Looks like I'm being invited to the dance - Phase 2 Study of Telaprevir (VX-950), Pegasys and Copegus in Hepatitis C

[miked]

Yesterday I heard from my doctor that they are trying to enroll me in the Phase 2 VX-950 trial, which is great news and something I've been asking for.

My dilema is that I'm absolutely swamped with commitments from work, church and family...more than usual.  I'd like to hear from the VX-950 people here on the board just how crappy they feel and if they are working effectively.  I own a business with a high profile role that require much travel.  

On my last tx with Peg-Intron and RBV I felt pretty worn down after 8 months.  I'm certain that I could take 3-6 months of this but would only do a year again if my health forced it.

My background is 49 year old male, contracted HCV about 25 years ago; geno 1b; Stage 1/Grade 0; started tx with 3M VL; no EVR but did get a 4log drop at week 2; eventually dropped to 9,600 but started to rise around month 8; game over.  Other that HCV and some newly found arthritis I'm in great shape and run 15-20 miles per week.

So, I really have a few questions that you guys could help me with:

1.) VX-950 people...how crappy do you feel?
2.) Who's done both Pegasys and Peg-Intron.  Which made you feel crappier?
3.) Given my stats, would you jump on the wagon now or wait to see if they can dial this tx down to 3 months, which I could do standing on my head.

Thanks,

Mike

[jmjm530]

Why not wait at least until the trials for non-responders produce some results? Why be a guinea pig when you're only stage 1? At least consider waiting out this year to see the results of the current trials for treatment naives. Personally, if I was a stage 1, I'd probably wait for a non-interferon therapy to come along although that may be awhile. I might change my mind, however, if the 12 week Vertex ARM produced decent odds for success. Hopefully, Fibroscan will be more readily available soon which should make "watch and wait" even more viable.

Be well,

-- Jim

[stangshelly]

I agree with jim, if I had to choose I would wait awhile.I like to see the results first before putting yourself through it all. best of luck :)shelly

[APKhaos]

Twelve weeks of VX + SOC followed by 12 weeks of SOC was moderately rough. I'm fortunate to be able to control my work schedule, but being VP of a major national club created more demand that I was wanting.

Got through it OK, but since I've been off tx a surprising number of people have told me that I looked like death around the time that was the last three months of tx. A high profile front line role that required a lot of public appearances or tough negotiation would not be much fun.

As Jim say, your current stage allows the luxury of waiting a little to see the results of the VX Prove 3 non-responder trial, and other current trials. If any of these have a high SVR rate for non-responders, you are in great shape.  Countering that, the trial is available now, if free [tx drugs, labs, and clinical care], and offers a higher level of monitoring than you will get from most private practitioners. Its your call, but you are in a great position to choose.

[FlGuy]

The part I'll respond to is PegIntron vs Pegasys. TX1 = 24 weeks PegIntron/800 Riba.  TX2 Pegasys/1200 riba on 19 of 46 now.  I've found Pegasys less rude.  Tx's are about the same with respect to sides, junky feeling, ability to focus at work etc.  Since it's more riba, I think the impacts of Pegasys are less than PegIntron. But, other may have different experiences. Take all life matters into consideration and I hope you make the right decision for you.

[pln]

You are in a very good position right now, I know some people can not stand the thought of having the virus inside of them being stage 1 or not.

Vertex will treat you very good, as APK said you will have a higher level of monitoring than you will get from most private practitioners. and all meds are free. Do you know that you will not get placbo?

I did 24 weeks, I was lucky that I did not have to work, also I told no one I was treating, big mistake, lost some friends because of my riba rage. But If I would have had to go longer I clould not have stayed in the closet.

I was just reading that The stock price for Vertex is SO LOW right now.  I wonder if it is low because other people "know something" . I hope not. I go monday for my 8 week post. good luck to you . Pam

[pln]

Here is a site I got from willy over at hcv anonymous.

http://www.fool.com/investing/general/2007/03/01/know-your-drug-stock-abcs-part-2.aspx?source=eptyholnk303100&logvisit=y&npu=y

[GrandOak]

I don't understand how someone who is not tx naive can be enrolled in Phase 2 as I understood that to be a requirement for the PROVE2 trials. Also, are not most of the PROVE2 trials nearing completion?

Are you sure that it's the phase 2 trials, or could it be the PROVE3 trials which are now starting which I understand is targeted at nonresponders and relapsers?

[jmjm530]

Vertex prices have tripled in only two years.

The recent decline could simply be profit taking, i.e. buy on the rumor (expectation), sell on the news (the drug is working, hopefully). That said, I know nothing about investing to take this analysis for what it is :)

-- Jim

[bobbyullc]

i am svr now but if i could have waited i would have stage 3-3 and waited for 9 years. one year on the couch and now lingering fatigue from tx. at stage 1-0 with hcv for 29 years you will most likely die of old age before ever getting any symptoms. i forsee vx and others revolutionizing tx. shorter more success and hopefully someday a mono therapy.
your  sides will be the same as before(and maybe worse) as you are just adding one drug to the old stuff.

the results are sooooo close what can it hurt to wait 1 or 2 years to see. why take a year from your life needlessly?

[jmjm530]

Bobby: your sides will [most probably] be the same as before(and maybe worse) as you are just adding one drug to the old stuff.
----------------------------------------------
Well said and I think I'll steal that line from now on :)

Words in [    ] mine.


-- Jim

[bobbyullc]

i know i sound like a broken record but i just hate to see so many go through this now when new tx is so close.
if i had bad sides the first time stage 1 and could wait many more years i NEVER would have tx,d.
if i could go back and wait even today i would. if i knew that vx was so close even at 3-3 i may have waited.
hope your helth is improving.
bobby

[jmjm530]

I agree. But even if Vertex turns out not to work, I still would advise people who can afford to wait to do so. I didn't know anything about Vertex -- didn't exist back then -- but still waited as long as I could. Like you say, it's like adding one bad thing on top of another. Do it only if you have to.

-- Jim

[dointime]

I haven't had too bad a time on VX950 but I didn't get ribavirin and I didn't have to go to work.  Anyway, how it went for me is not the point, is it.   Point is that the sides are unpredictable.  If your commitments mean that you can't afford for things to go pear shaped with unpredictable sides then you have your answer.

dointime.

[mremeet]

That's a tough call. Like the others have said you only have an F1 liver, so you certainly have time to wait. Also, the Prove 3 trial is supposed to have a placebo group (which I consider unethical for SOC relapsers). Plus, if it's going to be run like Prove 1 and 2, rescue drugs will be prohibited during the VX/placebo dosing period. These two factors would really, REALLY give me pause. Especially considering (1) you've already been through the SOC grinder and (2) you only have F1 fibrosis. You need to really know the details of this trial, like ARE they really going to have a placebo group? Will rescue drugs really be prohibited initially? How long will the blinding period be for? I can assure you if these factors are in play, there's a lot more "sport" in this trial than you may currently imagine. Also, the average side effect profile is a lot more aggressive when telaprevir is added to SOC when compared to SOC alone. The VX + SOC dropout rate in the first 12 weeks of treatment for Prove 1 was three times that of SOC alone. And 34% of patients experienced rash during treatment with VX950+SOC. Gastro problems were also common on VX950 (i.e. diarreah and nausea), and VX950 contributed to anemia in some (although I don't think it's a powerful driver for anemia). So although it sounds like you tolerated your previous course of treatment well, the odds are not that unlikely you could run into more serious problems this time around.

Anyway, it's a tough call. But if you do decide to enroll, I would try your best to clear your plate or at least lighten your load during the trial. If you run into hardships, you'll need to be able to fall back and take it easy. If you dedicate yourself to doing it, make a committment to yourself to do whatever it takes to go the distance. If you overburden yourself, the chances of accomplishing this goal will be compromised. Your health always come first - without it, what else is there?

[bobbyullc]

i am mostly sorry for those out there that have a real fear of hcv that ruins their life. it is something to be feared but education can aleviate that fear if only they could have confidance in it. i keep hearing of "friends who died from hcv" but never heard of one who was stage 2 or even 3.
i also HATE they STIGMA many apply to hcv.

[jmjm530]

I forgot about the placebo group. A placebo group for previous non-responders? I still can't get over how unethical that is. In fact, I can't believe they'll really go through with that but maybe I'm just being naive. That is good enough reason alone for someone not to do the trial. Second time around, you want to change whatver you did the first time to give yourself a better shot. Getting stuck in the placebo group won't do that.

[miked]

Wow...thanks for all of your comments and information.

I copied the trial name directly from the clinicaltrials.gov website.  There's some confusion because Prove 3 is the Phase 2 Study of Telaprvir VX-950 and it IS for non-responders.

A placebo group with SOC tx for non-ersponder is cruel and stupid.  It didn't work the first time and the stats are like 1-2% that SVR could be had under the same regimin.  Some of these researchers should inject themselves a few times with Interferon.  I'd drop out if I smelled I was placebo.  Would Vertex give the real deal to placebo people after a period of time?

The fact that I have this thing in my body is driving me nuts, but, remebering the 7-8 months of fun on Interferon sure makes me think.  I too travel on business frequently and have constant meetings with groups large and small.  When I was treating last time there were days that I'd lock my self in the hotel after a long day and was SOOOO grateful not to have to interface with anyone else that day.  Plus I was taking anti-depressants for the Interferon and medication for the diarrhea that the anti-depressants gave me and on and on and on.

What's everyone's thoughts about where this thing is headed in terms of time for treatment?  Will they get this dialed into a 2-3 month thing in the near future?

I'm still thinking about my decision.  Thanks for listening to me ramble.

Mike

[FlGuy]

The VX'ers have reported here over the months about the time requirements for testing and blood-getting, especially in the early weeks.  So if you committ, your committing to time and the travel necessary to the trial site.

[APKhaos]

That's a VERY good point!

My trial clinic is maybe 15 minutes away, but many people travel considerable distances to a trail center. In either case, the visits are many, and non-negotiable. For most of the visits, the window is just 24 hours either side of the scheduled date.

[mremeet]

jim - Yeah I'm having trouble believing the FDA is going to flatly allow a placebo group amongst the relapsers. That's just insane, especially when combined with denial of rescue drugs. Hopefully they'll back off on that one.

miked - I didn't fully explain in my previous post the complete implication of what happens if you are on placebo and either your neutrophils or HGB drop below 750 or 10 respectively. If your ANC's go below 750, they will cut your IFN dose in an attempt to get the ANC's back up to acceptable levels (instead of giving you Neupogen which could prevent an IFN reduction). If your hemo goes below 10, they'll cut your riba (instead of giving you Procrit which could prevent a riba reduction). As you probably know, if you're an SOC relapser and happen to end up in the placebo group and experience an IFN and/or riba reduction early on in treatment (which is when rescue drugs are prohibited), then clearly that would all but devastate your chances of SVR-ing (much less clearing early). And even in the case of someone getting the real telaprevir, a dose reduction of either IFN or riba early on could cut your odds considerably. We have a few treatment naive Prove 1 folks here who received VX950 and were not successful at clearing the virus (one without riba and the other with no dose reductions if I'm not mistaken). So even if the telaprevir is in the mix, IFN and riba reductions could still have a very adverse effect on anti-viral performance, especially in an SOC relapser.

Also, flguy brings up a great point. There ARE a lot of visitations required. If you have a requirement to travel alot for your work, you'd better check out the required trial visitation itinerary. It's pretty rigorous, especially during the first 12 weeks (if the 12 week dosing period will be retained as it was for Prove 1 and 2). Plus of course there's the hassle of transporting all the drugs everywhere you go, including the always refrigerated IFN. Not suggesting that doesn't make it worth it, but it is definitely a factor to consider. I had to put off all long term work related travel during my treatment program. For me it wasn't a big problem, but if you can't easily get out of travel committments, then it will likely be a problem for you.

Take care...

[dointime]

Will a 3 month duration do the job?  That is one of the current burning questions, at least for me as that is what my trial arm does.  There is no data out yet on folk who only did 3 months and I haven't seen any of them report here either.  So the answer to this question right now is anybody's guess.  I hope that Vertex will choose to go public at the April EASDL conference in Barcelona on how the first 20 PROVE1 people who did 12 weeks are getting on.

dointime    

[web52]

vx950 w/ 1200 riba & pegasys 175, first time tx. started august. in 48 wk soc group. cleared at day 22. felt very crappy first 4 months. missed some work but not much due to screening, biopsy, frequent med appts to draw bloods etc. required by the study. missed 2 doses of vx & riba due to severe lower gi stuff, cramps constipation & vomiting for a day and a half. not sure how much was related to the vx, but i wound up taking miralax every day & still do, that really helps the gi stuff. since its my 1st time in tx, i cant compare it to plain soc or peg intron. my vl was around 4 mil pre tx, w/ good biopsy. chose to treat on docs rec. also, im 54 pretty healthy otherwise & didnt want to put it off, figure it would be tougher on me as i get older &/or less healthy. glad i made that decision given the results so far. overall my sx (have all the typical ones) were moderate to hi moderate for the 1st 4 months & moderate after that. they are getting better the past couple of weeks. some days are mild now. best of luck to you whatever you decide.  

[Willy50]

Mike, I might just abbreviate some of the information you have already received it sounds to me as if you may be a good candidate to wait based on your status and many of the factors you've described as important.

Your ability to conform to the study may be compromised; you travel a lot, have many commitments, and are attempting to maintain all prior commitments

Your ability to treat is not based on financial need (or so it sounds to me).  You may be able to (if Vertex is approved for HCV) treat in the future without financial hardship.  Many people may not have this option.  Treating in a trial may save them perhaps tens of thousands of dollars.

By waiting your outcome could be better;
1)  You are assured of getting the best treatment (not placebo)
2)  You are assured of being able to use rescue drugs if needed
3)  You need only treat as long as is required (we don't know how long that is at this moment).
4)  You may have more autonomy in making decisions about your own scheduling of treatment, it's dosage, it's duration.
5)  You would be starting treatment based on KNOWN outcomes and proven and refined treatments (which may occur in Phase 3, not an experiment, albeit a potentially great one).  Approved treatments could include reduced ribiviren, twice daily dosing, or an improved understanding of the treatment of sides associated with treating with Telaprevir.  (segue into #6)
6)  I'm not sure if this has been mentioned but it is always understood that an approved drug and treatment should be safer than is experienced during a trial.  What if Vertex were not approved for safety reasons?  Or what if it is approved but has some new quirky sides in a small sampling of patients?  You will be able to make a better informed decision in a relatively small amount of time.

In short, put together a "worst case scenario" involving joining a trial.  Would you be satisfied participating if you were given a placebo, had to do treatment for a long time or were denied the use of rescue drugs?  Now flip it; what components would be included in the best case scenario treatment?  Your decision will be based on which will be the best fit for you.  It may not necessarily be that for another person.  

(PS.....it's a different question but what about being able to get into the PHASE 3 (not Prove 3 for treatment failures) study?  That will be the next question, if and when the Phase 3 studies begin (seems like at possibly at the end of this year).

(PSS......it seems to me I've heard of worse sides associated with Peg-Intron but as you know people all respond differently)

Best wishes,
Willy

[Forseegood]

Just wanted to thank all of you for your contributions, I'm copying this thread for my own personal reasons, thanks a lot guys...

[jmjm530]

Nice recap!


-- Jim

[miked]

Thanks for all of your comments.  I think that I'll ask for an appointment with my doc to review all the options and make my decision.  Perhaps even request another chemical marker or biopsy to confirm that I've not progressed.

Again, thank you.

Mike