Electroencephalographic neonatal seizures
Conditions
Interventions
Trade Name: Briviact
Product Name: Briviact
Product Code: ucb 34714
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: BRIVARACETAM
Current Sponsor code: BRV
Other descriptive name: (2S)
Sponsors
UCB Biopharma SPRL
Eligibility
Sex/Gender
All
Inclusion 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 postmenstrual age (PMA) 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 Are the trial subjects under 18? yes Number of subjects for this age range: 42 F.1.2 Adults (18-64 years) no F.1.2.1 Number of subjects for this age range 0 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range 0
Exclusion criteria
Exclusion criteria: - 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 correctionof 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 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 - Subject with a severe cardiac condition, including subject with a diagnosis or signs of long QT syndrome (LQTS), and subject with a family history of LQTS.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: - 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 optimum BRV dose (Exploratory Cohort) for the treatment of subjects enrolled into the Confirmatory Cohorts of this study;Secondary Objective: - To evaluate the efficacy of brivaracetam (BRV) in severe and nonsevere seizure burden (defined as total minutes of electroencephalographic neonatal seizures [ENS] per hour) in neonates with seizures that are not adequately controlled with previous antiepileptic drug (AED) treatment - To evaluate the short-term safety and tolerability of BRV in neonates;Primary end point(s): Plasma concentration of Brivaracetam (BRV) following first dose on Day 1;Timepoint(s) of evaluation of this end point: 30-60 min, 2 to 4 hours, and 8 to 12 hours after the BRV infusion on Day 1 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Percentage of responders to brivaracetam (BRV) treatment from Baseline to 3 hours after the initial BRV dose 2. Percentage of subjects with at least 80% reduction in nonsevere seizure burden from Baseline to 3 hours after the initial BRV treatment 3. Percentage of subjects with at least 50% reduction in severe seizure burden from Baseline to 3 hours after the initial BRV treatment 4. Absolute change in average seizure burden measured by continuous video-electroencephalography (VEEG) from Baseline to the end of the 96-hour Evaluation Period 5. Percentage change in average seizure burden measured by continuous VEEG from Baseline to the end of the 96-hour Evaluation Period 6. Percentage of BRV responders at the end of the 96-hour Evaluation Period 7. Proportion of subjects who are seizure-free at 24 hours following the start of initial BRV treatment, categorised by subjects with nonsevere or severe seizure burden at Baseline 8. Time to reduction in seizure burden for BRV responders 9. Percentage of Subjects with Seizure Freedom at the end of Down-Titration Period 10. Percentage of Subjects with at least 50% reduction in electroencephalographic neonatal seizures (ENS) frequency per hour from Baseline to the end of the 96-hour Evaluation Period 11. Percentage of subjects who are seizure-free by time interval over the 96-hour evaluation period following following the start of the initial BRV treatment 12. 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 13. 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 14. Adverse Events (AEs) as reported by the Investigator ;Timepoint(s) of evaluation of this end point: 1, 2, 3: From Baseline to 3 hours after the initial BRV dose 4, 5, 6, 10, 12, 14, 16, 17, 18, 19, 21, 22: From Ba | — |
Countries
Belgium, Czech Republic, France, Germany, Hungary, Ireland, Italy, Netherlands, United Kingdom
Contacts
Public ContactClin Trial Reg & Results Disclosure
UCB BIOSCIENCES GmbH
Outcome results
None listed