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

Sponsor
UCB Pharma SA (Industry)
Overall Status
Completed
CT.gov ID
NCT01364597
Collaborator
(none)
257
46
1
126.1
5.6
0

Study Details

Study Description

Brief Summary

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

Condition or Disease Intervention/Treatment Phase
  • Drug: Brivaracetam (BRV)
Phase 3

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.

Study Design

Study Type:
Interventional
Actual Enrollment :
257 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 :
Aug 1, 2011
Actual Primary Completion Date :
Feb 3, 2022
Actual Study Completion Date :
Feb 3, 2022

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures

  1. Incidence of treatment-emergent adverse events (TEAEs) during the study [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 [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 [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 [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) [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 [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 [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) [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).

Eligibility Criteria

Criteria

Ages Eligible for Study:
28 Days to 17 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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.

Contacts and Locations

Locations

Site City State Country Postal Code
1 N01266 108 Gulf Breeze Florida United States 32561
2 N01266 103 Loxahatchee Groves Florida United States 33470
3 N01266 118 Chicago Illinois United States 60611
4 N01266 106 Boston Massachusetts United States 02111
5 N01266 101 Saint Paul Minnesota United States 55102
6 N01266 113 Chesterfield Missouri United States 63017
7 N01266 105 Buffalo New York United States 14222
8 N01266 252 New York New York United States 10029
9 N01266 104 Rochester New York United States 14642
10 N01266 237 Durham North Carolina United States 27710
11 N01266 107 Cincinnati Ohio United States 45229
12 N01266 111 Columbus Ohio United States 43205
13 N01266 114 Pittsburgh Pennsylvania United States 15201
14 N01266 117 Houston Texas United States 77030
15 N01266 202 Brussels Belgium
16 N01266 203 Brussels Belgium
17 N01266 201 Leuven Belgium
18 N01266 502 Hradec Králové Czechia
19 N01266 504 Ostrava Prouba Czechia
20 N01266 240 Praha 4 Czechia
21 N01266 209 Freiburg Germany
22 N01266 210 Budapest Hungary
23 N01266 224 Budapest Hungary
24 N01266 247 Budapest Hungary
25 N01266 222 Debrecen Hungary
26 N01266 232 Miskolc Hungary
27 N01266 238 Pavia Italy
28 N01266 239 Pavia Italy
29 N01266 230 Roma Italy
30 N01266 223 Aguascalientes Mexico
31 N01266 611 Chihuahua Mexico
32 N01266 609 Culiacán Mexico
33 N01266 603 Guadalajara Mexico
34 N01266 610 Monterrey Mexico
35 N01266 404 Białystok Poland
36 N01266 403 Gdańsk Poland
37 N01266 406 Kielce Poland
38 N01266 402 Kraków Poland
39 N01266 401 Poznań Poland
40 N01266 407 Szczecin Poland
41 N01266 405 Wrocław Poland
42 N01266 309 Barcelona Spain
43 N01266 306 Madrid Spain
44 N01266 301 Palma De Mallorca Spain
45 N01266 248 Sevilla Spain
46 N01266 308 Valencia Spain

Sponsors and Collaborators

  • UCB Pharma SA

Investigators

  • Study Director: UCB Cares, +1 877 822 9493 (UCB)

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
UCB Pharma SA
ClinicalTrials.gov Identifier:
NCT01364597
Other Study ID Numbers:
  • N01266
  • 2011-000374-60
First Posted:
Jun 2, 2011
Last Update Posted:
Feb 8, 2022
Last Verified:
Feb 1, 2022
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by UCB Pharma SA
Additional relevant MeSH terms:

Study Results

No Results Posted as of Feb 8, 2022