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

Sponsor

Praxis Precision Medicines (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05818553

Collaborator

(none)

Enrollment

Location

Arms

10.9

Anticipated Duration (Months)

1.8

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
SCN2A Encephalopathy SCN8A Encephalopathy	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	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

20 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Parallel groupParallel group

Masking:

Triple (Participant, Care Provider, Investigator)

Masking Description:

Double-blind

Primary Purpose:

Treatment

Official Title:

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)

Anticipated Study Start Date :

Apr 17, 2023

Anticipated Primary Completion Date :

Sep 15, 2023

Anticipated Study Completion Date :

Mar 15, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Part A: Randomized, Double-Blind 0.5mg/kg/day PRAX-562 or PRAX-562/Placebo 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 Once daily oral or G-tube treatment. Drug: Part A: 0.5mg/kg/day PRAX-562 for 12 Weeks and Matching Placebo for 4 Weeks Once daily oral or G-tube treatment with PRAX-562 for 12 weeks and matching placebo for 4 weeks.
Experimental: Part B: Open-Label Extension Treatment 0.5mg/kg/day PRAX-562 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 Once daily oral or G-tube treatment.

Arm

Intervention/Treatment

Experimental: Part A: Randomized, Double-Blind 0.5mg/kg/day PRAX-562 or PRAX-562/Placebo

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

Once daily oral or G-tube treatment.

Drug: Part A: 0.5mg/kg/day PRAX-562 for 12 Weeks and Matching Placebo for 4 Weeks

Once daily oral or G-tube treatment with PRAX-562 for 12 weeks and matching placebo for 4 weeks.

Experimental: Part B: Open-Label Extension Treatment 0.5mg/kg/day PRAX-562

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

Once daily oral or G-tube treatment.

Outcome Measures

Primary Outcome Measures

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

Secondary Outcome Measures

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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

2 Years to 18 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.