A study to test the pharmacokinetics, efficacy, and safety of brivaracetam in newborns with repeated electroencephalographic seizures.

• Register: EUCTR
• Last refreshed on: 17 January 2022
• Main ID: EUCTR2015-002756-27-IE
• Date of registration: 22/03/2017
• Prospective Registration: Yes
• Primary sponsor: UCB Biopharma SPRL
• 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 - PETITE
• Target sample size: 42
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2015-002756-27
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no; Randomised: Open: yes; Single blind: no; Double blind: no; Parallel group: no; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: no; Other: no
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Belgium, Czech Republic, France, Germany, Hungary, Ireland, Italy, Netherlands, United Kingdom

Contacts

• Name: Clin Trial Reg & Results Disclosure
• Affiliation: UCB BIOSCIENCES GmbH

• Name: Clin Trial Reg & Results Disclosure
• Affiliation: UCB BIOSCIENCES GmbH

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 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:
- 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 <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
- 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.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Electroencephalographic neonatal seizures

Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

Intervention(s)

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)-2-[(4R)-2-oxo-4-propylpyrrolidin-1-yl] butanamide
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 10-

Trade Name: Briviact
Product Name: Briviact
Product Code: E139204
Pharmaceutical Form: Oral solution
INN or Proposed INN: BRIVARACETAM
Other descriptive name: (2S)-2-[(4R)-2-oxo-4-propylpyrrolidin-1-yl] butanamide
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 10-

Primary Outcome(s)

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

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

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

Primary end point(s): Plasma concentration of Brivaracetam (BRV) following first dose on Day 1

Secondary Outcome(s)

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 Baseline to the end of the 96-hour Evaluation Period
13, 15: At each 3-hour interval from Baseline to the end of the 96-hour Evaluation Period
8: From Baseline to the first timepoint when BRV responder criteria is met
7: From Baseline to 24 hours after the initial BRV treatment
9: From Baseline to the end of the end of the Down-Titration Period (up to 42 days)
11: From 3 hours following the start of the initial BRV treatment to the end of the 96-hour Evaluation Period
12., 13. From Baseline to the end of the 24-hour Evaluation Period
14. Adverse Events were collected from Screening Period until the Safety Follow-Up Period (up to 75 days)

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

Secondary ID(s)

N01349

Source(s) of Monetary Support

UCB Biopharma SPRL