Clinical trial NCT05737784: A Clinical Trial of PRAX-222 in Pediatric Participants with Early Onset SCN2A Developmental and Epileptic Encephalopathy
Official title: A Seamless, Clinical Trial to Investigate the Safety and Efficacy of Multiple Doses of PRAX-222 in Pediatric Participants with Early Onset SCN2A Developmental and Epileptic Encephalopathy
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: SCN2A-DEE
Epilepsy
Keywords: Antisense Oligonucleotide
NaV1.2 Voltage-Gated Sodium Channel
Voltage-Gated Sodium Channel Blockers
SCN2A variant
Pediatric epilepsy
Developmental and Epileptic Encephalopathy
DEE
Lead sponsor: Praxis Precision Medicines
Sponsor class: INDUSTRY
First posted: 2023-02-21
Enrollment: 60
Sex: ALL
Minimum age (years): 2
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Seamless study design with sequential study parts, including an open-label safety part; a double-blind, randomized dose-escalation part; a double-blind, randomized confirmatory part; and an open-label extension part.
Primary purpose: TREATMENT

Brief summary: The goal of this trial is to learn about the effect of PRAX-222 in pediatric participants with early onset SCN2A developmental and epileptic encephalopathy (DEE), aged 2 to 18 years.


Eligibility criteria: Inclusion Criteria:

* Has onset of seizures prior to 3 months of age.
* Has a minimum weight of at least 10 kg at screening.
* Has a documented SCN2A variant through genetic testing obtained via a laboratory accredited per Clinical Laboratory Improvement Amendments (CLIA) or College of American Pathologists (CAP) or equivalent.
* Additional inclusion criteria apply and will be assessed by the study team

Exclusion Criteria:

* Has any clinically significant or known pathogenic genetic variant other than in the SCN2A gene, or a genetic variant that may explain or contribute to the participant's epilepsy and/or developmental disorder.
* Is taking more than 2 sodium channel blocking anti-seizure medications
* Additional exclusion criteria apply and will be assessed by the study team

Primary outcomes:
measure: Number of participants with treatment-emergent adverse events (Preliminary Safety, Dose Escalation)
timeFrame: Screening (-8 weeks) through up to 92 weeks
measure: Seizure frequency (Confirmatory Phase)
timeFrame: 36 to 40 weeks
Secondary outcomes:
measure: Seizure frequency (Preliminary Safety)
timeFrame: 12 to 16 weeks
measure: Seizure frequency (Preliminary Safety)
timeFrame: 0 to 4 weeks, 4 to 8 weeks, 8 to 12 weeks
measure: Percent change in seizure frequency (Preliminary Safety)
timeFrame: 0 to 4 weeks, 4 to 8 weeks, 8 to 12 weeks
measure: Number of participants with a treatment response (Preliminary Safety)
timeFrame: 0 to 4 weeks, 4 to 8 weeks, 8 to 12 weeks
measure: Seizure frequency (Dose Escalation Phase)
timeFrame: 24 to 28 weeks (Group 1), 30 to 34 weeks (Group 2, optional)
measure: Seizure frequency (Dose Escalation Phase)
timeFrame: 0 to 4 weeks, 4 to 8 weeks, 8 to 12 weeks, 12 to 16 weeks, 18 to 22 weeks, 30 to 34 weeks (Group 1, optional), 36 to 40 weeks (Group 1, optional), 42 to 46 weeks (Group 1, optional), 48 to 52 weeks (Group 1, optional), 54 to 58 weeks (Group 1, optional)
measure: Seizure frequency (Confirmatory Phase)
timeFrame: 0 to 4 weeks, 6 to 10 weeks, 12 to 16 weeks, 18 to 22 weeks, 24 to 28 weeks
measure: Percent change in seizure frequency (Dose Escalation Phase)
timeFrame: 0 to 4 weeks, 4 to 8 weeks, 8 to 12 weeks, 12 to 16 weeks, 18 to 22 weeks, 30 to 34 weeks (optional), 36 to 40 weeks (optional), 42 to 46 weeks (optional), 48 to 52 weeks (optional), 54 to 58 weeks (optional)
measure: Percent change in seizure frequency (Confirmatory Phase)
timeFrame: 0 to 4 weeks, 6 to 10 weeks, 12 to 16 weeks, 18 to 22 weeks, 24 to 28 weeks
measure: Number of participants with a treatment response (Dose Escalation Phase)
timeFrame: 0 to 4 weeks, 4 to 8 weeks, 8 to 12 weeks, 12 to 16 weeks, 18 to 22 weeks, 30 to 34 weeks (optional), 36 to 40 weeks (optional), 42 to 46 weeks (optional), 48 to 52 weeks (optional), 54 to 58 weeks (optional)
measure: Number of participants with a treatment response (Confirmatory Phase)
timeFrame: 0 to 4 weeks, 6 to 10 weeks, 12 to 16 weeks, 18 to 22 weeks, 24 to 28 weeks
measure: Changes in EEG-based outcome measures (Confirmatory Phase)
timeFrame: Week 2, Week 42
measure: Change from baseline in Clinical Global Impression-Severity (CGI-S) score (Confirmatory Phase)
timeFrame: 6 weeks, 12 weeks, 18 weeks, 24 weeks, 36 weeks, 60 weeks
measure: Change from baseline in Caregiver Global Impression-Severity (CgGI-S) score (Confirmatory Phase)
timeFrame: 6 weeks, 12 weeks, 18 weeks, 24 weeks, 36 weeks, 60 weeks
measure: Clinical Global Impression-Improvement (CGI-I) score (Confirmatory Phase)
timeFrame: 6 weeks, 12 weeks, 18 weeks, 24 weeks, 36 weeks, 60 weeks
measure: Caregiver Global Impression-Improvement (CgGI-I) score (Confirmatory Phase)
timeFrame: 6 weeks, 12 weeks, 18 weeks, 24 weeks, 36 weeks, 60 weeks
measure: Developmental milestones (Confirmatory Phase)
timeFrame: 36 weeks
measure: Quality of life as assessed by Quality of Life Inventory-Disability (Confirmatory Phase)
timeFrame: 36 weeks
measure: Behavior as assessed by Vineland Adaptive Behavior Scale-3rd edition (Vineland-3; Confirmatory Phase)
timeFrame: 36 weeks
measure: Behavior as assessed by Aberrant Behaviors Checklist-2nd edition (ABC-2; Confirmatory Phase)
timeFrame: 36 weeks
measure: Sleep as assessed by Sleep Disturbance Scale for Children (Confirmatory Phase)
timeFrame: 36 weeks
Other outcomes:
Locations:
city: Memphis
country: United States
facility: Le Bonheur Childrens Hospital
state: Tennessee
city: Porto Alegre
country: Brazil
facility: Hospital de Clinicas de Porto Alegre
state: Rio Grande do Sul
Study officials:
affiliation: Praxis Precision Medicines
name: Medical Director
role: STUDY_DIRECTOR
References: