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

NCT04836559 | Completed Phase 2 Results FDA Drug

• 3 other identifiers: CR10894340411813EPY20012020-003698-24
• Study Type: interventional
• Target: 110
• Locations: 8 countries
• Sites: 69

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).

Conditions

Focal Onset Seizures

Outcome Measures

Primary Outcomes (1)

• Cohort 1 and 2: Time to Baseline Monthly Seizure Count up to the End of the 12-week Double-blind (DB) Treatment Period

  Time (in days) to baseline monthly seizure count was defined as the number of days until the participants cumulative seizure count during the DB period was equal to their baseline monthly seizure count. The baseline monthly seizure count was defined as the number of observable focal onset seizures occurred during the 8-week baseline period (Day -56 to -1), multiplied by 28/XBL, where XBL was the number of days comprising the participants baseline period. Observable focal onset seizures included focal aware seizures with motor signs, focal impaired awareness seizures and focal to bilateral tonic-clonic seizures. Focal aware seizures without motor signs, myoclonic, or other generalized seizures was not counted towards baseline monthly seizure count. Cluster seizures were counted as a single seizure. Kaplan-Meier method was used for the analysis.

  From DB period Day 1 up to Day 85

Secondary Outcomes (21)

• Cohort 1 and 2: Percent Reduction in the Open Label Extension (OLE) Period Monthly Seizure Rate

  From OLE baseline (Day 1 of OLE) up to 24 months after start of OLE (the actual OLE starting time varied for each participant)

• Cohort 1 and 2: Number of Participants With Seizure Freedom at the End of OLE Period

  From OLE baseline (Day 1 of OLE) up to 24 months after start of OLE (the actual OLE starting time varied for each participant)

• Cohort 1 and 2: Number of Participants With at Least 50 Percent (%) Reduction (Response) in the OLE Monthly Seizure Count

  From OLE baseline (Day 1 of OLE) up to 24 months after start of OLE (the actual OLE starting time varied for each participant)

• OLE Period: Cohort 1 and 2: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)

  From OLE baseline (Day 1 of OLE) up to 5 days after last dose of OLE period (5 days + 24 months after start of OLE) (the actual OLE starting time varied for each participant)

• OLE Period: Cohort 1 and 2: Number of Participants With Treatment-emergent (TE) Clinically Important Changes in Vital Signs

  From OLE baseline (Day 1 of OLE) up to 24 months + 5 days after start of OLE (the actual OLE starting time varied for each participant)

Study Arms (2)

JNJ-40411813

EXPERIMENTAL

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.

Drug: JNJ-40411813

Placebo

PLACEBO COMPARATOR

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.

Drug: JNJ-40411813; Drug: Placebo

Interventions

JNJ-40411813 DRUG

JNJ-40411813 will be administered orally.

JNJ-40411813; Placebo

Placebo DRUG

Placebo will be administered orally.

Placebo

Eligibility Criteria

• Age: 18 Years - 69 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Janssen Research & Development, LLC: lead

Study Sites (69)

Tucson Neuroscience Research

Tucson, Arizona, 85710, United States

Location

Research Institution of Orlando, LLC

Orlando, Florida, 32806, United States

Location

Accel Research Sites

Port Orange, Florida, 32127, United States

Location

Maine Medical Center

Scarborough, Maine, 04074, United States

Location

Mid-Atlantic Epilepsy and Sleep Center

Bethesda, Maryland, 20817, United States

Location

Thomas Jefferson University Hospital

Philadelphia, Pennsylvania, 19107, United States

Location

University of Virginia

Charlottesville, Virginia, 22903, United States

Location

AZ Sint-Jan

Bruges, 8000, Belgium

Location

Cliniques Universitaires Saint Luc

Brussels, 1200, Belgium

Location

UZ Antwerpen

Edegem, 2650, Belgium

Location

Az Groeninge

Kortrijk, 8500, Belgium

Location

UZ Leuven

Leuven, B-3000, Belgium

Location

CHU UCL Namur - Site Godinne

Yvoir, 5530, Belgium

Location

Vivantes Humboldt Klinikum

Berlin, 13509, Germany

Location

Krankenhaus Mara - Bethel

Bielefeld, 33617, Germany

Location

Universitatsklinikum Bonn

Bonn, 53127, Germany

Location

Universitaetsklinik Erlangen

Erlangen, 91054, Germany

Location

Universitaetsklinikum Frankfurt

Frankfurt, 60590, Germany

Location

Diakonie Kork - Epilepsiezentrum

Kehl-Kork, 77694, Germany

Location

Universitaetsklinikum Giessen und Marburg GmbH

Marburg, 35043, Germany

Location

Centrum Medyczne Neuromed Sp z o. o.

Bydgoszcz, 85-163, Poland

Location

Copernicus Podmiot Leczniczy Sp. z o.o

Gdansk, 80-803, Poland

Location

MA LEK AM Maciejowscy Spolka Cywilna Centrum Terapii SM

Katowice, 40 571, Poland

Location

NEURO MEDIC Janusz Zbrojkiewicz Poradnia Wielospecjalistyczna

Katowice, 40 686, Poland

Location

NZOZ Wielospecjalistyczna Poradnia Lekarska 'Synapsis'

Katowice, 40-123, Poland

Location

Specjalistyczne Gabinety Lekarskie

Krakow, 31 156, Poland

Location

Centrum Leczenia Padaczki i Migreny NZOZ

Krakow, 31 209, Poland

Location

Centrum Opieki Zdrowotnej Orkan Med Stec Michalska sj

Ksawerów, 95 054, Poland

Location

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

Lublin, 20-078, Poland

Location

Twoja Przychodnia - Centrum Medyczne Nowa Sol

Nowa Sól, 67-100, Poland

Location

Clinical Research Center sp z o o MEDIC R s k

Poznan, 61 731, Poland

Location

NZOZ NEURO KARD Ilkowski i Partnerzy Sp Partnerska Lekarzy

Poznan, 61 853, Poland

Location

MTZ Clinical Research Powered by Pratia

Warsaw, 02-172, Poland

Location

Neurosphera

Warsaw, 02-952, Poland

Location

Institute of Psychiatry and Neurology

Warsaw, 02-957, Poland

Location

Centrum Medyczne Oporow

Wroclaw, 52 416, Poland

Location

ProNeuro Centrum Medyczne

Żory, 44-240, Poland

Location

Republic Clinical Hospital

Kazan', 420064, Russia

Location

Research Medical Center Your Health

Kazan', 420097, Russia

Location

Specialized clinical psychiatric hospital #1

Krasnodar, 350007, Russia

Location

Clinical City Hospital #1

Moscow, 119049, Russia

Location

Nizny Novgorod clinical psychiatric hospital 1

Nizny Novgorod, 603155, Russia

Location

Psychoneurological Dispensary of Frunzensky District

Saint Petersburg, 190013, Russia

Location

St-Petersburg Bekhterev Psychoneurological Research Institute

Saint Petersburg, 192109, Russia

Location

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

Saratov, 410028, Russia

Location

Smolensk Regional Clinical Hospital

Smolensk, 214018, Russia

Location

Yaroslavl State Medical University

Yaroslavl, 150000, Russia

Location

Chungnam National University Hospital

Daejeon, 35015, South Korea

Location

Seoul National University Hospital

Seoul, 03080, South Korea

Location

Severance Hospital Yonsei University Health System

Seoul, 03722, South Korea

Location

Konkuk University Medical Center

Seoul, 05030, South Korea

Location

Asan Medical Center

Seoul, 05505, South Korea

Location

Samsung Medical Center

Seoul, 06351, South Korea

Location

Hosp. Del Mar

Barcelona, 08003, Spain

Location

Hosp Univ Vall D Hebron

Barcelona, 08035, Spain

Location

Hosp Clinic de Barcelona

Barcelona, 08036, Spain

Location

Hosp. de La Santa Creu I Sant Pau

Barcelona, 08041, Spain

Location

Hosp. Univ. de La Princesa

Madrid, 28006, Spain

Location

Hosp Regional Univ de Malaga

Málaga, 29010, Spain

Location

Centro Neurologia Avanzada Sevilla

Seville, 41013, Spain

Location

Hosp. Mutua Terrassa

Terrassa, 08222, Spain

Location

Centro de Inv. Avanzada Neurociencias

Zaragoza, 50001, Spain

Location

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

Dnipro, 49005, Ukraine

Location

Medical Center of Private Enterprise Neuron

Kharkiv, 61091, Ukraine

Location

Cnce of Lviv Regional Council 'Lviv Regional Clinical Hospital'

Lviv, 79010, Ukraine

Location

Mnpe 'Regional Clinical Psychiatric Hospital of Kirovohrad Regional Council'

Nove Settlement, 25491, Ukraine

Location

Mnce 'Ternopil Regional Clinical Psychoneurology Hospital' of Trb

Ternopil, 46027, Ukraine

Location

Llc Diamed Medical Center

Uzhhorod, 88000, Ukraine

Location

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

Vinnytsia, 21037, Ukraine

Location

MeSH Terms

Conditions

Seizures

Interventions

1-butyl-3-chloro-4-(4-phenyl-1-piperidinyl)-(1H)-pyridone

Condition Hierarchy (Ancestors)

Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Executive Medical Director Neuro
• Organization: Janssen Research & Development, LLC

ClinicalTrialDisclosure@its.jnj.com

844-434-4210

Study Officials

• Janssen Research & Development, LLC Clinical Trial

  Janssen Research & Development, LLC

  STUDY DIRECTOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 24, 2021
• First Posted: April 8, 2021
• Study Start: May 18, 2021
• Primary Completion: February 8, 2024
• Study Completion: February 8, 2024
• Last Updated: July 3, 2025
• Results First Posted: July 3, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will share

Locations

DE (7); BE (6); KR (6); UA (7); PL (17); US (7); RU (10); ES (9)