A Clinical Trial of PRAX-562 in Subjects With Developmental and Epileptic Encephalopathies (DEE)

Study Overview
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Brief Summary
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This is a Phase 2, double-blind, randomized clinical trial to explore the safety, tolerability, efficacy, and pharmacokinetics of PRAX-562 in pediatric participants who have seizures associated with early-onset SCN2A-DEE and SCN8A-DEE.

Official Title
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A Phase 2,Double-Blind,Randomized Clinical Trial to Explore the Safety,Tolerability,Efficacy, and Pharmacokinetics of PRAX-562 in Pediatric Participants With Developmental and Epileptic Encephalopathies Followed by Open-Label Extension(OLE)

Conditions
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SCN2A Encephalopathy, SCN8A Encephalopathy

Intervention / Treatment
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* Drug: Part A: 0.5mg/kg/day PRAX-562 for 16 Weeks
* Drug: Part A: 0.5mg/kg/day PRAX-562 for 12 Weeks and Matching Placebo for 4 Weeks
* Drug: Part B: 0.5mg/kg/day PRAX-562


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Has a documented rare missense variant in SCN2A with onset of seizures occurring in the first three months of life or has a documented de novo (not observed in either parent) missense variant in SCN8A with onset of seizures occurring in the first six months of life. Has a seizure frequency as follows: At least 8 countable motor seizures (as defined in the note below) in the 4 weeks immediately prior to Screening as reported by the parent/legal guardian or in the opinion of the investigator AND At least 8 countable motor seizures (as defined in the note below) 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 exclusion criteria apply and will be assessed by the study team.

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Parallel group
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part A: Randomized, Double-Blind 0.5mg/kg/day PRAX-562 or PRAX-562/Placebo<br>Eligible participants from each cohort will be randomized in a 1:1 ratio to either 0.5 milligrams/kilograms/day (mg/kg/day) PRAX-562 for 16 weeks (PRAX-562 arm) or 0.5 mg/kg/day PRAX-562 for 12 weeks and matching placebo for 4 weeks (PRAX-562/placebo arm) administered orally or via gastrostomy tube (G-tube). | Drug: Part A: 0.5mg/kg/day PRAX-562 for 16 Weeks<br>* Once daily oral or G-tube treatment.<br>Drug: Part A: 0.5mg/kg/day PRAX-562 for 12 Weeks and Matching Placebo for 4 Weeks<br>* Once daily oral or G-tube treatment with PRAX-562 for 12 weeks and matching placebo for 4 weeks.<br>|
| Experimental: Part B: Open-Label Extension Treatment 0.5mg/kg/day PRAX-562<br>Eligible participants will receive 0.5mg/kg/day administered orally or via G-tube for 48 weeks. | Drug: Part B: 0.5mg/kg/day PRAX-562<br>* Once daily oral or G-tube treatment.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Treatment-Emergent Adverse Events (TAEs) [Safety and Tolerability]) | The number of participants with treatment-emergent adverse events will be reported by severity and preferred term. | 16 weeks | 
| To evaluate the long-term safety and tolerability of PRAX-562 in pediatric participants with DEEs | Incidence and severity of TEAEs | 48 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To assess the effect of PRAX-562 on the frequency of countable motor seizures in pediatric participants with DEEs | Changes from baseline in monthly (28-day) motor seizure frequency | 16 weeks | 
| Plasma concentrations of PRAX-562 | Sparse pharmacokinetic (PK) sampling will be used to calculate mean concentrations at baseline, and at Weeks 2, 4, 6, 8,10, 12 and 16. | 16 weeks | 
| Seizure Frequency (OLE Extension) | Efficacy assessments (seizure diary) will be collected daily and reviewed at timepoints Day 1, Week 16, Week 32, and Week 48. | 48 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pediatric epilepsy, NaV1.2 Voltage-Gated Sodium Channel, SCN2A variant, SCN8A variant, Developmental and epileptic encephalopathy