Anakinra for Meniere's Disease

Overseen By Ginny Mullooly, RN

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Northwell Health

Must be taking: Corticosteroids

Must not be taking: Methotrexate, TNF-antagonists

Disqualifiers: Immunodeficiency, Chronic infections, Cancer, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

57 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests anakinra, a medication, to determine its effectiveness for individuals with Meniere's disease or autoimmune inner ear disease who cannot use steroids or find them ineffective. Participants will receive either anakinra or a placebo (a harmless pill with no effect) to compare results. The goal is to assess whether anakinra can improve hearing and other symptoms. Suitable candidates have Meniere's disease or autoimmune inner ear disease, have tried steroids without success, and experience worsening hearing. As a Phase 2 trial, this research measures anakinra's effectiveness in an initial, smaller group, offering a chance to potentially benefit from an innovative treatment.

Do I need to stop my current medications to join the trial?

The trial does not specify if you need to stop taking your current medications, but you cannot be on methotrexate, TNF-antagonist therapy, or any other immunosuppressive therapy. No new diuretics can be started or doses increased 28 days before joining the trial.

Is there any evidence suggesting that anakinra is likely to be safe for humans?

Research shows that anakinra, the treatment under study, may help with Meniere's disease and autoimmune inner ear disease. Studies have found that anakinra can lessen ear-related symptoms and help protect ear function.

Regarding safety, previous studies indicate that anakinra is generally well-tolerated by patients. Some people might experience side effects, but these are usually mild. Anakinra's safety has been tested in other conditions, and it is already approved by the FDA for other uses, suggesting it is reasonably safe.

Overall, existing research provides a positive view of anakinra's safety for those considering joining this trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for Meniere's disease?

Unlike standard treatments for Meniere's Disease, which typically include diuretics, vestibular suppressants, or intratympanic injections, anakinra offers a novel approach by targeting the underlying inflammatory processes. Anakinra is unique because it blocks the activity of interleukin-1 (IL-1), a protein that plays a significant role in inflammation. Researchers are excited about this treatment because it focuses on reducing inflammation directly, potentially addressing the root cause of symptoms rather than just managing them. This different mechanism of action could lead to more effective relief for patients suffering from the debilitating vertigo and hearing issues associated with Meniere's Disease.

What evidence suggests that anakinra might be an effective treatment for Meniere's disease?

Research has shown that anakinra might help with Meniere's disease by reducing inflammation. In animal studies, anakinra improved hearing and balance by protecting the cochlear nerve, which is crucial for hearing. Some early studies in humans also demonstrated improved hearing in patients treated with anakinra. In this trial, participants will be randomized into different groups to receive anakinra or a placebo in varying sequences. These findings suggest that anakinra could benefit those who don't respond well to steroids, a common treatment for Meniere's disease. However, more research is needed to confirm these results in larger groups of people. ^{1 2 6 7 8}

Who Is on the Research Team?

Andrea Vambutas, MD

Principal Investigator

Northwell Health

Are You a Good Fit for This Trial?

This trial is for adults with severe hearing loss due to Meniere's Disease or Autoimmune Inner Ear Disease who haven't improved with steroids. Participants must have stable or worsening hearing, not be on certain immunosuppressives, and can't start new diuretics before the trial. They should understand English, use effective birth control, and not have specific ear conditions or infections.

Inclusion Criteria

Patients must be fluent in English

Females of childbearing potential must be practicing a method of birth control

Patients may have other autoimmune disease(s)

Exclusion Criteria

Pregnant or lactating females

Evidence of retrocochlear pathology or inner ear malformation based on imaging

History of active narcotic abuse

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Period 1

Participants receive either anakinra or placebo for 42 consecutive days

6 weeks

Daily self-administration

Treatment Period 2

Participants continue with either anakinra or switch to placebo for an additional 42 consecutive days

6 weeks

Daily self-administration

Observation

A 264-day observation period where hearing declines may be re-treated with anakinra

264 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Anakinra

Trial Overview The study tests Anakinra (a drug) against a placebo in patients resistant to corticosteroids over two periods of 42 days each. Patients are randomly chosen to receive either Anakinra or placebo in a 2:1 ratio. After these periods, there's an observation phase where declines in hearing may be treated again with Anakinra.

How Is the Trial Designed?

Group I: Group C Experimental Treatment 2 Interventions

This group will be randomized to receive intervention of placebo for 42 consecutive days in period 1 followed by 42 consecutive days of anakinra (100mg/0.67ml) in period 2

Group II: Group B Experimental Treatment 2 Interventions

This group will be randomized to receive intervention of 42 consecutive days of anakinra (100 mg/0.67ml) in period 1 followed by 42 consecutive days of placebo in period 2

Group III: Group A Experimental Treatment 2 Interventions

This group will be randomized to receive intervention of 42 consecutive days of anakinra (100mg/0.67ml) in period 1 followed by an additional 42 consecutive days of anakinra (100mg/0.67ml) in period 2

Anakinra is already approved in European Union, United States for the following indications:

Approved in European Union as Kineret for:

• Rheumatoid arthritis
• Cryopyrin-associated periodic syndromes
• Deficiency of interleukin-1 receptor antagonist
• COVID-19

Approved in United States as Kineret for:

• Rheumatoid arthritis
• Deficiency of interleukin-1 receptor antagonist
• Neonatal-onset multisystem inflammatory disease (NOMID)
• COVID-19

Who Is Running the Clinical Trial?

Northwell Health

Lead Sponsor

Trials

481

Recruited

470,000+

Swedish Orphan Biovitrum

Industry Sponsor

Trials

103

Recruited

13,300+

Dr. Guido Oelkers

Swedish Orphan Biovitrum

Chief Executive Officer since 2017

PhD in Economics

Dr. Lydia Abad-Franch

Swedish Orphan Biovitrum

Chief Medical Officer since 2023

MD, MBA

Published Research Related to This Trial

Meniett therapy has been shown to effectively reduce the frequency of vertigo attacks in patients with Ménière's disease, based on a meta-analysis of 14 studies involving 345 patients.

The therapy may also help alleviate functional deficits associated with the disease, although its impact on hearing remains unclear, and the benefits may last for about 18 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Meniett Therapy for Ménière's Disease: An Updated Meta-analysis. Zhang, SL., Leng, Y., Liu, B., et al.[2018]

In a study of 33 patients with unilateral Ménière's disease, 90.9% responded to questionnaires, showing that the Meniett® device significantly alleviated symptoms, with 63.3% reporting reduced vertigo and tinnitus.

The Meniett® device is a well-tolerated and minimally invasive treatment option for Ménière's disease, providing a beneficial alternative before considering more invasive and potentially harmful therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Initial UK experience of patient satisfaction with the Meniett® device for Ménière's disease treatment. Buchanan, MA., Rai, A., Prinsley, PR.[2019]

Intratympanic steroid treatment may slightly reduce the frequency of vertiginous attacks in patients with Menière's disease, but the evidence is weak and based on very low-quality studies.

No serious adverse events were reported, indicating that the treatment is likely safe; however, further research is necessary to determine its overall efficacy and safety in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intratympanic Steroid for Menière's Disease: A Systematic Review. Devantier, L., Djurhuus, BD., Hougaard, DD., et al.[2020]

The Meniett device is a safe and minimally invasive treatment that effectively reduces vestibular symptoms in patients with delayed endolymphatic hydrops (DEH) and Meniere's disease (MD), with 57% of MD patients and 100% of DEH patients remaining free from vertigo spells after treatment.

In a study involving 33 patients who had not responded to other medical treatments, 74% maintained stable hearing levels, indicating that the Meniett device does not adversely affect hearing while providing symptom relief.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term effects of the Meniett device in Japanese patients with Meniere's disease and delayed endolymphatic hydrops reported by the Middle Ear Pressure Treatment Research Group of Japan. Shojaku, H., Watanabe, Y., Mineta, H., et al.[2011]

In a 2-year follow-up study of 61 participants with unilateral Ménière's disease, 67% experienced significant improvement in vertigo frequency using the Meniett device, indicating its efficacy as a treatment option.

The majority of participants who achieved remission (80%) maintained their improvement long-term, suggesting that the Meniett device is a safe and effective alternative for those unresponsive to traditional medical treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Meniett clinical trial: long-term follow-up. Gates, GA., Verrall, A., Green, JD., et al.[2015]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT03587701

Effects of Anakinra in Subjects With Corticosteroid-resistant ... Study Overview​​ A Phase II randomized, placebo controlled study design of anakinra (Kineret) in corticosteroid-resistant or intolerant Meniere's disease (CR-MD) ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9798291/

Protective effect of anakinra on audiovestibular function in a ... In summary, our results demonstrated that anakinra attenuated EH, improved auditory and vestibular function, protected cochlear nerve in a murine model of EH.

3. clinicaltrial.be clinicaltrial.be/en/details/68065?per_page=20&only_recruiting=0&only_eligible=0&only_active=0

Effects of Anakinra in Subjects With Corticosteroid-resis... This study will be evaluating whether or not anakinra (kineret) is superior to placebo for improving sustained hearing thresholds in patients with CR or ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4160092/

Early efficacy trial of anakinra in corticosteroid-resistant ... During the 180 day post-treatment observation phase, 3 patients who experienced initial improvement in hearing while taking anakinra exhibited ...

5. nature.com nature.com/articles/s41598-022-08967-7

NaCl exposure results in increased expression and ... NaCl exposure results in increased expression and processing of IL-1β in Meniere's disease patients ... Are diuretics effective for Ménière's ...

6. go.drugbank.com go.drugbank.com/drugs/DB00026/clinical_trials?conditions=DBCOND0050160%2CDBCOND0066647&phase=2&purpose=treatment&status=recruiting

Anakinra Recruiting Phase 2 Trials for Menière's Disease ... Anakinra Recruiting Phase 2 Trials for Menière's Disease / Autoimmune Inner Ear Disease Treatment · Sign up for a demo of our new platform and AI assistant!

7. sciencedirect.com sciencedirect.com/science/article/pii/S0013935123017760

Meniere's disease: Pathogenesis, treatments, and ... Early results have been promising, and some studies have passed phase three and four clinical trials. To determine the safety and efficacy of ...

8. centerwatch.com centerwatch.com/clinical-trials/listings/NCT03587701/effects-of-anakinra-in-subjects-with-corticosteroid-resistant-intolerant-menieres-disease-and-autoimmune-inner-ear-disease

Effects of Anakinra in Subjects With Corticosteroid-resistant ... A Phase II randomized, placebo controlled study design of anakinra (Kineret) in corticosteroid-resistant or intolerant Meniere's disease ...