A Multicenter, Open-Label, Single-Arm Study to Evaluate Long-Term Safety, Tolerability, and Efficacy of Brivaracetam in Study Participants 2 to 26 Years of Age With Childhood Absence Epilepsy or Juvenile Absence Epilepsy
Phase: PHASE3
Conditions: Childhood Absence Epilepsy, Juvenile Absence Epilepsy
Sponsor: UCB Biopharma SRL

UCB 
29 Mar 2021 
Clinical Study Protocol Amendment 2 
Brivaracetam 
EP0132 
Confidential 
Page 1 of 83 
A MULTICENTER, OPEN-LABEL, SINGLE-ARM STUDY TO 
EVALUATE LONG-TERM SAFETY, TOLERABILITY, AND 
EFFICACY OF BRIVARACETAM IN STUDY PARTICIPANTS 
2 TO 26 YEARS OF AGE WITH CHILDHOOD ABSENCE 
EPILEPSY OR JUVENILE ABSENCE EPILEPSY  
PROTOCOL EP0132 AMENDMENT 2 
PHASE 3 
SHORT TITLE: 
A long-term safety, tolerability, and efficacy study of brivaracetam in study participants 2 to 
26 years of age with childhood absence epilepsy or juvenile absence epilepsy. 
Sponsor: 
UCB Biopharma SRL 
Allée de la Recherche 60 
1070 Brussels 
BELGIUM 
Regulatory agency identifying number(s): 
Eudra CT Number: 
2020-002769-33 
IND Number: 
151255 
Confidential Material 
Confidential 
This document is the property of UCB and may not – in full or in part – be passed on, 
reproduced, published, or otherwise used without the express permission of UCB. 
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29 Mar 2021 
Clinical Study Protocol Amendment 2 
Brivaracetam 
EP0132 
 
 
 
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Page 2 of 83 
PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE 
Document History 
Document 
Date 
Type of amendment 
Amendment 2 
29 Mar 2021 
Substantial 
Amendment 1 
08 Sep 2020 
Substantial 
Original Protocol 
15 Jun 2020 
Not applicable 
 
Amendment 2 (29 Mar 2021) 
Overall Rationale for the Amendment 
EP0132 Protocol Amendment 2, dated 29 Mar 2021, was completed to: 
• Address Health Authority feedback  
• Correct minor errors/inconsistencies  
• Provide additional clarifying information  
EP0132 Protocol Amendment History is detailed in Section 10.11. 
Section # and Name 
Description of Change 
Brief Rationale 
Synopsis 
Text was added to the key 
inclusion/exclusion criteria description to 
include end-stage kidney disease requiring 
dialysis and hepatic impairment in the list of 
exclusion criteria noted. 
Clarification, as well as to note 
the newly added exclusion 
criterion (Section 5.2). 
Section 1.2 (Schema)  Revised the study schema to add visit 
windows for the MEV, FEV, YEV, and FV 
and frequency for the MEV, FEV, YEV, and 
SV. Additional dosing information was 
added for participants weighing less than 
50kg. 
Clarification of the EP0132 
study design. 
Section 1.3 (Schedule 
of Activities)  
Added text to footnote "c" describing the 
Down-titration Period to clarify that study 
participations who require down-titration 
will complete their daily seizure diaries 
during the Down-titration Period. 
Added "X’s” to Table 1‒2 to denote that 
participant diaries would be dispensed and 
retrieved during the Down-titration Period. 
Clarification of procedures for 
completion of the seizure 
diary. 
Section 1.3 (Schedule 
of Activities) 
Removed former footnote "d" and revised 
footnote "k" (previously footnote "l") to 
remove text that stated a BRV plasma 
concentration should be taken within 1 day 
of the occurrence of an SAE. There are no 
Error correction; not 
applicable for this study. 
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Brivaracetam 
EP0132 
 
 
 
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Section # and Name 
Description of Change 
Brief Rationale 
time approximation points to relate SAEs to 
BRV plasma concentrations for this study  
Section 1.3 (Schedule 
of Activities) 
Edited footnote "d" (previously footnote "e"), 
which stated no study drug will be dispensed 
at the FV or EDV to clarify that study drug 
will only be dispensed at these visits if the 
study participant is discontinuing study drug 
and requires down-titration.  
Error correction and further 
clarification of the procedures 
at the FV or EDV. 
Section 1.3 (Schedule 
of Activities) 
Removed inclusion of body weight/height 
and psychiatric/mental status assessments 
from footnotes "f" and "g"  (previously 
footnotes "g" and "h") describing complete 
and brief physical and neurological 
examinations as these assessments are 
presented as separate line items in Table 1‒2. 
Body weight, height, and 
psychiatric/mental status 
assessments are included in 
Table 1-2 as separate line 
items so need not be noted in 
the descriptions of brief and 
complete 
physical/neurological exams. 
Section 1.3 (Schedule 
of Activities) 
Added EEG assessments to FEV and 
YEV/EDV/FV to align with the text 
provided in Section 7.3.1 detailing seizure 
data based on EEG. 
Error correction.  
Section 1.3 (Schedule 
of Activities) 
Added text to footnote "m" (previously 
footnote "n") describing assessments 
conducted for Unscheduled Visits. 
Clarification that, in addition 
to the assessments noted in the 
Schedule of Activities table, 
additional assessments can be 
performed per the 
Investigator’s discretion. 
Section 2.3 
(Benefit/risk 
assessment) 
Added text and supportive publications 
describing the current approved treatments 
for absence seizure and their limitations. 
 
Text was added to include the risk 
assessment regarding the potential 
interaction if concomitant use of BRV and a 
COVID-19 vaccination were to occur. 
Response to Health Authority 
feedback.  
 
 
Inclusion of the risk 
assessment for concomitant 
use of a COVID-19 vaccine 
and BRV. 
Section 5.2 
(Exclusion criteria) 
Added an exclusion criteria for clinically 
relevant ECG abnormalities.  
Added a hepatic impairment exclusion 
criterion, with Child Pugh Score A, B, or C 
as the basis for determination by the 
Investigator. 
Added a new exclusion criterion for 
participants with known fructose intolerance 
or hypersensitivity to any of the ingredients 
in BRV oral solution. 
Consistency with parent study, 
N01269 
Response to Health Authority 
feedback. 
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Clinical Study Protocol Amendment 2 
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EP0132 
 
 
 
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Section # and Name 
Description of Change 
Brief Rationale 
Added a new exclusion criterion for 
participants with end-stage kidney disease 
requiring dialysis.  
Section 5.3 (Lifestyle 
restrictions) 
Added text to note that concomitant intake of 
alcohol is prohibited. 
Response to Health Authority 
feedback. 
Section 6.1.1 
(Alternative study 
treatment supply due 
to COVID-19) 
Removed "depot to participant" as a method 
for providing IMP to a study participant who 
is unable to return to the site but wishes to 
remain in the study. 
This method is not permitted 
due to privacy issues. 
Section 6.5.2 
(Prohibited 
concomitant 
treatments 
[medications and 
therapies]) 
Added text that use of substrates of alcohol 
dehydrogenase is prohibited.  
Response to Health Authority 
feedback. 
Section 6.5.3 (Rescue 
medication) 
Revised text to specify that rescue 
medication includes any treatment with 
permitted AEDs, including benzodiazepines. 
Clarification that 
benzodiazepines are permitted 
as rescue medication. 
Section 7.3.1 
(Seizure data based 
on EEG) 
Removed sentence stating the further 
information on EEG evaluation will be 
detailed in the EEG manual. 
Error correction; there is no 
manual for locally read EEGs. 
Section 7.3.2 
(Seizure diary) 
Added text to clarify that study participations 
who require down-titration will complete 
their daily seizure diaries during the Down-
titration Period 
Clarification of procedures for 
completion of the seizure 
diary. 
Section 8.1.2 (Body 
weight and height)  
Section added for body weight and height, 
and moved the applicable text from its 
former location in Section 8.1.1 (Physical 
examination). 
Body weight and height are 
assessed on a different 
schedule than for physical 
examinations; these 
assessments are presented 
separately in Table 1‒2. 
Section 8.1.4 
(Psychiatric and 
mental status 
evaluation) 
Section added to provide information 
regarding the psychiatric and mental status 
evaluation conducted as a part of each 
complete neurological examination. 
Alignment with the schedule 
of activities and the CRF. 
Section 8.1.5 (Vital 
signs) 
Revised text to state that 1 pulse and 1 blood 
pressure measurement will be recorded 
instead of an average of 3 consecutive blood 
pressure measurements. 
Alignment with the CRF. 
Section 8.1.8 
(Suicidal risk 
monitoring) 
Revised text to clarify administration of the 
C-SSRS consistently throughout the 
protocol. 
Consistent presentation of 
C-SSRS administration. 
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Clinical Study Protocol Amendment 2 
Brivaracetam 
EP0132 
 
 
 
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Section # and Name 
Description of Change 
Brief Rationale 
Section 8.2.5  
(Pregnancy), 
Section 10.4 
(Contraceptive 
guidance and 
collection of 
pregnancy 
information). 
Revised text to clarify that a pregnancy will 
be followed for at least 30 days after the birth 
of the child and, in certain circumstances, for 
up to 12 months. 
Clarification and consistency 
of this information across 
sections of the protocol. 
Section 8.4 
(Treatment of 
overdose) 
Revised text to specify that an overdose 
should be reported “within 24 hours” instead 
of “immediately.” 
Alignment with the 24-hour 
requirement for reporting of 
SAEs. 
Section 8.5 
(Pharmacokinetics) 
Revised text to specify that drug 
concentration information that may unblind 
N01269 will not be reported to investigative 
sites or blinded personnel until the study has 
completed (last patient last visit). 
Clarification of previously 
ambiguous text. 
Section 9.2 (General 
statistical 
considerations) 
Minor text revisions to refer to all AE 
outputs and not just AE tables, and remove 
"blinded" from the description of the data 
evaluation meeting. 
Clarification and error 
correction. 
Section 10.1.6 
(Source documents) 
Provide study-specific details regarding the 
electronic source document system that will 
be used for direct data capture. 
Clarification and alignment 
with ICH-GCP.  
Section 10.2 
(Appendix 2: Clinical 
laboratory tests) 
Revised text to specify that laboratory results 
that could unblind N01269 will not be 
reported to investigative sites or blinded 
personnel until the study has been unblinded. 
Clarification of previously 
ambiguous text. 
AE=adverse event; AED=antiepileptic drug; BRV=brivaracetam; COVID-19=coronavirus disease 2019; CRF=case 
report form; C-SSRS=Columbia-Suicide Severity Rating Scale; EDV=Early Discontinuation Visit; 
EEG=electroencephalogram; FEV=Full Evaluation Visit; FV=Final Visit; GCP=Good Clinical Practice; 
ICH=International Council for Harmonisation; IMP=investigational medicinal product; MEV=Minimal Evaluation 
Visit; MHRA=Medicines and Healthcare Products Regulatory Agency; RA=Regulatory Authority; SAE=serious 
adverse event; SV=Safety Visit; YEV=Yearly Evaluation Visit  
 
 
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Clinical Study Protocol Amendment 2 
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EP0132 
 
 
 
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SERIOUS ADVERSE EVENT REPORTING 
Serious adverse event reporting (24h) 
Fax 
Europe and Rest of the World: +32 2 386 24 21 
US and Canada: +1 800 880 6949 or +1 866 890 3175 
Email 
Global: DS_ICT@ucb.com 
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Clinical Study Protocol Amendment 2 
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EP0132 
 
 
 
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TABLE OF CONTENTS 
1 
PROTOCOL SUMMARY ............................................................................................... 11 
1.1 
Synopsis ....................................................................................................................... 11 
1.2 
Schema ......................................................................................................................... 18 
1.3 
Schedule of activities ................................................................................................... 19 
2 
INTRODUCTION ........................................................................................................... 23 
2.1 
Study rationale ............................................................................................................. 23 
2.2 
Background .................................................................................................................. 23 
2.3 
Benefit/risk assessment ................................................................................................ 24 
3 
OBJECTIVES AND ENDPOINTS ................................................................................. 25 
4 
STUDY DESIGN ............................................................................................................. 30 
4.1 
Overall design .............................................................................................................. 30 
4.1.1 
Study conduct due to coronavirus disease ........................................................... 31 
4.2 
Scientific rationale for study design ............................................................................ 32 
4.3 
Justification for dose .................................................................................................... 32 
4.4 
End of study definition................................................................................................. 33 
5 
STUDY POPULATION .................................................................................................. 33 
5.1 
Inclusion criteria .......................................................................................................... 33 
5.2 
Exclusion criteria ......................................................................................................... 34 
5.3 
Lifestyle restrictions..................................................................................................... 34 
5.4 
Screen failures .............................................................................................................. 35 
6 
STUDY TREATMENTS ................................................................................................. 35 
6.1 
Treatments administered .............................................................................................. 35 
6.1.1 
Alternative study treatment supply due to COVID-19 ........................................ 35 
6.2 
Preparation, handling, storage, and accountability requirements ................................ 35 
6.2.1 
Drug accountability/Device accountability ......................................................... 36 
6.3 
Measures to minimize bias: randomization and blinding ............................................ 36 
6.4 
Treatment compliance .................................................................................................. 36 
6.5 
Concomitant medication(s)/treatment(s) ..................................................................... 37 
6.5.1 
Permitted concomitant treatments (medications and therapies) .......................... 37 
6.5.2 
Prohibited concomitant treatments (medications and therapies) ......................... 37 
6.5.3 
Rescue medication ............................................................................................... 37 
6.6 
Dose modification ........................................................................................................ 37 
6.7 
Treatment after the end of the study ............................................................................ 38 
7 
DISCONTINUATION OF STUDY MEDICATION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL ........................................................................ 38 
7.1 
Discontinuation of study medication ........................................................................... 38 
7.1.1 
Liver chemistry stopping criteria ......................................................................... 38 
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7.1.2 
QTc stopping criteria ........................................................................................... 39 
7.2 
Participant discontinuation/withdrawal from the study ............................................... 39 
7.3 
Lost to follow up .......................................................................................................... 40 
8 
STUDY ASSESSMENTS AND PROCEDURES ........................................................... 41 
8.1 
Efficacy assessments .................................................................................................... 40 
8.1.1 
Seizure data based on EEG .................................................................................. 41 
8.1.2 
Seizure diary ........................................................................................................ 41 
8.2 
Safety assessments ....................................................................................................... 42 
8.2.1 
Physical examination ........................................................................................... 42 
8.2.2 
Neurological examination .................................................................................... 42 
8.2.3 
Psychiatric and mental status ............................................................................... 43 
8.2.4 
Vital signs ............................................................................................................ 43 
8.2.5 
Electrocardiograms .............................................................................................. 43 
8.2.6 
Clinical safety laboratory assessments ................................................................ 43 
8.2.7 
Suicidal risk monitoring ...................................................................................... 44 
8.2.8 
Participant- or caregiver-reported outcomes........................................................ 44 
8.2.8.1 
EpiTrack Junior ......................................................................................... 45 
8.2.8.2 
Pediatric Quality of Life Inventory ........................................................... 45 
8.2.9 
Nonabsence seizures ............................................................................................ 46 
8.2.9.1 
Nonabsence seizure incidence after first BRV treatment during the study 
based on EEG ............................................................................................ 46 
8.2.9.2 
Nonabsence seizure incidence after first BRV treatment during the study 
based on study participant diary ................................................................ 46 
8.3 
Adverse events and serious adverse events ................................................................. 46 
8.3.1 
Time period and frequency for collecting AE and SAE information .................. 47 
8.3.2 
Method of detecting AEs and SAEs .................................................................... 47 
8.3.3 
Follow-up of AEs and SAEs ................................................................................ 47 
8.3.4 
Regulatory reporting requirements for SAEs ...................................................... 47 
8.3.5 
Pregnancy ............................................................................................................ 48 
8.3.6 
Adverse events of special interest ........................................................................ 48 
8.3.7 
Anticipated serious adverse events ...................................................................... 49 
8.4 
Safety signal detection ................................................................................................. 49 
8.5 
Treatment of overdose ................................................................................................. 50 
8.6 
Pharmacokinetics ......................................................................................................... 50 
8.7 
Genetics........................................................................................................................ 50 
8.8 
Pharmacodynamics ...................................................................................................... 50 
8.9 
Biomarkers ................................................................................................................... 50 
8.10 
Health economics ......................................................................................................... 51 
9 
STATISTICAL CONSIDERATIONS ............................................................................. 51 
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9.1 
Definition of analysis sets ............................................................................................ 51 
9.2 
General statistical considerations ................................................................................. 51 
9.3 
Planned efficacy analyses ............................................................................................ 51 
9.3.1 
Analysis of the secondary efficacy endpoint ....................................................... 51 
9.4 
Planned safety and other analyses................................................................................ 52 
9.4.1 
Safety analyses ..................................................................................................... 52 
9.4.2 
Pharmacokinetic analyses .................................................................................... 52 
9.4.3 
Other analyses ...................................................................................................... 52 
9.5 
Handling of protocol deviations................................................................................... 52 
9.6 
Handling of dropouts or missing data .......................................................................... 52 
9.7 
Planned interim analysis and data monitoring ............................................................. 53 
9.8 
Determination of sample size ....................................................................................... 53 
10 SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS... 53 
10.1 
Appendix 1: Regulatory, ethical, and study oversight considerations ......................... 53 
10.1.1 
Regulatory and ethical considerations ................................................................. 53 
10.1.2 
Financial disclosure ............................................................................................. 54 
10.1.3 
Informed consent process .................................................................................... 54 
10.1.4 
Data protection ..................................................................................................... 54 
10.1.5 
Data quality assurance ......................................................................................... 55 
10.1.5.1 
Case report form completion ..................................................................... 56 
10.1.5.2 
Apps ........................................................................................................... 56 
10.1.6 
Source documents ................................................................................................ 56 
10.1.7 
Study and site closure .......................................................................................... 56 
10.1.8 
Publication policy ................................................................................................ 57 
10.2 
Appendix 2: Clinical laboratory tests .......................................................................... 58 
10.3 
Appendix 3: Adverse events – definitions and procedures for recording, evaluating, 
follow-up, and reporting .............................................................................................. 60 
10.4 
Appendix 4: Contraceptive guidance and collection of pregnancy information ......... 65 
10.5 
Appendix 5: Genetics ................................................................................................... 69 
10.6 
Appendix 6: Liver safety – suggested actions and follow-up assessments ................. 70 
10.7 
Appendix 7: Medical device AEs, adverse device effects, SAEs and device 
deficiencies: definition and procedures for recording, evaluating, follow-up, and 
reporting ....................................................................................................................... 73 
10.8 
Appendix 8: Rapid alert procedures ............................................................................ 74 
10.9 
Appendix 9: Country-specific requirements ................................................................ 75 
10.10 Appendix 10: Abbreviations and trademarks .............................................................. 76 
10.11 Appendix 11: Protocol amendment history ................................................................. 78 
11 REFERENCES ................................................................................................................ 82 
SPONSOR DECLARATION .................................................................................................. 83 
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Clinical Study Protocol Amendment 2 
Brivaracetam 
EP0132 
 
 
 
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LIST OF TABLES 
Table 1‒1: 
EP0132 schema ................................................................................................ 18 
Table 1‒2: 
Schedule of activities ....................................................................................... 19 
Table 8‒1: 
Participant- or caregiver-reported outcomes .................................................... 45 
Table 8‒2: 
Anticipated SAEs for the pediatric epilepsy population .................................. 49 
 
LIST OF FIGURES 
Figure 7‒1: 
Phase 3 liver chemistry stopping criteria and increased monitoring 
algorithm .......................................................................................................... 38 
Figure 7‒2: 
Liver chemistry increased monitoring algorithm with continued study 
intervention for participants with ALT ≥3xULN but <8xULN ....................... 39 
 
 
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1 
PROTOCOL SUMMARY 
1.1 
Synopsis 
Protocol title: A Multicenter, Open-label, Single-arm Study to Evaluate Long-term Safety, 
Tolerability, and Efficacy of Brivaracetam in Study Participants 2 to 26 Years of Age with 
Childhood Absence Epilepsy or Juvenile Absence Epilepsy 
Short Title: A long-term safety, tolerability, and efficacy study of brivaracetam in study 
participants 2 to 26 years of age with childhood absence epilepsy or juvenile absence epilepsy. 
Rationale: In a proof of principle study in study participants with photosensitive epilepsy, 
brivaracetam (BRV) showed dose-dependent efficacy with complete abolishment of the evoked 
generalized photoparoxysmal electroencephalogram (EEG) response after treatment of study 
participants with an 80mg single dose (Kasteleijn-Nolst Trenité et al, 2007). The effect compared 
favorably to the effect seen in a previous study with levetiracetam (LEV) using the same model. 
Response to treatment in the photosensitivity model may be more indicative of efficacy in 
generalized epilepsy rather than focal epilepsy (Yuen and Sims, 2014)  and both childhood 
absence epilepsy (CAE) and juvenile absence epilepsy (JAE) are types of generalized epilepsy. 
Given the limited current treatment options for CAE and JAE, BRV has the potential to be a 
valuable alternative to the monotherapy treatments currently available for patients with typical 
absence seizures. An antiepileptic drug (AED) used in monotherapy is preferable as it may 
improve adherence and tolerability, compared to the use as adjunctive therapy. Brivaracetam 
treatment is well tolerated and is easy to use without the need for titration. 
Objectives and Endpoints 
Objectives 
Endpoints/Estimands 
Primary objective 
Primary endpoints 
To investigate the long-
term safety and tolerability 
of BRV in pediatric study 
participants with CAE or 
JAE 
• Treatment-emergent adverse events 
Estimand 
1. Population: population as defined in the protocol-specified 
inclusion/exclusion criteria reflecting the target patient 
population who receive at least 1 dose of BRV during the 
study. 
2. Study participant-level outcome: TEAE occurrence. 
3. Intercurrent event handling: The intercurrent event of 
concomitant medication use is handled by using a treatment 
policy strategy in which all TEAE data are included, 
regardless of receipt of any concomitant medication. 
The intercurrent event of treatment discontinuation is 
handled by using a while-on-treatment strategy where 
observation ends at 14 days after treatment is stopped. 
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4. Population-level summary measure: incidence rates of 
TEAEs or incidence rates of TEAEs leading to 
discontinuation. 
To investigate the long-
term safety and tolerability 
of BRV in pediatric study 
participants with CAE or 
JAE 
• Treatment-emergent adverse events leading to 
discontinuation of study drug 
Estimand 
1. Population: population as defined in the protocol-specified 
inclusion/exclusion criteria reflecting the target patient 
population who receive at least 1 dose of BRV during the 
study. 
2. Study participant-level outcome: TEAE leading to 
discontinuation occurrence. 
3. Intercurrent event handling: The intercurrent event of 
concomitant medication use is handled by using a treatment 
policy strategy in which all TEAE data are included, 
regardless of receipt of any concomitant medication. 
4. Population-level summary measure: incidence rates of 
TEAEs or incidence rates of TEAEs leading to 
discontinuation. 
Primary objective 
Secondary endpoints 
To investigate the long-
term safety and tolerability 
of BRV in pediatric study 
participants with CAE or 
JAE 
• SAEs 
• Study drug-related TEAEs 
Estimand 
1. Population: population as defined in the protocol-specified 
inclusion/exclusion criteria reflecting the target patient 
population who receive at least 1 dose of BRV during the 
study. 
2. Study participant-level outcome: occurrence of events in the 
list above. 
3. Intercurrent event handling: The intercurrent event of 
concomitant medication use is handled by using a treatment 
policy strategy in which all TEAE data are included, 
regardless of receipt of any concomitant medication. 
The intercurrent event of treatment discontinuation is 
handled by using a while-on-treatment strategy where 
observation ends at 14 days after treatment is stopped. 
4. Population-level summary measure: incidence rates. 
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Primary objective 
Other endpoints 
To investigate the long-
term safety and tolerability 
of BRV in pediatric study 
participants with CAE or 
JAE 
• TEAEs requiring a change in BRV dose 
• Maximum intensity TEAE experienced (mild, moderate, and 
severe) 
• Drug-related serious TEAEs 
• Fatal AEs  
• TEAEs by maximum relationship (related and not related to 
BRV) 
• SAEs by maximum relationship (related and not related to 
BRV) 
Occurrence of other seizure types, including GTCS, based on 
diary or EEG: 
• Nonabsence seizures based on 1-hour EEG 
• Nonabsence seizures based on diary 
Estimand: 
1. Population: population as defined in the protocol-specified 
inclusion/exclusion criteria reflecting the target patient 
population who receive at least 1 dose BRV during the 
study. 
2. Study participant-level outcome: occurrence of events in the 
list of endpoints above. 
3. Intercurrent event handling: the intercurrent event of 
concomitant medication use is handled by using a treatment 
policy strategy in which all TEAE data are included, 
regardless of receipt of any concomitant medication. 
The intercurrent event of treatment discontinuation is 
handled by using a while-on-treatment strategy where 
observation ends at 14 days after treatment is stopped. 
• Population-level summary measure: incidence rates. 
To investigate the long-
term safety and tolerability 
of BRV in pediatric study 
participants with CAE or 
JAE 
• Change from Baseline to each applicable visit in safety 
laboratory tests  
• Change from Baseline to each applicable visit in ECG 
parameters 
• ECG findings at each applicable visit 
• Physical and neurological examinations findings at each 
applicable visit 
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• Psychiatric and mental status at each applicable visit 
• Changes from Baseline to each applicable visit in vital signs 
(blood pressure, pulse rate, body temperature)  
• Changes from Baseline to each applicable visit in body 
weight and height 
Secondary objective 
Secondary endpoints 
To investigate long-term 
efficacy of BRV in 
pediatric study participants 
with CAE or JAE 
• Absence seizure freedom within 4 days prior to or during the 
1-hour EEG at each applicable visit 
Estimand: 
1. Population: the study participant population as defined in the 
protocol-specified inclusion/exclusion criteria reflecting the 
target patient population. 
2. Study participant-level outcome: seizure freedom response 
while awake on 1-hour EEG at each applicable visit.  
3. Intercurrent event handling: The intercurrent event of 
concomitant use of any permitted AED, including 
benzodiazepines, within 4 days prior to or during the 1-hour 
EEG is handled in the definition of the participant-level 
variable implementing a composite strategy in which 
receiving any permitted concomitant AED, including 
benzodiazepines, within 4 days prior to or during the 1-hour 
EEG is counted as nonresponse (ie, considered as having 
absence seizures during the EEG). 
4. Population-level summary measure: percentage of study 
participants free from absence seizures. 
To investigate long-term 
efficacy of BRV in 
pediatric study participants 
with CAE or JAE 
• Absence seizure freedom based on diary over the entire 
evaluation period and by 3-month time intervals 
Estimand 
1. Population: the study participant population as defined in the 
protocol-specified inclusion/exclusion criteria reflecting the 
target patient population. 
2. Study participant-level outcome: seizure freedom response 
on diary over the evaluation period and by 3-month time 
intervals.  
3. Intercurrent event handling: The intercurrent event of 
concomitant use of any permitted AED, including 
benzodiazepines, during each applicable 3-month period is 
handled in the definition of the participant-level variable 
implementing a composite strategy in which receiving any 
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permitted concomitant AED, including benzodiazepines, in 
the 3-month period or during the visit is counted as 
nonresponse (ie, considered as having absence seizures). 
The intercurrent event of diary completion during each 
applicable period is handled in the definition of the 
participant-level variable implementing a composite strategy 
in which completing less than 80% of diaries during the 3-
month period is counted as nonresponse (ie, considered as 
having absence seizures). 
4. Population-level summary measure: percentage of study 
participants free from clinical absence seizures. 
Secondary objective 
Other endpoints 
To investigate long-term 
efficacy of BRV in 
pediatric study participants 
with CAE or JAE 
• Consecutive absence seizure freedom in 6-month periods 
based on EEG 
• Consecutive absence seizure freedom in 6-month periods 
based on diary 
Tertiary/Exploratory 
Other endpoints 
To investigate the long-
term effect of BRV on 
behavior, cognition, and 
quality of life in pediatric 
study participants with 
CAE or JAE 
• Change from Baseline to each applicable visit in the 
EpiTrack Junior scores (for study participants 6 to <18 years 
old) 
• Change from Baseline to each applicable visit in PedsQL 
Generic Core scale scores from the study participant 
self-reports (separate questionnaires for participants age in 
years: 5 to ≤7, 8 to ≤12, 13 to ≤17 years)  
• Change from Baseline to each applicable visit in PedsQL 
Generic Core scale scores from the parent proxy-reports 
(separate questionnaires for participants age in years: 2 to 
≤4, 5 to ≤7, 8 to ≤12, 13 to ≤17 years) 
AE=adverse event; AED=antiepileptic drug; BRV=brivaracetam; CAE=childhood absence epilepsy; 
ECG=electrocardiogram; EEG=electroencephalogram; GTCS=generalized tonic-clonic seizure; JAE=juvenile 
absence epilepsy; PedsQL=Pediatric Quality of Life; SAE=serious adverse event; TEAE=treatment-emergent 
adverse event 
Key inclusion/exclusion criteria 
Study participants who previously participated in N01269 and qualify for entry into EP0132 with 
a confirmed diagnosis of CAE or JAE, and for whom a reasonable benefit from long-term 
administration of BRV is expected, in the opinion of the Investigator, are eligible to participate. 
Study participants must not have severe medical, neurological, or psychiatric disorders or 
laboratory values, which could, at the discretion of the Investigator, affect safe participation in 
the study or would preclude appropriate study participation. Study participants must also not 
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have end-stage kidney disease requiring dialysis, hepatic impairment, active suicide ideation, or 
a lifetime history of suicide attempt. 
Overall design 
This is a Phase 3, open-label, single-arm, multicenter, long-term follow-up study to evaluate the 
safety, tolerability, and efficacy of BRV in pediatric study participants with CAE or JAE. The 
study is designed for study participants in the age range of 2 to 26 years of age, who have 
participated in study N01269 and qualify for entry into EP0132.  
Upon enrollment, eligible study participants will enter the Evaluation Period and start on a BRV 
dose of 100mg/day (or equivalent dose of 2mg/kg/day for study participants weighing less than 
50kg). The dose may be adjusted after 3 days in the range of 50 to 200mg/day (or equivalent 
dose of 1 to 4mg/kg/day for study participants weighing less than 50kg) based on the individual 
needs. 
The Entry Visit (EV) is the first study visit and is equivalent to last study visit of the core study 
as defined in the study protocol of N01269. Two weeks (±2 days) after study start, the study 
participant will be contacted by phone to check on the appropriateness of the BRV dose. Within 
each year of study participation during the Evaluation Period, Minimal Evaluation Visits 
(MEVs) will be performed at Months 3 and 9, Full Evaluation Visits (FEVs) will be performed 
at Month 6, and Yearly Evaluation Visits (YEVs) will be performed at Month 12. At any time, 
the study participant may have an Unscheduled Visit if the Investigator or the participant and/or 
parent(s)/legal representative(s) consider it necessary. For study participants who continue in the 
study until it ends, the Evaluation Period will last from the EV to the Final Visit (FV). For study 
participants who prematurely discontinue the study, the Evaluation Period will last from the EV 
until the Early Discontinuation Visit (EDV). 
For study participants who transition to another BRV study or a managed access program or 
similar type of program or who convert to commercial BRV (if, when, and where available), the 
FV instead of the EDV will need to be completed; however, down-titration and the Safety Visit 
(SV) will not be applicable.  
For study participants who will discontinue BRV treatment following the EDV or FV, the BRV 
dose will be reduced by a maximum of half the dose every week for a maximum of 4 weeks until 
a dose of 1mg/kg/day (50mg/day for study participants with body weight >50kg) is reached 
(Down-Titration Period). A Down-Titration Visit (DTV) will be performed at the end of the 
Down-Titration Period, and study drug will be discontinued at the DTV. After 2 weeks free of 
study drug (Safety Period), study participants will complete the SV.  
Number of Participants 
Approximately 140 study participants may enroll in this study, based upon the rollover 
expectations from N01269 into EP0132. 
Treatment Groups and Duration 
Brivaracetam (tablet or oral solution) will be administered twice per day in equal doses. Twice 
daily dosing with equivalent morning and evening doses approximately 12 hours apart is 
recommended to achieve more regular exposure over the 24-hour interval; however, the dosing 
amount and schedule may be adjusted as needed to improve tolerability and efficacy in 
consultation with the Investigator. 
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Upon enrollment, eligible study participants will enter the Evaluation Period and start on a BRV 
dose of 100mg/day (or equivalent dose of 2mg/kg/day for study participants weighing less than 
50kg). The dose may be adjusted after 3 days in the range of 50 to 200mg/day (or equivalent 
dose of 1 to 4mg/kg/day for study participants weighing less than 50kg) based on the individual 
needs. The maximum allowed daily dose in EP0132 is 200mg/day (or equivalent dose of 
4mg/kg/day for study participants weighing less than 50kg). Dose adjustments of BRV and/or 
concomitant AEDs based on clinical judgment are allowed at any time, 3 days after study start 
and onwards. 
The duration of the study per study participant will be 2 years at minimum, until approval of 
BRV for the indication of CAE or JAE has been obtained for pediatric participants 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 indication is stopped by the Sponsor, whichever comes first.
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1.2 
Schema 
Table 1‒1: 
EP0132 schema 
Study Period 
Evaluation Period 
Down-
Titration 
Period 
Safety 
Period 
Visit Type 
EV 
TCa 
MEV 
FEV 
MEV 
YEV 
FV 
EDV 
DTV 
SV 
Visit Timing 
Y1, D1 
Y1, D14 
Y1, M3/ 
Y2, M15 
Y1, M6/ 
Y2, M18 
Y1, M9/ 
Y2, M21 
Y1, M12 
Y2, M24c 
As 
needed 
 
Visit Window 
±7 Days 
±2 Days 
±7 Days 
±7 Days  
±7 Days 
±7 Days 
±7 Days 
 
 
 
Frequency 
 
3 months 
after EV and 
3 months 
after YEV 
for every 
year of 
participation 
6 months 
after EV and 
6 months 
after YEV 
for every 
year of 
participation 
9 months 
after EV and 
9 months 
after YEV 
for every 
year of 
participation 
12 
months 
after EV 
 
 
2 weeks 
after last 
dose of 
study drug 
BRV 
Treatment 
100mg/day 
(2mg/kg/day for 
participants 
weighing less 
than 50kg) 
Individual doseb 
Reduce max 
dose by ½ 
until 
1mg/kg/day 
BRV-free 
period 
Duration 
≥2 yearsc 
Up to 4 weeks 
2 weeks 
BRV=brivaracetam; CAE=childhood absence epilepsy; D=Day; DTV=Down-titration Visit; EDV=Early Discontinuation Visit; EV=Entry Visit; FEV=Full 
Evaluation Visit; FV=Final Visit; JAE=juvenile absence epilepsy; max=maximum; M=month; MEV=Minimal Evaluation Visit; SV=Safety Visit; 
TC=telephone call; Y=treatment year; YEV=Yearly Evaluation Visit 
a Study participants will be contacted after 2 weeks (±2 days) to check for appropriateness of dose. 
b Participants will receive 100mg/day upon entry into EP0132. The dose may be adjusted after 3 days in the range of 50 to 200mg/day (or equivalent dose of 1 to 
4mg/kg/day for study participants weighing less than 50kg) based on the individual needs. 
c The duration of the study per study participant will be 2 years at minimum, until approval of BRV for the indication of CAE or JAE has been obtained for 
pediatric participants 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 indication is stopped by the Sponsor, 
whichever comes first.  
 
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1.3 
Schedule of activities 
Table 1‒2: 
Schedule of activities 
Study period 
Evaluation Period 
Down-
Titration 
Period 
Safety 
Period 
Visit 
EVa 
TC 
MEV 
FEV 
YEV/EDVb/FV 
UV 
DTVc 
SV 
Frequency 
 
After 
2 weeks 
± 2 days 
Months 3 and 9 
during each year 
of participation 
Month 6 
during each 
year of 
participation 
Month 12 
during each 
year of 
participation 
(YEV)/ 
Month 24 or 
later (FV) 
 
 
 
Procedures 
 
Written informed consent 
X 
 
 
 
 
 
 
 
Assent form (if applicable) 
X 
 
 
 
 
 
 
 
Study participant identification card 
X 
 
 
 
 
 
 
 
Inclusion/exclusion criteria 
X 
 
 
 
 
 
 
 
Prior and concomitant medications 
and medical procedures 
X 
 
X 
X 
X 
X 
X 
X 
IXRS 
X 
 
X 
X 
X 
X 
X 
X 
Recording of AEs 
X 
X 
X 
X 
X 
X 
X 
X 
Study drug dispensed 
X 
X 
(as 
applicable) 
X 
X 
Xd 
X 
(as 
applicable) 
 
 
Study drug returnede 
 
 
X 
X 
X 
X 
(as 
applicable) 
X 
 
Participant diary dispensed 
X 
 
X 
X 
Xd 
 
X 
 
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Study period 
Evaluation Period 
Down-
Titration 
Period 
Safety 
Period 
Visit 
EVa 
TC 
MEV 
FEV 
YEV/EDVb/FV 
UV 
DTVc 
SV 
Frequency 
 
After 
2 weeks 
± 2 days 
Months 3 and 9 
during each year 
of participation 
Month 6 
during each 
year of 
participation 
Month 12 
during each 
year of 
participation 
(YEV)/ 
Month 24 or 
later (FV) 
 
 
 
Procedures 
 
Participant diary retrieved 
 
 
X 
X 
X 
 
X 
 
Assessment of childbearing potential  
 
 
X 
X 
X 
 
 
 
Complete physical/neurological 
examinationf 
 
 
  
X 
X 
 
 
X 
Brief physical/neurological 
examinationg 
 
 
X 
 
 
X 
 
 
Psychiatric and mental status 
 
 
 
X 
X 
 
 
X 
Vital signsh 
 
 
X 
X 
X 
 
X 
X 
Dose adaptation (optional) 
 
X 
X 
X 
X 
X 
 
 
Body weight, height 
 
 
X 
X 
X 
 
 
 
Laboratory assessments for safetyi 
 
 
X 
X 
X 
 
 
Xj 
BRV plasma concentrationk 
 
 
 
X 
X 
 
 
 
C-SSRSl 
 
 
X 
X 
X 
Xm 
X 
X 
EpiTrack Juniorn 
 
 
 
X 
X 
 
 
X 
PedsQLn 
 
 
 
X 
X 
 
 
 
ECGo 
 
 
 
 
X 
 
 
Xj 
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Study period 
Evaluation Period 
Down-
Titration 
Period 
Safety 
Period 
Visit 
EVa 
TC 
MEV 
FEV 
YEV/EDVb/FV 
UV 
DTVc 
SV 
Frequency 
 
After 
2 weeks 
± 2 days 
Months 3 and 9 
during each year 
of participation 
Month 6 
during each 
year of 
participation 
Month 12 
during each 
year of 
participation 
(YEV)/ 
Month 24 or 
later (FV) 
 
 
 
Procedures 
 
EEG (1h EEG/HV)p  
 
 
 
X 
X 
X 
(as 
applicable) 
 
 
End of study status 
 
 
 
 
Xq  
 
 
X 
AE=adverse event; AED=antiepileptic drug; ALP=alkaline phosphatase; ALT=alanine aminotransferase; AST=aspartate aminotransferase; 
BRV=brivaracetam; C-SSRS=Columbia-Suicide Severity Rating Scale; DTV=Down-Titration Visit; ECG=electrocardiogram; eCRF=electronic case report 
form; EDV=Early Discontinuation Visit; EEG=electroencephalogram; EV=Entry Visit; FEV=Full Evaluation Visit; FV=Final Visit; 
GGT=gamma-glutamyltransferase; HV=hyperventilation; IXRS=interactive voice or web response system; MEV=Minimal Evaluation Visit; 
PedsQL=Pediatric Quality of Life Inventory; PK=pharmacokinetic; S=on-site visit; SAE=serious adverse event; SV=Safety Visit; TC=telephone call; 
UV=Unscheduled Visit; YEV=Yearly Evaluation Visit 
a The EV is also the last completed study visit of N01269. The following Baseline data will be obtained from N01269 and should not be recorded on the eCRF 
for this study's EV: demographics, general medical and procedure history, epilepsy history, AED history, seizure count/ absence seizure count, ECG, laboratory 
assessments for safety, vital signs, body weight, height, physical and neurological examinations, psychiatric and mental status, and recording of epileptic 
seizures. 
b Participants who discontinue from the study before Month 24 will complete an EDV, unless the participant is transitioning to another BRV study, in which case 
an FV will be completed (see Section 4.1). 
c Visit should be scheduled at the end of the Down Titration Period. The duration of the Down Titration Period will depend on when the final dose of the study 
drug was taken during the Evaluation Period, with a maximum duration of 4 weeks. Study participants requiring down titration will complete their daily seizure 
diaries during the Down-titration Period. 
d No study participant diary will be dispensed at the FV or EDV. Study drug will only be dispensed at the FDV or EDV if the study participant is discontinuing 
study drug and requires down titration.  
e Drug return includes study drug intake recording and accountability and recording of concomitant AEDs. 
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f A complete physical examination will include, at a minimum, general appearance; eyes, ear, nose, and throat; skin; and assessments of the cardiovascular, 
respiratory, gastrointestinal, and musculoskeletal systems. A complete neurological examination will include, at a minimum, assessments of cranial nerves, 
motor and sensory systems, deep tendon reflexes, coordination, and gait. 
g A brief physical examination will include, at a minimum, general appearance; assessments of the skin, respiratory system, and cardiovascular systems; and 
abdomen (liver and spleen). A brief neurological examination will include, at a minimum, assessments of cranial nerves, motor system, coordination, and gait. 
h Vital sign measurements include blood pressure and pulse rate. 
i Full laboratory assessments for safety include hematology and biochemistry (including hepatic monitoring of ALT, AST, ALP, total bilirubin, and GGT) for all 
study participants and urinalysis for study participants for whom sample collection is feasible. Female study participants of childbearing potential should have a 
urine pregnancy test done at all laboratory assessment visits. Endocrinology testing will be performed for all study participants <18 years of age at the 
YEV/FV. For study participants on study drug for more than 12 months, laboratory assessments at MEV can be omitted. 
j At the SV, ECGs and laboratory assessments for safety will be performed only if abnormal at the EDV or FV. 
k At the FEV and YEV/EDV/FV Visits, when PK sampling is planned, study participants should not take their morning BRV dose prior to arriving in the clinic.  
l The C-SSRS will be completed by study participants ≥6 years of age. The “Since Last Visit” version of the C-SSRS will be used, with the following exception: 
If study participant turns 6 years of age during EP0132, the “Already Enrolled” version of the C-SSRS should be completed at the first visit after the sixth 
birthday, and the “Since Last Visit” version of the C-SSRS should be completed at subsequent visits. 
m If an Unscheduled Visit is needed, the assessments noted will be performed. Additional assessments can be performed at the Investigator’s discretion. If an 
unscheduled visit is conducted due to safety or efficacy reasons, the C-SSRS will be performed for study participants ≥6 year of age. 
n Additional details for the patient-reported outcomes (ie, versions and ages) are provided in Table 8‒1. 
o An ECG must be scheduled once a year at the YEV and at the EDV in the case of early discontinuation.  
p The investigator/designated EEG reader should attempt to keep the study participant awake for the duration of the 1-hour EEG; a minimum of 30 minutes of 
awake time will be required for evaluability. 
q End of study status only for study participants who continue in the study until it ends (SV) and for whom the visit corresponds to the FV. 
 
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2 
INTRODUCTION 
2.1 
Study rationale 
Childhood absence epilepsy (CAE) and Juvenile absence epilepsy (JAE) present with typical 
absences and are classified by the International League Against Epilepsy (ILAE) as idiopathic 
generalized epilepsy types (ILAE, 2019). Treatment options are limited: Ethosuximide (ESM) is 
considered effective against absence but not against other types of seizures like generalized tonic 
clonic or myoclonic seizures. Valproic acid (VPA) is a broad-spectrum and effective treatment 
but there are important safety issues, including negative impact on attention and cognitive 
development, liver and bone marrow toxicity, and teratogenesis, which raises important concerns 
for the treatment of females. Lamotrigine (LTG) is an alternative, even though not approved for 
the treatment of absence seizures in the US; however, it is less efficacious than VPA and ESM 
and needs a very long titration time due to the risk of severe cutaneous reactions. Further, LTG 
has a high potential for relevant drug-drug interactions, including oral hormonal contraceptives. 
This limits the value of LTG in female patients of childbearing potential. Moreover, in CAE, 
approximately one-third of patients continue to have seizures despite an initial and second 
therapy, meeting the criteria for drug resistance (Cnaan et al, 2017). The seizure outcomes of 
patients with JAE is even less favorable (Tovia et al, 2006). Therefore, there is a need for 
additional monotherapy treatments. 
N01269 is a multicenter, double-blind, placebo-controlled, parallel-group study with an adaptive 
design to evaluate the efficacy, safety, and tolerability of brivaracetam (BRV) monotherapy in 
study participants 2 to 25 years of age with CAE or JAE. An AED used in monotherapy is 
preferable as it may improve treatment adherence and tolerability as compared with its use as 
adjunctive therapy. Brivaracetam treatment is well tolerated and is easy to use with no titration. 
Given limited current treatment options, BRV has the potential to be a valuable addition to 
monotherapy treatment of patients with typical absence seizures. 
EP0132 is Phase 3, multicenter, open-label, single-arm study to evaluate the long-term safety, 
tolerability, and efficacy of BRV in pediatric study participants with CAE or JAE, who are 
rolling over from study N01269 (core study). Study participants who participated in N01269 and 
qualify for entry into EP0132 and for whom a reasonable benefit from long-term administration 
of BRV is expected will get the opportunity to participate.  
2.2 
Background 
Brivaracetam ((2S)-2-[(4R)-2-oxo-4-propyltetrahydro-1H-pyrrol-1-yl]butanamide) is a 
2-pyrrolidone derivative. Brivaracetam displays a high and selective affinity for the synaptic 
vesicle protein 2A (SV2A) in the brain. Binding to SV2A is believed to be the primary 
mechanism for BRV anticonvulsant activity. 
The recommended starting dosage for adjunctive therapy in focal seizures in adults is 50mg 
twice daily (bid; 100mg/day) with 100mg bid (200mg/day) being the maximum recommended 
dose. The dosage may be adjusted between 25mg bid (50mg/day) and 100mg bid (200mg/day) 
based on individual patient tolerability and therapeutic response. 
Between 2016 and 2019, marketing authorization for the use of oral and intravenous (iv) BRV as 
adjunctive treatment for partial-onset seizures (POS) was granted in the EU, US, Turkey, 
Mexico, Australia, Argentina, Brazil, Taiwan, Israel, United Arab Emirates, Qatar, Hong Kong, 
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and Saudi Arabia for patients 16 years of age and older with epilepsy and in Switzerland and 
Canada for patients 18 years of age and older with epilepsy. In addition, use of oral BRV was 
approved in Russia, India, Colombia, Lebanon, Korea, and Kuwait. 
Brivaracetam has been approved in the US as monotherapy, based on extrapolation, for the 
treatment of POS in patients with epilepsy aged 16 years and older. An application for the 
extension of indication to the pediatric population from 4 years of age in the EU (adjunctive) and 
the US (adjunctive and monotherapy) based on the concept of extrapolation of efficacy data from 
the adult population was approved in 2018. In Taiwan, BRV was approved as monotherapy and 
adjunctive therapy for POS in adults and children aged 4 years and older in 2019. Of note, in the 
US and in Taiwan, iv BRV is indicated for the treatment of POS only in adult patients (16 years 
of age and older). The extension of the indication to the pediatric population from 4 years of age 
in Israel and Australia (adjunctive) based on the concept of extrapolation of efficacy data from 
the adult population was approved in 2019. In Argentina, BRV has been approved as 
monotherapy and adjunctive therapy for POS in adults aged 16 years and older. 
2.3 
Benefit/risk assessment 
According to the current approved indication, BRV is indicated as monotherapy and adjunctive 
therapy for focal/POS with or without secondary generalization in patients from 4 years of age 
with epilepsy. The approved indications for BRV may vary according to the countries of 
authorization. 
Four antiseizure medications have been approved for the treatment of absence seizures, namely 
ethosuximide, valproate, lamotrigine and clonazepam, with the first 3 being commonly used as 
initial monotherapy (Glauser et al, 2010). While ethosuximide is usually effective against 
absence seizures, it is not considered effective against other seizure types such as tonic-clonic 
seizures, limiting its use for patients with JAE, in which this type of seizure is common. 
Ethosuximide’s use, especially in children, is also limited by gastrointestinal side effects and the 
need for monitoring liver function. Valproate is a broad-spectrum antiseizure medication, 
however, there are significant safety concerns with its use, including the negative impact on 
attention, liver and bone marrow toxicity, and teratogenicity. Lamotrigine is limited by its very 
long up-titration needs, the high potential for drug-drug interactions, and the potential for severe 
cutaneous adverse reactions. Moreover, a number of patients with CAE are drug resistant to the 
3 commonly used antiseizure medications, as shown in a large multicenter study, in which 
approximately one third of patients with CAE met ILAE criteria for drug resistance (Cnaan et al, 
2017). Due to the limitations in currently available treatments, UCB believes BRV could be a 
valuable addition. 
Clinical development is ongoing for the following indications in relation to epilepsy: 
monotherapy and adjunctive therapy of POS in children and infants aged from 1 month to 
≤4 years of age with epilepsy, treatment of neonatal seizures, and treatment of CAE and JAE. 
Cumulatively, approximately 4536 study participants have been enrolled in the BRV clinical 
development program; an estimated 4087 study participants were exposed to BRV in completed 
and ongoing clinical trials as of the current safety update report data lock point of 14 Jan 2020. 
Additionally, there were: 194 study participants exposed in the ongoing blinded study EP0083 
where the randomization scheme is 1:1:1 (placebo:BRV 50mg/day:BRV 200mg/day); 
47 Japanese study participants exposed in the ongoing long-term follow-up (LTFU) study 
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(EP0085); and 44 study participants in ongoing open-label study of iv BRV (EP0065). Based on 
marketing experience, the exposure to BRV is estimated at 88,532 patient-years during this 
reporting interval and at 188,177 patient-years cumulatively since the International Birth Date. 
In total, 263 pediatric study participants (1 month to <17 years of age) received BRV in other 
studies, of which 44 were from EP0065, 99 were from N01263, and 120 were directly enrolled 
into N01266. Based on the information supplied in the pediatric efficacy supplement where the 
pharmacokinetics (PK), efficacy, and safety profiles have been established for pediatric patients 
with POS 4 years to <16 years of age, it was determined that the benefits of BRV treatment for 
pediatric patients are similar to those for adults. In general, the safety profile of BRV in the 
pediatric population is similar to that reported in adults with POS and the risks characterized in 
the adult population are applicable to the pediatric population. 
Brivaracetam seems a promising candidate for the treatment of typical absence seizures. Both 
BRV and levetiracetam (LEV), an AED with a similar mechanism of action as BRV, have been 
shown to be active in a preclinical rat model for absence seizures (genetic absence epilepsy rat 
from Strasbourg), with BRV being more efficacious compared with LEV (Matagne et al, 2008). 
Furthermore, in a proof-of-concept study in participants with photosensitive epilepsy, BRV 
showed dose-dependent efficacy with complete abolishment of photosensitive epilepsy after 
treatment of study participants with an 80mg single dose (Kasteleijn-Nolst Trenité et al, 2007). 
In addition, LEV was effective in treating typical absence seizures in a randomized 
placebo-controlled study with newly diagnosed CAE and JAE study participants (Fattore et al, 
2011). 
In conclusion, given the study design, patient population, and safety monitoring proposed, it is 
UCB’s opinion that the anticipated therapeutic benefits of BRV will outweigh any potential risks 
possibly associated with this Phase 2/3 study. This study is part of a larger pediatric development 
program which aims to evaluate the safety and tolerability of BRV in pediatric subjects, which 
will ultimately provide relevant information of potential benefit and risk to this population of 
patients with a recognized medical need. 
Furthermore, and in face of the current SARS-CoV-2 (COVID-19) pandemic, there are no 
expected interactions between brivaracetam and COVID-19 vaccines, based on the mechanism 
of action of BRV. Therefore, the benefit-risk profile of BRV remains favorable. 
More detailed information about the known and expected benefits and risks and reasonably 
expected adverse events (AEs) of BRV may be found in the Investigator's Brochure (IB) or 
Summary of Product Characteristics. 
3 
OBJECTIVES AND ENDPOINTS 
Objectives 
Endpoints/Estimands 
Primary objective 
Primary endpoints 
To investigate the long-
term safety and tolerability 
of BRV in pediatric study 
participants with CAE or 
JAE 
• Treatment-emergent adverse events 
Estimand 
1. Population: population as defined in the protocol-specified 
inclusion/exclusion criteria reflecting the target patient 
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Objectives 
Endpoints/Estimands 
population who receive at least 1 dose of BRV during the 
study. 
2. Study participant-level outcome: TEAE occurrence. 
3. Intercurrent event handling: The intercurrent event of 
concomitant medication use is handled by using a treatment 
policy strategy in which all TEAE data are included, 
regardless of receipt of any concomitant medication. 
The intercurrent event of treatment discontinuation is 
handled by using a while-on-treatment strategy where 
observation ends at 14 days after treatment is stopped. 
4. Population-level summary measure: incidence rates of 
TEAEs or incidence rates of TEAEs leading to 
discontinuation. 
To investigate the long-
term safety and tolerability 
of BRV in pediatric study 
participants with CAE or 
JAE 
• Treatment-emergent adverse events leading to 
discontinuation of study drug 
Estimand 
1. Population: population as defined in the protocol-specified 
inclusion/exclusion criteria reflecting the target patient 
population who receive at least 1 dose of BRV during the 
study. 
2. Study participant-level outcome: TEAE leading to 
discontinuation occurrence. 
3. Intercurrent event handling: The intercurrent event of 
concomitant medication use is handled by using a treatment 
policy strategy in which all TEAE data are included, 
regardless of receipt of any concomitant medication. 
4. Population-level summary measure: incidence rates of 
TEAEs or incidence rates of TEAEs leading to 
discontinuation. 
Primary objective 
Secondary endpoints 
To investigate the long-
term safety and tolerability 
of BRV in pediatric study 
participants with CAE or 
JAE 
• SAEs 
• Study drug-related TEAEs 
Estimand 
1. Population: population as defined in the protocol-specified 
inclusion/exclusion criteria reflecting the target patient 
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Objectives 
Endpoints/Estimands 
population who receive at least 1 dose of BRV during the 
study. 
2. Study participant-level outcome: occurrence of events in the 
list above. 
3. Intercurrent event handling: The intercurrent event of 
concomitant medication use is handled by using a treatment 
policy strategy in which all TEAE data are included, 
regardless of receipt of any concomitant medication. 
The intercurrent event of treatment discontinuation is 
handled by using a while-on-treatment strategy where 
observation ends at 14 days after treatment is stopped. 
4. Population-level summary measure: incidence rates. 
Primary objective 
Other endpoints 
To investigate the long-
term safety and tolerability 
of BRV in pediatric study 
participants with CAE or 
JAE 
• TEAEs requiring a change in BRV dose 
• Maximum intensity TEAE experienced (mild, moderate, and 
severe) 
• Drug-related serious TEAEs 
• Fatal AEs  
• TEAEs by maximum relationship (related and not related to 
BRV) 
• SAEs by maximum relationship (related and not related to 
BRV) 
Occurrence of other seizure types, including GTCS, based on 
diary or EEG: 
• Nonabsence seizures based on 1-hour EEG 
• Nonabsence seizures based on diary 
Estimand: 
1. Population: population as defined in the protocol-specified 
inclusion/exclusion criteria reflecting the target patient 
population who receive at least 1 dose BRV during the 
study. 
2. Study participant-level outcome: occurrence of events in the 
list of endpoints above. 
3. Intercurrent event handling: the intercurrent event of 
concomitant medication use is handled by using a treatment 
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Objectives 
Endpoints/Estimands 
policy strategy in which all TEAE data are included, 
regardless of receipt of any concomitant medication. 
The intercurrent event of treatment discontinuation is 
handled by using a while-on-treatment strategy where 
observation ends at 14 days after treatment is stopped. 
• Population-level summary measure: incidence rates. 
To investigate the long-
term safety and tolerability 
of BRV in pediatric study 
participants with CAE or 
JAE 
• Change from Baseline to each applicable visit in safety 
laboratory tests  
• Change from Baseline to each applicable visit in ECG 
parameters 
• ECG findings at each applicable visit 
• Physical and neurological examinations findings at each 
applicable visit 
• Psychiatric and mental status at each applicable visit 
• Changes from Baseline to each applicable visit in vital signs 
(blood pressure, pulse rate, body temperature)  
• Changes from Baseline to each applicable visit in body 
weight and height 
Secondary objective 
Secondary endpoints 
To investigate long-term 
efficacy of BRV in 
pediatric study participants 
with CAE or JAE 
• Absence seizure freedom within 4 days prior to or during the 
1-hour EEG at each applicable visit 
Estimand: 
1. Population: the study participant population as defined in the 
protocol-specified inclusion/exclusion criteria reflecting the 
target patient population. 
2. Study participant-level outcome: seizure freedom response 
while awake on 1-hour EEG at each applicable visit.  
3. Intercurrent event handling: The intercurrent event of 
concomitant use of any permitted AED, including 
benzodiazepines, within 4 days prior to or during the 1-hour 
EEG is handled in the definition of the participant-level 
variable implementing a composite strategy in which 
receiving any permitted concomitant AED, including 
benzodiazepines, within 4 days prior to or during the 1-hour 
EEG is counted as nonresponse (ie, considered as having 
absence seizures during the EEG). 
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Objectives 
Endpoints/Estimands 
4. Population-level summary measure: percentage of study 
participants free from absence seizures. 
To investigate long-term 
efficacy of BRV in 
pediatric study participants 
with CAE or JAE 
• Absence seizure freedom based on diary over the entire 
evaluation period and by 3-month time intervals 
Estimand 
1. Population: the study participant population as defined in the 
protocol-specified inclusion/exclusion criteria reflecting the 
target patient population. 
2. Study participant-level outcome: seizure freedom response 
on diary over the evaluation period and by 3-month time 
intervals.  
3. Intercurrent event handling: The intercurrent event of 
concomitant use of any permitted AED, including 
benzodiazepines, during each applicable 3-month period is 
handled in the definition of the participant-level variable 
implementing a composite strategy in which receiving any 
permitted concomitant AED, including benzodiazepines, in 
the 3-month period or during the visit is counted as 
nonresponse (ie, considered as having absence seizures). 
The intercurrent event of diary completion during each 
applicable period is handled in the definition of the 
participant-level variable implementing a composite strategy 
in which completing less than 80% of diaries during the 3-
month period is counted as nonresponse (ie, considered as 
having absence seizures). 
4. Population-level summary measure: percentage of study 
participants free from clinical absence seizures. 
Secondary objective 
Other endpoints 
To investigate long-term 
efficacy of BRV in 
pediatric study participants 
with CAE or JAE 
• Consecutive absence seizure freedom in 6-month periods 
based on EEG 
• Consecutive absence seizure freedom in 6-month periods 
based on diary 
Tertiary/Exploratory 
Other endpoints 
To investigate the long-
term effect of BRV on 
behavior, cognition, and 
quality of life in pediatric 
• Change from Baseline to each applicable visit in the 
EpiTrack Junior scores (for study participants 6 to <18 years 
old) 
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Objectives 
Endpoints/Estimands 
study participants with 
CAE or JAE 
• Change from Baseline to each applicable visit in PedsQL 
Generic Core scale scores from the study participant 
self-reports (separate questionnaires for participants age in 
years: 5 to ≤7, 8 to ≤12, 13 to ≤17 years)  
• Change from Baseline to each applicable visit in PedsQL 
Generic Core scale scores from the parent proxy-reports 
(separate questionnaires for participants age in years: 2 to 
≤4, 5 to ≤7, 8 to ≤12, 13 to ≤17 years) 
AE=adverse event; AED=antiepileptic drug; BRV=brivaracetam; CAE=childhood absence epilepsy; 
ECG=electrocardiogram; EEG=electroencephalogram; GTCS=generalized tonic-clonic seizure; JAE=juvenile 
absence epilepsy; PedsQL=Pediatric Quality of Life; SAE=serious adverse event; TEAE=treatment-emergent 
adverse event 
4 
STUDY DESIGN 
4.1 
Overall design 
This is a Phase 3, open-label, single-arm, multicenter, LTFU study to evaluate the safety, 
tolerability, and efficacy of BRV in pediatric study participants with CAE or JAE. The study is 
designed for study participants in the age range of 2 to 26 years of age who have participated in 
study N01269 and qualify for entry into EP0132.  
Upon enrollment, eligible study participants will enter the Evaluation Period and start on a BRV 
dose of 100mg/day (or equivalent dose of 2mg/kg/day for study participants weighing less than 
50kg). The dose may be adjusted after 3 days in the range of 50 to 200mg/day (or equivalent 
dose of 1 to 4mg/kg/day for study participants weighing less than 50kg) based on the individual 
needs. 
The Entry Visit (EV) is the first study visit and is equivalent to last study visit of the core study 
as defined in the study protocol of N01269. Two weeks (±2 days) after study start, the study 
participant will be contacted by phone to check on the appropriateness of the BRV dose. Within 
each year of study participation during the Evaluation Period, Minimal Evaluation Visits 
(MEVs) will be performed at Months 3 and 9, Full Evaluation Visits (FEVs) will be performed 
at Month 6, and Yearly Evaluation Visits (YEVs) will be performed at Month 12. At any time, 
the study participant may have an Unscheduled Visit if the Investigator or the participant and/or 
parent(s)/legal representative(s) consider it necessary. For study participants who continue in the 
study until it ends, the Evaluation Period will last from the EV to the Final Visit (FV). For study 
participants who prematurely discontinue the study, the Evaluation Period will last from the EV 
until the Early Discontinuation Visit (EDV). 
For study participants who transition to another BRV study or a managed access program or 
similar type of program or who convert to commercial BRV (if, when, and where available), the 
FV instead of the EDV will need to be completed; however, down-titration and the Safety Visit 
(SV) will not be applicable. 
For study participants who will discontinue BRV treatment following the EDV or FV, the BRV 
dose will be reduced by a maximum of half the dose every week for a maximum of 4 weeks until 
a dose of 1mg/kg/day (50mg/day for study participants with body weight >50kg) is reached 
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(Down-Titration Period). A Down-Titration Visit (DTV) will be performed at the end of the 
Down-Titration Period, and study drug will be discontinued at the DTV. After 2 weeks free of 
study drug (Safety Period), study participants will complete the SV.  
Brivaracetam (tablet and oral solution) will be administered twice per day in equal doses. The 
maximum allowed daily dose in EP0132 is 200mg/day (4mg/kg/day). Dose adjustments of BRV 
and/or concomitant AEDs based on clinical judgment are allowed at any time, 3 days after study 
start and onwards. 
The duration of the study per study participant will be 2 years at minimum, until approval of 
BRV for the indication of CAE or JAE has been obtained for pediatric participants 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 indication is stopped by the Sponsor, whichever comes first. 
This study will be conducted using a site-based model; all study assessments will be conducted 
at the study site. 
4.1.1 
Study conduct due to coronavirus disease 
The protocol-mandated visit schedule should be followed to the extent possible, considering the 
individual benefit-risk assessment by the Investigator. If necessary, remote visits may be 
conducted, and the study participants or caregivers will be contacted by telephone or 
videoconference. Remote follow-up, at a minimum with telephone call after 3 months, must be 
done (preferably more frequently and as needed to follow-up on participant safety assessments).  
Ad hoc study participant contact may be warranted  to understand the current health status of 
the study participants, to follow up on AEs, and to inform them of any protective measures taken 
by the clinical site as a result of the COVID-19 pandemic (eg, any measures that may limit access 
to the site or may require additional actions by the study participant prior to entry to the site). 
Investigators and study coordinators may use discretion when determining the need to perform a 
home visit (eg, for safety laboratory parameters or PK samples). 
Under COVID-19 circumstances, a maximum of 2 visits that are required to be on-site visits 
(FEV/YEV) is considered acceptable to be conducted remotely. Participants who miss more than 
the defined visits will need to discontinue study participation. 
If a participant must be discontinued and cannot come into the clinic, then appropriate tapering 
instructions will be provided, and a visit will be scheduled to perform safety assessments as soon 
as possible. 
In situations where a study participant is unable to return to the study site, Investigators will 
assess and document the study participant’s safety via telephone contact. Based on information 
gathered from the telephone contact, Investigators will confirm whether the participant could 
continue the current study treatment based upon the outcome of the safety assessment. Study 
participants’ agreement to implement this procedure should be obtained and documented prior to 
implementing any changes. Changes in the study treatment supply in this situation are described 
in Section 6.1.1. 
If a study participant visits another facility for a medical issue (or has to switch sites for some 
COVID-19-related reason), the Investigator should request contact with the physician providing 
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care to provide a detailed explanation of the study participant’s condition and his/her 
participation in the study. Study participants or caregivers shall be reminded to completely 
collect and keep records of this visit. 
In case laboratory assessments cannot be conducted via central laboratory vendor due to 
restricted site access and home visits by study health care providers are not an option, local 
laboratory safety assessments may need to be conducted in a format that allows the Investigator 
to receive and review these results and include as source documentation. 
Deviations to data collection including inability to perform some assessments, such as EEG, 
ECG, blood collection for safety laboratory assessments and PK, or alternative methods of 
assessment, such as phone calls, should be recorded in the source documentation and notated as 
“not done” in the electronic case report form (eCRF). 
In cases where study participants cannot return to the clinic, and it will not be possible to 
dispense a new seizure diary, study participants will be instructed to continue recording of 
seizures in a manner that is mutually agreed with the Investigator (eg, hand-written notes, 
recording on a smart device). Any recording of seizures in a manner outside of the study seizure 
diary must be carefully documented in the source medical records (copies or printouts of these 
recordings will be brought to and retained at site).   
4.2 
Scientific rationale for study design 
This Phase 3, multicenter, open-label, single-arm study will allow evaluation of long-term data to 
establish the long-term safety, tolerability, and efficacy of BRV in pediatric study participants 
with CAE or JAE who are rolling over from study N01269 (core study). Study participants who 
participated in N01269 and qualify for entry into EP0132 and for whom a reasonable benefit 
from long-term administration of BRV is expected will get the opportunity to participate. Study 
participants will begin the open-label study on 100mg/day (or equivalent dose of 2mg/kg/day for 
study participants weighing less than 50kg). The study participant’s dose can be adapted in the 
range of 50 to 200mg/day (or equivalent dose of 1 to 4mg/kg/day for study participants weighing 
less than 50kg) based on safety and efficacy as it would be done in clinical practice. 
For the estimands to address the primary objective, the treatment policy strategy has been 
selected as the approach for the handling of the intercurrent event of concomitant medication 
because use of concomitant medications is allowed in the study and reflects clinical practice, and 
in addition for the TEAE primary endpoint only, the while-on-treatment strategy has been 
selected for the approach for handling of the intercurrent event of treatment discontinuation to 
capture all AEs occurring after the end of BRV treatment.  
For the estimands to address the secondary objective, the treatment policy strategy has been 
selected as the approach for the intercurrent event handling because the use of concomitant 
antiepileptic drugs (AEDs), including benzodiazepines, is allowed in the study and the treatment 
effect will therefore reflect the effectiveness of BRV in the real world. 
4.3 
Justification for dose 
Based on the labeling of other AEDs and published data, the BRV doses selected for this study 
are in the range of the currently labeled BRV doses for POS. Further, in the study in participants 
with photosensitive epilepsy, BRV showed dose-dependent efficacy with complete abolishment 
of photosensitive epilepsy after treatment of study participants with an 80mg single dose 
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(Kastelijn-Nolst Trenité et al, 2007). As this model is considered predictive for generalized 
seizures, the dose used in that study is also used as a guidance. 
4.4 
End of study definition 
The end of the study is defined as the date of the last visit of the last participant in the study or 
last scheduled procedure shown in the Schedule of Assessments (Table 1‒2) for the last 
participant in the study globally. 
5 
STUDY POPULATION 
Prospective approval of protocol deviations to recruitment and enrollment criteria, also known as 
protocol waivers or exemptions, is not permitted. 
5.1 
Inclusion criteria 
Participants are eligible to be included in the study only if all of the following criteria apply: 
Type of participant and disease characteristics 
1. Participants who previously participated in N01269 and qualify for entry into EP0132 as per 
N01269 protocol with a confirmed diagnosis of CAE or JAE, and for whom a reasonable 
benefit from long-term administration of BRV is expected, in the opinion of the Investigator. 
Sex 
2. Male and female 
− A sexually active male study participant must agree to use contraception as detailed in 
Appendix 4 (Section 10.4) of this protocol during the treatment period and for at least 
2 days, corresponding to the time needed to eliminate study treatment, after the last dose 
of study treatment and refrain from donating sperm during this period. 
− A female study participant is eligible to participate if she is not pregnant (see Appendix 4 
[Section 10.4]), not breastfeeding, and at least 1 of the following conditions applies: 
◦ 
The study participant is premenarchal 
OR 
A woman of childbearing potential (WOCBP) who agrees to follow the contraceptive 
guidance in Appendix 4 during the treatment period and for at least 2 days after the 
last dose of study medication, corresponding to the time needed to eliminate study 
treatment. 
Informed consent 
3. Study participant is capable of and provides consent/assent, and the study participant’s 
parent/legal representative/caregiver provides signed informed consent for minor study 
participants, as described in Appendix 1 (Section 10.1), which includes compliance with the 
requirements and restrictions listed in the informed consent form (ICF) and in this protocol. 
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5.2 
Exclusion criteria 
Participants are excluded from the study if any of the following criteria apply: 
Medical conditions 
1. Study participant has a history or presence of paroxysmal nonepileptic seizures. 
2. Study participant has severe medical, neurological, or psychiatric disorders or laboratory 
values, which could, at the discretion of the Investigator, affect safe participation in the study 
or would preclude appropriate study participation. 
3. Study participant has a clinically relevant ECG abnormality in the opinion of the Principal 
Investigator. 
4. Study participant has hepatic impairment (Child Pugh Score A, B, or C) based on the 
Investigator’s assessment. 
5. Study participant has active suicidal ideation prior to study entry as indicated by a positive 
response (“Yes”) to either Question 4 or Question 5 of the Columbia Suicide Severity Rating 
Scale (C-SSRS) (for study participants 6 years or older) or clinical judgment (for study 
participants younger than 6 years). The study participant should be referred immediately to a 
Mental Healthcare Professional. 
6. Study participant has a lifetime history of suicide attempt (including an active attempt, 
interrupted attempt, or aborted attempt). The Investigator must immediately refer the study 
participant to a Mental Healthcare Professional. 
7. Participant has any medical or psychiatric condition that, in the opinion of the Investigator, 
could jeopardize or would compromise the study participant’s ability to participate in this 
study. 
8. Participant has known fructose intolerance or a known hypersensitivity to any components of 
BRV or excipients or a drug with similar chemical structure. Note that the tablets contain 
lactose. 
9. Study participant has end-stage kidney disease requiring dialysis. 
Prior/Concomitant therapy 
10. Concomitant use of carbamazepine, felbamate, gabapentin, oxcarbazepine, phenobarbital, 
phenytoin, tiagabine, or vigabatrin. 
Prior/Concurrent clinical study experience 
11. Study participant has planned participation in any clinical study on an investigational drug or 
device. 
Other exclusions 
12. Study participant has poor compliance with the visit schedule or medication intake in the 
core study in the opinion of the Investigator. 
5.3 
Lifestyle restrictions 
Concomitant intake of alcohol is prohibited. 
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5.4 
Screen failures 
Screen failures are defined as participants who consent to participate in the clinical study but are 
not subsequently entered in the study. A minimal set of screen failure information is required to 
ensure transparent reporting of screen failure participants to meet the Consolidated Standards of 
Reporting Trials publishing requirements and to respond to queries from regulatory authorities. 
Minimal information includes demography, screen failure details, eligibility criteria, and any 
serious adverse event (SAE).  
6 
STUDY TREATMENTS 
Study treatment is defined as any investigational treatment(s), marketed product(s), placebo, or 
medical device(s) intended to be administered to a study participant according to the study 
protocol. 
6.1 
Treatments administered 
Brivaracetam (tablet [10, 25, or 50mg] or oral solution [10mg/mL]) will be administered twice 
per day in equal doses in the range of 50 to 200mg/day (or equivalent doses of 1 to 4mg/kg/day 
for study participants weighing less than 50kg, not to exceed 200mg/day [or equivalent dose of 
4mg/kg/day for participants weighing less than 50kg]). Study participants will be treated in the 
study for at least 2 years. Twice daily dosing with equivalent morning and evening doses 
approximately 12 hours apart is recommended to achieve more regular exposure over the 
24-hour interval; however, the dosing amount and schedule may be adjusted as needed to 
improve tolerability and efficacy in consultation with the Investigator. 
This is an open-label study; no reference therapy will be used. 
6.1.1 
Alternative study treatment supply due to COVID-19 
When a study participant can no longer return to the study site but will continue in the study, the 
following method may be used to provide study treatment: 
• Site to participant: Where possible, site staff can ship study treatment dispensed from the site 
pharmacy supply directly to the study participant. 
6.2 
Preparation, handling, storage, and accountability requirements 
The Investigator or designee must confirm appropriate temperature conditions have been 
maintained during transit for all study treatment received and any discrepancies are reported and 
resolved before use of the study treatment. 
Only participants enrolled in the study may receive study treatment and only authorized site staff 
may supply or administer study treatment. All study treatments must be stored in a secure, 
environmentally controlled, and monitored (manual or automated) area in accordance with the 
labeled storage conditions with access limited to the Investigator and authorized site staff. 
The Investigator, institution, or the head of the medical institution (where applicable) is 
responsible for study treatment accountability, reconciliation, and record maintenance 
(ie, receipt, reconciliation, and final disposition records). 
In case an out-of-range temperature is noted, it must be immediately reported as per instructions 
contained in the Investigational Medicinal Product (IMP) Handling Manual. 
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The Investigator (or designee) will instruct the participant to store the study medication 
following the instructions on the label. 
Further guidance and information for the final disposition of unused study treatment are provided 
in the Study Reference Manual.  
6.2.1 
Drug accountability/device accountability  
The case report form (CRF) will be used to record study medication dispensing and return 
information on a by-participant basis and will serve as source documentation during the course 
of the study. Details of any study medication lost, damaged (due to breakage or wastage), not 
used, partially used, disposed of at the study site, or returned to the Sponsor or designee must 
also be recorded on the appropriate forms. All supplies and pharmacy documentation must be 
made available throughout the study for UCB (or designee) to review. 
The Investigator (or designee) is responsible for retaining all used, unused, and partially used 
containers of study medication until returned or destroyed. 
The Investigator may assign some of the Investigator’s duties for drug accountability at the study 
site to an appropriate pharmacist/designee. 
The Investigator must ensure that the study medication is used only in accordance with the 
protocol. 
Periodically, and/or after completion of the clinical phase of the study, all used (including empty 
containers)/partially used, unused, damaged, and/or expired study medication must be reconciled 
and either destroyed at the site according to local laws, regulations, and UCB standard operating 
procedures or returned to UCB (or designee). Investigational medicinal product intended for the 
study cannot be used for any other purpose than that described in this protocol. 
6.3 
Measures to minimize bias: randomization and blinding 
This is an open-label study. There is no randomization or blinding. 
Each participant will start on a BRV dose of 100mg/day (or equivalent dose of 2mg/kg/day for 
study participants weighing less than 50kg). 
To enroll a participant (EV), the Investigator will contact the interactive voice or web response 
system (IXRS) and provide brief details about the participant to be enrolled. Participants will 
continue with the 5-digit study participant number assigned by the IXRS in the core study. The 
study participant number will be required in all communication between the Investigator (or 
designee) and the IXRS regarding a particular participant. Participants’ status and the dispensing 
of IMP (bottle numbers) will be tracked via the IXRS. 
6.4 
Treatment compliance 
At each visit after study medication is dispensed, participants must return all unused study 
medication and empty study medication containers. Drug accountability must be done in the 
participant’s presence in order to obtain explanations regarding discrepancies in compliance with 
the dosing regimen. Drug accountability must be recorded on the Drug Accountability form. 
If a participant is found to be persistently noncompliant (defined as taking <85% or >115% of 
prescribed dose), the Sponsor, in conjunction with the Investigator, will make a decision as to 
whether the participant should be withdrawn from the study. 
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6.5 
Concomitant medication(s)/treatment(s) 
6.5.1 
Permitted concomitant treatments (medications and therapies) 
All concomitant medications except those specified in Section 6.5.2 are permitted during the 
study.  
6.5.2 
Prohibited concomitant treatments (medications and therapies) 
The following concomitant medications are prohibited during the study: 
• Carbamazepine 
• Felbamate 
• Gabapentin 
• Oxcarbazepine 
• Phenobarbital 
• Phenytoin 
• Tiagabine  
• Vigabatrin 
The use of substrates of alcohol dehydrogenase is prohibited.  
6.5.3 
Rescue medication 
Rescue medication in this study is considered as any treatment with permitted AEDs, including 
benzodiazepines. Rescue medication can be given at any time if considered necessary by the 
Investigator. The study site may supply locally obtained rescue medication as per the 
Investigator’s assessment/recommendation.  
The date of rescue medication onset and end as well as the name and dosage regimen of the 
rescue medication must be recorded.  
6.6 
Dose modification 
Study participants will start on a BRV dose of 100mg/day (or equivalent dose of 2mg/kg/day for 
study participants weighing less than 50kg). The dose may be adjusted after 3 days in the range 
of 50 to 200mg/day (or equivalent dose of 1 to 4mg/kg/day for study participants weighing less 
than 50kg) based on the individual needs.  
For study participants who will discontinue BRV treatment following the EDV or FV, the BRV 
dose will be reduced by a maximum of half the dose every week for a maximum of 4 weeks until 
a dose of 1mg/kg/day (50mg/day for study participants with body weight >50kg) is reached 
(Down-Titration Period). A DTV will be performed at the end of the Down-Titration Period, and 
study drug will be discontinued at the DTV. After 2 weeks free of study drug (Safety Period), 
study participants will complete the SV.  
For study participants who transition to another BRV study or a managed access program or 
similar type of program or who convert to commercial BRV (if, when, and where available), the 
FV instead of the EDV will need to be completed; however, down-titration and the SV will not 
be applicable.  
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6.7 
Treatment after the end of the study 
After their participation in EP0132 is complete, study participants may transition without 
down-titration to another BRV study; may be initiated without down-titration in a managed 
access program, named patient program, compassionate use program, or similar type of access 
program as allowed per country-specific requirements in addition to legal and regulatory 
guidelines; or convert to commercial BRV (if, when, and where available).  
7 
DISCONTINUATION OF STUDY MEDICATION AND 
PARTICIPANT DISCONTINUATION/WITHDRAWAL 
7.1 
Discontinuation of study medication 
7.1.1 
Liver chemistry stopping criteria 
Discontinuation of study treatment for abnormal liver function should be considered by the 
Investigator when a participant meets one of the conditions outlined in Figure 7‒1 or if the 
Investigator believes that it is in best interest of the participant. The increased monitoring 
algorithm and continued study intervention for study participants with alanine aminotransferase 
(ALT) ≥3x upper limit of normal (ULN) but <8xULN is presented in Figure 7‒2. 
Figure 7‒1: Phase 3 liver chemistry stopping criteria and increased monitoring 
algorithm 
ALT=alanine transaminase; AST=aspartate aminotransferase; INR=international normalized ratio; SAE=serious 
adverse event; ULN=upper limit of normal 
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Figure 7‒2: Liver chemistry increased monitoring algorithm with continued study 
intervention for participants with ALT ≥3xULN but <8xULN 
ALT=alanine transaminase; AST=aspartate aminotransferase; INR=international normalized ratio; SAE=serious 
adverse event; ULN=upper limit of normal 
Specific assessments and follow up actions for potential drug-induced liver injury (PDILI) are 
provided in Appendix 6 (Section 10.6).  
7.1.2 
QTc stopping criteria 
If a clinically significant finding is identified, including, but not limited to changes from Baseline 
in QT interval (corrected using Bazett’s formula) after enrollment, the Investigator or qualified 
designee will determine if the participant can continue in the study and if any change in 
participant management is needed. This review of the ECG printed at the time of collection must 
be documented. Any new clinically relevant finding should be reported as an AE and should be 
followed up as deemed necessary by the Investigator. 
See the Schedule of Assessments (Table 1‒2) for data to be collected at the time of treatment 
discontinuation and follow-up and for any further evaluations that need to be completed. 
7.2 
Participant discontinuation/withdrawal from the study 
Participants are free to withdraw from the study at any time, without prejudice to their continued 
care. 
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A participant may withdraw from the study at any time at his/her own request, or may be 
withdrawn at any time at the discretion of the Investigator for safety, behavioral, compliance, or 
administrative reasons. 
If the participant withdraws consent for disclosure of future information, the Sponsor may retain 
and continue to use any data collected before such a withdrawal of consent. 
If a participant withdraws from the study, he/she may request destruction of any samples taken 
and not tested, and the Investigator must document this in the site study records. 
See the Schedule of Assessments (Table 1‒2) for data to be collected at the time of study 
discontinuation and follow-up and for any further evaluations that need to be completed. 
Participants should be withdrawn from the study if any of the following events occur: 
1. Study participant develops any medical or psychiatric condition that, in the opinion of the 
Investigator, could negatively impact the study participant's safety. 
2. Study participant develops an illness that, in the opinion of the Investigator, would interfere 
with his/her continued participation or would potentially be detrimental to his/her 
physical/mental health. 
3. Participant is noncompliant with the study procedures or medications in the opinion of the 
Investigator. 
4. Participant takes prohibited concomitant medications as defined in this protocol. 
Participants must be withdrawn from the study if any of the following events occur: 
1. Study participant (or parent[s] or legal representative[s]) withdraws his/her consent (or 
assent, if applicable). 
2. There is confirmation of a pregnancy during the study, as evidenced by a positive pregnancy 
test. 
3. The Sponsor or a regulatory agency requests withdrawal of the participant. 
4. Investigator decides that withdrawal from further participation would be in the study 
participant’s best interest. 
5. Study participant has active suicidal ideation since study start as indicated by a positive 
response (“Yes”) to either Question 4 or Question 5 of the C-SSRS (for study participants 
6 years or older) or clinical judgment (for study participants younger than 6 years). The study 
participant should be referred immediately to a Mental Healthcare Professional and must be 
withdrawn from the study. 
6. Study participant has a history of suicide attempt since study start (including an active 
attempt, interrupted attempt, or aborted attempt). The study participant should be referred 
immediately to a Mental Healthcare Professional and must be withdrawn from the study. 
Investigators should contact the Medical Monitor, whenever possible, to discuss the withdrawal 
of a participant in advance. Refer to Section 6.6 for down-titration instructions. 
7.3 
Efficacy assessments 
Planned time points for all efficacy assessments are provided in Table 1‒2. 
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7.3.1 
Seizure data based on EEG 
For the assessment of the secondary and other efficacy endpoints, a 1-hour EEG will be 
performed at FEVs, YEVs, and EDV or FV (as applicable). The awake time from the EEG will 
be analyzed for absence seizures. The awake and asleep time from the EEG will be analyzed for 
other seizure types. Every 1-hour EEG will include hyperventilation as a standard provocation 
test at the beginning of the EEG. The investigator/designated EEG reader should attempt to keep 
the study participant awake for the duration of the 1-hour EEG; a minimum of 30 minutes of 
awake time will be required for evaluability. 
7.3.2 
Seizure diary 
During the study, study participants will keep a diary to record daily seizure activity from the EV 
until the EDV or FV (as applicable). Study participants who discontinue study drug and require 
down titration will also complete their daily seizure diaries during the Down-titration Period. 
Study participants will be reminded to bring their diary with them to each clinic visit. 
The written information is discussed with the study participants at each visit in order to ensure 
completeness and accuracy. As a result of the discussion, the Investigator will assess and confirm 
the seizures according to the ILAE codes and record the seizure types in the eCRF/diary; he/she 
will also confirm the presence of AEs, if applicable. 
Study participants will record all types of seizures that occur in their diaries and will be educated 
to complete their diary entries after each seizure or at least once a day. A parent or caregiver may 
assist in completing the diary if necessary.  
7.4 
Lost to follow up 
A participant will be considered lost to follow-up if he or she repeatedly fails to return for 
scheduled visits and is unable to be contacted by the study site.  
The following actions must be taken if a participant fails to return to the clinic for a required 
study visit: 
• The site must attempt to contact the participant and reschedule the missed visit as soon as 
possible and counsel the participant on the importance of maintaining the assigned visit 
schedule and ascertain whether or not the participant wishes to and/or should continue in the 
study. 
• Before a participant is deemed lost to follow up, the Investigator or designee must make 
every effort to regain contact with the participant (at least 1 phone call and 1 written message 
to the participant), and document his/her effort (date and summary of the phone call and copy 
of the written message in the source documents), to complete the final evaluation. All results 
of these evaluations and observations, together with a narrative description of the reason(s) 
for removing the participant, must be recorded in the source documents. The CRF must 
document the primary reason for withdrawal. 
Should the participant continue to be unreachable, he/she will be considered to have withdrawn 
from the study with a primary reason of lost to follow-up documented in the CRF.  
8 
STUDY ASSESSMENTS AND PROCEDURES 
Study procedures and their timing are summarized in the Schedule of Assessments (Table 1‒2).  
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Immediate safety concerns should be discussed with the Sponsor immediately upon occurrence 
or awareness to determine if the participant should continue or discontinue study treatment. 
Adherence to the study design requirements, including those specified in the Schedule of 
Assessments, is essential and required for study conduct.  
The maximum amount of blood collected from each participant over the duration of the study, 
including any extra assessments that may be required, will not exceed 3% of the participant’s 
total blood volume within 4 weeks. Repeat or unscheduled samples may be taken for safety 
reasons or for technical issues with the samples. 
8.1 
Safety assessments 
Planned time points for all safety assessments are provided in Table 1‒2. 
8.1.1 
Physical examination 
A complete physical examination is performed at FEVs, YEVs, EDV or FV (as applicable), and 
SVs. A brief physical examination is performed at MEVs and UVs.  
A complete physical examination will include, at a minimum, general appearance; eyes, ear, 
nose, and throat; skin; and assessments of the respiratory, cardiovascular, gastrointestinal, and 
musculoskeletal systems.  
A brief physical examination will include, at a minimum, general appearance; assessments of the 
skin, respiratory, and cardiovascular systems; and abdomen (liver and spleen). 
Investigators should pay special attention to clinical signs related to previous serious illnesses. 
Clinically relevant findings or worsening of previous findings will be recorded as AEs. 
8.1.2 
Body height and weight 
Body weight and height will be measured and recorded during the Evaluation Period at MEV, 
FEV, YEV, EDV, and FV. 
8.1.3 
Neurological examination 
A complete neurological examination is performed at FEVs, YEVs, EDV or FV (as applicable), 
and SVs. A brief neurological examination is performed at MEVs and UVs. 
A complete neurological examination will include, at a minimum, assessments of:  
• Psychiatric and mental status evaluation 
• Cranial nerves 
• Motor and sensory systems 
• Deep tendon reflexes 
• Coordination 
• Gait 
A brief neurological examination will include, at a minimum, assessments of cranial nerves, 
motor system, coordination, and gait. 
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8.1.4 
Psychiatric and mental status 
An examination of psychiatric and mental status is performed as part of the complete 
neurological examination at FEVs, YEVs, EDV, or FV (as applicable) and SVs, as noted in 
Table 1‒2. At a minimum, the presence of psychiatric symptoms, mental impairment, and 
behavioral problems should be assessed. 
8.1.5 
Vital signs 
Oral temperature, pulse rate, respiratory rate, body weight, and blood pressure (systolic and 
diastolic) will be assessed. 
Blood pressure and pulse measurements will be assessed in a seated position with a completely 
automated device. Manual techniques will be used only if an automated device is not available. 
Blood pressure and pulse rate measurements should be preceded by at least 5 minutes of rest for 
the participant in a quiet setting without distractions (eg, television, cell phones). 
Vital signs should be obtained prior to blood collection for safety laboratory assessments per 
Schedule of Activities (Table 1‒2). Only 1 measurement of blood pressure and pulse rate are 
required. 
8.1.6 
Electrocardiograms 
A standard 12-lead ECG will be obtained as outlined in the Schedule of Assessments (Table 1‒2) 
to capture abnormalities during the study. If abnormal values were detected during N01269, prior 
to the participant’s entry into EP0132, or during EP0132, the ECG will be repeated until the 
participant’s values return to normal or Baseline, or are no longer considered clinically 
significant by the Investigator or Medical Monitor. Clinically significant abnormalities will be 
reported as TEAEs. Refer to Section 7.1.2 for QTc withdrawal criteria and any additional QTc 
readings that may be necessary. 
The original ECG tracing is signed or initialed and dated by the Investigator, and retained as part 
of the source documentation. 
8.1.7 
Clinical safety laboratory assessments 
See Appendix 2 (Section 10.2) for the list of clinical laboratory tests to be performed and the 
Schedule of Assessments (Table 1‒2) for the timing and frequency. The possibly clinically 
significant treatment-emergent (PCST) criteria are provided in the Statistical Analysis Plan 
(SAP). 
The Investigator must review the laboratory report, document this review, and record any 
clinically relevant changes occurring during the study in the AE section of the CRF. The 
laboratory reports must be filed with the source documents. Clinically significant abnormal 
laboratory findings are those which are not associated with the underlying disease, unless judged 
by the Investigator to be more severe than expected for the participant's condition. 
All laboratory tests with values considered clinically significantly abnormal from any point after 
administration of first IMP until the end of the Safety Period should be repeated until the values 
return to normal or Baseline or are no longer considered clinically significant by the Investigator 
or Medical Monitor. Participants who enter EP0132 from N01269 with clinically significantly 
abnormal values will be monitored during EP0132. 
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If such values do not return to normal/Baseline within a period of time judged reasonable by the 
Investigator, the etiology should be identified and the Sponsor notified. 
All protocol-required laboratory assessments, as defined in Appendix 2 (Section 10.2), must be 
conducted in accordance with the laboratory manual and the Schedule of Assessments.  
If laboratory values from nonprotocol-specified laboratory assessments performed at the 
institution’s local laboratory require a change in participant management or are considered 
clinically significant by the Investigator (eg, SAE or AE or dose modification), then the results 
must be recorded in the CRF. 
8.1.8 
Suicidal risk monitoring 
Brivaracetam is considered to be an AED. Suicidal ideation and behavior have been reported in 
patients treated with antiepileptic agents in several indications. A meta-analysis of randomized 
placebo-controlled studies of AEDs has also shown a small increased risk of suicidal ideation 
and behavior. The mechanism of this risk is not known and the available data do not exclude the 
possibility of an increased risk for BRV. 
Participants being treated with IMP should be monitored appropriately and observed closely for 
suicidal ideation and behavior or any other unusual changes in behavior. Consideration should be 
given to discontinuing IMP in participants who experience signs of suicidal ideation or behavior.  
Families and caregivers of participants being treated with IMP should be instructed to monitor 
participants for the emergence of unusual changes in behavior, as well as the emergence of 
suicidal ideation and behavior, and to report such symptoms immediately to the study 
Investigator. 
Treatment-emergent suicidal ideation and behavior will be monitored by trained study personnel 
using the C-SSRS for all study participants ≥6 years of age at the time of enrollment into 
EP0132. The “Since Last Visit” version of the C-SSRS will be used at each visit unless the 
participant turns 6 years of age while enrolled in EP0132. If the participant turns 6 years of age 
during enrollment, the “Already Enrolled” version of the C-SSRS should be completed at the 
first visit after the participant’s sixth birthday. Thereafter, the “Since Last Visit” version of the 
C-SSRS should be completed at all subsequent visits as indicated in the Schedule of Activities 
(Table 1‒2).   
8.1.9 
Participant- or caregiver-reported outcomes 
The patient- or parent-reported outcomes that will be assessed in this study are summarized in 
Table 8‒1 and described in the following subsections. 
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Table 8‒1: 
Participant- or caregiver-reported outcomes 
Assessment 
Time points assessed 
Participant age at assessmenta 
EpiTrack Junior 
FEV, YEV, and EDV or FV (as 
applicable) 
6 to <18 years  
PedsQL Core Module 
FEV, YEV, and EDV or FV (as 
applicable) 
Participant self-report: 5 to ≤7, 8 to 
≤12, and 13 to ≤17 years 
Parent proxy-report: 2 to ≤4, 5 to 
≤7, 8 to ≤12, and 13 to ≤17 years 
EDV=Early Discontinuation Visit; FEV=Full Evaluation Visit; FV=Final Visit; PedsQL=Pediatric Quality of Life; 
YEV=Yearly Evaluation Visit 
Note: Whole years are considered when determining participant age; ie, a 5-year-old is considered 5 until they turn 
6 years old.   
a The version of the assessment test should be in accordance with the study participant’s age at the time of the 
assessment. If the participant has aged into a different version of the assessment test since the initial assessment in 
N01269, then the same version of the assessment should be completed at the initial assessment in EP0132, and 
subsequently, the version of the assessment test in accordance with the study participant’s age at the time of the 
assessment should be used. 
8.1.9.1 
EpiTrack Junior 
The EpiTrack Junior is a 15-minute screening tool intended to assess and track the cognitive side 
effects of AEDs in children with epilepsy. This will be conducted at FEVs, YEVs, EDV or FV 
(as applicable), and SV for study participants between 6 and 18 years old at the time of 
assessment. Study participants who become 6 years old after Baseline (EV), will be assessed for 
all visits they are aged 6 or above. The screening tool consists of 6 subtests, which will each be 
scored from 1 to 7 with greater differentiation in the lower range, thus aiming more at deficits: 
Speed, Flexibility, Planning, Response Inhibition, Word Fluency, and Working Memory. Overall 
EpiTrack Junior score will be calculated by summing the scores of the 6 domains and correcting 
for age at study entry. EpiTrack age correction is presented in the SAP and comes from the 
Helmstaedter et al (2010) manuscript. The same age correction (age at EV) will be applied at all 
visits even if a study participant changes age category during the study. If a study participant is 
missing any of the raw scores then the subtest and EpiTrack total score will be missing. 
8.1.9.2 
Pediatric Quality of Life Inventory 
The Pediatric Quality of Life (PedsQL) Measurement Model is a modular approach to measuring 
health-related quality of life in healthy children and adolescents and those with acute and chronic 
health conditions (Varni et al, 2001).  
The 23-item Generic core module is reliable and valid, has been used in a variety of health 
conditions and is responsive to change over time.  
Two versions are available: Study Participant Self-Report Ages 5 to ≤7, 8 to ≤12, and 13 to ≤18; 
Parent Proxy-Report Ages 2 to ≤4, 5 to ≤7, 8 to ≤12, and 13 to ≤18. In study participants aged 
2 to 4 years at the time of assessment, the caregiver will complete the Parent Proxy Report for 
2 to ≤4 years old. In study participants aged 5 to 7 years at the time of assessment, the participant 
will complete the Study Participant Self-Report PedsQL for 5 to ≤7 years old, and the caregiver 
will complete the Parent Proxy Report for 5 to ≤7 years old. In study participants aged 8 to 
12 years at the time of assessment, the participant will complete the Study Participant 
Self-Report PedsQL for 8 to ≤12 years old, and the caregiver will complete the Parent Proxy 
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Report for 8 to ≤12 years old. In study participants aged 13 to 17 years at the time of assessment, 
the participant will complete the Study Participant Self-Report PedsQL for 13 to ≤18 years old, 
and the caregiver will complete the Parent Proxy Report for 13 to ≤18 years old. 
The version of the PedsQL used should be consistent with the study participant’s age at the time 
of assessment with the following exception: If a study participant ages up to the next PedsQL 
between the initial assessment in the core study and the initial assessment in EP0132, the 
PedsQL that was used at the initial assessment in the core study should be completed through 
and including the initial assessment in EP0132, and subsequently the PedsQL consistent with the 
age at the time of assessment should be completed. The assessment will be done in study 
participants from 2 to ≤17 years of age. 
The following scores will be computed: 
• Physical, Emotional, Social, School Functioning; total score, physical health summary score, 
and psychosocial health summary score 
PedsQL data will be collected at FEVs, YEVs, and EDV or FV (as applicable) using the 1-week 
recall period version. 
The underlying score values 0 to 4 (representing responses of: never/not at all [0], almost never 
[1], sometimes [2], often [3], and almost always/a lot [4]) will be transformed by the function: 
(100 – [response x 25]) in order to generate scores of 0, 25, 50, 75, and 100, where a higher 
value represents a better quality of life. 
8.1.10 
Nonabsence seizures 
8.1.10.1 
Nonabsence seizure incidence after first BRV treatment during the 
study based on EEG  
All nonabsence seizure types observed while awake or asleep on EEG (1-hour) will be 
categorized into 1 of 3 nonabsence seizure types: 
• Partial seizures: ‘POS’  
• Tonic clonic seizures: ‘Tonic clonic’ 
• All other seizure types 
8.1.10.2 
Nonabsence seizure incidence after first BRV treatment during the 
study based on study participant diary 
The identification of nonabsence seizures described in Section 8.1.10.1 will be repeated using all 
nonabsence seizures observed from the study participant diary.  
8.2 
Adverse events and serious adverse events 
The definitions of an AE or SAE can be found in Appendix 3 (Section 10.3). Adverse events will 
be reported by the participant (or, when appropriate, by a caregiver, surrogate, or the 
participant’s legally authorized representative). 
The Investigator and any designees are responsible for detecting, documenting, and recording 
events that meet the definition of an AE or SAE and remain responsible for following up AEs 
that are serious, considered related to the study medication or study procedures, or that caused 
the participant to discontinue IMP or EP0132 (see Section 7). 
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Occurrence of COVID-19 in participants should be reported as either “suspected COVID-19” or 
“confirmed COVID-19” along with all available relevant data including diagnostic and 
laboratory data. For participants where COVID-19 is still suspected despite a negative viral test, 
please report as “suspected COVID-19” and provide relevant data to support the diagnosis as 
well as the test results. 
8.2.1 
Time period and frequency for collecting AE and SAE information 
All AEs and SAEs will be collected from the signing of the ICF until the SV, at the time points 
specified in the Schedule of Assessments (Table 1‒2). 
In order to ensure complete safety data collection, all AEs occurring during the study (ie, after 
the signing of the ICF), including any pretreatment and posttreatment periods required by the 
protocol, must be reported in the eCRF even if no study medication was taken but specific study 
procedures were conducted. This includes all AEs not present prior to the initial visit and all AEs 
that recurred or worsened after the initial visit. 
All SAEs will be recorded and reported to the Sponsor or designee within 24 hours, as indicated 
in Appendix 3 (Section 10.3). The Investigator will submit any updated SAE data to the Sponsor 
within 24 hours of it being available. 
The Investigator is specifically requested to collect and report to UCB (or its representative) any 
SAEs (even if the Investigator is certain that they are in no way associated with the study 
medication), up to 30 days from the end of the study for each participant, and to also inform 
participants of the need to inform the Investigator of any SAE within this period. Serious AEs 
that the Investigator thinks may be associated with the study medication must be reported to 
UCB regardless of the time between the event and the end of the study. 
The method of recording, evaluating, and assessing causality of AE and SAE and the procedures 
for completing and transmitting SAE reports are provided in Appendix 3 (Section 10.3). 
8.2.2 
Method of detecting AEs and SAEs 
Care will be taken not to introduce bias when detecting AEs and/or SAEs. Open-ended and 
nonleading verbal questioning of the participant is the preferred method to inquire about 
AE occurrences.  
8.2.3 
Follow-up of AEs and SAEs 
After the initial AE/SAE report, the Investigator is required to proactively follow each 
participant at subsequent visits/contacts. All SAEs, and nonserious AEs of special interest (as 
defined in Section 8.2.6), will be followed until resolution, stabilization, the Investigator 
determines that it is no longer clinically significant, the event is otherwise explained, or the 
participant is lost to follow-up (as defined in Section 7.3). Further information on follow-up 
procedures is given in Appendix 3 (Section 10.3). 
8.2.4 
Regulatory reporting requirements for SAEs 
Prompt notification by the Investigator to the Sponsor of a SAE is essential so that legal 
obligations and ethical responsibilities towards the safety of participants and the safety of a study 
treatment under clinical investigation are met.  
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The Sponsor has a legal responsibility to notify both the local regulatory authority and other 
regulatory agencies about the safety of a study treatment under clinical investigation. The 
Sponsor will comply with country-specific regulatory requirements relating to safety reporting to 
the regulatory authority, Institutional Review Boards (IRB)/Independent Ethics Committees 
(IEC), and Investigators. 
Investigator safety reports must be prepared for suspected unexpected serious adverse reactions 
according to local regulatory requirements and Sponsor policy and forwarded to Investigators as 
necessary. 
An Investigator who receives an Investigator safety report describing a SAE or other specific 
safety information (eg, summary or listing of SAEs) from the Sponsor will review and then file it 
along with the IB and will notify the IRB/IEC, if appropriate according to local requirements. 
8.2.5 
Pregnancy 
Details of all pregnancies in female participants and female partners of male participants will be 
collected after the start of study treatment and until 2 days (ie, 5 half-lives) after the last dose of 
study medication. 
If a pregnancy is reported, the Investigator must immediately inform the Sponsor within 24 hours 
of learning of the pregnancy and should follow the procedures outlined in Appendix 4 
(Section 10.4). 
Should a participant become pregnant during the study, she should be withdrawn from the study 
as soon as pregnancy is known (by positive pregnancy test), and the following should be 
completed: 
• The participant should return for an EDV. 
• The participant should immediately stop the intake of the study medication or be 
down-titrated as instructed at the EDV.  
• An SV should be scheduled 2 weeks after the participant has discontinued her study 
medication. 
Every reasonable attempt should be made to follow the health of the child for at least 30 days 
after birth for any significant medical issues. In certain circumstances, UCB may request that 
follow up is continued for a period up to 12 months. Abnormal pregnancy outcomes (eg, 
spontaneous abortion, fetal death, stillbirth, congenital anomalies, ectopic pregnancy) are 
considered SAEs. 
8.2.6 
Adverse events of special interest 
An AE of special interest is any AE that a regulatory authority has mandated be reported on an 
expedited basis, regardless of the seriousness, expectedness, or relatedness of the AE to the 
administration of a UCB product/compound. 
For BRV, the following events require immediate reporting (within 24 hours regardless of 
seriousness) to UCB: 
• Autoimmune nephritis 
• Nephritis 
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• Nephritis allergic 
• Tubulointerstitial nephritis 
• Tubulointerstitial nephritis and uveitis syndrome  
• Potential Hy’s Law, defined as ≥3xULN ALT or aspartate aminotransferase with coexisting 
≥2xULN total bilirubin in the absence of ≥2xULN alkaline phosphatase, with no alternative 
explanation for the biochemical abnormality, must ALWAYS be reported to UCB as an AE 
of special interest (ie, without waiting for any additional etiologic investigations to have been 
concluded). Follow-up information should then be reported if an alternative etiology is 
identified during investigation and monitoring of the participants. 
8.2.7 
Anticipated serious adverse events 
The Anticipated SAEs in Table 8‒2  are anticipated to occur in the population studied in this 
protocol at some frequency that is independent of drug exposure.  
This list does not change the Investigator’s obligation to report all SAEs (including Anticipated 
SAEs) as detailed in Section 8.2.1 and Appendix 3 (Section 10.3). 
Table 8‒2: 
Anticipated SAEs for the pediatric epilepsy population 
MedDRA SOC 
MedDRA PT 
Congenital, familial and genetic disorders 
Teratogenicity 
General disorders and administration site conditions 
Sudden unexpected death in epilepsy 
Nervous system disorders 
Convulsiona 
Status epilepticus 
Pregnancy, puerperium and perinatal disorders 
Abortion spontaneous 
Psychiatric disorders 
Psychotic behavior 
Abnormal behavior 
Anxiety 
Sleep disorder 
MedDRA=Medical Dictionary for Regulatory Activities; PT=preferred term; SOC=system organ class 
a Convulsion if consistent with the seizure type known for the study participant. 
8.3 
Safety signal detection 
Selected data from this study will be reviewed periodically to detect as early as possible any 
safety concern(s) related to the study medication so that Investigators, clinical study participants, 
regulatory authorities, and IRBs/IECs will be informed appropriately and as early as possible. 
The Study Physician or medically qualified designee/equivalent will conduct an ongoing review 
of SAEs and perform ongoing SAE reconciliations in collaboration with the Patient Safety 
representative. 
As appropriate for the stage of development and accumulated experience with the study 
medication, medically qualified personnel at UCB may identify additional safety measures 
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(eg, AEs, vital signs, laboratory or ECG results) for which data will be periodically reviewed 
during the course of the study. 
8.4 
Treatment of overdose 
For this study, any dose of BRV greater than that prescribed in the protocol will be considered an 
overdose. Overdose events are only considered AEs or SAEs if there are associated clinical signs 
and/or symptoms or if the act of taking the excess study medication itself is an AE or SAE 
(eg, suicide attempt). 
UCB does not recommend specific treatment for an overdose. In the event of an overdose, the 
Investigator should: 
1. Contact the Medical Monitor within 24 hours. 
2. Closely monitor the participant for any AE/SAE and laboratory abnormalities until study 
treatment can no longer be detected systemically (at least 2 days). 
3. Obtain a plasma sample for PK analysis within 2 days from the date of the last dose of study 
treatment if requested by the Medical Monitor (determined on a case-by-case basis). 
4. Document the quantity of the excess dose as well as the duration of the overdose in the CRF. 
Decisions regarding dose interruptions or modifications will be made by the Investigator in 
consultation with the Medical Monitor based on the clinical evaluation of the participant. 
8.5 
Pharmacokinetics 
Blood samples of approximately 2 mL will be collected for measurement of BRV plasma 
concentration as specified in the Schedule of Assessments (Table 1‒2). At the FEV and 
YEV/EDV/FV Visits, when PK sampling is planned, study participants should not take their 
morning BRV dose prior to arriving in the clinic.  
A topical anesthetic (EMLA® or similar product) can be used locally prior to venipuncture or 
insertion of a catheter. Instructions for the collection and handling of biological samples will be 
provided by the Sponsor. The actual date and time (24-hour clock time) of each sample will be 
recorded. 
Each plasma sample will be divided into 2 aliquots (1 each for PK, and a back-up).  
Drug concentration information that may unblind the N01269 study will not be reported to 
investigative sites or blinded personnel until the completion of the study (last patient last visit). 
8.6 
Genetics 
Genetics are not evaluated in this study. 
8.7 
Pharmacodynamics 
The efficacy assessments described in Section 7.3 may be used in pharmacodynamic analyses. 
8.8 
Biomarkers 
Biomarkers are not evaluated in this study. 
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8.9 
Health economics 
Not applicable. 
9 
STATISTICAL CONSIDERATIONS 
A description of statistical methods follows and will be described in more detail in the SAP. 
9.1 
Definition of analysis sets 
The analysis sets will be defined as follows: 
• The All Study Participants Screened Set will consist of all screened study participants who 
gave informed consent (and informed assent where required).  
• The Safety Set (SS) will consist of all enrolled study participants who took at least 1 dose of 
study drug in the LTFU study. All analyses will be performed on the SS, except where 
specifically noted. 
• The PK analysis set will consist of all enrolled study participants who during the study took 
at least 1 dose of study drug in the LTFU study and had at least 1 PK measurement.  
9.2 
General statistical considerations 
All computations for the non-PK analyses will be performed using SAS® version 9.3 or later 
(SAS Institute, NC, USA). 
Descriptive statistics, such as the mean, standard deviation, median, minimum value, and 
maximum value for quantitative variables, and counts and percentages for categorical variables, 
will be provided. Key supporting data will be provided in data listings. No hypothesis testing 
will be conducted. 
All outputs will be produced for all participants. Adverse event outputs will be produced for the 
Evaluation Period, 3-month periods within the Evaluation Period, the Down-Titration Period, 
and the Safety Period. Selected outputs may also be produced by modal dose, maximum BRV 
dose, exposure duration, 3-month periods during the Evaluation Period and study period. 
Statistical outliers are defined as values that are discordant with other values and are clinically 
implausible. Exclusion of outliers from an analysis requires thorough justification based on 
statistical and clinical grounds. In such cases, unless otherwise specified, the analysis may be run 
both with and without the values. Any outliers will be reviewed during the data evaluation 
meeting. Study participant data listings will be provided and will present source data and key 
derived variables for statistical analyses, outliers excluded from analysis will be clearly marked. 
9.3 
Planned efficacy analyses 
9.3.1 
Analysis of the secondary efficacy endpoint 
All efficacy outcomes will be summarized with descriptive statistics only on the SS: 
• Absence seizure freedom on 1-hour ambulatory awake EEG at each applicable visit 
• Absence seizure freedom based on diary over the evaluation period and by 3-month time 
intervals  
All EEG and diary data will be reported individually using data listings. 
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9.4 
Planned safety and other analyses 
9.4.1 
Safety analyses 
Adverse event summary tables will be presented over the Evaluation Period, by 3-month 
intervals during the Evaluation Period, the Down-Titration Period, and Safety Period for the SS.  
All safety variables will be analyzed by descriptive methods on the SS. Adverse events will be 
coded using the Medical Dictionary for Regulatory Activities (MedDRA®). Treatment-emergent 
AEs (TEAEs) will be summarized by MedDRA System Organ Class and Preferred Term. The 
incidence of TEAEs, SAEs, TEAEs leading to discontinuation, and study treatment-related 
TEAEs will also be summarized. 
Other safety variables, including laboratory values, vital signs, weight and height will be 
summarized by scheduled visit. All PCST abnormalities for laboratory values, vital signs and 
weight will be summarized by scheduled visit and listed. All ECG findings, as well as physical 
and neurological examination findings and psychiatric/mental status, will be listed.  
The nonabsence seizure incidence will be summarized descriptively based on EEG and 
participant diary at each scheduled visit. 
9.4.2 
Pharmacokinetic analyses 
Descriptive statistics will be used to describe the plasma concentration data on the PK analysis 
set. Data may be used for additional PK and PK-pharmacodynamic analyses, either as a 
standalone analysis or in combination with data from other relevant studies. In that case, a 
separate Data Analysis Plan will be written. 
9.4.3 
Other analyses 
The questionnaire scores and change scores for EpiTrack Junior and PedsQL will be summarized 
in a descriptive manner by visit. Change from Baseline will be calculated only if the 
questionnaire is the same version at both time points. 
9.5 
Handling of protocol deviations 
Important protocol deviations are deviations from the protocol, which potentially could have a 
meaningful impact on either the primary efficacy outcome or key safety outcomes for an 
individual study participant. The criteria for identifying important protocol deviations and the 
classification of important protocol deviations are defined within the project Data Cleaning Plan. 
To the extent feasible, the rules for identifying protocol deviations are defined without review of 
the data and without the consideration of the frequency of occurrence of such deviations. 
Whenever possible, criteria for identifying important protocol deviations are implemented 
algorithmically to ensure consistency in the classification of important protocol deviations across 
all study participants. 
9.6 
Handling of dropouts or missing data 
Study participants who prematurely discontinue the study will be evaluated based on the data 
collected at each visit attended. 
No imputation of missing values associated with an individual date or visit is planned for the 
safety analysis, with the exception of partial date information for AEs and concomitant 
medications in order to determine whether they are treatment emergent. 
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9.7 
Planned interim analysis and data monitoring 
No formal interim analysis is planned; however, data may be reported prior to the completion of 
this study to support ongoing data cleaning, annual reports, regulatory submissions, and 
publications. 
9.8 
Determination of sample size 
No formal sample size calculation was performed for this study. Approximately 140 study 
participants may enroll in this study, based upon the rollover expectations from N01269 into 
EP0132. 
10 
SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS 
10.1 
Appendix 1: Regulatory, ethical, and study oversight 
considerations 
10.1.1 
Regulatory and ethical considerations 
The study will be conducted under the auspices of an IRB/IEC, as defined in local regulations, 
International Council for Harmonisation (ICH)-Good Clinical Practice (GCP), and in accordance 
with the ethical principles that have their origin in the Declaration of Helsinki. 
The Investigator/UCB will ensure that an appropriately constituted IRB/IEC that complies with 
the requirements of the current ICH-GCP version or applicable country-specific regulations will 
be responsible for the initial and continuing review and approval of the clinical study. Prior to 
initiation of the study, the Investigator/UCB will forward copies of the protocol, ICF, IB, 
Investigator’s curriculum vitae (if applicable), advertisement (if applicable), and all other 
participant-related documents to be used for the study to the IRB/IEC for its review and 
approval. 
Before initiating a study, the Investigator will have written and dated full approval from the 
responsible IRB/IEC for the protocol. 
The Investigator will also promptly report to the IRB/IEC all changes in the study, all 
unanticipated problems involving risks to participants or others, and any protocol deviations, to 
eliminate immediate hazards to participants. 
The Investigator will not make any changes in the study or study conduct without IRB/IEC 
approval, except where necessary to eliminate apparent immediate hazards to the participants. 
For minor changes to a previously approved protocol during the period covered by the original 
approval, it may be possible for the Investigator to obtain an expedited review by the IRB/IEC as 
allowed. 
As part of the IRB/IEC requirements for continuing review of approved studies, the Investigator 
will be responsible for submitting periodic progress reports to the IRB/IEC (based on IRB/IEC 
requirements), at intervals appropriate to the degree of participant risk involved, but no less than 
once per year. The Investigator should provide a final report to the IRB/IEC following study 
completion. 
UCB (or its representative) will communicate safety information to the appropriate regulatory 
authorities and all active investigators in accordance with applicable regulatory requirements. 
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The appropriate IRB/IEC will also be informed by the Investigator or the Sponsor, as specified 
by the applicable regulatory requirements in each concerned country. Where applicable, 
Investigators are to provide the Sponsor (or its representative) with evidence of such IRB/IEC 
notification. 
10.1.2 
Financial disclosure 
Insurance coverage will be handled according to local requirements. 
Finance and insurance are addressed in the Investigator and/or contract research organization 
agreements, as applicable. 
10.1.3 
Informed consent process 
Participant’s informed consent must be obtained and documented in accordance with local 
regulations, ICH-GCP requirements, and the ethical principles that have their origin in the 
principles of the Declaration of Helsinki. 
Prior to obtaining informed consent, information should be given in a language and at a level of 
complexity understandable to the participant in both oral and written form by the Investigator (or 
designee). Parent(s), legal representative(s), and study participant, if applicable, will have the 
opportunity to discuss the study and its alternatives with the Investigator. 
Prior to participation in the study, the ICF should be signed and personally dated by the 
participant, or his/her parent/legal representative, and by the person who conducted the informed 
consent discussion (Investigator or designee). Adult study participants will provide consent; 
minor study participants will provide assent and consent will be provided by the 
parent/caregiver. As the definitions of “adult” and “minor” vary by location/region, the 
appropriate ICF assent/consent will be achieved by each site based upon its location and the 
applicable definitions. The participant or his/her legal representative must receive a copy of the 
signed and dated ICF. As part of the consent process, each participant must consent to direct 
access to his/her medical records for study-related monitoring, auditing, IRB/IEC review, and 
regulatory inspection. 
If the ICF is amended during the study, the Investigator (or the Sponsor, if applicable) must 
follow all applicable regulatory requirements pertaining to the approval of the amended ICF by 
the IRB/IEC and use of the amended form. 
All studies conducted at centers in the United States must include the use of a Health Insurance 
Portability and Accountability Act Authorization form. 
The participant may withdraw his/her consent to participate in the study at any time. A 
participant is considered as enrolled in the study when he/she has signed the ICF, whether or not 
any study procedures are actually performed; in the event that no study procedures are performed 
after the ICF is signed, the participant would be recorded as a screen failure. A CRF must not be 
started, nor may any study specific procedure be performed for a given participant, without 
having obtained his/her written consent to participate in the study. 
10.1.4 
Data protection 
UCB staff (or designee) will affirm and uphold the participant’s confidentiality. Throughout this 
study, all data forwarded to UCB (or designee) will be identified only by the participant number 
assigned at Screening. 
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The Investigator agrees that representatives of UCB, its designee, representatives of the relevant 
IRB/IEC, or representatives of regulatory authorities will be allowed to review that portion of the 
participant’s primary medical records that directly concerns this study (including, but not limited 
to, laboratory test result reports, ECG reports, admission/discharge summaries for hospital 
admissions occurring during a participant’s study participation, and autopsy reports for deaths 
occurring during the study). 
The participant must be informed that his/her personal study-related data will be used by the 
Sponsor in accordance with local data protection law. The level of disclosure must also be 
explained to the participant.  
The participant must be informed that his/her medical records may be examined by Clinical 
Quality Assurance auditors or other authorized personnel appointed by the Sponsor, by 
appropriate IRB/IEC members, and by inspectors from regulatory authorities. 
10.1.5 
Data quality assurance 
All participant data relating to the study will be recorded on printed or electronic CRF unless 
transmitted to the Sponsor or designee electronically (eg, laboratory data). The Investigator is 
responsible for verifying that data entries are accurate and correct by physically or electronically 
signing the CRF.  
The Investigator must maintain accurate documentation (source data) that supports the 
information entered in the CRF.  
The Investigator must permit study-related monitoring, audits, IRB/IEC review, and regulatory 
agency inspections and provide direct access to source data documents.  
The Sponsor or designee is responsible for the data management of this study including quality 
checking of the data.  
Study monitors will perform ongoing source data verification to confirm that data entered into 
the CRF by authorized site personnel are accurate, legible, contemporaneous, original, and 
attributable from source documents; that the safety and rights of participants are being protected; 
and that the study is being conducted in accordance with the currently approved protocol and any 
other study agreements, ICH-GCP, and all applicable regulatory requirements. Remote 
monitoring visits may be conducted during the COVID-19 pandemic or under other exceptional 
circumstances as deemed appropriate to ensure study participants’ safety. 
All essential documents must be retained by the Investigator for the minimum retention period 
mandatory under the applicable local laws and regulations. The Investigator will contact UCB 
for authorization prior to the destruction of any study records or in the event of accidental loss or 
destruction of any study records. The Investigator will also notify UCB should he/she relocate or 
move the study-related files to a location other than that specified in the Sponsor’s trial master 
file. 
Quality tolerance limits will be established for the study using parameters related to patient 
safety reporting and reliability of study results. The parameters will be monitored throughout the 
study to identify systematic issues. Parameters used, parameter values, important deviations from 
the quality tolerance limits, and actions taken will be summarized in the clinical study report. 
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10.1.5.1 
Case report form completion 
Unless specified otherwise, eCRFs will be used in this study. For assessments that require paper 
CRFs (eg, patient-reported outcomes), the information will be collected and loaded into the 
electronic data capture system. The Investigator is responsible for prompt reporting of accurate, 
complete, and legible data in the CRFs and in all required reports. Corrections made after the 
Investigator’s review and approval of the completed CRF will be re-signed and dated by the 
Investigator (via a password/electronic signature for eCRFs), and must be accompanied by a 
reason for the change. 
The Investigator should maintain a list of personnel authorized to enter data into the CRF/eCRF.  
Detailed instructions will be provided in the CRF Completion Guidelines. 
10.1.5.2 
Apps 
Not applicable. 
10.1.6 
Source documents 
This study will be utilizing an electronic source document system (e-Source) for direct data 
capture. As applicable, sites will utilize e-Source to enter original records in the data capture 
system to which raw data are first recorded. Information to be originally captured and reviewed 
electronically shall include details of the study participant visit and the protocol-required 
assessments performed. These data will be collected into a system that is secured and fully 
validated. Data recorded in the e-Source will be monitored directly from the system and will not 
require additional source data verification (SDV). Access to data from e-Source can be obtained 
using the system portal once appropriate training has been completed and designated study staff 
has been assigned. Investigators and study staff will be responsible for ensuring the quality and 
integrity of the data entered into the e-Source system.  
In the event data cannot be captured in e-Source, alternative source documents may be utilized. 
All source documents must meet the same fundamental elements of data quality (eg, attributable, 
legible, contemporaneous, original, and accurate) for both paper and e-Source. They should be 
made using some permanent form of recording (ink, typing, printing, optical disc). They should 
not be obscured by correction fluid or have temporary attachments (such as removable self-stick 
notes). These may include hospital/clinic/general practitioner records, charts, diaries, x-rays, 
laboratory results, printouts, pharmacy records, care records, ECG or other printouts, completed 
scales, quality of life questionnaires, or video. Source documents that are computer generated 
and stored electronically must be printed for review by the monitor for SDV. Once printed, these 
copies should be signed and dated by the Investigator and become a permanent part of the 
participant’s source documents. The Investigator will facilitate the process for enabling the 
monitor to compare the content of the printout and the data stored in the data capture to ensure 
all data are consistent. 
10.1.7 
Study and site closure 
The Sponsor designee reserves the right to close the study site or terminate the study at any time 
for any reason at the sole discretion of the Sponsor. Study sites will be closed upon study 
completion. A study site is considered closed when all required documents and study supplies 
have been collected and a study-site closure visit has been performed. 
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The Investigator may initiate study-site closure at any time, provided there is reasonable cause 
and sufficient notice is given in advance of the intended termination. 
Reasons for the early closure of a study site by the Sponsor or Investigator may include but are 
not limited to: 
• Failure of the Investigator to comply with the protocol, the requirements of the IRB/IEC or 
local health authorities, the Sponsor’s procedures, or GCP guidelines 
• Inadequate recruitment of participants by the Investigator 
• Discontinuation of further study medication development 
10.1.8 
Publication policy 
The results of this study may be published or presented at scientific meetings. If this is foreseen, 
the Investigator agrees to submit all manuscripts or abstracts to the Sponsor before submission. 
This allows the Sponsor to protect proprietary information and to provide comments.  
The Sponsor will comply with the requirements for publication of study results. In accordance 
with standard editorial and ethical practice, the Sponsor will generally support publication of 
multicenter studies only in their entirety and not as individual site data. In this case, a 
Coordinating Investigator will be designated by mutual agreement. 
Authorship will be determined by mutual agreement and in line with International Committee of 
Medical Journal Editors authorship requirements. 
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10.2 
Appendix 2: Clinical laboratory tests 
• The tests detailed in the table below will be performed by a central laboratory. 
• Local laboratory results are only anticipated in the event that the central laboratory results are 
not available in time for either study treatment administration and/or response evaluation. If a 
local sample is required, it is important that the sample for central analysis is obtained at the 
same time. Additionally, if the local laboratory results are used to make either a study 
treatment decision or response evaluation, the results must be entered into the CRF. 
• Protocol-specific requirements for inclusion or exclusion of participants are detailed in 
Section 5.1 and Section 5.2 of the protocol. 
• Additional tests may be performed at any time during the study as determined necessary by 
the Investigator or required by local regulations. 
Protocol-Required Safety Laboratory Assessments 
Laboratory 
Assessments 
Parameters 
Hematology 
Platelet Count  
RBC Indices: 
MCV 
MCH 
%Reticulocytes 
WBC Count with 
Differential: 
Neutrophils 
Lymphocytes 
Monocytes 
Eosinophils 
Basophils 
RBC Count 
Hemoglobin 
Hematocrit 
Clinical 
Chemistry1 
BUN 
Potassium 
AST/SGOT 
Total and 
direct bilirubin 
 
Creatinine 
Sodium 
ALT/SGPT 
Total Protein 
 
Glucose 
Calcium 
Alkaline phosphatase 
 
Endocrinology 
tests 
The following tests will be collected in study participants <18 years of age: 
• 
Follicle-stimulating hormone 
• 
Luteinizing hormone 
• 
Thyroid-stimulating hormone 
• 
Triiodothyronine 
• 
Thyroxine 
Routine 
Urinalysis 
• 
Specific gravity 
• 
pH, glucose, protein, blood, ketones, bilirubin, urobilinogen, nitrite, and 
leukocyte esterase by dipstick 
• 
Microscopic examination (if blood or protein is abnormal) 
Other Screening 
Tests 
• 
Follicle-stimulating hormone and estradiol (as needed in women of 
nonchildbearing potential only) 
• 
Urine hCG pregnancy test (as needed for women of childbearing potential)2 
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ALT=alanine aminotransferase; AST=aspartate aminotransferase; BUN=blood urea nitrogen; hCG=human 
chorionic gonadotropin; IEC=Independent Ethics Committee; INR=international normalized ratio; 
IRB=Institutional Review Board; MCH=mean corpuscular hemoglobin; MCV=mean corpuscular volume; 
RBC=red blood cell; SAE=serious adverse event; SGOT=serum glutamic-oxaloacetic transaminase; 
SGPT=serum glutamic-pyruvic transaminase; ULN=upper limit of normal; WBC=white blood cell 
NOTES: 
1 Details of liver chemistry stopping criteria and required actions and follow-up assessments after liver stopping 
or monitoring event are given in Section 7.1.1 and Appendix 6 (Section 10.6). All events of ALT 3×ULN and 
bilirubin 2×ULN (>35% direct bilirubin) or ALT 3×ULN and INR >1.5, if INR measured, may indicate 
severe liver injury (possible Hy’s Law) and must be reported as an SAE (excluding studies of hepatic 
impairment or cirrhosis). 
2 Local urine testing will be standard for the protocol unless serum testing is required by local regulation or 
IRB/IEC. 
Investigators must document their review of each laboratory safety report. 
Laboratory results that could unblind the N01269 study will not be reported to investigative sites 
or other blinded personnel until the study has been unblinded. 
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10.4 
Appendix 4: Contraceptive guidance and collection of 
pregnancy information 
Definitions 
Woman of childbearing potential (WOCBP) 
A woman is considered fertile following menarche and until becoming post-menopausal unless 
permanently sterile (see below). 
Women in the following categories are not considered WOCBP: 
1. Premenarchal 
2. Premenopausal female with 1 of the following: 
− Documented hysterectomy 
− Documented bilateral salpingectomy 
− Documented bilateral oophorectomy 
Note:  Documentation can come from the site personnel’s review of the participant’s medical 
records, medical examination, or medical history interview. 
3. Postmenopausal female 
− A postmenopausal state is defined as no menses for 12 months without an alternative 
medical cause. A high follicle-stimulating hormone (FSH) level in the postmenopausal 
range may be used to confirm a postmenopausal state in women not using hormonal 
contraception or hormonal replacement therapy (HRT). However, in the absence of 
12 months of amenorrhea, a single FSH measurement is insufficient. 
− Females on HRT and whose menopausal status is in doubt will be required to use one of 
the nonestrogen hormonal highly effective contraception methods if they wish to 
continue their HRT during the study. Otherwise, they must discontinue HRT to allow 
confirmation of postmenopausal status before study enrollment. 
Contraception guidance 
Male participants 
Male participants with female partners of childbearing potential are eligible to participate if they 
agree to ONE of the following and for 5 half-lives (2 days) after the last dose of study 
medication: 
• Are abstinent from penile-vaginal intercourse as their usual and preferred lifestyle (abstinent 
on a long term and persistent basis) and agree to remain abstinent. 
• Agree to use a male condom when having penile-vaginal intercourse with a woman of 
childbearing potential who is not currently pregnant. 
In addition male participants must refrain from donating sperm for the duration of the study and 
for 2 days after the last dose of study medication. 
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Male participants with a pregnant or breastfeeding partner must agree to remain abstinent from 
penile-vaginal intercourse or use a male condom during each episode of penile penetration for 
the duration of the study and for 2 days after the last dose of study medication. 
Female participants 
Female participants of childbearing potential are eligible to participate if they agree to use a 
highly effective method of contraception consistently and correctly as described in the table 
below. 
Highly Effective Contraceptive Methodsa 
Highly Effective Contraceptive Methods That Are User Dependentb 
Failure rate of <1% per year when used consistently and correctly.  
Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of 
ovulationc  
• 
Oral  
• 
Intravaginal  
• 
Transdermal  
Progestogen only hormonal contraception associated with inhibition of ovulation 
• 
Oral  
• 
Injectable  
Highly Effective Methods That Are User Independentc 
Implantable progestogen only hormonal contraception associated with inhibition of ovulation 
• 
Intrauterine device (IUD) 
• 
Intrauterine hormone-releasing system 
• 
Bilateral tubal occlusion 
Vasectomized partner  
A vasectomized partner is a highly effective contraception method provided that the partner is the sole 
male sexual partner of the WOCBP and the absence of sperm has been confirmed. If not, an additional 
highly effective method of contraception should be used.  
Sexual abstinence  
Sexual abstinence is considered a highly effective method only if defined as refraining from heterosexual 
intercourse during the entire period of risk associated with the study medication. The reliability of sexual 
abstinence needs to be evaluated in relation to the duration of the study and the preferred and usual 
lifestyle of the participant.  
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NOTES:  
a) In case of newly started contraception pills/IUDs, the Principal Investigator should consider the correct 
timing of starting/applying such methods in relation to the menstrual cycle and the manufacturing 
instruction as when these newly started methods would become effective. 
b) Typical use failure rates may differ from those when used consistently and correctly. Use should be 
consistent with local regulations regarding the use of contraceptive methods for participants participating 
in clinical studies.  
c) Hormonal contraception may be susceptible to interaction with the study medication, which may 
reduce the efficacy of the contraceptive method. In this case, two highly effective methods of 
contraception should be utilized during the treatment period and for at least 2 days after the last dose of 
study medication  
Pregnancy testing 
• WOCBP should only be included after a confirmed menstrual period and a negative highly 
sensitive urine pregnancy test. 
• Pregnancy testing will be performed as specified in the Schedule of Assessments (Table 1‒2) 
during the study and 2 days after the last dose of study medication, or as required locally.  
• Pregnancy testing will be performed whenever a menstrual cycle is missed or when 
pregnancy is otherwise suspected. 
Male participants with partners who become pregnant 
• The Investigator will attempt to collect pregnancy information on any male participant’s 
female partner who becomes pregnant while the male participant is in this study. 
• After obtaining the necessary signed informed consent from the pregnant female partner 
directly, the Investigator will record pregnancy information on the appropriate form and 
submit it to the Sponsor within 1 working day of learning of the partner’s pregnancy. The 
female partner will also be followed to determine the outcome of the pregnancy. Information 
on the status of the mother and child will be forwarded to the Sponsor. Generally, the 
follow-up will be at least 30 days and up to 12 months after the delivery date. Any 
termination of the pregnancy will be reported regardless of fetal status (presence or absence 
of anomalies) or indication for the procedure. 
Female participants who become pregnant 
• Any female participant who becomes pregnant while participating in the study will 
discontinue study medication or be withdrawn from the study. 
• The Investigator will collect pregnancy information on any female participant who becomes 
pregnant while participating in this study. Information will be recorded on the appropriate 
form and submitted to the Sponsor within 1 working day of learning of a participant’s 
pregnancy. The participant will be followed to determine the outcome of the pregnancy. The 
Investigator will collect follow-up information on the participant and the neonate and the 
information will be forwarded to the Sponsor. Generally, the follow-up will be at least 
30 days and up to 12 months after the delivery date. Any termination of pregnancy will be 
reported, regardless of fetal status (presence or absence of anomalies) or indication for the 
procedure. 
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• While pregnancy itself is not considered to be an AE or SAE, any pregnancy complication or 
elective termination of a pregnancy will be reported as an AE or SAE. A spontaneous 
abortion is always considered to be an SAE and will be reported as such. Any post-study 
pregnancy related SAE considered reasonably related to the study medication by the 
Investigator will be reported to the Sponsor as described in Section 8.2.5. While the 
Investigator is not obligated to actively seek this information in former study participants, he 
or she may learn of an SAE through spontaneous reporting.  
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10.5 
Appendix 5: Genetics 
Not applicable. 
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10.6 
Appendix 6: Liver safety – suggested actions and follow-up 
assessments 
Participants with PDILI must be assessed to determine if study medication must be discontinued. 
In addition, all concomitant medications and herbal supplements that are not medically necessary 
should also be discontinued. 
Investigators should attempt to obtain information on study participants in the case of study 
medication discontinuation to complete the final evaluation.  
Study participants with PDILI should not be withdrawn from the study until investigation and 
monitoring are complete. All results of these evaluations and observations, as well as the 
reason(s) for study medication discontinuation and/or participant withdrawal (if applicable), 
must be recorded in the source documents. The CRF must document the primary reason for 
discontinuation of study medication.  
A specific monitoring plan must be agreed between the UCB Study Physician and the 
Investigator for study participants who have ALT >5 ULN. The monitoring plan should include 
any necessary follow-up assessments (until resolution of the abnormal lab values).  
Phase 3-4 liver chemistry stopping criteria and follow-up assessments  
Liver Chemistry Stopping Criteria 
ALT-absolute 
ALT 8xULN 
ALT Increase 
ALT 5xULN but <8xULN persists for 2 weeks 
ALT 3xULN but <5xULN persists for 4 weeks 
Bilirubina,b  
ALT 3xULN and bilirubin 2xULN (>35% direct bilirubin)  
INRb 
ALT 3xULN and INR >1.5, if INR measured 
Cannot 
Monitor 
ALT 5xULN but <8xULN and cannot be monitored weekly for 2 weeks 
ALT 3xULN but <5xULN and cannot be monitored weekly for 4 weeks 
Symptomaticc 
ALT 3xULN associated with symptoms (new or worsening) believed to be related 
to liver injury or hypersensitivity 
Suggested Actions and Follow up Assessments 
Actions 
Follow Up Assessments 
• 
Immediately discontinue study medication. 
• 
Report the event to UCB within 24 hours. 
• 
Complete the liver event CRF, and complete a 
SAE data collection tool if the event also met 
the criteria for an SAE.b  
• 
Perform liver chemistry follow-up assessments.  
• 
Monitor the participant until liver chemistry 
test abnormalities resolve, stabilize, or return to 
Baseline (see MONITORING). 
• 
Viral hepatitis serologyd 
• 
Obtain INR and recheck with each liver 
chemistry assessment until the 
transaminases values show downward trend 
• 
Only in those with underlying chronic 
hepatitis B at study entry (identified by 
positive hepatitis B surface antigen), 
quantitative hepatitis B DNA and hepatitis 
delta antibodye 
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Liver Chemistry Stopping Criteria 
• 
Do not restart/rechallenge participant with 
study medication unless allowed per protocol 
and UCB approval is granted. 
• 
If restart/rechallenge not allowed per protocol 
or not granted, permanently discontinue study 
medication and continue participant in the 
study for any protocol specified follow up 
assessments.Consider the need for a toxicology 
screening. 
 
MONITORING: 
For bilirubin or INR criteria  
• 
Repeat liver chemistry tests (include ALT, 
AST, alkaline phosphatase, bilirubin) and 
perform liver event follow-up assessments 
within 24 hours. 
• 
Monitor participant twice weekly until liver 
chemistry test abnormalities resolve, stabilize, 
or return to Baseline. 
• 
A specialist or hepatology consultation is 
recommended. 
For all other criteria  
• 
Repeat liver chemistry tests (include ALT, 
AST, alkaline phosphatase, bilirubin) and 
perform liver chemistry follow-up assessments 
within 24 to 72 hours. 
• 
Monitor participants weekly until liver 
chemistry abnormalities resolve, stabilize, or 
return to Baseline. 
• 
Obtain blood sample for PK analysis within 
2 days after the most recent dosef 
• 
Serum CPK and LDH 
• 
Fractionate bilirubin, if total bilirubin 
 2xULN 
• 
Obtain complete blood count with 
differential to assess eosinophilia 
• 
Record the appearance or worsening of 
clinical symptoms of liver injury (eg, 
fatigue, nausea, vomiting, right upper 
quadrant pain), or hypersensitivity, on the 
AE report form 
• 
Record use of concomitant medications 
(including acetaminophen, herbal remedies, 
and other over-the-counter medications) on 
the concomitant medications CRF. 
• 
Record alcohol use on the liver event 
alcohol intake CRF 
• 
Exclude pregnancy 
For bilirubin or INR criteria: 
• 
Anti-nuclear antibody, anti-smooth muscle 
antibody, Type 1 anti-liver kidney 
microsomal antibodies, and quantitative 
total IgG or gamma globulins. 
• 
Serum acetaminophen adduct HPLC assay 
(quantifies potential acetaminophen 
contribution to liver injury in participants 
with definite or likely acetaminophen use in 
the preceding week [James et al, 2009]).  
NOTE: Not required in China. 
• 
Liver imaging (ultrasound, magnetic 
resonance, or computerized tomography) 
and/or liver biopsy to evaluate liver disease; 
complete Liver Imaging and/or Liver 
Biopsy CRFs. 
AE=adverse event; ALP=alkaline phosphatase; ALT=alanine aminotransferase; AST=aspartate aminotransferase; 
CPK=creatine phosphokinase; CRF=case report form; HbcAb=hepatitis B core antibody; HbsAg=hepatitis B 
surface antigen; HPLC=high performance liquid chromatography; IgG=immunoglobulin G; IgM=immunoglobulin 
M; INR=international normalized ratio; LDH=lactate dehydrogenase; PCR=polymerase chain reaction; 
PK=pharmacokinetic; SAE=serious adverse event; ULN=upper limit of normal 
a Serum bilirubin fractionation should be performed if testing is available. If serum bilirubin fractionation is not 
immediately available, discontinue study medication if ALT ≥3xULN and bilirubin ≥2xULN. Additionally, if 
serum bilirubin fractionation testing is unavailable, record the absence/presence of detectable urinary bilirubin 
on dipstick which is indicative of direct bilirubin elevations suggesting liver injury.  
b All events of ALT ≥3xULN and bilirubin ≥2xULN (>35% direct bilirubin) or ALT ≥3xULN and INR >1.5 may 
indicate severe liver injury (possible ‘Hy’s Law’) and must be reported as an SAE (excluding studies of 
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hepatic impairment or cirrhosis). The INR measurement is not required and the stated threshold value will not 
apply to participants receiving anticoagulants.  
c New or worsening symptoms believed to be related to liver injury (such as fatigue, nausea, vomiting, right upper 
quadrant pain or tenderness, or jaundice) or hypersensitivity (such as fever, rash, or eosinophilia). 
d Includes: Hepatitis A IgM antibody; HbsAg and HbcAb; hepatitis C RNA; cytomegalovirus IgM antibody; 
Epstein-Barr viral capsid antigen IgM antibody (or if unavailable, heterophile antibody or monospot testing); and 
hepatitis E IgM antibody. 
e If hepatitis delta antibody assay cannot be performed, it can be replaced with a PCR of hepatitis D RNA virus 
(where needed) [Le Gal et al, 2005]. 
f PK sample may not be required for participants known to be receiving placebo or noncomparator interventions. 
Record the date/time of the PK blood sample draw and the date/time of the last dose of study medication prior to 
the PK blood sample draw on the CRF. If the date or time of the last dose is unclear, provide the participant’s best 
approximation. If the date/time of the last dose cannot be approximated OR a PK sample cannot be collected in the 
time period indicated above, do not obtain a PK sample. Instructions for sample handling and shipping are in the 
Study Reference Manual. 
 
Phase 3-4 liver chemistry increased monitoring criteria with continued study 
medication 
Liver Chemistry Increased Monitoring Criteria 
Criteria 
Actions 
 
ALT 5xULN and <8xULN and bilirubin 
<2xULN without symptoms believed to 
be related to liver injury or 
hypersensitivity, and who can be 
monitored weekly for 2 weeks. 
OR 
ALT 3xULN and <5xULN and bilirubin 
<2xULN without symptoms believed to 
be related to liver injury or 
hypersensitivity, and who can be 
monitored weekly for 4 weeks. 
 
• 
Notify UCB Medical Monitor within 24 hours of 
learning of the abnormality to discuss participant 
safety.  
• 
Participant can continue study medication 
• 
Participant must return weekly for repeat liver 
chemistry tests (ALT, AST, alkaline phosphatase, 
bilirubin) until the abnormalities resolve, stabilize, or 
return to Baseline.  
• 
If at any time, the participant meets liver chemistry 
stopping criteria, proceed as described in Section 7.1. 
• 
If ALT decreases from ALT 5xULN and <8xULN to 
≥3xULN but <5xULN, continue to monitor liver 
chemistries weekly.  
• 
If, after 4 weeks of monitoring, ALT <3xULN and 
bilirubin <2xULN, monitor participants twice 
monthly until liver chemistry tests resolve, stabilize, 
or return to Baseline. 
ALT=alanine aminotransferase; AST=aspartate aminotransferase; ULN=upper limit of normal 
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10.7 
Appendix 7: Medical device AEs, adverse device effects, SAEs 
and device deficiencies: definition and procedures for 
recording, evaluating, follow-up, and reporting 
Not applicable. 
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10.8 
Appendix 8: Rapid alert procedures 
Not applicable. 
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10.9 
Appendix 9: Country-specific requirements 
Not applicable.  
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10.10 
Appendix 10: Abbreviations and trademarks 
AE 
adverse event 
AED 
antiepileptic drug 
ALT 
alanine aminotransferase 
bid 
twice daily 
BRV 
brivaracetam 
CAE 
childhood absence epilepsy 
COVID-19 
coronavirus disease 
CRF 
case report form 
C-SSRS 
Columbia Suicide Severity Rating Scale 
DTV 
Down-Titration Visit 
ECG 
electrocardiogram 
eCRF 
electronic case report form 
EDV 
Early Discontinuation Visit 
EEG 
electroencephalogram 
ESM 
ethosuximide 
EV 
Entry Visit 
FEV 
Full Evaluation Visit 
FSH 
follicle-stimulating hormone 
FV 
Final Visit 
GCP 
Good Clinical Practice 
HRT 
hormone replacement therapy 
IB 
Investigator’s Brochure 
ICF 
informed consent form 
ICH 
International Council for Harmonisation 
IEC 
Independent Ethics Committee 
ILAE 
International League Against Epilepsy 
IMP 
investigational medicinal product 
IRB 
Institutional Review Board 
IUD 
intrauterine device 
iv 
intravenous 
IXRS 
interactive voice or web response system 
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JAE 
juvenile absence epilepsy 
LEV 
levetiracetam 
LTFU 
long-term follow-up 
LTG 
lamotrigine 
MedDRA® 
Medical Dictionary for Regulatory Activities 
MEV 
Minimal Evaluation Visit 
PCST 
possibly clinically significant treatment-emergent 
PDILI 
potential drug-induced liver injury 
PedsQL 
Pediatric Quality of Life 
PK 
pharmacokinetic(s) 
POS 
partial-onset seizure(s) 
SAE 
serious adverse event 
SAP 
Statistical Analysis Plan 
SDV 
source data verification 
SS 
Safety Set 
SV 
Safety Visit 
SV2A 
synaptic vesicle protein 2A 
TEAE 
treatment-emergent adverse event 
ULN 
upper limit of normal 
VPA 
valproic acid 
WOCBP 
woman of childbearing potential 
YEV 
Yearly Evaluation Visit 
 
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10.11 
Appendix 11: Protocol amendment history 
The Protocol Amendment Summary of Changes Table for the current amendment is located 
directly before the Table of Contents. 
Amendment 1 (08 Sep 2020) 
Overall Rationale for the Amendment 
EP0132 Protocol Amendment 1, dated 08 Sep 2020, was completed to remove all decentralized 
study components as it was decided that all participant visits will occur on site. Centrally read 
24-hour electroencephalogram (EEGs) were removed; locally read 1-hour EEGs that reflect 
normal clinical practice will be used in this study. In addition, the Conners Continuous 
Performance Tests (CPT), Achenbach Childhood Behavior Checklist (CBCL), and EuroQol 5-
Dimension (EQ-5D) Quality of Life Assessments have been removed from the list of participant- 
and caregiver-reported outcomes and the wearable EEG (SeizeIT) substudy has been removed.   
Section # and Name 
Description of Change 
Brief Rationale 
Synopsis and Section 3 
(Objectives and Endpoints) 
Centrally read 24-hour EEGs 
were removed and replaced by 
1-hour locally read EEGs.  
Obtaining a 1-hour EEG mimics 
routine clinical practice and it was 
determined that there will be no 
central reader in EP0132. 
Synopsis and Section 3 
(Objectives and Endpoints) 
The Achenbach CBCL, Conners 
CPT, and EQ-5D Assessments 
were removed as endpoints for 
the exploratory objective of this 
study. 
Removed assessments to reduce 
overall complexity, patient burden, 
and to address logistical challenges. 
Synopsis and Section 3 
(Objectives and Endpoints) 
Removed the exploratory 
objective planned to investigate 
the use of a wearable EEG 
device (SeizeIT) in a subset of 
study participants. 
Removed wearable device substudy 
to reduce complexity and 
participant/site burden. 
Section 1.3  
(Schedule of activities) 
Removed header row from 
Table 1-2 designating each visit 
as a decentralized visit or a site 
visit. 
The virtual visits were removed as 
the visit schedule of the study is close 
to the standard visit schedule of 
pediatric epilepsy patients in clinical 
practice; therefore, the additional 
burden of the patients going to the 
sites is minimal. 
Section 1.3 
(Schedule of activities) 
Removed information regarding 
the Achenbach CBCL, Conners 
CPT, and EQ-5D Assessments. 
Removed assessments to reduce 
overall complexity, patient burden, 
and to address logistical challenges. 
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Section # and Name 
Description of Change 
Brief Rationale 
Section 1.3  
(Schedule of activities) 
Removed information regarding 
the wearable EEG (SeizeIT) 
substudy. 
Removed wearable device substudy 
to reduce complexity and 
participant/site burden. 
Section 1.3  
(Schedule of activities) 
Added a new footnote to define 
the EDV. 
Provide additional informational 
details. 
Section 1.3  
(Schedule of activities) 
Added text to the footnote 
describing PK assessment visits 
to clarify that on the FEV, YEV, 
EDV, and FV Visits, 
participants should not take 
their morning BRV dose prior to 
arriving at the clinic. 
Provide additional clarifying detail 
that for visits when PK assessments 
are planned, the morning BRV dose 
will be administered at the clinical 
unit. 
Section 1.3  
(Schedule of activities) 
Added a new footnote to clarify 
that the investigator/designated 
EEG reader should attempt to 
keep the study participant 
awake for the duration of the 1-
hour EEG to ensure that the 
minimum period of awake time 
(30 minutes) required for 
evaluability is achieved. 
Provide additional clarifying details 
to ensure that the 1-hour EEGs 
achieve the minimum period of 
awake time (30 minutes) required for 
evaluability. 
Section 4.1.1  
(Site-based model) 
Removed section and relocated 
text stating that all study 
assessments will be conducted 
on site to Section 4.1. 
Post-approval decision that a site-
based model will be used by all 
countries. 
Section 4.1.2  
(Decentralized model) 
Removed section describing the 
decentralized model. 
The virtual visits were removed as 
the visit schedule of the study is close 
to the standard visit schedule of 
pediatric epilepsy patients in clinical 
practice; therefore, the additional 
burden of the patients going to the 
sites is minimal. 
Section 6.1.1  
(Medical devices) 
Removed section describing the 
wearable EEG (SeizeIT) 
substudy. 
Removed wearable device substudy 
to reduce complexity and 
participant/site burden. 
Section 6.5.3  
(Rescue medication) 
Removed text referencing the 
24-hour EEG. 
The 24-hour EEG will no longer be 
performed as a 1-hour EEG mimics 
routine clinical practice. 
Section 8.1.1  
(Seizure data based on 
EEG) 
Revised text previously 
describing 24-hour ambulatory 
EEGs to describe 1-hour EEGs. 
Obtaining a 1-hour EEG mimics 
routine clinical practice. 
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Section # and Name 
Description of Change 
Brief Rationale 
Section 8.1.1  
(Seizure data based on 
EEG) 
Removed text describing EEG 
procedures for countries where 
the decentralized model was to 
be used.  
The virtual visits were removed as 
the visit schedule of the study is close 
to the standard visit schedule of 
pediatric epilepsy patients in clinical 
practice; therefore, the additional 
burden of the patients going to the 
sites is minimal. 
Section 8.1.2  
(Seizure diary) 
Removed reference to an 
electronic diary for recording 
daily seizure activity. 
Post approval decision to use paper 
diaries instead of electronic diaries in 
this study. 
Section 8.2.4 
(Electrocardiograms) 
Text was added to clarify that 
for abnormal ECG values 
observed during N01269, prior 
to participant’s entry into 
EP0132, or during EP0132, 
ECGs will be repeated until the 
participant’s values return to 
normal or Baseline or are no 
longer considered clinically 
significant. 
Provide clarifying details regarding 
the follow up of abnormal ECGs 
during this study. 
Section 8.2.6  
(Suicidal risk monitoring) 
Text was added to clarify that 
the C-SSRS will only be 
conducted in participants 
≥6 years of age and to provide 
details for procedures to follow 
when a participant turns 
6 during the study. 
Provide clarification of the 
participants’ ages in which the 
C-SSRS will be used, in addition to 
further procedural details. 
Section 8.2.7  
(Participant- or caregiver-
reported outcomes) 
Removed the Achenbach 
CBCL, Conners Performance 
Tests, and EQ-5D Quality of 
Life Assessments from the 
tabular presentation (Table 8-1) 
of the participant- and 
caregiver-reported outcomes. 
Removed assessments to reduce 
overall complexity, patient burden, 
and to address logistical challenges 
Section 8.2.7.1  
(Achenbach Childhood 
Behavior Checklist) 
Removed section describing the 
Achenbach CBCL. 
Assessment has been omitted from 
the protocol. 
Section 8.2.7.3 
(Conners Continuous 
Performance Test) 
Removed section describing the 
Conners CPT. 
Assessment has been omitted from 
the protocol. 
Section 8.2.7.4  
(Pediatric Quality of Life 
Inventory) 
Revised the text to state that the 
1-week recall version of the 
PedsQL will be used for all 
planned assessment timepoints. 
The 1-week recall version of the 
PedsQL will be used for all 
assessment timepoints in N01269; 
therefore, using the same version in 
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Section # and Name 
Description of Change 
Brief Rationale 
this LTFU study will allow for 
consistent comparisons. 
Section 8.2.7.5  
(EuroQol-5-Dimension 
Quality of Life 
Assessment) 
Removed section describing the 
EQ-5D Quality of Life 
Assessment. 
Assessment has been omitted from 
the protocol. 
Section 8.2.8.1 
(Nonabsence seizure 
incidence after first BRV 
treatment during the study 
based on EEG) 
Removed text describing 
24-hour EEG. 
Post approval decision to only 
conduct 1-hour locally read EEGs, 
which aligns with routine clinical 
practice. 
Section 8.3.8  
(Medical device – AEs and 
device deficiencies) 
Removed section describing the 
SeizeIT wearable EEG device.  
Not applicable to EP0132 since the 
SeizeIT device has been omitted from 
the protocol. 
Section 8.6 
(Pharmacokinetics) 
Added text describing the PK 
assessment visits to note that on 
the FEV, YEV, EDV, and FV, 
participants should not take 
their morning BRV dose prior to 
arriving at the clinic. 
Provide additional clarifying detail 
that for visits when PK assessments 
are planned, the morning BRV dose 
will be administered at the clinical 
unit. 
Section 9.3.1  
(Analysis of the secondary 
efficacy endpoint) 
Revised text describing 24-hour 
ambulatory EEG to 1-hour 
EEG. 
Post approval decision to only 
conduct 1-hour locally read EEGs, 
which aligns with routine clinical 
practice. 
Section 9.4.3  
(Other analyses) 
Revised text to remove 
reference to the Conners CPT, 
Achenbach CBCL, and EQ-5D 
Assessments. Also removed 
reference to the wearable EEG 
device (SeizeIT). 
Removed assessments and the 
wearable EEG substudy from the 
protocol to reduce overall 
complexity, patient burden, and to 
address logistical challenges. 
Section 10.7  
(Appendix 7: Medical 
device AEs , adverse 
device effects, SAEs and 
device deficiencies: 
definition and procedures 
for recording, evaluating, 
follow-up, and reporting) 
Removed appendix text 
describing medical device AEs. 
Not applicable to EP0132 since the 
SeizeIT device has been omitted from 
the protocol. 
AE=adverse event; BRV=brivaracetam; CBCL=Childhood Behavior Checklist; CPT=Continuous Performance 
Test; C-SSRS=Columbia Suicide Severity Rating Scale; EDV=Early Discontinuation Visit; 
EEG=electroencephalogram; EQ-5D=EuroQol 5-Dimensions Quality of Life Assessment; FEV=Full 
Evaluation Visit; FV=Final Visit; PedsQL=Pediatric Quality of Life; PK=pharmacokinetic; SAE=serious 
adverse event; YEV=Yearly Evaluation Visit 
 
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11 
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UCB 
 
29 Mar 2021 
Clinical Study Protocol Amendment 2 
Brivaracetam 
EP0132 
 
 
 
Confidential 
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SPONSOR DECLARATION 
I confirm that I have carefully read and understand this protocol and agree to conduct this 
clinical study as outlined in this protocol and according to current Good Clinical Practice. 
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application and any extensions or variations thereof.

PUBLIC COPY 
This document cannot be used to support any marketing authorization 
application and any extensions or variations thereof.