Main objective: To assess the efficacy of NBI-921352 as adjunctive therapy on the frequency of countable motor seizuresSecondary Objectives • To evaluate the efficacy of NBI-921352 using the Clinical and Parent/Caregiver Global Impression of Change…
ID
Source
Brief title
Condition
- Encephalopathies
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Percentage change from baseline in 28-day seizure frequency for countable motor
seizures during the treatment period of the study.
Secondary outcome
• Treatment response of >= 50% decrease for countable motor seizures
• Treatment response of >= 25%, >= 75%, or 100% decrease in countable motor
seizures
• Clinical Global Impression of Change (CGIC) at each study visit
• Parent/Caregiver Global Impression of Change (GIC) at each study visit
• Change from Baseline in Clinical Global Impression of Severity (CGIS)
• Change from Baseline in Parent/Caregiver Global Impression of Severity (GIS)"
Other secondary endpoints (maintenance period):
• Percentage Change from Baseline in 28-day Seizure Frequency for countable
motor seizures
• Treatment response of >= 25%, >= 50%, >= 75%, or 100% decrease for countable
motor seizures
Background summary
This Phase 2 randomized, double-blind, placebo-controlled study is designed to
evaluate the efficacy, safety, tolerability, and PK of NBI-921352 doses
administered tid as adjunctive therapy in subjects with Developmental and
Epileptic Encephalopathy Syndrome (SCN8A-DEE).
Study objective
Main objective:
To assess the efficacy of NBI-921352 as adjunctive therapy on the frequency of
countable motor seizures
Secondary Objectives
• To evaluate the efficacy of NBI-921352 using the Clinical and
Parent/Caregiver Global Impression of Change scales and the Clinical and
Parent/Caregiver Global Impression of Severity scales.
• To characterize the pharmacokinetics of NBI-921352 and determine the effect
of NBI-921352 on plasma levels of concomitant ASMs and
evaluated metabolites.
• To evaluate the safety and tolerability of NBI-921352.
Study design
This is 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-DEE. Approximately 52 male and
female subjects will be randomized for study participation according to the
study eligibility criteria. Subjects will be randomized 1:1
(NBI-921352:placebo).
Intervention
Subjects will be randomized 1:1 to NBI-921352 versus placebo. Both NBI-921352
and placebo will be administered orally. The starting dose of NBI-921352 will
be based on the subject's weight at the screening visit. The dose will be
titrated (increased) every week at each of the 2 lowest titration dose levels
and every 2 weeks at each of highest titration dose levels. Subjects will
continue to receive the highest tolerated dose during the maintenance period.
Study burden and risks
Subjects will participate in the study for the duration of 30 weeks. Subjects
will need to come to the hospital more often than they normally would and
undergo additional tests. These include physical and neurological examinations,
ECGs, pregnancy tests, urine/blood/saliva tests, and questionnaires, including
mental health assessments. Aside from these interventions, participation in
this study involves blood draws (venipuncture) and in the course of 30 weeks
(7-9 visits) 92-116 ml blood will be taken. Risks may include adverse effects
of the study drug. Subjects may also feel discomfort during some of the tests.
Currently no therapies are indicated to treat SCN8A-DEE, and seizures in
SCN8A-DEE patients are typically very resistant to existing antiseizure
medications (ASMs). SCN8A-DEE patients are at risk for developmental delay,
cognitive impairment, life-threatening status epilepticus, and SUDEP, and the
lack of an effective therapy for these patients establishes a clear unmet
medical need. The available NBI-921352 data suggest that targeting the VSD4
binding site enables the improved potency, selectivity, and favorable
nonclinical safety profile of NBI-921352 relative to other sodium channel
inhibitors.
12780 El Camino Real -
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12780 El Camino Real -
San Diego CA 92130
US
Listed location countries
Age
Inclusion criteria
• Be a male or female 12 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 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 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). 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
• Have, at the screening visit, an ECG finding of a corrected QT interval using
Fridericia's formula (QTcF) >450 msec or presence of any significant cardiac
abnormality.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2020-003140-83-NL |
| ClinicalTrials.gov | NCT04873869 |
| CCMO | NL79058.056.21 |