A Study to Investigate JNJ-40411813 in Combination With Levetiracetam or Brivaracetam in Epilepsy

NCT ID: NCT04836559

Last Updated: 2025-07-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 110 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-05-18
• Study Completion Date: 2024-02-08

Brief Summary

The purpose of this study is to evaluate the efficacy of up to 3 dose levels of adjunctive JNJ-40411813 compared to placebo based on the time to baseline monthly seizure count in participants with focal onset seizures who are receiving levetiracetam or brivaracetam and up to 3 other anti-epileptic drugs (AEDs) (double-blind treatment period) and to evaluate the long-term efficacy and safety of adjunctive therapy with JNJ-40411813 in participants with epilepsy (open-label extension [OLE] period).

Detailed Description

JNJ-40411813 is a positive allosteric modulator (PAM) of the metabotropic glutamate receptor-2 (mGlu2), which is abundantly expressed in the forebrain and cerebellum. The mGlu2 receptor functions as a presynaptic auto-receptor that, upon activation, decreases the release of the excitatory neurotransmitter glutamate. Positive allosteric modulation of a receptor will result in the direct enhancement of the agonist-induced signal while PAMs themselves have generally no or low intrinsic activity at the receptor. The net effect of JNJ-40411813 is hypothesized to be a normalization of hyper-glutamatergic transmission. JNJ-40411813 is being evaluated for the treatment of disorders of the central nervous systems (CNS), such as epilepsy, and has been evaluated in schizophrenia and anxious depression. This study will consist of 1 to a maximum of 3 cohorts. In each cohort, for each participant the study consists of a screening period (up to minus [-] 8 weeks), an 8-week prospective pretreatment baseline period, an up to 12-week double-blind treatment period and a 2-year OLE period or a follow-up telephone visit 2 weeks after the last dose of study intervention. Safety assessments including physical and neurological examination, vital signs, 12 lead electrocardiogram (ECG), clinical chemistry, hematology, and urinalysis will be performed. The total maximal duration of the study is up to 2 years and 5 months.

Conditions

Focal Onset Seizures

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

JNJ-40411813

Participants will receive JNJ-40411813 twice a day (bid) up to 12 weeks in double blind period. Up to 3 different doses (low, medium, high) of JNJ-40411813 will be administered in this study. Participants will also receive concomitant anti-epileptic drugs (AEDs) one of which must include levetiracetam or brivaracetam. Immediately after the last study drug intake by the participants in the double-blind period, participants will enter into a 2-year open label extension (OLE) period and continue receiving JNJ-40411813 as well as the AEDs during OLE period.

Group Type: EXPERIMENTAL

JNJ-40411813

Intervention Type: DRUG

JNJ-40411813 will be administered orally.

Placebo

Participants will receive JNJ-40411813 matching placebo (bid) up to 12 weeks. Participants will also receive concomitant AEDs one of which must include levetiracetam or brivaracetam during double blind period. Participants who had been receiving placebo in double blind period will start with the JNJ-40411813 dose in the OLE period.

Group Type: PLACEBO_COMPARATOR

JNJ-40411813

Intervention Type: DRUG

JNJ-40411813 will be administered orally.

Placebo

Intervention Type: DRUG

Placebo will be administered orally.

Interventions

JNJ-40411813

JNJ-40411813 will be administered orally.

Intervention Type: DRUG

Placebo

Placebo will be administered orally.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Body mass index (BMI) between 18 and 35 kilogram per meter square (kg/m^2, inclusive (BMI = weight/height^2). Minimum body weight should be 40-kilogram (kg)
• Established diagnosis of focal epilepsy, for at least 1 year using the International League Against Epilepsy (ILAE) criteria. Participants should not be enrolled if they are known to have had fewer than 3 or more than 100 seizures in any monthly period in the past 6 months. It is preferred that participants have experience in maintaining a seizure e-diary
• Must have had a neuroimaging procedure within 10 years, including a computed tomography (CT) scan or magnetic resonance imaging (MRI), that excluded a progressive neurologic disorder; these procedures may be performed within the 8-week baseline period
• Cohort 1: Current treatment with at least 1 and up to 4 anti-epileptic drugs (AEDs) (including levetiracetam), administered at stable dosage(s) for at least 1 month before screening, and no new AEDs added for the previous 2 months; these AEDs must remain unchanged throughout the pretreatment and double-blind treatment periods (with the exception of dosage reductions of concomitant AEDs because of suspected elevated AED levels or side effects) Cohort 2 and beyond: Current treatment with at least 1 and up to 4 AEDs (including levetiracetam or brivaracetam), administered at the appropriate dosage(s) and for a sufficient treatment period before screening. These AEDs must remain unchanged throughout the pretreatment and double-blind treatment periods (with the exception of dosage reductions of concomitant AEDs because of suspected elevated AED levels or side effects). Important note: screening of participants receiving brivaracetam will start when enrolling for Cohort 2
• Currently showing inadequate response to levetiracetam, administered at the appropriate dosage(s) and for a sufficient treatment period, based on the judgment of the investigator
• Healthy based on clinical laboratory tests, physical examination, medical history, vital signs, and 12-lead ECG
• Men or women between 18 and 69 years old

Exclusion Criteria

• Have a generalized epileptic syndrome
• Diagnosis of Lennox-Gastaut Syndrome
• Currently experiencing seizures that cannot be counted accurately
• History of any current or past nonepileptic seizures, including psychogenic seizures
• Known allergies, hypersensitivity, or intolerance to placebo, JNJ-40411813 or its excipients
• Current treatment with vagus nerve stimulation, deep brain and cortical stimulation for 1 year or less
• Planned epilepsy surgery within the next 6 months or completed epilepsy surgery less than (<) 6 months ago
• Current treatment with vigabatrin
• History of malignancy within 5 years before screening (exceptions are squamous and basal cell carcinomas of the skin and carcinoma in situ of the cervix, or malignancy, which is considered cured with minimal risk of recurrence)
• Current or past (within the past year) major psychotic disorder, such as schizophrenia, bipolar disorder, or other psychotic conditions, recent (within the past 6 months) interictal psychosis, and major depressive disorder (MDD) with psychotic features
• Exacerbation of MDD within the past 6 months; antidepressant use is allowed
• Has a current or recent history of clinically significant suicidal ideation within the past 6 months, corresponding to a score of 4 (active suicidal ideation with some intent to act, without specific plan) or 5 (active suicidal ideation with specific plan and intent) for ideation on the Columbia Suicide Severity Rating Scale (C-SSRS), or a history of suicidal behavior within the past 1 year, as validated by the CSSRS at screening
• Has a history of at least mild drug or alcohol use disorder according to Diagnostic and Statistical Manual of Mental Disorders (5th edition) (DSM-5) criteria within 1 year before Screening

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 69 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Janssen Research & Development, LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Janssen Research & Development, LLC Clinical Trial

Role: STUDY_DIRECTOR

Janssen Research & Development, LLC

Locations

Tucson Neuroscience Research

Tucson, Arizona, United States

Research Institution of Orlando, LLC

Orlando, Florida, United States

Accel Research Sites

Port Orange, Florida, United States

Maine Medical Center

Scarborough, Maine, United States

Mid-Atlantic Epilepsy and Sleep Center

Bethesda, Maryland, United States

Thomas Jefferson University Hospital

Philadelphia, Pennsylvania, United States

University of Virginia

Charlottesville, Virginia, United States

AZ Sint-Jan

Bruges, , Belgium

Cliniques Universitaires Saint Luc

Brussels, , Belgium

UZ Antwerpen

Edegem, , Belgium

Az Groeninge

Kortrijk, , Belgium

UZ Leuven

Leuven, , Belgium

CHU UCL Namur - Site Godinne

Yvoir, , Belgium

Vivantes Humboldt Klinikum

Berlin, , Germany

Krankenhaus Mara - Bethel

Bielefeld, , Germany

Universitatsklinikum Bonn

Bonn, , Germany

Universitaetsklinik Erlangen

Erlangen, , Germany

Universitaetsklinikum Frankfurt

Frankfurt, , Germany

Diakonie Kork - Epilepsiezentrum

Kehl-Kork, , Germany

Universitaetsklinikum Giessen und Marburg GmbH

Marburg, , Germany

Centrum Medyczne Neuromed Sp z o. o.

Bydgoszcz, , Poland

Copernicus Podmiot Leczniczy Sp. z o.o

Gdansk, , Poland

MA LEK AM Maciejowscy Spolka Cywilna Centrum Terapii SM

Katowice, , Poland

NEURO MEDIC Janusz Zbrojkiewicz Poradnia Wielospecjalistyczna

Katowice, , Poland

NZOZ Wielospecjalistyczna Poradnia Lekarska 'Synapsis'

Katowice, , Poland

Specjalistyczne Gabinety Lekarskie

Krakow, , Poland

Centrum Leczenia Padaczki i Migreny NZOZ

Krakow, , Poland

Centrum Opieki Zdrowotnej Orkan Med Stec Michalska sj

Ksawerów, , Poland

Clinical Best Solutions Sp. z o.o., Sp. K.

Lublin, , Poland

Twoja Przychodnia - Centrum Medyczne Nowa Sol

Nowa Sól, , Poland

Clinical Research Center sp z o o MEDIC R s k

Poznan, , Poland

NZOZ NEURO KARD Ilkowski i Partnerzy Sp Partnerska Lekarzy

Poznan, , Poland

MTZ Clinical Research Powered by Pratia

Warsaw, , Poland

Neurosphera

Warsaw, , Poland

Institute of Psychiatry and Neurology

Warsaw, , Poland

Centrum Medyczne Oporow

Wroclaw, , Poland

ProNeuro Centrum Medyczne

Żory, , Poland

Republic Clinical Hospital

Kazan', , Russia

Research Medical Center Your Health

Kazan', , Russia

Specialized clinical psychiatric hospital #1

Krasnodar, , Russia

Clinical City Hospital #1

Moscow, , Russia

Nizny Novgorod clinical psychiatric hospital 1

Nizny Novgorod, , Russia

Psychoneurological Dispensary of Frunzensky District

Saint Petersburg, , Russia

St-Petersburg Bekhterev Psychoneurological Research Institute

Saint Petersburg, , Russia

SHI 'Saratov City Clinical Hospital 2 n.a V.I. Razumovsky

Saratov, , Russia

Smolensk Regional Clinical Hospital

Smolensk, , Russia

Yaroslavl State Medical University

Yaroslavl, , Russia

Chungnam National University Hospital

Daejeon, , South Korea

Seoul National University Hospital

Seoul, , South Korea

Severance Hospital Yonsei University Health System

Seoul, , South Korea

Konkuk University Medical Center

Seoul, , South Korea

Asan Medical Center

Seoul, , South Korea

Samsung Medical Center

Seoul, , South Korea

Hosp. Del Mar

Barcelona, , Spain

Hosp Univ Vall D Hebron

Barcelona, , Spain

Hosp Clinic de Barcelona

Barcelona, , Spain

Hosp. de La Santa Creu I Sant Pau

Barcelona, , Spain

Hosp. Univ. de La Princesa

Madrid, , Spain

Hosp Regional Univ de Malaga

Málaga, , Spain

Centro Neurologia Avanzada Sevilla

Seville, , Spain

Hosp. Mutua Terrassa

Terrassa, , Spain

Centro de Inv. Avanzada Neurociencias

Zaragoza, , Spain

Ce 'Dnipropetrovsk Regional Clinical Hospital N.A. Mechnikov' of Dnipropetrovsk Rc

Dnipro, , Ukraine

Medical Center of Private Enterprise Neuron

Kharkiv, , Ukraine

Cnce of Lviv Regional Council 'Lviv Regional Clinical Hospital'

Lviv, , Ukraine

Mnpe 'Regional Clinical Psychiatric Hospital of Kirovohrad Regional Council'

Nove Settlement, , Ukraine

Mnce 'Ternopil Regional Clinical Psychoneurology Hospital' of Trb

Ternopil, , Ukraine

Llc Diamed Medical Center

Uzhhorod, , Ukraine

Cnpe 'Vinnytsia Regional Clinical Psycho-Neurological Hospital N.A. Ac. O.I. Yushchenko' of Vrc

Vinnytsia, , Ukraine

Countries

United States; Belgium; Germany; Poland; Russia; South Korea; Spain; Ukraine

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

40411813EPY2001

Identifier Type: OTHER

Identifier Source: secondary_id

2020-003698-24

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CR108943

Identifier Type: -

Identifier Source: org_study_id