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Efficacy and Safety of Vormatrigine in Adults with Focal Epilepsy Receiving Concomitant Antiseizure Medications: A Randomized, Double-Blind, Placebo-Controlled Trial

Trial ID: 2025-524038-24-00
Protocol: PRAX-628-322
Sponsor: Praxis Precision Medicines Inc.

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Diseases & Conditions

Partial seizures

Objectives

The primary objective is to evaluate the efficacy of vormatrigine compared to placebo regarding focal seizure frequency in adults currently receiving one to three anti-seizure medications (ASMs). 5, 6

Secondary objectives include:

Assessment of efficacy trends over time in relation to seizure frequency.
Evaluation of efficacy using PGI-C and CGI-C scales.
Assessment of safety and tolerability.

4, 5, 13

Participants

This clinical trial involves 240 patients diagnosed with focal epilepsy. The study population consists of adults, including both male and female participants, aged between 18 and 85 years. Eligible individuals must have confirmed focal onset seizures according to the International League Against Epilepsy Classification and have evidence from CT or MRI ruling out progressive causes of epilepsy. Participants are required to be on stable doses of one to three anti-seizure medications for a minimum of four weeks prior to screening. Selection is based on the presence of a specific number of countable seizures during a defined observation period and the ability to maintain a seizure diary.

Plans and Procedures

This Phase 3, double-blind, randomized, placebo-controlled clinical trial is designed to evaluate the efficacy and safety of vormatrigine in adults diagnosed with focal epilepsy. The study compares the effects of oral vormatrigine against a placebo on the frequency of focal seizures in individuals currently receiving stable doses of one to three anti-seizure medications. The research methodology involves an initial observation period to establish baseline seizure frequency via a seizure diary, followed by a treatment period. The primary endpoint is the proportion of 50% responders, defined as achieving at least a 50% reduction in seizure frequency compared to the observation period. Secondary objectives include assessing seizure freedom, changes in monthly seizure frequency, and the incidence of treatment-emergent adverse events. Study procedures include a screening visit to confirm eligibility through clinical diagnosis and neuroimaging, such as CT or MRI, and subsequent follow-up assessments to monitor clinical laboratory results, ECG parameters, and vital signs.

Treatment

The experimental medication is vormatrigine, administered as a tablet. The oral administration of this investigational product involves a dose of 00 mg.

The comparator treatment consists of a placebo used for the purpose of comparison against the test substance.

Efficacy

The efficacy of vormatrigine in adults with focal epilepsy is evaluated by comparing the test product to a placebo. The primary endpoint is the 50% Responder rate, which is defined as a minimum 50% reduction in focal seizure frequency from the Observation Period to the Treatment Period.

Secondary efficacy parameters include:

Change from baseline in seizure frequency from the Observation Period to the Treatment Period across the 20 mg, 30 mg, and 40 mg dose groups.
Seizure Freedom during the final period.
Time required to achieve a 50% seizure reduction from the Observation Period.
Monthly change from baseline in focal seizure frequency compared to placebo.
Impact on PGI-C and CGI-C.
Changes in suicidality as assessed by the C-SSRS.

Inclusion and Exclusion Criteria

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Inclusion Criteria

I 1. Participant and caregiver, if applicable, is willing to sign an informed consent document in accordance with ICH/GCP guidelines, indicating that they understand the purpose of the clinical trial; understands, and can perform, complete, and comply with all the procedures and assessments that are required during the clinical trial, including the seizure diary and is willing and able to adhere to the contraception methods (defined in Section 5.4.3 and Section 5.4.4), as applicable, and is willing to participate in the clinical trial.
I 2. Aged ≥18 to ≤85 at the time of consent for this trial.
I 3. Has a diagnosis of focal onset epilepsy according to the International League Against Epilepsy Classification of Epilepsy (2017).
I 4. 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.
I 5. Participant must attest to be taking stable doses of 1 or up to 3 acceptable ASMs (none listed as a prohibited concomitant medication) for at least 4 weeks prior to screening and during screening prior to Day 1. ASM doses should not be greater than the maximum indicated daily dosage in the local product information.
I 6. Has at least XXX countable focal onset seizures during the XXX weeks of Observation Period immediately prior to randomization with no more than XXX days seizure free during this period.
I 7. Seizure diary must be completed for ≥80% days in the Observation Period.

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Exclusion Criteria

E 1. Participant has had any of the following within the 12-month period preceding trial entry: a) evidence of experiencing pseudo or psychogenic seizures b) cluster seizures where the individual seizures cannot be counted c) an episode of convulsive status epilepticus requiring hospitalization and intubation d) seizures secondary to illicit drug or alcohol use
E 2. Seizures secondary to ongoing infection, neoplasia, demyelinating disease, progressive degenerative disease, metabolic illness deemed progressive, progressive structural lesion or encephalopathy. Evidence by CT or MRI for a progressive cause of epilepsy.
E 3. Previously documented EEG which shows any pattern not consistent with focal etiology of seizures (a new EEG is not required, if not available).
E 4. Planned epilepsy surgery during the course of the clinical trial.
E 5. History of any of the following: a) neurosurgery for seizures <1 year prior to enrollment b) radiosurgery <2 years prior to enrollment c) neurostimulator placed <1 year prior to Screening d) neurostimulator placed >1 year prior to Screening but settings have not been stable for at least 2 months prior to Screening
E 6. 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.
E 7. 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 that in the judgement of the investigator in consultation with the medical monitor and/or sponsor designee, might jeopardize the participant’s safety or influence or confound the clinical trial objectives.
E 8. Participants with a history of malignancy, myeloproliferative or lymphoproliferative disorders within the past 3 years are excluded. Exceptions:1) Participants with completely excised non-melanoma skin cancer (such as basal cell carcinoma or squamous cell carcinoma), cervical carcinoma in situ, ductal breast carcinoma in situ, are permitted at any time, or 2) Participants with a history of other malignancies deemed cured by adequate treatment are also permitted at any time. Participants with a history of indolent or early-stage malignancies that are unlikely to progress or other malignancies deemed cured by adequate treatment are also permitted at any time.
E 9. History or presence of uncontrolled cardiac diseases including conduction and structural abnormalities (e.g. family history of sudden death, long QT syndrome, familial short QT syndrome, Brugada syndrome, myocardial infarction, or sustained ventricular arrythmia, etc.) which may place patients at increased risk as determined by the investigator.
E 10. Total bilirubin value >1.5×ULN; an ALT or AST value >3×ULN. As an exception, participants that present with elevated bilirubin in the absence of elevations in ALT or AST that fits the pattern of Gilbert’s syndrome may be enrolled after discussion with the medical monitor and/or sponsor designee if their conjugated bilirubin is below the ULN.
E 11. 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.
E 12. 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.
E 13. Vigabatrin: Use in the last 5 years without stable visual fields tested twice over the 12 months after the last dose of vigabatrin.
E 14. 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.
E 15. Patient is receiving prohibited medication(s) as per the prohibited concomitant medications section of the protocol (including Appendix 4).
E 16. 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.
E 17. 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.
E 18. Previous exposure to vormatrigine or known hypersensitivity to any component used in the vormatrigine formulation.

Trial Status by Country

Country	Status	Start of Recruitment	Planned Patients
Czechia	Not Yet Recruiting	01 Apr 2026	6
Germany	Not Yet Recruiting	01 Apr 2026	9
Italy	Not Yet Recruiting	01 Apr 2026	12
Poland	Not Yet Recruiting	01 Apr 2026	12
Spain	Not Yet Recruiting	01 Apr 2026	21

Sites & Investigators

Research sites

Hospital Vall d’Hebron Università degli studi Gabriele D’Annunzio Chieti-Pescara Centro di Studi e tecnologie avanzate Niepubliczny Zaklad Opieki Zdrowotnej Wielospecjalistyczna Poradnia Lekarska Synapsis Lech Szczechowski Associazione La Nostra Famiglia

Investigators

Belen D. F.Irene G. M.Anatol M.Alberto D.

Investigational Products

Details about the medicinal products being studied in this clinical trial.

Product Name	Role in Trial	Formulation	Administration	Max Daily Dose	Treatment Duration	EU MP Number
Placebo for PRAX-628	Placebo	N/A	—	—	—	N/A
PRAX-628	Test	TABLET	ORAL	00	12	PRD12935302
PRAX-628	Test	TABLET	ORAL	00	12	PRD12935304
PRAX-628	Test	TABLET	ORAL	00	12	PRD12935303

Conditions Studied in This Trial

Interventions Studied in This Trial

vaccines

VORMATRIGINE

2 trials

Also investigated for

Partial seizures 2 Generalised tonic-clonic seizure 1