-center-retrospective-study

neonatal seizures: safety and efficacy of lacosamide therapy Lacosamide was a safe and effective adjunctive therapy for neonatal seizures in our experience (including several premature neonates) with refractory acute ...

4. cdn.clinicaltrials.gov cdn.clinicaltrials.gov/large-docs/45/NCT04519645/Prot_000.pdf

PUBLIC COPY This document cannot be used to support any ... Study of lacosamide in neonatal seizures ... outcome ... blockers in neonatal seizures, LCM will potentially be effective in reducing seizure burden in.

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/36972493/

Tolerability and Safety of Lacosamide in Neonatal Population Lacosamide is a newer antiepileptic medication used in refractory neonatal seizures with limited safety and efficacy data.

6. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2023/216185s000lbl.pdf

Motpoly™ XR - accessdata.fda.gov Use of MOTPOLY XR in this pediatric group is supported by evidence from adequate and well-controlled studies of lacosamide in adults with partial-onset seizures ...

7. en.wikipedia.org en.wikipedia.org/wiki/Lacosamide

Lacosamide Lacosamide, sold under the brand name Vimpat among others, is a medication used for the treatment of partial-onset seizures and primary generalized tonic-clonic ...

8. publications.aap.org publications.aap.org/pediatriccare/drug-monograph/18/5889/Lacosamide

Lacosamide | Drug Lookup | Pediatric Care Online Seizures, refractory: Limited data available: Infants ≥6 months, Children ... Lacosamide cardiac safety: clinical trials in patients with partial-onset seizures.

9. pubchem.ncbi.nlm.nih.gov pubchem.ncbi.nlm.nih.gov/compound/Lacosamide

Lacosamide | C13H18N2O3 | CID 219078 - PubChem - NIH Lacosamide is an antiepileptic drug used to treat seizures. As a chiral functionalized amino acid, it works by blocking slowly inactivating components of ...