Anakinra vs Tocilizumab for Status Epilepticus

(COMBAT-NORSE Trial)

Not yet recruiting at 32 trial locations
CC
TM
Overseen ByTara McPartland
Age: Any Age
Sex: Any
Trial Phase: Phase 3
Sponsor: Yale University
Must be taking: Anakinra, Tocilizumab
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Pivotal Trial (Near Approval)This treatment is in the last trial phase before FDA approval
Prior Safety DataThis treatment has passed at least one previous human trial

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial investigates whether two medications, anakinra and tocilizumab, can effectively treat NORSE, a rare brain condition causing continuous seizures in previously healthy individuals. These drugs are already used when standard treatments fail, but it remains unclear which works better or when to use them. Participants will either be randomly assigned to receive one of these drugs or be observed if randomization is not possible. Individuals who have recently experienced continuous seizures, have no underlying neurological conditions, and whose doctors are considering these medications as a treatment option might be eligible to join. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Do I have to stop taking my current medications for the trial?

The trial information does not specify if you need to stop taking your current medications. However, you cannot use TNF blocking agents while participating. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that both anakinra and tocilizumab are generally safe, each with specific safety profiles. Anakinra has lowered seizure frequency in some patients, though not all become seizure-free. Studies report that patients tolerated the drug well, with no major side effects during long-term use.

For tocilizumab, research indicates it can help children with certain seizure conditions regain consciousness. One study showed it stopped seizures in six out of seven patients within three days. While individual results can vary, these findings suggest the drug is usually well-tolerated.

Both medications are already used to treat other conditions, supporting their safety. However, patients should always consult their healthcare provider about potential risks and benefits before starting any new treatment.12345

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for status epilepticus because they each target inflammation in unique ways. Anakinra is distinct because it blocks the interleukin-1 receptor, potentially reducing brain inflammation more directly and quickly than traditional anti-seizure medications. Tocilizumab, on the other hand, inhibits the interleukin-6 receptor, offering a different approach to dampening the immune response that can exacerbate seizures. These targeted immunotherapies are promising because they might work faster and more effectively in managing seizures compared to the usual treatments, which often focus on controlling symptoms rather than addressing underlying inflammation.

What evidence suggests that this trial's treatments could be effective for NORSE?

This trial will compare Anakinra with Tocilizumab for treating status epilepticus. Research has shown that both Anakinra and Tocilizumab may help treat conditions like NORSE, which causes ongoing seizures. Participants may receive Anakinra, which studies have found can reduce seizure frequency and lead to noticeable improvements, although the long-term effects remain uncertain. Some patients experienced a significant drop in seizures soon after starting the treatment. Alternatively, participants may receive Tocilizumab, which has also been effective in stopping seizures and improving patient outcomes, with some reports of seizures stopping completely. Patients using Tocilizumab also experienced a significant decrease in seizure severity. While both treatments offer hope, more research is needed to better understand their effectiveness for this challenging condition.12346

Who Is on the Research Team?

LH

Lawrence Hirsch, MD

Principal Investigator

Yale University

Are You a Good Fit for This Trial?

This trial is for children and adults with a severe brain condition called NORSE, which causes ongoing seizures that don't stop with usual treatments. Participants must be within the first 7 days of illness and their doctors were already considering using anakinra or tocilizumab.

Inclusion Criteria

I am considered for Anakinra or tocilizumab treatment, and my side effects started within the last 7 days.
I am at least 2 years old.
In their usual state of health prior to their onset of SE
See 1 more

Exclusion Criteria

I do not have any severe illnesses like advanced cancer or uncontrolled diabetes.
Additional Exclusion Criteria for the Randomized Control Cohort: Contraindication to either anakinra or tocilizumab as listed in the prescribing information: Known hypersensitivity to E. Coli-derived proteins, anakinra, tocilizumab, or any component of the products. Active serious infection at the time of initiation. Concomitant use of TNF blocking agents; absolute neutrophil count < 2000; platelet count < 100,000 per mm³; or ALT or AST > 1.5 X the upper limit of normal. Elevated risk of GI perforation.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive either anakinra or tocilizumab within the first 7 days of their illness

7 days
In-hospital treatment

Follow-up

Participants are monitored for safety and effectiveness after treatment, including medical evaluations and surveys

12 months
Regular follow-up assessments

Long-term follow-up

Some participants may be followed annually beyond one year

Annually beyond 12 months

What Are the Treatments Tested in This Trial?

Interventions

  • Anakinra
  • Tocilizumab

Trial Overview

The study compares two drugs, anakinra and tocilizumab, to see which is more effective in treating NORSE. Patients are randomly assigned to one of the drugs if eligible or observed for treatment timing effects if they can't be randomized.

How Is the Trial Designed?

2

Treatment groups

Experimental Treatment

Active Control

Group I: Observational CohortExperimental Treatment1 Intervention
Group II: Randomized Controlled Trial (RCT) CohortActive Control2 Interventions

Find a Clinic Near You

Who Is Running the Clinical Trial?

Yale University

Lead Sponsor

Trials
1,963
Recruited
3,046,000+

Patient-Centered Outcomes Research Institute

Collaborator

Trials
592
Recruited
27,110,000+

Citations

The Beneficial Outcome of Subsequent Treatment with ...

Upon starting anakinra in the chronic phase, seizures were reduced to four per day without any subsequent exacerbations. This suggests that ...

Anakinra and tocilizumab in the chronic phase of febrile ...

Median treatment duration was 9months (IQR: 7–20). While no patients became seizure-free, 20–50% reduction in seizure frequency was reported in 3/5 patients ...

Response to anakinra in new-onset refractory status ...

At day 28, anakinra at 5mg/kg every 12 hours was started, which resulted in notable clinical and EEG improvements, without SE recurrence after ...

Immunotherapy for Refractory Status Epilepticus

The overall impact of anakinra on long-term outcomes remains unclear given the lack of controlled trials. ... efficacy data are highly variable.

Long-term neuropsychological outcomes in children with ...

These findings are concordant with data supporting that super-refractory status epilepticus causes worse neurological outcomes and lower rates of return to ...

Anakinra and tocilizumab in the chronic phase of febrile ...

Conclusion: This study provides promising data on effectiveness/safety of anakinra and tocilizumab in the chronic phase of FIRES. These ...