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

[Nucleo]

Whatever may or may not happen in the future, as founder of Tinnitus Talk and a team member of Team Trobalt, and as a person who has frequently conversed with @attheedgeofscience, I just want to say that most people here have no idea how much time and dedication he has put into driving our cause, basically being a catalyst of many things.

Whenever I think about that, it humbles me, as he has so relentlessly worked on a variety of initiatives both publicly as well as behind the scenes, one of the recent ones of course being the Auris Medical sponsorship.

So I would say with confidence that he does have quite a bit more know-how and experience than the majority here. Myself included.

I honestly think that he has a more than valid point about the social media likes. I have a few other unrelated heath conditions myself, and I think tinnitus takes the cake when it comes to lack of engagement on social media. And it's such a simple act to become a fan, follow, like, and maybe even share. Compared to the thousands of hours of combined work that has been spent behind the scenes by @attheedgeofscience, @Team Trobalt and the @Moderators.

Thereby, I would invite everyone to like this post of mine to show some gratitude for @attheedgeofscience's, @Team Trobalt's and the @Moderators' efforts.

Finally, I would ask everyone to get back to topic, which here is Autifony's QUIET-1 trial. Let's try and keep this on-topic from now on. It's a long thread as is.

Sincerely,
Markku

There's no denying that the tinnitus community has a lot of drive out of all other chronic illnesses support forums. No doubt all thanks to you guys.

 

[RaZaH]

I might just have missed this , never seen that link before ? But my memory sucks , think I would have remembered if i would have felt this was some major initiative. Maybe its the name Pharmocodynamics in the whatchamacallit?
Seems on a quick glance to be something I would never understand

I was also in a T group on fb, had to quit as I was constantly getting some T updates while trying to work....was NOT helping. Having said that I think we should collectively consider what has been said here in this thread about lethargy of the T community , there is some truth to that .

 

[Aaron123]

In the spirit of trying to keep this on-topic, it would be great if the folks working behind the scenes would keep their ears open for Autifony's future plans - and if they could let them know of our interest in a second phase 2 study to look at duration and/or dosage.

We don't yet know that AUT00063 does not work. What we know today is that 800 mg for 28 days does not appear to work. We don't know whether 1600 mg for 3 months or some other dosage/duration combination might work. I hope that Autifony will choose to take another shot at this. If I recall from the Q&A, there was already discussion of a second phase 2 trial to look at dosage even if this one showed effectiveness. Of course this will take more time and money.

 

[attheedgeofscience]

I have spoken with a number of people within the research community throughout the last two days. It's been very intense. The consensus seems to be that for the QUIET-1 trial to have been terminated based on interim data, it must mean that there has been very little efficacy shown. My own opinion regarding sample size (i.e. N = 58) being too small is also reflected by the opinions of those I have been in touch with. Sub-group characteristics will be hard to pick-up in this case (i.e. partial efficacy of the sample population will go undetected, probably).

This is what I can say. Perhaps additional findings will materialize from the CLARITY-1 trial, where participants - besides age related non-cochlear hearing loss - may also see an improvement in their tinnitus (as a bi-product of the trial). I am not sure about the inclusion criteria, and so, it could be that patients with tinnitus are excluded (in which case the argument doesn't hold). Autifony should be able to comment on this, however.

 

[Zug]

@attheedgeofscience I can only speak for me. As it turns out my girlfriend is a survivor of Breast Cancer, it was her decision about when to come public with her decease, and who to tell and who not to tell. In my case I'm fairly known in my field in my country and most of my "followers" are not friend or family, so yes, in my case it would be a public statement that I don't feel ready to make - I'm 100% certain that people will ask whats going on, even the PR person who works with me told me to think if and when I disclose it, because there is not turning back and I should be comfortable with it. I'm not making my case special, everyone has their reasons. I think that's good advice to everyone around here.

Which doesn't mean I want you to stop the work you're doing. We can disagree and I can still try to help you, since you are trying to help all of us anyway.

What I'm saying is that if there are thousand of people who follow this group and don't even register, maybe there are other ways of unleashing the Tinnitus community in a positive way. If there is a fundraising, for instance, for a valid research milestone, a crowdfunding for the first off label Tinnitus medicine, a way to do market research about the size of the Tinnitus drug market and lobby for more research, or whichever idea may appear, I think people may be more comfortable contributing and acting. There are success cases on sufferers of a disease moving things forward. I'm sure we can find ways of working and helping each other in positive ways.

 

[amandine]

Related to this.

Okay so have liked it and shared it.... It says 42 likes and 1 share......we need to get 1000 of these likes/shares combined at least....come on people....read the literature but dont know how many reads it has.....

 

[Aaron123]

This is what I can say. Perhaps additional findings will materialize from the CLARITY-1 trial, where participants - besides age related hearing loss - may also see an improvement in their tinnitus (as a bi-product of the trial). I am not sure about the inclusion criteria, and so, it could be that patients with tinnitus are excluded (in which case the argument doesn't hold). Autifony should be able to comment this, however.

According to the information on clinicaltrials.gov (https://clinicaltrials.gov/ct2/show/NCT02345031?term=AUT022063&rank=1), tinnitus is not an exclusion criterion. It is mentioned as a side-effect of hearing loss, but it isn't specifically mentioned as an outcome.

The primary and secondary measures are

Primary Outcome Measures:

• Change in hearing loss after 4 weeks of treatment [ Time Frame: 28 days ] [ Designated as safety issue: No ]
  To compare the change from baseline (Day 1 to Day 28) between AUT00063 and placebo, on a speech-in-noise deficit

Secondary Outcome Measures:

• Change in parameters of hearing performance from baseline to day 28 [ Time Frame: 28 days ] [ Designated as safety issue: No ]
  Changes in hearing tests
  
  
• To further investigate the safety and tolerability profile of repeat administration of AUT00063 by assessing vital signs, physical examination, laboratory exams and ECG [ Time Frame: 42 days ] [ Designated as safety issue: Yes ]
  To investigate the safety and tolerability of AUT00063 by assessing vital signs, physical examination, laboratory exams and ECG
  
  
• Pharmacokinetic of AUT00063, plasma levels [ Time Frame: 28 days ] [ Designated as safety issue: No ]
  Exposure of AUT00063 ng/ml, in plasma levels at Day 28

I want to be optimistic, but it is really hard to see how 28 days of a lower dose of AUT00063 is going to improve hearing or even speech-in-noise issues. I do hope it works though.

 

[attheedgeofscience]

Which doesn't mean I want you to stop the work you're doing. We can disagree and I can still try to help you, since you are trying to help all of us anyway.

I fully appreciate you words. Please understand, however, that I am not really interested in debating who is right (or wrong). This is about a call to action. If folks do not wish to contribute, then don't contribute. It's pretty simple, really.

If people wish to debate, then they should consider a job as a politician. People like me, who come from the executive business world, we understand that results, not words, matter. This is the point.

It's a simple click we are talking about.

 

[Zug]

Cool @attheedgeofscience I'm also in business, if only on another continent. If there is anything I can do without using my Facebook account (at least for now), let me know.

 

[Mark662]

Just to remind us all, Autifony received £2.2M in funding from the UK government to carry out research with the tinnitus trial of AUT00063

http://www.tinnitus.org.uk/autifony-awarded-22m-to-progress-drug-trial-for-tinnitus

 

[Aaron123]

My own opinion regarding sample size (i.e. N = 58) being too small is also reflected by the opinions of those I have been in touch with. Sub-group characteristics will be hard to pick-up in this case (i.e. partial efficacy of the sample population will go undetected, probably).

The sample size is really disappointing. From the sound of it, this is the number of people who have completed the study. There are presumably some/many people who are not through their 28 days or who haven't completed whatever follow-up visit(s) are required. It appears like data on these individuals will be lost which is a shame. I would think will affect Autifony's ability to publish the results if they want to do that.

It's really perplexing that they would do this "intermediate" analysis so close to the end of the study. This leads me to wonder if the study was sufficiently behind schedule that it would not have concluded in the next month or so anyway. After all, there were people on here who had appointments scheduled for later this month or into next month to start the trial. They were after all planning on a sample of 150 so to have data on only 58 at this point suggests some difficulty in recruiting.

The results must have been pretty grim to conclude that the probability of finding a significant result was very low even if the sample size almost tripled. Will be interesting to see what data they share.

 

[attheedgeofscience]

The results must have been pretty grim to conclude that the probability of finding a significant result was very low even if the sample size almost tripled.

That is exactly the point which I have been hearing as well. So... efficacy must be very "absent" from the study. A while back, I shared the patent paper from Autifony...

www.tinnitustalk.com/threads/collect-money-to-get-autifony-drug.7562/#post-87120

...and it would seem (if I recall correctly) that they have patented +25 compounds (some probably just to dominate the type of chemical niche they are operating within). It is however possible that they may have other options within their portfolio of compounds (but this is pure speculation on my part). In addition, it is perhaps possible that some kind of final conclusion will materialize later on.

This is what I know, and, I am sharing my own opinion. So please do not take the above as facts.

 

[attheedgeofscience]

So if Corrine felt like a guinea pig during her trail period, just imagine how badly Autifony wants to study her now. After all, it would be one hell of a coincidence if her T only got quiet for the weeks she was on 063!

Currently we are doing a very small study on Trobalt here on the forum. One of the criteria is that participants must be chronic (T > 6 months) and non-fluctuating. Because of this set of similar criteria, efficacy should be easier to observe for the QUIET-1 study. I am also surprised, knowing at least some of the anecdotal accounts, that the study from Autifony has been terminated (assuming the anecdotal accounts are true, of course). Efficacy was present. But the interim data must have been poor.

 

[Blackbird26]

I knew it. Sad.

 

[Danny]

life goes on....

 

[valeri]

@attheedgeofscience

Is the deal still on?

 

[attheedgeofscience]

In addition, I can say from previous testimony this summer, that the compounds patented by Autifony were apparently not designed specifically for tinnitus. It was more a question of "we have some compounds already patented, let's see what efficacy they might have." (Sorry if it sounds a little too crude to be true, but this was the gist of the input I got).

 

[attheedgeofscience]

@attheedgeofscience

Is the deal still on?

Sure. I cannot promise that the researchers in the USA will (be able) to help (time moves on, after all). But I can say that:

• I will do my part to further increase the ratings (as indicated), and
• I will contact the researchers and explain to them the awareness created (and which I have done before).

If that extra awareness in itself does not create any momentum, then we can contact HL/T-organizations for monetary help to finance a study (for the researchers). And we can also try to find out what input the researchers would have (from their side). It is possible - in light of the AUT63 trial - that there will increased focus on the Kv7.x-channels (instead). Science is a dynamic entity.

 

[Aaron123]

In addition, I can say from previous testimony this summer, that the compounds patented by Autifony were apparently not designed specifically for tinnitus. It was more a question of "we have some compounds already patented, let's see what efficacy they might have." (Sorry if it sounds a little to crude to be true, but this was the gist of the input I got).

That's interesting (and a bit troubling). Did you learn if there was a specific target for any of compounds or are hearing loss and schizophrenia also shots in the dark?

 

[attheedgeofscience]

Did you learn if there was a specific target for any of compounds or are hearing loss and schizophrenia also shots in the dark?

I have no opinion on that. What I can say is that the HL is that of hearing clarity (i.e. not related to hearing thresholds). There will be no auditory improvement in terms of hearing thresholds from the drug, AUT00063. There is no improvement in the cochlea, and hence, a participant will not gain, say, 10db of threshold from 20db HL to 10db HL (EXAMPLE ONLY).

 

[Gill Hayes]

Facebook page liked and shared.

 

[valeri]

So TT members cut the crap please and do as told.
If some of you are so concerned about bits and pieces of FB then you should probably deactivate it all together.
No big deal in clicking a like and sharing.
No body is asking you to write a post: I have tinnitus!

Just simple click on like and share!



How many other things we like there?

What @attheedgeofscience has to offer is invaluable!
He did more for this community than ATA and BTA together so TT members time to get off your asses and help!

For a long time now I've been thinking that we deserve this, we deserve to be exactly where we are!
We don't deserve help since we obviously don't need it bad enough!

The lethargy to do something instead of endlesly complaining is appalling!

So off your asses and start clicking! Share with friends and family and ask them to do the same!

If nothing comes out of this @Silvio Sabo ie to activate that thing he's ridding and use as he see fit

C'mon people!

 

[SteveSkis92]

Liked and shared. There are people here who support your efforts and hard work @attheedgeofscience , even if it doesn't seem like it at times!

 

[Mic]

Ok Aut63 failed... so what... 80% of all first in class drug candidates fail. So lets get over it and continue the search for a real cure.

The only well known drug that can silence T is Lidocaïne (temporary total silence for up to 70% of participants of corresponding clinical trails, see this research from the 90's). Maybe it is time to stop developing drug candidates from scratch every time with experiments on mice and bunny's and start reverse engineering the neuro-biological reason why this magical molocule of Lidocaïne is, in the majority of cases, very effective to silence the shit out of T (for unfortunately a short time)!

 

[valeri]

@attheedgeofscience

One question: one of my friends just shared the FB post and I must say it comes up as a HEAVY topic to read.
I personally, would never even open something like that to read!

Now, is there something bit more "down to earth" that would interest general non tinnitus community?
Any other post from hub page that people would be interested to open and read?
I'm also going to try my daughters friends, all young kids so maybe we should think how to make this bit more appealing!

 

[attheedgeofscience]

One question: one of my friends just shared the FB post and I must say it comes up as a HEAVY topic to read.
I personally, would never even open something like that to read!

Agreed. But... the abstract is pretty straight forward, and, actually mentions the treatment of tinnitus in the first sentence.

Alternatively, we have also shared the following update a couple of times...

www.tinnitustalk.com/threads/team-trobalt-update-%E2%80%94-april-9-2015.9064

...however, Trobalt is but one of many topics mentioned in that update (which makes it less specific to share).

As I say, whoever wishes to contribute, use the tools available to you. And that would include asking the staff of TinnitusTalk to release a new, and perhaps more "friendly" update explaining the purpose of the post (but still including the paper by Prof. Moore). But the wording of the original post is still pretty good, I think.

You are more than welcome to ask (as you have done), but I do not really wish to get drawn into decision making. I have done SO much behind-the-scenes already. My e-mail inbox counts +100 A4 pages (if printed) from researchers and representatives of otology pharma companies. Not to mention my almost 2000 posts here on TT.

The most important factor is to draw attention to your post. So use the social media; use the internal alert system; ask the staff of TinnitusTalk to share an update via the electronic newsletter. The choice is yours. But again, you do not have to do this. There are +1000 members per month who log in to TT as well. So...

 

[valeri]

@Markku
@Steve

Can I please have your opinion on what I wrote?
We need to have a united approach here otherwise it's not making a lot of sense to do bits and pieces all over the place.
Is there something that can be used not only as promotional but also as educational read that general population would like to open, read and potentially share?
Targeting younger generations would be great but to get their interest it needs to be sweet and short!

Anyone else please chip in

 

[JohnnyMx]

As an engineer i have learned this: the process of success is something like fail-fail-almost success-fail-fail-success.

AUT news are bad, but also tells me, that we are getting closer to our goal. They have learned that the current design of this drug does not work, so they can make changes (or another company or research group) and start over again.

Things will look brighter soon, don't be so sad.

 

[attheedgeofscience]

@Markku
@Steve

Can I please have your opinion on what I wrote?
We need to have a united approach here otherwise it's not making a lot of sense to do bits and pieces all over the place.
Is there something that can be used not only as promotional but also as educational read that general population would like to open, read and potentially share?
Targeting younger generations would be great but to get their interest it needs to be sweet and short!

Anyone else please chip in

You can (also) consider being added to [USERGROUP=11]@Team Trobalt[/USERGROUP] or [USERGROUP=14]@Team Awareness[/USERGROUP] for a more in-depth strategy on the wording. Team Trobalt contains confidential information, however.

 

[valeri]

You can (also) consider being added to [USERGROUP=11]@Team Trobalt[/USERGROUP] or [USERGROUP=14]@Team Awareness[/USERGROUP] for a more in-depth strategy on the wording. Team Trobalt contains confidential information, however.

My understanding is that all teams are non active at the moment.