A study to learn if brivaracetam works and is safe in children and young adults 2 to 25 years of age with childhood absence epilepsy or juvenile absence epilepsy

Overview

Sponsor-declared trial summary

Key facts

Sponsor

UCB Biopharma

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Trial duration

10 Mar 2022 → 4 Mar 2026

Decision date (initial)

2024-06-18

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

External identifiers

EU CT number

2023-510428-55-00

EudraCT number

2020-002750-24

WHO UTN

U1111-1303-2521

ClinicalTrials.gov

NCT04666610

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Others, Pharmacokinetic, Safety, Dose response

Investigate the efficacy of brivaracetam monotherapy in study participants 2 to 25 years of age inclusive, with childhood absence epilepsy (CAE) or juvenile absence epilepsy (JAE)

Secondary objectives 1

1. Evaluate the safety and tolerability of brivaracetam monotherapy in study participants 2 to 25 years of age inclusive, with CAE or JAE

Conditions and MedDRA coding

Childhood Absence Epilepsy Juvenile Absence Epilepsy

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

EMA paediatric investigation plan (PIP)

EMEA-000332-PIP02-17

Plan to share IPD

Yes

IPD plan description

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.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

1. -Study participant is 2 to 25 years of age inclusive, at the time of signing the informed consent. No study participants from 2 to <4 years of age will be included in Stage 1. -Study participant is diagnosed with either childhood absence epilepsy (CAE) or juvenile absence epilepsy (JAE) as defined by the International League Against Epilepsy (ILAE) criteria -Study participants 2 to <4 years of age and participants who had onset of absence seizures at an age younger than 4 years must have a negative glucose transporter type 1 deficiency syndrome (GLUT1DS) genetic test -Study participant is untreated with antiepileptic drugs (AEDs) or pretreated for absence seizures with a maximum of 2 historical AEDs, but without AED treatment for a period of at least 5 half-lives of the AED before randomization into this study. The UCB study physician should be consulted if in doubt -Study participant has electroencephalogram (EEG) evidence of bilateral synchronous, symmetric generalized paroxysmal spike waves (2.5-6 hertz) with normal background activity and with at least 1 electrographically recorded seizure lasting 3 seconds or more on a 1-hour EEG with hyperventilation (HV) while awake at Visit 1 (V1), or on a historical EEG up to 12 weeks before enrollment -Study participant has a history of clinically evident absence seizures occurring on at least 3 days per week in the 2 weeks prior to enrollment -Study participant is without treatment with psychoactive drugs or on a stable dose for at least 2 weeks prior to randomization -Study participant has normal neurological examination, head size, development and cognition -Body weight is ≥9 kg -Male and female a) A sexually active male study participant must agree to use contraception during the treatment period and for at least 2 days, corresponding to the time needed to eliminate study treatment, after the last dose of study treatment and refrain from donating sperm during this period b) A female study participant is eligible to participate if she is not pregnant, not breastfeeding, and at least 1 of the following conditions applies: The study participant is premenarchial OR A woman of childbearing potential (WOCBP) who agrees to follow the contraceptive guidance during the treatment period and for at least 2 days after the last dose of study treatment, corresponding to the time needed to eliminate study treatment -Study participant provides consent/assent, and the study participant’s parent/legal representative/caregiver provides signed informed consent for minor study participants, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.

Exclusion criteria 1

1. -Study participant has a history of nonfebrile seizures other than absence seizures (eg, generalized tonic-clonic seizures or myoclonic seizures) -Study participant has a history of absence status epilepticus -Study participant has a history or presence of paroxysmal nonepileptic seizures -Study participant has a clinically relevant electrocardiogram (ECG) abnormality in the opinion of the Principal Investigator -Study participant has hepatic impairment (Child Pugh Score A, B, or C) based on the Investigator’s assessment -Study participant has a history of major psychiatric disease or any clinically significant medical condition that would preclude appropriate study participation -Study participant has active suicidal ideation prior to study entry as indicated by a positive response (“Yes”) to either Question 4 or Question 5 of the Columbia-Suicide Severity Rating Scale (C-SSRS; for study participants 6 years or older) or clinical judgement (for study participants younger than 6 years). The study participant should be referred immediately to a Mental Healthcare Professional -Study participant has a lifetime history of suicide attempt (including an active attempt, interrupted attempt, or aborted attempt). The study participant should be immediately evaluated by a Mental Healthcare Professional to address safety concerns -Study participant with known fructose intolerance or hypersensitivity of any of the ingredients in brivaracetam oral solution -Study participant has end-stage kidney disease requiring dialysis -Concomitant use of rifampicin/rifampin; prior use must have been stopped at least 2 months before randomization -Concomitant use of strong CYP2C19 inhibitors like fluconazole, fluoxetine and fluvoxamine, prior use must have been stopped at least 1 week before randomization -Study participant has participated in another study of an investigational medicinal product (IMP; and/or an investigational device) within the previous 30 days prior to informed consent -Study participant has clinical or EEG findings not consistent with a diagnosis of childhood absence epilepsy (CAE) or juvenile absence epilepsy (JAE)

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Percentage of participants who met the criteria for absence seizure freedom within 4 days prior to or during the 24-hour ambulatory electroencephalogram (EEG) at Day 14

Secondary endpoints 9

1. 1. Percentage of participants who met the criteria for absence seizure freedom during the randomized withdrawal (RDW) period as determined by electroencephalogram (EEG)
2. 2. Percent change from Baseline to Day 14 in number of absence seizures on 24-hour ambulatory electroencephalogram (EEG)
3. 3. Percentage of participants who met the criteria for absence seizure freedom based on diary during the 4 days prior to the visit at Day 14
4. 4. Percentage of participants who met the criteria for absence seizure freedom on 24-hour ambulatory electroencephalogram (EEG) at Week 12
5. 5. Percentage of participants who met the criteria for absence seizure freedom based on diary during the 4 days prior to the visit at Week 12
6. 6. Percentage of participants with treatment-emergent adverse events (TEAEs) during the study
7. 7. Percentage of participants with treatment-emergent adverse events (TEAEs) leading to discontinuation of study treatment
8. 8. Percentage of participants with serious adverse events (SAEs) during the study
9. 9. Percentage of participants with drug-related treatment-emergent adverse events (TEAEs) during the study

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 3

Placebo 1

Auxiliary 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

UCB Biopharma

Sponsor organisation

UCB Biopharma

Address

Researchdreef 60

City

Anderlecht

Postcode

1070

Country

Belgium

Scientific contact point

Organisation

UCB Biopharma

Contact name

UCB Cares

Public contact point

Organisation

UCB Biopharma

Contact name

UCB Cares

Third parties 10

Locations

4 EU/EEA countries · 14 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 88 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

5 submissions — initial application plus substantial / non-substantial modifications