http://ir.aurismedical.com/phoenix.zhtml?c=253572&p=irol-newsArticle&ID=2263955
Auris Medical Reports Key Results from Keyzilen® AMPACT2 Open-Label Extension Study
"We are very pleased that AMPACT2 provides further evidence of good tolerance and safety for Keyzilen® and shows this, for the first time, also for chronic intermittent use," commented Thomas Meyer, Auris Medical's founder, Chairman and Chief Executive Officer. "In addition, the exploratory efficacy data from AMPACT2 lend further support to our therapeutic approach of treating tinnitus early, while the symptom is still of peripheral rather than central character." In 2015, an interim analysis of data from patients with post-acute tinnitus in TACTT3 provided first suggestions that improvements were more pronounced the earlier they had enrolled in the trial.
AMPACT2 is one of two open-label extension studies with Keyzilen® that were conducted at the request of the US Food and Drug Administration (FDA) to generate safety data from chronic intermittent use of Keyzilen® for up to 12 months. Participants who completed the TACTT3 trial were offered the option to roll over into AMPACT2, while still blinded to the treatment allocation. Patients were given the choice to receive up to three treatment cycles with each cycle comprising three intratympanic administrations of Keyzilen®, followed by a treatment-free observation period of 12 weeks. Of the approximately 660 patients enrolled in the TACTT3 trial up to June 2016, 485 patients rolled over into AMPACT2 and provided safety data; 422 of these patients provided exploratory efficacy data. At the time of enrollment into AMPACT2, all patients were in the post-acute stage; approximately half were from Stratum A (originally enrolled in TACTT3 during the acute stage; i.e. up to three months from onset) and the other half were from Stratum B (originally enrolled during the post-acute stage; i.e. between three and 12 months from onset).
The primary safety endpoint of AMPACT2 was the incidence of clinically relevant hearing deterioration five weeks after the start of a treatment cycle. In line with the results from previous trials with Keyzilen®, such incidence was low, amounting to 4-8% with no significant difference between one, two or three treatment cycles. During the course of AMPACT2, the patients' hearing threshold at the average of 4, 6 and 8 kHz was stable. The vast majority of adverse events that were considered related to the study drug or treatment procedure were rated as either mild or moderate in intensity. Seven patients experienced a total of eight non-fatal, serious adverse events, none of which was considered related to the study drug. Confirming previous data, 96-98% of tympanic membranes were already closed at the time of the first follow-up visit.
Exploratory efficacy analyses of AMPACT2 show improvements in the Tinnitus Functional Index (TFI) that were more pronounced for Stratum A patients compared to Stratum B patients. For Stratum A patients, the TFI decreased on average by 7.6 points (95% confidence interval 5.5 to 9.6; baseline of 40.3 points) to the last follow-up visit. For Stratum B patients, the TFI decreased on average by 3.5 points (1.4 to 5.6; baseline of 42.3 points) when enrolled in TACTT3 between three and six months from onset and by 2.5 points (-1.1 to 6.1; baseline of 45.3 points) when enrolled in TACTT3 between six and 12 months from onset.
Auris Medical expects to announce results from AMPACT1, the open-label extension study related to TACTT2, later this quarter. TACTT3 has been extended to recruit an additional 60 patients in each of Stratum A and B, and enrollment is ongoing; top-line results are expected in early 2018. As recruitment for AMPACT2 has completed, the open-label extension is not offered to patients currently enrolling in the extended TACTT3 trial.
Auris Medical Reports Key Results from Keyzilen® AMPACT2 Open-Label Extension Study
- Trial outcomes show positive safety profile of Keyzilen® for chronic intermittent use
- Exploratory efficacy results support therapeutic concept of early tinnitus treatment
"We are very pleased that AMPACT2 provides further evidence of good tolerance and safety for Keyzilen® and shows this, for the first time, also for chronic intermittent use," commented Thomas Meyer, Auris Medical's founder, Chairman and Chief Executive Officer. "In addition, the exploratory efficacy data from AMPACT2 lend further support to our therapeutic approach of treating tinnitus early, while the symptom is still of peripheral rather than central character." In 2015, an interim analysis of data from patients with post-acute tinnitus in TACTT3 provided first suggestions that improvements were more pronounced the earlier they had enrolled in the trial.
AMPACT2 is one of two open-label extension studies with Keyzilen® that were conducted at the request of the US Food and Drug Administration (FDA) to generate safety data from chronic intermittent use of Keyzilen® for up to 12 months. Participants who completed the TACTT3 trial were offered the option to roll over into AMPACT2, while still blinded to the treatment allocation. Patients were given the choice to receive up to three treatment cycles with each cycle comprising three intratympanic administrations of Keyzilen®, followed by a treatment-free observation period of 12 weeks. Of the approximately 660 patients enrolled in the TACTT3 trial up to June 2016, 485 patients rolled over into AMPACT2 and provided safety data; 422 of these patients provided exploratory efficacy data. At the time of enrollment into AMPACT2, all patients were in the post-acute stage; approximately half were from Stratum A (originally enrolled in TACTT3 during the acute stage; i.e. up to three months from onset) and the other half were from Stratum B (originally enrolled during the post-acute stage; i.e. between three and 12 months from onset).
The primary safety endpoint of AMPACT2 was the incidence of clinically relevant hearing deterioration five weeks after the start of a treatment cycle. In line with the results from previous trials with Keyzilen®, such incidence was low, amounting to 4-8% with no significant difference between one, two or three treatment cycles. During the course of AMPACT2, the patients' hearing threshold at the average of 4, 6 and 8 kHz was stable. The vast majority of adverse events that were considered related to the study drug or treatment procedure were rated as either mild or moderate in intensity. Seven patients experienced a total of eight non-fatal, serious adverse events, none of which was considered related to the study drug. Confirming previous data, 96-98% of tympanic membranes were already closed at the time of the first follow-up visit.
Exploratory efficacy analyses of AMPACT2 show improvements in the Tinnitus Functional Index (TFI) that were more pronounced for Stratum A patients compared to Stratum B patients. For Stratum A patients, the TFI decreased on average by 7.6 points (95% confidence interval 5.5 to 9.6; baseline of 40.3 points) to the last follow-up visit. For Stratum B patients, the TFI decreased on average by 3.5 points (1.4 to 5.6; baseline of 42.3 points) when enrolled in TACTT3 between three and six months from onset and by 2.5 points (-1.1 to 6.1; baseline of 45.3 points) when enrolled in TACTT3 between six and 12 months from onset.
Auris Medical expects to announce results from AMPACT1, the open-label extension study related to TACTT2, later this quarter. TACTT3 has been extended to recruit an additional 60 patients in each of Stratum A and B, and enrollment is ongoing; top-line results are expected in early 2018. As recruitment for AMPACT2 has completed, the open-label extension is not offered to patients currently enrolling in the extended TACTT3 trial.
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