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| ID | Type | Description | Link |
|---|---|---|---|
| 2020-002750-24 | EudraCT Number | ||
| 2023-510428-55-00 | Registry Identifier | CTIS | |
| U1111-1303-2521 | Other Identifier | Universal Trial Number (UTN) |
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The purpose of the study is to test the efficacy, safety and tolerability of brivaracetam monotherapy in study participants 2 to 25 years of age inclusive with childhood absence epilepsy (CAE) or juvenile absence epilepsy (JAE).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Brivaracetam 200 mg | Experimental | 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. |
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| Placebo to 200 mg brivaracetam | Experimental | 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. |
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| Brivaracetam 100 mg | Experimental | 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. |
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| Placebo to 100 mg brivaracetam | Experimental | 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. |
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| Optimal dose of BRV (defined following Stage 1) |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Brivaracetam | Drug |
Brivaracetam (oral solution [10 mg/ml, 5 mg/ml or 2.5 mg/ml] will be administered. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of participants who met the criteria for absence seizure freedom within 4 days prior to or during the 24-hour ambulatory electroencephalogram (EEG) at Day 14 | A 24-hour ambulatory electroencephalogram (EEG) will be performed at day 14. The awake hours from the EEG will be analyzed for absence seizures. Every 24-hour EEG will include hyperventilation as a standard provocation test at the beginning of the EEG. Patient will be regarded as not meeting the criteria for absence seizure freedom if they received benzodiazepine in the 4 days prior to the EEG or during the EEG. | Day 14 |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of participants who met the criteria for absence seizure freedom during the randomized withdrawal (RDW) period as determined by electroencephalogram (EEG) | Study participants (or their care givers) who believe they are experiencing a recurrence of absence seizures will contact the clinical site for a 1-hour EEG (with hyperventilation (HV)). If no absence seizure is observed during this 1hr EEG (locally read), the study participant will receive a 24-hour ambulatory EEG. If an absence seizure is observed during either EEG, the study participant will be considered as not Absence seizure free and leave the study. If no absence seizures are determined by 1/24hr ambulatory EEG the participant will conduct a 24-hour EEG at week 17. Patient will be regarded as not meeting the criteria for absence seizure freedom if they received benzodiazepine in the 4 days prior to the EEG or during the EEG. The awake hours from the EEG will be analyzed for absence seizures. Every 24-hour EEG will include HV as a standard provocation test at the beginning of the EEG. |
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Inclusion Criteria:
Study participant is 2 to 25 years of age inclusive, at the time of signing the informed consent. No study participants from 2 to <4 years of age will be included in Stage 1
Study participant is diagnosed with either childhood absence epilepsy (CAE) or juvenile absence epilepsy (JAE) as defined by the International League Against Epilepsy (ILAE) criteria
Study participants 2 to <4 years of age and participants who had onset of absence seizures at an age younger than 4 years must have a negative glucose transporter type 1 deficiency syndrome (GLUT1DS) genetic test
Study participant is untreated with antiepileptic drugs (AEDs) or pretreated for absence seizures with a maximum of 2 historical AEDs, but without AED treatment for a period of at least 5 half-lives of the AED before randomization into this study. The UCB study physician should be consulted if in doubt
Study participant has electroencephalogram (EEG) evidence of bilateral synchronous, symmetric generalized paroxysmal spike waves (2.5-6 hertz) with normal background activity and with at least 1 electrographically recorded seizure lasting 3 seconds or more on a 1-hour EEG with hyperventilation (HV) while awake at Visit 1 (V1), or on a historical EEG up to 12 weeks before enrollment
Study participant has a history of clinically evident absence seizures occurring on at least 3 days per week in the 2 weeks prior to enrollment
Study participant is without treatment with psychoactive drugs or on a stable dose for at least 2 weeks prior to randomization
Study participant has normal neurological examination, head size, development and cognition
Body weight is more than or equal to 9 kg
Male and female
a) A sexually active male study participant must agree to use contraception during the treatment period and for at least 2 days, corresponding to the time needed to eliminate study treatment, after the last dose of study treatment and refrain from donating sperm during this period b) A female study participant is eligible to participate if she is not pregnant, not breastfeeding, and at least 1 of the following conditions applies: The study participant is premenarchial OR A woman of childbearing potential (WOCBP) who agrees to follow the contraceptive guidance during the treatment period and for at least 2 days after the last dose of study treatment, corresponding to the time needed to eliminate study treatment
Study participant provides consent/assent, and the study participant's parent/legal representative/caregiver provides signed informed consent for minor study participants, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| UCB Cares | 001 844 599 2273 (UCB) | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| N01269 115 | Birmingham | Alabama | 35233 | United States | ||
| N01269 105 |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 35844134 | Result | Bast T, Schulz AL, Floricel F, Morita D, Cleveland JM, Elshoff JP. Efficacy and tolerability of brivaracetam monotherapy in childhood and juvenile absence epilepsy: An innovative adaptive trial design. Epilepsia Open. 2022 Dec;7(4):588-597. doi: 10.1002/epi4.12628. Epub 2022 Aug 4. |
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Data from this trial may be requested by qualified researchers six months after product approval in the US and/or Europe, or global development is discontinued, and 18 months after trial completion. Investigators may request access to anonymized individual patient-level data and redacted trial documents which may include: analysis-ready datasets, study protocol, annotated case report form, statistical analysis plan, dataset specifications, and clinical study report. Prior to use of the data, proposals need to be approved by an independent review panel at www.Vivli.org and a signed data sharing agreement will need to be executed. All documents are available in English only, for a prespecified time, typically 12 months, on a password protected portal. This plan may change if the risk of re-identifying trial participants is determined to be too high after the trial is completed; in this case and to protect participants, individual patient-level data would not be made available.
Data from this trial may be requested by qualified researchers six months after product approval in the US and/or Europe or global development is discontinued, and 18 months after trial completion.
Qualified researchers may request access to anonymized IPD and redacted study documents which may include: raw datasets, analysis-ready datasets, study protocol, blank case report form, annotated case report form, statistical analysis plan, dataset specifications, and clinical study report. Prior to use of the data, proposals need to be approved by an independent review panel at www.Vivli.org and a signed data sharing agreement will need to be executed. All documents are available in English only, for a pre-specified time, typically 12 months, on a password protected portal.
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| Experimental |
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. |
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| Placebo to BRV optimal dose (defined following Stage 1) | Experimental | 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. |
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| Brivaracetam received during RDW | Experimental | 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. |
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| Placebo received during RDW | Experimental | 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. |
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| Placebo | Other | Subjects will receive placebo at pre-specified time-points to maintain the blinding. |
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| From Week 13 to Week 17 |
| Percent change from Baseline to Day 14 in number of absence seizures on 24-hour ambulatory electroencephalogram (EEG) | A 24-hour ambulatory electroencephalogram (EEG) will be performed at baseline and day 14. The awake hours from the EEG will be analyzed for absence seizures. Every 24-hour EEG will include hyperventilation as a standard provocation test at the beginning of the EEG. This endpoint is the difference between the number of seizures at baseline and Day 14. | From Baseline to Day 14 |
| Percentage of participants who met the criteria for absence seizure freedom based on diary during the 4 days prior to the visit at Day 14 | During the study subjects will keep a diary to record daily seizure activity from Visit 1 until end of the randomized withdrawal (RDW) Period. Each seizure type experienced will be recorded. The last 4 study days prior to Day 14 EEG are used for this endpoint. Patient will be regarded as not meeting the criteria for absence seizure freedom if they received benzodiazepine in the 4 days prior to the EEG or during the EEG. | Day 14 |
| Percentage of participants who met the criteria for absence seizure freedom on 24-hour ambulatory electroencephalogram (EEG) at Week 12 | A 24-hour ambulatory electroencephalogram (EEG) will be performed at day 14. The awake hours from the EEG will be analyzed for absence seizures. Every 24-hour EEG will include hyperventilation as a standard provocation test at the beginning of the EEG. Patient will be regarded as not meeting the criteria for absence seizure freedom if they received benzodiazepine in the 4 days prior to the EEG or during the EEG. | Week 12 |
| Percentage of participants who met the criteria for absence seizure freedom based on diary during the 4 days prior to the visit at Week 12 | During the study subjects will keep a diary to record daily seizure activity from Visit 1 until end of the randomized withdrawal (RDW) Period. Each seizure type experienced will be recorded. The last 4 study days prior to Week 12 EEG are used for this endpoint. Patient will be regarded as not meeting the criteria for absence seizure freedom if they received benzodiazepine in the 4 days prior to the EEG or during the EEG. | Week 12 |
| Percentage of participants with treatment-emergent adverse events (TEAEs) during the study | An adverse event (AE) is defined as any untoward medical occurrence, unintended disease or injury, or untoward clinical signs (including abnormal laboratory finding) in study participants, users, or other persons, whether or not related to the investigational medicinal product (IMP). | From Day 1 until End of Safety Follow-Up (up to Week 23) |
| Percentage of participants with treatment-emergent adverse events (TEAEs) leading to discontinuation of study treatment | An adverse event (AE) is defined as any untoward medical occurrence, unintended disease or injury, or untoward clinical signs (including abnormal laboratory finding) in study participants, users, or other persons, whether or not related to the investigational medicinal product (IMP). | From Day 1 until End of Down Titration Period (up to Week 21) |
| Percentage of participants with serious adverse events (SAEs) during the study | A Serious Adverse Event (SAE) is any untoward medical occurrence that at any dose:
| From Screening Period (Day -14 to Day -2) until End of Safety Follow-Up (up to Week 23) |
| Percentage of participants with drug-related treatment-emergent adverse events (TEAEs) during the study | An adverse event (AE) is defined as any untoward medical occurrence, unintended disease or injury, or untoward clinical signs (including abnormal laboratory finding) in study participants, users, or other persons, whether or not related to the investigational medicinal product (IMP). 'Drug related AEs' are the subset of AEs that the investigator considers as related to the study drug. | From Baseline (Day -1) until End of Safety Follow-Up (up to Week 23) |
| Orange |
| California |
| 92868-3874 |
| United States |
| N01269 116 | Denver | Colorado | 80202 | United States |
| N01269 111 | Miami | Florida | 33155-3009 | United States |
| N01269 101 | Tampa | Florida | 33612 | United States |
| N01269 104 | Winter Park | Florida | 32789 | United States |
| N01269 110 | Augusta | Georgia | 30912 | United States |
| N01269 100 | New Brunswick | New Jersey | 08901 | United States |
| N01269 109 | Winston-Salem | North Carolina | 27109 | United States |
| N01269 106 | Philadelphia | Pennsylvania | 19134 | United States |
| N01269 400 | Tbilisi | Georgia |
| N01269 401 | Tbilisi | Georgia |
| N01269 402 | Tbilisi | Georgia |
| N01269 403 | Tbilisi | Georgia |
| N01269 405 | Tbilisi | Georgia |
| N01269 323 | Messina | Italy |
| N01269 321 | Milan | Italy |
| N01269 324 | Milan | Italy |
| N01269 320 | Pavia | Italy |
| N01269 322 | Roma | Italy |
| N01269 325 | Roma | Italy |
| N01269 326 | Verona | Italy |
| N01269 562 | Bucharest | Romania |
| N01269 563 | Bucharest | Romania |
| N01269 560 | Iași | Romania |
| N01269 561 | Timişoara, Judeţ Timiş | Romania |
| N01269 632 | Bardejov | Slovakia |
| N01269 630 | Dubnica nad Váhom | Slovakia |
| N01269 631 | Nové Zámky | Slovakia |
| N01269 354 | Terrassa | Spain |
| N01269 600 | Dnipro | Ukraine |
| N01269 601 | Dnipro | Ukraine |
| N01269 604 | Kharkiv | Ukraine |
| N01269 607 | Uzhhorod | Ukraine |
| N01269 602 | Vinnytsia | Ukraine |
| ID | Term |
|---|---|
| D004832 | Epilepsy, Absence |
| D004827 | Epilepsy |
| ID | Term |
|---|---|
| D004829 | Epilepsy, Generalized |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D000073376 | Epileptic Syndromes |
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| ID | Term |
|---|---|
| C482793 | brivaracetam |
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