Extension Study to Evaluate How Safe and Tolerable NBI-921352 is as an Adjunctive Therapy for Participants With SCN8A-DEE

A Prospective, Long-Term, Interventional, Active Extension Study to Evaluate the Safety and Tolerability of NBI-921352 as Adjunctive Therapy in Subjects With SCN8A Developmental and Epileptic Encephalopathy Syndrome (SCN8A-DEE)

Extension study to evaluate how safe and tolerable the drug NBI-921352 is when used as adjunctive therapy in participants with SCN8A developmental and epileptic encephalopathy syndrome (SCN8A-DEE).

Study Overview

• Status: Enrolling by invitation
• Conditions: SCN8A Developmental and Epileptic Encephalopathy Syndrome
• Intervention / Treatment: Drug: NBI-921352

• Study Type: Interventional
• Enrollment (Estimated): 52
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • San Francisco, California, United States, 94143
      • UCSF Medical Center
  • District of Columbia
    • Washington, 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 and older (Child, Adult)
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

For Participants Who Participated in NBI-921352-DEE2012:

• Written or oral pediatric assent from the participant and written informed consent from the participant's parent(s) or legal guardian(s) for pediatric participants and adult participants who are not capable of providing consent. Adult participant who are ≥18 years of age and capable of providing consent should sign an Informed Consent Form (ICF).
• Completed 16 weeks of treatment in Study NBI-921352-DEE2012.
• Continue to use a nocturnal alerting system or practice consistent with standards of care for the duration of the study.
• Have an adequate rescue medication regimen per the investigator's judgment in place for the duration of the study.

For Participants Who did not Participate in NBI-921352-DEE2012:

• Written or oral pediatric assent from the participant if deemed capable of providing assent and written informed consent from the participant's parent(s) or legal guardian(s) for pediatric participants and for adult participants who are not capable of providing consent. Adult participants who are capable of providing consent should sign an ICF.
• Be a 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.
• Have a body weight of at least 10 kilograms.

Key Exclusion Criteria

For Participants Who Participated in NBI-921352-DEE2012:

- Have developed any other disorder for which the treatment takes priority over treatment of SCN8A-DEE or is likely to interfere with study treatment or impair treatment compliance.

For Participants Who did not Participate in NBI-921352-DEE2012:

• Have symptoms that would be more consistent with another epilepsy disorder such as Dravet syndrome (for example, fever-induced episodes of status epilepticus, frequent myoclonic seizures, worsening on sodium channel blockers, absence seizures with generalized spike-and-wave electroencephalogram [EEG] as the sole seizure type).
• Currently receiving cannabinoids or medical marijuana except Epidiolex/Epidyolex, unless approved by the Sponsor.
• Currently taking systemic steroids (excluding inhaled medication for asthma treatments and intranasal steroids for allergies) such as adrenocorticotropin hormone, high-dose prednisolone for epileptic spasms. If participant has received these medications in the past, they 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 non-epilepsy-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 participant 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 participants 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 milliseconds (msec) or presence of any significant cardiac abnormality.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: NBI-921352; 106 week treatment Period	Drug: NBI-921352; Administered orally

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The participant incidence of serious treatment-emergent adverse events (TEAEs), TEAEs leading to discontinuation of study treatment, and fatal TEAEs.	Day 1 to Week 106

Secondary Outcome Measures

Outcome Measure	Time Frame
Percentage change from baseline in 28-day seizure frequency for countable motor seizures during the Treatment Period of the study at (End of) Weeks 30, 54, 78, and 104.	(End of) Weeks 30, 54, 78, and 104

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): July 12, 2022
• Primary Completion (Estimated): March 1, 2026
• Study Completion (Estimated): May 1, 2026

Study Registration Dates

• First Submitted: January 26, 2022
• First Submitted That Met QC Criteria: January 26, 2022
• First Posted (Actual): February 7, 2022

Study Record Updates

• Last Update Posted (Actual): November 2, 2023
• Last Update Submitted That Met QC Criteria: October 31, 2023
• Last Verified: October 1, 2023

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: Pathologic Processes; Central Nervous System Diseases; Nervous System Diseases; Disease; Epilepsy; Syndrome; Brain Diseases
• Other Study ID Numbers: NBI-921352-DEE2013; 2021-004393-62 (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