VORMATRIGINE for Focal epilepsy|Focal seizures

Inclusion criteria

• {"criterion_text":"- I 1.\tParticipant 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.\n- I 2.\tAged ≥18 to ≤85 at the time of consent for this trial.\n- I 3.\tHas a diagnosis of focal onset epilepsy according to the International League Against Epilepsy Classification of Epilepsy (2017).\n- I 4.\tPrior 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.\n- I 5.\tParticipant 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.\n- I 6.\tHas 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.\n- I 7.\tSeizure diary must be completed for ≥80% days in the Observation Period."}

Exclusion criteria

• {"criterion_text":"- E 1.\tParticipant has had any of the following within the 12-month period preceding trial entry: a)\tevidence of experiencing pseudo or psychogenic seizures b)\tcluster seizures where the individual seizures cannot be counted c)\tan episode of convulsive status epilepticus requiring hospitalization and intubation d)\tseizures secondary to illicit drug or alcohol use\n- E 10.\tTotal 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.\n- E 11.\tHistory 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.\n- E 12.\tHas 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.\n- E 13.\tVigabatrin: Use in the last 5 years without stable visual fields tested twice over the 12 months after the last dose of vigabatrin.\n- E 14.\tFelbamate: 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.\n- E 15.\tPatient is receiving prohibited medication(s) as per the prohibited concomitant medications section of the protocol (including Appendix 4).\n- E 16.\tSignificant 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.\n- E 17.\tIs 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.\n- E 18.\tPrevious exposure to vormatrigine or known hypersensitivity to any component used in the vormatrigine formulation.\n- E 2.\tSeizures 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.\n- E 3.\tPreviously documented EEG which shows any pattern not consistent with focal etiology of seizures (a new EEG is not required, if not available).\n- E 4.\tPlanned epilepsy surgery during the course of the clinical trial.\n- E 5.\tHistory of any of the following: a)\tneurosurgery for seizures <1 year prior to enrollment b)\tradiosurgery <2 years prior to enrollment c)\t neurostimulator placed <1 year prior to Screening d)\tneurostimulator placed >1 year prior to Screening but settings have not been stable for at least 2 months prior to Screening\n- E 6.\tActive 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.\n- E 7.\tHas 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.\n- E 8.\tParticipants 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.\n- E 9.\tHistory 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."}

Primary endpoints

• {"endpoint_text":"- 50% Responder, defined as at least a 50% reduction in focal seizure frequency from the Observation Period to the Treatment Period","definition_or_measurement_approach":"Defined as at least a 50% reduction in focal seizure frequency from the Observation Period to the Treatment Period (responder analysis comparing vormatrigine to placebo)."}

Secondary endpoints

• {"endpoint_text":"- Change from baseline in seizure frequency from the Observation Period to the Treatment Period as assessed across the vormatrigine 20 mg, 30 mg and 40 mg dose groups","definition_or_measurement_approach":"Change from baseline seizure frequency comparing each vormatrigine dose group (20 mg, 30 mg, 40 mg) to placebo."}
• {"endpoint_text":"- Seizure Freedom, during the last period","definition_or_measurement_approach":"Proportion of participants who are seizure-free during the final assessment period of treatment."}
• {"endpoint_text":"- Time to achieve 50% seizure reduction from the Observation Period","definition_or_measurement_approach":"Time-to-event measured from randomization to first time point where a ≥50% reduction in focal seizure frequency vs Observation Period is observed."}
• {"endpoint_text":"- Change from baseline in monthly focal seizure frequency from the Observation Period to each month of the Treatment Period for vormatrigine compared with placebo","definition_or_measurement_approach":"Monthly seizure frequency change vs baseline (Observation Period) for each month of treatment comparing vormatrigine to placebo."}
• {"endpoint_text":"- Impact of vormatrigine compared to placebo on PGI-C and CGI-C","definition_or_measurement_approach":"Change or difference on Patient Global Impression of Change (PGI-C) and Clinical Global Impression of Change (CGI-C) scales comparing active treatment to placebo."}
• {"endpoint_text":"- Incidence and severity of TEAEs, including discontinuation of study drug due to TEAEs","definition_or_measurement_approach":"Safety assessment: frequency and severity grading of treatment-emergent adverse events and treatment discontinuations due to TEAEs."}
• {"endpoint_text":"- Changes in vital sign measurements","definition_or_measurement_approach":"Assessment of vital sign parameters over time compared to baseline."}
• {"endpoint_text":"- Changes in clinical laboratory results","definition_or_measurement_approach":"Monitoring of laboratory safety parameters (e.g., chemistry, hematology) and changes from baseline."}
• {"endpoint_text":"- Changes in ECG parameters","definition_or_measurement_approach":"ECG measurements and changes from baseline (e.g., intervals, rhythms)."}
• {"endpoint_text":"- Changes in suicidality, as assessed by C-SSRS","definition_or_measurement_approach":"Assessment of suicidality using the Columbia-Suicide Severity Rating Scale (C-SSRS)."}

Methods

• Paid Search (digital advertising) — documented for Spain, Germany, Poland, Czechia (materials named 'Paid Search' per country).
• Landing page / Homepage recruitment (country-specific landing page manuscripts present for ES, DE, CZ, PL) — directs potential participants to prescreener or study information.
• HCP-to-HCP referral letters and HCP forms (healthcare professional referral) — country-specific HCP referral materials available (IT, ES, DE, PL, CZ).
• Patient-facing print/digital materials (PatientFlyer, Patient Letter) — country-specific patient flyers/letters (ES, IT, DE, PL, CZ).
• Prescreener survey (online prescreening) — country-specific prescreener surveys (ES, DE, PL, CZ).
• Coded emails / texts and Media Assets — email/text templates and media assets available (country-specific).
• eConsent / Zoho Consent Forms — electronic consent platforms and forms specified (country-specific eConsent documents present).
• Paid digital search and landing page combined with local HCP referral and patient flyers — multi-channel approach combining digital and HCP referral in each listed country.

Italy

Earliest CTIS Part Ii Submission Date

17-03-2026

Latest Decision Or Authorization Date

23-04-2026

Processing Time Days

37

Number Of Sites

9

Number Of Participants

12

Spain

Earliest CTIS Part Ii Submission Date

12-03-2026

Latest Decision Or Authorization Date

23-04-2026

Processing Time Days

42

Number Of Sites

11

Number Of Participants

21

Germany

Earliest CTIS Part Ii Submission Date

27-02-2026

Latest Decision Or Authorization Date

13-04-2026

Processing Time Days

45

Number Of Sites

4

Number Of Participants

9

Poland

Earliest CTIS Part Ii Submission Date

25-03-2026

Latest Decision Or Authorization Date

20-04-2026

Processing Time Days

26

Number Of Sites

4

Number Of Participants

12

Czechia

Earliest CTIS Part Ii Submission Date

08-04-2026

Latest Decision Or Authorization Date

23-04-2026

Processing Time Days

15

Number Of Sites

3

Number Of Participants

6

Primary sponsor

Full Name

Praxis Precision Medicines Inc.

Organisation Type

Pharmaceutical company

Country Of Registered Address

United States

Contract research organisations

Name

Pivotal S.L.

Responsibilities

Sponsor duties codes: 1,12,13,2,5 (as listed in CTIS third parties).

Name

PPD Global Central Labs

Responsibilities

Sponsor duties codes: 4 (central laboratory services).

Name

Medrio Inc.

Responsibilities

Sponsor duties codes: 7 (electronic data capture/eConsent vendor as per listed third parties).

Third parties

• {"country":"United States","full_name":"Greenphire LLC","duties_or_roles":"Patient reimbursement of travel/meal expenses","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Medrio Inc.","duties_or_roles":"Sponsor duties codes: 7","organisation_type":"Pharmaceutical company"}
• {"country":"Belgium","full_name":"PPD Global Central Labs","duties_or_roles":"Sponsor duties codes: 4","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Pharmastart , LLC dba Firma Clinical Research","duties_or_roles":"Home Health Vendor","organisation_type":"Health care"}
• {"country":"United States","full_name":"Mms Holdings Inc.","duties_or_roles":"Sponsor duties codes: 8","organisation_type":"Pharmaceutical company"}
• {"country":"Spain","full_name":"Pivotal S.L.","duties_or_roles":"Sponsor duties codes: 1,12,13,2,5","organisation_type":"Pharmaceutical company"}
• {"country":"Ireland","full_name":"Transcrip Ireland Limited","duties_or_roles":"Sponsor duties codes: 12","organisation_type":"Pharmaceutical company"}