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Efficacy and Safety of AM-111 in the Treatment of Acute Sensorineural Hearing Loss: A Double-Blind, Randomized, Placebo-Controlled Phase II Study

Suckfuell, Markus*; Lisowska, Grazyna; Domka, Wojciech; Kabacinska, Anna§; Morawski, Krzysztof; Bodlaj, Robert; Klimak, Petr#; Kostrica, Rom**; Meyer, Thomas††

doi: 10.1097/MAO.0000000000000466
Sensorineural Hearing Loss & Tinnitus

Objective: To evaluate the efficacy and safety of AM-111, a c-Jun N-terminal Kinase (JNK) ligand, in patients with acute sensorineural hearing loss (ASNHL).

Study Design: Prospective, double-blind, randomized, placebo-controlled study with follow-up visits on Days 3, 7, 30, and 90.

Setting: Twenty-five European sites (academic tertiary referral centers, private ENT practices).

Patients: Approximately 210 patients aged 18 to 61 years presenting within 48 hours after acute acoustic trauma or idiopathic sudden sensorineural hearing loss with mean hearing loss of 30 dB or greater at the 3 most affected contiguous test frequencies.

Interventions: Single-dose intratympanic injection of AM-111 (0.4 or 2.0 mg/ml) or placebo; optionally, oral prednisolone if hearing improvement was less than 10 dB at Day 7.

Main Outcome Measures: Efficacy was assessed by absolute hearing improvement (primary end point, Day 7), percentage hearing improvement, complete hearing recovery, speech discrimination improvement, and complete tinnitus remission. Safety was evaluated by the frequency of clinically relevant hearing deterioration and adverse events.

Results: The study failed to demonstrate a treatment benefit for the entire study population because mild-to-moderate ASNHL cases showed unexpectedly strong spontaneous recovery. In severe-to-profound ASNHL patients (threshold ≥60 dB), AM-111 0.4 mg/ml showed statistically significant, clinically relevant, and persistent improvements in hearing and speech discrimination and higher tinnitus remission compared with placebo. The study drug and the intratympanic injections were well tolerated.

Conclusion: The study established proof of concept for AM-111 in the treatment of severe-to-profound ASNHL. Control for spontaneous hearing recovery is essential for ASNHL studies.

*Department of ENT, Head and Neck Surgery, Martha Maria Hospital, Munich, Germany; †Department of Otolaryngology in Zabrze, Medical University of Silesia, Katowice; ‡Department of Otolaryngology, District Specialist Hospital, Rzeszow; §Department of Otolaryngology and ENT Oncology, Pomeranian Medical University, Szczecin; ∥Department of Otolaryngology, Medical University of Warsaw, Warsaw, Poland; ¶Private ENT practice, Lichtenfels, Germany; #Department of ENT, Head and Neck Surgery, Regional Hospital, Kladno; **Department of ENT, Head and Neck Surgery, Masaryk University, Brno, Czech Republic; and ††Auris Medical AG, Basel, Switzerland

Address correspondence and reprint requests to Thomas Meyer, Ph.D., Auris Medical AG, Falknerstrasse 4, 4001 Basel, Switzerland; E-mail: tm@aurismedical.com

The study was supported in full by Auris Medical AG. M. S. received honoraria from the Sponsor as medical expert in discussions with a regulatory body and as safety officer for an unrelated study. T. M. is the Managing Director and a major shareholder of Auris Medical AG.

The other authors disclose no conflicts of interest.

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