Rilonacept for Treatment of Autoimmune Neurosensory Hearing Loss

Ten (10) patients in total will be enrolled in this study at Metroplex Clinical Research
Center in Dallas, TX. Patients may be identified and referred by local area audiologist. The
ANSHL study population will be defined by inclusion and exclusion criteria designed to limit
enrollment to individuals with idiopathic, progressive, bilateral sensorineural hearing loss,
to ensure appropriate candidates for treatment with study medications, and to identify those
with a high likelihood of complying with the study protocol.

Inclusion Criteria:

1. 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.

2. 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.

3. 18-75 years of age

4. Able and willing to give written informed consent and comply with the requirements of
the study protocol

5. 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.

Exclusion Criteria:

1. Pregnant or nursing, or planning to become pregnant or father a child within 3 months
after receiving the last dose of study drug

2. 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.

3. 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

4. Uncontrolled diabetes at the baseline visit (defined as HbA1c ≥9.0%)

5. Patients requiring dialysis

6. Patients who have had an organ transplant

7. 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.

8. Prohibited Medications:

1. Strong CYP3A4 inhibitors, protease inhibitors or P-gp inhibitors.

2. Long-acting or extended release forms of opiates.

3. Live or live-attenuated vaccines are excluded during the course of the study

4. IA and IM glucocorticoid injections. Long-acting steroid preparations are not
allowed during study (this includes suspensions and all forms of dexamethasone).

9. History of a demyelinating disease or symptoms suggestive of multiple sclerosis

10. Treatment with a live or live-attenuated virus vaccine during the 3 months prior to
baseline

11. Estimated glomerular filtration rate (eGFR) of <20 mL/min/1.73m2 or patients planning
to start dialysis within a year from the screening visit

12. Baseline laboratory test results meeting any of the following criteria:

1. Hemoglobin (Hgb)<8.5 g/dL (85 g/L)

2. Neutrophil count<1.5 x 103/μL

3. Platelet count<100 x 103/μL

4. Total bilirubin exceeding 1.5 times the upper limit of normal (ULN) unless
consistent with Gilbert's syndrome

5. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) exceeding 2
times the ULN

13. Positive history of human immunodeficiency virus (HIV) by clinical or serological
testing.

14. Presence of hepatitis B surface antigen (HBsAg) and/or hepatitis C antibody (HCV) by
serologic testing

15. History of active TB prior to screening or chest x-ray showing evidence of malignancy
or any abnormalities suggestive of prior tuberculosis (TB) infection, including, but
not limited to, apical scarring, apical fibrosis, or multiple calcified granulomata.

16. A positive intradermal skin tuberculin test (purified protein derivative [PPD] 5
tuberculin unit [TU]) of ≥5 mm induration read at 48 to 72 hours or positive
QuantiFERON-gold testing. Signs or symptoms suggestive of active TB (e.g. new cough
lasting >14 days or a change in chronic cough, persistent fever, unintentional weight
loss, night sweats) upon review of medical history and/or physical examination. If the
patient is thought to have a false-positive PPD because of prior BCG vaccination and
it is known that the patient has been negative on testing obtained outside the
protocol for M. tuberculosis infection using a cell-based interferon gamma assay the
patient is eligible for enrollment.

17. Recent close contact with a person with active TB

18. History of latent untreated TB. Patients who have been adequately treated for latent
TB are eligible for enrollment.

19. Any other medical condition that in the opinion of the investigator could adversely
affect the patient's participation or interfere with evaluations. This includes
significant concomitant illness such as, but not limited to, cardiac, renal,
neurological, endocrinological, metabolic, pulmonary, gastrointestinal, or psychiatric
disease.

20. History or presence of malignancy within 5 years of the screening visit (other than a
successfully treated non-metastatic cutaneous squamous cell or basal cell carcinoma
and/or localized carcinoma in situ of the cervix)

21. History of a myeloproliferative disorder

22. History of alcohol abuse within last 5 years or current intake of 21 or more
alcohol-containing drinks per week

23. History of drug abuse within the 5 years prior to screening

24. Patients with previous exposure to rilonacept

25. Use of any investigational drug within 30 days or within 5 half-lives (whichever is
longer) prior to the screening visit

26. Sexually active men or women of childbearing potential who are unwilling to practice
adequate contraception during the study (adequate contraceptive measures are defined
as the use of two highly effective forms of birth control, include stable use of oral
contraceptives or other prescription pharmaceutical contraceptives; intrauterine
device; bilateral tubal ligation; vasectomy; condom plus contraceptive sponge, foam,
or jelly, or diaphragm plus contraceptive sponge, foam, or jelly)

27. Known moderate-to-severe liver disease (Child-Pugh class B or C)

28. Known hypersensitivity to CHO cell derived therapeutics or proteins or any components
of rilonacept