ORCID

0000-0002-5247-8562 (Volsky)

Document Type

Article

Publication Date

2026

DOI

10.1007/s10162-026-01061-z

Publication Title

Journal of the Association for Research in Otolaryngology

Volume

Advance online publication

Pages

17 pp.

Abstract

Purpose

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.

Methods

This was a single dose, dose-ascending, randomized, double-blind, Placebo-controlled Phase 1/2 study conducted at 7 enrolling clinical sites in the U.S. 110 participants (56% female) enrolled had self-reported speech-in-noise (SIN) difficulties that were confirmed by a SIN test and were randomized to OTO-413 or Placebo. OTO-413 dose range was escalated from 0.01 mg to 1.5 mg within 7 Cohorts. Safety evaluations included monitoring for treatment-emergent adverse events, physical and audiological examinations, and monitoring for plasma BDNF and anti-BDNF antibodies. Exploratory efficacy outcomes included three SIN tests with the Digits-in-Noise Test (DIN), Words in Noise Test (WIN), and the American English Matrix Test (AEMT) and self-reported Patient Global Impression of Change (PGIC).

Results

There were no study drug-related serious adverse events, and no audiometric safety concerns at any OTO-413 dose. Plasma levels of BDNF were comparable to endogenous levels of BDNF and anti-BDNF antibodies were not detected. An exploratory responder analysis indicated a numerical advantage for OTO-413 versus placebo over the three months of observation. Improvement was particularly evident with the WIN at the 0.3 mg dose. No improvement in PGIC was noted.

Conclusion

This exploratory study demonstrated that a single intratympanic injection of OTO-413 was safe and well tolerated and provided evidence for a SIN hearing treatment benefit of 0.3 mg OTO-413.

Trial Registration

NCT04129775.

Rights

© 2026 The Authors.

This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original authors and the source, provide a link to the Creative Commons license, and indicate if you modified the licensed material. You do not have permission under this license to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder.

Data Availability

Article states: "Due to the patient consent conditions under which this clinical trial was conducted, individual patient data cannot be made available beyond that presented in the manuscript."

Original Publication Citation

Foster, A. C., Anderson, J. J., Moore, D. R., Fuentes, M. O., Wang, Y., Volsky, P. G., Boyev, K. P., & Sanchez, V. A. (2026). 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. Journal of the Association for Research in Otolaryngology. Advance online publication. https://doi.org/10.1007/s10162-026-01061-z

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