AM-101 Clinical Trial — Participants Updates and Discussion

[ryant]

AM-101 is back in the news: https://globenewswire.com/news-rele...us-Program-Following-Regulatory-Feedback.html

They are resuming enrollment for treating tinnitus with Keyzilen (AM-101). I really wish I had something good to say about this drug, but I don't. I went through two rounds of injections (1st round blind - not sure if I got the drug, 2nd round was the actual drug), and I had no improvement. My tinnitus is the same as the day I went in for the 1st injection. Actually my tinnitus worsened after the treatments and then went back to where it was before the injection after about 2-3 months. I haven't read any long-term success stories on this thread either with Keyzilen.

 

[VRZ78]

If you look at their presentation of the result you'd see that the drug only seems usefull for people that have T due to Otitis Media

 

[Alue]

AM-101 is back in the news: https://globenewswire.com/news-rele...us-Program-Following-Regulatory-Feedback.html

They are resuming enrollment for treating tinnitus with Keyzilen (AM-101). I really wish I had something good to say about this drug, but I don't. I went through two rounds of injections (1st round blind - not sure if I got the drug, 2nd round was the actual drug), and I had no improvement. My tinnitus is the same as the day I went in for the 1st injection. Actually my tinnitus worsened after the treatments and then went back to where it was before the injection after about 2-3 months. I haven't read any long-term success stories on this thread either with Keyzilen.

Yeah, I saw this: http://www.econotimes.com/Auris-Med...-Program-Following-Regulatory-Feedback-436024

And was about to post it.

Auris Medical Holding AG (NASDAQ: EARS), a clinical-stage company dedicated to developing therapeutics that address important unmet medical needs in otolaryngology, today confirmed that the TACTT3 Phase 3 trial with KeyzilenTM (AM-101) will resume enrollment in early 2017 as per previous guidance. This announcement follows receipt of key approvals from regulatory agencies and ethics committees in Europe on the recently submitted TACTT3 protocol amendment.
"We believe that the protocol amendment we are implementing improves TACTT3's probability of success, and we look forward to top-line results from this trial in early 2018," commented Thomas Meyer, Auris Medical's founder, Chairman and Chief Executive Officer. "With Keyzilen's strong safety profile and positive data from several trials, we are working to realize the potential of what could become the first pharmacological treatment for patients who suffer from acute tinnitus of the inner ear."
As previously announced, the TACTT3 protocol was amended based on analysis of the TACTT2 Phase 3 trial outcomes. The amended protocol elevates the Tinnitus Functional Index score from a key secondary endpoint to an alternate primary efficacy endpoint, includes certain patient subgroups in confirmatory statistical testing and increases the trial size with the enrollment of an additional 120 patients.

I'm not sure what adjustments are being made, maybe focusing on people with Otitis Media, or trying to have people get the injection sooner after onset.

I also had minimal results from AM101. I did 2 open label rounds. Still, I would like them to be successful with one of their products. Even though it may not help us, any pharmaceutical getting approval for Tinnitus would open up the door for more research.

I'm not too optimistic either. I more or less gave up hope for any sort of cure or treatment any time soon. In my desperation, I had put a lot of hope in AM101 helping me which set me up for a lot of disappointment.

If you look at their presentation of the result you'd see that the drug only seems usefull for people that have T due to Otitis Media

This wasn't true for phase II, but phase III has been disappointing. Which presentation were you referring to?

 

[Path Maker]

Here's the thing: If they DO succeed, even with a small subgroup, do you realize the MASSIVE PAID MARKETING CAMPAIGN they will put into this?

That alone will advance the cause of all tinnitus sufferers, because a drug company wants to succeed in marketing to profit from their product, and the airwaves and print media will be extremely well-funded and significant, because especially if this drug needs to be taken quickly after onset of tinnitus, it will be important to get the message out to all people, so that when a person first gets tinnitus, they have heard of the drug and know to go ask for it. The drug company will fund that!

More than any "public awareness" campaign, the success of the first drug to treat tinnitus will be important due to the advertising that goes hand in glove with that.

I hope they are successful.

 

[JurgenG]

So I have a chance to get in the trials with a low amount of T.
I's going up and down, the last days it was worse again, so thats why I am considering.
It's been almost a month since my "accoustic trauma."

Should I or shouldn't I.. I am scared it will turn out the wrong way if I see the statistics.

 

[Hopeful1]

Please dont do this...it would cause some hearimg loss and worsen your T and ETD

 

[VRZ78]

So I have a chance to get in the trials with a low amount ofThegoing up and down, the last days it was worse again, so thats why I am considering.
It's been almost a month since my "accoustic trauma."

Should I or shouldn't I.. I am scared it will turn out the wrong way if I see the statistics.

I think you shouldn't. There was absolutely zero improvements for people suffering from acoustic trauma. The only people that saw improvement were people that got it from otitis media or people that have very bad T

 

[ryant]

So I have a chance to get in the trials with a low amount of T.
I's going up and down, the last days it was worse again, so thats why I am considering.
It's been almost a month since my "accoustic trauma."

Should I or shouldn't I.. I am scared it will turn out the wrong way if I see the statistics.

AM-101 doesn't work for acoustic trauma. I haven't read any reports of it being a cure or even significantly improving symptoms of tinnitus for anyone. My tinnitus got worse after both treatments (blind study - not sure if it was the drug, and open label -100% drug). It's been several months since and my tinnitus is no different than the day it started. In fact, I would say it is a bit worse, and that may be due to having needles and gel inserted into my eardrums 6 times in each ear. If I had a chance to do it again I would not.

 

[Alue]

Please dont do this...it would cause some hearimg loss and worsen your T and ETD

Please stop spreading misinformation. It hasn't been shown effective for acoustic traumas, but it has been shown safe for most people according to the data.

AM-101 doesn't work for acoustic trauma. I haven't read any reports of it being a cure or even significantly improving symptoms of tinnitus for anyone. My tinnitus got worse after both treatments (blind study - not sure if it was the drug, and open label -100% drug). It's been several months since and my tinnitus is no different than the day it started. In fact, I would say it is a bit worse, and that may be due to having needles and gel inserted into my eardrums 6 times in each ear. If I had a chance to do it again I would not.

I'm curious if you and others that had worsening during the treatments had suctioning done? The only time I had a real worsening was when they suctioned my ear before the injection.

 

[ryant]

Please stop spreading misinformation. It hasn't been shown effective for acoustic traumas, but it has been shown safe for most people according to the data.


I'm curious if you and others that had worsening during the treatments had suctioning done? The only time I had a real worsening was when they suctioned my ear before the injection.

the worsening of my tinnitus post-treatment lasted for a few weeks, and worsened immediately after the injections. My tinnitus went from a volume of 5-6 to a 8-9 scale (10 would be unimaginable loudness for me, haven't experienced that). I couldn't sleep at night, woke up in the middle of one night thinking there was a fire alarm going off, nope just my ears. It did go down a few weeks after the injections but never improved beyond where it first started. All I can hear at this moment is EEEEEEEEEEEEEEEEEEEEEEEEEEEEEEE: to infinity. AM-101 did nothing for me.

 

[Alue]

the worsening of my tinnitus post-treatment lasted for a few weeks, and worsened immediately after the injections. My tinnitus went from a volume of 5-6 to a 8-9 scale (10 would be unimaginable loudness for me, haven't experienced that). I couldn't sleep at night, woke up in the middle of one night thinking there was a fire alarm going off, nope just my ears. It did go down a few weeks after the injections but never improved beyond where it first started. All I can hear at this moment is EEEEEEEEEEEEEEEEEEEEEEEEEEEEEEE: to infinity. AM-101 did nothing for me.

Did you get suctioning with lidocaine or phenol with no suctioning?

 

[ryant]

Did you get suctioning with lidocaine or phenol with no suctioning?

Lidocaine with suctioning - it was really loud, but it worked. I didn't feel the needle go in my ear at all.

 

[Alue]

Lidocaine with suctioning - it was really loud, but it worked. I didn't feel the needle go in my ear at all.

I had phenol, but had one of my ears suctioned once, and that one time I got a loud new tone that lasted about an hour then died down into something softer, then it took about a month for that new tone to disappear completely. I'm 100% sure it was the suctioning that caused it for me and not the injection or the medication.

I'm sure it's different for everyone, but that's why I ask.

 

[Nick07]

It sucks that it doesn't work for acoustic trauma. I'm not 100% sure that that's what caused it, but I was really hoping to try it out. It's still somewhat early, so maybe it will go away on it's own.

 

[John D]

My sensitivity to different noises is a little worse after treatment and had a bad spike for over two weeks. + I don't get as many good days now being 3-4.

 

[Alue]

It sucks that it doesn't work for acoustic trauma. I'm not 100% sure that that's what caused it, but I was really hoping to try it out. It's still somewhat early, so maybe it will go away on it's own.

I've said this before, but based on the data I think it could still be helpful for acoustic trauma, but the window of opportunity is much shorter than they thought it would be. It could be a better version of the steroid treatment (48 hour window). But nobody got the injection in less than 2 weeks in the phase III trials. I applied within a week of my acoustic trauma and it was 2 months after onset when I was able to get my first (double blind) injection. That, and I think using lidocane in some and suctioning it out was a mistake. They should have just used phenol in everyone. There is no need to suction it out and there is no false reduction of tinnitus sound with phenol.

 

[Scorpius]

The problem with AM-101 was definitely clinical trial design. The animal model of inducing hearing loss on rats/mice and then treating them inside a window of 3 months only mimics the human case of acoustic trauma and otis media. But most tinnitus is due to accumulated hearing loss over a long period of time, treating the last bit that triggered the onset of tinnitus isn't going to help. That is why (imho) AM-101 failed, the prevalence for 'acute inner ear tinnitus' is low.

But this actually has me worried if other pharmaceutical companies use the same model for clinical trial design, money could be wasted on a model that has no base in reality. This can then make tinnitus an unattractive area of research, because for investors it looks like a too difficult area.

I therefor hope most companies will focus on designing treatments for chronic cases.

 

[beeeep]

Not really big news, as Auris already announced they would continue the phase 3 trial with an "amended protocol". Seems like that restart just happened.

Auris Medical Resumes Enrollment in TACTT3 Phase 3 Trial of Keyzilen in Acute and Post-Acute Tinnitus

[...]

"Following the swift approval by regulatory agencies and ethics committees, we are pleased to resume enrollment under the amended protocol in the TACTT3 Phase 3 clinical trial of Keyzilen," commented Thomas Meyer, Auris Medical's founder, Chairman and Chief Executive Officer. "We have applied key learnings from the TACTT2 trial that we believe substantially strengthen TACTT3's probability of success, and we look forward to top-line results in early 2018."

[...]

 

[TC426]

Overview of past updates:
24 hours after last injections
1 week after last injections
3 week after last injections (unplanned)
1 month after last injections
2 months after last injections
3 months after last injections (final update and summary)

Hey guys

I had disappeared for quite a while, and never delivered a final summary after my two rounds of AM-101.
By now, it's been about 9 months since my last injections, and I cannot report any relevant or lasting improvement.

Summed up, I would say that I came into the trial with high-pitched T, symmetrically in both ears. Intensity varied from day to day, but T was easy to mask with music and other sounds.

After AM-101, it has become much harder to mask the high pitch noise, even though the general intensity has decreased and does not usually bother me as much as it used to. However, the initially temporary hum that I got after round 2 in my right ear has become much more dominant and is pretty permanent by now (and much more distracting than the high frequency). Generally, my left ear seems to be pretty much the same as prior to the trial, but my right ear has gotten worse. I.e. the whole thing has shifted to the right side of my head.

I still do not think that the medicine itself has caused the worsening, but I am very sceptical towards the procedure as such, especially any sort of suction (see previous post). It was the right decision to go for the trial, but from today's point of view, I would not do it again.

 

[Ian Mac]

Hey guys

I had disappeared for quite a while, and never delivered a final summary after my two rounds of AM-101.
By now, it's been about 9 months since my last injections, and I cannot report any relevant or lasting improvement.

Summed up, I would say that I came into the trial with high-pitched T, symmetrically in both ears. Intensity varied from day to day, but T was easy to mask with music and other sounds.

After AM-101, it has become much harder to mask the high pitch noise, even though the general intensity has decreased and does not usually bother me as much as it used to. However, the initially temporary hum that I got after round 2 in my right ear has become much more dominant and is pretty permanent by now (and much more distracting than the high frequency). Generally, my left ear seems to be pretty much the same as prior to the trial, but my right ear has gotten worse. I.e. the whole thing has shifted to the right side of my head.

I still do not think that the medicine itself has caused the worsening, but I am very sceptical towards the procedure as such, especially any sort of suction (see previous post). It was the right decision to go for the trial, but from today's point of view, I would not do it again.

Does the HUM literally "HUM" does it change, even slightly? Then it's probably a venous hum or heart murmur or blood flow issue that can be resolved when you release the tension. I'm sorry if I am wrong.

 

[Reno]

Hi,

I'm just over 1 month after acoustic trauma (concert), with high-pitched T that eventually settled in the left ear only (that was not as clear in the early days)

I'm sorry I can't read the whole of the 77 page thread, could someone please summarize :

- Why was the US study considered a failure (at least by the stock markets) in 2016 ? My understanding is that it was a technicality : they picked the wrong primary outcome to measure, but that the drug actually works by some other measure and results are still very encouraging. Is that correct ?

- Do we have anyone here who got better with AM-101 after acoustic trauma ? If so, when did you get the injections ?

Thanks !

 

[Hopeful1]

None from noise damage...plenty got worse from it including me.

 

[Reno]

If you look at their presentation of the result you'd see that the drug only seems usefull for people that have T due to Otitis Media

None from noise damage...plenty got worse from it including me.

Oh really ? I had seen at least one positive testimony so I was hopeful :
https://www.tinnitustalk.com/thread...our-experiences-before-entering-phase-3.7643/

My understanding was that the US study TACTT2 was only considered a failure because of a technicality : they had picked the wrong "primary endpoints" (criteria), but by another measure (TFI, if I recall correctly) it was pretty successful. Is that wrong ?

 

[Hopeful1]

You are wrong. At my test centre only one of 10 have positive results and at least 2 including me has very bad results.

Do this at your own peril.

 

[Elgringo32]

I fully agree with @Hopeful1 and I regret a lot for having participated in this trial last year. We have only one life!

Never do this trial.

In most cases it will be worse after AM101 and it is not related to the procedure but by the drug itself (I know many people who performed the second round with the real drug and who got worsened whereas the procedure was the same during the 2 rounds).

It is also confirmed if you look at the "Keyzilen program update presentation" from "October 2016" where people with trauma receiving the placebo had better improvement than the ones with this sh%t AM101!!

Good luck to all.

Cheers.

 

[Alue]

I fully agree with @Hopeful1 and I regret a lot for having participated in this trial last year. We have only one life!

Never do this trial.

In most cases it will be worse after AM101 and it is not related to the procedure but by the drug itself (I know many people who performed the second round with the real drug and who got worsened whereas the procedure was the same during the 2 rounds).

It is also confirmed if you look at the "Keyzilen program update presentation" from "October 2016" where people with trauma receiving the placebo had better improvement than the ones with this sh%t AM101!!

Good luck to all.

Cheers.

Did you both get suctioning done? Lidocaine plus suctioning? Who are these other people?

 

[Hopeful1]

Yes i had the suctioning

 

[attheedgeofscience]

Auris Medical has announced the completion of patient enrollment in the extended phase-III trial taking place in Europe (TACTT3). The trial was extended with 60+60 participants after the North American trial (TACTT2) failed to demonstrate a statistically significant result last summer. There is hence still a possibility that AM-101 could be approved in early 2018. A separate open-label trial involving injections in addition to the placebo-injections of the clinical trial already demonstrated a statistically significant result for those who received 3 rounds of injections (with 3 injections in each round) vs. those who only did one round of injections.

The news release was posted here:

http://markets.businessinsider.com/...n-in-Acute-and-Post-Acute-Tinnitus-1002422467

 

[Paulmanlike]

So Auris will continue testing both acute (0-3 months) and post acute (3-6 months) for both otitis media and traumatic cochlear Injury (I guess from noise?).

Let's just say that by, imo, the slim chance that this trial is successful, will they release it to market or would they continue trials to see if it works for people for example who have had tinnitus for years? Or would a successful outcome of post acute state immediately mean that doctors can administer this treatment to any chronic case? I know it's a long shot but it's a very important question for a lot of people. Also, does anybody know of the "certain patient subgroups" they talk about in their amended protocol?

Will the outcome of this trial affect OTO-311 and will it affect AM-102?

All very important questions that I can only speculate answers too.

 

[attheedgeofscience]

Let's just say that by, imo, the slim chance that this trial is successful, will they release it to market or would they continue trials to see if it works for people for example who have had tinnitus for years?

It would be released to the market if found successful and certainly not delayed (while paying attention to the amendments they have put forward for criteria of success re: the clinical trial).

Or would a successful outcome of post acute state immediately mean that doctors can administer this treatment to any chronic case?

A doctor could administer it for any reason (regardless). Off-label procedures are not uncommon in medicine.

Also, does anybody know of the "certain patient subgroups" they talk about in their amended protocol?

See below. Sub-groups with a statistically meaningful result were: otitis media and those who had severe tinnitus.

Will the outcome of this trial affect OTO-311 and will it affect AM-102?

At this point, OTO-311 is more likely to be impacted by OTO-104 than AM-101. As for AM-102, I don't know... (well, I do have an opinion, but I don't want to share it in public...).