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

PRAX-628-322 (POWER 2) is a Phase 3, multicenter, double-blind, randomized, placebo-controlled clinical trial to evaluate the efficacy and safety of vormatrigine in adults with focal seizures.

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:

• evidence of experiencing pseudo or psychogenic seizures
• cluster seizures where the individual seizures cannot be counted
• an episode of convulsive status epilepticus requiring hospitalization and intubation
• 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:

• neurosurgery for seizures <1 year prior to enrollment
• radiosurgery <2 years prior to enrollment
• neurostimulator placed <1 year prior to Screening
• 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.