Well, here's the first specific information that I am aware of on Audion's clinical trial: http://www.isrctn.com/ISRCTN59733689
Like the Genvec trial, it is a Phase 1/2 trial which is why they talked about starting Phase 1 and Phase 2 in 2017 (though in one place they say it starts in 2016 and ends in 2017). The "intention to publish" date is January 2020. As is standard, part (phase) 1 is the safety trial and part (phase) 2 is efficacy. There is no placebo.
They are using the Notch inhibitor LY3056480. I have not found any information about this drug yet. As expected, the hypothesis is "LY3056480 may induce transdifferentiation of supporting cells into inner-ear hair cells and lead to a subsequent improvement of hearing in patients with sensorineural hearing loss (SNHL)." Thus, if this works it will directly transform supporting cells into hair cells.
Planned enrollment is 62.
Part 1 will be a series of 3 injections. It looks like they are starting at 25 micrograms, and the first people will get 3 injections at that level. Like Genvec they are using "ascending dose cohorts". So there will be a cohort (of unknown size at this point) at 25, then cohorts at 125, 200, and 250 micrograms. They are looking for the "Maximum Tolerated Dose". (It is not clear how they are determining this.)
In the second part (phase) participants are randomized to receive either the MTD or one dose below that. The idea is to look at efficacy at the MTD but to also look for a dose-response effect - is there a bigger effect at MTD compared to one dose below? (The highest tolerated dose may not be the most effective.) It looks like part 2 is another series of injections: "Injections are delivered in the same process as the first part of the study."
What isn't clear is whether the Part 1 participants also participate in Part 2 or if the Part 2 participants are new. It would make sense that the Part 2 participants would be new, but the Plain English Summary says "If participants find their maximum tolerated dose (MTD) then they are enrolled in the second part of the study." This suggests a patient specific MTD and that the same people are in both parts. We will have to see when more information becomes available.
Inclusion criteria:
1. Male or female between 18 and 80 years of age
2. A primary complaint of hearing loss of ˂ 10 years in duration, the history suggesting this hearing-loss to be of age-related, noise-induced or idiopathic origin
3. A bilateral, symmetrical (<15 dBHL difference) SNHL with a pure-tone average threshold across the frequencies 0.5, 1, 2, 4 and 8 kHz of between 25 and 60 dBHL with 2 or more frequencies less than 60 dBHL
Exclusion criteria:
1. Presenting with a primary complaint of tinnitus
2. A 'true' air-bone gap >15 dBHL in 3 or more contiguous frequencies between 0.5, 1, 2, 4 kHz
3. History of suspected or diagnosed genetic cause of hearing loss
4. Suspected or known diagnosis of inner ear pathology, congenital hearing loss, fluctuating hearing loss, Ménière's disease, or secondary endolymphatic hydrops, perilymph fistula, cochlear barotrauma, autoimmune hearing loss, radiation-induced hearing loss, retro-cochlear lesion
5. Evidence of acute or chronic otitis media or otitis externa on examination; or a history of middle ear pathology and/or surgery
6. Any therapy known as ototoxic within 12 months of screening
Like the Genvec trial, it is a Phase 1/2 trial which is why they talked about starting Phase 1 and Phase 2 in 2017 (though in one place they say it starts in 2016 and ends in 2017). The "intention to publish" date is January 2020. As is standard, part (phase) 1 is the safety trial and part (phase) 2 is efficacy. There is no placebo.
They are using the Notch inhibitor LY3056480. I have not found any information about this drug yet. As expected, the hypothesis is "LY3056480 may induce transdifferentiation of supporting cells into inner-ear hair cells and lead to a subsequent improvement of hearing in patients with sensorineural hearing loss (SNHL)." Thus, if this works it will directly transform supporting cells into hair cells.
Planned enrollment is 62.
Part 1 will be a series of 3 injections. It looks like they are starting at 25 micrograms, and the first people will get 3 injections at that level. Like Genvec they are using "ascending dose cohorts". So there will be a cohort (of unknown size at this point) at 25, then cohorts at 125, 200, and 250 micrograms. They are looking for the "Maximum Tolerated Dose". (It is not clear how they are determining this.)
In the second part (phase) participants are randomized to receive either the MTD or one dose below that. The idea is to look at efficacy at the MTD but to also look for a dose-response effect - is there a bigger effect at MTD compared to one dose below? (The highest tolerated dose may not be the most effective.) It looks like part 2 is another series of injections: "Injections are delivered in the same process as the first part of the study."
What isn't clear is whether the Part 1 participants also participate in Part 2 or if the Part 2 participants are new. It would make sense that the Part 2 participants would be new, but the Plain English Summary says "If participants find their maximum tolerated dose (MTD) then they are enrolled in the second part of the study." This suggests a patient specific MTD and that the same people are in both parts. We will have to see when more information becomes available.
Inclusion criteria:
1. Male or female between 18 and 80 years of age
2. A primary complaint of hearing loss of ˂ 10 years in duration, the history suggesting this hearing-loss to be of age-related, noise-induced or idiopathic origin
3. A bilateral, symmetrical (<15 dBHL difference) SNHL with a pure-tone average threshold across the frequencies 0.5, 1, 2, 4 and 8 kHz of between 25 and 60 dBHL with 2 or more frequencies less than 60 dBHL
Exclusion criteria:
1. Presenting with a primary complaint of tinnitus
2. A 'true' air-bone gap >15 dBHL in 3 or more contiguous frequencies between 0.5, 1, 2, 4 kHz
3. History of suspected or diagnosed genetic cause of hearing loss
4. Suspected or known diagnosis of inner ear pathology, congenital hearing loss, fluctuating hearing loss, Ménière's disease, or secondary endolymphatic hydrops, perilymph fistula, cochlear barotrauma, autoimmune hearing loss, radiation-induced hearing loss, retro-cochlear lesion
5. Evidence of acute or chronic otitis media or otitis externa on examination; or a history of middle ear pathology and/or surgery
6. Any therapy known as ototoxic within 12 months of screening
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