Clinical Trials

Date: 2012-11-13

Type of information: Results

phase: 2b

Announcement: results

Company: Auris Medical (Switzerland)

Product: AM-111

Action mechanism:

• peptide/kinase inhibitor. AM-111 contains the synthetic peptide D-JNKI-1 (D-stereoisomer of c-Jun N-terminal Kinase Inhibitor 1), an inhibitor of the JNK stress kinase coupled to an intracellular transporter. D-JNKI-1 is formulated in a biocompatible and fully biodegradable gel. It is administered by a single dose intratympanic injection into the middle ear. From there the drug diffuses through the round window membrane into the cochlea.
• JNK is a signal transmitting enzyme that regulates a number of important cellular activities, including activation of genes encoding inflammatory molecules or promoting cell death (apoptosis). JNK is activated following various types of cochlear insults (stress) that may lead to acute inner ear hearing loss. AM-111 enters cells and binds to JNK, thereby inhibiting activation of transcription factors such as c-jun and c-fos. This in turn prevents JNK mediated apoptosis and inflammatory response, which could otherwise result in irreversible loss of hair cells and cochlear neurons. AM-111 supports natural recovery processes and helps to prevent or reduce chronic hearing loss.

Disease: acute sensorineural hearing loss (ASNHL)

Therapeutic area: Otorhinolaryngology

Country: Germany, Czech Republic, Poland

Trial details:

• The double-blind, randomized, placebo-controlled phase IIb study with AM-111 was conducted in Germany, Poland and the Czech Republic, involving more than 30 sites. A total of 210 patients suffering from acute acoustic trauma or sudden deafness were enrolled within the first 48 hours following the incident. Their hearing loss, measured against a reference value, had to be at least 30 dB at the average of 3 contiguous audiometric test frequencies. Study participants received one single dose of either AM-111 at 0.4 or 2 mg/ml or placebo by way of i.t. injection and were followed for 90 days. In case of insufficient hearing recovery by Day 7, they were given the option of receiving oral prednisolone as a reserve therapy.

Latest news:

• • On November 13, 2012, Auris Medical has announced positive results from a phase IIb clinical trial with AM-111, its investigational drug for the intratympanic treatment of acute sensorineural hearing loss. The study demonstrated that the treatment was well tolerated and showed a statistically significant and clinically relevant treatment effect. Preliminary results from the phase IIb study show that the local treatment with AM-111 was well tolerated. In addition, the study demonstrated a substantial improvement in hearing threshold and speech discrimination score. In subjects with severe to profound hearing loss who were treated with AM-111 0.4 mg/mL, the primary study endpoint, absolute hearing improvement in the 3 most affected contiguous test frequencies from baseline to Day 7, was met (p < 0.02, compared with placebo). The outcome was confirmed by the co-primary endpoint “% of hearing loss recovered at Day 7” (p < 0.03); the odds ratio for complete hearing recovery was > 2.2. Importantly, the improvement in the speech discrimination score from baseline to Day 7 showed also a statistically significant difference between AM-111 and placebo treated study subjects (p < 0.02). The differences in hearing and speech discrimination recovery between treatment groups appeared as early as on Day 3 and were clinically relevant. Further information on the clinical trial and detailed outcomes shall be presented in a scientific journal. In a next step, Auris Medical is planning to discuss the phase IIb results and further clinical development with AM-111 with regulatory agencies. •  On April 20, 2012,  Auris Medical has announced  that enrolment has been completed for its phase IIb clinical trial with AM-111 for the treatment of ASNHL. A total of 210 patients were enrolled in the study to receive a single dose intratympanic injection of either AM-111 at 0.4 or 2 mg/ml or placebo. The study recruited patients suffering from acute acoustic trauma or sudden deafness with a mean hearing loss of at least 30 dB in 3 contiguous frequencies within the first 48 hours following the incident. Results from the AM-111 trial are expected to become available in fall 2012. • On January 17, 2011, Auris Medical has announced that enrolment has started for the second dose cohort in its phase IIb clinical trial with AM-111 for the treatment of acute sensorineural hearing loss . It is planned to enrol slightly more than 100 patients in the cohort. The inclusion criteria require among others that patients show up for treatment within 48 hours from ASNHL onset and that the average hearing loss is at least 30 dB in 3 contiguous frequencies. Recruitment for the phase IIb trial with AM-111 is expected to be completed in early 2012.

Is general: Yes