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Purpose <p>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.</p> Methods <p>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&#xa0;mg to 1.5&#xa0;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).</p> Results <p>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&#xa0;mg dose. No improvement in PGIC was noted.</p> Conclusion <p>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&#xa0;mg OTO-413.</p> Trial registration <p>NCT04129775.</p>

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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

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  • 发表日期：

    2026年7月21日

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  • Alan C. Foster,
  • Jeffery J. Anderson,
  • David R. Moore,
  • Morgan Oktela Fuentes,
  • Yiwei Wang,
  • Peter G. Volsky,
  • K. Paul Boyev,
  • Victoria A. Sanchez

摘要

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.