JNJ-40411813 + Standard Epilepsy Meds for Epilepsy

No longer recruiting at 117 trial locations

Overseen By Study Contact

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Janssen Research & Development, LLC

Must be taking: Levetiracetam, Brivaracetam

Must not be taking: Vigabatrin

Disqualifiers: Generalized epilepsy, Lennox-Gastaut, others

Stay on Your Current Meds You can continue your current medications while participating

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 5

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new drug, JNJ-40411813, to determine if it can reduce seizures in people with focal onset epilepsy who are already taking medications like levetiracetam or brivaracetam. Participants will receive either the new drug or a placebo (a look-alike with no active ingredients) alongside their usual medications. The goal is to find out if the new drug can lower monthly seizure counts. This study targets individuals who have had focal epilepsy for at least a year and continue to experience seizures despite current treatment. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, allowing participants to contribute to important findings.

Will I have to stop taking my current medications?

No, you will not have to stop taking your current epilepsy medications. The trial requires that you continue your existing anti-epileptic drugs (AEDs) at stable dosages throughout the study, except for possible dosage reductions due to side effects.

Is there any evidence suggesting that JNJ-40411813 is likely to be safe for humans?

Research has shown that JNJ-40411813 was tested in animals with epilepsy and demonstrated promising safety results. In earlier studies with people, the treatment was generally well-tolerated. Some mild to moderate side effects were reported, but serious side effects were uncommon.

Although clear information about severe side effects is lacking, ongoing research is carefully monitoring the treatment's safety. As this is a Phase 2 study, researchers are still gathering more detailed safety information to ensure it is safe for a broader population.

It is important to remember that while earlier research is helpful, each person's experience may differ. Participants in this trial will be closely monitored to ensure their safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for epilepsy?

Researchers are excited about JNJ-40411813 because it offers a fresh approach to treating epilepsy. Unlike standard treatments that often focus on controlling seizures through existing anti-epileptic drugs, JNJ-40411813 is being tested for its potential to work with those drugs, like levetiracetam or brivaracetam, to enhance their effectiveness. It features a novel mechanism that could provide better seizure control by targeting different pathways. Additionally, the trial includes an open-label extension where participants can continue using JNJ-40411813, potentially offering long-term benefits beyond the initial study period.

What evidence suggests that JNJ-40411813 could be an effective treatment for epilepsy?

Research has shown that JNJ-40411813, also known as ADX71149, might help reduce seizures in people with epilepsy. In this trial, some participants will receive JNJ-40411813 alongside common epilepsy medications like levetiracetam or brivaracetam, which may decrease the number of seizures. The treatment affects specific brain areas that help control seizures. Although more information is needed, initial results are promising and suggest that JNJ-40411813 could be a helpful additional therapy for managing focal onset seizures. ^{3 6 7 8 9}

Who Is on the Research Team?

Janssen Research & Development, LLC Clinical Trial

Principal Investigator

Janssen Research & Development, LLC

Are You a Good Fit for This Trial?

Adults aged 18-69 with focal epilepsy, not well-controlled on current medications including levetiracetam or brivaracetam, can join this trial. They should have a BMI of 18-35 kg/m^2 and weigh at least 40 kg. Participants must have had stable seizure frequency (3 to 100 monthly) for the past six months and be able to maintain a seizure e-diary.

Inclusion Criteria

Participants should have experience in maintaining a seizure e-diary

I am currently taking 1 to 4 seizure medications, including either levetiracetam or brivaracetam.

I have been diagnosed with focal epilepsy for over a year and have had 3-100 seizures monthly for the past 6 months.

Exclusion Criteria

You are having seizures that are not easily measured or tracked.

My depression has worsened in the last 6 months, but I am taking antidepressants.

I have had seizures that are not caused by epilepsy.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

up to 8 weeks

Baseline

Participants undergo an 8-week prospective pretreatment baseline period to establish seizure count

8 weeks

Double-blind Treatment

Participants receive JNJ-40411813 or placebo in combination with AEDs to evaluate efficacy and safety

up to 12 weeks

Visits at baseline, weeks 4, 8, and 12

Open-label Extension

Participants continue receiving JNJ-40411813 and AEDs to evaluate long-term efficacy and safety

up to 2 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 weeks

1 follow-up telephone visit

What Are the Treatments Tested in This Trial?

Interventions

• JNJ-40411813
• Placebo

Trial Overview The study is testing JNJ-40411813 as an additional treatment alongside standard anti-epileptic drugs like levetiracetam or brivaracetam. It will compare different doses of JNJ-40411813 against a placebo to see if it helps reduce the number of seizures over time.

How Is the Trial Designed?

Group I: JNJ-40411813 Experimental Treatment 1 Intervention

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 II: Placebo Placebo Group 2 Interventions

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.

Who Is Running the Clinical Trial?

Janssen Research & Development, LLC

Lead Sponsor

Trials

1,022

Recruited

6,408,000+

Joaquin Duato

Janssen Research & Development, LLC

Chief Executive Officer since 2022

MBA from ESADE, Master of International Management from Thunderbird School of Global Management

Dr. Jijo James, MD

Janssen Research & Development, LLC

Chief Medical Officer since 2014

MD from St. Johns Medical College, MPH from Columbia University

Published Research Related to This Trial

Concerns have been raised about the safety of prolonged placebo exposure in epilepsy trials, as it may lead to uncontrolled epilepsy and an increased risk of sudden unexpected death, with a meta-analysis showing a 3- to 5-fold higher risk in participants on placebo.

The Research Roundtable in Epilepsy proposed new trial designs, such as active-control add-on trials and adaptive designs, to reduce placebo exposure while still ensuring rigorous evidence of the efficacy of new antiepileptic drugs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reducing placebo exposure in trials: Considerations from the Research Roundtable in Epilepsy. Fureman, BE., Friedman, D., Baulac, M., et al.[2017]

Newer antiepileptic drugs developed since the 1990s, such as gabapentin and lamotrigine, offer wider therapeutic benefits, fewer side effects, and reduced drug interactions compared to older medications, making them safer options for treating epilepsy.

These newer drugs not only effectively reduce seizures but also have additional benefits, such as managing chronic neuropathic pain and providing mood stabilization or anti-anxiety effects, highlighting their potential for broader neurological protection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Newer antiepileptic drugs]. Matsuura, M.[2018]

Newer antiepileptic drugs developed since the 1990s, such as gabapentin and lamotrigine, offer wider therapeutic benefits, fewer side effects, and reduced drug interactions compared to older medications, making them safer options for treating epilepsy.

These newer drugs not only effectively reduce seizures but also have additional benefits, such as managing chronic neuropathic pain and providing mood stabilization or anti-anxiety effects, highlighting their potential for broader neurological applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Newer antiepileptic drugs]. Matsuura, M.[2007]

In a simulation study using data from 684,825 seizures, it was found that placebos consistently reduced seizure frequency, suggesting that some of the observed placebo effects in epilepsy trials may be due to the natural progression of the disease rather than the placebo itself.

Modifying trial design elements, such as study start time or reducing the baseline population, can significantly enhance the ability of an effective drug to show superiority over placebo, highlighting the importance of careful clinical trial design in epilepsy research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Confusing placebo effect with natural history in epilepsy: A big data approach. Goldenholz, DM., Moss, R., Scott, J., et al.[2019]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04836559

NCT04836559 | A Study to Investigate JNJ-40411813 in ... 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 ...

2. addextherapeutics.com addextherapeutics.com/en/investors/press-releases/addex-adx71149-phase-2-epilepsy-study-expected-readout-data-q2-2024/

Addex ADX71149 Phase 2 Epilepsy Study Expected to ... Addex ADX71149 Phase 2 Epilepsy Study Expected to Readout Data in Q2 2024 ... Results evaluating the efficacy, safety and tolerability of ADX71149 ...

3. cdn.clinicaltrials.gov cdn.clinicaltrials.gov/large-docs/59/NCT04836559/SAP_001.pdf

NCT04836559 The primary objective 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 ...

4. addextherapeutics.com addextherapeutics.com/en/investors/press-releases/addex-adx71149-receives-ind-approval-start-phase-2a-clinical-study-epilepsy/

Addex ADX71149 Receives IND Approval to Start a Phase 2a ... The primary objective of the study is to evaluate the efficacy of JNJ-40411813 (ADX71149) in combination with levetiracetam using a time-to-event endpoint. “ ...

5. sec.gov sec.gov/Archives/edgar/data/1574232/000117184323007060/exh_991.htm

EdgarFiling ... (JNJ-40411813) Phase 2 epilepsy clinical study. Results evaluating the efficacy, safety and tolerability of ADX71149 in combination with ...

6. cdn.clinicaltrials.gov cdn.clinicaltrials.gov/large-docs/59/NCT04836559/Prot_000.pdf

NCT04836559 unblinded review of all cumulative safety, PK and efficacy data of JNJ-40411813 available to that date will be performed to decide on the dose in the ...

7. addextherapeutics.com addextherapeutics.com/en/investors/press-releases/addex-starts-phase-2-clinical-study-adx71149-epilepsy/

Addex Starts Phase 2 Clinical Study of ADX71149 for Epilepsy Proof of concept data with JNJ-40411813 (ADX71149) and other mGlu2 PAMs in animal models of epilepsy have been published in peer-reviewed ...

8. sec.gov sec.gov/Archives/edgar/data/1574232/000117184321007893/exh_991.htm

EdgarFiling Proof of concept data with JNJ-40411813 (ADX71149) and other mGlu2 PAMs in animal models of epilepsy have been published in peer-reviewed journals (Metcalf et ...

9. synapse.patsnap.com synapse.patsnap.com/article/partner-halts-adx71149-development-for-epilepsy

Partner Halts ADX71149 Development for Epilepsy The Phase 2 study of ADX71149 was a multi-center trial designed to evaluate the drug's efficacy, safety, tolerability, and pharmacokinetics when ...