Evaluation of Brivaracetam Monotherapy Efficacy and Safety in Pediatric and Young Adult Patients with Childhood or Juvenile Absence Epilepsy

The primary objective of this study is to **investigate the efficacy** of brivaracetam monotherapy in participants aged 2 to 25 years with Childhood Absence Epilepsy (CAE) or Juvenile Absence Epilepsy (JAE). This is clinically relevant as it aims to determine the effectiveness of brivaracetam in managing these specific types of epilepsy, potentially offering a targeted treatment option for this age group.

Secondary objectives include evaluating the **safety and tolerability** of brivaracetam monotherapy in the same participant group. Assessing safety and tolerability is crucial to ensure that the treatment is not only effective but also safe for long-term use in young patients.

The clinical trial involves a total of **90 participants** diagnosed with either **childhood absence epilepsy** (CAE) or **juvenile absence epilepsy** (JAE), as defined by the International League Against Epilepsy (ILAE) criteria. The study population includes both male and female subjects, ranging in age from 2 to 25 years. Participants are required to have a normal neurological examination, head size, development, and cognition, and must weigh at least 9 kg. The trial includes individuals who are untreated with antiepileptic drugs (AEDs) or have been pretreated with a maximum of two historical AEDs, provided they have not received AED treatment for a period of at least five half-lives of the AED before randomization. Participants must have electroencephalogram (EEG) evidence of bilateral synchronous, symmetric generalized paroxysmal spike waves with normal background activity and a history of clinically evident absence seizures occurring on at least three days per week in the two weeks prior to enrollment. The trial population was selected based on these criteria, ensuring that participants are without treatment with psychoactive drugs or are on a stable dose for at least two weeks prior to randomization. The study also includes vulnerable populations, and all participants or their legal representatives have provided informed consent. Lifestyle considerations such as diet and physical activity are not specified in the available data.

The clinical trial is designed to evaluate the **efficacy**, safety, and tolerability of **brivaracetam** as monotherapy in patients aged 2 to 25 years with childhood absence epilepsy or juvenile absence epilepsy. This study employs a randomized, double-blind, placebo-controlled, parallel-group multicenter approach with a two-stage adaptive design and randomized withdrawal. The trial is expected to span from March 2022 to February 2027, with participant involvement lasting up to 19 weeks. The study will include an initial screening visit, followed by multiple follow-up visits, and conclude with an end-of-study visit. The primary endpoint is the percentage of participants achieving absence seizure freedom within 4 days prior to or during the 24-hour ambulatory electroencephalogram (EEG) at Day 14. Secondary endpoints include various measures of seizure freedom and treatment-emergent adverse events.

Participants will be required to attend a screening visit to confirm eligibility, which includes criteria such as age, diagnosis, and EEG evidence of seizures. Following randomization, participants will undergo regular follow-up visits to monitor treatment response and safety. The end-of-study visit will assess the overall outcomes and any adverse events. Participants may be withdrawn from the study early if they experience significant adverse events or fail to comply with study protocols. The trial aims to provide comprehensive data on the use of brivaracetam in this patient population, contributing to the understanding of its potential as a treatment option for absence epilepsy.

The clinical trial involves the administration of **brivaracetam**, an experimental medication, in the form of an **oral solution**. The active substance, brivaracetam, is chemically derived and produced by UCB Biopharma SRL. The maximum daily dose of brivaracetam is 200 mg, with a total maximum dose of 200 mg over a treatment period of 19 days. The medication is administered orally, and the trial aims to evaluate its efficacy, safety, and tolerability as monotherapy in patients aged 2 to 25 years with childhood absence epilepsy or juvenile absence epilepsy. Participant compliance with the dosing schedule will be monitored throughout the study.

In addition to the experimental treatment, a **placebo** matching the brivaracetam oral solution is used in the study. The placebo does not contain any active substance and serves as a control to assess the efficacy of the experimental medication. The placebo is administered in the same manner as the brivaracetam oral solution, ensuring blinding in the double-blind, placebo-controlled study design.

Non-experimental treatments in the study include **benzodiazepine derivatives**, categorized under ATC codes N05CD, N03AE, and N05BA. These substances are used as auxiliary treatments and are not the primary focus of the trial. The pharmaceutical forms of these derivatives are coded as PHF00245MIG, PHF00221MIG, and PHF00006MIG, respectively. The specific routes of administration for these substances are not defined in the trial data, and their use is limited to a maximum treatment period of 1 day. These auxiliary treatments are included to support the study's objectives and ensure comprehensive evaluation of the experimental medication's effects.

The efficacy of **brivaracetam** as monotherapy in patients with childhood absence epilepsy (CAE) or juvenile absence epilepsy (JAE) will be assessed through a series of primary and secondary endpoints. The primary endpoint is the percentage of participants who achieve absence seizure freedom within 4 days prior to or during the 24-hour ambulatory electroencephalogram (EEG) at Day 14. Secondary endpoints include:

• Percentage of participants who achieve absence seizure freedom during the randomized withdrawal period as determined by EEG.
• Percent change from Baseline to Day 14 in the number of absence seizures on a 24-hour ambulatory EEG.
• Percentage of participants who achieve absence seizure freedom based on diary entries during the 4 days prior to the visit at Day 14.
• Percentage of participants who achieve absence seizure freedom on a 24-hour ambulatory EEG at Week 12.
• Percentage of participants who achieve absence seizure freedom based on diary entries during the 4 days prior to the visit at Week 12.
• Percentage of participants with treatment-emergent adverse events (TEAEs) during the study.
• Percentage of participants with TEAEs leading to discontinuation of study treatment.
• Percentage of participants with serious adverse events (SAEs) during the study.
• Percentage of participants with drug-related TEAEs during the study.

These efficacy parameters will be measured using validated tools such as the 24-hour ambulatory EEG and patient diaries. The assessments will be conducted at specified timepoints, including Day 14 and Week 12, to evaluate the treatment's impact on seizure frequency and freedom. The data collected will be analyzed to determine the efficacy of brivaracetam in achieving seizure control in the target population.