Brivaracetam for Absence Epilepsy

(EXPAND Trial)

Recruiting at 35 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

Trial Summary

What is the purpose of this trial?

This trial is testing if the drug brivaracetam, used alone, is safe and effective for children and young adults aged 2 to 25 with certain types of epilepsy. The drug works by helping to control brain activity to prevent seizures.

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 Brivaracetam safe for humans?

Brivaracetam has been studied for safety in both children and adults with epilepsy, showing it is generally well-tolerated as an add-on therapy for seizures. While specific safety data for absence epilepsy is still being evaluated, existing studies suggest it is safe for use in humans. ^{1 2 3 4 5}

How is the drug brivaracetam unique for treating absence epilepsy?

Brivaracetam is unique because it is being studied as a monotherapy (single drug treatment) for absence epilepsy, which is different from its usual use as an add-on therapy for other types of epilepsy. It binds to a specific protein in the brain with higher selectivity and affinity than similar drugs, potentially offering a new option for patients with limited treatment choices. ^{1 2 6 7 8}

Research Team

UCB Cares

Principal Investigator

001 844 599 2273 (UCB)

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

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]

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]

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]

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 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]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

Brivaracetam: First Global Approval. [2018]

2. United States pubmed.ncbi.nlm.nih.gov

Efficacy and tolerability of brivaracetam monotherapy in childhood and juvenile absence epilepsy: An innovative adaptive trial design. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Brivaracetam (Briviact): A Novel Adjunctive Therapy for Partial-Onset Seizures. [2020]

4. Iran pubmed.ncbi.nlm.nih.gov

Brivaracetam in treating epileptic encephalopathy and refractory focal epilepsies in patients under 14 years of age. [2022]

5. United States 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. [2023]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Brivaracetam in the Treatment of Patients with Epilepsy-First Clinical Experiences. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

Retention of brivaracetam in adults with drug-resistant epilepsy at a single tertiary care center. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Brivaracetam add-on therapy for drug-resistant epilepsy. [2022]