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

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)

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).

Study Overview

• Status: Terminated
• Conditions: SCN8A Developmental and Epileptic Encephalopathy Syndrome
• Intervention / Treatment: Drug: Placebo; Drug: NBI-921352

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • San Francisco, California, United States, 94158
      • UCSF Medical Center
  • District of Columbia
    • Washington D.C., District of Columbia, United States, 20010
      • Children's National Hospital
  • New York
    • Rochester, New York, United States, 14642
      • University of Rochester
  • Texas
    • Fort Worth, Texas, United States, 76104
      • Cook Children's Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 21 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Percentage Change From Baseline in 28-day Seizure Frequency for Countable Motor Seizures During the 16-week Treatment Period	Planned time frame: Baseline to Week 16

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With a Treatment Response	Treatment response was defined as a ≥50% decrease from baseline in 28-day seizure frequency for countable motor seizures during the treatment period of the study.	Planned time frame: Baseline to Week 16
Percentage Change From Baseline in 28-day Seizure Frequency for Countable Motor Seizures During the 10-week Maintenance Period		Planned time frame: Baseline, Week 6 to Week 16
Percentage of Participants With a ≥ 25%, ≥ 75%, or 100% Treatment Response During the 16-week Treatment Period	Treatment response was defined as a ≥25%, ≥50%, ≥75%, or 100% decrease from baseline in 28-day seizure frequency for countable motor seizures during the treatment period of the study.	Planned time frame: Baseline to Week 16
Percentage of Participants With a ≥25%, ≥50%, ≥75%, or 100% Treatment Response During the 10-week Maintenance Period	Treatment response was defined as a ≥25%, ≥50%, ≥75%, or 100% decrease from baseline in 28-day seizure frequency for countable motor seizures during the treatment period of the study.	Planned time frame: Baseline, Week 6 to Week 16
Clinical Global Impression of Change (CGIC) Score at Each Visit During the 16-week Treatment Period	The CGIC scale, which is based on a 7-point scale (range: 1=very much improved to 7=very much worse), was used to rate the overall global improvement since the initiation of study treatment dosing, as rated by the investigator (or qualified designee).	Planned time frame: Up to Week 16
Parent/Caregiver Global Impression of Change (GIC) Score at Each Visit During the 16-week Treatment Period	The GIC scale was used to assess the parent/caregiver's impression of change in the participant's overall condition since starting study treatment and was rated on a 7-point scale (1=very much improved to 7=very much worse).	Planned time frame: Up to Week 16
Change From Baseline in Clinical Global Impression of Severity (CGIS) Scores at Each Visit During the 16-week Treatment Period	The CGIS scale was used to assess overall severity on a 5-point scale (range: 1=normal, not at all ill to 5=among the most extremely ill).	Planned time frame: Baseline to Week 16
Change From Baseline in Parent/Caregiver Global Impression of Severity (GIS) Scores at Each Visit During the 16-week Treatment Period	The GIS scale was used to assess overall severity on a 5-point scale (range: 1=none to 5=very severe).	Planned time frame: Baseline through Week 16

Collaborators and Investigators

• Sponsor: Neurocrine Biosciences
• Investigators: Study Director: Clinical Development Lead, Neurocrine Biosciences

Publications and helpful links

Helpful Links

• Study Website - Kayak Study

Study record dates

Study Major Dates

• Study Start (Actual): January 31, 2022
• Primary Completion (Actual): March 17, 2023
• Study Completion (Actual): March 17, 2023

Study Registration Dates

• First Submitted: April 30, 2021
• First Submitted That Met QC Criteria: April 30, 2021
• First Posted (Actual): May 5, 2021

Study Record Updates

• Last Update Posted (Estimated): October 16, 2025
• Last Update Submitted That Met QC Criteria: September 30, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: Epilepsy; voltage-gated; Sodium channel; type VIII; alpha subunit (SCN8A); NaV1.6 inhibitor
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Epilepsy
• Other Study ID Numbers: NBI-921352-DEE2012; 2020-003140-83 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No