Open-label Long-term Study of Adjunctive Brivaracetam in Pediatric Subjects With Epilepsy

• Register: ClinicalTrials.gov
• Last refreshed on: 11 December 2023
• Main ID: NCT01364597
• Date of registration: 31/05/2011
• Prospective Registration: Yes
• Primary sponsor: UCB Pharma SA
• Public title: Open-label Long-term Study of Adjunctive Brivaracetam in Pediatric Subjects With Epilepsy
• Scientific title: Open-label, Single-arm, Multicenter, Long-term Study to Evaluate Safety and Efficacy of Brivaracetam Used as Adjunctive Treatment in Pediatric Subjects With Epilepsy
• Date of first enrolment: August 1, 2011
• Target sample size: 257
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/ct2/show/NCT01364597
• Study type: Interventional
• Study design: Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 3

Countries of recruitment

Belgium, Czech Republic, Czechia, France, Germany, Hungary, Ireland, Italy, Mexico, Netherlands, Poland, Spain, United Kingdom, United States

Contacts

• Name: UCB Cares
• Affiliation: [phone] (UCB)

Key inclusion & exclusion criteria

Inclusion Criteria:

All Subjects:

- Informed Consent form (ICF) is signed and dated by the parent(s) or legal
representative(s)

- Subject/legal representative is considered reliable and capable of adhering to the
protocol

- For female subjects:

- Subject is not of childbearing potential

OR if women of childbearing potential, and sexually active only if:

- Adequate Contraceptive method

- Negative pregnancy test

- Understands the consequences and potential risks of inadequately protected sexual
activity, understands and properly uses contraceptive methods, and is willing to
inform the Investigator of any contraception changes

Long Term Follow-up Subjects:

- Male or female subjects having participated in a core study with a confirmed diagnosis of
epilepsy and for whom a reasonable benefit from long-term administration of BRV is expected

Directly Enrolled Subjects:

- Subject is a male or female =4 years to <17 years of age

- Subject has a clinical diagnosis of partial-onset seizures (POS) according to the
International League Against Epilepsy (ILAE) classification

- Subject has an EEG compatible with the clinical diagnosis of POS

- Subject has been observed to have uncontrolled POS after an adequate course of
treatment (in the opinion of the Investigator) with at least 1 antiepileptic drug
(AED; concurrently or sequentially)

- Subject had at least 1 seizure (POS) during the 3 weeks before the Screening Visit
(ScrV)

- Subject is taking at least 1 AED. All AEDs need to be at a stable dose for at least 7
days before the ScrV. Vagal nerve stimulator stable for at least 2 weeks before the
ScrV is allowed and will be counted as a concomitant AED. Benzodiazepines taken more
than once a week (for any indication) will be considered as a concomitant AED

Exclusion Criteria:

All Subjects:

- Subject is a pregnant or nursing female

- Subject has severe medical, neurological, or psychiatric disorders or laboratory
values, which may have an impact on the safety of the subject.

- Subject has planned participation in any clinical study of another investigational
drug or device.

- Subject has >1.5x upper limit of normal (ULN) of any of the following: alanine
aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP),
or >1.0xULN total bilirubin (=1.5xULN total bilirubin if known Gilbert's syndrome). If
subject has elevations only in total bilirubin that are >ULN and <1.5xULN, fractionate
bilirubin to identify possible undiagnosed Gilbert's syndrome (ie, direct bilirubin
<35%). N01349 subjects with a total bilirubin > ULN may be considered for the study if
benign unconjugated hyperbilirubinemia is suspected in the context of prolonged
neonatal jaundice, after discussion with the medical monitor. For randomized subjects
with a baseline result >ULN for ALT, AST, ALP, or total bilirubin, a baseline
diagnosis and/or the cause of any clinically meaningful elevation must be understood
and recorded in the eCRF. If subject has >ULN ALT, AST, or ALP that does not meet the
exclusion limit at the baseline referenced in Table 5-1 for LTFU subjects and at the
Screening Visit for directly enrolled subjects, repeat the tests, if possible, prior
to dosing to ensure there is no further ongoing clinically relevant increase. In case
of a clinically relevant increase, inclusion of the subject must be discussed with the
Medical Monitor. Tests that result in ALT, AST, or ALP up to 25% above the exclusion
limit may be repeated once for confirmation. This includes re-screening.

- Subject has chronic liver disease.

Long Term Follow-up Subjects:

- Subject had hypersensitivity to BRV or excipients or comparative drugs as stated in
this protocol during the course of the core study.

- Subject had poor compliance with the visit schedule or medication intake in the core
study.

- Subject =6 years of age has a lifetime history of suicide attempt (including actual
attempt, interrupted attempt, or aborted attempt), or has suicidal ideation in the
past 6 months as indicated by a positive response ("Yes") to Question 5 of the
Columbia-Suicide Severity Rating Scale (C-SSRS) at the EV. If a subject has active
suicidal ideation without a specific plan as indicated by a positive response ("Yes")
to Question 4 of Columbia-Suicide Severity Rating Scale (C SSRS) at the EV, the
subject should be referred immediately to a Mental Healthcare Professional and may be
excluded from the study based upon the Investigator's judgment of benefit/risk of
continuing the subject in the study/on study medication.

Directly Enrolled Subjects:

- Subject has previously received BRV.

- Subject had concomitant use of LEV at the ScrV. In addition, the use of LEV is
prohibited for at least 4 weeks prior to the ScrV.

- Subject has epilepsy secondary to a progressive cerebral disease or tumor, or any
other progressively neurodegenerative disease. Stable arteriovenous malformations,
meningiomas or other benign tumors may be acceptable according to Investigator's
opinion.

- Subject has a history of primary generalized epilepsy.

- Subject has a history of status epilepticus in the month immediately prior to the ScrV
or during the Up Titration Period.

- Subject has a history or presence of pseudoseizures.

- Subject is suffering only from febrile seizures.

- Subject is on felbamate with less than 18 months continuous exposure. Subject who has
taken felbamate for a combined duration of treatment and wash out of <18 months before
the ScrV.

- Subjects treated with vigabatrin who have visual field defects.

- Subject has an allergy to pyrrolidone derivatives or investigational product
excipients or a history of multiple drug allergies.

- Subject has any clinically significant acute or chronic illness as determined during
the physical examination or from other information available to the Investigator (eg,
bone marrow depression, chronic hepatic disease, severe renal impairment, psychiatric
disorder).

- Subject has an underlying disease or is receiving a treatment that may interfere with
the absorption, distribution, metabolism, and elimination of the study drug.

- Subject has any medical condition that might interfere with his/her study
participation (eg, serious infection or scheduled elective surgery).




Age minimum: 28 Days
Age maximum: 17 Years
Gender: All

Health Condition(s) or Problem(s) studied

Epilepsy

Intervention(s)

Drug: Brivaracetam (BRV)

Primary Outcome(s)

Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) During the Study [Time Frame: From Baseline to end of study (up to 10 years)]

Percentage of Participants With Treatment-emergent Serious Adverse Events (SAEs) During the Study [Time Frame: From Baseline to end of study (up to 10 years)]

Secondary Outcome(s)

50% Responder Rate for Participants <2 Years of Age for Total Seizures (All Types) (Based on EEG Data) [Time Frame: From Baseline (LTFU participants: Baseline of previous studies N01263 [NCT00422422] or N01349 [NCT03325439]) to the end of the evaluation period (up to 10 years)]

Absolute Change in Average Daily Frequency (ADF) of Partial-onset-seizures (POS) in Participants <2 Years of Age With POS Only (Based on EEG Data) [Time Frame: From Baseline (LTFU participants: Baseline of previous studies N01263 [NCT00422422] or N01349 [NCT03325439]) to the end of the evaluation period (up to 10 years)]

50% Responder Rate for Participants =2 Years of Age for Total Seizures (All Types) (Based on DRC Data) [Time Frame: From Baseline (LTFU participants: Baseline of previous studies N01263 [NCT00422422]; and DE participants: Baseline of current study) to the end of the evaluation period (up to 10 years)]

Percent Change in 28-days Adjusted Partial-onset-seizure (POS) Frequency for Participants Aged =2 Years From Baseline to the End of the Evaluation Period in Participants With POS Only (Based on DRC Data) [Time Frame: From Baseline (LTFU participants: Baseline of previous studies N01263 [NCT00422422]; and DE participants: Baseline of current study) to the end of the evaluation period (up to 10 years)]

50% Responder Rate for Total Seizures (All Types) in Participants <2 Years of Age With Typical Absence Seizures (Based on EEG Data) [Time Frame: From Baseline (LTFU participants: Baseline of previous studies N01263 [NCT00422422] or N01349 [NCT03325439]) to the end of the evaluation period (up to 10 years)]

Absolute Change in 28-days Adjusted Partial-onset-seizure (POS) Frequency for Participants Aged =2 Years From Baseline to the End of the Evaluation Period in Participants With POS Only (Based on Daily Record Card [DRC]) [Time Frame: From Baseline (LTFU participants: Baseline of previous studies N01263 [NCT00422422]; and DE participants: Baseline of current study) to the end of the evaluation period (up to 10 years)]

Absolute Change in Average Daily Frequency of POS in Participants <2 Years of Age With Typical Absence Seizures (Based on EEG Data) [Time Frame: From Baseline (LTFU participants: Baseline of previous studies N01263 [NCT00422422] or N01349 [NCT03325439]) to the end of the evaluation period (up to 10 years)]

Percent Change in Average Daily Frequency (ADF) of Partial-onset-seizures (POS) in Participants <2 Years of Age With POS Only (Based on EEG Data) [Time Frame: From Baseline (LTFU participants: Baseline of previous studies N01263 [NCT00422422] or N01349 [NCT03325439]) to the end of the evaluation period (up to 10 years)]

Percent Change in Average Daily Frequency of POS in Participants <2 Years of Age With Typical Absence Seizures (Based on EEG Data) [Time Frame: From Baseline (LTFU participants: Baseline of previous studies N01263 [NCT00422422] or N01349 [NCT03325439]) to the end of the evaluation period (up to 10 years)]

Secondary ID(s)

N01266

2011-000374-60

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 29/08/2022
• URL: https://clinicaltrials.gov/ct2/show/results/NCT01364597