Prove2 no-riba, 2nd breakthrough - it's over

Hi All,

For those who don't already know my story, I have hepc 1b, starting VL 2 milllion, mild fibrosis, liver enzymes under 50, age late 50's, no idea where or when I got it.

I did the Prove2 Vertex trial and got the no-riba 12 week duration arm.  (peg and VX950 only).  I was UND at day 15 and had viral breakthrough by day 28, VL shot up to 200,000 and stayed there.

I continued on SOC, peg 180 and riba 1200mg, dosing straight through, no missed shots.  I was UND again at weeks 8 and 12.  I have just had the confirmation that I had a 2nd viral breakthrough between weeks 12 and 18 of SOC, ie. by week 30 of interferon dosing.  VL again shot straight up to 250,000.  

I was 100% compliant throughout my tx.  I am the first person I have heard of who did 12 weeks VX950 no-riba followed by SOC and did not make it to 24 weeks.  

There's something else I noticed.  Each time before the breakthrough I got a bad rash.  The rash subsided and within days the breakthrough happened.  This makes me wonder if there is a correlation between rash and breakthrough.  I mean, what if the immune system gets very exhausted when it freaks out with the allergic reaction which causes the rash.  If there's any virus still alive at that point maybe the immune system is too weak to hold it down, even with the interferon booster.  Both times my rashes were early in treatment when it was likely there was still live virus present.

Wel that's the bare bones of my story to add to the valuable body of information on the Prove trials that we have on this forum.  I've left out my own thoughts and feelings of devastation.  I'm still on the floor from this 2nd shock.  I may post that stuff another day, I'll see.

dointime.        

[dointime]

"I am the first person I have heard of who did 12 weeks VX950 no-riba followed by SOC and did not make it to 24 weeks."

This sentence should have said "did not make it to 24 weeks SOC".  

[zazza]

My thoughts are with you. I can't help wondering... from what I have read viral breakthrough without dose reduction is uncommon, could the VX950 have anything to do with the later oncoming breakthrough or is it just a coincidence? Also is there someone else on forum who did a 12 week trial and then went on with SOC by their own choice, or is it your prior posts I remember?

It must just be so devastating to you, you have really given it your best effort. Let's hope that the triple treatment will do it for you in the future. We know now that treating without riba makes no sense, as long as you can tolerate it. Best wishes, Zazza

PS. Aren't we all just doing time?

[meki]

Ayyyyy - Wow - I'm so very sorry...

But I have to admit - the topic you brought up about the rash - that might lead to some very interesting discussion.

[Andiamo1]

My thoughts are with you.  I know how you feel, since I failed 7 previous times with various flavors of SOC.  I hope you are not really 100 years old and will have many years of a productive life when a better treatment is available.

My doctor told me that BI has a protease inhibitor in early trials that acts on a different genome sequence and so might compliment Telepravir.

[FloridaMouse]

So sorry to hear this.  I think all of you who are in trials are doing GREAT things for the rest of us.  I tried so hard to get into the 796 trial (thank goodness I didn't qualify since they have now pulled it) but they would not take my 'cause if  my prior history of Leukemia.

You are an inspiration.

Mouse

[mremeet]

Sorry to hear it dointime, I was really hoping against hope that the last PCR was a false positive. I know you're taking it hard, but hopefully you're not taking it too hard. I would concentrate on getting better and feeling better. And you WILL start feeling much better, the drugs and their effects will be leaving soon. Then after you have time to sort things out emotionally you can plot your next move. And the good news is is that your fibrosis is mild, so you've got time on your side there. Plus with any luck next time you'll have full control of your treatment, NO blinds or limitations on how you are treated or tested. Anyway, I really hope you're feeling better soon, take care.

[Willy50]

I'm really sorry to hear that you had this result.  Many people were pulling for you and still are.  This is one setback but doesn't mean that there won't be another successful run.  There continue to be several new drugs in development that are coming and which could be used in conjunction with Telaprevir in the future (like SGP's).  Even the drug that got pulled from trials, HCV796 while unlikely could still possibly be used in a coctail or in a shorter term or at reduced dosages.  Often they also discover new ways to use old drugs in which treatment response can be improved.  It ain't over till it's over.

One question that remains for me is the methods of the trial.  IF a person has a viral breakthough how fast are they able to "roll" this person into a second "parachute" treatment?   My second question is IF the most robust viral response so far has been with triple therapy....... why would the trial design roll a trial failure into a SOC only treatment as opposed to an SOC WITH Telaprevir arm?  I could also see attempting elevated or more frequent dosage in an attempt to "give it their best shot" with whatever arsenal is available.  Which way would you have preferred to have gone?

What is the reason in which they would follow one failed therapy (dual dosage TVR and IFN) with another dual dosage therapy (IFN and RBV) INSTEAD of triple therapy?  

Is there an improvement that could be made to the parachute treatments with follow trial treatment failures?  You notice that I am posing this as a question and not a crticism or suggestion of how they should run their trial.  I'd just like to understand the reasoning.  I know that we've theorized that maybe the varient VX resistant mutations might not be helped by triple therapy dosing following a failure.  It would be interesting to see the failure rates compared in the two therapies following a failure; triple dosing versus basic SOC dosing.  

Sorry to rattle on.  I just wish that there was an improved parachute treatment for trial viral breakthroughs.  I'm very very sorry to hear about this outcome.

Take care,
Willy

[miked]

I'm 16-17 weelks into Prove 3.  UND @ week 4 and 12.

Dude, I'm riding on the knowledge of you, Nick, Susan400, etc. ,I read all of your posts early on about the VL brealthroughs without Ribaviren,

Going into Prove 3 I knew that if they handed me a bag with VX950 (or placebo) and INF but NO Ribaviriin,  I was opting out of the study Day One, period.

It sounds like your in good shape and the future is bright.  Treatment sucks though and who wants to go through this again.

Thanks for for moving the ball forward.

Mike.

[ladybug52]

Your post does raise questions re: rash and breakthrough. There must be an immune system response that is the precursor for your breakthroughs. Let's say that the rash is a histamine response to the body's perception of an enemy. Your immune system has decided that the meds that were helping are now a threat to your body. Your body has developed an IgE antibody that is fighting the meds? Causing a rash? Do dr's measure the IgE antibody during tx? Is it present when we're exposed to hep C? Would antihistimines help reduce the # of IgE and enable you to tolerate tx without breakthrough or relapse?
Of course I'm sorry to hear the news, but I'm trying to make sense out of this also. I tolerated 16 weeks of tx, but my itching (couldn't see a rash till after tx) really peaked after I stopped the meds. I was miserable for about 10 days post. I tried benadryl, atarax, zyrtec, hydrocortizone creams and finally found relief through a steroid injection. What if I had continued tx, and had a viral breakthrough? Maybe stopping the meds when I was clear actually saved me from relapse???
Just wondering out loud.
Wish I could say something to pick you up, you fought the good fight and there is still fight left in you. Just hold on, hang on, take deep breaths and keep going forward. You'll be OK, your liver is still in good shape and your enzymes are  not bad either.
Take care.
Bug

[dointime]

"Also is there someone else on forum who did a 12 week trial and then went on with SOC by their own choice, or is it your prior posts I remember?"

Yes there was somebody else but they were clear at 12 weeks then chose to go on to SOC and are still clear as far as I know.

Here's how I should have put this sentence :-
"I am the first person I have heard of who did the 12 weeks VX950 no-riba, had breakthrough, then took up Vertex's offer of 48 weeks SOC and had breakthrough again."      

[susan400]

I tried to post this before and there was a glitch...

Dointime, I'm so sorry to hear this, I know how you feel..., better days ahead.

Willy, there's usually a requirement of anywhere from 3 mon-1 year of being treatment free-before the trials will accept.  It's referred to as a 'clear-out' period.

Susan

[mary55]

I am so sorry for your viral breakthrough. I'm probably toast as well. I just wish I had more info. I did the no riba arm of the study as well. I have had no viral break through but I'm being led to believe that I am clear. Susan was taken out at week five due to her break through and me at week 12 because of rash issues. We all have to wait until October or November to get our results. I'm already putting out the feelers for round 5. Please hang in there. My thoughts and prayers are with you.

Mary

[wyntre9]

I am so sorry to hear of the breakthrough.

hang in there . . .

Wyntre

[dointime]

Really good to get all your comments and advice folks.  I guess I've now joined the elite group of hard-to-cure and non-responders so I have the best of company.

I'm looking forward to interesting times ahead when they get this right and we all get out of jail.  My money is on a combo of PI + polymerase inhibitor + SOC.  An anti-fibrotic in the meantime would also be nice.  :))

dointime - taking your example and getting up off the floor.            

[dmhrdh]

I'm so sorry to hear this news.
That's an interesting observation about the rash/breakthrough.
Again, I'm sorry.