Clinical trial NCT05159908: A Study to Investigate How Effective, Safe and Tolerable the Drug NBI-921352 is When Used With Anti-seizure Medications in Adults With Focal Onset Seizures
Official title: A Phase 2 Randomized, Double-Blind, Placebo-Controlled, Dose-Finding Study to Investigate Safety, Tolerability, Pharmacokinetics, and Efficacy of NBI-921352 as Adjunctive Therapy in Adult Subjects With Focal Onset Seizures (FOS)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Focal Onset Seizure
Focal Onset Epilepsy
Keywords: Epilepsy
focal seizure
sodium channel
voltage-gated
alpha subunit
Nav1.6 inhibitor
Antiseizure medication
ASM
Antiepileptic drug
AED
partial seizure
partial onset epilepsy
Lead sponsor: Neurocrine Biosciences
Sponsor class: INDUSTRY
First posted: 2021-12-16
Enrollment: 101
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study will evaluate the safety, pharmacokinetics, and efficacy of three different doses of NBI-921352 versus placebo in adults with focal onset seizures


Eligibility criteria: Key Inclusion Criteria:

1. Capable of providing consent and has completed the written informed consent.
2. Male or female, 18 to 65 years of age, inclusive, with a body mass index (BMI) \< 40 kg/m\^2.
3. Diagnosis of focal onset epilepsy according to the International League Against Epilepsy (ILAE) Classification of Epilepsy (2017) at least 18 months before screening.
4. History of uncontrolled seizures despite adequate treatment with at least 1 anti-seizure medication (ASM) for at least 18 months prior to screening.
5. Treatment with at least 1 but not more than 4 ASMs for at least 1 month before screening, during the baseline seizure diary data collection, and throughout the duration of the study.
6. Be able to keep accurate seizure diaries.
7. Documented seizure frequency in the baseline seizure diary of ≥8 countable focal seizures during the 8-week seizure baseline period.

Key Exclusion Criteria:

1. History of epilepsy with only nonmotor seizures without an observable component, psychogenic nonepileptic seizures, or primary generalized seizures.
2. Presence or previous history of developmental and/or epileptic encephalopathy.
3. Presence of seizure types other than FOS.
4. Status epilepticus within the last 12 months before enrollment.
5. Any suicidal behavior or suicidal ideation of type 4 (active suicidal ideation with some intent to act, without specific plan) or type 5 (active suicidal ideation with specific plan and intent) based on the C-SSRS in the 2 years before screening, a history of suicide attempt in the last 2 years, or more than 1 lifetime suicide attempt.
6. Multiple drug allergies or a severe drug reaction to an ASM(s), including dermatological (eg, Stevens-Johnson syndrome), hematological, or organ toxicity reactions.
7. An implanted responsive neurostimulator system (RNS).

Primary outcomes:
measure: Number of Participants with Serious Treatment-emergent Adverse Events (TEAEs), TEAEs Leading to Discontinuation of Study Treatment, and Fatal TEAEs
timeFrame: Through Week 15
measure: NBI-921352 exposure-efficacy response relationship, defined as the slope of the relationship between reduction in monthly focal onset seizure frequency and plasma concentration at steady state
timeFrame: Baseline to Week 11
Secondary outcomes:
measure: Percent Change from Baseline in Monthly Focal Onset Seizure Frequency During the Treatment Period
timeFrame: Baseline and Weeks 1 to 11
measure: Percent Change from Baseline in Monthly Focal Onset Seizure Frequency During the Maintenance period
timeFrame: Baseline and Weeks 4 to 11
measure: Clinical Global Impression of Change (CGIC) Scores at Week 11
timeFrame: Week 11
measure: Percentage of Participants with a ≥ 50% reduction in monthly (28 days) focal onset seizure frequency during the treatment period
timeFrame: Baseline and Weeks 1 to 11
Other outcomes:
Locations:
city: Randwick
country: Australia
facility: Neurocrine Clinical Site
state: New South Wales
city: Ivanhoe
country: Australia
facility: Neurocrine Clinical Site
state: Victoria
city: Melbourne
country: Australia
facility: Neurocrine Clinical Site
state: Victoria
city: Parkville
country: Australia
facility: Neurocrine Clinical Site
state: Victoria
city: Prahran
country: Australia
facility: Neurocrine Clinical Site
state: Victoria
city: Bruxelles
country: Belgium
facility: Neurocrine Clinical Site
city: Gent
country: Belgium
facility: Neurocrine Clinical Site
city: Leuven
country: Belgium
facility: Neurocrine Clinical Site
city: Brno
country: Czechia
facility: Neurocrine Clinical Site
city: Ostrava
country: Czechia
facility: Neurocrine Clinical Site
city: Praha 5
country: Czechia
facility: Neurocrine Clinical Site
city: Praha 6
country: Czechia
facility: Neurocrine Clinical Site
city: Praha 8
country: Czechia
facility: Neurocrine Clinical Site
city: Rychnov Nad Kněžnou
country: Czechia
facility: Neurocrine Clinical Site
city: Bron
country: France
facility: Neurocrine Clinical Site
city: Lille
country: France
facility: Neurocrine Clinical Site
city: Rennes
country: France
facility: Neurocrine Clinical Site
city: Toulouse
country: France
facility: Neurocrine Clinical Site
city: Budapest
country: Hungary
facility: Neurocrine Clinical Site
city: Debrecen
country: Hungary
facility: Neurocrine Clinical Site
city: Pécs
country: Hungary
facility: Neurocrine Clinical Site
city: Bologna
country: Italy
facility: Neurocrine Clinical Site
city: Milano
country: Italy
facility: Neurocrine Clinical Site
city: Pavia
country: Italy
facility: Neurocrine Clinical Site
city: Barcelona
country: Spain
facility: Neurocrine Clinical Site
city: Madrid
country: Spain
facility: Neurocrine Clinical Site
city: Madrid
country: Spain
facility: Neurocrine Clinical Site
city: Valencia
country: Spain
facility: Neurocrine Clinical Site
Study officials:
affiliation: Neurocrine Biosciences
name: Clinical Development Lead
role: STUDY_DIRECTOR
References: