Rilonacept for Treatment of Autoimmune Neurosensory Hearing Loss

NCT02828033 | Unknown Early Phase 1 FDA Drug

• 1 other identifier: Rilonacept IIS 1604
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

This study is an open label proof of concept study of rilonacept for patients with ANSHL

Conditions

Autoimmune Neurosensory Hearing Loss (ANSHL)

Outcome Measures

Primary Outcomes (1)

• Improvement in hearing in comparison to baseline values

  1. An improvement in pure tone average (500 to 3000 Hz) by 10 dB in at least one ear or 2. An improvement of word identification score of at least 12 percent; both relative to baseline values

  24 weeks

Secondary Outcomes (4)

• Pt reported evaluation of auditory acuity

  24 weeks

• Vertigo evaluation

  24 weeks

• Tinnitus evaluation

  24 weeks

• Quality of Life assessment

  24 weeks

Study Arms (1)

Rilonacept

EXPERIMENTAL

A loading dose of 320 mg the first dose then be a once-weekly injection of 160 mg for 24 weeks

Drug: Rilonacept

Interventions

Rilonacept DRUG

All patients will receive rilonacept with an initial loading dose of 320 mg delivered as two, 2-mL, subcutaneous injections of 160 mg each given on the same day at two different sites. The initial dose will be administered at the study site by study personnel. Dosing will then be a once-weekly injection of 160 mg administered as a single, 2-mL, subcutaneous injection by the patient at home. Patients will be dosed for 24 weeks.

Also known as: IL-1 Trap, Arcalyst

Rilonacept

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• The presence of progressive sensironeural hearing loss greater than or equal to 30 dB in both ears at one or more frequencies (250, 500, 1000, 2000, 3000, 4000, 6000 or 8000 Hz) and idiopathic-based on clinical evaluation, blood tests, and radiographic imaging.
• Documented improvement in hearing by audiogram after 30 days of treatment with high dose prednisone 40-60 mg/d. Improvement is defined by 10 dB improvement in pure tone average (500-3000 dB) or an improvement in word identification score of at least 12% in either ear (both relative to baseline). Prednisone could be started at screening but patients may have received prednisone prior to screening and the pre prednisone audiogram will be used as the screening audiogram for this study. It is expected the majority of these patients will screen for the study in this fashion as they are referred from otoloaryngology after initial treatment.
• years of age
• Able and willing to give written informed consent and comply with the requirements of the study protocol
• Negative serum pregnancy test (for women of child bearing potential). Males and Females of child bearing potential must agree to consistently use 2 forms of highly effective birth control (at least 1 of which must be a barrier method) starting at screening and throughout the study period and for 3 months after the final study drug administration.

You may not qualify if:

• Pregnant or nursing, or planning to become pregnant or father a child within 3 months after receiving the last dose of study drug
• Have a known or suspected current active infection or a history of chronic or recurrent infectious disease including, but not limited to, chronic renal infection, chronic chest infections, chronic sinusitis, recurrent urinary tract infections, an open, draining, infected skin wound.
• Within 2 months of first study drug administration, have had a serious infection, have been hospitalized for an infection, have been treated with PO antibiotics for longer than 2 weeks, or have been treated with intravenous (IV) antibiotics for an infection
• Uncontrolled diabetes at the baseline visit (defined as HbA1c ≥9.0%)
• Patients requiring dialysis
• Patients who have had an organ transplant
• Treatment with any systemic {non-glucocorticoid} immunosuppressants (e.g. methotrexate, azathioprine, cyclosporine, mercaptopurine, mycophenolate mofetil, tacrolimus, sirolimus within 4 weeks of baseline rilonacept administration. No leflunomide treatment within 8 weeks prior to baseline administration. No etanercept, adalimumab, infliximab, tocilizumab, abatacept, or natalizumab, within 2 months prior to baseline visit; No rituxan for 12 months prior to baseline and evidence of normal B cell count required. Patients previously treated with anakinra for ANSHL cannot be enrolled.
• Prohibited Medications:
• Strong CYP3A4 inhibitors, protease inhibitors or P-gp inhibitors.
• Long-acting or extended release forms of opiates.
• Live or live-attenuated vaccines are excluded during the course of the study
• IA and IM glucocorticoid injections. Long-acting steroid preparations are not allowed during study (this includes suspensions and all forms of dexamethasone).
• History of a demyelinating disease or symptoms suggestive of multiple sclerosis
• Treatment with a live or live-attenuated virus vaccine during the 3 months prior to baseline
• Estimated glomerular filtration rate (eGFR) of \<20 mL/min/1.73m2 or patients planning to start dialysis within a year from the screening visit

Sponsors & Collaborators

• Stanley Cohen: lead
• Regeneron Pharmaceuticals: collaborator

Study Sites (1)

Metroplex Clinical Research Center

Dallas, Texas, 75231, United States

RECRUITING

Related Publications (20)

• McCabe BF. Autoimmune sensorineural hearing loss. Ann Otol Rhinol Laryngol. 1979 Sep-Oct;88(5 Pt 1):585-9. doi: 10.1177/000348947908800501.

  PMID: 496191 BACKGROUND

• Harris JP, Sharp PA. Inner ear autoantibodies in patients with rapidly progressive sensorineural hearing loss. Laryngoscope. 1990 May;100(5):516-24. doi: 10.1288/00005537-199005000-00015.

  PMID: 2329911 BACKGROUND

• Moscicki RA, San Martin JE, Quintero CH, Rauch SD, Nadol JB Jr, Bloch KJ. Serum antibody to inner ear proteins in patients with progressive hearing loss. Correlation with disease activity and response to corticosteroid treatment. JAMA. 1994 Aug 24-31;272(8):611-6.

  PMID: 8057517 BACKGROUND

• Tebo AE, Szankasi P, Hillman TA, Litwin CM, Hill HR. Antibody reactivity to heat shock protein 70 and inner ear-specific proteins in patients with idiopathic sensorineural hearing loss. Clin Exp Immunol. 2006 Dec;146(3):427-32. doi: 10.1111/j.1365-2249.2006.03227.x.

  PMID: 17100761 BACKGROUND

• Hirose K, Wener MH, Duckert LG. Utility of laboratory testing in autoimmune inner ear disease. Laryngoscope. 1999 Nov;109(11):1749-54. doi: 10.1097/00005537-199911000-00005.

  PMID: 10569401 BACKGROUND

• Bouman H, Klis SF, Meeuwsen F, de Groot JC, Smoorenburg GF, Veldman JE. Experimental autoimmune inner ear disease: an electrocochleographic and histophysiologic study. Ann Otol Rhinol Laryngol. 2000 May;109(5):457-66. doi: 10.1177/000348940010900504.

  PMID: 10823474 BACKGROUND

• McCabe BF. Autoimmune inner ear disease: therapy. Am J Otol. 1989 May;10(3):196-7.

  PMID: 2750868 BACKGROUND

• Saracaydin A, Katircioglu S, Katircioglu S, Karatay MC. Azathioprine in combination with steroids in the treatment of autoimmune inner-ear disease. J Int Med Res. 1993 Jul-Aug;21(4):192-6. doi: 10.1177/030006059302100404.

  PMID: 8112477 BACKGROUND

• Sismanis A, Wise CM, Johnson GD. Methotrexate management of immune-mediated cochleovestibular disorders. Otolaryngol Head Neck Surg. 1997 Feb;116(2):146-52. doi: 10.1016/S0194-59989770316-4.

  PMID: 9051055 BACKGROUND

• Luetje CM. Theoretical and practical implications for plasmapheresis in autoimmune inner ear disease. Laryngoscope. 1989 Nov;99(11):1137-46. doi: 10.1288/00005537-198911000-00006.

  PMID: 2811552 BACKGROUND

• Kitashara M, Yazawa.Y, Uchida K. Immunoglobulin treatment for advance cases of bilateral Meniere's disease. In: Nadol JB ed. Meniere's disease: pathogenesis, pathophysiology, diagnosis and treatment. Berkeley, Ca: Kugler Publications; 1989; 411-419.

  BACKGROUND

• Harris JP, Weisman MH, Derebery JM, Espeland MA, Gantz BJ, Gulya AJ, Hammerschlag PE, Hannley M, Hughes GB, Moscicki R, Nelson RA, Niparko JK, Rauch SD, Telian SA, Brookhouser PE. Treatment of corticosteroid-responsive autoimmune inner ear disease with methotrexate: a randomized controlled trial. JAMA. 2003 Oct 8;290(14):1875-83. doi: 10.1001/jama.290.14.1875.

  PMID: 14532316 BACKGROUND

• Broughton SS, Meyerhoff WE, Cohen SB. Immune-mediated inner ear disease: 10-year experience. Semin Arthritis Rheum. 2004 Oct;34(2):544-8. doi: 10.1016/j.semarthrit.2004.07.001.

  PMID: 15505770 BACKGROUND

• Cohen S, Shoup A, Weisman MH, Harris J. Etanercept treatment for autoimmune inner ear disease: results of a pilot placebo-controlled study. Otol Neurotol. 2005 Sep;26(5):903-7. doi: 10.1097/01.mao.0000185082.28598.87.

  PMID: 16151336 BACKGROUND

• Rahman MU, Poe DS, Choi HK. Etanercept therapy for immune-mediated cochleovestibular disorders: preliminary results in a pilot study. Otol Neurotol. 2001 Sep;22(5):619-24. doi: 10.1097/00129492-200109000-00010.

  PMID: 11568668 BACKGROUND

• Cohen S, Roland P, Shoup A, Lowenstein M, Silverstein H, Kavanaugh A, Harris J. A pilot study of rituximab in immune-mediated inner ear disease. Audiol Neurootol. 2011;16(4):214-21. doi: 10.1159/000320606. Epub 2010 Oct 27.

  PMID: 20980741 BACKGROUND

• Rynne M, Maclean C, Bybee A, McDermott MF, Emery P. Hearing improvement in a patient with variant Muckle-Wells syndrome in response to interleukin 1 receptor antagonism. Ann Rheum Dis. 2006 Apr;65(4):533-4. doi: 10.1136/ard.2005.038091.

  PMID: 16531551 BACKGROUND

• Yamazaki T, Masumoto J, Agematsu K, Sawai N, Kobayashi S, Shigemura T, Yasui K, Koike K. Anakinra improves sensory deafness in a Japanese patient with Muckle-Wells syndrome, possibly by inhibiting the cryopyrin inflammasome. Arthritis Rheum. 2008 Mar;58(3):864-8. doi: 10.1002/art.23261.

  PMID: 18311804 BACKGROUND

• Pathak S, Goldofsky E, Vivas EX, Bonagura VR, Vambutas A. IL-1beta is overexpressed and aberrantly regulated in corticosteroid nonresponders with autoimmune inner ear disease. J Immunol. 2011 Feb 1;186(3):1870-9. doi: 10.4049/jimmunol.1002275. Epub 2011 Jan 3.

  PMID: 21199898 BACKGROUND

• Vambutas A, Lesser M, Mullooly V, Pathak S, Zahtz G, Rosen L, Goldofsky E. Early efficacy trial of anakinra in corticosteroid-resistant autoimmune inner ear disease. J Clin Invest. 2014 Sep;124(9):4115-22. doi: 10.1172/JCI76503. Epub 2014 Aug 18.

  PMID: 25133431 BACKGROUND

MeSH Terms

Interventions

rilonacept

Study Officials

• Stanley B Cohen, MD

  Metroplex Clinical Research Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Stanley B Cohen, MD

CONTACT

214-879-6737; scohen@arthdocs.com

Cindy Cabrera

CONTACT

214-879-6737; ccabrera@mcrcdallas.com

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: July 1, 2016
• First Posted: July 11, 2016
• Study Start: February 1, 2017
• Primary Completion: March 1, 2018
• Study Completion: March 1, 2018
• Last Updated: September 13, 2017

Record last verified: 2017-09

Data Sharing

• IPD Sharing: Will share

Locations

US (1)