Phase I/IIa Study Evaluating Safety and Efficacy of an Intratympanic Dose of PIPE-505 in Subjects With Hearing Loss

Study Overview
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Brief Summary
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This is a randomized, double-blind study of PIPE-505, or placebo, in subjects with hearing loss associated with speech-in-noise impairment.

Detailed Description
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This is a randomized-controlled, double-blind study of PIPE-505 or placebo given as an injection one time in subjects with sensorineural hearing loss associated with speech-in-noise difficulty. Visits to the clinic will occur at baseline, dosing, and days 1, 7, 14, 30, 60 and 90 after treatment. Safety will be assessed by periodic measurement of vital signs, ear examination, electrocardiogram (ECG), blood laboratory analyses and occurrence of adverse events (AE). Efficacy will be assessed by periodic audiometry and other audiological tests.

Official Title
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A Phase I/IIa, Randomized, Double-Blind, Placebo-Controlled, Safety, Pharmacokinetic, and Preliminary Efficacy Study of Unilateral Intratympanic PIPE-505 in Subjects With Sensorineural Hearing Loss Associated With Speech-in-Noise Impairment

Conditions
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Sensorineural Hearing Loss

Intervention / Treatment
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* Drug: PIPE-505
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject's primary language is English. Male or female between 18 and 75 years of age, inclusive, at randomization. Diagnosis of bilateral sensorineural hearing loss (SNHL). Normal tympanogram in the ear intended for injection (as defined in protocol) at Screening. Male or female subjects with reproductive potential agree to comply with protocol-approved double barrier contraceptive method during and for 3 months after study drug administration. The subject is in general good medical health with no clinically significant or relevant abnormalities, including medical history, physical exam, vital signs, ECG, and laboratory evaluations (hematology, chemistry, and urinalysis) as assessed by the Investigator. Exclusion Criteria: History of chronic otitis externa or media, other chronic middle ear disorders, barotrauma, Meniere's disease, endolymphatic hydrops, perilymph fistula, herpes zoster oticus or other infectious etiology of hearing loss. Presence of a genetic, syndromal or developmental auditory disorder or of an autoimmune or serious neurological disorder that could contribute to auditory loss. Evidence of current conductive hearing loss, mixed hearing loss or otosclerosis. History of auditory loss related to exposure to known high-dose ototoxic drugs; any prior exposure to platinum-based medications. Otological disorders that would preclude safe tympanic injection. Presence of a cochlear implant. Evidence of bothersome tinnitus as determined by the Investigator. Intratympanic injection within 6 months of randomization. Use of an investigational product or intervention other than a non-interventional registry study (including vaccine studies) within the greater of 30 days or 5 half-lives (if known) prior to Screening or expected during the study. History of malignancy under current active treatment or considered at substantial risk for progression or recurrence during the study interval, as determined by the Investigator. Note, central nervous system neoplasms or head and neck cancer are excluded from eligibility regardless of treatment status.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PIPE-505<br> | Drug: PIPE-505<br>* Intratympanic injection<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Intratympanic injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety: Treatment-Emergent Adverse Events (TEAE) | Number of participants with TEAEs | From baseline to 3 months follow up | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics: Area under the curve (AUC) |  | From baseline to 3 months follow up | 
| Pharmacokinetics: t1/2 (half life) |  | From baseline to 3 months follow up | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hearing Loss, Cochlear synaptopathy, Deafness, Speech-in-noise hearing difficulty