(380) Phase I and II Clinical Trial for AC102 Treating SSNHL

Introduction: Sudden Sensorineural Hearing Loss (SSNHL) is a serious condition that often has severe psychosocial consequences. While the causes are often unknown, there is consensus that they include permanent loss of outer hair cells (OHCs) and synaptic disconnection of inner hair cells (IHCs) from the auditory nerve. Currently, SSNHL is mostly treated with steroids, which lack reliable efficacy data and are therefore not approved for the treatment of SSNHL. AC102 almost completely reversed noise-induced hearing loss in preclinical models by counteracting apoptotic death of OHCs and reversing synaptic disconnection of IHCs, making it a promising drug candidate for the treatment of SSNHL.

Methods: In the Phase I clinical trial, AC102 was compared to placebo in healthy volunteers who received either placebo or AC102 by a single intratympanic (IT) injection into one ear at increasing concentrations and volumes. Safety and tolerability of AC102 were evaluated, including audiologic and vestibular function. The randomized, blinded, two-arm Phase II clinical trial is comparing AC102 to systemic steroid treatment in patients with SSNHL. Half of the subjects will receive a single injection of AC102 into one ear along with an oral placebo. The other half will receive a placebo injection and oral prednisolone, the standard of care. Primary endpoints are improvement in pure tone audiometry (PTA) results and speech recognition.

Results: In the Phase I clinical trial, AC102 elicited only mild and transient Treatment-Emergent Adverse Events (TEAEs) with only low systemic drug concentrations. The Phase II study is currently ongoing in 7 European countries, including Germany, the Netherlands, Austria, Serbia, Poland, the Czech Republic and Bulgaria. Several of up to 200 patients have been enrolled.

Conclusions: After evaluating the safety and good tolerability of AC102, the current Phase II trial may prove its efficacy in patients as demonstrated in preclinical models. AC102 is therefore a promising therapeutic candidate to address the significant unmet medical need of patients with SSNHL.