A long-term study to assess the safety and tolerability of NBI-827104 in children with encephalopathic epilepsy with continuous Spike-Wave discharges during sleep

Zusammenfassung der Studie

The study is designed to assess the efficacy, safety, and tolerability of the active ingredient NBI-827104 against placebo in approximately 24 pediatric participants aged 4 to (inclusive) 12 years with epileptic encephalopathy with continuous Spike-Wave discharges during sleep (EECSWS). Participants who completed treatment in the previously positively evaluated study NBI-827104-CSWS2010 will have the opportunity to participate in this study. The study medication will be administered according to dosing and intake instructions that each participant will receive. The expected study duration for each participant is 110 weeks for participants transitioning directly into this study and 114 weeks for participants not transitioning directly into this study. The study duration includes: -Screening: up to 4 weeks (for participants not transitioning directly into this study) -Treatment: 104 weeks, including a 3-week titration phase and a 101-week treatment phase Withdrawal phase: up to 2 weeks -Safety period after treatment: 4 weeks The end of the safety period after treatment marks the end of the study.

(BASEC)

Untersuchte Intervention

Approximately 24 male and female pediatric participants aged 4 to (inclusive) 12 years with CSWS may be included in the study, who have completed the positively evaluated study NBI-827104-CSWS2010. The study medication will be available in the form of 2 mg mini-tablets to be taken in the morning. The initial dose of the active ingredient is based on weight classes defined in the clinical study protocol.

The long-term safety and tolerability of the active ingredient will be assessed using video-EEG and through the participants' seizure diaries as well as through questionnaires and checklists filled out independently by the participants.

Safety and tolerability of the active ingredient will be monitored throughout the study, including the assessment of adverse events, clinical laboratory parameters, measurement of vital signs, physical and neurological examinations, ECGs, and ophthalmological examinations.

(BASEC)

Untersuchte Krankheit(en)

Epilepsy with continuous Spike-Wave discharges during sleep is a very rare neurological disorder, a form of epilepsy that affects the brain, where brain activity becomes abnormal, leading to seizures or periods of unusual behavior, sometimes accompanied by loss of consciousness. It is not an independent epileptic syndrome but is often associated with extensive brain function impairment and various forms of epilepsy and neurodevelopmental issues. It is an epileptic syndrome that occurs in childhood and significantly impairs cognitive function in preschool-aged children. This type of epilepsy affects children between 2 and 12 years old (on average between 4-5 years old). Epileptic encephalopathy with continuous Spike-Wave discharges during sleep (EECSWS) is a spectrum of disorders that includes seizures, increased brain activity during sleep, and mental disorders (neurocognitive regression/stagnation). Epileptic seizures, various levels of extensive brain dysfunction, and bioelectrical status epilepticus during sleep (ESES) are the main manifestations of epilepsy with continuous Spike-Wave discharges during sleep (CSWS). The incidence of CSWS is 0.2% to 0.5% of childhood epilepsies. Although spontaneous improvement is observed before puberty in EECSWS, neurocognitive regression may persist. Increased brain activity during sleep can interfere with normal restorative functions during sleep, negatively impacting learning ability, language, memory, and other cognitive areas. The cause of CSWS is often a brain malformation (when an area of the brain is formed differently at birth), genetic variation, or metabolic disorders. For the routine treatment of this condition, the following medications are used: benzodiazepines, valproate, corticosteroids, and immunoglobulins. During the study, participants will continue to take their standard treatment as prescribed and, upon inclusion in the study, will receive the study treatment or placebo in addition to their previous treatment.

(BASEC)

Sponsor

Neurocrine Biosciences, Inc. Biotec Regulatory Consulting GmbH

(BASEC)

Name der bewilligenden Ethikkommission (bei multizentrischen Studien nur die Leitkommission)

Ethikkommission Nordwest- und Zentralschweiz EKNZ

(BASEC)

Datum der Bewilligung durch die Ethikkommission

06.04.2022

(BASEC)

Ergebnisse der Studie