Double-blind, Randomized Clinical Trial Evaluating the Efficacy and Safety of Vormatrigine in Adults With Focal Seizures (POWER2)

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

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

Study Overview

• Status: Recruiting
• Conditions: Focal Epilepsy
• Intervention / Treatment: Drug: Placebo; Drug: 40 mg/day vormatrogine for 12 weeks; Drug: 30 mg/day vormatrogine for 12 weeks; Drug: 20 mg/day vormatrogine for 12 weeks

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 300
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Senior Medical Director Clinical Development; Phone Number: 773-939-6858; Email: clinicaltrials@praxismedicines.com

Study Locations

• United States
  • Florida
    • Miami, Florida, United States, 33133
      • Recruiting
      • Praxis Research Site
    • Miami Lakes, Florida, United States, 33016
      • Recruiting
      • Praxis Research Site
    • Naples, Florida, United States, 34116
      • Not yet recruiting
      • Praxis Research Site
  • New Jersey
    • Marlboro, New Jersey, United States, 07746
      • Recruiting
      • Praxis Research Site
  • New York
    • Niagara Falls, New York, United States, 14304
      • Recruiting
      • Praxis Research Site
  • North Carolina
    • Raleigh, North Carolina, United States, 27607
      • Recruiting
      • Praxis Research Site
  • Texas
    • Houston, Texas, United States, 77058
      • Recruiting
      • Praxis Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 40 mg/day vormatrogine for 12 weeks; Participants who meet all eligibility criteria will be randomized at Visit 1 (Day 1) to receive 40 mg of vormatrogine	Drug: 40 mg/day vormatrogine for 12 weeks; Once daily oral
Experimental: 30 mg/day vormatrogine for 12 weeks; Participants who meet all eligibility criteria will be randomized at Visit 1 (Day 1) to receive 30 mg of vormatrogine	Drug: 30 mg/day vormatrogine for 12 weeks; Once daily oral
Experimental: 20 mg/day vormatrogine for 12 weeks; Participants who meet all eligibility criteria will be randomized at Visit 1 (Day 1) to receive 20 mg of vormatrogine	Drug: 20 mg/day vormatrogine for 12 weeks; Once daily oral
Placebo Comparator: Placebo per day for 12 weeks; Participants who meet all eligibility criteria will be randomized at Visit 1 (Day 1) to receive placebo	Drug: Placebo; Once daily oral

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To evaluate the efficacy of vormatrigine compared to placebo on focal seizure frequency in adults currently taking 1 to 3 ASMs	Median percent change in monthly (28 days) focal seizure frequency from the Screening/Observation Period to the Treatment Period for vormatrogine compared to placebo.	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To further evaluate the efficacy of vormatrigine compared to placebo on focal seizure frequency in adults currently taking 1 to 3 ASMs	Proportion of participants experiencing a ≥50% reduction in monthly (28 days) focal seizure frequency from the Screening/Observation Period to the Treatment Period (Responder Rate) for vormatrogine compared to placebo	12 weeks
To assess trends over time in efficacy of vormatrogine on focal seizure frequency	Percent change in monthly focal seizure frequency from the Screening/Observation Period to the Treatment Period for vormatrogine compared with placebo.	12 weeks
To assess the safety and tolerability of vormatrigine in adults with focal seizures	Incidence and severity of TEAEs, including discontinuation of study drug due to TEAEs	12 weeks
To assess the safety and tolerability of vormatrigine in adults with focal seizures	Change in tympanic temperature in Celsius	12 weeks
To assess the safety and tolerability of vormatrigine in adults with focal seizures	Change in heart rate in beats per minute	12 weeks
To assess the safety and tolerability of vormatrigine in adults with focal seizures	Change in blood pressure in mm/Hg	12 weeks
To assess the safety and tolerability of vormatrigine in adults with focal seizures	Change in respiratory rate in breaths per minute	12 weeks
To assess the safety and tolerability of vormatrigine in adults with focal seizures	The principal investigator (PI) or sub investigator will review the laboratory report and document this review. Any clinically significant adverse changes occurring during the clinical trial will be documented as adverse events	12 weeks
To assess the safety and tolerability of vormatrigine in adults with focal seizures	Incidence of clinically significant ECG abnormalities	12 weeks
To assess the safety and tolerability of vormatrigine in adults with focal seizures	Changes in suicidality, as assessed by C-SSRS	12 weeks

Collaborators and Investigators

• Sponsor: Praxis Precision Medicines
• Investigators: Study Director: Praxis Precision Medicines, Praxis Precision Medicines

Study record dates

Study Major Dates

• Study Start (Actual): January 29, 2026
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): May 1, 2027

Study Registration Dates

• First Submitted: March 26, 2026
• First Submitted That Met QC Criteria: March 26, 2026
• First Posted (Actual): April 1, 2026

Study Record Updates

• Last Update Posted (Actual): April 1, 2026
• Last Update Submitted That Met QC Criteria: March 26, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: focal epilepsy
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Epilepsy; Epilepsies, Partial
• Other Study ID Numbers: PRAX-628-322

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No