Clinical trial NCT04666610: A Study to Evaluate the Efficacy, Safety, and Tolerability of Brivaracetam as Monotherapy in Patients 2 to 25 Years of Age With Childhood Absence Epilepsy or Juvenile Absence Epilepsy
Official title: A Randomized, Dose-Finding and Confirmatory, Double-Blind, Placebo-Controlled, Parallel-Group Multicenter Study With a 2 Stage Adaptive Design and Randomized Withdrawal to Evaluate the Efficacy, Safety, and Tolerability of Brivaracetam as Monotherapy in Patients 2 to 25 Years of Age With Childhood Absence Epilepsy or Juvenile Absence Epilepsy
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Childhood Absence Epilepsy
Juvenile Absence Epilepsy
Keywords: Brivaracetam
Briviact
Epilepsy
Childhood absence Epilepsy
Juvenile absence epilepsy
CAE
JAE
Lead sponsor: UCB Pharma
Sponsor class: INDUSTRY
First posted: 2020-12-14
Enrollment: 160
Sex: ALL
Minimum age (years): 2
Maximum age (years): 25
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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).


Eligibility criteria: 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 ≥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:

* Study participant has a history of nonfebrile seizures other than absence seizures (eg, generalized tonic-clonic seizures or myoclonic seizures)
* Study participant has a history of absence status epilepticus
* Study participant has a history or presence of paroxysmal nonepileptic seizures
* Study participant has a clinically relevant electrocardiogram (ECG) abnormality in the opinion of the Principal Investigator
* Study participant has hepatic impairment (Child Pugh Score A, B, or C) based on the Investigator's assessment
* Study participant has a history of major psychiatric disease or any clinically significant medical condition that would preclude appropriate study participation
* Study participant has active suicidal ideation prior to study entry as indicated by a positive response ("Yes") to either Question 4 or Question 5 of the Columbia-Suicide Severity Rating Scale (C-SSRS; for study participants 6 years or older) or clinical judgement (for study participants younger than 6 years). The study participant should be referred immediately to a Mental Healthcare Professional
* Study participant has a lifetime history of suicide attempt (including an active attempt, interrupted attempt, or aborted attempt). The study participant should be immediately evaluated by a Mental Healthcare Professional to address safety concerns
* Study participant with known fructose intolerance or hypersensitivity of any of the ingredients in brivaracetam oral solution
* Study participant has end-stage kidney disease requiring dialysis
* Concomitant use of rifampicin/rifampin; prior use must have been stopped at least 2 months before randomization
* Concomitant use of strong CYP2C19 inhibitors like fluconazole, fluoxetine and fluvoxamine, prior use must have been stopped at least 1 week before randomization
* Study participant has participated in another study of an investigational medicinal product (IMP; and/or an investigational device) within the previous 30 days prior to informed consent
* Study participant has clinical or EEG findings not consistent with a diagnosis of childhood absence epilepsy (CAE) or juvenile absence epilepsy (JAE)

Primary outcomes:
measure: 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
timeFrame: Day 14
Secondary outcomes:
measure: Percentage of participants who met the criteria for absence seizure freedom during the randomized withdrawal (RDW) period as determined by electroencephalogram (EEG)
timeFrame: From Week 13 to Week 17
measure: Percent change from Baseline to Day 14 in number of absence seizures on 24-hour ambulatory electroencephalogram (EEG)
timeFrame: From Baseline to Day 14
measure: 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
timeFrame: Day 14
measure: Percentage of participants who met the criteria for absence seizure freedom on 24-hour ambulatory electroencephalogram (EEG) at Week 12
timeFrame: Week 12
measure: 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
timeFrame: Week 12
measure: Percentage of participants with treatment-emergent adverse events (TEAEs) during the study
timeFrame: From Day 1 until End of Safety Follow-Up (up to Week 23)
measure: Percentage of participants with treatment-emergent adverse events (TEAEs) leading to discontinuation of study treatment
timeFrame: From Day 1 until End of Down Titration Period (up to Week 21)
measure: Percentage of participants with serious adverse events (SAEs) during the study
timeFrame: From Screening Period (Day -14 to Day -2) until End of Safety Follow-Up (up to Week 23)
measure: Percentage of participants with drug-related treatment-emergent adverse events (TEAEs) during the study
timeFrame: From Baseline (Day -1) until End of Safety Follow-Up (up to Week 23)
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: N01269 115
state: Alabama
city: Long Beach
country: United States
facility: N01269 118
state: California
city: Orange
country: United States
facility: N01269 105
state: California
city: Denver
country: United States
facility: N01269 116
state: Colorado
city: Loxahatchee Groves
country: United States
facility: N01269 103
state: Florida
city: Miami
country: United States
facility: N01269 111
state: Florida
city: Tampa
country: United States
facility: N01269 101
state: Florida
city: Winter Park
country: United States
facility: N01269 104
state: Florida
city: Augusta
country: United States
facility: N01269 110
state: Georgia
city: New Brunswick
country: United States
facility: N01269 100
state: New Jersey
city: Winston-Salem
country: United States
facility: N01269 109
state: North Carolina
city: Philadelphia
country: United States
facility: N01269 106
state: Pennsylvania
city: Heidelberg
country: Australia
facility: N01269 203
city: Melbourne
country: Australia
facility: N01269 202
city: Randwick
country: Australia
facility: N01269 200
city: South Brisbane
country: Australia
facility: N01269 201
city: Bruxelles
country: Belgium
facility: N01269 301
city: Edegem
country: Belgium
facility: N01269 300
city: Tbilisi
country: Georgia
facility: N01269 400
city: Tbilisi
country: Georgia
facility: N01269 401
city: Tbilisi
country: Georgia
facility: N01269 402
city: Tbilisi
country: Georgia
facility: N01269 403
city: Tbilisi
country: Georgia
facility: N01269 405
city: Messina
country: Italy
facility: N01269 323
city: Milano
country: Italy
facility: N01269 321
city: Milano
country: Italy
facility: N01269 324
city: Pavia
country: Italy
facility: N01269 320
city: Roma
country: Italy
facility: N01269 322
city: Roma
country: Italy
facility: N01269 325
city: Verona
country: Italy
facility: N01269 326
city: Gdansk
country: Poland
facility: N01269 533
city: Krakow
country: Poland
facility: N01269 530
city: Lodz
country: Poland
facility: N01269 534
city: Lublin
country: Poland
facility: N01269 531
city: Warszawa
country: Poland
facility: N01269 532
city: Bucuresti
country: Romania
facility: N01269 562
city: Bucuresti
country: Romania
facility: N01269 563
city: Iasi
country: Romania
facility: N01269 560
city: Timişoara, Judeţ Timiş
country: Romania
facility: N01269 561
city: Bardejov
country: Slovakia
facility: N01269 632
city: Dubnica Nad Vahom
country: Slovakia
facility: N01269 630
city: Nove Zamky
country: Slovakia
facility: N01269 631
city: Madrid
country: Spain
facility: N01269 351
city: Sevilla
country: Spain
facility: N01269 353
city: Terrassa
country: Spain
facility: N01269 354
city: Dnipro
country: Ukraine
facility: N01269 600
city: Dnipro
country: Ukraine
facility: N01269 601
city: Kharkiv
country: Ukraine
facility: N01269 604
city: Kharkiv
country: Ukraine
facility: N01269 608
city: Kyiv
country: Ukraine
facility: N01269 603
city: Kyiv
country: Ukraine
facility: N01269 606
city: Uzhgorod
country: Ukraine
facility: N01269 607
city: Vinnytsia
country: Ukraine
facility: N01269 602
Study officials:
affiliation: 001 844 599 2273 (UCB)
name: UCB Cares
role: STUDY_DIRECTOR
References:
citation: 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.