JNJ-40411813 + Standard Epilepsy Meds for Epilepsy

Recruiting at 90 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

110 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing JNJ-40411813, a new drug for people with focal onset seizures not fully controlled by other medications. The drug aims to reduce excessive brain activity by lowering glutamate levels. Participants will take this drug along with their current epilepsy medications.

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.

What evidence supports the effectiveness of the drug JNJ-40411813 for epilepsy?

The effectiveness of new antiepileptic drugs, like JNJ-40411813, is often evaluated through placebo-controlled add-on trials, which have been successful in identifying effective treatments for epilepsy. These trials compare the new drug with a placebo while patients continue their standard epilepsy medications, providing evidence of the drug's potential benefits. ^{1 2 3 4 5}

How is the drug JNJ-40411813 different from other epilepsy drugs?

JNJ-40411813 is being studied in combination with standard epilepsy medications to see if it can help reduce seizures in people with epilepsy. This drug is unique because it is being tested specifically for its potential to work alongside existing treatments, which might offer a new option for patients who do not respond well to current medications. ^{6 7 8 9 10}

Research Team

Janssen Research & Development, LLC Clinical Trial

Principal Investigator

Janssen Research & Development, LLC

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Giacomo Salvadore

Janssen Research & Development, LLC

Chief Medical Officer since 2023

MD from the University of Rome, Tor Vergata

Ricardo Attar

Janssen Research & Development, LLC

Chief Executive Officer since 2008

PhD in Molecular Biology from the University of Buenos Aires

Findings from Research

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]

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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Reducing placebo exposure in trials: Considerations from the Research Roundtable in Epilepsy. [2017]

2. United States pubmed.ncbi.nlm.nih.gov

Confusing placebo effect with natural history in epilepsy: A big data approach. [2019]

3. United States pubmed.ncbi.nlm.nih.gov

Placebo-corrected efficacy of modern antiepileptic drugs for refractory epilepsy: systematic review and meta-analysis. [2018]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Adverse events, placebo and nocebo effects in placebo-treated paediatric patients with refractory focal epilepsies. Analysis of double-blind studies. [2014]

5. New Zealand pubmed.ncbi.nlm.nih.gov

Evaluation of antiepileptic drug efficacy. A review of clinical trial design. [2018]

6. Japan pubmed.ncbi.nlm.nih.gov

[Newer antiepileptic drugs]. [2018]

7. India pubmed.ncbi.nlm.nih.gov

Differential improvement of the sleep quality among patients with juvenile myoclonic epilepsy with valproic acid: A longitudinal sleep questionnaire-based study. [2020]

8. United States pubmed.ncbi.nlm.nih.gov

Effects of levetiracetam on EEG abnormalities in juvenile myoclonic epilepsy. [2022]

9. Netherlands pubmed.ncbi.nlm.nih.gov

Evaluation of JNJ-26489112 in patients with photosensitive epilepsy: a placebo-controlled, exploratory study. [2014]

10. Japan pubmed.ncbi.nlm.nih.gov

[Newer antiepileptic drugs]. [2007]