Suckfuell Markus, Lisowska Grazyna, Domka Wojciech, Kabacinska Anna, Morawski Krzysztof, Bodlaj Robert, Klimak Petr, Kostrica Rom, Meyer Thomas
*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.
Otol Neurotol. 2014 Sep;35(8):1317-26. doi: 10.1097/MAO.0000000000000466.
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).
Prospective, double-blind, randomized, placebo-controlled study with follow-up visits on Days 3, 7, 30, and 90.
Twenty-five European sites (academic tertiary referral centers, private ENT practices).
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.
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.
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.
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.
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.
评估c-Jun氨基末端激酶（JNK）配体AM-111治疗急性感音神经性听力损失（ASNHL）患者的疗效和安全性。
前瞻性、双盲、随机、安慰剂对照研究，在第3、7、30和90天进行随访。
25个欧洲地点（学术三级转诊中心、私立耳鼻喉科诊所）。
约210名年龄在18至61岁之间的患者，在急性声创伤或特发性突发感音神经性听力损失后48小时内就诊，在3个受影响最严重的连续测试频率下平均听力损失30dB或更高。
单剂量鼓室内注射AM-111（0.4或2.0mg/ml）或安慰剂；如果第7天听力改善小于10dB，可选择口服泼尼松龙。
疗效通过绝对听力改善（主要终点，第7天）、听力改善百分比、完全听力恢复、言语辨别改善和耳鸣完全缓解来评估。安全性通过临床相关听力恶化和不良事件的发生率来评估。
该研究未能证明对整个研究人群有治疗益处，因为轻度至中度ASNHL病例显示出意外强烈的自发恢复。在重度至极重度ASNHL患者（阈值≥60dB）中，与安慰剂相比，0.4mg/ml的AM-111在听力和言语辨别方面显示出统计学上显著的、临床相关的和持续的改善，耳鸣缓解率更高。研究药物和鼓室内注射耐受性良好。
该研究确立了AM-111治疗重度至极重度ASNHL的概念验证。对于ASNHL研究，控制自发听力恢复至关重要。
