PRAX-222 for Epileptic Encephalopathy

Recruiting at 2 trial locations

Overseen By Head of Pharmacovigilance

Age: < 65

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Praxis Precision Medicines

Must not be taking: Sodium channel blockers

Disqualifiers: Other genetic variants, others

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

Compensation: Varies

Number of Visits: Unknown

60 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effects of PRAX-222 (also known as Elsunersen) for children with a specific type of epilepsy linked to a genetic variant in the SCN2A gene. The trial aims to understand the treatment's impact on children who began having seizures before three months of age. Participants will receive varying doses of PRAX-222 or a placebo to ensure accurate results. Children with a genetic variant in the SCN2A gene who weigh at least 10 kg may be suitable for this trial. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the chance to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but you cannot be on more than 2 sodium channel blocking anti-seizure medications.

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

Research has shown that PRAX-222, also known as elsunersen, has been safe in earlier studies. One study reported no severe or serious side effects after 19 doses given over 20 weeks, indicating that participants tolerated the treatment well. Additionally, the European Medical Agency granted PRAX-222 a special status, often awarded when a treatment appears safe and effective. These findings provide some confidence in the safety of PRAX-222 for treating certain types of epilepsy in children. ^{1 2 3 4 5}

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

Researchers are excited about PRAX-222 for epileptic encephalopathy because it represents a novel approach to treating this challenging condition. Unlike traditional anticonvulsants like valproate or lamotrigine, PRAX-222 is designed to specifically target the genetic mutations that often cause epileptic encephalopathy. This precision approach could potentially reduce seizures more effectively and with fewer side effects. Additionally, the study includes multiple phases of dosing, including an innovative dose escalation process, allowing researchers to fine-tune the treatment for maximum efficacy and safety.

What evidence suggests that PRAX-222 might be an effective treatment for epileptic encephalopathy?

Research has shown that PRAX-222, which participants in this trial may receive, may help treat early onset SCN2A developmental and epileptic encephalopathy (DEE). In an early study, patients experienced a 44% drop in seizures after three doses of PRAX-222. Another report found that one patient had over a 60% decrease in seizures, suggesting significant benefits. These results highlight PRAX-222's potential to reduce seizures, offering hope for those with this challenging condition. ^{1 6 7 8 9}

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 aged 2-18 with early onset SCN2A developmental and epileptic encephalopathy, who had seizures start before 3 months old, weigh at least 10 kg, and have a specific genetic variant. Kids can't join if they have other significant genetic changes or are on more than two sodium channel blocking seizure meds.

Inclusion Criteria

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

Has onset of seizures prior to 3 months of age

I weigh at least 10 kg.

Exclusion Criteria

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

My epilepsy or developmental disorder is not caused by known genetic changes outside of the SCN2A gene.

I am taking more than two medications for seizures that block sodium channels.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

8 weeks

Preliminary Safety

Open-label PRAX-222 administration to assess initial safety and seizure frequency

12 to 16 weeks

Dose Escalation

Double-blind ascending doses of PRAX-222 or placebo to determine optimal dosing

24 to 28 weeks

Confirmatory Dosing

Double-blind fixed-dose PRAX-222 or placebo to confirm efficacy and safety

60 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• PRAX-222

Trial Overview The study tests PRAX-222's effects in various doses compared to a placebo. It starts with an initial dose of PRAX-222, followed by increasing amounts if safe, and then settles on fixed doses to see how well it works for these young epilepsy patients.

How Is the Trial Designed?

Group I: Preliminary Safety Experimental Treatment 1 Intervention

Open-label PRAX-222

Group II: Optional Dose Escalation - PRAX-222 Experimental Treatment 1 Intervention

Optional dose escalation consisting of double-blind ascending doses of PRAX-222

Group III: Open-label PRAX-222 Experimental Treatment 1 Intervention

Open-label PRAX-222

Group IV: Dose Escalation - PRAX-222 Experimental Treatment 1 Intervention

Initial dose escalation consisting of double-blind ascending doses of PRAX-222

Group V: Confirmatory Dosing - Placebo Experimental Treatment 1 Intervention

Double-blind placebo procedure

Group VI: Confirmatory Dosing - PRAX-222 Experimental Treatment 1 Intervention

Double-blind fixed-dose PRAX-222

Group VII: Dose Escalation - Placebo Placebo Group 1 Intervention

Double-blind placebo procedure

Group VIII: Optional Dose Escalation - Placebo Placebo Group 1 Intervention

Double-blind placebo procedure

PRAX-222 is already approved in European Union, United States for the following indications:

Approved in European Union as Elsunersen for:

• SCN2A Gain of Function developmental and epileptic encephalopathy (DEE)

Approved in United States as Elsunersen for:

• SCN2A Gain of Function developmental and epileptic encephalopathy (DEE)

Who Is Running the Clinical Trial?

Praxis Precision Medicines

Lead Sponsor

Trials

11

Recruited

1,300+

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05737784

NCT05737784 | A Clinical Trial of PRAX-222 in Pediatric ... 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) ...

2. investors.praxismedicines.com investors.praxismedicines.com/news-releases/news-release-details/praxis-precision-medicines-provides-portfolio-update-2023-rd-day

Praxis Precision Medicines Provides Portfolio Update at ... Positive results from preliminary analysis of PRAX-222 Part 1 showed 44% median reduction in seizures after three doses for ...

3. trialfinder.panfoundation.org trialfinder.panfoundation.org/en-US/trial/listing/548322

A Clinical Trial of PRAX-222 in Pediatric Participants With ... 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 ( ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12283366/

Antisense oligonucleotide treatment in a preterm infant with ... A >60% reduction in seizure frequency corresponding to five to seven seizures per hour was observed, which has been sustained during follow-up ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT07019922

NCT07019922 | A Clinical Trial of Elsunersen in Pediatric ... To assess secondary efficacy outcomes of elsunersen in participants with early-onset SCN2A DEE, Change in motor seizure-free days from baseline, 24 weeks ; CGI-S ...

6. investors.praxismedicines.com investors.praxismedicines.com/news-releases/news-release-details/praxis-precision-medicines-receives-prime-designation-ema

Press Release The European Medical Agency (EMA) has awarded its Priority Medicines (PRIME) designation for elsunersen (PRAX-222) for the treatment of SCN2A Gain of Function ...

7. aesnet.org aesnet.org/abstractslisting/embrave-a-clinical-trial-of-prax-222-a-novel-antisense-oligonucleotide-in-pediatric-participants-with-early-onset-scn2a-developmental-and-epileptic-encephalopathy

embrave: a clinical trial of prax-222, a novel antisense ... A first-in-human clinical trial designed to investigate the safety and efficacy of PRAX-222 in pediatric participants with early-onset SCN2A-DEE.

8. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40263630/

Antisense oligonucleotide treatment in a preterm infant with ... Elsunersen treatment demonstrated a favorable safety profile with no severe or serious adverse events reported after 19 intrathecal administrations over 20 ...

9. ctv.veeva.com ctv.veeva.com/study/randomized-double-blind-trial-of-elsunersen-in-pediatric-scn2a-dee-to-assess-efficacy-and-safety

A Clinical Trial of Elsunersen in Pediatric SCN2A-DEE to ... Has a documented Gain of Function SCN2A variant confirmed through genetic testing. Has onset of seizures prior to 3 months of age.