First in Human Safety Study of FX-345 in Adults With Sensorineural Hearing Loss

Study Overview
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Brief Summary
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This single-blind, placebo-controlled trial will be conducted to evaluate the safety of FX-345 administered as a single intratympanic injection in adults with acquired sensorineural hearing loss. The primary objectives are to assess the local safety, systemic safety, and pharmacokinetic (PK) profile to determine systemic exposure.

Detailed Description
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This study will enroll two cohorts. Cohort 1 (n=9) will be enrolled first to rapidly assess safety and drug exposure. After the sponsor completes an unblinded safety review, Cohort 2 (n=27) will be enrolled to continue safety evaluation of FX-345.

Official Title
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A Phase 1b, Prospective, Randomized, Single-Blind, Placebo-Controlled, Multicenter Study to Evaluate the Safety of FX-345 Administered as a Single Intratympanic Injection in Adults With Acquired Adult-Onset Sensorineural Hearing Loss

Conditions
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Hearing Loss, Sensorineural

Intervention / Treatment
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* Drug: FX-345
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult aged 18-67 years (inclusive) Documented medical history consistent with acquired, adult onset, sensorineural hearing loss At the Screening, Lead-in (Visit 2) and Treatment (Day 1) Visits, a pure tone average of 40- 80 dBHL at 500Hz, 1000Hz, 2000Hz, and 4000Hz in the potential study ear to be injected Female participants must not be pregnant, breastfeeding, or lactating. Women of child-bearing potential must agree to use a highly effective contraceptive method and must have a negative urine pregnancy test. Male participants must refrain from donating sperm and agree to be either abstinent or use a barrier method of contraception Exclusion Criteria: Randomization in a FX-322 (laduviglusib and sodium valproate) clinical trial Perforation of tympanic membrane or other tympanic membrane disorders that would interfere with the delivery and safety assessment of an intratympanic medication or reasonably be suspected to affect tympanic membrane healing after injection in study ear. This includes a current tympanostomy tube. Any conductive hearing loss of greater than 15 dB at a single frequency or greater than 10 dB at two or more contiguous octave frequencies in the study ear at the Screening, Lead-in (Visit 2) or Treatment (Day 1) Visits, based on the investigator's judgment. Active chronic middle ear disease or a history of major middle ear surgery, as an adult, in the ear to be injected. Within 3 months of screening visit any of the following: 1) an intratympanic injection in either ear 2) treatment with steroids 3) onset of sudden sensorineural hearing loss Evidence of or previous diagnosis of traumatic brain injury, Meniere's disease, or genetic hearing loss History of head or neck radiation, significant systemic autoimmune disease, and/or chronic, recurrent clinically significant vestibular symptoms Exposure to another investigational drug within 28 days prior to screening visit

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 67 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: FX-345 Cohort 1<br>Patients in the first cohort receiving FX-345 intratympanic injection | Drug: FX-345<br>* Single intratympanic injection of FX-345<br>|
| Placebo Comparator: Placebo Cohort 1<br>Patients in the first cohort receiving placebo intratympanic injection | Drug: Placebo<br>* Single intratympanic injection of placebo<br>|
| Experimental: FX-345 Cohort 2<br>Patients in the second cohort receiving FX-345 intratympanic injection | Drug: FX-345<br>* Single intratympanic injection of FX-345<br>|
| Placebo Comparator: Placebo Cohort 2<br>Patients in the second cohort receiving placebo intratympanic injection | Drug: Placebo<br>* Single intratympanic injection of placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Treatment-emergent Adverse Event(s) (TEAEs) |  | Baseline Through Day 90 | 
| Cmax | Maximum (peak) observed plasma drug concentration of FX04 and FX00 in cohort 1 participants | Data points taken pre-dose and 0.5, 1, 2, 4, 6, 24 hours post-dose | 
| AUClast | Area under the concentration-time curve of FX04 and FX00 in cohort 1 participants | Data points taken pre-dose and 0.5, 1, 2, 4, 6, 24 hours post-dose | 
| CL/F | Apparent total body clearance of FX04 and FX00 in cohort 1 participants | Data points taken pre-dose and 0.5, 1, 2, 4, 6, 24 hours post-dose | 
| Vss | Apparent volume of distribution at steady state of FX04 and FX00 in cohort 1 participants | Data points taken pre-dose and 0.5, 1, 2, 4, 6, 24 hours post-dose | 
| t1/2 | Elimination half-life of FX04 and FX00 in cohort 1 participants | Data points taken pre-dose and 0.5, 1, 2, 4, 6, 24 hours post-dose | 
| Tmax | Time to reach maximum (peak) plasma drug concentration of FX04 and FX00 in cohort 1 participants | Data points taken pre-dose and 0.5, 1, 2, 4, 6, 24 hours post-dose | 
| Elimination rate constant | The rate at which FX04 and FX00 is removed from the human system in cohort 1 participants | Data points taken pre-dose and 0.5, 1, 2, 4, 6, 24 hours post-dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hearing loss, Intratympanic Injection