Brivaracetam for Absence Epilepsy

(EXPAND Trial)

Recruiting at 42 trial locations

Overseen By UCB Cares

Age: < 65

Sex: Any

Trial Phase: Phase 3

Sponsor: UCB Biopharma SRL

Must not be taking: Rifampin, Fluconazole, others

Disqualifiers: Nonfebrile seizures, Hepatic impairment, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 5 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

160 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to evaluate the effectiveness and safety of brivaracetam for treating absence epilepsy, a condition causing brief, sudden lapses in attention. The study includes several groups testing different doses of brivaracetam to identify the most effective one. Individuals who have experienced frequent absence seizures for at least three days a week and have been diagnosed with childhood or juvenile absence epilepsy may be suitable candidates for this trial. As a Phase 3 trial, it represents the final step before FDA approval, offering participants the opportunity to contribute to a potentially groundbreaking treatment.

Will I have to stop taking my current medications?

If you are currently taking antiepileptic drugs (AEDs), you must stop them for a period of at least 5 half-lives of the AED before joining the study. If you are taking psychoactive drugs, you need to be on a stable dose for at least 2 weeks before joining. Also, you cannot use certain medications like rifampicin or strong CYP2C19 inhibitors close to the study start.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that brivaracetam is generally safe and well-tolerated for both children and adults with epilepsy. The FDA has already approved it for treating focal (partial) seizures in young children, indicating a strong safety record.

Studies identified the most common side effects as sleepiness, headache, and dizziness, which are usually mild. Long-term research also demonstrates that brivaracetam is effective for children with various types of seizures.

Overall, evidence suggests that brivaracetam is a well-tolerated treatment option for epilepsy. However, like any medication, it may have some side effects. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for epilepsy?

Researchers are excited about brivaracetam for absence epilepsy because it offers a new approach to managing seizures. Unlike traditional treatments like ethosuximide, valproate, and lamotrigine, which have been the mainstay for absence epilepsy, brivaracetam targets synaptic vesicle protein 2A (SV2A) in the brain. This new mechanism of action could potentially lead to more effective seizure control with fewer side effects. Additionally, the ability to fine-tune the dosage, as seen in the trial's exploration of optimal dosing, suggests personalized treatment possibilities that could enhance its effectiveness and safety for patients.

What evidence suggests that brivaracetam might be an effective treatment for absence epilepsy?

Research has shown that brivaracetam can help with various types of seizures. It has proven effective for individuals with focal-onset seizures and generalized-onset seizures, similar to absence seizures. In one study, more than half of the participants taking doses between 50 to 200 mg per day responded positively to the treatment. The medication was well tolerated, with most participants experiencing no serious side effects. In this trial, participants will receive different doses of brivaracetam, including 100 mg and 200 mg, to evaluate its effectiveness for absence epilepsy. These findings suggest that brivaracetam might also be beneficial for absence epilepsy. ^{3 5 6 7 8}

Who Is on the Research Team?

UCB Cares

Principal Investigator

001 844 599 2273 (UCB)

Are You a Good Fit for This Trial?

This trial is for children and young adults aged 2 to 25 with childhood absence epilepsy (CAE) or juvenile absence epilepsy (JAE). Participants must have frequent seizures, be off psychoactive drugs or on a stable dose, and not have used certain antiepileptic drugs recently. They need normal neurological function and an EEG showing specific seizure patterns. Those under 4 years old require a negative GLUT1DS genetic test.

Inclusion Criteria

I agree to use contraception and not donate sperm during and for 2 days after treatment.

I have been diagnosed with CAE or JAE according to ILAE criteria.

I am not pregnant or breastfeeding and can follow the study's birth control advice if needed.

Exclusion Criteria

The doctor in charge of the study thinks there is a heart problem based on the ECG test.

My liver is not working properly.

I stopped taking strong CYP2C19 inhibitors like fluconazole a week ago.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2 weeks

Placebo-Controlled Period

Participants receive either placebo or brivaracetam during this period

2 weeks

1 visit (in-person)

Active Treatment Period

Participants receive brivaracetam at the assigned dose

11 weeks

Multiple visits (in-person)

Randomized Withdrawal Period

Participants who are seizure-free continue with brivaracetam or placebo

4 weeks

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

up to 4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Brivaracetam
• Placebo

Trial Overview The study tests the effectiveness, safety, and tolerability of brivaracetam as a single treatment compared to placebo in participants with CAE or JAE. It aims to see if brivaracetam can help control seizures without causing significant side effects.

How Is the Trial Designed?

Group I: Placebo to BRV optimal dose (defined following Stage 1) Experimental Treatment 2 Interventions

Placebo-Controlled (PC) and Active Treatment (AT) Period: Stage 2: Study participants will be randomized in Stage 2 of the study to 'placebo to BRV optimal dose'. Study participants randomized to placebo to brivaracetam (BRV) optimal dose will receive placebo during the PC period followed by BRV optimal dose during the AT period.

Group II: Placebo to 200 mg brivaracetam Experimental Treatment 2 Interventions

Placebo-Controlled (PC) and Active Treatment (AT) Period: Stage 1: Study participants randomized to 'placebo to BRV 200mg/day' (or equivalent dose) will receive placebo during the PC period followed by BRV 200mg/day (or equivalent dose) during the AT period.

Group III: Placebo to 100 mg brivaracetam Experimental Treatment 2 Interventions

Placebo-Controlled (PC) and Active Treatment (AT) Period: Stage 1: Study participants randomized to 'placebo to BRV 100mg/day' (or equivalent dose) will receive placebo during the PC period followed by BRV 100mg/day (or equivalent dose) during the AT period.

Group IV: Placebo received during RDW Experimental Treatment 2 Interventions

Randomized Withdrawal (RDW) Period: Only study participants who are absence seizure-free based on the outcome of the 24h EEG of Visit 5 will enter the RDW Period. Study participants who are randomized to the placebo arm in the RDW Period will be tapered down to 0 mg and receive 0 mg for 2 weeks.

Group V: Optimal dose of BRV (defined following Stage 1) Experimental Treatment 1 Intervention

Placebo-Controlled (PC) and Active Treatment Period (AT): Stage 2: Study participants will be randomized in Stage 2 to receive a fixed dose of the optimal dose of brivaracetam (defined following Stage 1). Study participants randomized to the BRV optimal dose will receive this dose during the 2-week PC period and subsequent 11-week AT period.

Group VI: Brivaracetam received during RDW Experimental Treatment 1 Intervention

Randomized Withdrawal (RDW) Period: Only study participants who are absence seizure-free based on the outcome of the 24h EEG of Visit 5 will enter the RDW Period. Participants who are randomized to this arm will continue on the Brivaracetam dose they were receiving in the AT period.

Group VII: Brivaracetam 200 mg Experimental Treatment 1 Intervention

Placebo-Controlled (PC) and Active Treatment (AT) Period: Stage 1: Study participants randomized to brivaracetam (BRV) 200mg/day (or equivalent dose) will receive these doses during the 2-week PC period and subsequent 11-week AT period.

Group VIII: Brivaracetam 100 mg Experimental Treatment 1 Intervention

Placebo-Controlled (PC) and Active Treatment (AT) Period: Stage 1: Study participants randomized to BRV 100mg/day (or equivalent dose) will receive these doses during the 2-week PC period and subsequent 11-week AT period.

Brivaracetam is already approved in European Union, United States, Canada for the following indications:

Approved in European Union as Briviact for:

• Partial-onset seizures with or without secondary generalisation

Approved in United States as Briviact for:

• Focal (partial) onset seizures in epilepsy patients 1 month of age and older

Approved in Canada as Brivlera for:

• Partial-onset seizures with or without secondary generalisation

Who Is Running the Clinical Trial?

UCB Biopharma SRL

Lead Sponsor

Trials

118

Recruited

23,200+

Jean-Christophe Tellier

UCB Biopharma SRL

Chief Executive Officer since 2015

MD from University of Reims Champagne-Ardenne, Rheumatology specialization from University of Paris V, Executive business programs at Harvard and INSEAD

Dr. Iris Loew-Friedrich

UCB Biopharma SRL

Chief Medical Officer since 2014

MD from University of Leuven, PhD in Medical Sciences from University of Leuven

Published Research Related to This Trial

In a study of 200 adults with focal epilepsy treated with brivaracetam (BRV) over an average follow-up of 707 days, only 6.5% achieved seizure freedom for at least six months, while 23% experienced a significant reduction in seizure frequency.

BRV was generally well-tolerated compared to levetiracetam (LEV), with fewer side effects reported; however, 51% of discontinuations were due to side effects, particularly in patients also taking carbamazepine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Retention of brivaracetam in adults with drug-resistant epilepsy at a single tertiary care center. Green, SF., Hare, N., Kassam, M., et al.[2022]

Brivaracetam, as an add-on therapy for drug-resistant epilepsy, significantly reduces seizure frequency and increases the likelihood of achieving seizure freedom, based on a review of six trials with 2411 participants.

While brivaracetam is effective, it is associated with a higher rate of treatment withdrawals due to adverse events compared to placebo, indicating that while it can help manage seizures, some patients may experience side effects that lead them to stop treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brivaracetam add-on therapy for drug-resistant epilepsy. Bresnahan, R., Panebianco, M., Marson, AG.[2022]

In a study of 228 adult patients with epilepsy treated with brivaracetam (BRV) over 12 months, 46.3% experienced a significant reduction in seizure frequency, indicating that BRV can be an effective add-on therapy for managing seizures in a real-world setting.

While BRV showed promising results, particularly in maintaining early responses, the most common side effects included sedation and cognitive slowing, affecting 14.5% of patients, highlighting the need for careful monitoring of tolerability.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The efficacy and tolerability of adjunctive brivaracetam for the treatment of adult epilepsy: An Australian multi-center retrospective real-world observational cohort study. Halliday, AJ., Vogrin, S., Ignatiadis, S., et al.[2023]

Brivaracetam, approved in the EU for treating partial-onset seizures, binds more selectively and with 15- to 30-fold higher affinity to the synaptic vesicle glycoprotein 2a (SV2A) compared to levetiracetam, which may enhance its therapeutic effects.

Clinical trials have shown that brivaracetam effectively reduces the frequency of partial-onset seizures, supporting its use as an adjunctive therapy for adults with uncontrolled epilepsy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brivaracetam: First Global Approval. Markham, A.[2018]

Brivaracetam (Briviact) is a new treatment option specifically designed as an adjunctive therapy for patients experiencing partial-onset seizures.

Clinical studies have demonstrated that brivaracetam effectively reduces seizure frequency, making it a valuable addition to existing epilepsy treatment regimens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brivaracetam (Briviact): A Novel Adjunctive Therapy for Partial-Onset Seizures. Khaleghi, F., Nemec, EC.[2020]

The ongoing phase 2/3 trial is evaluating the efficacy, safety, and tolerability of brivaracetam (BRV) as a monotherapy for childhood absence epilepsy (CAE) and juvenile absence epilepsy (JAE) in patients aged 2-25, using a two-stage adaptive design to optimize dosing and reduce trial duration.

This trial includes a robust assessment of seizure activity through 24-hour EEG monitoring and seizure diaries, which will help determine the effectiveness of BRV and may provide a new treatment option for these epilepsy types.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and tolerability of brivaracetam monotherapy in childhood and juvenile absence epilepsy: An innovative adaptive trial design. Bast, T., Schulz, AL., Floricel, F., et al.[2022]

In a study of 93 epilepsy patients treated with brivaracetam (BRV), 35.1% of those with more than one seizure per month became responders, with 8.8% achieving complete seizure freedom after an average follow-up of about 4.85 months.

Switching from levetiracetam (LEV) to BRV significantly reduced adverse events, particularly behavioral ones, suggesting that BRV is a safer alternative for patients, especially those with psychiatric comorbidities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brivaracetam in the Treatment of Patients with Epilepsy-First Clinical Experiences. Zahnert, F., Krause, K., Immisch, I., et al.[2022]

In a study of eight pediatric patients with epileptic encephalopathy or unresponsive focal epilepsy, Brivaracetam (BRV) was found to be effective, with all patients experiencing at least a 50% reduction in seizure frequency, and 37.5% becoming seizure-free.

Brivaracetam was particularly effective for patients with epilepsy onset greater than 12 months and a duration of less than 6 years, showing a positive impact on seizures during sleep without significant side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brivaracetam in treating epileptic encephalopathy and refractory focal epilepsies in patients under 14 years of age. Russo, A., Cuteri, V., Bansal, L., et al.[2022]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40614390/

Brivaracetam effectiveness and patient-reported outcomes ... Brivaracetam was effective in patients with difficult-to-control focal-onset seizures; as shown by brivaracetam retention at 12 months.

2. sciencedirect.com sciencedirect.com/science/article/pii/S1525505025003099

Long-term tolerability and efficacy of adjunctive ... In this study, BRV treatment was well tolerated and efficacious in children with generalized-onset seizures. Behavior and emotional functioning scores were ...

3. withpower.com withpower.com/trial/phase-3-epilepsy-6-2021-52d6a

Brivaracetam for Absence Epilepsy (EXPAND Trial) In a study of 200 adults with focal epilepsy treated with brivaracetam (BRV) over an average follow-up of 707 days, only 6.5% achieved seizure freedom for at ...

4. epilepsybehavior.com epilepsybehavior.com/article/S1525-5050(25)00309-9/pdf

Subgroup a - Epilepsy & Behavior Conclusions: Long-term adjunctive brivaracetam was well tolerated and efficacious in children with generalized- onset seizures. Behavior/ ...

5. seizure-journal.com seizure-journal.com/article/S1059-1311(22)00234-5/pdf

Narrative review of brivaracetam for genetic generalized ... Results: Promising results were found with doses ranging from 50 to 200 mg/day in terms of efficacy (with > 50% responder rates between 36 and ...

6. epilepsy.com epilepsy.com/tools-resources/seizure-medication-list/brivaracetam

Brivaracetam Basic Seizure Medication Brivaracetam is FDA approved for use for treatment of focal (partial) seizures in children down to 1 month of age. This approval was based on safety data in ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9886169/

Brivaracetam to Treat Partial Onset Seizures in Adults - PMC The most commonly reported adverse effects that patients who were taking brivaracetam experienced were somnolence, headache, and dizziness.

8. epilepsybehavior.com epilepsybehavior.com/article/S1525-5050(19)30822-4/pdf

Safety and tolerability of adjunctive brivaracetam in epilepsy The current summary provides an in-depth, comprehensive analysis of pooled safety data from two phase II dose-ranging trials [6,7], three fixed- ...