A Study to Test the Pharmacokinetics, Efficacy, and Safety of Brivaracetam in Newborns With Repeated Electroencephalographic Seizures

• Register: ClinicalTrials.gov
• Last refreshed on: 15 April 2024
• Main ID: NCT03325439
• Date of registration: 25/10/2017
• Prospective Registration: Yes
• Primary sponsor: UCB Biopharma SRL
• Public title: A Study to Test the Pharmacokinetics, Efficacy, and Safety of Brivaracetam in Newborns With Repeated Electroencephalographic Seizures
• Scientific title: A Multicenter, Open-Label, Single-Arm Study to Evaluate the Pharmacokinetics, Efficacy, and Safety of Brivaracetam in Neonates With Repeated Electroencephalographic Seizures
• Date of first enrolment: May 7, 2019
• Target sample size: 9
• Recruitment status: Terminated
• URL: https://clinicaltrials.gov/ct2/show/NCT03325439
• Study type: Interventional
• Study design: Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 3

Countries of recruitment

Belgium, Czechia, France, Germany, Ireland, Italy, Netherlands, United Kingdom

Contacts

• Name: UCB Cares
• Affiliation: UCB ([phone])

Key inclusion & exclusion criteria

Inclusion Criteria:

- Confirmation on video-electroencephalography (VEEG) of >= 2 minutes of cumulative
electroencephalographic neonatal seizures (ENS), or >=3 identifiable ENS prior to
entering the Evaluation Period, despite receiving previous antiepileptic drug
treatment for the treatment of electroencephalographic seizures. The occurrence of ENS
during an up to 1-hour period must be confirmed either by the local or central VEEG
reader prior to drug administration. Preferably, the central VEEG reader should
confirm the required ENS

- Subject is male or female and must be at least 34 weeks of corrected gestational age
(CGA). In addition, term neonates up to 27 days of postnatal age (PNA) and preterm
neonates up to 40 weeks of CGA and 27 days of PNA can be enrolled

- Subject weighs at least 2.3 kg at the time of enrollment

- Subjects with or without concomitant hypothermia treatment

Exclusion Criteria:

Subjects are not permitted to be enrolled in the study if any of the following criteria are
met:

- Subject receiving antiepileptic drug (AED) treatment other than phenobarbital,
midazolam, phenytoin, levetiracetam (=60 mg/kg/day), or lidocaine for the treatment of
seizures prior to or at the time of enrollment (Confirmatory Cohorts only)

- Subject with seizures responding to any of the following: previous AED treatment
immediately prior to BRV treatment, pyridoxine treatment, or correction of metabolic
disturbances (hypoglycemia, hypomagnesemia, or hypocalcemia)

- Subject requires extra corporeal membrane oxygenation

- Subject has seizures related to prenatal maternal drug use or drug withdrawal

- Subject has known severe disturbance of hemostasis, as assessed by the Investigator

- Subject has a poor prognosis for survival, as judged by the Investigator

- Subject has 2x upper limit of normal (ULN) of any of the following: aspartate
aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase
(ALP), with the following exception:

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

- Subject has direct (conjugated) bilirubin levels >2 mg/dL

- Subject requiring or expected to require phototherapy or exchange transfusion due to
elevated bilirubin

- Subject with rapidly increasing bilirubin that may preclude the subject from inclusion
in the study at the discretion of the Investigator



Age minimum: 1 Day
Age maximum: 28 Days
Gender: All

Health Condition(s) or Problem(s) studied

Electroencephalographic Neonatal Seizures

Intervention(s)

Drug: Brivaracetam (BRV) oral

Drug: Brivaracetam (BRV) intravenous (iv)

Primary Outcome(s)

Plasma Concentration of Brivaracetam (BRV) Following First Dose on Day 1 [Time Frame: 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 Outcome(s)

Absolute Change in Average Seizure Burden Measured by Continuous Video-electroencephalography (VEEG) From Baseline to the End of the 96-hour Evaluation Period [Time Frame: From Baseline to the end of the 96-hour Evaluation Period]

Percentage of BRV Responders at the End of the 96-hour Evaluation Period [Time Frame: From Baseline to the end of the 96-hour Evaluation Period]

Time to Reduction in Seizure Burden for BRV Responders [Time Frame: From Baseline to the first timepoint when BRV responder criteria are met (up to 96-hour Evaluation Period)]

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 [Time Frame: From Baseline to the end of the 96-hour Evaluation Period]

Percentage of Participants With at Least 50% Reduction in Severe Seizure Burden From Baseline to 3 Hours After the Initial BRV Treatment [Time Frame: From Baseline to 3 hours after the initial BRV treatment]

Percentage Change in Average Seizure Burden Measured by Continuous VEEG From Baseline to the End of the 96-hour Evaluation Period [Time Frame: From Baseline to the end of the 96-hour Evaluation Period]

Percentage of Participants With at Least 80% Reduction in Nonsevere Seizure Burden From Baseline to 3 Hours After the Initial BRV Treatment [Time Frame: From Baseline to 3 hours after the initial BRV treatment]

Percentage of Responders to BRV Treatment From Baseline to 3 Hours After the Initial BRV Treatment [Time Frame: From Baseline to 3 hours after the initial BRV treatment]

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 [Time Frame: From Baseline to 24 hours after the initial BRV treatment]

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 [Time Frame: From Baseline to the end of the 24-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 [Time Frame: From 3 hours following the start of the initial BRV treatment to the end of the 96-hour Evaluation Period]

Percentage of Participants With Adverse Events (AEs) as Reported by the Investigator [Time Frame: Adverse Events were collected from Screening Period until the Safety Follow-Up Visit (up to Day 75)]

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 [Time Frame: From Baseline to the end of the 24-hour Evaluation Period]

Percentage of Participants With Seizure Freedom at the End of the Down-Titration Period [Time Frame: From Baseline to the end of the Down-Titration Period (up to 97 days)]

Secondary ID(s)

2015-002756-27

N01349

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 16/01/2024
• URL: https://clinicaltrials.gov/ct2/show/results/NCT03325439