Section 4 of 6
Clinical evidence
75 evidence topics · 17 sources
Study summaries
EMBOLD
Objective
Initial protocol: safety, tolerability, efficacy, and pharmacokinetics
Location and study date
Study design
Multicenter randomized study
EMBOLD: confirmatory cohort study design
EMBOLD: confirmatory cohort interim analysis
Eligibility criteria
EMBOLD: cohort 1 age and weight criteria
Cohort 1: genetic disease eligibility
Initial protocol: exclusion of loss-of-function variants
Initial protocol: SCN2A seizure-onset eligibility
Treatment
EMBOLD: confirmatory cohort treatment regimens
| Regimen | Direct quotations |
|---|---|
| Relutrigine throughout treatment | “Relutrigine for 4 x 4 weeks” |
| Relutrigine and placebo periods | “Placebo for 1 x 4 weeks”· “Relutrigine for 3 x 4 weeks” |
| Dose | “1 mg/kg/day” |
Study outcomes
Rationale for using monthly motor seizure frequency as the primary endpoint
Confirmatory cohort: primary outcome definition
Rationale for endpoint selection
No evidence found.
Statistical analysis description
Number of participants (Planned and analyzed)
EMBOLD: cohort 2 enrollment
Description of analysis sets
Efficacy analysis population
Efficacy model: adjustment factors
Cohort 1: derivation of placebo-adjusted percentage reduction
Results
Participant disposition
Baseline characteristics
Cohort 2: relutrigine-exposed population
| Characteristic | Value |
|---|---|
| Age, mean (minimum, maximum), years | “6.0 (1, 18)” |
| SCN2A, participants (%) | “13 (25%)” |
| SCN8A, participants (%) | “38 (75%)” |
Efficacy results
EMBOLD: primary efficacy results, first and confirmatory cohorts
EMBOLD: cohort 1 seizure-freedom report at 16 weeks
EMBOLD cohort 2: motor seizure-free days
| “Key Secondary” | Estimate | p-value |
|---|---|---|
| Motor seizure-free days | “+66.2%” | “0.0340” |
Health-related quality of life and patient-reported outcomes
EMBOLD cohort 2: clinician and caregiver global improvement
| “Key Secondary” | Estimate | p-value |
|---|---|---|
| CGI-I (Clinician) | “-2.62” | “<0.0001” |
| CgGI-I (Caregiver) | “-3.7” | “0.002” |
Relutrigine-specific health-related quality-of-life instrument results
No evidence found.
Safety results
EMBOLD: cohort 1 most common adverse events
EMBOLD: cohort 1 serious adverse events
Cohort 2: adverse-event severity
Cohort 2: adverse event leading to discontinuation during relutrigine exposure
Study limitations
Summary
Cohort 1 randomized 16 participants, with 15 eligible for efficacy assessment. Cohort 2 randomized 53 participants and stopped early after an efficacy interim analysis. Its relutrigine and placebo exposure populations overlap because some participants received both treatments during masked periods; the exposure counts should not be interpreted as independent parallel groups. The extension result at 11 months concerns 13 participants without a concurrent placebo comparison. Clinician and caregiver global-improvement scales are reported, but they should not be treated as equivalent to a direct health-related quality-of-life measure.
EMERALD
Objective
Location and study date
Countries recruiting in the protocol presentation
Actual study start and completion dates
No evidence found.
Study design
Randomization ratio
Eligibility criteria
Treatment
Relutrigine starting dose
Study outcomes
Rationale for using monthly motor seizure frequency as the primary endpoint
Primary outcome definition
Rationale for endpoint selection
No evidence found.
Statistical analysis description
Number of participants (Planned and analyzed)
EMERALD: enrollment update
Analyzed population
No evidence found.
Description of analysis sets
No evidence found.
Results
Participant disposition
Baseline characteristics
No evidence found.
Efficacy results
No evidence found.
Health-related quality of life and patient-reported outcomes
No evidence found.
Safety results
No evidence found.
Study limitations
Summary
The protocol presentation planned approximately 160 participants, while the subsequent corporate update reported approximately 200 enrolled. The study includes a broader DEE population than the indication addressed in this report. Recruitment completion and a planned fourth-quarter 2026 topline announcement do not establish efficacy or safety results, and the report contains no analyzed outcome dataset for EMERALD.
Single-patient emergency use: new zealand
Objective
Location and study date
New Zealand case: treatment initiation
Study design
Eligibility criteria
Treatment
Starting daily dose
Study outcomes
Rationale for using motor seizure frequency as the reported outcome
Not applicable.
Statistical analysis description
Number of participants (Planned and analyzed)
Description of analysis sets
Not applicable.
Results
Participant disposition
Baseline characteristics
Diagnosis and age at treatment initiation
Efficacy results
Single-patient emergency use: SCN2A-DEE, New Zealand
Health-related quality of life and patient-reported outcomes
Clinical observation of alertness and responsiveness
Safety results
Reported adverse-event findings
Study limitations
Summary
This report describes one participant treated from four months of age. The observations are uncontrolled, and the reported seizure reduction at 3 mg/kg/day cannot establish comparative effectiveness or population-level safety. Alertness and responsiveness are clinical observations, not a randomized assessment of health-related quality of life.
Single-patient emergency use: germany
Objective
Location and study date
Treating center location
Exact date of relutrigine initiation
No evidence found.
Study design
Eligibility criteria
Treatment
Adjunctive relutrigine dose
Study outcomes
Rationale for using seizure frequency as the reported outcome
Not applicable.
Statistical analysis description
Number of participants (Planned and analyzed)
Description of analysis sets
Not applicable.
Results
Participant disposition
Baseline characteristics
Efficacy results
Seizure frequency after adjunctive relutrigine
Emergency-use case: antisense oligonucleotide treatment combined with precision sodium channel modulation
Health-related quality of life and patient-reported outcomes
Safety results
Safety after adjunctive relutrigine
Study limitations
Summary
This is one emergency-use case, not a randomized study. Relutrigine was used in a treatment course that also included an antisense oligonucleotide and carbamazepine. The report therefore does not isolate the effect of relutrigine from other treatment changes, and the reduction in carbamazepine dosage should not be interpreted as proof of efficacy for relutrigine alone.
PRAX-562-101
Objective
Location and study date
No evidence found.
Study design
Parts A and B: ascending-dose study
Part C: food-effect study
Eligibility criteria
Healthy-adult age range
Treatment
Dose ranges and food-effect dose
| Study part | Dose |
|---|---|
| Part A, single dose | “2.5 to 150 mg” |
| Part B, repeated once-daily dosing | “30 to 120 mg” |
| Part C, fed and fasted dosing | “90 mg” |
Study outcomes
Rationale for using safety and tolerability as the primary endpoint
Not applicable.
Statistical analysis description
Number of participants (Planned and analyzed)
Description of analysis sets
Safety analysis sets: inclusion of all participants
Results
Participant disposition
Baseline characteristics
Efficacy results
Not applicable.
Health-related quality of life and patient-reported outcomes
Not applicable.
Safety results
Severe treatment-emergent adverse events
Study limitations
Summary
The study enrolled 112 healthy-adult participants rather than participants with SCN2A- or SCN8A-related DEE. Single-dose, repeated-dose, and food-effect findings inform pharmacokinetics and short-term tolerability, but do not establish seizure efficacy, pediatric effectiveness, or long-term safety in the target population.
PRAX-562-102
Objective
Healthy-adult pharmacology objectives
Location and study date
No evidence found.
Study design
Eligibility criteria
Healthy-participant age range
Treatment
PRAX-562-102: phase 1 healthy-volunteer study, oxcarbazepine combination, part B treatment
Study outcomes
Rationale for using safety and tolerability as the primary endpoint
Not applicable.
Statistical analysis description
Number of participants (Planned and analyzed)
Description of analysis sets
No evidence found.
Results
Participant disposition
PRAX-562-102: early termination of the combination part
Baseline characteristics
Part A: age, mean (minimum, maximum), years
| Treatment | Age |
|---|---|
| Relutrigine | “38.7 (22, 53)” |
| Placebo | “37.3 (24, 49)” |
Efficacy results
Not applicable.
Health-related quality of life and patient-reported outcomes
Not applicable.
Safety results
PRAX-562-102: serious adverse events and study termination
Study limitations
Summary
This healthy-volunteer study enrolled 48 participants, with 30 in Part A and 18 in Part B. The 28-day treatment design does not establish long-term safety or therapeutic efficacy in pediatric DEE. One participant in the oxcarbazepine combination part experienced three study-drug-related serious adverse events, and Part B stopped early. Findings from that combination and dose should be distinguished from the separate EMBOLD pediatric regimen.