SCN8A Developmental and Epileptic Encephalopathy Syndrome
Conditions
Keywords
Epilepsy, Sodium channel, voltage-gated, type VIII, alpha subunit (SCN8A), NaV1.6 inhibitor
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).
Interventions
DRUGNBI-921352
Administered orally
DRUGPlacebo
Administered orally
Sponsors
Neurocrine Biosciences
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
2 Years to 21 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 | Planned time frame: Baseline to Week 16 | 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. |
| Percentage of Participants With a ≥25%, ≥50%, ≥75%, or 100% Treatment Response During the 10-week Maintenance Period | Planned time frame: Baseline, Week 6 to Week 16 | 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. |
| Percentage of Participants With a Treatment Response | Planned time frame: Baseline to Week 16 | 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. |
| Parent/Caregiver Global Impression of Change (GIC) Score at Each Visit During the 16-week Treatment Period | Planned time frame: Up to Week 16 | 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). |
| Change From Baseline in Clinical Global Impression of Severity (CGIS) Scores at Each Visit During the 16-week Treatment Period | Planned time frame: Baseline to Week 16 | 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). |
| Change From Baseline in Parent/Caregiver Global Impression of Severity (GIS) Scores at Each Visit During the 16-week Treatment Period | Planned time frame: Baseline through Week 16 | The GIS scale was used to assess overall severity on a 5-point scale (range: 1=none to 5=very severe). |
| Clinical Global Impression of Change (CGIC) Score at Each Visit During the 16-week Treatment Period | Planned time frame: Up to Week 16 | 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). |
Countries
United States
Participant flow
Recruitment details
Study was prematurely terminated due to sponsor decision. Due to the early termination, only 8 participants were enrolled and completed the study. As prespecified, analyses were pooled by treatment received (NBI-921352 or placebo), rather than specific dose level received.
Participants by arm
| Arm | Count |
|---|---|
| NBI-921352 Participants received oral doses of NBI-921352 3 times a day based on body weight. | 4 |
| Placebo Participants received oral doses of placebo matching NBI-921352 3 times a day. | 4 |
| Total | 8 |
Baseline characteristics
| Characteristic | Placebo | Total | NBI-921352 |
|---|---|---|---|
| Age, Continuous | 9.17 years STANDARD_DEVIATION 4.87 | 6.81 years STANDARD_DEVIATION 4.4 | 4.46 years STANDARD_DEVIATION 2.6 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 1 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 4 Participants | 7 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 4 Participants | 8 Participants | 4 Participants |
| Sex: Female, Male Female | 2 Participants | 4 Participants | 2 Participants |
| Sex: Female, Male Male | 2 Participants | 4 Participants | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 4 | 0 / 4 |
| other Total, other adverse events | 4 / 4 | 4 / 4 |
| serious Total, serious adverse events | 2 / 4 | 1 / 4 |
Outcome results
Primary
Percentage Change From Baseline in 28-day Seizure Frequency for Countable Motor Seizures During the 16-week Treatment Period
Time frame: Planned time frame: Baseline to Week 16
Population: Due to early study termination, analyses of efficacy data were not performed due to an insufficient sample size to allow for meaningful statistical analysis of the data, as pre-specified in the protocol.
Secondary
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).
Time frame: Planned time frame: Baseline to Week 16
Population: Due to early study termination, analyses of efficacy data were not performed due to an insufficient sample size to allow for meaningful statistical analysis of the data, as pre-specified in the protocol.
Secondary
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).
Time frame: Planned time frame: Baseline through Week 16
Population: Due to early study termination, analyses of efficacy data were not performed due to an insufficient sample size to allow for meaningful statistical analysis of the data, as pre-specified in the protocol.
Secondary
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).
Time frame: Planned time frame: Up to Week 16
Population: Due to early study termination, analyses of efficacy data were not performed due to an insufficient sample size to allow for meaningful statistical analysis of the data, as pre-specified in the protocol.
Secondary
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).
Time frame: Planned time frame: Up to Week 16
Population: Due to early study termination, analyses of efficacy data were not performed due to an insufficient sample size to allow for meaningful statistical analysis of the data, as pre-specified in the protocol.
Secondary
Percentage Change From Baseline in 28-day Seizure Frequency for Countable Motor Seizures During the 10-week Maintenance Period
Time frame: Planned time frame: Baseline, Week 6 to Week 16
Population: Due to early study termination, analyses of efficacy data were not performed due to an insufficient sample size to allow for meaningful statistical analysis of the data, as pre-specified in the protocol.
Secondary
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.
Time frame: Planned time frame: Baseline, Week 6 to Week 16
Population: Due to early study termination, analyses of efficacy data were not performed due to an insufficient sample size to allow for meaningful statistical analysis of the data, as pre-specified in the protocol.
Secondary
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.
Time frame: Planned time frame: Baseline to Week 16
Population: Due to early study termination, analyses of efficacy data were not performed due to an insufficient sample size to allow for meaningful statistical analysis of the data, as pre-specified in the protocol.
Secondary
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.
Time frame: Planned time frame: Baseline to Week 16
Population: Due to early study termination, analyses of efficacy data were not performed due to an insufficient sample size to allow for meaningful statistical analysis of the data, as pre-specified in the protocol.