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Trial record 1 of 1 for:    NCT01364597
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Open-label Long-term Study of Adjunctive Brivaracetam in Pediatric Subjects With Epilepsy

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ClinicalTrials.gov Identifier: NCT01364597
Recruitment Status : Enrolling by invitation
First Posted : June 2, 2011
Last Update Posted : November 20, 2020
Sponsor:
Information provided by (Responsible Party):
UCB Pharma ( UCB Pharma SA )

Brief Summary:
This study will evaluate the safety and tolerability of brivaracetam in pediatric subjects with epilepsy.

Condition or disease Intervention/treatment Phase
Epilepsy Drug: Brivaracetam (BRV) Phase 3

Expanded Access : An investigational treatment associated with this study is available outside the clinical trial.   More info ...

Detailed Description:

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 was initially designed for pediatric subjects who had completed a previous BRV study.

With protocol amendment 4, enrollment for "directly enrolled" subjects was modified from 'up to' an additional 100 subjects to "at least" 100 subjects, keeping the planned total enrollment of approximately 600 subjects to allow flexibility in the number of patients reaching 1 year of exposure.

With protocol amendment 5, entry criteria for subjects coming for other pediatric core studies in development were included. Additional clarity was provided for subjects enrolled in N01266 that temporary roll over to one of those studies and resume participation in N01266.

With protocol amendment 6, central EEG reading and entry visit EEG were removed. Some clarifications on study assessments (questionnaires, EEGs) was provided and inclusion criteria were aligned from an earlier local amendment.

With protocol amendment 7, the pregnancy section was updated to clarify that Pregnancy Report and Outcome Form has to be completed in all pregnancies.

With protocol amendment 8, re-categorization of study variables in compliance with reporting registries was performed. Modifications due to COVID19 pandemic were implemented and clarification provided that participants may transition to another BRV study.

The primary objective is to evaluate the long-term safety and tolerability of BRV. The secondary objective is to assess the efficacy of BRV during long-term exposure.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 600 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official 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
Actual Study Start Date : August 2011
Estimated Primary Completion Date : January 2022
Estimated Study Completion Date : January 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Epilepsy

Arm Intervention/treatment
Experimental: Brivaracetam Drug: Brivaracetam (BRV)
The max BRV dose will be 5.0 mg/kg/day, not to exceed a dose of 200 mg/day for subjects with body weight >40kg. Subjects may receive oral solution or oral tablets. The LTFU subjects will start dosing in N01266 on the individualized BRV dose they were receiving at the completion of the core study. Subjects must be able to tolerate the min BRV dose specified in the core study to be eligible for entry into the Evaluation Period of N01266. Dose can be adjusted as considered necessary by the Investigator and required by the subject's medical condition. All subjects who prematurely discontinue the study should complete an EDV and have their BRV dose down titrated by a maximum of half the dose every week for a maximum of 4 weeks until a dose of 1 mg/kg/day (50 mg/day for subjects with body weights >50kg) is reached.




Primary Outcome Measures :
  1. Incidence of treatment-emergent adverse events (TEAEs) during the study [ Time Frame: From Baseline to end of Study (up to 10 years) ]
    An Adverse Event (AE) is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product.

  2. Incidence of treatment-emergent serious adverse events (SAEs) during the study [ Time Frame: From Baseline to end of Study (up to 10 years) ]

    A serious adverse event (SAE) is any untoward medical occurrence that at any dose:

    • Results in death
    • Is life-threatening
    • Requires in patient hospitalization or prolongation of existing hospitalization
    • Is a congenital anomaly or birth defect
    • Is an infection that requires treatment parenteral antibiotics
    • Other important medical events which based on medical or scientific judgement may jeopardize the patients, or may require medical or surgical intervention to prevent any of the above


Secondary Outcome Measures :
  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 [ Time Frame: From Baseline to the end of the Evaluation Period (up to 10 years) ]
    This Outcome Measure applies to subjects ≥2 years of age (based on daily record card (DRC) data).

  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 [ Time Frame: From Baseline to the end of the Evaluation Period (up to 10 years) ]
    This Outcome Measure applies to subjects ≥2 years of age (based on daily record card (DRC) data).

  3. 50% responder rate for total seizures (all types) [ Time Frame: From Baseline to end of Study (up to 10 years) ]
    This Outcome Measure applies to subjects ≥2 years of age (based on daily record card (DRC) data).

  4. Absolute change in average daily frequency of partial-onset-seizures (POS) in subjects with POS only [ Time Frame: From Baseline to end of Study (up to 10 years) ]
    This Outcome Measure applies to subjects <2 years of age (based on electroencephalogram (EEG) data [recorded at least 24 hours]) or subjects with typical absence seizures (based on EEG data).

  5. Percent change in average daily frequency (ADF) of partial-onset-seizures (POS) in subjects with POS only [ Time Frame: From Baseline to end of Study (up to 10 years) ]
    This Outcome Measure applies to subjects <2 years of age (based on electroencephalogram (EEG) data [recorded at least 24 hours]) or subjects with typical absence seizures (based on EEG data).

  6. 50% responder rate for total seizures (all types) [ Time Frame: From Baseline to end of Study (up to 10 years) ]
    This Outcome Measure applies to subjects <2 years of age (based on electroencephalogram (EEG) data [recorded at least 24 hours]) or subjects with typical absence seizures (based on EEG data).



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   up to 17 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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).
  • 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01364597


Locations
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Sponsors and Collaborators
UCB Pharma SA
Investigators
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Study Director: UCB Cares +1 877 822 9493 (UCB)
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: UCB Pharma SA
ClinicalTrials.gov Identifier: NCT01364597    
Other Study ID Numbers: N01266
2011-000374-60 ( EudraCT Number )
First Posted: June 2, 2011    Key Record Dates
Last Update Posted: November 20, 2020
Last Verified: November 2020

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by UCB Pharma ( UCB Pharma SA ):
Brivaracetam
Epilepsy
Child
Infant
Adolescents
Partial onset seizures
Additional relevant MeSH terms:
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Epilepsy
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Brivaracetam
Anticonvulsants