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

Childhood Absence Epilepsy Clinical Trial

— EXPAND  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04666610
• Other study ID #: N01269
• Secondary ID: 2020-002750-24
• Status: Recruiting
• Phase: Phase 3
• Start date: July 29, 2021
• Est. completion date: February 25, 2026

Study information

• Verified date: March 2024
• Source: UCB Pharma
• Contact: UCB Cares
• Phone: +1844599
• Email: UCBCares[@]ucb.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 160
• Est. completion date: February 25, 2026
• Est. primary completion date: February 25, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 2 Years to 25 Years

Eligibility

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 is capable of and 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)

Related Conditions & MeSH terms

• Childhood Absence Epilepsy
• Epilepsy
• Epilepsy, Absence
• Juvenile Absence Epilepsy

Intervention

Drug:
• Brivaracetam
Pharmaceutical form: Oral solution Route of administration: Oral use Brivaracetam (oral solution [10 mg/ml, 5 mg/ml or 2.5 mg/ml] will be administered.

Other:
• Placebo
Subjects will receive placebo at pre-specified time-points to maintain the blinding.

Locations

Country	Name	City	State
Australia	N01269 203	Heidelberg
Australia	N01269 202	Melbourne
Australia	N01269 200	Randwick
Australia	N01269 201	South Brisbane
Belgium	N01269 301	Bruxelles
Belgium	N01269 300	Edegem
Georgia	N01269 400	Tbilisi
Georgia	N01269 401	Tbilisi
Georgia	N01269 402	Tbilisi
Georgia	N01269 403	Tbilisi
Georgia	N01269 405	Tbilisi
Italy	N01269 323	Messina
Italy	N01269 321	Milano
Italy	N01269 324	Milano
Italy	N01269 320	Pavia
Italy	N01269 322	Roma
Italy	N01269 325	Roma
Italy	N01269 326	Verona
Poland	N01269 533	Gdansk
Poland	N01269 530	Krakow
Poland	N01269 534	Lodz
Poland	N01269 531	Lublin
Poland	N01269 532	Warszawa
Romania	N01269 562	Bucuresti
Romania	N01269 563	Bucuresti
Romania	N01269 560	Iasi
Romania	N01269 561	Timisoara, Judet Timis
Slovakia	N01269 632	Bardejov
Slovakia	N01269 630	Dubnica Nad Vahom
Slovakia	N01269 631	Nove Zamky
Spain	N01269 351	Madrid
Spain	N01269 353	Sevilla
Spain	N01269 354	Terrassa
Ukraine	N01269 600	Dnipro
Ukraine	N01269 601	Dnipro
Ukraine	N01269 604	Kharkiv
Ukraine	N01269 608	Kharkiv
Ukraine	N01269 603	Kyiv
Ukraine	N01269 606	Kyiv
Ukraine	N01269 607	Uzhgorod
Ukraine	N01269 602	Vinnytsia
United States	N01269 110	Augusta	Georgia
United States	N01269 115	Birmingham	Alabama
United States	N01269 116	Denver	Colorado
United States	N01269 118	Long Beach	California
United States	N01269 103	Loxahatchee Groves	Florida
United States	N01269 111	Miami	Florida
United States	N01269 100	New Brunswick	New Jersey
United States	N01269 105	Orange	California
United States	N01269 106	Philadelphia	Pennsylvania
United States	N01269 101	Tampa	Florida
United States	N01269 109	Winston-Salem	North Carolina
United States	N01269 104	Winter Park	Florida

Sponsors (1)

Lead Sponsor	Collaborator
UCB Biopharma SRL

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Georgia,  Italy,  Poland,  Romania,  Slovakia,  Spain,  Ukraine, 

References & Publications (1)

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/e — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Secondary	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.	From Week 13 to Week 17
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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)
Secondary	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)
Secondary	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: Results in death; Is life-threatening; Requires in patient hospitalization or prolongation of existing hospitalization; Is a congenital anomaly or birth defect; Results in permanent or significant disability/incapacity; Other important medical events which based on medical or scientific judgement may jeopardize the patients, or may require medical or surgical intervention to prevent any of the above	From Screening Period (Day -14 to Day -2) until End of Safety Follow-Up (up to Week 23)
Secondary	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)