Biomedical Catalyst – Clinical proof of concept trial of a Kv3 modulator for the treatment of tinnitus

Tinnitus is a chronic, under-recognised condition that affects over 10% of adults, causing significant suffering. There are no approved drugs and current treatments, such as counselling, only help patients to cope with symptoms. This project will provide clinical proof-of-concept evaluation of the efficacy of a novel ion channel drug in patients with tinnitus. AUT00063, currently completing Phase I trials, is being developed by Autifony Therapeutics for the treatment of age-related hearing loss; however, there is a strong scientific rationale to suggest potential for the drug to help control tinnitus. Autifony will work in collaboration with leading tinnitus expert, Prof Deborah Hall, Director and Research lead for Tinnitus aetiology and management at the National Institute for Health Research, Nottingham Hearing Biomedical Research Unit, University of Nottingham, on this clinical trial as a major step towards potentially the first effective oral drug to treat tinnitus.

The trial is a proof-of-concept Phase II efficacy and safety study of AUT00063 in patients with tinnitus arising from age-related or noise-induced cochlear damage. The trial will evaluate the ability of the drug to alleviate tinnitus, measured using a self-report scale, the Tinnitus Functional Index (TFI, Meikle et al., 2012 Ear Hear 33:153-76), following 4 weeks of treatment. The trial will have a randomised, double-blind, placebo-controlled, 3-arm parallel-group design testing two doses of AUT00063 (400 and 600mg) vs placebo. Secondary objective markers of efficacy will also be used to address scientific and mechanistic questions concerning the nature of tinnitus and the actions of the drug within the central auditory system. These will include measures of tinnitus loudness (Henry et al., 2013 J Rehab Res Dev 50:573-4) and change in electrophysiological correlates at both brainstem and cortical levels (auditory brainstem response, Schaette and McAlpine 2011 J Neurosci 31:13452-57, and resting state EEG, Adjamian et al., 2012 JARO 13:715-31). Historically, the quality of tinnitus trials has been poor (Hoare et al., 2012 JARO 13: 543-59). Our innovative trial design aims to address the weakness of previous tinnitus trials by implementing gold-standard methodologies. Importantly, two interim analyses will be conducted using an Independent Data Management Committee (IDMC) to test for trial futility, and to allow for adaptation of recruitment to favour inclusion of likely responders. i