title: Efficacy and safety of AM-111 in the treatment of acute sensorineural hearing loss: a double-blind, randomized, placebo-controlled phase II study.
abstract: 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).
  
  
  METHODS
  Prospective, double-blind, randomized, placebo-controlled study with follow-up visits on Days 3, 7, 30, and 90.
  
  
  METHODS
  Twenty-five European sites (academic tertiary referral centers, private ENT practices).
  
  
  METHODS
  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.
  
  
  METHODS
  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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors: *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.
authors: Markus
authors: M
authors: Suckfuell
authors: Grazyna
authors: G
authors: Lisowska
authors: Wojciech
authors: W
authors: Domka
authors: Anna
authors: A
authors: Kabacinska
authors: Krzysztof
authors: K
authors: Morawski
authors: Robert
authors: R
authors: Bodlaj
authors: Petr
authors: P
authors: Klimak
authors: Rom
authors: R
authors: Kostrica
authors: Thomas
authors: T
authors: Meyer
mesh_terms: D000293:Adolescent; D000328:Adult; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006319:Hearing Loss, Sensorineural / Q000188:drug therapy*; D003639:Hearing Loss, Sudden / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D018696:Neuroprotective Agents / Q000008:administration & dosage* / Q000009:adverse effects; D010455:Peptides / Q000008:administration & dosage* / Q000009:adverse effects; D011446:Prospective Studies; D014012:Tinnitus / Q000188:drug therapy; D016896:Treatment Outcome; D014432:Tympanic Membrane / Q000187:drug effects; D055815:Young Adult
chemical_list: D018696:Neuroprotective Agents; D010455:Peptides; C478085:D-JNKI-1