Vormatrigine for adults with focal seizures

A Double-blind, Randomized Clinical Trial Evaluating the Efficacy and Safety of Vormatrigine in Adults With Focal Seizures

This trial will try daily vormatrigine at three different doses versus placebo in adults with focal seizures to see if it reduces seizure frequency and is safe.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 300 (estimated)
• Ages: 18 Years to 85 Years
• Sex: All
• Sponsor: Praxis Precision Medicines (Industry-sponsored)
• Locations: 7 sites (Miami, Florida and 6 other locations)
• Trial ID: NCT07505004 on ClinicalTrials.gov

What this trial studies

This is a Phase 3, multicenter, double-blind, randomized, placebo-controlled trial testing three fixed daily doses of vormatrigine (20, 30, 40 mg) taken for 12 weeks compared with placebo. Adults must have focal onset epilepsy, be on 1–3 stable anti-seizure medications, and document at least four countable focal seizures during a 4‑week baseline observation with good diary adherence. Participants are randomized to one of the active dose groups or placebo and followed for seizure frequency and safety outcomes. The primary focus is on seizure reduction and tolerability across the treatment period.

Who should consider this trial

Good fit: Adults with focal onset epilepsy who are on 1–3 stable anti-seizure medications, have at least four countable focal seizures during a 4‑week baseline, and can maintain a seizure diary are ideal candidates.

Not a fit: People with progressive structural causes of epilepsy, documented psychogenic non-epileptic seizures, unclear or uncountable cluster seizures, unstable ASM regimens, or who cannot meet diary or visit requirements are unlikely to benefit from participation.

Why it matters

Potential benefit: If successful, vormatrigine could offer an additional oral treatment option that reduces seizure frequency and improves seizure control for adults with focal epilepsy.

How similar studies have performed: Earlier-phase trials of vormatrigine showed enough promise to advance to this Phase 3 program, but definitive large-scale Phase 3 results are not yet available.

Eligibility criteria

Inclusion Criteria:

* Has a diagnosis of focal onset epilepsy according to the International League Against Epilepsy Classification of Epilepsy (2017).
* Prior to randomization, past evidence by CT or MRI that has ruled out a progressive cause of epilepsy in the judgement of the investigator and/or in consultation with the medical monitor.
* Participant must attest to be taking stable doses of 1 or up to 3 acceptable ASMs for at least 4 weeks prior to screening and during screening prior to Day 1.
* Has at least 4 countable focal onset seizures during the 4 weeks of Observation Period immediately prior to randomization with no more than 21 days seizure free during this period.
* Seizure diary must be completed for ≥80% days in the Observation Period.

Exclusion Criteria:

* Participant has had any of the following within the 12-month period preceding trial entry:

  1. evidence of experiencing pseudo or psychogenic seizures
  2. cluster seizures where the individual seizures cannot be counted
  3. an episode of convulsive status epilepticus requiring hospitalization and intubation
  4. seizures secondary to illicit drug or alcohol use
* Seizures secondary to ongoing infection, neoplasia, demyelinating disease, progressive degenerative disease, metabolic illness deemed progressive, progressive structural lesion or encephalopathy.
* Previously documented EEG which shows any pattern not consistent with focal etiology of seizures.
* Planned epilepsy surgery during the course of the clinical trial.
* History of any of the following:

  1. neurosurgery for seizures \<1 year prior to enrollment
  2. radiosurgery \<2 years prior to enrollment
  3. neurostimulator placed \<1 year prior to Screening
  4. neurostimulator placed \>1 year prior to Screening but settings have not been stable for at least 2 months prior to Screening
* Active suicidal plan/intent in the past 6 months, or a history of suicide attempt in the last 2 years, or more than 1 lifetime suicide attempt, as confirmed by C-SSRS.
* Has any significant ongoing disease, disorder, laboratory abnormalities, alcohol or drug abuse or dependence, environmental factor, or ongoing or recent history of any psychiatric, medical, or surgical condition.
* Participants with a history of malignancy, myeloproliferative or lymphoproliferative disorders within the past 3 years are excluded.
* History or presence of uncontrolled cardiac diseases including conduction and structural abnormalities.
* Total bilirubin value \>1.5×ULN; an ALT or AST value \>3×ULN.
* History of or active HIV infection or positive screening result for: HIV 1 or 2 antibodies. Evidence of active hepatitis B or hepatitis C infection, as determined by relevant screening assessments.
* Has received any other experimental or investigational drug, device or other therapy within 30 days or 5 half-lives (whichever is longer) prior to Screening, or any prior use of gene or cell therapy.
* Vigabatrin: Use in the last 5 years without stable visual fields tested twice over the 12 months after the last dose of vigabatrin.
* Felbamate: If used as a concomitant ASM, patients must be on felbamate for at least 2 years, with a stable dose for 2 months prior to Screening. If a patient received felbamate in the past, it must have been discontinued 2 months prior to screening.
* Significant allergic reaction to an ASM(s), including dermatological (e.g. Stevens-Johnson syndrome), hematological, or organ toxicity reactions. Severe reactions do not include simple maculopapular eruption and allergic rhinitis.
* Is pregnant or breastfeeding at the time of Screening or has a positive serum pregnancy test at Screening or is planning to become pregnant during the clinical trial or prior to end of study visit.
* Previous exposure to vormatrigine or known hypersensitivity to any component used in the vormatrigine formulation.

Where this trial is running

Miami, Florida and 6 other locations

• Praxis Research Site — Miami, Florida, United States (Recruiting)
• Praxis Research Site — Miami Lakes, Florida, United States (Recruiting)
• Praxis Research Site — Naples, Florida, United States (Not_yet_recruiting)
• Praxis Research Site — Marlboro, New Jersey, United States (Recruiting)
• Praxis Research Site — Niagara Falls, New York, United States (Recruiting)
• Praxis Research Site — Raleigh, North Carolina, United States (Recruiting)
• Praxis Research Site — Houston, Texas, United States (Recruiting)

Study contacts

• Study coordinator: Senior Medical Director Clinical Development

Conditions Focal Epilepsy; focal epilepsy