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

Exclusion Criteria25

• 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.