Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| 2015-002756-27 | EudraCT Number |
Not provided
Not provided
Not provided
Terminated (The study stopped prematurely due to enrolment challenges, the termination was not linked to any safety issues.)
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
The purpose of the study is to evaluate the pharmacokinetics (PK) of brivaracetam (BRV) in neonates who have seizures that are not adequately controlled with previous antiepileptic drug (AED) treatment, and to identify the optimal BRV dose (Exploratory Cohort) for the treatment of subjects enrolled into the Confirmatory Cohorts of this study.
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Brivaracetam (BRV) | Experimental | Exploratory Cohort and Confirmatory Cohorts |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Brivaracetam (BRV) intravenous (iv) | Drug | Exploratory Cohort: Subjects will be dosed with BRV (0.5 mg/kg twice daily (bid)) according to the sites standard procedures. Treatment with 1 or more of the following antiepileptic drugs (AEDs): phenobarbital (PB), midazolam (MDZ), phenytoin (PHT), levetiracetam (LEV), or lidocaine (LDC) (first-line, second-line, or subsequent treatment) will continue in parallel with BRV treatment. Confirmatory Cohort: For subjects who enter the Confirmatory Cohorts, for the strength of BRV 1 mg/kg bid (2 mg/kg/day) has been determined based on the Pharmacokinetic (PK) findings of the Exploratory Cohort. Based on further monitoring of PK and safety findings dosing may be adjusted as new data are available. Administration of BRV is proposed as approximately 15-minute intravenous (iv) infusions. Treatment with previous antiepileptic drugs is permitted to continue if the subject is on a stable dose from 1 hour prior to initiation of the BRV treatment. |
| Measure | Description | Time Frame |
|---|---|---|
| Plasma Concentration of Brivaracetam (BRV) Following First Dose on Day 1 | Pharmacokinetic blood samples were taken 0.5 to 1 hour, 2 to 4 hours, and 8 to 12 hours after the BRV infusion on Day 1 to determine the BRV plasma concentration. | Pharmacokinetic blood samples were taken 0.5 to 1 hour, 2 to 4 hours, and 8 to 12 hours after the BRV infusion on Day 1 |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Responders to BRV Treatment From Baseline to 3 Hours After the Initial BRV Treatment | A BRV responder was defined as a participant who achieved the following reduction in seizure burden (electroencephalographic neonatal seizures (ENS) in minutes per hour) without need for rescue medication, compared to the seizure burden measured during the Baseline Period immediately prior to BRV administration, evaluated for a 2-hour period starting 1 hour after the start of initial BRV treatment: At least 80% reduction in nonsevere seizure burden (Nonsevere seizure burden is defined as <=50% seizure activity on video-electroencephalography (VEEG) in all 30-minute timespans), OR At least 50 % reduction in severe seizure burden (Severe seizure burden is defined as >50 % seizure activity on VEEG in any 30-minute timespan). Timespans of 30 minutes refer to the following intervals within the 2-hour period: 0 to <= 30 minutes, > 30 to <= 60 minutes, >60 to <= 90 minutes, and >90 to <= 120 minutes. |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Subjects are not permitted to be enrolled in the study if any of the following criteria are met:
For subjects with perinatal asphyxia, elevation of AST, ALT or ALP <5x ULN is acceptable, if initial and peak elevation of liver function tests (LFTs) occurs within 5 days after birth, and the time course of LFT elevation is compatible with hepatic injury due to perinatal asphyxia. The determination of ULN will be based on the subject's gestational age (GA) and the site's normal range values for the respective GA
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| UCB Cares | UCB (+1 844 599 2273) | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| N01349 204 | Leuven | Belgium | ||||
| N01349 205 |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 38049197 | Result | Pressler R, Boylan G, Dempsey E, Klotz KA, Krauwinkel W, Will E, Morita D, Floricel F, Elshoff JP, van den Anker J. Pharmacokinetics and safety of brivaracetam in neonates with repeated electroencephalographic seizures: A multicenter, open-label, single-arm study. Epilepsia Open. 2024 Apr;9(2):522-533. doi: 10.1002/epi4.12875. Epub 2024 Jan 11. |
| Label | URL |
|---|---|
| Product Information | View source |
Not provided
Data from this trial may be requested by qualified researchers six months after product approval in the US and/or Europe, or global development is discontinued, and 18 months after trial completion. Investigators may request access to anonymized individual patient-level data and redacted trial documents which may include: analysis-ready datasets, study protocol, annotated case report form, statistical analysis plan, dataset specifications, and clinical study report. Prior to use of the data, proposals need to be approved by an independent review panel at www.Vivli.org and a signed data sharing agreement will need to be executed. All documents are available in English only, for a prespecified time, typically 12 months, on a password protected portal. This plan may change if the risk of re-identifying trial participants is determined to be too high after the trial is completed; in this case and to protect participants, individual patient-level data would not be made available.
Data from this trial may be requested by qualified researchers six months after product approval in the US and/or Europe or global development is discontinued, and 18 months after trial completion.
Qualified researchers may request access to anonymized IPD and redacted study documents which may include: raw datasets, analysis-ready datasets, study protocol, blank case report form, annotated case report form, statistical analysis plan, dataset specifications, and clinical study report. Prior to use of the data, proposals need to be approved by an independent review panel at www.Vivli.org and a signed data sharing agreement will need to be executed. All documents are available in English only, for a pre-specified time, typically 12 months, on a password protected portal.
No eligible study participants were enrolled in the Confirmatory Cohorts. The study stopped prematurely due to enrolment challenges, the termination was not linked to any safety issues. The Participant Flow refers to the All Subjects Screened.
The study started to enroll participants in May 2019 and concluded in May 2021.
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | Exploratory Cohort | Participants in this arm received brivaracetam (BRV) 0.5 milligram per kilogram (mg/kg) administered as an intravenous (iv) solution for injection twice daily (bid) during the 48-hour Evaluation Period. An additional 3 doses of BRV (0.5 mg/kg) could have been administered every 12 hours for 48 hours (at the discretion of the Investigator). Treatment with antiepileptic drugs (AEDs) per standard of care (SToC) (first-line, second-line, or subsequent treatment) were continued in parallel with BRV treatment. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
Not provided
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | May 24, 2021 | Jun 22, 2022 |
Not provided
Not provided
Not provided
Not provided
Not provided
|
|
| Brivaracetam (BRV) oral | Drug | Subjects can switch from intravenous (iv) to oral brivaracetam (BRV) at any time during the BRV Extension Period |
|
|
| From Baseline to 3 hours after the initial BRV treatment |
| Percentage of Participants With at Least 80% Reduction in Nonsevere Seizure Burden From Baseline to 3 Hours After the Initial BRV Treatment | Nonsevere seizure burden was defined as <=50% seizure activity on VEEG in all 30-minute timespans. Seizure burden was measured during the Baseline Period immediately prior to BRV administration and evaluated for a 2-hour period starting 1 hour after the start of initial BRV. Timespans of 30 minutes refer to the following intervals within the 2-hour period: 0 to <= 30 minutes, > 30 to <= 60 minutes, >60 to <= 90 minutes, and >90 to <= 120 minutes. | From Baseline to 3 hours after the initial BRV treatment |
| Percentage of Participants With at Least 50% Reduction in Severe Seizure Burden From Baseline to 3 Hours After the Initial BRV Treatment | Severe seizure burden was defined as >50% seizure activity on VEEG in any 30-minute timespan. Seizure burden was measured during the Baseline Period immediately prior to BRV administration and evaluated for a 2-hour period starting 1 hour after the start of initial BRV. Timespans of 30 minutes refer to the following intervals within the 2-hour period: 0 to <= 30 minutes, > 30 to <= 60 minutes, >60 to <= 90 minutes, and >90 to <= 120 minutes. | From Baseline to 3 hours after the initial BRV treatment |
| Absolute Change in Average Seizure Burden Measured by Continuous Video-electroencephalography (VEEG) From Baseline to the End of the 96-hour Evaluation Period | Seizure burden was measured by continuous video-electroencephalography (VEEG). Baseline seizure burden is defined as seizure burden measured on the continuous VEEG (total electroencephalographic neonatal seizures (ENS) in minutes per hour) during a period of up to 1 hour immediately prior to the first administration of study drug. | From Baseline to the end of the 96-hour Evaluation Period |
| Percentage Change in Average Seizure Burden Measured by Continuous VEEG From Baseline to the End of the 96-hour Evaluation Period | Seizure burden was measured by continuous video-electroencephalography (VEEG). Baseline seizure burden was defined as seizure burden measured on the continuous VEEG (total electroencephalographic neonatal seizures (ENS) in minutes per hour) during a period of up to 1 hour immediately prior to the first administration of study drug. | From Baseline to the end of the 96-hour Evaluation Period |
| Percentage of BRV Responders at the End of the 96-hour Evaluation Period | A BRV responder was defined as a participant who achieves the following reduction in seizure burden (electroencephalographic neonatal seizures (ENS) in minutes per hour) without need for rescue medication, compared to the seizure burden measured during the Baseline Period immediately prior to BRV administration, evaluated for a 2-hour period starting 1 hour after the start of initial BRV treatment: At least 80% reduction in nonsevere seizure burden (Nonsevere seizure burden is defined as <=50% seizure activity on VEEG in all 30-minute timespans), OR At least 50% reduction in severe seizure burden (Severe seizure burden is defined as >50% seizure activity on VEEG in any 30-minute timespan). | From Baseline to the end of the 96-hour Evaluation Period |
| Percentage of Participants Who Are Seizure-free at 24 Hours Following the Start of Initial BRV Treatment, Categorized by Subjects With Nonsevere or Severe Seizure Burden at Baseline | Seizure freedom is defined as 100 % reduction in seizure burden from Baseline. | From Baseline to 24 hours after the initial BRV treatment |
| Time to Reduction in Seizure Burden for BRV Responders | A BRV responder was defined as a participant who achieves the following reduction in seizure burden (electroencephalographic neonatal seizures (ENS) in minutes per hour) without need for rescue medication, compared to the seizure burden measured during the Baseline Period immediately prior to BRV administration, evaluated for a 2-hour period starting 1 hour after the start of initial BRV treatment: At least 80% reduction in nonsevere seizure burden (Nonsevere seizure burden is defined as <=50% seizure activity on VEEG in all 30-minute timespans), OR At least 50% reduction in severe seizure burden (Severe seizure burden is defined as >50% seizure activity on VEEG in any 30-minute timespan). | From Baseline to the first timepoint when BRV responder criteria are met (up to 96-hour Evaluation Period) |
| Percentage of Participants With Seizure Freedom at the End of the Down-Titration Period | Seizure freedom was defined as 100% reduction in seizure burden from Baseline. | From Baseline to the end of the Down-Titration Period (up to 97 days) |
| Percentage of Participants With at Least 50% Reduction in Electroencephalographic Neonatal Seizures (ENS) Frequency Per Hour From Baseline to the End of the 96-hour Evaluation Period | For this study, an ENS was defined as an EEG seizure lasting for at least 10 seconds on VEEG. Baseline seizure burden was defined as seizure burden measured on the continuous VEEG (total ENS in minutes per hour) during a period of up to 1 hour immediately prior to the first administration of study drug. | From Baseline to the end of the 96-hour Evaluation Period |
| Percentage of Participants Who Are Seizure-free by Time Interval Over the 96-hour Evaluation Period Following the Start of the Initial BRV Treatment | Seizure freedom was defined as 100% reduction in seizure burden from Baseline. | From 3 hours following the start of the initial BRV treatment to the end of the 96-hour Evaluation Period |
| Absolute Difference in Clinical Seizures at the End of the 24-hour Evaluation Period From Baseline for Neonates With Motor Seizures at the Time of Inclusion | Seizures was measured by continuous video-electroencephalography (VEEG). | From Baseline to the end of the 24-hour Evaluation Period |
| Percent Difference in Clinical Seizures at the End of the 24-hour Evaluation Period From Baseline for Neonates With Motor Seizures at the Time of Inclusion | Seizures was measured by continuous video-electroencephalography (VEEG). | From Baseline to the end of the 24-hour Evaluation Period |
| Percentage of Participants With Adverse Events (AEs) as Reported by the Investigator | An adverse event (AE) was any untoward medical occurrence in a patient or clinical investigation study participant administered a pharmaceutical product that did not necessarily have a causal relationship with this treatment. | Adverse Events were collected from Screening Period until the Safety Follow-Up Visit (up to Day 75) |
| Prague |
| Czechia |
| N01349 207 | Lille | France |
| N01349 206 | Paris | France |
| N01349 218 | Erlangen | Germany |
| N01349 209 | Freiburg im Breisgau | Germany |
| N01349 211 | Cork | Ireland |
| N01349 212 | Messina | Italy |
| N01349 213 | Parma | Italy |
| N01349 256 | Roma | Italy |
| N01349 251 | Cambridge | United Kingdom |
| N01349 216 | London | United Kingdom |
| FDA Safety Alerts and Recalls | View source |
| Treated | Only 6 of 9 participants were treated with BRV. |
|
| COMPLETED |
|
| NOT COMPLETED |
|
|
Baseline Characteristics refer to the All Study Participants Screened Set which consisted of all study participants who had signed the Informed Consent form (ICF) and underwent the study inclusion and exclusion criteria of the current protocol. No eligible study participants were enrolled in the Confirmatory Cohorts. The study stopped prematurely due to enrolment challenges, the termination was not linked to any safety issues.
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Exploratory Cohort | Participants in this arm received brivaracetam (BRV) 0.5 milligram per kilogram (mg/kg) administered as an intravenous (iv) solution for injection twice daily (bid) during the 48-hour Evaluation Period. An additional 3 doses of BRV (0.5 mg/kg) could have been administered every 12 hours for 48 hours (at the discretion of the Investigator). Treatment with antiepileptic drugs (AEDs) per standard of care (SToC) (first-line, second-line, or subsequent treatment) were continued in parallel with BRV treatment. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | |||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Corrected gestational age at time of enrollment is reported. | Mean | Standard Deviation | weeks |
| |||||||||||||||||||||
| Age, Customized | Count of Participants | Participants |
| |||||||||||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| |||||||||||||||||||||||
| Race/Ethnicity, Customized | Count of Participants | Participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Plasma Concentration of Brivaracetam (BRV) Following First Dose on Day 1 | Pharmacokinetic blood samples were taken 0.5 to 1 hour, 2 to 4 hours, and 8 to 12 hours after the BRV infusion on Day 1 to determine the BRV plasma concentration. | The Pharmacokinetic Per-Protocol Set (PK-PPS) consisted of all study participants who provided at least 1 measurable post-Baseline plasma sample (with recorded sampling time) on at least 1 post-Baseline Visit with documented study drug intake times. Each participant was assessed once within the specified time-range and the average of the participants included in the given time-range is presented here. Here, 'n' (Number analyzed) signifies participants who were evaluable at specified time points. | Posted | Geometric Mean | Geometric Coefficient of Variation | nanograms per milliliter (ng/mL) | Pharmacokinetic blood samples were taken 0.5 to 1 hour, 2 to 4 hours, and 8 to 12 hours after the BRV infusion on Day 1 |
|
|
| |||||||||||||||||||||||||||
| Secondary | Percentage of Responders to BRV Treatment From Baseline to 3 Hours After the Initial BRV Treatment | A BRV responder was defined as a participant who achieved the following reduction in seizure burden (electroencephalographic neonatal seizures (ENS) in minutes per hour) without need for rescue medication, compared to the seizure burden measured during the Baseline Period immediately prior to BRV administration, evaluated for a 2-hour period starting 1 hour after the start of initial BRV treatment: At least 80% reduction in nonsevere seizure burden (Nonsevere seizure burden is defined as <=50% seizure activity on video-electroencephalography (VEEG) in all 30-minute timespans), OR At least 50 % reduction in severe seizure burden (Severe seizure burden is defined as >50 % seizure activity on VEEG in any 30-minute timespan). Timespans of 30 minutes refer to the following intervals within the 2-hour period: 0 to <= 30 minutes, > 30 to <= 60 minutes, >60 to <= 90 minutes, and >90 to <= 120 minutes. | Efficacy was not evaluated since the study was stopped after the completion of required enrollment of the Exploratory Cohort due to the lack of enrollment of eligible study participants in the Confirmatory Cohorts. Efficacy analyses was planned to be performed on Confirmatory Cohorts only. | Posted | From Baseline to 3 hours after the initial BRV treatment |
| ||||||||||||||||||||||||||||||||
| Secondary | Percentage of Participants With at Least 80% Reduction in Nonsevere Seizure Burden From Baseline to 3 Hours After the Initial BRV Treatment | Nonsevere seizure burden was defined as <=50% seizure activity on VEEG in all 30-minute timespans. Seizure burden was measured during the Baseline Period immediately prior to BRV administration and evaluated for a 2-hour period starting 1 hour after the start of initial BRV. Timespans of 30 minutes refer to the following intervals within the 2-hour period: 0 to <= 30 minutes, > 30 to <= 60 minutes, >60 to <= 90 minutes, and >90 to <= 120 minutes. | Efficacy was not evaluated since the study was stopped after the completion of required enrollment of the Exploratory Cohort due to the lack of enrollment of eligible study participants in the Confirmatory Cohorts. Efficacy analyses was planned to be performed on Confirmatory Cohorts only. | Posted | From Baseline to 3 hours after the initial BRV treatment |
|
| |||||||||||||||||||||||||||||||
| Secondary | Percentage of Participants With at Least 50% Reduction in Severe Seizure Burden From Baseline to 3 Hours After the Initial BRV Treatment | Severe seizure burden was defined as >50% seizure activity on VEEG in any 30-minute timespan. Seizure burden was measured during the Baseline Period immediately prior to BRV administration and evaluated for a 2-hour period starting 1 hour after the start of initial BRV. Timespans of 30 minutes refer to the following intervals within the 2-hour period: 0 to <= 30 minutes, > 30 to <= 60 minutes, >60 to <= 90 minutes, and >90 to <= 120 minutes. | Efficacy was not evaluated since the study was stopped after the completion of required enrollment of the Exploratory Cohort due to the lack of enrollment of eligible study participants in the Confirmatory Cohorts. Efficacy analyses was planned to be performed on Confirmatory Cohorts only. | Posted | From Baseline to 3 hours after the initial BRV treatment |
|
| |||||||||||||||||||||||||||||||
| Secondary | Absolute Change in Average Seizure Burden Measured by Continuous Video-electroencephalography (VEEG) From Baseline to the End of the 96-hour Evaluation Period | Seizure burden was measured by continuous video-electroencephalography (VEEG). Baseline seizure burden is defined as seizure burden measured on the continuous VEEG (total electroencephalographic neonatal seizures (ENS) in minutes per hour) during a period of up to 1 hour immediately prior to the first administration of study drug. | Efficacy was not evaluated since the study was stopped after the completion of required enrollment of the Exploratory Cohort due to the lack of enrollment of eligible study participants in the Confirmatory Cohorts. Efficacy analyses was planned to be performed on Confirmatory Cohorts only. | Posted | From Baseline to the end of the 96-hour Evaluation Period |
|
| |||||||||||||||||||||||||||||||
| Secondary | Percentage Change in Average Seizure Burden Measured by Continuous VEEG From Baseline to the End of the 96-hour Evaluation Period | Seizure burden was measured by continuous video-electroencephalography (VEEG). Baseline seizure burden was defined as seizure burden measured on the continuous VEEG (total electroencephalographic neonatal seizures (ENS) in minutes per hour) during a period of up to 1 hour immediately prior to the first administration of study drug. | Efficacy was not evaluated since the study was stopped after the completion of required enrollment of the Exploratory Cohort due to the lack of enrollment of eligible study participants in the Confirmatory Cohorts. Efficacy analyses was planned to be performed on Confirmatory Cohorts only. | Posted | From Baseline to the end of the 96-hour Evaluation Period |
|
| |||||||||||||||||||||||||||||||
| Secondary | Percentage of BRV Responders at the End of the 96-hour Evaluation Period | A BRV responder was defined as a participant who achieves the following reduction in seizure burden (electroencephalographic neonatal seizures (ENS) in minutes per hour) without need for rescue medication, compared to the seizure burden measured during the Baseline Period immediately prior to BRV administration, evaluated for a 2-hour period starting 1 hour after the start of initial BRV treatment: At least 80% reduction in nonsevere seizure burden (Nonsevere seizure burden is defined as <=50% seizure activity on VEEG in all 30-minute timespans), OR At least 50% reduction in severe seizure burden (Severe seizure burden is defined as >50% seizure activity on VEEG in any 30-minute timespan). | Efficacy was not evaluated since the study was stopped after the completion of required enrollment of the Exploratory Cohort due to the lack of enrollment of eligible study participants in the Confirmatory Cohorts. Efficacy analyses was planned to be performed on Confirmatory Cohorts only. | Posted | From Baseline to the end of the 96-hour Evaluation Period |
|
| |||||||||||||||||||||||||||||||
| Secondary | Percentage of Participants Who Are Seizure-free at 24 Hours Following the Start of Initial BRV Treatment, Categorized by Subjects With Nonsevere or Severe Seizure Burden at Baseline | Seizure freedom is defined as 100 % reduction in seizure burden from Baseline. | Efficacy was not evaluated since the study was stopped after the completion of required enrollment of the Exploratory Cohort due to the lack of enrollment of eligible study participants in the Confirmatory Cohorts. Efficacy analyses was planned to be performed on Confirmatory Cohorts only. | Posted | From Baseline to 24 hours after the initial BRV treatment |
|
| |||||||||||||||||||||||||||||||
| Secondary | Time to Reduction in Seizure Burden for BRV Responders | A BRV responder was defined as a participant who achieves the following reduction in seizure burden (electroencephalographic neonatal seizures (ENS) in minutes per hour) without need for rescue medication, compared to the seizure burden measured during the Baseline Period immediately prior to BRV administration, evaluated for a 2-hour period starting 1 hour after the start of initial BRV treatment: At least 80% reduction in nonsevere seizure burden (Nonsevere seizure burden is defined as <=50% seizure activity on VEEG in all 30-minute timespans), OR At least 50% reduction in severe seizure burden (Severe seizure burden is defined as >50% seizure activity on VEEG in any 30-minute timespan). | Efficacy was not evaluated since the study was stopped after the completion of required enrollment of the Exploratory Cohort due to the lack of enrollment of eligible study participants in the Confirmatory Cohorts. Efficacy analyses was planned to be performed on Confirmatory Cohorts only. | Posted | From Baseline to the first timepoint when BRV responder criteria are met (up to 96-hour Evaluation Period) |
|
| |||||||||||||||||||||||||||||||
| Secondary | Percentage of Participants With Seizure Freedom at the End of the Down-Titration Period | Seizure freedom was defined as 100% reduction in seizure burden from Baseline. | Efficacy was not evaluated since the study was stopped after the completion of required enrollment of the Exploratory Cohort due to the lack of enrollment of eligible study participants in the Confirmatory Cohorts. Efficacy analyses was planned to be performed on Confirmatory Cohorts only. | Posted | From Baseline to the end of the Down-Titration Period (up to 97 days) |
|
| |||||||||||||||||||||||||||||||
| Secondary | Percentage of Participants With at Least 50% Reduction in Electroencephalographic Neonatal Seizures (ENS) Frequency Per Hour From Baseline to the End of the 96-hour Evaluation Period | For this study, an ENS was defined as an EEG seizure lasting for at least 10 seconds on VEEG. Baseline seizure burden was defined as seizure burden measured on the continuous VEEG (total ENS in minutes per hour) during a period of up to 1 hour immediately prior to the first administration of study drug. | Efficacy was not evaluated since the study was stopped after the completion of required enrollment of the Exploratory Cohort due to the lack of enrollment of eligible study participants in the Confirmatory Cohorts. Efficacy analyses was planned to be performed on Confirmatory Cohorts only. | Posted | From Baseline to the end of the 96-hour Evaluation Period |
|
| |||||||||||||||||||||||||||||||
| Secondary | Percentage of Participants Who Are Seizure-free by Time Interval Over the 96-hour Evaluation Period Following the Start of the Initial BRV Treatment | Seizure freedom was defined as 100% reduction in seizure burden from Baseline. | Efficacy was not evaluated since the study was stopped after the completion of required enrollment of the Exploratory Cohort due to the lack of enrollment of eligible study participants in the Confirmatory Cohorts. Efficacy analyses was planned to be performed on Confirmatory Cohorts only. | Posted | From 3 hours following the start of the initial BRV treatment to the end of the 96-hour Evaluation Period |
|
| |||||||||||||||||||||||||||||||
| Secondary | Absolute Difference in Clinical Seizures at the End of the 24-hour Evaluation Period From Baseline for Neonates With Motor Seizures at the Time of Inclusion | Seizures was measured by continuous video-electroencephalography (VEEG). | Efficacy was not evaluated since the study was stopped after the completion of required enrollment of the Exploratory Cohort due to the lack of enrollment of eligible study participants in the Confirmatory Cohorts. Efficacy analyses was planned to be performed on Confirmatory Cohorts only. | Posted | From Baseline to the end of the 24-hour Evaluation Period |
|
| |||||||||||||||||||||||||||||||
| Secondary | Percent Difference in Clinical Seizures at the End of the 24-hour Evaluation Period From Baseline for Neonates With Motor Seizures at the Time of Inclusion | Seizures was measured by continuous video-electroencephalography (VEEG). | Efficacy was not evaluated since the study was stopped after the completion of required enrollment of the Exploratory Cohort due to the lack of enrollment of eligible study participants in the Confirmatory Cohorts. Efficacy analyses was planned to be performed on Confirmatory Cohorts only. | Posted | From Baseline to the end of the 24-hour Evaluation Period |
|
| |||||||||||||||||||||||||||||||
| Secondary | Percentage of Participants With Adverse Events (AEs) as Reported by the Investigator | An adverse event (AE) was any untoward medical occurrence in a patient or clinical investigation study participant administered a pharmaceutical product that did not necessarily have a causal relationship with this treatment. | The All Study Participants Screened Set consisted of all study participants who had signed the ICF and underwent the study inclusion and exclusion criteria of the current protocol. | Posted | Number | percentage of participants | Adverse Events were collected from Screening Period until the Safety Follow-Up Visit (up to Day 75) |
|
Adverse Events were collected from Screening Period until the Safety Follow-Up Visit (up to Day 75)
An AE was any untoward medical occurrence in a patient or clinical investigation study participant administered pharmaceutical product that did not necessarily have a causal relationship with this treatment. Safety analysis was done on All Study Participants Screened Set. Only 6 of 9 participants were treated with BRV. No eligible study participants were enrolled in Confirmatory Cohorts. The study stopped prematurely due to enrolment challenges, termination was not linked to any safety issues.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Exploratory Cohort | Participants in this arm received brivaracetam (BRV) 0.5 milligram per kilogram (mg/kg) administered as an intravenous (iv) solution for injection twice daily (bid) during the 48-hour Evaluation Period. An additional 3 doses of BRV (0.5 mg/kg) could have been administered every 12 hours for 48 hours (at the discretion of the Investigator). Treatment with antiepileptic drugs (AEDs) per standard of care (SToC) (first-line, second-line, or subsequent treatment) were continued in parallel with BRV treatment. | 0 | 9 | 1 | 9 | 5 | 9 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Apnoea | Respiratory, thoracic and mediastinal disorders | MedDRA Version 18.1 | Non-systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA Version 18.1 | Non-systematic Assessment |
| |
| Dry eye | Eye disorders | MedDRA Version 18.1 | Non-systematic Assessment |
| |
| Ammonia increased | Investigations | MedDRA Version 18.1 | Non-systematic Assessment |
| |
| Liver function test abnormal | Investigations | MedDRA Version 18.1 | Non-systematic Assessment |
| |
| Oxygen saturation decreased | Investigations | MedDRA Version 18.1 | Non-systematic Assessment |
| |
| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA Version 18.1 | Non-systematic Assessment |
| |
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA Version 18.1 | Non-systematic Assessment |
|
No eligible study participants were enrolled in the Confirmatory Cohorts. The study stopped prematurely due to enrolment challenges, the termination was not linked to any safety issues.
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| UCB | Cares | 001 844 599 2273 | UCBCares@ucb.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | May 13, 2021 | Jun 22, 2022 | SAP_001.pdf |
| ID | Term |
|---|---|
| D004827 | Epilepsy |
| ID | Term |
|---|---|
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| C482793 | brivaracetam |
Not provided
Not provided
Not provided
|
| 8-12 hours |
|
|
| Units | Counts |
|---|---|
| Participants |
|
| Participants |
|
| Participants |
|
|
|