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

NCT05159908 | Completed Phase 2 DMC

• 2 other identifiers: NBI-921352-FOS20212021-001433-39
• Study Type: interventional
• Target: 101
• Locations: 7 countries
• Sites: 28

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

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

Outcome Measures

Primary Outcomes (2)

• Number of Participants with Serious Treatment-emergent Adverse Events (TEAEs), TEAEs Leading to Discontinuation of Study Treatment, and Fatal TEAEs

  Through Week 15

• 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

  Baseline to Week 11

Secondary Outcomes (4)

• Percent Change from Baseline in Monthly Focal Onset Seizure Frequency During the Treatment Period

  Baseline and Weeks 1 to 11

• Percent Change from Baseline in Monthly Focal Onset Seizure Frequency During the Maintenance period

  Baseline and Weeks 4 to 11

• Clinical Global Impression of Change (CGIC) Scores at Week 11

  Week 11

• Percentage of Participants with a ≥ 50% reduction in monthly (28 days) focal onset seizure frequency during the treatment period

  Baseline and Weeks 1 to 11

Study Arms (4)

Placebo schedule

PLACEBO COMPARATOR

Participant follows Placebo schedule (13 weeks)

Drug: Placebo

Dose schedule A

EXPERIMENTAL

Participant follows Dose schedule A (13 weeks)

Drug: NBI-921352

Dose schedule B

EXPERIMENTAL

Participant follows Dose schedule B (13 weeks)

Drug: NBI-921352

Dose schedule C

EXPERIMENTAL

Participant follows Dose schedule C (13 weeks)

Drug: NBI-921352

Interventions

NBI-921352 DRUG

Tablets for oral administration

Dose schedule A; Dose schedule B; Dose schedule C

Placebo DRUG

Matching placebo tablets for oral administration

Placebo schedule

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Capable of providing consent and has completed the written informed consent.
• Male or female, 18 to 65 years of age, inclusive, with a body mass index (BMI) \< 40 kg/m\^2.
• Diagnosis of focal onset epilepsy according to the International League Against Epilepsy (ILAE) Classification of Epilepsy (2017) at least 18 months before screening.
• History of uncontrolled seizures despite adequate treatment with at least 1 anti-seizure medication (ASM) for at least 18 months prior to screening.
• 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.
• Be able to keep accurate seizure diaries.
• Documented seizure frequency in the baseline seizure diary of ≥8 countable focal seizures during the 8-week seizure baseline period.

You may not qualify if:

• History of epilepsy with only nonmotor seizures without an observable component, psychogenic nonepileptic seizures, or primary generalized seizures.
• Presence or previous history of developmental and/or epileptic encephalopathy.
• Presence of seizure types other than FOS.
• Status epilepticus within the last 12 months before enrollment.
• 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.
• Multiple drug allergies or a severe drug reaction to an ASM(s), including dermatological (eg, Stevens-Johnson syndrome), hematological, or organ toxicity reactions.
• An implanted responsive neurostimulator system (RNS).

Sponsors & Collaborators

• Neurocrine Biosciences: lead

Study Sites (28)

Neurocrine Clinical Site

Randwick, New South Wales, 2031, Australia

Location

Neurocrine Clinical Site

Ivanhoe, Victoria, 3079, Australia

Location

Neurocrine Clinical Site

Melbourne, Victoria, 3065, Australia

Location

Neurocrine Clinical Site

Parkville, Victoria, 3050, Australia

Location

Neurocrine Clinical Site

Prahran, Victoria, 3181, Australia

Location

Neurocrine Clinical Site

Brussels, 1070, Belgium

Location

Neurocrine Clinical Site

Ghent, 9000, Belgium

Location

Neurocrine Clinical Site

Leuven, 3000, Belgium

Location

Neurocrine Clinical Site

Brno, 656 91, Czechia

Location

Neurocrine Clinical Site

Ostrava, 708 52, Czechia

Location

Neurocrine Clinical Site

Prague, 150 06, Czechia

Location

Neurocrine Clinical Site

Prague, 160 00, Czechia

Location

Neurocrine Clinical Site

Prague, 186 00, Czechia

Location

Neurocrine Clinical Site

Rychnov nad Kněžnou, 516 01, Czechia

Location

Neurocrine Clinical Site

Bron, 69677, France

Location

Neurocrine Clinical Site

Lille, 59037, France

Location

Neurocrine Clinical Site

Rennes, 35033, France

Location

Neurocrine Clinical Site

Toulouse, 31059, France

Location

Neurocrine Clinical Site

Budapest, 1145, Hungary

Location

Neurocrine Clinical Site

Debrecen, 4032, Hungary

Location

Neurocrine Clinical Site

Pécs, 7623, Hungary

Location

Neurocrine Clinical Site

Bologna, 40139, Italy

Location

Neurocrine Clinical Site

Milan, 20133, Italy

Location

Neurocrine Clinical Site

Pavia, 27100, Italy

Location

Neurocrine Clinical Site

Barcelona, 08035, Spain

Location

Neurocrine Clinical Site

Madrid, 28034, Spain

Location

Neurocrine Clinical Site

Madrid, 28040, Spain

Location

Neurocrine Clinical Site

Valencia, 46026, Spain

Location

MeSH Terms

Conditions

Seizures; Epilepsy

Condition Hierarchy (Ancestors)

Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Brain Diseases; Central Nervous System Diseases

Study Officials

• Clinical Development Lead

  Neurocrine Biosciences

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 30, 2021
• First Posted: December 16, 2021
• Study Start: November 8, 2021
• Primary Completion: August 21, 2023
• Study Completion: August 21, 2023
• Last Updated: September 26, 2024

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will not share

Locations

FR (4); BE (3); HU (3); ES (4); CZ (6); AU (5); IT (3)