Clinical trial NCT04015141: A Study to Evaluate Efficacy and Safety of Perampanel Administered as an Adjunctive Therapy in Pediatric Participants With Childhood Epilepsy
Official title: An Open-Label Study With Extension Phase to Evaluate the Efficacy and Safety of Perampanel Administered as an Adjunctive Therapy in Pediatric Subjects (Age 1 Month to Less Than 18 Years) With Childhood Epilepsy
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Pediatric Epileptic Syndrome
Partial-onset Seizures
Keywords: Partial-onset seizures
Pediatric epileptic syndrome
Epilepsy
Childhood epilepsy
Epilepsy in children
Refractory seizures
Inadequately controlled seizures
E2007
Fycompa
Perampanel
Lead sponsor: Eisai Inc.
Sponsor class: INDUSTRY
First posted: 2019-07-10
Enrollment: 100
Sex: ALL
Minimum age (years): 1
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of the study is to evaluate the efficacy of perampanel as measured by the 50 percent (%) responder rate during the maintenance period of the core study for seizure frequency in participants with pediatric epileptic syndrome (Cohort 1) and partial-onset seizures (POS) (Cohort 2).

Detailed description: This study will consist of a Core Study, Extension Phase A and Extension Phase B.

1. Core Study will consist of the following 2 phases: Pretreatment (4 weeks screening or baseline period) and Treatment Period. The Treatment Period (23 weeks) of Core study include Titration period (10 weeks) and Maintenance period (13 weeks).
2. Extension Phase A will consist of a Treatment Period (33 weeks) and a Follow-up Period (4 weeks). All participants who will complete the Core Study will be eligible to participate in Extension Phase A of the study.
3. Extension Phase B will only be for participants who reside in countries where perampanel (oral tablets or oral suspension) is not commercially available or an extended access program (EAP) is not yet implemented, participants have completed Extension Phase A, and who, in the opinion of the investigator, will continue to benefit from treatment with perampanel.

Eligibility criteria: Inclusion Criteria:

* Male or female participants. Cohort 1: age 1 month to less than 18 years; Cohort 2: age 1 month to less than 2 years at the time of informed consent/assent. Participants below the age of 1 year must have been at least 36 weeks of gestational age at birth.
* Have a diagnosis of epilepsy with a pediatric epileptic syndrome (Cohort 1) or epilepsy with POS with or without secondary generalization (Cohort 2).
* Have had equal or greater than 4 seizures over the 4-week interval prior to enrollment visit.
* Absence of any progressive cause of epilepsy that has been confirmed clinically or based on brain imaging (example, magnetic resonance imaging \[MRI\] scan or computed tomography \[CT\] or ultrasound \[for less than 1 year old\]).
* Currently maintained on stable doses of 1 to a maximum of 4 approved antiepileptic drugs (AEDs). A prescription medical marijuana (including products containing cannabidiol) is counted as 1 of the maximum of 4 allowed AEDs; however, it cannot be the only concomitant AED if this product is not an approved AED in the country where the study site is located. Doses must be stable for at least 4 weeks (at least 2 weeks for participant less than \[\<\] 6 months old) before Visit 1/Baseline or screening; only 1 enzyme-inducing antiepileptic drug (EIAED) (defined as carbamazepine, phenytoin, oxcarbazepine, or eslicarbazepine) out of the maximum of 4 AEDs is allowed.

Exclusion Criteria:

* Current or history of pseudo-seizures (psychogenic nonepileptic seizures) within approximately 5 years before screening visit.
* Have a history of status epilepticus that required hospitalization within 6 months before screening visit.
* Have an unstable psychiatric diagnosis that may confound participant's ability to participate in the study or that may prevent completion of the protocol specified tests (example, significant suicide risk, including suicidal behavior and ideation within 6 months before screening visit 1, current psychotic disorder, acute mania).
* Any suicidal ideation with intent with or without a plan within 6 months before enrollment visit (answering "Yes" to questions 4 or 5 on the Suicidal Ideation section of the C-SSRS) in participants aged 6 and above or based on the opinion of the Investigator for participants less than 6 years.
* Are scheduled or confirmed or both to have epilepsy surgery within 6 months after screening visit; however, those who have previously documented "failed" epilepsy surgery will be allowed.
* Have a progressive central nervous system (CNS) disease, including degenerative CNS diseases and progressive tumors.
* Benzodiazepines for any indications other than epilepsy (example, anxiety/sleep disorders) prohibited from 1 month before Visit 1/Baseline or screening and during the study. Benzodiazepines for seizure control and as rescue medication are allowed.
* A vagal nerve stimulator (VNS), responsive neurostimulator (RNS), or deep brain stimulator (DBS) implanted less than 5 months before screening visit or changes in parameter less than 4 weeks before screening visit (or thereafter during the study).
* Use of perampanel within 30 days before screening visit, or perampanel was discontinued due to adverse reactions (perampanel-related) or lack of efficacy in case of previous exposure.
* Weight less than 4.0 kilogram (kg) at Visit 1 (Baseline or screening).

Primary outcomes:
measure: Proportion of 50% Responders For All Seizures During the Maintenance Period of Core Study
timeFrame: Week 10 to Week 23
Secondary outcomes:
measure: Proportion of 50% Responders During Treatment Period of Core Study and Extension Phase A
timeFrame: Treatment Period of Core Study and Extension Phase A: Week 0 to Week 56
measure: Proportion of 25% and 75% Responders for all Seizures, During Maintenance Period of Core Study and During Treatment Period of Core Study and Extension Phase A
timeFrame: Maintenance Period of Core study: Week 10 to Week 23; Treatment Period of Core Study and Extension Phase A: Week 0 to Week 56
measure: Proportion of Participants Who Are Seizure-Free During the Maintenance Period of Core Study and During the Treatment Period of Core Study and Extension Phase A
timeFrame: Maintenance Period of Core study: Week 10 to Week 23; Treatment Period of Core Study and Extension Phase A: Week 0 to Week 56
measure: Change From Baseline in Seizure Frequency For All Seizures During the Treatment Period of Core Study and During the Treatment Period of Core Study and Extension Phase A
timeFrame: Baseline, Treatment Period of Core study: Week 23, Treatment Period of Core Study and Extension Phase A: Week 56
measure: Percent Change From Baseline in Seizure Frequency For All Seizures During the Treatment Period of Core Study and During the Treatment Period of Core Study and Extension Phase A
timeFrame: Baseline, Treatment Period of Core study: Week 23, Treatment Period of Core Study and Extension Phase A: Week 56
measure: Clinical Global Impression of Change (CGIC) at the End of the Treatment Period of Core Study and at the End of Extension Phase A
timeFrame: Treatment Period of Core Study: Week 23, Extension Phase A: Week 56
measure: Subject Global Impression of Change (SGIC) at the End of the Treatment Period of Core Study and at the End of Extension Phase A
timeFrame: Treatment Period of Core Study: Week 23, Extension Phase A: Week 56
measure: Change From Baseline in the Cognitive Drug Research (CDR) Parameter at the End of the Treatment Period of Core Study and at the End of Extension Phase A
timeFrame: Baseline, Treatment Period of Core Study: Week 23, Extension Phase A: Week 56
measure: Change from Baseline in CBCL Parameters at the End of the Treatment Period of Core Study and at the End of Extension Phase A
timeFrame: Baseline, Treatment Period of Core Study: Week 23, Extension Phase A: Week 56
measure: Change from Baseline in Lafayette Grooved Pegboard Test (LGPT) Parameters at the End of the Treatment Period of Core Study and at the End of Extension Phase A
timeFrame: Baseline, Treatment Period of Core Study: Week 23, Extension Phase A: Week 56
measure: Change from Baseline in Growth and Development Parameter - Height
timeFrame: Baseline, Treatment Period of Core Study: Week 23; Extension Phase A: Weeks 28, 40, and 56
measure: Change from Baseline in Growth and Development Parameter - Weight
timeFrame: Baseline, Treatment Period of Core Study: Weeks 2, 5, 8, 10, 14, 18 and 23; Extension Phase A: Weeks 28, 40, 56, and 60
measure: Change from Baseline in Growth and Development Parameter - Free Triiodothyronine (fT3) and Free Thyroxine (fT4) Levels in Blood
timeFrame: Baseline, Treatment Period of Core Study: Week 23, Extension Phase A: Week 56
measure: Change from Baseline in Growth and Development Parameter - Thyroid-Stimulating Hormone (TSH) Levels in Blood
timeFrame: Baseline, Treatment Period of Core Study: Week 23, Extension Phase A: Week 56
measure: Change from Baseline in Growth and Development Parameter - Insulin Like Growth Factors (IGF)-1
timeFrame: Baseline, Treatment Period of Core Study: Week 23, Extension Phase A: Week 56
measure: Change from Baseline in Growth and Development Parameter- Sexual Maturation Assessed by Tanner Staging
timeFrame: Baseline, Treatment Period of Core Study: Week 23, Extension Phase A: Week 56
measure: Proportion of Participants with any Treatment-Emergent Reports of Suicidal Ideation and Behavior on the Columbia-Suicide Severity Rating Scale (C-SSRS) and Intensity of These Behaviors Assessed using C-SSRS Scores
timeFrame: Treatment period of Core Study: Weeks 0, 2, 5, 8, 10, 14, 18, and 23; Extension Phase A: Weeks 28, 46, 56 and 60
measure: Change from Baseline in Number of Seizures Recorded on Electroencephalogram (EEG) at the End of the Treatment Period of Core Study and at the End of Extension Phase A
timeFrame: Baseline, End of the Treatment Period of Core Study: Week 23, End of Extension Phase A: Week 56
measure: Number of Participants with at Least One Treatment Emergent Adverse Event (TEAE) and Serious Adverse Event (SAE)
timeFrame: From date of first dose of perampanel up to 28 days after the last dose of perampanel (Week 60)
measure: Number of Participants with Treatment Emergent Markedly Abnormal Laboratory Values
timeFrame: From date of first dose of perampanel up to Week 60
measure: Number of Participants with Clinically Notable Vital Sign Results
timeFrame: From date of first dose of perampanel up to 28 days after the last dose of perampanel (Week 60)
measure: Number of Participants with Clinically Significant Abnormal Electrocardiograms
timeFrame: From date of first dose of perampanel up to Week 60
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Phoenix Childrens Hospital
state: Arizona
city: Tucson
country: United States
facility: Center For Neurosciences
state: Arizona
city: Los Angeles
country: United States
facility: David Geffen School of Medicine at UCLA
state: California
city: Aurora
country: United States
facility: Childrens Hospital Colorado
state: Colorado
city: Wilmington
country: United States
facility: Nemours Foundation Alfred Dupont Children's Hospital
state: Delaware
city: Miami
country: United States
facility: Nicklaus Children's Hospital
state: Florida
city: Orlando
country: United States
facility: Pediatric Neurology PA
state: Florida
city: Tampa
country: United States
facility: Pediatric Epilepsy and Neurology Specialists
state: Florida
city: Atlanta
country: United States
facility: PANDA
state: Georgia
city: Savannah
country: United States
facility: Meridian Clinical Research-(Savannah Georgia)
state: Georgia
city: Detroit
country: United States
facility: Children's Hospital of Michigan
state: Michigan
city: Hackensack
country: United States
facility: Northeast Regional Epilepsy Group
state: New Jersey
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Winston-Salem
country: United States
facility: Wake Forest Baptist Medical Center - PPDS
state: North Carolina
city: Cleveland
country: United States
facility: University Hospitals Cleveland Medical Center
state: Ohio
city: Dayton
country: United States
facility: Dayton Children's Hospital
state: Ohio
city: Portland
country: United States
facility: Doernbecher Children's Hospital
state: Oregon
city: Austin
country: United States
facility: Child Neurology Consultants of Austin
state: Texas
city: San Antonio
country: United States
facility: Road Runner Research Ltd
state: Texas
city: Norfolk
country: United States
facility: Children's Specialty Group
state: Virginia
city: Richmond
country: United States
facility: Children's Hospital of Richmond at VCU - CHoR-PIN
state: Virginia
city: Seattle
country: United States
facility: Seattle Children's Hospital
state: Washington
city: Ottignies
country: Belgium
facility: Centre Neurologique William Lennox
state: Brabant Wallon
city: Brussel
country: Belgium
facility: UZ Brussel
state: Brussels
city: Bruxelles
country: Belgium
facility: Cliniques Universitaires Saint-Luc
state: Brussels
city: Bruxelles
country: Belgium
facility: Hôpital Universitaire des Enfants Reine Fabiola
state: Brussels
city: Gent
country: Belgium
facility: UZ Gent
state: Oost-Vlaanderen
city: Anderlecht
country: Belgium
facility: Hôpital Erasme
city: Brno
country: Czechia
facility: Fakultni nemocnice Brno
city: Ostrava
country: Czechia
facility: Fakultni nemocnice Ostrava
city: Plzen
country: Czechia
facility: Fakultni nemocnice Plzen
city: Aarhus N
country: Denmark
facility: Aarhus Universitetshospital
state: Central Jutland
city: Randers
country: Denmark
facility: Regionshospitalet Randers
city: Marseille
country: France
facility: Hopitaux de La Timone
state: Bouches-du-Rhône
city: Bordeaux
country: France
facility: Hôpital Pellegrin-Enfants
city: Paris
country: France
facility: Hopital Necker
city: Paris
country: France
facility: Hopitaux de Paris CHU Hopital Robert Debre - Inserm U676
city: Rennes
country: France
facility: CHRU Rennes
city: Toulouse Cedex 9
country: France
facility: Centre Hospitalier Universitaire de Toulouse
city: Freiburg
country: Germany
facility: Eisai Trial Site #4
city: Jena
country: Germany
facility: Eisai Trial Site #2
city: Munich
country: Germany
facility: Eisai Trial Site #3
city: Radeberg
country: Germany
facility: Eisai Trial Site #1
city: Barcelona
country: Spain
facility: Centro Medico Teknon - Grupo Quironsalud
city: Madrid
country: Spain
facility: Hospital Clinico San Carlos
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Marañón
city: Pamplona
country: Spain
facility: Complejo Hospitalario de Navarra
city: Santiago de Compostela
country: Spain
facility: CHUS - H. Clinico U. de Santiago
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocio
Study officials:
References: