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 (EXPAND)

UCB

Status and phase: Enrolling; Phase 3

Conditions: Juvenile Absence Epilepsy; Childhood Absence Epilepsy

Treatments: Drug: Brivaracetam; Other: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT04666610

2023-510428-55-00 (Registry Identifier)

2020-002750-24 (EudraCT Number)

N01269

U1111-1303-2521 (Other Identifier)

Details and patient eligibility

About

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).

Enrollment: 160 estimated patients

Sex: All

Ages: 2 to 25 years old

Volunteers: No Healthy Volunteers

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)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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160 participants in 8 patient groups

Brivaracetam 200 mg

Experimental group

Description:

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.

Treatment:

Drug: Brivaracetam

Placebo to 200 mg brivaracetam

Experimental group

Description:

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.

Treatment:

Other: Placebo

Drug: Brivaracetam

Brivaracetam 100 mg

Experimental group

Description:

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.

Treatment:

Drug: Brivaracetam

Placebo to 100 mg brivaracetam

Experimental group

Description:

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.

Treatment:

Other: Placebo

Drug: Brivaracetam

Optimal dose of BRV (defined following Stage 1)

Experimental group

Description:

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.

Treatment:

Drug: Brivaracetam

Placebo to BRV optimal dose (defined following Stage 1)

Experimental group

Description:

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.

Treatment:

Other: Placebo

Drug: Brivaracetam

Brivaracetam received during RDW

Experimental group

Description:

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.

Treatment:

Drug: Brivaracetam

Placebo received during RDW

Experimental group

Description:

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.

Treatment:

Other: Placebo

Drug: Brivaracetam