Trial questions

[chcnme]

Hi everyone. I'm getting nervous about a trial I've been told I can participate in with a poly-inhibitor  (and one I've said I want to participate in.)  

http://www.hivandhepatitis.com/hep_c/news/2006/082906_c.html

I was told that it's "looking very good so far."  That's all I've been told, (well that - and I've been told I'll be getting the regular 48 weeks of combo if things go like they're supposed to, that I might get a placebo, and that I should be getting a call in a few wks for enrollment, and that I should be on treatment by sometime in mid/late Feb.

I was first called in September about this trial.  I’ve been reading about it since.  The more I read, the more confused I feel.  Before I start asking my research facility a bunch of questions,  I wanted to ask for help here.   (continued).

[chcnme]

FROM  
SOUREC:  http://www.natap.org/2006/DDW/DDW_18.htm

http://www.natap.org/2006/DDW/DDW_18.htm

Could someone please go to that link above and see the chart “HCV RNA Change From Basline”  (where the viral load decline after day 4 is observed to go back up).  I think in the 500 mg dose it even looks like it went above baseline.  

Here is one of my questions:  If the virus has been shown in phase I to rebound and at around day 14 is back to baseline, then what is the drug doing that’s supposed to be “good”?    AND is this were Peg/Rib are supposed to.... knock the virus back down?

And on the “drug resistance issue”:  If one gets a “drug resistance” does it mean that future treatment would be more difficult with.... say....newer drugs, i.e. protease inhibitors or polymerase inhibitors?  

Thanks a lot if you have time to comment, or -- I would also greatly appreciate if someone can give me some suggestions on questions I might want to ask now  (before I get that phone call - or - questions I can ask WHEN I get the phone call)  That would also help me a lot.  

Thanks.

[NYgirl]

you haven't treated before?

if you are going to take the chance of getting the placebo but also doing the 48 weeks of SOC...then it's really just LIKE doing regular treatment (except I think you have many disadvantages being blinded personally) but you have a CHANCE of getting an extra boosting virus killing drug!

To me the question is really since i'm going to be doing SOC anyway what do I want more...a chance at getting the extra drug OR the ability to have all my data at my fingertips to make decisions by.

If you are willing to not know and trust the doctors...then it's no big deal.  I had to have a 4 week that I could look at because I'm just a nosey witch.

It is a very hard decision but I'd keep it as simple as possible and use a formula like that.

Also - WILL they let you have rescue drugs?  To me...I would have had to stop treatment without them. So that is a big factor.

[NYgirl]

I'm not smart enough for all of the stuff above so I tried to give you my opinion not using it.  Sorry. I'd like to help but...even BEFORE brain fog I was never the sharpest tack in the box - knife in the drawer...whatever ;)

[Imagine]

I have studied those graphs and the remarks and understand your questioning of why even add this to the standard mix. I see where almost all were back to baseline after 14 days. The biggest dip appeared to be day 4. Continuing treating with SOC would appear to be as if you had never taken the experimental drug.

Your questions seem very logical to me. Since initially the attempt was to be a stand alone product (at least the vx-950) that these inhibitors are now being targeted as a tag along with standard combo to achieve the maximum evr in the crucial first 12wk phase of tx. Are you adding in the possible factor of strain resistance by introducing this specific inhibitor? I sure can't answer that question but you have to wonder in looking at the data what causes the rise to baseline after 4 days of 14 days that the inhibitor is used in conjunction with SOC.

This would be one of the first questions I would ask the research co ordinator.

Since you would be still doing the standard tx of 48wks you would definitely get the benefit from it and would really doubt if it would be a factor that would affect it in a negative way.

It seems the length of time to continue to treat after becoming undetected seems to play a prime role in the success/failure of tx. I am starting to have concerns with the wide range of pcr sensitivity testing. When is undetected really undetected and....Well that needs to be a topic of a new thread so I won't talk about that anymore here.

I know this probably does not answer your questions but you have addressed many concerns that I have been having. Since I was a super responder with the standard combo is it of any value to me to retreat with the added ingredient of inhibitors but this leads me back to the undetected test and length of time. Again I have not seen enough data on SVR comparisons.

Maybe you can just look at it as doing the standard 48wks with a potential positive factor added in.

Imagine

[Imagine]

As a relapser I also have wondered what would happen if I relasped with the added inhibitor with SOC. Would that mean it would be all the much harder for me to retreat for a third time due to the resistance factor? I have answered myself (oops I am not really talking to myself, at least yet:), with the following logic. Interferon/Riba treats all strains of the virus so I would hope if I was to retreat this combo would still apply to the possible "altered strain". As far as retreating with newer drugs the only thing I can come up with in my head is that like antibiotics there would be other types that would be available if you became "immune" to that particuliar antibiotic. Again this is my own though process to help with my fears about all this. I hope this helps in some small way.

Easy to say but harder to do, try to relax a bit, you know you need to treat and you would be getting that with the proposed trial offered to you. As far as the added drug you would only take for 14 days (I think) and it might prove to be that little extra push to attain SVR.

Good Luck, wish you the best,
Imagine

Imagine

[Bill1954]

LOL! Of course you know that your being a side effect of my treatment experience probably affects your memory also, Scott! Seriously, I just wanted to say hello and see how you’ve been doing lately. I read down below that you’re sister-in-law is still intact, and on the TP list. I wish both of you well,

Bill

[desrt]

It's why they're called trials - a lot of the questions you have will be answered *after* your data comes in. Since you had so many adverse sides the first time you attempted tx, the main question I'd be asking is 'will they let you use whatever rescue drugs you need?'.

[chcnme]

Thank you both!  NYgirl, I had two weeks of Peg and Cop in 2003 and had to come off and chose at that time to go in Watch and Wait under a new doc.  I like my doc a lot and trust him.

When he called in Sept about this trial, he said that even with the two weeks prior I had before, I can still get in this trial because it is for treatment naïve and nonresponders and because someone with only two weeks can get in.  

While in this watchful waiting these past few years, it was understood I would treat with regular SOC if doc said “it’s time”, OR - if a trial came along with the newer drugs that I could get in, I'd go that route IF I wanted to.  And so, it has come to that point  (trial has come along I can get in.)   AND with this trial I will also get 48 weeks SOC (very important to me.)  This trial, even though this is not a tremendously potent drug as compared to VX, meets my needs, so to speak. I am getting SOC AND a newer drug that is showing some ... decent results  (I guess :)

We have discussed rescue drugs. It's still up in the air  (or was last time I spoke with doc a few weeks ago.)  The coordinator told me last month (over the phone, very quickly)  that this trial did not allow them.  That worried me and I asked my doc to call.  He called and said I might be able to get them IF I needed them but that even I could not get them, he thinks I will do OK and that he is not worried about them at this time.  I want to think I will OK, too, and even though I’m worried about the availability  (or lack of)  rescue drugs,  I don’t think it's worth my saying  (at this point)  “no”.   I think it's going to be a "we will cross that bridge IF and when we have to" approach.

I don’t understand all what “blinding” encompasses, really.  I know I don’t care if I am subject to get a placebo (since I will be getting the SOC, the risk of a getting a placebo doesn’t matter to me.)  The drug resistance issue  (or my lack of knowledge on what it means), though, does concern me.  

Gosh I hope they let me know what my 4, 6, 12, and 24 week labs show. Since I‘m blinded, will I not know?  

hmmm....maybe I might be just as well off NOT knowing all the details when all this starts because "knowing" (in my case) is not knowing a whole heck of a lot because by the time I figure out what it means, something new has come along or it went away : )

Coffee time!  

Thank you both very much.

[chcnme]

Hi desrt.  I had been extremely worried about that (the first go-around.)  And so my questions have basically been centered around that  (and how we are going to prevent a "here we go again" scenerio).  Doc has assured me these past six months (especially since he told me about the trial)  that when they began me on treatment back in 2003, my counts were all low going in and that it was certain I was going to have some major complications.  He was flipping through my labs on my first visit and he kind of laughed and said "you didn't have a chance back then."  I have not seen my labs from then; I don't know what they were when they started me, and I don't even want to know what they were.  It would probably scare me too bad.  I know what happened when they began me, and I know it scared the **** outta me when all the mess went down, and yeah... I'm still scared in that regard, but I am trying my best to put some faith in what my doc now keeps telling me, and that is - you are OK now.  And by OK, he means my labs are good, I'm not low platelets, low wbcs, low rbcs going in.  He knows I've been real scared, and he has tried to reassure me that it does matter about labs going into treatment  (and that it matters now that mine are OK).  

My peridontist has also given me the green light and has told my doc he will clean me with a note from him that says I'm OK to get the cleanings.  I will be dosed with the antibiotics, etc. Yeah this scares the **** outta me,  but I just guess I have to bite the bullet and trust him??   (biting nails here.)  

Thanks!

[chcnme]

LMAO!  Please be here when /if I begin treatment.  I need a figment in my imagination.

[mremeet]

chquote: "Here is one of my questions: If the virus has been shown in phase I to rebound and at around day 14 is back to baseline, then what is the drug doing that’s supposed to be “good”?"

It appears from the data provided (in my opinion), that the drug is probably not suitable as a monotherapy. In other words its effectiveness is insufficient to eradicate or clear the virus by itself. That doesn't mean it can't be an effective adjunct when given in combination with IFN and possibly ribavirin. The drugs used today to fight HCV aren't very effective all by themselves. For instance, ribavirin is a very poor HCV antiviral all by itself. And Peg IFN is only a mildy effective antiviral agent by itself (in regards to its very limited ability to deliver an SVR). However, when you add weight based ribavirin to peg IFN, suddenly the anti-viral effectiveness greatly improves. The two drugs have a synergistic effect on one another which makes them much more effective in combination than they are as respective monotherapies. Together they constitute a reasonably effective therapy for type 1's, offering a reasonable hope of achieving an SVR, whereas separately their performance is rather dismal.

So the point is, is that just because this drug's demonstrated anti-viral effectiveness tapers off pretty quickly after 14 days, that doesn't mean it won't pack a potent punch (or increase SVR rates) when given in combination with IFN and possibly ribavirin. This is especially true because the two (or three) drugs work on the virus using different mechanisms. The way in which this PI, IFN and riba fight the virus is different. This is important because coming at the virus with two or three different kinds of mousetraps makes it much more difficult for the virus to mutate into resistant strains that know how to avoid the various kinds of mousetraps (and thereby continue to survive/replicate within your body). Viruses are usually good at coming up with defenses against a singular mode of attack, but they can have great trouble adapting to (and dealing with) multiple modes of inhibition/eradication working on them simultaneously. This is also why HIV is fought using drug "cocktails". A mixture of drugs working in differing ways are used (very successfully) to apply pressure to the virus from different angles. Again, this makes it much harder for the virus to adapt (via mutation) to the multi-pronged assault on its existence and ability to reproduce.

"AND is this were Peg/Rib are supposed to.... knock the virus back down?"

They probably plan on dosing this PI with IFN and perhaps riba too in future trial(s). As stated above, hopefully this PI along with IFN/riba together will work exponentially better than their respective monotherapies. I suspect this PI's viral decay curve will look an awful lot different when given in combination with IFN/riba than all by itself.


"And on the “drug resistance issue”: If one gets a “drug resistance” does it mean that future treatment would be more difficult with.... say....newer drugs, i.e. protease inhibitors or polymerase inhibitors?"

The reason the virus rebounded after ~14 days was probably because of resistant strains becoming dominant in the population (with non-resistant strains dying off). They allude to this possibility in the study, but don't conclusively claim that (still being determined, I guess). But again, that doesn't mean the same thing would happen with combo therapy. The PI would attack in one way, and even if the PI resistant HCV strains survive the initial effects of the PI, they're not likely to also be resistant to the effects of IFN and ribavirin. Therefore, they'll be less likely to selectively survive and grow to dominate the surviving population.


"I would also greatly appreciate if someone can give me some suggestions on questions I might want to ask now (before I get that phone call - or - questions I can ask WHEN I get the phone call)"

If it is a blind study with a control group, I can speak with experience that it can be very emotionally taxing to be in a study like this. It can be harder on you than you realize (going in) to be deprived of knowing if you're responding (with blinded VL's), what duration group you're going to end up in (if the study has varied duration groups) and whether or not you're even receiving the research drug at all (if there is a placebo group). This is especially true if you start having serious side effects and are suffering a great deal (making it impossible to know if it's worth hanging in there). If they deny you rescue drugs during part or all of the trial (which they probably will), like neupogen and procrit, than that can very well lead to dose reductions in IFN and/or riba in order to deal with low HGB and/or low neutrophils (that otherwise would have been avoidable on SOC). And dose reductions will result in a lowered chance of SVR-ing, *especially* if you're in the placebo/control group. Knowing all of this forces you to endlessly juggle and consider all of these issues (and all the usual nightmares associated with SOC) and experiences with an IFN/riba addled mind. Believe me, it can really put the zap on your brain!

[NYgirl]

Gosh I hope they let me know what my 4, 6, 12, and 24 week labs show. Since I‘m blinded, will I not know?



I thought when you participated in a trial it pretty much guaranteed you wouldn't get these results until whatever week you were finally allowed to.  

I am a big believer in using the Berg and Sanchez studies to tailor treatment and so that wouldn't work for me.

I needed the 4, 12 and 24 week pcr results to make my decisions with WAY too much! I thank God I had them or my treatment would have been totally messed up.

I have to tell you...without the hope of rescue drugs I would have failed treatment miserably and had to quit at about week 4. My hemo went from 15+ to 9 in TEN days or so. I could not have continued on without the Epogen.

So that worries me big time. Of course...if I fail on these 72 weeks for any reason I would most likely have to wait and then do a trial eventually when they allowed us to get in...so then I'd be in the same boat and most likely not make it through.

So much for us to THINK about isn't there? Yet there are people who just go OK doc tell me what to do and then do it and NEVER think about it again.

I almost wish I could fall into that category instead of "hopelessly endlessly obsessed by data and opinion" group...but I'm not.

I wish you the best you know - no matter WHICH way you decide to go. I'm sorry there is just no easy answer.

[chcnme]

Mrmeet, you just don't know how much I have appreciate and valued your input here and all you have been willing to share as far as your knowledge on this stuff.  It has meant the world to me (and I'm sure so many others.)  You too NYgirl! You too Imagine!)  

Mike and NYgirl, I just wanted to let you both know I just now read your notes  (and they are so appreciated).  I have to go right now, though, and won't be back until later this evening, but thanks so much for responding and giving great input and for ....just being here!  

For now I can say that I am almost 100% certain I'm going to do this (this treatment in this trial.)  I've been thinking a bout this for over two years now, and .. the time is right, I think.  (or as right as it's going to get.)  

Mike thanks so much.  I so appreciate your explanations.  I'll be back later!  Hope you're doing OK and that the rash has subsided some.  Whew!  you've  been a fighter!

[Chev55]

Please take a look, again, at the thread indicated below.  Thanks.  (dated 12//09/06)  I've been vacationing the last few weeks, and understand you have as well - I hope this is a good year for all of us!

http://www.medhelp.org/perl6/hepatitis/messages/44113.html

[crsrph]

i asked about rescue drugs on the vx950 study and was told that after the end of the dosing on the trial drug and during the soc therapy that rescue drugs could be used but that the trial would not pay for them . i would ask to see if that was the case for you also

[BThompson4]

The new drug is meant to be used with interferon and riba.  Getting a large drop in the virus by day 4 could give you a nice jump start or head start in getting viral levels low enough that treatment to get svr might be shortened and thereby less toxic. Kind of like the idea of pre-dosing riba prior to taking your first interferon shot, but hopefully much more effective.

A study has shown that (can't find a link) that some mutations occur with vx-950, but that these strains happen to be not very resistant to peg and riba, so in combination the vx-950, peg, and riba is a potent combination.

If I were a geno 1, I would consider avoiding a study that limits SOC treatment to 48 weeks, unless I were low pre-tx viral load and had no or little fibrosis.  Recent studies have shown the value of extending if you are a slow responder; and this board has shown that even rapid responding geno 1's often relapse after 48 weeks.    The study pays for your meds, but I don't think it is worth it giving up the treatment changes that might be warranted once your pcr's and other information come in during treatment.

[Hepatitis Researcher]

I did not find any question of yours in the thread that you indicated. Mistake?

[ladybug52]

How are you? Good to see your name for a change. I went to the archives trying to find your question but couldn't find it either. I don't know about your computer, but for me trying to look for something in the archives is like trying to look for  something underwater with the tide against you. It's so slow! I wanted to help but had to give up. Just repost the question.
Take care
Bug

[Chev55]

My mistake in not being clear.   It was an attempt in assisting another hepper.  Scott (Revenire) addresses you in this thread regarding an exchange (between the two of you) on 12/09.  You had mentioned at that time you would be away.  Perhaps you've already noted his email addy above,   I remember it clearly before leaving, thinking it quite interesting due to the fact it is a case of HCV/AIH.  Although it does not pertain to me, would be interested in your thoughts as well.

Hi bug, bless your heart... stop searching!!  I am glad to see you - (and wishing you a 'healthier' 2007!  I miss many of you,  

Depression:  I took some time to read a bit yesterday and saw Chellski (Hi Chelley!) and Alady mention post depression.  This may not help the depression but might explain it.  During the time I've been here (Jan '04 to present), I have seen many, many people mention post tx depression.  I experienced it myself.  And, like many mention, it was something that was not part of their lives prior to dx and tx.  I can't explain it scientifically, but believe there is a change in our brain chemistry.  So for some of us, there is a recuperation period post tx.  I pray that you do not suffer long.  Please know there is light at the end of the tunnel.  There were times during 2005 and early 2006, where I feared I would not pull myself out of the darkness, but I have - Life looks great,  I feel positive.  I believe you will too.  A couple of my very good friend Nolee (neal) and TonyZ (whom I keep in contact) had very similar post sx that I've experienced.  And  many others.,, so KNOW you are not alone and it is not permanent.  I found daily exercise, seeking out as much sunshine as possible, good diet, SAMe, socializing with good people, and prayer, (if you're so inclined) has found me quite content.  I think of those with HCV daily.  Although I have held my SVR for two and half years, well... you know, once a hepper, always a hepper (and thus the kinship).

[chcnme]

Thanks crsrph,mrmeet,bthomp (and all)

crs and mrmeet - let me ask you all this (if you can tell me). Since you all have been there / done that you might be able to answer this for me.  I have not been told yes or no (even though I have a feeling I can get them after the dosing).  And so my question to you all is -- IF I want a definitive yes / no answer on this, should I just wait and ask whoever is going to be calling me?  And -- is that most likely going to be my research coordinator who will be calling me?

And Bthompson, Thank you.  What you said about the “jump start” is about the way my doc explained it a while back, and what mremeet said was also about the same way he described it.   I read about the mutations and wild viruses with VX (and that they were suppressed in vitro with peg/rib),  but I wasn’t able to find anything on the 796 in that regard.  

I found this
From
http://www.clinicalcareoptions.com/Hepatitis/Conference%20Coverage/Los%20Angeles%202006/Tracks/New%20Data/Conference%20Report/Pages/Page%206.aspx

Nezam H. Afdhal, MD:
I agree with Dr. Kowdley that it is worth highlighting that there was an unusual event in this study. Unlike the other 2 HCV polymerase inhibitors in clinical development—valopicitabine (NM 283) and R1626—HCV-796 actually produced the maximal viral suppression at Day 4, and then there was a gradual rebound of HCV RNA from Day 5 through Day 14. In the 1000-mg cohort, the maximal effect was observed quickly, followed by a slow increase, so that by Day 14 the viral load reduction from baseline was only 0.7 logs. This clearly indicates that this agent will have to be used as part of combination therapy to provide maximal efficacy and prevention of resistance, not as monotherapy.


And
http://www.prnewswire.com/cgi-bin/stories.pl?ACCT=104&STORY=/www/story/05-21-2006/0004365778&EDATE=

Since doc has not said he feels I am a better candidate to attempt 72 vs. 48 weeks, I am not interested in weighing that into my decision at this time  (although it is in the back of my mind - ya know - like uh -- will I be one who one day will be recommended for 72 weeks).  

And even though it’s a definite plus to be able to be getting SOC and 796 and all labs at no cost, (well, might be placebo :) the main reason I’m going with the trial is - I have wanted the best management and treatment I can get, and - I think I have it with this doc.

We’ve talked about future treatment  (if I have to be pulled)  and he’s said if I have to be pulled or am not responding that there would be a wash out period (three months) and that we would go from there. If he recommends 72 weeks at some point,  I’ll definitely go with that recommendation (but so far that has not come up, yet, at least.)  

I went to him back in Sept 2005 because he’s supposed to be one of the best.  The research facility is 3 hours away, but it's been worth every mile and every 3 month visit.  He's a very nice doc, and since he is one of the best, I think it’s best for me to trust him.  Since he thinks this trial is worth my trying, I’m going with it. I have had my moments of wondering if I‘m doing the right thing, but - I think I am  (doing the right thing.)  If it doesn’t work, I hope I will still think I did the right thing :)

------------------

And uh.... I really don't know what to say about the other stuff that appeared here but feel I need to say something about it.  I don't know what it means or what's going on.  If someone is super super depressed, I am very sorry you're going through tough times.  I don't have time to read from the links, and so if I've missed something, I'm sorry -- I just wish you all the best.  

THanks

[mremeet]

I'm not sure what your question was in your last post. But I'm assuming you're asking about what you should inquire about concerning the possible use of rescue drugs during a prospective trial with this drug? If so simply ask them directly and also about all of the details governing the trial protocol. For the VX950 Prove 1 trial, there were four groups you could be randomly assigned to. One was the placebo group, this group received SOC+placebo for 12 weeks and then SOC for 36 weeks thereafter. One group received SOC+VX950 for 12 weeks, and then stopped. One group received SOC+VX950 for 12 weeks and then SOC for 12 more weeks (24 weeks total). And one group received SOC+VX950 for 12 weeks followed by 36 more weeks of SOC (48 weeks total).

Procrit and neupogen were forbidden for the first 12 weeks (i.e. during the VX950/placebo dosing cycle), but are allowed (as needed) after that. The reason they did this is because they wanted to see what effect the VX might be having on the trial participant's neutrophils and HGB. If VX dosing patients who experienced low HGB and/or neutrophils started taking neupogen and/or procrit, then this would shield and obstruct the view of what the full effect VX was having on these patient's white/red blood cell counts. This is understandable, and they did find that VX950 could exacerbate anemia in some patients; something that might not have been identified without the deprivation of the rescue drugs.

However, from a patient's perspective, the deprivation of rescue drugs during the critical early phase of treatment (i.e. the first 12 weeks) could have very negative consequences. The reason this is true, is because if you end up in the placebo group and you experience low HGB and/or ANC's(which many people do), then the only way they can deal with it is to decrease your riba and/or IFN as required (riba lowers hgb, IFN lowers neuts). And unfortunately, lowering your dose of IFN and/or riba can have a really negative effect on your SVR odds, especially early in treatment when knocking the virus down as quickly as possible is desirable and also if you start out with negative factors against you (i.e. high starting VL, extensive fibrosis, older age, high BMI etc). Effectively this scenario could easily lower your SVR odds well below what you could achieve with SOC (and the use of rescue drugs).

For example, PLN had her HGB take a nose dive shortly after starting. They cut her riba in half right off the bat to deal with it. PDS came close to having low HGB too, which would have resulted in her riba being cut (she made it without a reduction, but is taking procrit now). My neutrophils dropped to like 600, where the study I think says you should lower the IFN dose if it goes below 750. Fortunately my doc knew that lab readings for neuts could come back falsely low (due to the fragility of neuts in transit to the lab). Duplicate tests were run locally which were higher, saving me from an IFN dose reduction. Also, in practice an otherwise healthy HCV patient can usually tolerate neuts below 750 (within reason of course). But I'm sure there are some poor saps in the placebo group that experienced reductions in IFN/riba. They'll experience a lower likelihood of SVR-ing than if they were simply taking SOC as a consequence of that. So that's something important to think about before signing up for a trial with a placebo group (if your study is structured like the VX950 Prove 1).

Lastly, are you sure this drug is the right one for you? There might be more promising ones coming along or already in a similar phase of development. I'd check it out real good before committing yourself. Take care...

[chcnme]

Hey Mike, thanks so much for that explanation. And no - to be honest (after sitting here for the last several days reading from several sites and compiling data on the trial design, dosing, etc. and trying to figure out what the H it all means) I'm not sure about anything anymore - lol.  I was under the impression (because I was asked "do you have any problems with the idea of possibly getting a placebo", which I don't) that this 796 trial would have a placebo control.  Now I'm not so sure after I've read the trial design and have compared it to trial designs I KNOW had placebo control. I don't know that 796 DOESN'T have a placebo or that it's not blinded, but on the trial design it doesn't have "double blind"  or "placebo control"  anywhere  (not at clinical trials dot gov or Virompharma site).

Here is what it says from

http://www.clinicaltrials.gov/ct/show/NCT00367887?order=1

A Study Evaluating the Safety and Clinical Activity of HCV-796 in Treatment-Naive and Non-Responder Subjects

This study is currently recruiting patients.
Verified by Wyeth December 2006

Purpose

This is a phase 2, randomized, open-label study comparing the safety, antiviral activity, and pharmacokinetics of HCV-796 administered in combination with peginterferon alfa 2B (Peg-Intron) plus concomitant Rebetol vs. Peg-Intron plus Rebetol in Hepatitis C Virus (HCV) genotype 1-infected subjects who are either naive to treatment or who have previously failed treatment (non-responders).

Study Type: Interventional
Study Design: Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Safety/Efficacy Study

Official Title: A Phase 2, Randomized, Open-Label Study of the Safety, Antiviral Activity, and Pharmacokinetics of HCV-796 Administered in Combination With Peginterferon Alfa 2B (Peg-Intron) Plus Ribavirin (Rebetol) Versus Peg-Intron Plus Rebetol in Subjects With Hepatitis C Virus Genotype 1 Infection

-------------------

OK - then this is off the Viropharma site, giving more info on the Phase II design

http://phx.corporate-ir.net/phoenix.zhtml?c=92320&p=irol-researchNewsArticle&ID=920335&highlight=

Phase 2 Design

The Phase 2 study is a randomized, open-label study of the safety, tolerability, antiviral activity, and pharmacokinetics of HCV-796 administered in combination with pegylated interferon plus ribavirin versus pegylated interferon plus ribavirin in HCV genotype 1-infected subjects who are naive to treatment. The combination of HCV-796, pegylated interferon and ribavirin will also be assessed in a group of HCV genotype 1 patients who have previously failed treatment (non-responders). Participation in all dose cohorts will include up to 48 weeks of treatment with combination therapy including HCV-796, and a 24-week follow-up period.

Initially, approximately 267 patients will be enrolled to target a minimum of 222 patients into 3 dosing groups:

(1) 74 treatment naive patients receiving pegylated interferon and ribavirin (control therapy);

(2) 74 treatment naive patients receiving pegylated interferon, ribavirin, and 500 mg of HCV-796 every 12 hours; and

(3) 74 non-responders receiving pegylated interferon, ribavirin, and 500 mg of HCV-796 every 12 hours.

After 12 weeks of dosing the 500 mg cohorts, tolerability and antiviral data will be reviewed to identify the additional dose group(s) to further elucidate dose response. The subsequent dose cohort(s) will be enrolled in the same manner as the initial 500 mg cohort.

Outcomes assessed in the treatment groups will include:

*  Antiviral activity and percentage of subjects with undetectable plasma HCV RNA levels at weeks 4, 12, 24, and 48;

*  Percentage of subjects with sustained virologic response (SVR), defined as undetectable (less than 10 IU/mL, as measured by the Roche COBAS TaqMan(R) assay) plasma HCV RNA levels at 24 weeks after the end of treatment

(and it's continued with more info on what PhaseI showed)
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Does the trial design mean there is no placebo control and that it's not blinded?  I have not been told anything specific about the trial (other than "it looks good" and that I'll also be getting 48 weeks of SOC, and that I could read more about it on-line).  I was never under the impression, though, that I would be getting 796 for perhaps 48 weeks  (but the trial design sure looks it's planned to do that with some cohorts and that it's going to be determined as time goes by who will be dosed with what and for how long.  I'm not able to interpret it all, to be honest. I need to call someone at the research facility, I guess, or either just wait for them to call me and then start asking questions - same ones I've asked here.  

Thanks for listening to me and providing me with some great input.  Coming here is like having a personal consultant lol!  It truly is!  You would never get this much time, input, feedback, and food for thought from just "routine appointments" with the doc or from talking to the research coordinators.  This (the feedback here) has put me directly on a "missing link" that I didn't even know before today was sitting in front of me. You all have helped me think of the questions I need to ask to make my decision BEFORE I commit.  Thank you so much!

[crsrph]

open-label study would mean that you and treatment team would know exactly what you are getting for drugs would also guess that they would give you all lab results including vl's since nothing should be held back ( my thoughts). dont know if they are going to consider you a non responder or treatment niave (understand you dosed for 2 weeks prior ) might be better to be a nonresponder seems that every one in that group gets the study med where the niave group gets split in 2 1 receives soc the other soc + 796 . not sure if the soc group would get offered the 796 after 12 weeks or not but that may also be pos depending results of the 2 other groups . this study seems to be more flexable than most i have run across and may allow for more of an individual treatment and better results than the more rigided  studies usually run . wish the vx950 had been set more along thes lines  this seems more pt friendly hope this goes well for you  all the best chuck

[chcnme]

Thank you, Chuck.  I thought that's what it might mean, too - after reading the definition of what an "open label study" is, I thought it might mean that I'll know, they'll know, everyone will know, etc.

I don't know if I'll be tx naive or nonresponder (good point.) The last impression my doc left me with was -- possibly, just possibly the rescue drug issue would possibly be something that we could institute (possibly)  lol -hung up on "possibly" here.  (guess I'm just hoping so much that it might be able to happen if I need it vs. reducing.) I really don't want to pass this chance up - it would be a huge let-down if I did, and it would be like....like just so much wasted time and effort and energy, etc. I guess if I just fall totally to and through the floor, someone can scoop me up and throw me out with the garbage :)  

Thanks a lot for you help.  All of you've been great!  Have a great night!

[ChrisDDD]

Well, what an interesting thread this is.  I thank all of you for this vast amount of information.  This is a great site with people who really are on top of this whole issue.  I'm so glad I stumbled onto it, and it's really the only one I visit anymore.  I'm glad I checked it tonight, because I wanted to see if any more VX trial patients had posted their findings.

The relapse at 14 days is discouraging, to say the least, because I had my hopes pinned on being able to do the VX+IFN+Riba this coming year in a clinical trial.  I feel pretty sure that if I'm not able to use rescue drugs, I won't make it to the 12th week.  At week 9 of Infergen/Riba my white and red blood cell counts were dropping, but not enough to start me on Procrit and Neupogen quite yet.  As it turned out, week 9 was the furthest I got because I developed retinal hemorrhaging.  I already have that obstacle to overcome in any future treatment, so the possibility of my being able to drop the VX and continue on the IFN+Riba isn't of much use to me.  I already failed that treatment regimen seven years ago.

It's good to know these things before I put myself through any more treatment, however.  All three treatments I went through, monotherapy in '98, Peg+Riba in '00, and Infergen+Riba in '05 were a real ***** to get through, and I failed all three of them.

I need to look into this more, but I'm a little irritated at a certain notorious rock star mentioned on this board when I read what he had to say to MSNBC or some talk show.  It seemed to me that he was underplaying how difficult treatment is, but even worse, it appeared to me that he was giving the impression that he could just walk in, do 11 months of treatment, and be cured and go on with his life.  Umm, doesn't he have to have follow-up labs to determine an SVR?  Was he just "lucky" that he cleared in his first round of treatment, or did he get something we don't get because he's a celebrity?  What about the rest of us languishing while we wait for a cure, those who have died of this disease, those on transplant lists, etc.?  It seems to me he just took us a few steps backwards with his comments, which most likely the public is going to listen to.

Jeez, I guess I'm just feeling pretty pessimistic about my prognosis if the claim is that whether it's VX 950 or 796 or NM 283, we always have Peg and Riba to fall back on!  Not for me!  I hope to get into the upcoming Prove 2 trial.  Pre-screening of patients is supposed to start about mid-January.  I just don't think I'll get in, and I can't do maintenance IFN either because of my eyes.  I'm pretty bummed.  I'm really happy for all of those who are able to beat this, though!  Congrats!

[mremeet]

If you're intolerant to IFN and/or riba, then I'd try to hang in there and wait for the first HCV PI cocktail trials. They probably wont be along for a few years, but sooner or later they're going to try combining two or more of the HCV protease/polymerase inhibitors currently being developed. It would be the natural next step, as many folks have intolerances to IFN and/or riba. Speaking for myself, I can handle the IFN but the damned riba is a backbreaker from my experience. The riba might well be my undoing, as currently I'm hanging by a thread in my treatment (currently 21st week).

Protease inhibitor cocktails are how they suppress the virus in HIV patients, frequently to persistently undetectable levels (as long as the drugs are taken continuously). This has largely "converted" an HIV+ status from an almost certain eventual death sentence, to a largely manageable disease, albeit remaining chronic and incurable (and is why Magic Johnson et al are still with us and remain relatively healthy after being HIV+ for 10+ years). Hopefully HCV PI cocktails will eventually be shown to not only very effectively lower HCV VL's, but also to have the ability to permanently "eradicate" HCV in the host. I use "quotations" around the word eradicate because of the current research suggesting viral persistance in long term HCV SVR's. i.e. The virus appears to persist at very low levels within certain tissues of most SVR patients; thereby casting some doubt on the concepts of complete eradication and/or "cure".

Lastly, on a cautious note, unfortunately the PI's can come with their own problems. PDS and myself developed a bad rash from the VX950 we were taking after about 2 months of dosing it with IFN/riba. From what I've heard, the HIV PI's can cause nasty rashes in some patients too. HR commented once on why they do this, although I didn't really understand exactly what he said. But it was something to do with the drug's shape, I believe on a molecular level. And this shape can somehow result in a negative reaction with your immune system, possibly resulting in a rash. I think I have that right(?), but don't hold me to it (and hr if you're reading this feel free to chime in!). Anyway, HIV PI's can cause a lot of other problems too that aren't related to rash. HCV PI's may eventually prove to have some similar side effects, especially if they have to be taken for a relatively long period of time. Although even if they do cause problems, hopefully they will be manageable and their onset will be temporary. HCV has been shown to be capable of being eradicated (possible exclusions previously noted notwithstanding) and so the dosing period will likely be finite, whereas HIV patients cannot stop their meds and must continue with the drugs for the rest of their lives (at least for now, anyway). This makes the PI side effect issue much more serious for the HIV patient than it probably will turn out to be for HCV patients.

Best of luck with your future treatment options, take care.

[ChrisDDD]

Thanks so much for this hope.  My local doc thinks the same thing, though he hadn't mentioned combining PI's.  I'm still going to hope for this next trial and that I won't have the eye problem this time because I didn't ever previously, only on 15 mg daily with Infergen, a dose both docs agreed was high for my size and body weight, but we were "going for the cure".  I'll let you know!