Efficacy and Safety Study of Once-Daily Extended-Release Levetiracetam in Drug-resistant Focal Onset Seizures

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Neuraxpharm Pharmaceuticals S.L.

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Trial duration

12 Mar 2025 → ongoing

Decision date (initial)

2025-02-12

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Neuraxpharm Pharmaceuticals S.L.

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

The primary objective is to assess the reduction in weekly Focal Onset Seizures (FOS) frequency of levetiracetam extended release (XR) compared to levetiracetam immediate release (IR) in subjects with drug-resistant FOS.

Secondary objectives 3

1. The key secondary objective is to assess the reduction in weekly FOS frequency of levetiracetam XR compared to placebo in subjects with drug-resistant FOS.
2. To evaluate the efficacy of levetiracetam XR compared to placebo.
3. To explore the effect of levetiracetam XR compared to levetiracetam IR and placebo on health related quality of life (HRQoL).

Conditions and MedDRA coding

Refractory Partial Onset Epilepsy

Study design 4 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. Male and female, between 12 and 80 years of age, both inclusive for Spain, Poland and Bulgaria while the other countries will include only adult subjects.
2. Willingness and capability to provide informed consent form (ICF), be compliant with study procedures such as eDiary completion, be compliant with background anti-seizure medication (ASM) and Investigational Medicinal Product (IMP) intake.
3. Diagnosis of epilepsy with Focal-onset seizures (FOS) with or without secondary generalization according to the International League Against Epilepsy Classification of epileptic seizures.
4. On stable doses of ASM for at least 4 weeks prior to screening. List of allowed ASM medications are provided in Appendix 18.2.
5. Confirmed drug-resistant FOS despite 1-3 stable ASM with at least 6 seizures during the 8 week observational period
6. Patients who have Vagal Nerve Stimulator (VNS) must have stable settings > 3 months prior to screening and expected to remain unchanged during the duration of the study
7. Females of childbearing potential, if not abstinent, should use a highly effective contraception, started 60 days prior to study entry and 30 days after end of study drug administration: Combined (Estrogen and progesterone containing) hormonal contraception associated with inhibition of ovulation: -Oral -Intravaginal -Transdermal; Progesterone-only hormonal contraception associated with inhibition of ovulation -Oral -Injectable -Implantable; Intrauterine device; Intrauterine hormone-releasing system; Bilateral tubal occlusion; Vasectomized partner; Sexual abstinence. See Appendix 18.1 for additional details.
8. Females of non-childbearing potential: either surgically sterilized (e.g. bilateral tubal ligation), had undergone hysterectomy or is at least 1 year postmenopausal (amenorrhea duration of at least 12 months)
9. Sexually active males with partner of childbearing potential commit to use an acceptable method of birth control consistently and correctly (oral, transdermal, systemic or implant contraception birth control, intrauterine devices) for 90 days after the last study drug administration.

Exclusion criteria 20

1. Presence of primary generalized epilepsies or seizures, such as absences, myoclonic epilepsies, Lennox-Gastaut syndrome.
2. Alcohol abuse as per Diagnostic and Statistical Manual of Mental Disorders version 5 (DSM-V) in the past year.
3. Positive for hepatitis C virus (HCV) or hepatitis B surface antigen (HBsAg) or Human Immunodeficiency Virus (HIV) infection at screening.
4. Subjects presenting symptoms of coronavirus disease COVID-19.
5. Known allergic reaction or intolerance to levetiracetam or other pyrrolidone derivatives or to any of the excipients.
6. Participation in a study involving administration of an investigational product within one month prior to screening or within five half-lives of the previous study investigational compound, whichever is longer.
7. Women who are currently pregnant, who intend to become pregnant during the study, or who are breastfeeding.
8. Subjects with a diagnosis of Congenital Short QT Syndrome (SQTS). Subjects with a family history of Congenital Short QT Syndrome (SQTS) or family history of sudden death of unknown cause.
9. The corrected QT interval by Fredericia (QTcF) ≥ 450 msec in male and 470 msec in female subjects.
10. Laboratory values at screening: • Platelets < 100,000/mm3 • Absolute neutrophil count < 1500/mm3 • Haemoglobin < 10.0g/dL • Aspartate aminotransferase or alanine aminotransferase > 3x upper limit of normal • Estimated Glomerular Filtration Rate < 80
11. History of status epilepticus in the past 3 months prior to screening.
12. Seizure clusters where individual seizures cannot be counted.
13. History of non-epileptic seizures.
14. Evidence of clinically significant disease (cardiac, respiratory, gastrointestinal, hepatic, hematologic or renal disease, neoplastic malignancies etc.) that in the opinion of the investigator could affect the subject's safety or trial conduct.
15. Neurodegenerative and other progressive neurological disorders.
16. Diagnosis of active psychiatric disease, except depressed subjects on stable doses of selective serotonin reuptake inhibitors/serotonin and norepinephrine reuptake inhibitors for at least 12 weeks prior to screening.
17. History of prior suicide attempt or imminent risk of self-harm based on investigator’s judgment or with a “yes” answer on item 4 or 5 on the Columbia Suicide Severity Rating Scale (CSSR-S).
18. History of drug abuse as defined by Diagnostic and Statistical Manual of Mental Disorders version 5 (DSM-V) and/or positive drug screening other than prescribed drugs.
19. Body weight < 50kg.
20. Current use of levetiracetam.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Percent change from baseline* in FOS frequency per week over the 12 week double-blind period.

Secondary endpoints 7

1. Change from baseline* in absolute FOS over the 12 week double-blind period.
2. Proportion of subjects with at least 50% reduction from baseline* in total seizure frequency per week over the 12 week double-blind period.
3. Proportion of subjects with at least 50% reduction from baseline* in total seizures over the 12 week double-blind period.
4. Number of days free of FOS over the treatment period of 12 weeks.
5. Response in Weekly FOS Frequency (Categorized Into 6 Categories According to Reduction) Over the Treatment Period of 12 Weeks).
6. Change in the Quality of Life in Epilepsy (QoLIE-31) scale score (patients ≥18 years) and QoLIE- AD-48 (age <18 years) over the study period.
7. Improving medication compliance and patient satisfaction with the treatment over the study period.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Comparator 1

Placebo 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Neuraxpharm Pharmaceuticals S.L.

Sponsor organisation

Neuraxpharm Pharmaceuticals S.L.

Address

Avinguda De Barcelona 69

City

Sant Joan Despi

Postcode

08970

Country

Spain

Scientific contact point

Organisation

Neuraxpharm Pharmaceuticals S.L.

Contact name

Abdelkarim Bendarraz

Public contact point

Organisation

Neuraxpharm Pharmaceuticals S.L.

Contact name

Abdelkarim Bendarraz

Third parties 19

Locations

9 EU/EEA countries · 53 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 232 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

12 submissions — initial application plus substantial / non-substantial modifications