Primary objective* To document the long-term safety and tolerability of BRVSecondary objective* To assess the efficacy of BRV during long-term exposureOther objectives* To explore direct cost parameters* To assess the effect of BRV on behavior using…
ID
Source
Brief title
Condition
- Seizures (incl subtypes)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Incidence of treatment-emergent adverse events (TEAEs) during the study.
Incidence of treatment-emergent serious adverse events (SAEs) during the study
Secondary outcome
For subjects *2 years of age (based on daily record card (DRC) data):
1. Absolute change in 28-days adjusted partial-onset seizures (POS) frequency
from Baseline to the end of the Evaluation Period in subjects with POS only
2. Percent change in 28-days adjusted partial-onset seizures (POS) frequency
from Baseline to the end of the Evaluation Period in subjects with POS only
3. 50% responder rate for total seizures (all types)
For subjects <2 years of age (based on EEG data [recorded at least 24 hours])
or subjects with typical absence seizures (based on EEG data):
4. Absolute change in average daily frequency of partial-onset-seizures (POS)
in subjects with POS only
5. Percent change in average daily frequency of partial-onset-seizures (POS) in
subjects with POS only
6. 50% responder rate for total seizures (all types)
Background summary
N01266 is designed for pediatric subjects *1 month to <17 years of age who have
completed core studies (LTFU subjects) and for at least 100 subjects *4 years
to <17 years of age with POS who have not participated in a core study
(directly enrolled subjects). The total enrollment planned for N01266 is
approximately 600 subjects.
N01266 will provide long-term safety and tolerability data on BRV in pediatric
subjects with epilepsy, while providing access to BRV for subjects who may
benefit from long-term treatment. The enrollment of directly enrolled subjects
is intended to provide both long-term safety and tolerably data and efficacy
data for subjects 4 years to <17 years of age with POS to supplement data
collected for subjects with POS in N01263.
Study objective
Primary objective
* To document the long-term safety and tolerability of BRV
Secondary objective
* To assess the efficacy of BRV during long-term exposure
Other objectives
* To explore direct cost parameters
* To assess the effect of BRV on behavior using the Achenbach CBCL in subjects
*18 months of age
* To explore the effect of BRV on cognition using the BRIEF-P/BRIEF in subjects
*2 years of age
* To assess the effect of BRV on cognition using the Bayley-III scales in
subjects <18 months of age (applicable only to LTFU subjects enrolled in
English-speaking countries)
* To explore the effect of BRV on health-related quality of life (HRQoL) using
the PedsQL in subjects *1 month of age
Study design
This is a Phase 3, open-label, single-arm, multicenter, long-term study to
evaluate the safety and efficacy of brivaracetam (BRV) in children with
epilepsy. This study is designed for pediatric subjects *1 month to <17 years
of age who have completed other pediatric BRV studies (herein referred to as
*long-term follow-up* [LTFU] subjects) and for at least 100 subjects *4 years
to <17 years of age with POS who had not previously enrolled in a pediatric BRV
study (herein referred to as *directly enrolled subjects*), with a planned
total enrollment of approximately 600 subjects.
Brivaracetam (tablet and oral solution) should be administered twice daily
(bid) in 2 equally divided doses. All LTFU subjects must be able to tolerate
the minimum dose specified in the core study to be eligible for entry into the
Evaluation Period of N01266. All directly enrolled subjects must be able to
tolerate at least 1mg/kg/day during the Up-Titration Period prior to entering
the Evaluation Period of N01266, as indicated in Section 7.2.
Subjects will receive BRV treatment in this study for at least 3 years, until
approval of BRV has been obtained for pediatric subjects in their age range,
until a managed access program is established as allowed per country-specific
requirements in addition to legal and regulatory guidelines, or until the
investigational product development in the related age range of the pediatric
population is stopped by the Sponsor, whichever comes first.
Intervention
Brivaracetam 10mg/ml - 300ml solution for oral use.
Brivaracetam - 10mg/25mg/50mg tablets for oral use.
Study burden and risks
Subjects will receive BRV treatment in this study for at least 3 years, until
approval of BRV has been obtained for pediatric subjects in their age range,
until a managed access program is established as allowed per country-specific
requirements in addition to legal and regulatory guidelines, or until the
investigational product development in the related age range of the pediatric
population is stopped by the Sponsor, whichever comes first.
The LTFU subjects will enter directly into the Evaluation Period at the Entry
Visit (EV) and will continue BRV treatment at the individualized dose they were
receiving at the completion of their core study. Directly enrolled subjects
will enter N01266 at the Screening Visit (ScrV) and then participate in up to 3
weeks of an Up-Titration Period. If a directly enrolled subject demonstrates,
in the opinion of the Investigator, acceptable tolerability and seizure control
on the same daily dose of BRV (no lower than 1mg/kg/day) for 7±2 days during the
Up-Titration Period, the subject will attend the EV and enter the Evaluation
Period on that dose.
For LTFU subjects, the EV is the first study visit. For directly enrolled
subjects, the EV occurs after subjects have completed the ScrV and at least 1
Titration Visit (TV), and have maintained acceptable tolerability and seizure
control on the same daily dose of BRV (no lower than the minimum specified
dose) for 7±2 days of the Up-Titration Period. For subjects who continue in
this study until it ends, the Evaluation Period will extend from the EV until
the final evaluation visit (Final Visit, FV). For subjects who prematurely
discontinue the study, the Evaluation Period will last from the EV until the
Early Discontinuation Visit (EDV), followed by a maximum 4-week Down-Titration
Period, a 2-week Safety (Drug-Free) Period, and a final Safety Visit (SV).
Subjects already enrolled in N01266 may participate in EP0065 (an intravenous
[iv] BRV study for pediatric subjects), if eligible, and then resume
participation in N01266.
During the Evaluation Period, Minimal Evaluation Visits (MEVs) and Full
Evaluation Visits (FEVs) will be performed alternatively every month during the
first 3 months and every 3 months thereafter, with a Yearly Evaluation Visit
(YEV) every 12 months.
Allée de la Recherche 60
Brussels B-1070
BE
Allée de la Recherche 60
Brussels B-1070
BE
Listed location countries
Age
Inclusion criteria
To be eligible to participate in this study, all of the following criteria must
be met as specified. , # Inclusion criteria for all subjects, - An
Institutional Review Board (IRB)/Independent Ethics Committee (IEC) approved
written Informed Consent form is signed and dated by the parent(s) or legal
representative(s). The Consent form or a specific Assent form, where required,
will be signed and dated by minors., - Subject/legal representative is
considered reliable and capable of adhering to the protocol (eg, able to
understand and complete diaries), visit schedule, or medication intake
(including BRV oral solution or tablets) according to the judgment of the
Investigator., - For female subjects, the subject is, 1) Not of childbearing
potential OR Of childbearing potential, and
- Is not sexually active
- Has a negative pregnancy test, OR , 2) Of childbearing potential, and Is
sexually active, Has a 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. Medically acceptable contraceptive methods for
the study include, but are not limited to:, Oral or depot contraceptive
treatment with at least ethinylestradiol 30*g per intake or ethinylestradiol
50*g per intake if also taking one of the following: carbamazepine,
phenobarbital, primidone, phenytoin, oxcarbazepine, St. John's Wort, or
rifampicin, Barrier contraception: intrauterine device, diaphragm with
spermicide, male or female condom with spermicide, Abstinence from sexual
intercourse, # Inclusion criteria for LTFU subjects only, - Male or female
subjects having participated in a core study with BRV with a confirmed
diagnosis of epilepsy and for whom a reasonable benefit from long-term
administration of BRV is expected., # Inclusion criteria for directly enrolled
subjects only, - Subject is a male or female *4 years to <17 years of age.,
- Subject has a clinical diagnosis of POS according to the 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 AED
(concurrently or sequentially)., - Subject had at least 1 seizure (POS) during
the 3 weeks before the 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
Subjects are not permitted to enroll in the study if any of the following
criteria are met as specified. , # Exclusion criteria for 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 any
medical condition, which in the Investigator*s opinion, warrants exclusion.,
-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)., -Subject has chronic liver disease., # Exclusion
criteria for LTFU subjects only, - 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., # Exclusion
criteria for directly enrolled subjects only, - 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)., - Subject
has a terminal illness., - Subject has any clinically significant deviations
from reference range values for laboratory parameters as determined by the
Investigator., - Subject has a clinically relevant ECG abnormality according to
the Investigator., - Subject had major surgery within 6 months prior to the
ScrV., - Subject received any investigational drug or device within the 30 days
prior to the ScrV. The use of AEDs marketed for adults but not approved for
pediatric use is not considered to be *investigational* for the purposes of
this study., - Investigators* and co Investigators* children may not be
included as subjects in the study., - Subject has a lifetime history of suicide
attempt (including an actual attempt, interrupted attempt, or aborted attempt),
or has suicidal ideation in the past 6 months as indicated by a positive
response (*Yes*) to either Question 4 or Question 5 of the C SSRS
Baseline/Screening at the ScrV.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2011-000374-60-NL |
| ClinicalTrials.gov | NCT01364597 |
| CCMO | NL61397.078.17 |