First in Human Safety Study of FX-322 in Adults Undergoing Cochlear Implantation

Study Overview
=================
Brief Summary
-----------------
This is a phase 1 safety study performed in male or female adult participants with an established diagnosis of severe to profound sensorineural hearing loss that meets the criteria for cochlear implantation and the participant has already chosen to undergo cochlear implant surgery.

Detailed Description
-----------------
Approximately 12 participants will be enrolled in the study. Assessed will be safety and tolerability of FX-322 administered by intratympanic injection. Also assessed will be the FX-322 concentration in cochlear fluid (perilymph), the pharmacokinetic (PK) profile of FX-322 to determine the systemic exposure to FX-322.

Official Title
-----------------
First in Human Safety Study of FX-322 in Adults Undergoing Cochlear Implantation

Conditions
-----------------
Hearing Loss

Intervention / Treatment
-----------------
* Drug: FX-322
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Male or female adult subjects with an established diagnosis of severe to profound sensorineural hearing loss audiometric threshold of 80 dB HL or poorer at 500 Hz that meets the criteria for cochlear implantation and the subject has already chosen to undergo cochlear implant surgery. Willingness and ability to comply with scheduled visits, ear examination, drug administration plan, auditory and laboratory tests, study restrictions, and all study procedures. Other protocol-defined inclusion criteria may apply Exclusion Criteria: Persistent perforation of tympanic membrane or other tympanic membrane disorder that would interfere with the delivery and safety assessment of an intra -tympanic medication or reasonably be suspected to affect tympanic membrane healing after injection. Any conductive component defined as air-bone gaps >10 dB at two or more frequencies. Other protocol-defined exclusion criteria may apply

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Other
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Active<br>Subjects will receive FX-322 as an intratympanic injection | Drug: FX-322<br>* intratympanic injection<br>|
| Placebo Comparator: Placebo<br>Subjects will receive Placebo as an intratympanic injection | Drug: Placebo<br>* intratympanic injection<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of treatment-emergent adverse events (Safety and Tolerability) of FX-322. | To assess the incidence of adverse safety events (vertigo, tinnitus, perforation) including severe adverse events. | Treatment-emergent adverse events will be assessed over a several hour to two week period | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma Pharmacokinetics | Drug exposure in the systemic circulation by evaluating Cmax and AUC Drug exposure evaluated by area under the plasma concentration versus time curve (AUC) | Systemic exposure will be evaluated over a 72 hour period | 
| Plasma Pharmacokinetics | Peak Plasma Concentration (Cmax) | Within a 24 hour period after injection | 
| Cochlear Perilymph Pharmacokinetics | single time point measurement in each patient of drug in cochlear perilymph | within a 24 hour period after injection |