invitation to participate in trial

I have been asked to participate in a randomized paralle-group dose ranging study to evaluate efficacy, safety pharmacokinetics and antiviral activity of vertex 222 and telaprevir in combination with and without peginterferon-Alfa-2a and Ribavirin  in treatment naive subjects with genotype 1.

There are 4 groups.
group A gets VX222 100mg   daily and telaprevir 1125 mg daily
Group b gets vx222 400 mg daily and telaprevir 1125 mg daily
group c gets vx222 100 mg 2x  telaprevir 1125 mg 2x  plus peg-ifn-alfa-2  180 mg 1 weekly.  RBV in 1000 mg daily  for  persons  under 160 llb and  1200mg for more than 160 lbs.  
group d gets vx222 400 mg 2x daily. telparevir 1125 mg 1x daily. plus  peg inf afa 2 180 mcg 1 weekly, and RBV 1000 mg  daily  less than 160 lbs and 1200 mg daily for persons over 160 lbs

If you get just the telaprevir and the VX 222 and get undetected by week 2 and stay undetected to week 8 then you stop treatment at week 12
If you get just the telaprevir and the VX 222 and dont get undetected by week 2 and stay undetected to week 8 then they will put you on the added peg and RBV for additional 24 weeks.

If you get the quad combo you stay on until 24 week.
If you get the quad combo and you do not get undected by week 12 they drop the teleprevir and vx222 and you go on soc for up to 48 weeks.

of course if you dont respond then you stop all treatment by week 12.

Any comments.  It seems like a good opportunity.  Like what I have been waiting for.  I was going to treat in June or so 2011 after the new teleprevir came out anyway.  

[nygirl7]

I think someone named Upbeat knows a lot about this subject. I don't because I treated a long time ago but I"ll bump it up so perhaps he sees it.

You can look for his posts they are pretty recent - I'm pretty sure it is Upbeat maybe I can find them for you.

[his3707]

I looked in the archives and found some coments on this study.  The comments all seem positive.  I have responded to the invitation and will go in tomorrow for the screening and go from there.  A little scary but I guess I need to take the action.  I dont know of a better alternative.  I just hope Im thinking clearly and making the right decision

[nygirl7]

I think someone named Upbeat knows a lot about this subject. I don't because I treated a long time ago but I"ll bump it up so perhaps he sees it.

You can look for his posts they are pretty recent - I'm pretty sure it is Upbeat maybe I can find them for you.

[nygirl7]

type vx-222 into the search bar and lots of threads come up...it was indeed Upbeat


vx-222
I'm going to try and get into the phase 2 trial for telap and vx-222 thats starting in La Jolla Ca I e-mailed the addre..

Almost kicked out of upcoming study with Telaprevir and VX222
I was lucky enough to gain a spot in Vertex's new study for either VX222 and Tealprevir, or those 2 drugs with SOC. 12 w...
vx-950 vx-222 trial
I just got off the phone with the lead coordinator in Colorado for the vx-950 vx-222 trial. She has been with all the ve...
Telaprevir and VX-222 in Phase 2 Trials
Just spoke to my contact at Vertex. Getting info on anything is very difficult because of the legal and in his own words ...
vx-950 vx-222 trial
They seem to be real slow in recruiting for this trial. Does anyone know which clinic or hospital in Aurora, Colorado is ...

[nutpea]

Id like to be in that.

[CoStudy]

Aurora Colorado is the University of Colorado Hospital Clinical Research Center 702-848-6666. This is also where I am in the Zymogenetics study. All is good, 5 injections left.

[dointime]

Here's what I think.  You have the certainty already of getting tela +SOC in 2011, presumably with all the rescue drugs you might need.  Against that if you do this trial you could end up with just tela and vx222 for 12 weeks.  Seems clear to me that the first option is better.

Don't be seduced by the idea of getting away with being cured in 12 weeks without SOC.  It's a great idea but totally unproven.  You are more likely to not be cured and develop resistance to tela, then you are really screwed till something else comes along.

I did the Prove2 vertex trial and got the no-riba option for 12 weeks.  At first I thought it was great, the easiest option to do, but it didn't work so it ended up not so great at all.  

dointime  

[his3707]

I went in for the initial screening and my ECG's, 3 of them,  two minutes apart , 2 of them came back abnormal.  I have a nonspecific ST and T wave abnormality  and prolonged QT on one, a nonspecific T wave abnormality and prolonged QT on another and then the 3rd one was normal.   .  I don't understand much about it. apparently the prolonged QT is an electronic delay of some sort.  They are concerned because the VX222 can make that worse if you have a prolonged QT.   I have been having some weird issues with the heart thing.  A few weeks back totally unrelated to this, I went in to get my colonoscopy pre op stuff done and had to have a ECG and the blood clotting test and that is when my ECG came back abnormal.  They sent me to a cardiologist and it came up normal over there.  I wore a 21 day heart monitor and not much came up on it except 2 brief periods of ventricle and atrial extra beats.  After i turned it in of course now my heart has been jumping around all over the place.  The cardiologist wants me to do a  nuclear  stress test next week before they clear me for the colonoscopy.   I want to get any tests done before I treat because when Im done I'll have to be dying before I let anyone touch me for an invasive test or surgery. This heart hurdle might make it so i cannot participate.   That would be sad for me.  

[his3707]

Did they offer to give you the soc and continue on?  Are you saying you did not clear and now you are resistant ?  On this one with the 2 drugs if you are not undetectable at 2 weeks they give you the SOC in addition.  I would have to look at the prove 2 trial.  I am not familiar with it.  You do bring up a good point.  That is why I am torn.  There are pros and cons    Even with insurance  in 2011 when the telaprevir comes out, the cost will break us.  That is one reason I am thinking about giving this a go.   If I become resistant to the telaprevir could I try again with the boceptravir (sp)

[his3707]

Thanks I am looking at the previous posts.  I wish someone would pipe up that has cleared with the VX222 and the Telaprevir

[dointime]

Yes, there are pros and cons and it is very hard to weigh up.  All I can tell you are the facts as I know them, so that you are in a position to make an informed choice for yourself.

On the Prove2 trial I was UND at day 15.  That is quite usual with a PI.  However the resistant mutations were slowly being selected out and by day 21 my viral load went back up.  That is one of the things I don't like about the design of this trial.  It will probably not be obvious by day 15 who is going to subsequently have a breakthrough.  So far all the research shows that when no ribavirin is given the chances of breakthrough are very much increased.  With 2 PI's it is hoped that this time it will be different, but do you really want to be on the front line of the people who are going to find that out for us?

I did subsequently get offered SOC, became UND again and then had another breakthrough.  So I have been left with resistant mutations.  The question nobody can answer is whether or not the triple therapy would have worked for me first time round if I had drawn the program with all 3 drugs.  I threw the dice and I lost.  That's a drugs trial for you.    

As to your point that if tela does not work for you then you will try with boc.  Both drugs have many resistant mutations in common, so it is by no means sure that if you become resistant to tela then you will be ok to treat with boc.  From what is currently known about resistance, it is possible but unlikely that people who fail with tela will succeed with boc.  However much is yet to be learned about cross-resistance and I am not an expert on it.        

I appreciate your point about the financial cost if you wait for the triple therapy with tela.  This is a hard one.  There are many other costs to tx as well.  It is a huge commitment in time and effort for you and your family.  The side effects can be hard and they can last well beyond the end of the drugs phase.  You really, really don't want to do it more than once, trust me on this.  Hard though it is, my advice would be to think carefully about what is your very best shot at SVR the first time round, and go for that regardless of the cost.

Best wishes,
dointime

[it'sallgood]

i never ceased to be amazed at the quality of advice on this forum.  i was also looking at this study, though with platelets hovering around 110 there is little chance that i would be accepted.  i came to the same conclusion as dointime.  unfortunately dointime leaned it the hard way, and now bless her heat she chooses to share that with us.  there is this hope that we can get away from the ribivirin and interferon, but i am wondering if that will happen in my lifetime.

about 3 years ago i was invited to join a phase II study. The liver doc was all excited about the drug, but i declined.  a few months into the study the researchers found that the study drug was causing cardiomyopathy and the study was stopped.

[RobertBeWell]

Doesn't everything eventually return to "wild state" after a year or so, even if the "resistant" mutations are selected out by a  inhibitor?

It's my understanding that HCV doesn't "proofread" when it makes copies of itself, thats why there are so many "bit errors", and hence mutations to start with. But as time goes on, the errors continue, and the "resistant mutations" become just another small drop in the bucket.

That's how I understand it anyhow. I don't think it's a lifetime thing.

Robert

[RobertBeWell]

"Doesn't everything eventually return to "wild state" after a year or so, even if the "resistant" mutations are selected out by a  inhibitor? "

That was supposed to say "selected out by a 'fill-in-the-blank' inhibitor?".

Robert

[nygirl7]

I wish someone would pipe up that has cleared with the VX222 and the Telaprevir "

I'm sorry I don't think we've had anyone on here who did succeed with this treatment that I can remember; however, we've had some major success with the tela and SOC.

How bad is your liver damage?

[dointime]

A virus population of HIV or HCV, even when it has mostly reverted back to wild type, has what is called an 'archival' memory.  This means that it has the equivalent of a memory of what it did last time to dodge a threat and it can do the same again but faster next time it meets the same threat.  This is better documented in the case of HIV.  Even if not one single resistant mutation were left in the population, resistance would develop quicker the 2nd time it met the same drug, meaning the drug would be less effective - although it might still have it's uses in a carefully chosen combo.  

Resistant mutations are never 'a small drop in the bucket'.  You only need to have one that can't be killed by your tx combo and the next thing your vl is back up in the millions.  You might as well not bother to treat unless you know you have a good chance of nailing that one pesky resistant mutation.

dointime      

[RobertBeWell]

"Resistant mutations are never 'a small drop in the bucket'.  You only need to have one that can't be killed by your tx combo and the next thing your vl is back up in the millions.  You might as well not bother to treat unless you know you have a good chance of nailing that one pesky resistant mutation. "

If that's the case, then how does one ever achieve SVR? I must be missing the whole mechanism of SVR.. which in my understanding is supression of the virus to so low a level that the immune system basically takes over and keeps it supressed. Hence "occult HCV" studies that have demonstrated over and over the presence of viral RNA after SVR.

So, if out of those trillions of virions in your body, you miss a single one with the drug combo, you're history? Frankly, I don't see how anyone ever achieves SVR. I thought the interferons (those produced by the immune system) were basically the thing that "mops up" after the DAA does the heavy lifting.

Well, I'm mighty glad I'm not taking an NS3/4A inhibitor. I can come back to them in the future if ever I need them.

[his3707]

I have not had a liver biopsy.  I have had two fibrosure tests done and both came up f0-f1.  My blood work is pretty normal.  AST 33 ALT  37    except for AFP  11.5  and alpha 2 macroglobulin 408.     myoglobin serum  39.Not sure what the macro and myo tests indicate.   They wont accept the fibrosure tests so they will do the liver biopsy.  How far can I go into the screening and back out.   I dont want to get too far in and then feel some obligation.  I had such a good feeling about this and now I am afraid Im making a mistake for all the reasons stated.  I dont want to do it more than once.  I know everyone is different.  It would be great to be one of the first people to be SVR without interferon!  That is the wave of the future it seems.  I suppose I was secretly thinking I would get the quad combo and go for 12-26 weeks and be done with it.
I need to talk to my study doc and ask about the real possibility of starting out with the vx222 and telaprevir, having to continue with the SOC and my chances of break thru and being resistant.    She did make it sound like  a sure bet that if needed,I would get the SOC on top of the telap and vx 222 if needed, and the outcome would be the same either way.  It just seemed implied which  as dointime did say  "seduced" me.  Maybe the heart situation will take care of me being ousted.  

@dointime    As I understand it the Prove 2 trial was the telaprevir only, or telaprevir and  SOC?  or am I wrong.  
Can this be compared as a simular situation?   Seeing that the telaprevir does not work alone, could the VX222 incombo have something to it?  

Did it work for anyone that you know of in that trial?  I see what nygirl wrote about not knowing of anyone, but i cant find in any article where it says no one SVR'd  

[his3707]

I am re reading all your posts on this thread.  It takes me a while to catch on and understand I have managed to ask some pretty redundant and or "stupid" scenario type questions in the past so please bare with me while I try to figure this out.   This is so confusing,  frustrating, maddening,   Thank you for all your advice and knowledge.  If it hadn't been for this forum I would have  jumped into SOC hastily.

[his3707]

not that your answer I checked isnt good  I just accidentally hit the check box best answer trying to get back to the forum.   sorry dont know how to undo that.   Everyones answers are very good!

[it'sallgood]

during the first trial with humans infected with hcv it became obvious that teleprevir was not going to work by itself -  resistance quickly appeared.  the arm that downtime was in included telaprevir and interferon but not ribiviron.  at least one other member of the forum had the same experience as dowintime.  because of the contribution of these brave souls we now know that you need to interferon and ribiviron in order to get SVR with telaprevir.  

one objective of this trial seeks is to see if another drug might do the job in the place of ribiviron and interferon.   assuming you do have little to no scaring and you have been infected for around 30 years, like most of us, then you may have some wiggle room.   you could have a go at the trial and hopefully they stop it if you get an adverse reaction to the drug combo.  if you don't clear then perhaps you can wait a while 5 to 10 years for the other drugs currently in the pipeline.  

[blondie717]

what is the NCT#. Back to the top you go

[dointime]

"So, if out of those trillions of virions in your body, you miss a single one with the drug combo, you're history? Frankly, I don't see how anyone ever achieves SVR. I thought the interferons (those produced by the immune system) were basically the thing that "mops up" after the DAA does the heavy lifting."

In virus population, or quasispecies, of a person who has never treated contains mostly wild type virus.  By definition, this is the strongest virus type, and although there are mutations around there are not very many of them because the wild type does not give them much 'elbow room'.  When you give a PI and drastically cut down the wild type virus, which is what a PI is designed to do, the mutations get the advantage and start to proliferate.  This is what is meant by the mutations being 'selected out'.  So you end up with a whole virus population of only progeny of those mutations which were not killed by the PI.  Your vl just goes right back up again and the PI from then on has no effect at all on it.  The body's own immune system cannot clear this population any better than it could clear the wild type population.  This vl pattern has been well studied and documented by Vertex among others.

Interferon and ribavirin are not direct antivirals like the PI's and the virus cannot so easily become resistant to them.  The idea of the triple therapies is for the SOC part to kill anything left over which has escaped the PI.  As we now know, this has had good success.  

What we don't yet know is whether the virus can mutate around 2 Pi's targeting different parts of it.  That is what makes this particular trial very exciting for onlookers and very risky for participants.  I fervently hope for my own sake that 2 PI's will not allow any escapees and SOC will not be needed to do the mopping up.  But yes, as I understand it, just one escapee could replicate and repopulate the whole vl and the body's own defense system would be unable to prevent it.

dointime            

[dointime]

"@dointime    As I understand it the Prove 2 trial was the telaprevir only, or telaprevir and  SOC?  or am I wrong.  
Can this be compared as a simular situation?   Seeing that the telaprevir does not work alone, could the VX222 incombo have something to it? "  

In the prove2 trial there was an arm that got all 3 drugs, an arm that got tela + ifn (no riba) and an arm that got SOC alone.  I got the no-riba arm, so I got the tela with ifn.

There were 9 people in my group.  2 people got all 3 drugs and both of them went on to SVR.  3 people got the no-riba arm and all failed.  

The comparison between the Prove2 trial and this trial is that some arms are no-riba arms, and added to that they are no-ifn either.

The vx222 + tela combination could certainly have something to it.  (see my reply to RobertBeWell above)   I have great hope that 2 PI's WITH SOC will be the magic bullet for the majority of people on this forum including myself.  However for 2 PI's without SOC the outcome is a complete unknown.  It's a case of 'well do you feel lucky today?'

By all means quiz your study doc on all aspects of this trial and leave no stone unturned, nothing implicit.  Remember that your study doc is getting paid to do this study and needs recruits and therefore is not impartial.  If you have an independent doc outside of this then he might be able to offer you a more objective opinion and it would be a good idea to take all the info you gather and run it by him.  Do the math yourself on the probabilities of which straw you will draw.  Find out about the use of rescue drugs.  In many cases rescue drugs can make the difference between SVR or not, so this matters.  Understand from the outset that the goals of your study doc are not the same as yours.  You want SVR.  Your study doc wants data for Vertex, and can achieve that by tracking your viral breakthrough and resistant mutations just as well as by reporting your SVR.

dointime                  

[blondie717]

frightnening

[his3707]

yes, frightening.  Thank you dointime  , itsallgood, and all for explaining very well. i will keep posting as I find out answers next week

[dointime]

To be completely fair about it, many people have attained SVR in trials.  You could have the luck of drawing the arm which turns out to be the most successful.  Two people in my group did just that and they are happily SVR today.  

The psychological twists and turns of drug trials are far greater than I ever imagined before I did one.  The choice you make to enter one is not the end of the agonizing about the right decision but in many cases just the start.

I suspect that after your answers are all in it is going to come down simply to whether you go for the bird in the hand (the approved triple therapy) or the two in the bush (the trial).  I think it is terrific that you even have this choice which has never before been available.

dointime        

[his3707]

After all the comments I received on this forum, I sent my study doctor this email.  We will see how she answers my questions.   just posting for anyone who might be interested in this trial and the outcomes and even participating in this or the next step which is something I might do if this trial is successful.   I dont think I am going to do this. If I didnt have any kids to finish raising and a husband to care for, I would do it.  Too risky for me I think at this stage.    I did go to my heart doctor and he said that I did not have prolong QT which is good news for me .  


Hi Cheryl, Im just going to start laying the questions out as they come to me and my thoughts and feelings.  

Questions

1.  If I get the arm that has the vx222 and telaprevir and become undected by 2 weeks and stay undetected by 8 and then at 12 and stop treatment, what is known about breakthrough or relapse

2.  If I do get the vx222 and telapreviir and end up with  breakthough or it not working, what about  the risk of becoming resistant.  

3.  If I get the vx222/telaprevir and soc and stop at 12 weeks. what is known about breakthrough/relapse

4.  also about becoming resistant after stopping for a period of time and having to restart treatment concerning possible relapse in question 3 .

5. What was the first of this trial and what were the results of that trial.

I want all information about using these two drugs without Riba/and interferon and why or how sure they are that these two drugs alone will work.  

How long have they been working on this.

6.  Liver biopsy   If I have a biopsy, I want any necessary medication to go along with that.  I see on the restricted drugs list that you sent me that they will only give you 1 dose of meds at the biopsy.  


7.   If i do not qualify for the trial or decide it is not for me, I still want to do these tests.  Would you just submit this on my health insurance like normal.  



8.  Where can I find info about all the possible sides effects of the new drugs.  What other trials have they done with other simular drugs and what were those results.


I saw this press release and it sounds very risky to me.   My goal is getting rid of HCV.  The studies goal is to determine the possibility of SVR with these new concepts of treating without interferon and Riba.

I have two boys ages 11 and 14.  The 14 year old does have antibodies for HCV but not the virus as far as I know right now.  I had a viral load test done on him and it came back undetected but I did not due a followup because there is no treatment for him at this time regardless.  When he is out of school I will have him retested and when better treatments are available if he does end up having virus.  
I would also want to do a trial like this so he or someone young could get treated without having to go thru that people now are going thru.   However, Since I do have the responsibility of seeing my children into adulthood, I don't think I can take the chance of becoming resistant to the new 3 drug combo by participating in this and missing my chance at SVR and getting very sick in the next 10 years and possibly dying premature due to HCV.  

If you could assure me that my chances of SVR would be the same and no chance of becoming resistant fighting the virus this way (more than what my chances would be when Telaprevir hits the market)  then I would be even more committed.  It was just the way you told me about it sounded like a win win situation but I don't think that is what reality is.  I don't blame you for presenting it to me in this manner, however, people like me don't know the right questions to ask and everything needs to be laid out on the table as far as weighing out the risks and the possible scenarios.  This way an ignorant person on this matter would know exactly the risks and benefits being taken.  That is the only fair way to get someone into a trial.  

Press Release

Vertex announced today that it has modified its clinical trial evaluating telaprevir dosed in combination with Vertex's lead HCV polymerase inhibitor, VX-222. The company will discontinue Arm A of this study as a result of patients meeting a pre-defined stopping rule related to viral breakthrough during the first four weeks of dosing. Arm A was designed to evaluate a two-drug regimen of VX-222 (low dose; 100 mg) and telaprevir (1,125 mg) both dosed twice daily without pegylated-interferon and ribavirin. The additional three arms of the study are continuing without modification, and no viral breakthrough has been reported in these arms.
This Phase 2 proof-of-concept trial began dosing patients in August 2010 and is designed to evaluate safety and SVR rates using 12-week response-guided regimens of telaprevir/VX-222-based combination therapy in people with genotype 1 hepatitis C. The trial is continuing to evaluate treatment regimens that include four-drug regimens of telaprevir, VX-222, pegylated-interferon and ribavirin, as well as a two-drug regimen of only telaprevir (1,125 mg) and a higher dose of VX-222 (400 mg), both dosed twice daily.
Trial sites have now completed patient recruitment, which Vertex expects will enable it to reach the initial target enrollment of 100 patients for the study. Vertex expects to obtain on-treatment clinical data from this trial in the first half of 2011 and SVR data in the second half of 2011.

So lets keep the line of communication open.  I have a feeling that you dont have time for me to think it over which now is what I want to do since I am finding out about what the outcome for me could mean.  This would be the most important decision I make concerning my health probably for the rest of my life.  

Thanks  

Lydia North