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

NCT03325439 | Terminated Phase 3 Results DMC

• 2 other identifiers: N013492015-002756-27
• Study Type: interventional
• Target: 9
• Locations: 7 countries
• Sites: 12

Brief Summary

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.

Conditions

Electroencephalographic Neonatal Seizures

Keywords

Electroencephalographic neonatal seizures; Brivaracetam; Epilepsy; ENS; Newborns; Pharmacokinetic

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (14)

• Percentage of Responders to BRV Treatment From Baseline to 3 Hours After the Initial BRV Treatment

  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

  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

  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

  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

  From Baseline to the end of the 96-hour Evaluation Period

Study Arms (1)

Brivaracetam (BRV)

EXPERIMENTAL

Exploratory Cohort and Confirmatory Cohorts

Drug: Brivaracetam (BRV) intravenous (iv); Drug: Brivaracetam (BRV) oral

Interventions

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.

Also known as: Briviact

Brivaracetam (BRV)

Brivaracetam (BRV) oral DRUG

Subjects can switch from intravenous (iv) to oral brivaracetam (BRV) at any time during the BRV Extension Period

Also known as: Briviact

Brivaracetam (BRV)

Eligibility Criteria

• Age: 1 Day - 28 Days
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• UCB Biopharma SRL: lead

Study Sites (12)

N01349 204

Leuven, Belgium

Location

N01349 205

Prague, Czechia

Location

N01349 207

Lille, France

Location

N01349 206

Paris, France

Location

N01349 218

Erlangen, Germany

Location

N01349 209

Freiburg im Breisgau, Germany

Location

N01349 211

Cork, Ireland

Location

N01349 212

Messina, Italy

Location

N01349 213

Parma, Italy

Location

N01349 256

Roma, Italy

Location

N01349 251

Cambridge, United Kingdom

Location

N01349 216

London, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 38049197 RESULT

Related Links

• Product Information
• FDA Safety Alerts and Recalls

MeSH Terms

Conditions

Epilepsy

Interventions

brivaracetam

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Limitations and Caveats

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.

Results Point of Contact

• Title: UCB
• Organization: Cares

UCBCares@ucb.com

001 844 599 2273

Study Officials

• UCB Cares

  UCB (+1 844 599 2273)

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 25, 2017
• First Posted: October 30, 2017
• Study Start: May 7, 2019
• Primary Completion: September 3, 2020
• Study Completion: May 29, 2021
• Last Updated: April 8, 2024
• Results First Posted: January 16, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: 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.
• Access Criteria: 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.

Locations

GB (2); FR (2); BE (1); DE (2); IE (1); CZ (1); IT (3)