SCN2A Encephalopathy, SCN8A Encephalopathy
Conditions
Keywords
Pediatric epilepsy, NaV1.2 Voltage-Gated Sodium Channel, SCN2A variant, SCN8A variant, Developmental and epileptic encephalopathy
Brief summary
A Clinical Trial of PRAX-562 in Subjects With Developmental and Epileptic Encephalopathies (DEE)
Detailed description
A Phase 2, double-blind, randomized clinical trial to evaluate the safety and tolerability of PRAX 562 in pediatric participants with SCN2A- and SCN8A- DEEs.
Interventions
DRUGPRAX-562
Once daily oral or G-tube treatment.
Sponsors
Praxis Precision Medicines
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Masking description
Double-blind
Intervention model description
Parallel group
Eligibility
Sex/Gender
ALL
Age
1 Years to 18 Years
Healthy volunteers
No
Inclusion criteria
* Has a documented variant in SCN2A with onset of seizures occurring in the first 3 months of life or has a diagnosis of SCN8A-DEE supported by both clinical and genetic findings. * Has a seizure frequency as follows: * At least 8 countable motor seizures in the 4 weeks immediately prior to Screening as reported by the parent/legal guardian or in the opinion of the investigator as documented in medical notes. AND o At least 8 countable motor seizures during the 28 day Baseline Observation Period (during which seizure frequency is recorded in a daily seizure diary). • Additional inclusion criteria apply and will be assessed by the study team.
Exclusion criteria
* Has any clinically significant or known pathogenic or likely pathogenic genetic variant other than in SCN2A and SCN8A or a genetic variant that may explain or contribute to the participant's epilepsy and/or developmental disorder. * Has a documented, functionally characterized loss-of-function (LoF) missense variant or a presumed LoF variant (nonsense or frameshift variant) based on genetic testing and/or clinical evidence that prior exposure to a sodium channel blocker (SCB) medication worsened seizures. * Has 2 or more episodes of convulsive status epilepticus requiring hospitalization and intubation in the 6 months prior to Screening. * Additional
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| PART A (Cohorts 1 and 2) RDB: To evaluate the safety and tolerability of PRAX 562 in pediatric participants with SCN2A- and SCN8A- DEEs | 16 weeks | Changes from baseline in monthly (28-day) motor seizure frequency |
| PART B (Cohorts 1 and 2) OLE: To evaluate the long-term safety and tolerability of PRAX-562 in pediatric participants with DEEs | 48 weeks | Incidence and severity of TEAEs |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| PART A (Cohorts 1 and 2) RDB: To assess the effect of PRAX-562 on the frequency of countable motor seizures in pediatric participants with DEEs | 16 weeks | Changes from baseline in monthly (28-day) motor seizure frequency |
| Plasma concentrations of PRAX-562 | 16 weeks | Sparse pharmacokinetic (PK) sampling will be used to calculate mean concentrations at baseline, and at Weeks 2, 4, 6, 8,10, 12 and 16. |
| Seizure Frequency (OLE Extension) | 48 weeks | Efficacy assessments (seizure diary) will be collected daily and reviewed at timepoints Day 1, Week 16, Week 32, and Week 48. |
| To assess the effect of PRAX-562 on the frequency of countable motor seizures in pediatric participants with DEEs | 16 weeks | Changes from baseline in monthly (28-day) motor seizure frequency |
| Incidence of Treatment-Emergent Adverse Events (TEAEs) [Safety and Tolerability]) | 16 weeks | The number of participants with treatment-emergent adverse events will be reported by severity and preferred term. |
Countries
Israel, Spain, United Kingdom, United States
Contacts
STUDY_DIRECTORMedical Director
Praxis Precision Medicines
Outcome results
None listed