A multicenter, double-blind, randomized, placebo-controlled clinical trial to evaluate the efficacy and safety of vormatrigine in adults with focal seizures (POWER2)

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:

  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.