PRAX-562 for Epilepsy

(EMBOLD Trial)

Recruiting at 6 trial locations

Overseen By Head of Pharmacovigilance

Age: < 65

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: Praxis Precision Medicines

Must not be taking: Sodium channel blockers

Disqualifiers: Other genetic variants, Status epilepticus, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

Duration: 16 weeks

100 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment called PRAX-562 for children with seizures due to specific rare genetic conditions, SCN2A-DEE and SCN8A-DEE. The goal is to determine if PRAX-562 is safe, effective, and well-tolerated. Participants will receive varying doses of PRAX-562, while some will receive a placebo (a pill resembling the treatment but containing no active drug) for comparison. Children who began having seizures early in life and experience at least eight motor seizures per month might be suitable candidates for this study. As a Phase 2, Phase 3 trial, this study is crucial for assessing the treatment's effectiveness and represents the final step before potential FDA approval, offering hope for improved seizure management.

Do I need to stop my current medications to join the trial?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the study team for guidance.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that PRAX-562 is generally safe for people. In a previous study, participants experienced no major safety issues. They maintained stable vital signs, normal lab results, and showed no problems in heart tests or physical exams. Additionally, they reported no serious side effects. Another study found that PRAX-562 reduced seizures by 46% compared to a placebo, with a safety profile similar to other drugs in its class. While these results are promising, it's important to remember that researchers are still studying this treatment to fully understand its safety and effectiveness. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for epilepsy?

PRAX-562 is unique because it offers a potential new approach to treating epilepsy by targeting specific brain pathways differently than most current medications. While standard epilepsy treatments like sodium channel blockers aim to reduce seizure activity broadly, PRAX-562 acts more precisely, which might improve effectiveness and reduce side effects. Researchers are excited because this targeted action could lead to better management of seizures with fewer downsides, offering hope for those who haven't found relief with existing options.

What evidence suggests that PRAX-562 might be an effective treatment for epilepsy?

Research has shown that PRAX-562 may help treat seizures. In one study, PRAX-562 reduced seizures by 46% compared to a placebo, significantly lowering the number of seizures. Another study found that over 30% of patients stopped having seizures while taking the drug. PRAX-562 targets sodium channels, which play a role in nerve communication in the brain. This action may help calm the overly active signals that cause seizures. These findings suggest PRAX-562 could be effective for people with certain types of epilepsy linked to gene changes like SCN2A and SCN8A. Participants in this trial will receive different dosages of PRAX-562, either 0.5 mg/kg/day or 1.0 mg/kg/day, with some receiving a placebo for a portion of the study. ^{1 4 6 7 8}

Who Is on the Research Team?

Medical Director

Principal Investigator

Praxis Precision Medicines

Are You a Good Fit for This Trial?

This trial is for children with rare genetic variants causing seizures within the first months of life. They must have frequent motor seizures, but can't join if they have other significant genetic disorders or a history of seizure worsening due to sodium channel blockers.

Inclusion Criteria

I've had at least 8 motor seizures in the last 4 weeks and during a 28-day observation period.

I have a rare SCN2A variant with seizures starting in the first 3 months, or a new SCN8A variant with seizures in the first 6 months.

Additional inclusion criteria apply and will be assessed by the study team

Exclusion Criteria

Additional exclusion criteria apply and will be assessed by the study team

I have a genetic variant linked to my epilepsy or developmental disorder, not related to SCN2A or SCN8A genes.

I've been hospitalized and intubated for seizures at least twice in the last 6 months.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either 1.0 mg/kg/day or 0.5 mg/kg/day PRAX-562 for 16 weeks, with some receiving placebo for the last 4 weeks

16 weeks

Regular visits for monitoring and PK sampling at Weeks 2, 4, 6, 8, 10, 12, and 16

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Open-label extension

Eligible participants receive 1.0 mg/kg/day or 0.5 mg/kg/day PRAX-562 for up to 144 weeks

Up to 144 weeks

Visits at Day 1, Week 16, Week 32, and Week 48 for efficacy assessments

What Are the Treatments Tested in This Trial?

Interventions

• PRAX-562

Trial Overview The study tests PRAX-562's safety and effectiveness in treating seizures associated with DEE. It involves different parts: some get the drug for up to 16 weeks, while others receive it alongside a placebo part of the time.

How Is the Trial Designed?

Group I: Part B: Open-Label Extension Treatment 0.5mg/kg/day PRAX-562 Experimental Treatment 1 Intervention

Eligible participants will receive 0.5mg/kg/day administered orally or via G-tube for up to 144 weeks.

Group II: Part A: Randomized, Double-Blind 1.0 mg/kg/day PRAX-562 or PRAX-562/Placebo Experimental Treatment 1 Intervention

Eligible participants from each cohort will be randomized in a 1:1 ratio to either 1.0 milligrams/kilograms/day (mg/kg/day) PRAX-562 for 16 weeks (PRAX-562 arm) or 1.0 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).

Group III: Part A: Randomized, Double-Blind 0.5mg/kg/day PRAX-562 or PRAX-562/Placebo Experimental Treatment 1 Intervention

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).

Group IV: Open-Label Extension Treatment 1.0 mg/kg/day PRAX-562 Experimental Treatment 1 Intervention

Eligible participants will receive 1.0 mg/kg/day administered orally or via G-tube for up to 144 weeks.

PRAX-562 is already approved in United States, European Union for the following indications:

Approved in United States as PRAX-562 for:

• Developmental and Epileptic Encephalopathies (DEE) associated with SCN2A and SCN8A mutations

Approved in European Union as PRAX-562 for:

• Developmental and Epileptic Encephalopathies (DEE) associated with SCN2A and SCN8A mutations

Who Is Running the Clinical Trial?

Praxis Precision Medicines

Lead Sponsor

Trials

11

Recruited

1,300+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9304232/

The novel persistent sodium current inhibitor PRAX‐562 ... The maximally efficacious dose of PRAX‐562 (10 mg/kg, conveying protection in 11 of 12 mice) prevented seizures but did not impair locomotor function. In ...

2. investors.praxismedicines.com investors.praxismedicines.com/news-releases/news-release-details/praxis-precision-medicines-announces-positive-topline-results-0

Press Release Over 30% of patients achieved seizure freedom status while on relutrigine. Meaningful gains observed in alertness, communication and seizure severity.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05818553

NCT05818553 | A Clinical Trial of PRAX-562 in Subjects ... This is a Phase 2, double-blind, randomized clinical trial to explore the safety, tolerability, efficacy, and pharmacokinetics of PRAX-562 in pediatric ...

4. scn2a.org scn2a.org/promising-initial-relutrigine-prax-562-clinical-data/

Promising Initial Relutrigine (Prax-562) Clinical Data The trial demonstrated a 46% reduction in seizures compared to placebo, with a safety profile consistent with other drugs in this class.

5. investors.praxismedicines.com investors.praxismedicines.com/news-releases/news-release-details/praxis-precision-medicines-provides-update-advancing-clinical

Praxis Precision Medicines Provides Update on Advancing ... Praxis continues to progress PRAX-562 as a unique sodium channel modulator targeting developmental and epileptic encephalopathies (DEEs).

6. praxismedicines.com praxismedicines.com/wp-content/uploads/2023/09/IEC2023_562-101_Final_QRcode.pdf

PRAX-562-101: A Phase 1 Trial Evaluating the Safety, ... PRAX-562 was well-tolerated with no clinically significant safety findings in vital signs, clinical laboratory results, physical exams, ECGs, or ...

7. investors.praxismedicines.com investors.praxismedicines.com/news-releases/news-release-details/praxis-precision-medicines-advance-prax-562-phase-2-study

Praxis Precision Medicines to Advance PRAX-562 Phase 2 ... In-vivo studies of PRAX-562 have demonstrated dose-dependent block of seizures up to complete inhibition of seizure activity in SCN2A, SCN8A and ...

8. neurology.org neurology.org/doi/10.1212/WNL.0000000000203113

PRAX-562-101: A Phase 1 Trial Evaluating the Safety ... PRAX-562 was well-tolerated with no clinically significant safety findings in vital signs, laboratory results, physical exams, ECGs, or C-SSRS data; TEAEs were ...