VX trial

[copyman]

last time at my docs office about a month ago he had mentioned that his clinic was thinking about hosting one of the vx-950 trials pending a meeting with vertex he was to attend a few days after i was there. well now one month later he told me it was on hold due to a problem with terrible rashes. i have read the posts awhile back from mrmeet & pln about their rash but now after what this doc said it may be more prevalent then we have been told. perhaps this is why nothing has been reported about the trial data as of yet. i'm trying to take this as not bad news but i can not think of any other way to take it. it just seems like we should have heard the trial data by now. something just does not add up. i pray to god i'm wrong because i was looking to VX as my glimmer of hope to successful tx.

[mremeet]

Hmm, not sure I'd read too much negativity into what your doc said, not yet anyway. The data has already been formally presented by Vertex reporting what the dropout rate and rash incidence was during the VX dosing period of prove 1. And although it was a little disappointing, the majority of participants got by without a rash and also experienced dramatically increased viral clearance rates (compared to SOC alone). And speaking for myself and PDS, even in those that did get a bad rash, we scored great RVR's which hopefully will take us to the finish line and translate into an SVR eventually. So I think there's definitely reason for optimism (albeit somewhat guarded). If I had to guess, I'd say telaprevir will make it, although it'll come with its own risks and headaches like the rest of these imperfect drugs.

The only thing that would worry me, is if the FDA is really raising eyebrows at the rashes and considering the risk profile too high for the general public. But I know verex is investigating the mechanism of the rash, so hopefully they'll be able to address the FDA's concerns through predictive tests that might be able to identify rash vulnerable people both prior to and during treatment with telaprevir.

Either way, time will tell.

[copyman]

thanks you were the one i had hoped would respond. i feel much better after your explanation. I had meant PDS not pln on my previous post. i remember what you two went through, it sounded awful and i prayed for you both. well i hope you are feeling well and on the way to svr!

[jmjm530]

Thanks for the heads up but if there's one thing I've discovered about trials, like Vertex, there is so much incomplete and often misleading information out there. So EVERYTHING must be verified and verfied again with reliable sources. Case in point is the mysterious "roll over" protocol for Group "A" in the Prove 3 trials for non-responders. At least three different interpretations, but I'm going to re-post mine again since I believe it's the most accurate. LOL. But seriously, did make some inquiries today and without going into details, the best advice I've heard or can give is to get a copy of and READ THE CONSENT FORM. Supposedly, it's all there, in black and white.

Anyway, what I found out today regarding Group "A":

Have nothing in writing, but did a little research and this is what I found out. For those interested, you should get hold of the trial CONSENT FORM. Supposedly, it's all there in black and white. So ask for a copy of the consent form well in advance of making your treatment decision.

Here's my version of how they're running group "A" :)

Group "A" will be given placebo, Pegasys and Copegus for 12 weeks. If patient does not achieve a two-log drop at week 12, then therapy will be STOPPED. The patient will then be giving an option to roll over into 24 weeks of Triple therapy (Vertex, Pegasys, Ribavirin. This triple therapy would start at what would be week 24. So in effect, there would be a 12-week gap between treatments -- actually probably a little less than 12 weeks since it probably will take a week or so to get back the blood results from the week 12 test.

To me, this protocol, while not ideal, is ethical, in that it gives non-responders the opportunity to quickly roll-over, thereby limiting their total exposure to only 36 weeks.

Again, the best way to confirm the above is to read your trial CONSENT FORM, but at first glance, this seems like the most reasonable protocol discussed so far.

-- Jim

[miked]

Jim: I've requested the Consent Form and hope to receive it soon.  What if I do get the 2 log drop (which I did on Peg-Intron but then had a slow decline until I experienced a viral breakthrough).  Will they want me to continue on SOC?

Copyman:  Where did you hear that Prove 3 is on hold?


Mike

[jmjm530]

Good question and don't have an answer. Personally, as a relapser, I'd be reluctant to continue on SOC unless I was at a minimum non-detectible at week 12, and preferably much ealier. Forget that two-log c*ap:) You should have some choice in the matter since I believe the consent form allows you stop treating at any time and hopefully they will be liberal in the "roll over" policy although I doubt that will be spelled out in the consent form. Please post pertinent parts of the consent form when you get it.

-- Jim

[willows]

There is much recruiting going on for Prove 3, so I do not think the rash is stopping all the trial sites.  My hospital was going to be a trial site, but decided not to because of lack of space, for the clinic, I assume.  

If IFN can be approved with suicidal ideation as one of  side effects, then I'm guessing that a rash will not stop approval of Telapravir.  If I am reading right what Jm is posting, it looks like the approach is X number of weeks with IFN and Telapravir and then a switch to IFN and riba.  I beleive this is because they believe the rash is from the combo of riba and telapravir.

But, then, that is why it is called a trial, right?  To test it all out?  Put the puzzle together in a lot of different ways to see which one looks the best?  Personally, I have always been lousy at puzzles and hate them.  But I am a goood waiter, as in wait and wait and wait.  

Willow waiting

[copyman]

Miked: not sure if the trial is on hold or just that this hepatologist i see does not want to be part of it "until he has more info on the rash problems". he did not elaborate on the "meeting" he had or even who it was with but he was very concerned with the bad rash that Vx can give you. I really think there is more to this rash thing that we will find out about later on this year.

JmJm: do you have a link to what vx has reported so far about the rashes? i recall reading something that mrmeet mentioned in his reply to me in this thread.
thanks

PS, where has HR been? last i heard he said he was going away for a few weeks. that was like over a month ago, have you heard from him?

[jmjm530]

I just read stuff about the rashes here. Both anecdotal, and something that was attributed to Vertex. Vertex seems to have a firewall on information but maybe you can find out more by speaking to one of the trial center coordinators or doctors.

[miked]

I just got an email from the clinic coordinator saying they have not yet received the Consent Form....hummm.

[jmjm530]

No doubt a lot of people never ask about those forms and they're treated like some formality to sign just before starting treatment. Reality is that's where it's all laid down what's REALLY gonna go down. Let us know if/when they finally get it.

-- Jim

[web52]

my start date was "supposed to be" alot sooner than it was after my screening. apparently there were last minute changes in consent form required from fda, maybe other reasons i dont know about. i think few new trials actually start by the proposed start date (just from what i hear, i have no data). anyhow, i had the rash but it wasnt anywhere near bad enough to discontinue the vx. other sx made me think about quitting but i hung in & am glad i did.  

[mremeet]

Jim thanks for the update, I read some of it on the other thread. And you're right, chaos and misinformation reign supreme, best to rely on the consent form. But unfortunately from my experience you can't even really depend on that 100%. For instance, our consent form stated that the odds of being assigned into any of the 4 groups were precisely 1 in 4 (because they were all of equal size). Only later to find out that the 12 week SOC + VX950 group was reduced in size from 80 people down to only 20 (as per FDA mandated changes, apparently). This effectively meant that the recalculated odds of randomly being assigned to the placebo group were increased from 25% upwards to about 31% or so. I thought that was pretty sloppy to have not have had that very accurately specified in the consent form, but there it was (or wasn't in this case) in black and white. Also, there were three revisions to our consent form as we've gone along, and they still haven't corrected the placebo part described above. Also, there's no mention of rescue drugs or the fact that they're not allowed. And there's certainly no explanation of what rescue drugs are and what they can do for you in terms of preventing dose reductions. Nor what those dose reductions might mean for your odds of SVR-ing, especially if you end up in the placebo group. They also don't address the issue of viral breakthrough. The consent form does not tell you at what VL threshold they will inform you that you are/were experiencing a breakthough while you're still blinded. And they also don't tell you at what ANC and HGB levels warrant riba and/or IFN dose reductions. And of course they don't explain how the somewhat confusing unblinding process would take place at week 20 (which ended up not taking place at week 20), nor how to interpret our silly a$$ed "29's" on our labwork.

These are just a few things, there are other issues the consent form leaves to your imagination as well. So even the consent form doesn't completely explain what's going to happen or how the trial is structured. These trials are actually pretty complicated when viewed from the inside and all of the possible details are considered.


copyman - In case you're interested I posted an excerpt about the reported side effect profile from Vertex a while back. It was reported on our revised consent form and addressed rash specifically (amongst other things) and how they were looking into its cause and resolution in those experiencing it. Here's the link (complete with apk's interesting response to my disclosure of this information):  ;-)

http://www.medhelp.org/forums/hepatitis/messages/44952.html

And here's the excerpted telaprevir side effect profile (from the link above) straight out of our consent form (verbatim from Vertex):

Blood Sampling: "If you already had a rash or if you develop a rash while on this study, one of the blood samples that have been collected will be used to look at certain genes in your immune cells. The samples will be used to see if there are changes in the genes that determine how these cells function. Certain enzymes that are involved in breaking down the drug will also be looked at to see if they have changed. Differences in these genes and enzymes may cause some people to have a higher risk of developing a skin rash.

Potential risks based on clinical studies: “Skin rash appears to be the most common side effect associated with telaprevir. About 34% of study subjects receiving telaprevir in combination with pegylated interferon and ribavirin for up to 3 months experienced rash. This is compared to about 15% of those who received pegylated interferon and ribavirin alone. Most rashes have been mild to moderate in intensity. Up to 3% of subjects have experienced severe rash. Some of the subjects with severe rash have also had swelling, swollen lymph nodes or fever. Many of the rashes have been associated with itching. The rashes have resolved following discontinuation of the study medications and treatments applied to the skin or taken orally.

Other side effects that may have been associated with telaprevir given in combination with pegylated interferon and ribavirin include low red blood cell count (anemia) requiring discontinuation of the study medications, gastrointestinal problems (nausea 36%, diarrhea 23%, vomiting 12% and hemorrhoids 10%). Each of these events also occurred in subjects treated with pegylated interferon and ribavirin without telaprevir, but in about 10% fewer subjects. Most of the gastrointestinal events have been mild or moderate in intensity.

Additional uncommon but serious side effects occurring in people taking telaprevir in combination with pegylated interferon and ribavirin included anxiety, mood disorder, itching skin, eye problems, heart attack and mass in a gland in the abdomen found on a CT scan.

Additional side effects that were reported by more than 10% of subjects in the study included fatigue, flu-like illness, redness at the Peg-IFN injection site, fever, chills, general rain (ed note: "rain" probably means "pain"), dizziness, insomnia, joint pain and muscle aches.

Potential Risks Based on Non- Clinical Studies: "Studies to look at the safety of telaprevir have also been done in laboratory tests and in animals. Some of the lab tests on a type of mouse cells done using a mixture of telaprevir and related substances showed that damage to the genetic material of cells could occur. Pure telaprevir, the drug that is used for human studies has been re-tested in these same tests and has not shown genetic damages.

In one study, rats in the higher dose groups, there were signs of damage to the testicles that included low sperm production and smaller and softer testicles. This was not seen in similar studies in dogs. Other tests showed that telaprevir may interfere with sex hormone receptors in rats but not in humans. Laboratory tests (inhibin B) to examine for changes in testicular function in humans have not shown adverse effects, but men in this study will continue to be studied."

[jmjm530]

Given what you say, it's a miracle that there's any consistency at all in these trials with no clear cut protocol laid out. How does one even start to explain that some of the trial doctors themselves didn't understand what "29" meant or that "<30" is really "<10". Makes you wonder what some of these results actually mean. Still, it's the best thing we got to go by but wouldn't it be nice if people (the professionals that is) took the time and really did it RIGHT! Nah, too much to ask. Anyway, looks like there will be "outs" and options for those Group "A" folks either saavy enough to take advantage or lucky enough to have doctors who will. It's like you almost have to have a medical degree to protect yourself in these trials. Sort of like a hospital stay in fact. If whatever brought you into the hospital doesn't get you, your hospital care surely might :) BTW stil don't think a public forum is the right place to discuss certain things, but some of your early-on "guerilla" tactics regarding the trial are starting to make a lot more sense to me. Within the somewhat chaotic structure, it's every man and woman for themself!

-- Jim

[FlGuy]

And it should be every rat for herself or himslef too.  With respect to the rats, 'rats in the higher dose groups, there were signs of damage to the testicles that included low sperm production and smaller and softer testicles'.  In the former situation, I know how they arrieve at the counts. There is a surgical, non-fatal test and such a test does not necessarily involve motivation by watching American Idol or even Dancing With The Stars.  The second 'observation' probably has an objective measurement as well. But, I fear that things did not end well with the rats. Make that, every rat for HIMself.

[pln]

http://www.clinicaltrials.gov/ct/show/NCT00420784?order=1