Single Intratympanic Injection of Proprietary Brain-Derived Neurotrophic Factor (OTO-413) in Subjects with Speech-in-Noise Hearing Impairment: a Randomized, Dose Escalating, Double-Blind, Placebo-Controlled Phase 1/2 Study

To evaluate the safety and tolerability and exploratory efficacy of OTO-413, an intratympanic-administered, sustained release formulation of brain-derived neurotrophic factor (BDNF) in a thermoreversible gel, in participants with speech-in-noise hearing difficulties.

✦ Clinical Takeaway ✦

No practice change warranted at this stage; this is a Phase 1/2 safety and dose-escalation trial — efficacy data are exploratory and insufficient to inform clinical decisions about treating speech-in-noise impairment.

✦ Why It Matters ✦

OTO-413 represents one of the first pharmacological attempts to restore cochlear synapse function in humans with hidden hearing loss, a condition currently lacking any approved treatment.

✦ Key Points ✦

01Phase 1/2 RCT of OTO-413 (BDNF formulation) delivered via single intratympanic injection.
02Target population: patients with speech-in-noise hearing impairment (potentially 'hidden hearing loss').
03Randomized, double-blind, placebo-controlled, dose-escalating design — methodologically rigorous for an early-phase trial.
04Primary focus is safety and tolerability; efficacy outcomes are exploratory.
05Represents a potentially novel pharmacological approach to cochlear synaptopathy in humans.

✦ Claims & Evidence ✦

ClaimEvidenceSupport

A single intratympanic injection of OTO-413 is being evaluated for safety and tolerability in humans with speech-in-noise hearing impairment.

studysupported

OTO-413 (BDNF formulation) may improve speech-in-noise hearing ability.

studyunclear

✦ Research metadata ✦

PMID: 42479273
DOI: 10.1007/s10162-026-01061-z.
Journal: JARO - Journal of the Association for Research in Otolaryngology
Publication type: research_article
Evidence level: 1b
Population: Adults with speech-in-noise hearing impairment (suspected cochlear synaptopathy / hidden hearing loss)
Intervention: Single intratympanic injection of OTO-413 (proprietary BDNF formulation) at escalating doses
Comparator: Placebo (intratympanic injection)

Primary outcomes

Safety and tolerability of OTO-413; Exploratory efficacy on speech-in-noise hearing measures

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