LONG TERM STUDY OF ADJUNCTIVE ADMINISTRATION OF BRIVARACETAM IN CHILDREN WITH EPILEPSY

• Register: EUCTR
• Last refreshed on: 19 April 2022
• Main ID: EUCTR2011-000374-60-BE
• Date of registration: 10/05/2011
• Prospective Registration: Yes
• Primary sponsor: UCB Pharma SA
• Public title: LONG TERM STUDY OF ADJUNCTIVE ADMINISTRATION OF BRIVARACETAM IN CHILDREN 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: 05/07/2011
• Target sample size: 600
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2011-000374-60
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no; Randomised: Open: yes; Single blind: Double blind: Parallel group: Cross over: Other: If controlled, specify comparator, Other Medicinial Product: Placebo: Other: Number of treatment arms in the trial: 1
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

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

Contacts

• Name: CT Registries & Results Disclosure
• Affiliation: UCB BIOSCIENCES GmbH

• Name: CT Registries & Results Disclosure
• Affiliation: UCB BIOSCIENCES GmbH

Key inclusion & exclusion criteria

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 30µg per intake or ethinylestradiol 50µg 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 in epilepsy with BRV 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.

Are the trial subjects under 18? yes
Number of subjects for this age range: 600
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

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 infect

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Localization-related, generalized or undetermined whether focal or generalized epileptic syndrome, according to ILAE classification
MedDRA version: 20.0 Level: PT Classification code 10015037 Term: Epilepsy System Organ Class: 10029205 - Nervous system disorders

Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

Intervention(s)

Trade Name: Briviact
Product Name: Brivaracetam
Product Code: ucb 34714
Pharmaceutical Form: Oral solution
INN or Proposed INN: BRIVARACETAM
CAS Number: 357336-20-0
Current Sponsor code: ucb 34714
Other descriptive name: (2S)-2-[(4R)-2-oxo-4-propylpyrrolidin-1-yl] butanamide
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 10-

Product Name: Brivaracetam
Product Code: ucb 34714
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: BRIVARACETAM
CAS Number: 357336-20-0
Current Sponsor code: ucb 34714
Other descriptive name: (2S)-2-[(4R)-2-oxo-4-propylpyrrolidin-1-yl] butanamide
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 10-

Product Name: Brivaracetam
Product Code: ucb 34714
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: BRIVARACETAM
CAS Number: 357336-20-0
Current Sponsor code: ucb 34714
Other descriptive name: (2S)-2-[(4R)-2-oxo-4-propylpyrrolidin-1-yl] butanamide
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 25-

Product Name: Brivaracetam
Product Code: ucb 34714
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: BRIVARACETAM
CAS Number: 357336-20-0
Current Sponsor code: ucb 34714
Other descriptive name: (2S)-2-[(4R)-2-oxo-4-propylpyrrolidin-1-yl] butanamide
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 50-

Primary Outcome(s)

Primary end point(s): The primary variables are the safety & tolerability measurements: adverse events, safety laboratory assessments, plasma concentrations of BRV and phenytoin (if applicable), ECGs, vital signs, physical and neurological examinations, psychiatric and mental status, and body weight and height.

Main Objective: To document the long-term safety and tolerability of BRV

Secondary Objective: To assess the efficacy of BRV during long-term exposure

Timepoint(s) of evaluation of this end point: Some or all of the primary end points are evaluated on: Minimal Evaluation Visit, Full Evaluation Visit, Yearly Evaluation Visit / Final visit, Early Discontinuation Visit, Unscheduled Visit, Down-Titration Visit, Safety Visit.

During the Evaluation Period, Minimal Evaluation Visits and Full Evaluation Visits will be performed alternatively every month during the first 3 months and every 3 months thereafter, with a Yearly Evaluation Visit every 12 months

Secondary Outcome(s)

Secondary end point(s): The secondary variables are the efficacy measurements:Seizure count information from Daily Record Cards (DRCs) or electroencephalograms (EEGs).

Timepoint(s) of evaluation of this end point: DRC: from Entry Visit until (drug free) Safety Visit
EEG: at the Full Evaluation visit (V5), at Yearly Evaluation thereafter, and at Early Discontinuation Visit
During the Evaluation Period, Full Evaluation Visits will be performed alternatively every month during the first 3 months and every 3 months thereafter, with a Yearly Evaluation Visit every 12 months

Secondary ID(s)

N01266

Source(s) of Monetary Support

UCB Pharma SA

Ethics review

Status: Approved
Approval date: 30/06/2011
Contact: