gms | German Medical Science

Introduction: New insights from recent clinical trials in sudden sensorineural hearing loss (SSNHL) have shown corticosteroids, the standard of care treatment, do not provide a satisfactory outcome for many patients and therefore new therapies are needed. The novel molecule AC102 outperformed corticosteroids in preclinical hearing loss models has entered the clinical stage as a potential therapeutic to address this unmet need.

Here, we discuss the choice of study population and audiological measures which allow the demonstration of safety and clinically meaningful improvement in hearing.

Methods: A Phase 1, placebo-controlled study evaluated safety and tolerability of a single intratympanic (i.t.) injection of AC102 with a dose escalation design. Healthy volunteers were chosen as study population to detect otic effects that might otherwise be masked in hearing loss patients. Beside standard assessments such as otoscopy, tympanometry and pure tone audiometry (PTA), also otoacoustic emissions (TEOAE/DPOAE) and brainstem evoked response audiometry (BERA) were performed to even assess potentially subtle effects on hearing in the 42 volunteers enrolled in the study.

The Phase 2 trial is a randomized, blinded study evaluating the efficacy of i.t. AC102 compared to oral prednisolone (60 mg/day, 14 days). In addition to PTA, word recognition tests in quiet and in noise are performed requiring careful selection of word lists that must be validated and standardized as patients are enrolled at 50 sites throughout Europe. An Excel Inclusion Tool was programmed to automate evaluation of audiological eligibility criteria and facilitate the work for audiologists and study nurses.

Results: Healthy volunteers completed the Phase 1 study without adverse effects on outer (OAEs) or inner hair cell function or any other parts of the audiological pathway (BERA) or vestibular function (vHIT). Transient adverse effects were mainly related to injection procedure (e.g. bleeding, pain) and the gel residing in the middle ear (e.g. lasting ≤4 days) conductive hearing loss).

The Phase 2 study has shown that the use of an Inclusion Tool facilitates patient enrolment. Furthermore, feedback from sites have proven that the chosen measures to standardize word recognition tests across multi languages make it possible to conduct a hearing loss study in a multi-lingual environment such as Europe.

Conclusion: The Phase 1 study has shown that AC102 is safe and well tolerated by healthy volunteers. This pathed the way for a Phase 2 study in which the audiological outcome measures are tailored to allow evaluation of its efficacy compared to corticosteroids in SSNHL patients.