Neither dose of AM-111 (Auris Medical Holding) led to a statistically significant improvement in hearing among patients with severe to profound sudden deafness in the HEALOS phase 3 clinical trial, the company says. However, one subgroup did show a benefit.
Auris announced that top-line results from the HEALOS trial showed AM-111 did not meet the primary efficacy endpoint of a statistically significant improvement in hearing from baseline to day 28 compared with placebo for either active treatment group. However, a post-hoc analysis of the subpopulation with profound acute hearing loss revealed a clinically and statistically significant improvement in the AM-111 0.4 mg/mL treatment group.
HEALOS is a randomized, double-blind, placebo-controlled study evaluating the efficacy, safety, and tolerability of AM-111. The trial was conducted in several European and Asian countries and enrolled 256 patients suffering from severe to profound sudden deafness within 72 hours from onset. Patients were randomized in a 1:1:1 ratio to receive a single dose of AM-111 0.4 mg/mL, AM-111 0.8 mg/mL, or placebo, administered into the middle ear.
The hearing improvement at the three worst affected contiguous test frequencies at day 28 was 38.4 dB for patients in the AM-111 0.4 mg/mL group compared with 33.4 dB for the placebo group (P = 0.226). For patients in the AM-111 0.8 mg/mL group the improvement was 36.6 dB (P = 0.448).
Post-hoc analysis in the subpopulation of patients with profound hearing loss (n = 98) showed an improvement at day 28 of 42.7 dB in the AM-111 0.4 mg/mL group versus 26.8 dB in the placebo group, which was statistically significant (P = 0.0176). The improvement was 37.3 dB in the AM-111 0.8 mg/mL group (P = 0.126).
AM-111 was well tolerated, and the primary safety endpoint was met. There was no significant difference in the occurrence of clinically relevant hearing deterioration between either of the active treated groups and the placebo group at day 28.
Based on the findings from the HEALOS trial, Auris has concluded that the very similar design of the currently ongoing ASSENT trial is no longer adequate for testing AM-111. The ASSENT trial will be terminated early.
Source: Auris Medical; November 28, 2017.