Título: Un ensayo multicéntrico, aleatorizado y doble ciego para evaluar la eficacia y la seguridad de PRAX-628 en adultos con convulsiones focales (POWER 1)

Especialidad: Neurología

Código de protocolo: PRAX-628-321

Número EudraCT: 2024-514559-13-00

Promotor: Praxis

Investigador principal: Dr. Ángel Aledo

Más información:

CRO: Pivotal

Criterios de inclusión: Participant and care giver, if applicable, is willing to sign an informed consent document in accordance with International Council for Harmonization (ICH)/Good Clinical Practice (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 use of appropriate contraception (as defined in Section 5.4.2), and is willing to participate in the clinical trial.
Aged 18 to 75 years of age at the time of consent.
A diagnosis of focal onset epilepsy according to the International League Against Epilepsy (ILAE) Classification of Epilepsy (2017).
Prior to randomization, past evidence by computed tomography (CT) or magnetic resonance imaging (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 (none listed as a prohibited concomitant medication in Table 10) for at least 4 weeks prior to screening (SC1).
Participant and/or their care giver reports at least 4 countable focal onset seizures in the 4 weeks immediately prior to screening (SC1) and records at least 8 countable focal onset seizures during the Screening/Observation Period. Countable focal seizures are defined as: (1) focal aware seizures with clear observable signs, (2) focal seizures with impaired awareness, or (3) focal to bilateral tonic-clonic seizures.
Seizure diary completion must occur on 80% days in the Screening/Observation Period.
The participant may not be seizure-free for a single period of more than 21 consecutive days during the 9-week Screening/Observation Period. The seizure distribution throughout this period will be evaluated to avoid including patients with only clustering seizures.eizure distribution throughout this period will be evaluated to avoid including patients with only clustering seizures.

Criterios de exclusión: History of pseudo or psychogenic seizures, or cluster seizures only, within the 12-month period preceding trial entry where the individual seizures cannot be counted, or an episode of convulsive status epilepticus requiring hospitalization and intubation in the 12 months prior to Screening.
Seizures secondary to illicit drug or alcohol use, ongoing infection, neoplasia, demyelinating disease or central nervous system disease deemed progressive, metabolic illness, or progressive degenerative disease, progressive structural lesion or encephalopathy.
Planned epilepsy surgery during the course of the clinical trial.
History of neurosurgery for seizures <1 year prior to enrollment, or radiosurgery <2 years prior to enrollment or vagus nerve stimulation (VNS) implantation.
Schizophrenia, obsessive-compulsive disorder, or other serious mental health disorders. Uncontrolled unipolar major depression where changes in pharmacotherapy are needed or anticipated during the trial.
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 Columbia-Suicide Severity Rating Scale (C-SSRS).
Has any significant ongoing disease, disorder, psychiatric, medical, or surgical condition, laboratory abnormalities, alcohol or drug abuse or dependence, or environmental factor at Screening that in the judgement of the investigator in consultation with the medical monitor and/or sponsor designee, might jeopardize the participants safety or interfere with the absorption, distribution, metabolism or excretion of PRAX-628; or impact the clinical trial objectives; or interfere with participation in the clinical trial.
History of malignancy, myeloproliferative or lymphoproliferative disorders within the past 5 years are excluded. Exceptions:1) Participants with completely excised non-melanoma skin cancer (such as basal cell carcinoma or squamous cell carcinoma) or cervical carcinoma in situ are permitted at any time 2) Participants with a history of other malignancies deemed cured by adequate treatment are also permitted at any time 3) low grade prostate cancer with Gleason score 2.
History of cardiac disease(s)/cardiac conduction disorders/or cardiac structural abnormality(ies) (eg, atrial or ventricular septal defects, valvular heart disease, coarctation of the aorta, left bundle branch block, arrhythmias, Brugada syndrome, congenital heart disease, familial short QT syndrome, or hypertrophic obstructive cardiomyopathy) or family history of sudden death or ventricular arrhythmias, including idiopathic ventricular fibrillation. (non-clinically significant patent foramen ovale [PFO] is not considered exclusionary).
Has any of the following: persistently abnormal test results at Screening: a serum total bilirubin value >1.5×upper limit of normal (ULN); a serum alanine aminotransferase (ALT) or aspartate aminotransferase (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 Gilberts syndrome may be enrolled after discussion with the medical monitor and/or sponsor designee if their conjugated bilirubin is below the ULN.
Has a positive test result or a known history of a positive test result for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or anti- hepatitis C virus (HCV) antibody at Screening.
Is pregnant or is 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 within 190 days of the last study drug dose.
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 therapy.
Use of vigabatrin in the last 5 years without stable visual fields tested twice over the 12 months after the last dose of vigabatrin.
Use of 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 participant received felbamate in the past, it must have been discontinued at least 2 months prior to Screening.
Participant is receiving a prohibited medication as per the prohibited concomitant medications section (Section 6.4.1).
History of allergies or a severe reaction to an ASM(s), including dermatological (eg, Stevens-Johnson syndrome), hematological, or organ toxicity reactions.
If on a ketogenic or other diet for management of seizures, must have started the diet at least 3 months prior to Screening with stable parameters for at least 1 month prior to Screening, with the intention to remain on a stable diet throughout the trial; diets are not counted as an ASM.

Centro: Vithas Madrid La Milagrosa