Efficacy and Safety Evaluation of PRAX-628 in Adults with Focal Epilepsy: A Double-Blind, Randomized, Multicenter Trial
- Trial ID
- 2024-514559-13-00
- Protocol
- PRAX-628-321
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to evaluate the **efficacy** of PRAX-628 compared to placebo on focal seizure frequency in adults with **Focal Epilepsy** who are currently taking 1 to 3 anti-seizure medications (ASMs). This is clinically relevant as it aims to determine the potential of PRAX-628 to reduce seizure frequency, which is a critical outcome for improving the quality of life in patients with focal epilepsy.
Secondary objectives include:
- Evaluating the efficacy of PRAX-628 compared to placebo on focal seizure frequency in adults currently taking 1 to 3 ASMs.
- Assessing the safety and tolerability of PRAX-628 in adults with focal seizures.
- Assessing trends over time in the efficacy of PRAX-628 on focal seizure frequency.
Participants
The clinical trial involves a total of **92 participants** diagnosed with **Focal Epilepsy**. The study population includes both male and female subjects, aged between 18 and 75 years. Participants are required to have a stable health status, specifically taking 1 to 3 anti-seizure medications (ASMs) for at least four weeks prior to screening. The selection process ensured that participants had a confirmed diagnosis of focal onset epilepsy, with prior imaging ruling out progressive causes. Lifestyle considerations include maintaining a seizure diary with at least 80% completion during the screening period, and participants must report a minimum of four countable focal onset seizures in the four weeks before screening. The trial does not include vulnerable populations, and participants must not have been seizure-free for more than 21 consecutive days during the nine-week observation period. The study aims to evaluate the efficacy of PRAX-628 compared to placebo in reducing focal seizure frequency in adults currently on ASMs.
Plans and Procedures
The clinical trial is designed to evaluate the **efficacy** and safety of PRAX-628 in adults diagnosed with **focal epilepsy**. This is a double-blind, randomized, multicenter trial, which includes a placebo control group. The trial is structured to assess the impact of PRAX-628 on focal seizure frequency in participants who are currently on 1 to 3 anti-seizure medications (ASMs). The trial is expected to commence recruitment in September 2024 and conclude by September 2026, with a maximum treatment period of 12 weeks for each participant.
Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, diagnosis, and seizure history. During the screening period, participants must document at least 8 countable focal onset seizures and maintain a seizure diary with at least 80% completion. Following successful screening, participants will be randomized to receive either PRAX-628 or a placebo, administered orally in capsule form. The trial will include regular follow-up visits to monitor seizure frequency, assess treatment efficacy, and evaluate safety through clinical assessments, laboratory tests, and ECGs.
The primary endpoint of the trial is the median percent change in monthly focal seizure frequency from the screening period to the treatment period. Secondary endpoints include the proportion of participants achieving a 50% reduction in seizure frequency, the time to reach the same number of seizures as during the screening period, and the incidence of treatment-emergent adverse events (TEAEs). The trial will also assess changes in vital signs, clinical laboratory results, and suicidality. Participants' involvement is expected to last up to 12 weeks, with conditions for early termination including significant adverse events or non-compliance with study procedures.
Treatment
The clinical trial involves the administration of **PRAX-628**, an investigational medication, to evaluate its efficacy and safety in adults with focal seizures. **PRAX-628** is provided in a **capsule** form and is administered **orally**. The active substance, **PRAX-628**, is of chemical origin and is manufactured by PRAXIS PRECISION MEDICINES INC. The maximum daily dose is **50 mg**, and the treatment period extends up to **12 weeks**. Participants are required to take the medication once daily, and compliance is monitored through regular assessments and pill counts to ensure adherence to the dosing schedule.
The study also includes a **placebo** group to serve as a comparator for evaluating the efficacy of **PRAX-628**. The placebo is designed to mimic the appearance of the **PRAX-628** capsule but contains no active pharmaceutical ingredient. It is also administered **orally** and follows the same dosing schedule as the experimental medication. The use of a placebo allows for a double-blind study design, ensuring that neither the participants nor the investigators are aware of the treatment assignments, thereby reducing bias in the assessment of outcomes.
Efficacy
The clinical trial aims to evaluate the efficacy of **PRAX-628** in adults with focal seizures. Efficacy will be assessed primarily by measuring the median percent change in monthly (28 days) focal seizure frequency from the Screening/Observation Period to the Treatment Period, comparing **PRAX-628** to placebo. Secondary endpoints include the proportion of participants experiencing a ≥50% reduction in monthly focal seizure frequency, the number of days post-randomization to reach the same number of monthly focal seizures as during the Screening/Observation Period, and the impact on Patient Global Impression of Severity (PGI-S) and Clinical Global Impression of Severity (CGI-S).
Data collection will involve the use of seizure diaries, which participants and/or their caregivers must complete on at least 80% of days during the Screening/Observation Period. The trial will also monitor the incidence and severity of treatment-emergent adverse events (TEAEs), changes in vital signs, clinical laboratory results, ECG parameters, and suicidality as assessed by the Columbia-Suicide Severity Rating Scale (C-SSRS). The trial is designed as a double-blind, randomized, multicenter study, with a maximum treatment period of 12 weeks for each participant.
Inclusion and Exclusion Criteria
Inclusion Criteria
- 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).
- At least XXXX countable focal onset seizures during the Screening/Observation Period and no less than XXXXX prior to Visit 1. Countable focal seizures are defined as: (1) focal aware seizures with clear observable signs by the patient or caregiver, (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 XXXX consecutive days during the XXXX-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.
Exclusion Criteria
- Participant has had any of the following within the 12-month period preceding trial entry: − evidence of experiencing pseudo or psychogenic seizures, − cluster seizures where the individual seizures cannot be counted, − an episode of convulsive status epilepticus requiring hospitalization and intubation.
- 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 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.
- 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 participant’s 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 indolent or early-stage malignancies that are unlikely to progress or other malignancies deemed cured by adequate treatment are also permitted at any time 3) low grade prostate cancer with Gleason score ≤2.
- History or presence of uncontrolled cardiac diseases including conduction and structural abnormalities (eg, family history of sudden death, long QT syndrome, familial short QT syndrome, Brugada syndrome, or sustained ventricular arrythmia) which may place patients at increased risk determined by the investigator.
- 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 Gilbert’s 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). Evidence of active hepatitis B or hepatitis C infection, as determined by relevant screening assessments.
- 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 14 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).
- Significant allergic 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.
- Previously documented EEG which shows any pattern not consistent with focal etiology of seizures. (A new EEG is not required, if not available).
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Italy | Not Recruiting | 01 Sept 2024 | 75 |
 Poland | Not Recruiting | 01 Sept 2024 | 30 |
 Spain | Not Recruiting | 01 Sept 2024 | 65 |
Sites & Investigators
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 |
|---|---|---|---|---|---|---|
PRAX-628 | Test | CAPSULE | ORAL | 50 | 12 | PRD9990075 |
Placebo for PRAX-628 | Placebo | N/A | — | — | — | N/A |