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

NCT04666610 | Active Not Recruiting Phase 3 DMC FDA Drug

• 4 other identifiers: N012692020-002750-242023-510428-55-00U1111-1303-2521
• Study Type: interventional
• Target: 153
• Locations: 7 countries
• Sites: 35

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).

Conditions

Childhood Absence Epilepsy; Juvenile Absence Epilepsy

Keywords

Brivaracetam; Briviact; Epilepsy; Childhood absence Epilepsy; Juvenile absence epilepsy; CAE; JAE

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (9)

• Percentage of participants who met the criteria for absence seizure freedom during the randomized withdrawal (RDW) period as determined by electroencephalogram (EEG)

  From Week 13 to Week 17

• Percent change from Baseline to Day 14 in number of absence seizures on 24-hour ambulatory electroencephalogram (EEG)

  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

  Day 14

• Percentage of participants who met the criteria for absence seizure freedom on 24-hour ambulatory electroencephalogram (EEG) at Week 12

  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

  Week 12

Study Arms (8)

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.

Drug: Brivaracetam

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.

Drug: Brivaracetam; Other: Placebo

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.

Drug: Brivaracetam

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.

Drug: Brivaracetam; Other: Placebo

Optimal dose of BRV (defined following Stage 1)

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.

Drug: Brivaracetam

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.

Drug: Brivaracetam; Other: Placebo

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.

Drug: Brivaracetam

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.

Drug: Brivaracetam; Other: Placebo

Interventions

Brivaracetam DRUG

* 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.

Also known as: BRV

Brivaracetam 100 mg; Brivaracetam 200 mg; Brivaracetam received during RDW; Optimal dose of BRV (defined following Stage 1); Placebo received during RDW; Placebo to 100 mg brivaracetam; Placebo to 200 mg brivaracetam; Placebo to BRV optimal dose (defined following Stage 1)

Placebo OTHER

Subjects will receive placebo at pre-specified time-points to maintain the blinding.

Also known as: PBO

Placebo received during RDW; Placebo to 100 mg brivaracetam; Placebo to 200 mg brivaracetam; Placebo to BRV optimal dose (defined following Stage 1)

Eligibility Criteria

• Age: 2 Years - 25 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• UCB Biopharma SRL: lead

Study Sites (35)

N01269 115

Birmingham, Alabama, 35233, United States

Location

N01269 105

Orange, California, 92868-3874, United States

Location

N01269 116

Denver, Colorado, 80202, United States

Location

N01269 111

Miami, Florida, 33155-3009, United States

Location

N01269 101

Tampa, Florida, 33612, United States

Location

N01269 104

Winter Park, Florida, 32789, United States

Location

N01269 110

Augusta, Georgia, 30912, United States

Location

N01269 100

New Brunswick, New Jersey, 08901, United States

Location

N01269 109

Winston-Salem, North Carolina, 27109, United States

Location

N01269 106

Philadelphia, Pennsylvania, 19134, United States

Location

N01269 400

Tbilisi, Georgia

Location

N01269 401

Tbilisi, Georgia

Location

N01269 402

Tbilisi, Georgia

Location

N01269 403

Tbilisi, Georgia

Location

N01269 405

Tbilisi, Georgia

Location

N01269 323

Messina, Italy

Location

N01269 321

Milan, Italy

Location

N01269 324

Milan, Italy

Location

N01269 320

Pavia, Italy

Location

N01269 322

Roma, Italy

Location

N01269 325

Roma, Italy

Location

N01269 326

Verona, Italy

Location

N01269 562

Bucharest, Romania

Location

N01269 563

Bucharest, Romania

Location

N01269 560

Iași, Romania

Location

N01269 561

Timişoara, Judeţ Timiş, Romania

Location

N01269 632

Bardejov, Slovakia

Location

N01269 630

Dubnica nad Váhom, Slovakia

Location

N01269 631

Nové Zámky, Slovakia

Location

N01269 354

Terrassa, Spain

Location

N01269 600

Dnipro, Ukraine

Location

N01269 601

Dnipro, Ukraine

Location

N01269 604

Kharkiv, Ukraine

Location

N01269 607

Uzhhorod, Ukraine

Location

N01269 602

Vinnytsia, Ukraine

Location

Related 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/epi4.12628. Epub 2022 Aug 4.

  PMID: 35844134 RESULT

MeSH Terms

Conditions

Epilepsy, Absence; Epilepsy

Interventions

brivaracetam

Condition Hierarchy (Ancestors)

Epilepsy, Generalized; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Epileptic Syndromes

Study Officials

• UCB Cares

  001 844 599 2273 (UCB)

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Study Record Dates

• First Submitted: December 7, 2020
• First Posted: December 14, 2020
• Study Start: July 29, 2021
• Primary Completion (Estimated): August 24, 2026
• Study Completion (Estimated): August 24, 2026
• Last Updated: March 13, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: 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.
• Access Criteria: 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.

Locations

GE (5); UA (5); SL (3); US (10); RO (4); ES (1); IT (7)