Clinical trial NCT04873869: Study to Evaluate NBI-921352 as Adjunctive Therapy in Subjects With SCN8A Developmental and Epileptic Encephalopathy Syndrome (SCN8A-DEE)
Official title: A Phase 2 Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy, Safety, Tolerability, and Pharmacokinetics of NBI-921352 as Adjunctive Therapy in Subjects With SCN8A Developmental and Epileptic Encephalopathy Syndrome (SCN8A-DEE)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: SCN8A Developmental and Epileptic Encephalopathy Syndrome
Keywords: Epilepsy
Sodium channel
voltage-gated
type VIII
alpha subunit (SCN8A)
NaV1.6 inhibitor
Lead sponsor: Neurocrine Biosciences
Sponsor class: INDUSTRY
First posted: 2021-05-05
Enrollment: 52
Sex: ALL
Minimum age (years): 2
Maximum age (years): 21
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The objective of this study is to assess the efficacy, safety, and pharmacokinetics of NBI-921352 as adjunctive therapy for seizures in subjects with SCN8A Developmental and Epileptic Encephalopathy Syndrome (SCN8A-DEE).


Eligibility criteria: Inclusion Criteria:

1. Male or female 2 to 21 years of age, inclusive.
2. Have a diagnosis of SCN8A-DEE supported by both clinical and genetic findings
3. Have on average at least 1 countable motor seizure per week and not be seizure-free for more than 20 consecutive days
4. Being treated with at least 1 other antiseizure medication (ASM), but no more than 4 ASMs
5. Have failed to achieve seizure freedom with at least 2 ASMs
6. Must be using a nocturnal alerting system or practice consistent with standards of care at the time of screening and continue to use this for the duration of the study
7. Must have an adequate rescue medication regimen per the investigator's judgment in place at the time of screening and for the duration of the study
8. Have a body weight of at least 10 kg
9. The subject's parent/caregiver is able to accurately identify seizure types, especially countable motor seizures (defined as GTCS, tonic, atonic or FOS with noticeable motor component) and is able to complete seizure diary

Exclusion Criteria:

1. Have previously been enrolled in this study and received blinded treatment
2. Have participated in an interventional clinical trial \< 30 days prior to screening
3. Have symptoms that would be more consistent with another epilepsy disorder such as Dravet syndrome (eg, fever-induced episodes of status epilepticus, frequent myoclonic seizures, worsening on sodium channel blockers, absence seizures with generalized spike-and-wave EEG as the sole seizure type)
4. Are currently receiving cannabinoids or medical marijuana except Epidiolex/Epidyolex, unless approved by the Sponsor
5. Are currently taking systemic steroids (excluding inhaled medication for asthma treatments and intranasal steroids for allergies). If subject has received these medications in the past, must be off these medications for at least 3 months prior to the screening visit and these drugs may not be initiated during the duration of the study. Intermittent steroids to treat nonepilepsy related diseases (such as allergies or dermatological conditions) are not exclusionary
6. Have a history of moderate or severe head trauma or other neurological disorders or systemic medical diseases that are, in the investigator's opinion, likely to affect nervous system functioning
7. Have a clinically significant medical condition or chronic disease, that in the opinion of the investigator would preclude the subject from participating in and completing the study or that could confound interpretation of study outcome
8. Have clinically significant abnormal vital signs at the screening visit as determined by the investigator
9. Have one or more clinical laboratory test values outside the reference range, based on blood samples taken at the screening visit, that are of potential risk to the subject's safety as determined by the investigator
10. Have, at the screening visit, an electrocardiogram (ECG) finding of a corrected QT interval using Fridericia's formula (QTcF) \> 450 msec or presence of any significant cardiac abnormality.

Primary outcomes:
measure: Percentage Change from Baseline in 28-day Seizure Frequency for Countable Motor Seizures During the Treatment Period
timeFrame: Baseline, Treatment Period: Day 1 to Week 16
Secondary outcomes:
measure: Percentage of Participants with a ≥ 50% Treatment Response for Countable Motor Seizures During the Treatment Period
timeFrame: Baseline, Treatment Period: Day 1 to Week 16
measure: Percentage Change from Baseline in 28-day Seizure Frequency for Countable Motor Seizures During the Maintenance Period
timeFrame: Baseline, Maintenance Period: Week 6 to Week 16
measure: Percentage of Participants with a ≥ 25%, ≥ 75%, or 100% Treatment Response During the Treatment Period
timeFrame: Baseline, Treatment Period: Day 1 to Week 16
measure: Percentage of Participants with a ≥ 25%, ≥ 50%, ≥ 75%, or 100% Treatment Response During the Maintenance Period
timeFrame: Baseline, Maintenance Period: Week 6 to Week 16
measure: Clinical Global Impression of Change (CGIC)
timeFrame: Treatment Period: Up to Week 16
measure: Parent/Caregiver Global Impression of Change (GIC)
timeFrame: Treatment Period: Up to Week 16
measure: Change from Baseline in Clinical Global Impression of Severity (CGIS)
timeFrame: Baseline, Treatment Period: Up to Week 16
measure: Change from Baseline in Parent/Caregiver Global Impression of Severity (GIS)
timeFrame: Baseline, Treatment Period: Up to Week 16
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: UCSF Medical Center
state: California
city: Washington
country: United States
facility: Children's National Hospital
state: District of Columbia
city: Chicago
country: United States
facility: Ann & Robert H. Lurie Children's Hospital of Chicago
state: Illinois
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Rochester
country: United States
facility: University of Rochester
state: New York
city: Winston-Salem
country: United States
facility: Wake Forest Baptist Health
state: North Carolina
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Fort Worth
country: United States
facility: Cook Children's Medical Center
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
Study officials:
affiliation: Neurocrine Biosciences
name: Clinical Development Lead
role: STUDY_DIRECTOR
References: