FX-322 in Sensorineural Hearing Loss

Study Overview
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Brief Summary
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This is a phase 1/2 study of FX-322 at two dose levels compared to placebo in male and female adults otherwise healthy with stable sensorineural hearing loss.

Detailed Description
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Sensorineural hearing loss (SNHL) accounts for about 90% of all cases of hearing loss. The study will assess the safety of FX-322 (laduviglusib and sodium valproate) given as a single intratympanic injection in subjects with a medical history of sensorineural hearing loss that is associated with noise exposure or sudden hearing loss. Safety will be evaluated both systemically (lab and clinical monitoring) and locally (otoscopy and audiometry) in 24 subjects, and a blood PK profile of FX-322 will also be determined.

Official Title
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A Phase 1/2 Randomized, Double-blind, Placebo-controlled Single Dose Study at Two Dose Levels of FX-322 Administered by Intratympanic Injection in Adults With Stable Sensorineural Hearing Loss

Conditions
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Sensorineural Hearing Loss

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult aged 18-65 years. Established diagnosis of stable sensorineural hearing loss (no changes of 10 dB or more at any frequency) by standard audiometric measures for >6 months. Documented medical history consistent with hearing loss being caused by noise exposure or sudden sensorineural hearing loss (documented audiogram at least 6 months prior to screening required). Female subjects must be of non-childbearing potential or will need to utilize two methods of highly effective contraception during the study participation (e.g. hormonal contraception or an intrauterine device and condoms) or remain abstinent. Male subjects should use condoms with spermicide during the course of the study or remain abstinent. Subjects should not donate sperm or ova during the study period. Exclusion Criteria: 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 either ear. This includes a current tympanostomy tubes. Any conductive hearing loss of 10 dB or more at two or more frequencies in either ear. A pure tone average of 70 dB or greater at 500Hz, 1000Hz, 2000Hz, and 4000Hz in the ear to be injected. Active chronic middle ear disease or a history of major middle ear surgery, as an adult, in the ear to be injected. Subject has had an intratympanic injection in either ear within 6 months of the screening visit. History of clinically significant vestibular symptoms at the discretion of the investigator. History of clinically significant systemic autoimmune disease (e.g. rheumatoid arthritis, Sjogren's syndrome, multiple sclerosis, psoriasis). History of head or neck radiation treatment or exposure. History of substance abuse within 2 years of the Screening Visit. Positive urine pregnancy test or breast-feeding. Any known factor, condition or disease that, in the view of the investigator, might interfere with treatment compliance, study conduct or interpretation of the results such as psychiatric disease or suicidal tendencies.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: FX-322 Low Dose<br>Cohort of 8. Single intratympanic injection | Drug: FX-322<br>* Intratympanic injection of FX-322 consists of laduviglusib and sodium valproate<br>|
| Experimental: FX-322 High Dose<br>Cohort of 8. Single intratympanic injection | Drug: FX-322<br>* Intratympanic injection of FX-322 consists of laduviglusib and sodium valproate<br>|
| Placebo Comparator: Placebo-Low Dose<br>Cohort of 4. Single intratympanic injection | Drug: Placebo<br>* Intratympanic injection<br>|
| Placebo Comparator: Placebo-High Dose<br>Cohort of 4. Single intratympanic injection | Drug: Placebo<br>* Intratympanic injection<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) | Treatment-emergent adverse events (TEAE) were defined as any untoward medical occurrence in a subject administered study drug that does not necessarily have a causal relationship with the treatment and were collected from the time of first dose through end of study (day 90). In particular, audiometric and otoscopic TEAEs were recorded per the American Speech-Language-Hearing Association (ASHA) guidelines. | Baseline through Day 90 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax | Maximum concentration (Cmax) of FX-322 (Laduviglusib and Sodium Valproate) directly from individual concentration-time data | Data points taken pre-dose and 0.5, 1, 2, 4, 8, 24 hours post-dose | 
| Tmax | Time to reach maximum concentration of FX-322 (Laduviglusib and Sodium Valproate) directly from individual concentration-time data | Data points taken pre-dose and 0.5, 1, 2, 4, 8, 24 hours post-dose | 
| AUClast | Area under the concentration-time curve of FX-322 (Laduviglusib and Sodium Valproate) from time zero to the time of the last quantifiable concentration, calculated using the linear trapezoidal rule | Data points taken pre-dose and 0.5, 1, 2, 4, 8, 24 hours post-dose | 
| t1/2 | The observed terminal elimination half-life of FX-322 (Laduviglusib and Sodium Valproate) | Data points taken pre-dose and 0.5, 1, 2, 4, 8, 24 hours post-dose | 
| CL/F | Apparent total body clearance after extravascular administration of FX-322 (Laduviglusib and Sodium Valproate) | Data points taken pre-dose and 0.5, 1, 2, 4, 8, 24 hours post-dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Intratympanic Administration, Hearing Restoration