Study to Evaluate NBI-921352 as Adjunctive Therapy in Subjects With SCN8A Developmental and Epileptic Encephalopathy Syndrome (SCN8A-DEE)

Sponsor

Neurocrine Biosciences (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04873869

Collaborator

(none)

Enrollment

Locations

Arms

Anticipated Duration (Months)

6.5

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
SCN8A Developmental and Epileptic Encephalopathy Syndrome	Drug: NBI-921352 Drug: Placebo	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

52 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Care Provider, Investigator)

Primary Purpose:

Treatment

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)

Actual Study Start Date :

Jan 31, 2022

Anticipated Primary Completion Date :

Jan 1, 2024

Anticipated Study Completion Date :

Feb 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo Participants will receive matching placebo for up to 18 weeks.	Drug: Placebo Administered orally
Experimental: NBI-921352 In the first 6 weeks participants will receive increasing doses of NBI-921352 (Titration Period) based on weight, followed by 10 weeks of treatment at their final tolerated dose (Maintenance Period) and 2 weeks of treatment with decreasing doses (Taper Period).	Drug: NBI-921352 Administered orally

Arm

Intervention/Treatment

Placebo Comparator: Placebo

Participants will receive matching placebo for up to 18 weeks.

Drug: Placebo

Administered orally

Experimental: NBI-921352

In the first 6 weeks participants will receive increasing doses of NBI-921352 (Titration Period) based on weight, followed by 10 weeks of treatment at their final tolerated dose (Maintenance Period) and 2 weeks of treatment with decreasing doses (Taper Period).

Drug: NBI-921352

Administered orally

Outcome Measures

Primary Outcome Measures

Percentage Change from Baseline in 28-day Seizure Frequency for Countable Motor Seizures During the Treatment Period [Baseline, Treatment Period: Day 1 to Week 16]

Secondary Outcome Measures

Percentage of Participants with a ≥ 50% Treatment Response for Countable Motor Seizures During the Treatment Period [Baseline, Treatment Period: Day 1 to Week 16]
Percentage Change from Baseline in 28-day Seizure Frequency for Countable Motor Seizures During the Maintenance Period [Baseline, Maintenance Period: Week 6 to Week 16]
Percentage of Participants with a ≥ 25%, ≥ 75%, or 100% Treatment Response During the Treatment Period [Baseline, Treatment Period: Day 1 to Week 16]
Percentage of Participants with a ≥ 25%, ≥ 50%, ≥ 75%, or 100% Treatment Response During the Maintenance Period [Baseline, Maintenance Period: Week 6 to Week 16]
Clinical Global Impression of Change (CGIC) [Treatment Period: Up to Week 16]
Parent/Caregiver Global Impression of Change (GIC) [Treatment Period: Up to Week 16]
Change from Baseline in Clinical Global Impression of Severity (CGIS) [Baseline, Treatment Period: Up to Week 16]
Change from Baseline in Parent/Caregiver Global Impression of Severity (GIS) [Baseline, Treatment Period: Up to Week 16]

Eligibility Criteria

Criteria

Ages Eligible for Study:

2 Years to 21 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Male or female 2 to 21 years of age, inclusive.
Have a diagnosis of SCN8A-DEE supported by both clinical and genetic findings
Have on average at least 1 countable motor seizure per week and not be seizure-free for more than 20 consecutive days
Being treated with at least 1 other antiseizure medication (ASM), but no more than 4 ASMs
Have failed to achieve seizure freedom with at least 2 ASMs
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
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
Have a body weight of at least 10 kg
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:

Have previously been enrolled in this study and received blinded treatment
Have participated in an interventional clinical trial < 30 days prior to screening
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)
Are currently receiving cannabinoids or medical marijuana except Epidiolex/Epidyolex, unless approved by the Sponsor
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
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
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
Have clinically significant abnormal vital signs at the screening visit as determined by the investigator
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
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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	UCSF Medical Center	San Francisco	California	United States	94158
2	Children's National Hospital	Washington	District of Columbia	United States	20010
3	Ann & Robert H. Lurie Children's Hospital of Chicago	Chicago	Illinois	United States	60611
4	University of Rochester	Rochester	New York	United States	14642
5	Wake Forest Baptist Health	Winston-Salem	North Carolina	United States	27157
6	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania	United States	19104
7	Cook Children's Medical Center	Fort Worth	Texas	United States	76104
8	University of Utah	Salt Lake City	Utah	United States	84132