Autifony Therapeutics Phase II Study for AUT00063, for the Treatment of Hearing Loss and Tinnitus

I've been in contact with Autifony and here is what they've told me so far:
(if anybody here has any good questions or worthwhile suggestions for Autifony, I'll be glad to forward and could act as official TT liason to Autifony )
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We do certainly wish to put subjects on study who are bothered by their tinnitus. Were they not to be bothered by it we don’t believe they would enroll in the study when they see all the time they would have to commit, and neither would we anticipate significant change on the TFI score - the primary endpoint!
Key point is that we have no prior knowledge of CNS drug interactions (except the laboratory tests that we have carried out) and any subject taking “heavyweight” CNS drugs will be excluded; they may become more sedated or fatigued. If they maybe need a low dose of, for example, a tricyclic at night would be OK but subjects who need significant antidepressants will not be OK for this first study. Obviously if they are not bothered by it then they will not fulfill the TFI entry criteria. Later on when we have more experience of CNS drug interactions then we hope that things will open up for a wider range of co-medications as well as other CNS pathologies.
We believe that the key to getting an answer in this study is to manage out heterogeneity. We shall be doing this in a variety of ways including stratifying for various parameters on study entry and balancing these across drug and placebo. One stratification variable is the severity of the tinnitus as measured by the TFI. All the experts, as well as the statistician, advised that we should NOT include all severeties of tinnitus but should instead have two (arbitrary) levels, mild to moderate (TFI 24-35) and moderate to severe (36-68). This we have done. They likened this to testing, for example, an antihypertensive where it is usual to start with less severe disease and work up as we build the knowledge, confirm the dosage levels etc etc.
- the second answer is that the experts advised that subject experiencing tinnitus severity >68 on the TFI score are almost “always” using something else to cope with their disturbed lives - usually antidepressants along with various pieces of equipment. This would likely render them subject to exclusion criteria. I realise that this is not totally categoric but we decided to draw the line as in the heterogeneity argument above.
I hope this seems clear even though it is a pragmatic way forward in an area of ignorance over exactly how best to test the medication. We did consider only mild, or only moderate tinnitus, only age-related, only noise-induced etc etc and we let the experts guide us here. We shall next year be looking at working up a study, for example with the military, evaluating 063 in noise-induced tinnitus with virtually no hearing loss but severe tinnitus…..again all under careful consideration. We are also talking next month with the the two largest VA centres in the US about possible work with them.

I value all your interest as well as feedback and ideas!
Many thanks and regards.

 

No hearing loss, but I guess I should really wait until the drug is fully released to find out if it'll work, despite this....

 

I love the way that basically, to summarize what Autifony are effectively saying, is they are not looking to allow the people MOST at need to participate - basically those who are severely effected by their tinnitus or who have had it a long time can just carry on and suffer while the newbs and people not that bothered by it can come on down and particiapte..... x 1000000000000000000000000000 doesn't even begin to express my ffrustration

Before anyone lectures me I KNOW they have their reasons...I know, I know

 

Lol...probably the only time ever someone has seemed genuinely disappointed not to have hearing loss

 

I totally understand your frustration, but lets look at it from their angle.
All they want to achieve at this point is to prove the drug works. They don't want to mess with severe cases because in layman's terms - we have too much shit going on. Another important reason is that they have no idea at what dose this drug is needed to help very severe tinnitus and for how long.
So as an example when they studied antihypertensives, they studied the milder cases first to establish dosaging and then moved on to more severe cases.
So in short they want to reduce variables as much as possible to compare this med against placebo.
By eliminating very severe cases they eliminate a variable and at the same time reduce wasting their time excluding all the hard cases that most likely are on hard medications to try to survive and also doing other sorts of therapies such as TRT and sound therapies -which would interfere with the study.

 

As someone else pointed out earlier on this thread, their intention at this point is not to help people, its to move this drug onto the market.

 

Look at it this way. Autifony believes their drug can help two groups of people:

1. Those with tinnitus
2. Those with hearing loss

Instead of conducting TWO clinical trials, they are conducting ONE. They evidently don't have the funding to afford two simultaneous trials, so instead of delaying further than they have to, they've elected to test both theories at the same time. We have to be realistic. They're trying to test a drug that could help 1/10th of the world population. That's about 700,000,000 people.

Are they supposed to have a survey to find our who among those 7 million need their drug the most? Are they supposed to pick the most difficult cases, the cases where they either run the risk of failure or are forced to extend the trial period to two, three, or six months?

Autifony is testing their drug in the fastest, most efficient way possible. They're not a government agency with unlimited resources. They're not big pharma. They're a small group of doctors and scientists with a research grant.

All this waiting is tough. But at least we have something to wait for.

 

That's what I said.

 

One of the eligibility criteria is hearing loss across the spectrum > 20db and < 60db. I asked my audiologist if I have hearing loss that fits the criteria. Her answer was what i wrote above... i.e. The criteria essentially describes somebody with a mild to moderate loss across the whole spectrum.

Most t sufferers don't fit this profile so i don't understand why this is a criteria. One person said they have probably combined the T trial and hearing loss trial in one for cost purposes. So two birds with one stone. Still it pisses me off because I was holding out for this for most T sufferers. Now we have to have hearing loss across the spectrum to get on

 

Jesus man, they'll get to us when the drug is proven effective in phase two study. We should encourage them to find the best people so they can prove it's efficiency to appease investors. I'm sorry if you can't be cured right away, remember some of us have had this longer than you.

 

Wow. Lose the judgement please. We are all suffering here and not in competition. Yes, I want a chance to get rid of this life demolishing 9 out of 10 T now.

 

I think the standard assumption is that most tinnitus sufferers do have mild to moderate hearing loss. A more sophisticated understanding would probably take in hearing loss outside of the test spectrum. They're going by ENT/audiologist norms.

 

Some more details. A bombshell for those hoping to travel, but some optimism as well. Get in there NHS patients and get results!

I asked about the hearing loss requirement in my reply, so will let you know if Dr Harris gets back to me with further details.

 

Disappointing

 

Just my opinion but I think some of you are setting yourselves up for some major disappointment if you happen to get on the trial and then receive the placebo, even though it would be good to get a few of us on so we can get some news good or bad before they release there findings, but even then we won't know if it's placebo or what so I think it is best not to get too excited, for me anyhow!

Even though I am suffering with this T and am more or less just existing rather than living I am just looking forward to the results of this trial and really hoping that it is successful.
At least then we know that it will just be a matter of a few years and all our suffering will be over!

 

the most disappointing aspect of the stringent criteria for the study is that very few people will qualify, and it will probably take a long time (thankfully there are only 152 spots). Whats the probability that a TinnitusTalk member will get in? For instance, with AM-101 I thought that the trial centers would be bombarded with people but apparently getting trial participants takes a long time. I think the trial location I went to said they would 'try' to take 10 participants total (as if even that number were too high). More so than that, it is very hard to get any feedback from people that go through the trials (e.g., AM-101 thread), and it doesn't seem as though there are any TinnitusTalk members that will qualify and report back. It would suck to not get any info about how the trial is going, because I have a feeling Autifony will not disclose much information for the trial duration. The reason I would like feedback is my decision to take retigabine depends partly on this trial (others on this forum might be in a similar situation). We need some TinnitusTalk confederates in this trial..... .

 

Who on earth would allow something like this?
What is the point to have it on the market if it doesn't help?

 

Valeri, what I meant was at this stage their primary goal is to get this drug approved and they have 4 weeks to show it works.

 

Nearly everyone with T has hearing loss.
Because the overactive neurons fire on those frequencies which are lost.
So nearly everyone will qualify. I cannot join since I live in Germany.
The thing that makes me most frustrating:
- If no one from here can join this, it will take a long time until we know if it works or not work
- Maybe for the long time sufferers, it will be too late (although benryu said it will work for chronic T, too).
- We all put much hope into this. If it will not work, what then? I don't need another disappointment at the moment.

 

If this doesn't work... I don't know, I don't know

 

We all put our hope in this. But for sure they are on the right way. Retigabine proved that potasium channel modulators are they key, We can only step forward in the right direction, i think its a matter of time

About the hearing lost test, @Martin69 you are right, but you forgot to mention the exception: Test is only made to frequencies till 8k, And some people have T in higher frequencies, Humans hear until 16k or so. Those can pass the test even with high T

 

There are tests available up to 16 kHz. But most tests go only up to 8 kHz since speech area is from 500 to 4000.
So if you do not hear above 8 kHz, it most probably doesn't matter.
You can make a test yourself by listening to audio tests on the web.
If I find a dog whistle tone where my T is, I cannot hear the dog whistle, only when tuned very loud.
But of course I also know people who have T in low area and no hearing loss.

Regarding the potassium channel modulators. Yes. I really hope they find the key.

 

Yes. This is the big downside. You set hope into something and this keeps you fighting.
It is like a good movie where the heros face challenges they could never overcome. Then they made it through the first and the next one is even more difficult and so on. And at the end, there is a happy end.
I hope we all see this happy end, too.

 

This might be the case but not across the whole spectrum. Most people with high T only have hearing loss in the desired magnitudes (>20db and <60db) above say 4kHz. That that anyone desires to have hearing loss!! But it is a criteria of trial inclusion. Below the 4khz (speech) most people with T have good hearing and not the mild to moderate hearing loss (inclusion criteria) that Autifony require.

Most people with T (esp high freq T) won't get on it because of the hearing loss inclusion criteria across the whole spectrum.

 

Can anyone link me to some specific proof regarding this hearing loss requirement for eligibility in the autifony phase IIA trial? It certainly is not listed on their website. Regarding their QUIET-1 study, the Autifony site specifically says that people who have had tinnitus for at least six months but no more than eighteen and are otherwise healthy will fit the criteria. Where is this hearing loss requirement talk coming from?

 

Hey Hudson,

Not sure if you missed it on the thread. Someone found it on the NHS website:

http://www.nhs.uk/Conditions/Tinnit...7-GB&Condition=Tinnitus~quiet&pn=1&Rec=0&CT=0

 

Thank you gentlemen. I must have missed that. I'm so used to checking the clinicaltrials.gov site of the US that I didn't even think about checking the NHS site for the UK. Pity they have that hearing loss requirement. I'm wondering if they are trying to see in the same stroke if AUT00063 has an effect on hearing thresholds as well? Or if the 20 db hearing loss requirement is there to sort of "guarantee" that the tinnitus is due to hearing damage and not some other cause? It is a bit odd, as there are a lot of people (myself included) who have no measurable hearing damage on a standard audiogram who still have tinnitus.

 

Agreed - it's been discussed quite a bit already in the thread... And correct - 2 birds with one stone approach is no doubt their MO. It's an obvious disappointment for a lot of T sufferers (on this thread and otherwise) because as you said a lot of us with T have little to no hearing loss so we'll be excluded on this round. However, so as not to repeat expressing my disappointment around it once again and having my head bitten off - i'll just say roll on round 2.

Good luck to anyone who fits the criteria. Pls feedback if you can.

 

I live in the UK but don't meet the criteria for hearing loss. Gutted!