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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04666610




Registration number
NCT04666610
Ethics application status
Date submitted
7/12/2020
Date registered
14/12/2020

Titles & IDs
Public title
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
Scientific 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
Secondary ID [1] 0 0
2020-002750-24
Secondary ID [2] 0 0
N01269
Universal Trial Number (UTN)
Trial acronym
EXPAND
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Childhood Absence Epilepsy 0 0
Juvenile Absence Epilepsy 0 0
Condition category
Condition code
Neurological 0 0 0 0
Epilepsy

Intervention/exposure
Study type
Interventional(has expanded access)
Description of intervention(s) / exposure
Treatment: Drugs - Brivaracetam
Other interventions - Placebo

Experimental: Brivaracetam 200 mg - 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.

Experimental: Placebo to 200 mg brivaracetam - 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.

Experimental: Brivaracetam 100 mg - 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.

Experimental: Placebo to 100 mg brivaracetam - 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.

Experimental: Optimal dose of BRV (defined following Stage 1) - 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.

Experimental: Placebo to BRV optimal dose (defined following Stage 1) - 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.

Experimental: Brivaracetam received during RDW - 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.

Experimental: Placebo received during RDW - 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: Drugs: 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 interventions: Placebo
Subjects will receive placebo at pre-specified time-points to maintain the blinding.
Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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
Timepoint [1] 0 0
Day 14
Secondary outcome [1] 0 0
Percentage of participants who met the criteria for absence seizure freedom during the randomized withdrawal (RDW) period as determined by electroencephalogram (EEG)
Timepoint [1] 0 0
From Week 13 to Week 17
Secondary outcome [2] 0 0
Percent change from Baseline to Day 14 in number of absence seizures on 24-hour ambulatory electroencephalogram (EEG)
Timepoint [2] 0 0
From Baseline to Day 14
Secondary outcome [3] 0 0
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
Timepoint [3] 0 0
Day 14
Secondary outcome [4] 0 0
Percentage of participants who met the criteria for absence seizure freedom on 24-hour ambulatory electroencephalogram (EEG) at Week 12
Timepoint [4] 0 0
Week 12
Secondary outcome [5] 0 0
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
Timepoint [5] 0 0
Week 12
Secondary outcome [6] 0 0
Percentage of participants with treatment-emergent adverse events (TEAEs) during the study
Timepoint [6] 0 0
From Day 1 until End of Safety Follow-Up (up to Week 23)
Secondary outcome [7] 0 0
Percentage of participants with treatment-emergent adverse events (TEAEs) leading to discontinuation of study treatment
Timepoint [7] 0 0
From Day 1 until End of Down Titration Period (up to Week 21)
Secondary outcome [8] 0 0
Percentage of participants with serious adverse events (SAEs) during the study
Timepoint [8] 0 0
From Screening Period (Day -14 to Day -2) until End of Safety Follow-Up (up to Week 23)
Secondary outcome [9] 0 0
Percentage of participants with drug-related treatment-emergent adverse events (TEAEs) during the study
Timepoint [9] 0 0
From Baseline (Day -1) until End of Safety Follow-Up (up to Week 23)

Eligibility
Key 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
Minimum age
2 Years
Maximum age
25 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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)

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
29/07/2021
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
25/02/2026
Actual
Sample size
Target
160
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
N01269 203 - Heidelberg
Recruitment hospital [2] 0 0
N01269 202 - Melbourne
Recruitment hospital [3] 0 0
N01269 200 - Randwick
Recruitment hospital [4] 0 0
N01269 201 - South Brisbane
Recruitment postcode(s) [1] 0 0
- Heidelberg
Recruitment postcode(s) [2] 0 0
- Melbourne
Recruitment postcode(s) [3] 0 0
- Randwick
Recruitment postcode(s) [4] 0 0
- South Brisbane
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Colorado
Country [4] 0 0
United States of America
State/province [4] 0 0
Florida
Country [5] 0 0
United States of America
State/province [5] 0 0
Georgia
Country [6] 0 0
United States of America
State/province [6] 0 0
New Jersey
Country [7] 0 0
United States of America
State/province [7] 0 0
North Carolina
Country [8] 0 0
United States of America
State/province [8] 0 0
Pennsylvania
Country [9] 0 0
Belgium
State/province [9] 0 0
Bruxelles
Country [10] 0 0
Belgium
State/province [10] 0 0
Edegem
Country [11] 0 0
Georgia
State/province [11] 0 0
Tbilisi
Country [12] 0 0
Italy
State/province [12] 0 0
Messina
Country [13] 0 0
Italy
State/province [13] 0 0
Milano
Country [14] 0 0
Italy
State/province [14] 0 0
Pavia
Country [15] 0 0
Italy
State/province [15] 0 0
Roma
Country [16] 0 0
Italy
State/province [16] 0 0
Verona
Country [17] 0 0
Poland
State/province [17] 0 0
Gdansk
Country [18] 0 0
Poland
State/province [18] 0 0
Krakow
Country [19] 0 0
Poland
State/province [19] 0 0
Lodz
Country [20] 0 0
Poland
State/province [20] 0 0
Lublin
Country [21] 0 0
Poland
State/province [21] 0 0
Warszawa
Country [22] 0 0
Romania
State/province [22] 0 0
Bucuresti
Country [23] 0 0
Romania
State/province [23] 0 0
Iasi
Country [24] 0 0
Romania
State/province [24] 0 0
Timisoara, Judet Timis
Country [25] 0 0
Slovakia
State/province [25] 0 0
Bardejov
Country [26] 0 0
Slovakia
State/province [26] 0 0
Dubnica Nad Vahom
Country [27] 0 0
Slovakia
State/province [27] 0 0
Nove Zamky
Country [28] 0 0
Spain
State/province [28] 0 0
Madrid
Country [29] 0 0
Spain
State/province [29] 0 0
Sevilla
Country [30] 0 0
Spain
State/province [30] 0 0
Terrassa
Country [31] 0 0
Ukraine
State/province [31] 0 0
Dnipro
Country [32] 0 0
Ukraine
State/province [32] 0 0
Kharkiv
Country [33] 0 0
Ukraine
State/province [33] 0 0
Kyiv
Country [34] 0 0
Ukraine
State/province [34] 0 0
Uzhgorod
Country [35] 0 0
Ukraine
State/province [35] 0 0
Vinnytsia

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
UCB Biopharma SRL
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
UCB Cares
Address 0 0
001 844 599 2273 (UCB)
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
UCB Cares
Address 0 0
Country 0 0
Phone 0 0
+1844599
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
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.

Supporting document/s available: Study protocol, Statistical analysis plan (SAP), Clinical study report (CSR)
When will data be available (start and end dates)?
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.
Available to whom?
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.
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: http://www.Vivli.org


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

TypeCitations or Other Details
Journal Bast T, Schulz AL, Floricel F, Morita D, Cleveland... [More Details]


Results not provided in https://clinicaltrials.gov/study/NCT04666610