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
Summary description of the study
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)
Intervention under investigation
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)
Disease under investigation
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)
1. Written or oral pediatric consent from the participant, if able to provide consent, and written consent from parents or a parent or legal representatives. 2. Completed 12-week treatment (3 weeks titration and 9 weeks of stable dose) in the study NBI-827104-CSWS2010. 3. Participants of childbearing potential must use highly effective contraceptive methods during the duration of study participation up to 90 days after the last dose of the study medication. (BASEC)
Exclusion criteria
1. Pregnant or breastfeeding 2. Use of another investigational product other than NBI-827104 in a clinical study within 30 days or 5 half-lives (whichever is longer) prior to Day 1 or planned use of an investigational product (other than NBI-827104) during the study. 3. Anticipated need for a prohibited or excluded medication within the study. (BASEC)
Trial sites
Basel, Zurich
(BASEC)
Sponsor
Neurocrine Biosciences, Inc. Biotec Regulatory Consulting GmbH
(BASEC)
Contact
Contact Person Switzerland
Cornelia Ulm
+41415448209
ulmrc@clutterhotmail.comBiotec Regulatory Consulting GmbH
(BASEC)
General Information
Accelsiors CRO and Consultancy Services Ltd.
+361299 0091
regulatory@accelsiors.com(ICTRP)
Scientific Information
Accelsiors CRO and Consultancy Services Ltd.
+361299 0091
regulatory@accelsiors.com(ICTRP)
Name of the authorising ethics committee (for multicentre studies, only the lead committee)
Ethics Committee northwest/central Switzerland EKNZ
(BASEC)
Date of authorisation
06.04.2022
(BASEC)
ICTRP Trial ID
EUCTR2021-006788-11 (ICTRP)
Official title (approved by ethics committee)
Long-Term, Open-Label Extension Study to Evaluate the Safety and Tolerability of NBI-827104 in Pediatric Subjects with Epileptic Encephalopathy with Continuous Spike-and-Wave During Sleep (BASEC)
Academic title
Long-Term, Open-Label Extension Study to Evaluate the Safety and Tolerability of NBI-827104 in Pediatric Subjects with Epileptic Encephalopathy with Continuous Spike-and-Wave During Sleep - NBI-827104-CSWS2025 (ICTRP)
Public title
A long-duration study to assess the safety and effectiveness of NBI-827104 in children with Epileptic Encephalopathy with Continuous Spike-and-Wave During Sleep. (ICTRP)
Disease under investigation
Epileptic Encephalopathy with Continuous Spike-and-Wave During Sleep (EECSWS)
MedDRA version: 20.0Level: PTClassification code 10077380Term: Epileptic encephalopathySystem Organ Class: 10029205 - Nervous system disorders;Therapeutic area: Diseases [C] - Nervous System Diseases [C10] (ICTRP)
Intervention under investigation
Product Name: NBI-827104
Product Code: NBI-827104
Pharmaceutical Form: Tablet
INN or Proposed INN: n/a
CAS Number: 1838651-58-3
Current Sponsor code: NBI-827104
Other descriptive name: N-[1-((5-cyanopyridin-2-yl)methyl)-1H-pyrazol-3-yl]-2-[4-(1-(trifluoromethyl)cyclopropyl)phenyl]acetamide
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 2-
(ICTRP)
Type of trial
Interventional clinical trial of medicinal product (ICTRP)
Trial design
Controlled: no Randomised: Open: Single blind: Double blind: Parallel group: Cross over: Other: If controlled, specify comparator, Other Medicinial Product: Placebo: Other: (ICTRP)
Inclusion/Exclusion criteria
Gender:
Female: yes
Male: yes
Inclusion criteria:
1. Completed 12 weeks of treatment in Study NBI-827104-CSWS2010.
2. For subjects who did not participate in Study NBI-827104-CSWS2010, they must have a diagnosis of EECSWS including confirmation by the Diagnosis Confirmation Panel.
Are the trial subjects under 18? yes
Number of subjects for this age range: 24
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range
(ICTRP)
Exclusion criteria:
1. Planned surgical intervention related to structural abnormalities of the brain from screening through the Week 6 Visit.
2. Used any active investigational drug other than NBI-827104 in the context of a clinical study within 30 days or 5 half-lives (whichever is longer) before Day 1 or plans to use such an investigational drug (other than NBI-827104) during the study.
3. Have developed any other disorder for which the treatment takes priority over treatment of EECSWS or is likely to interfere with study treatment or impair treatment compliance.
4. For subjects who did not participate in NBI-827104-CSWS2010, they must meet the above exclusion criteria in addition to the following (4-6): presence of relevant neurological disorders other than EECSWS and its underlying conditions as judged by the investigator. Symptomatic conditions underlying EECSWS (eg, neonatal strokes) have to be stable for at least 1 year prior to screening.
5. Body weight = 15 kg at Day 1
6. Clinically relevant findings related to cardiovascular or laboratory parameters at screening as determined by the investigator.
Primary and secondary end points
Main Objective: To evaluate the long-term safety and tolerability of NBI-827104 in pediatric subjects with epileptic encephalopathy with continuous spike-and-wave during sleep (EECSWS);Secondary Objective: Not applicable;Primary end point(s): The occurrence of serious Treatment-emergent adverse event (TEAEs);Timepoint(s) of evaluation of this end point: Up to 242 weeks. (ICTRP)
Secondary end point(s): Not applicable;Timepoint(s) of evaluation of this end point: Not applicable (ICTRP)
Registration date
11.02.2022 (ICTRP)
Incorporation of the first participant
25.03.2022 (ICTRP)
Secondary sponsors
not available
Additional contacts
Regulatory Unit, regulatory@accelsiors.com, +361299 0091, Accelsiors CRO and Consultancy Services Ltd. (ICTRP)
Secondary trial IDs
NBI-827104-CSWS2025, NCT05301894 (ICTRP)
Results-Individual Participant Data (IPD)
not available
Further information on the trial
https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2021-006788-11 (ICTRP)
Results of the trial
Results summary
not available
Link to the results in the primary register
not available