VX Trial dosing OVER!!

[APKhaos]

Its a great day!
Finished dosing yesterday after 24 weeks [12 VX & SOC + 12 SOC only]. Turned in my drug diary, extra meds, and presented my sharps container to my trial coordinator. Can't tell you how good it feels to be starting to wash out the tx meds and getting back to normal. You folks who do extended SOC and multiple rounds of tx have my complete respect.

Now we are into 48 weeks of follow up monitoring including PCRs every two weeks, which is different to the Consent schedule, but that's what I was told today. I've been UND since around day 15, so now we will see if SVR is possible for a geno 1 after 24 weeks of triple therapy. I guess the next six months will be as interesting as the last six, just a little easier.

[Cindy10]

Good for you, what a relief it must be. I truly hope for SVR for you. Keep us posted as too how you feel as the meds leave your system!

[jmjm530]

Congratulations !  How soon will you get the results of your week 2 and 4 post treatment PCR? Also, do you know any post treatment PCR results of the 12-week treatment group? Of course no one knows for sure yet, but my hunch is that the 24 week group is the group to be in. As they said in Goldilocks -- not too short, not too long, *just right* :)

All the best,

-- Jim

[miked]

I remember the day I stopped tx (although failed).  

About a week after stopping I remember listening to music again and actually turning up the VOLUME!

My family went to a hockey game and I didn't mind all the people and noise.  Food tasted good again.  I started gaining weight.

It was like winter was over!

Enjoy not taking meds!

[GrandOak]

Congrats and may you be blessed with SVR and a full life.

Like Mike, I know how good ending tx feels, both physically and mentally.  Keep us posted, and particularily with any future trial information to which you may be privy.

[APKhaos]

Once unblinded, our PCR results come from the lab as soon as they are processed, which is something like 5 - 7 days? On that basis, I'll be seeing them every two weeks starting 2 weeks and 5 - 7 days from today.

Thanks for the kind words on the 24 week issue, Jim. There have been some vocal naysayers here insisting the additional 48 weeks of SOC is the only sure way to SVR. Like you, I'm quietly confident that SVR will be demonstrated after 24 weeks of VX + SOC combo therapy. Nobody really knows until the data are in, so now its just wait and see. We will know more as more posters here move into the follow-up phase.

[pln]

Right behind you buddy. I can not wait for this week to be over. I too have a feeling the 24 arm is just right. Pam

[SnoWav]

Best of luck to the 24 week VX group. I sure hope that 24 weeks of triple threat works for SVR. I hope when I TX next time it is only 24 weeks.That would be a walk in the park,I could for sure do that standing on my head.later

[jmjm530]

I had advanced stage 3 or stage 4 liver damage, I might be apprehensive about doing only 24 weeks, but then again, no real guarantees (yet) with any of these drugs, for any duration. But for those with little or moderate liver damage, it seems that 24 weeks of VX-950 coupled with an RVR is a very reasonable treatment time. That said, it's still a *trial* and as the word implies something new is being tried. Of course I don't know if the 24 week group will work out or not, but if I had been in the study, I personally would have been most comfortable in the 24-week group, *especially* given the hindsight of knowing what 54 weeks of treatment did to my body, mind and soul.

All the best,

-- Jim

[jmjm530]

The first sentence should have had an "If", preceding the "I" and therefore read:

"If I had advanced stage 3 or stage 4 liver damage...."

[jmjm530]

Just to add a little to the 24 versus 48 week thing in terms of the VX-950 trial. The whole purpose of taking VX combined with SOC is to either shorten tx time and/or increase the odds of SVR. And from what I've heard anecdotally, the first part -- shortening treatment time -- was paramount on the minds of many involved with the study, i.e. to develop a shorter, kinder treatment. Therefore, not sure why someone would want to be in the 48 week group, as they just could have done 48 weeks of SOC, although the argument might be made that the odds of SVR might increase with the VX added to the mix. All these questions -- and who shot JR -- will be answered soon enough :) Oh, yeah, we know who shot JR, but it's just that I forgot, but then again, I did 54 weeks of tx and the memory ain't so hot these days :)

-- Jim

[jmjm530]

Just to clarify, didn't mean to imply that someone in the VX 48 week group shouldn't do 48 weeks, cause after all this is a trial and we really don't know what group will do what at this juncture. My point was simply that I couldn't understand why someone would criticize someone in the 24 week group, again given the fact that there is no hard data on how either group will perform.

-- Jim

[GrandOak]

Just to clarify your clarifications, are you per chance on tx meds or just have your flame retardent clothing at the cleaners? ;-)

[jmjm530]

Vetex tx length seems to have been added to our ever growing list of controversial topics which just about include everything now (early PCRs, MT, Booze, G*D, MJ, Caffeine, Herbs, etc, etc, etc,) with the exception maybe that SVR is good, but even that is seemingly under fire by some, therefore the clarfications :)

I hope this finds you well and as fully clarified as possible, but if you need anything further clarified -- except maybe Ghee (clarified butter) please let me know as this is a slow Monday for me.

-- Jim

[mremeet]

apk  quote: "There have been some vocal naysayers here insisting the additional 48 weeks of SOC is the only sure way to SVR."

I'm assuming you're referring to my previous comments to you in an earlier post regarding duration of treatment? If so, I didn't "insist" an "additional 48 weeks of SOC is the only sure way to SVR." To recap in summary, what I said was:

(1) If I were 50-something, had advanced fibrosis (i.e. F3) and a high starting VL, then I'd be apprehensive about stopping at 24 weeks. I'd be worried about it and would at least express some concern over the situation, although not necessarily extend treatment to 48 weeks.

(2) For the reasons specified in #1 above, I would be worried. And the reason I would be worried is because the consequences of failure/relapse could be very significant in a negative way, and perhaps even become life threatening in a relatively short period of time (with SOC being the only option for years to come). That's a fact, not an opinion.

(3) The SVR rate for a prospective patient taking 12 weeks (VX950+SOC) + 12 weeks (SOC) will not be 100% (probably far from it). It will be less than 100% no matter what. That's a fact, not an opinion.

(4) The SVR rate for a prospective patient taking 12 weeks (VX950+SOC) + 36 weeks (SOC) will not be 100%. It will be less than 100% no matter what. However, it will be greater than  the 24 week group described in #3 above. That's a fact, not an opinion.

(5) The SVR rate for VX950 has not been established. There is no (disclosed) track record whatsoever that has been established for VX950 in regards to its ability to deliver or enhance the probability of an SVR (yet). Therefore, any guesses on the statistical likelihood of VX950 greatly enhancing existing (mediocre) type 1 SVR rates, especially in lieu of simultaneously halving the normally prescribed duration of treatment in conjunction with having a relatively high risk profile, is just that: pure guesswork. That's a fact, not an opinion.

So, when you combine #1-#5 above, then you have the basic premise for what I was saying to you on a previous post. Nothing more, nothing less. And certainly not what you've simplistically mischaracterized in quotations above.

In the meantime, best of luck with your ongoing UND status. I'd guess your chances of SVR-ing are probably good (i.e. >50%); hopefully you'll reel one in. Take care...

[jmjm530]

Mre: (1) If I were 50-something, had advanced fibrosis (i.e. F3) and a high starting VL, then I'd be apprehensive about stopping at 24 weeks. I'd be worried about it and would at least express some concern over the situation, although not necessarily extend treatment to 48 weeks.
----------------------------
I know it's probably not wise to step in between the two of you on this one but since we seem to get along pretty well, here goes...

Assuming the patient above, I can understand your analysis to a certain degree, but what's missing is that the patient (and doctor) had knowledge of all this information prior to entering the study which would randomly deal out 12, 24 or 48 weeks of treatment. I would therefore then think that the time to question extending beyond one's trial Arm would be prior to treating -- i.e. not enrolling in the trial if that might be a problem -- as opposed to at this juncture. Unless, of course, something happened during the trial -- such as a late response -- that wasn't anticipated and might suggest the shorter course would be too risky.

So, I guess what I'm saying is that either your hypothetical person above, should either play out the cards dealt by the trial or should not have entered the trial -- both being valid decisions IMO. Personally, I think this hypothetical person, given an RVR, stands a very good chance of SVR without subjecting themself to a years worth of toxic medications,  but I don't know any more than anyone else, in fact probably a lot less.

Be well,

-- Jim

[willows]

Add to your list of issues that cause fights......When folks have done 4 days of treatment and are happy that they feel good...this is not a time to be cranky or envious.  I learned this yesterday from the world's longest post.  

I know what to call it!  Sides envy.  I think that was how some of my posts were perceived, although I was just venting at the world in general.  

Sides envy.  Sounds like me coveting your curly fries.  

Willow

[jmjm530]

Lady Willows,

Sorry to disagree, don't think your suffering from sfx envy :) The post mentioned went beyond simply reporting sfx from the get go and got into discussion of how balanced things are reported here, etc. I think you were just adding your perspective which was good.

Be well,

-- Jim

[APKhaos]

Nicely put, Jim. Could not agree more.

[willows]

Still want the curly fries.

Willow

[mremeet]

jimquote: "...but what's missing is that the patient (and doctor) had knowledge of all this information prior to entering the study which would randomly deal out 12, 24 or 48 weeks of treatment. I would therefore then think that the time to question extending beyond one's trial Arm would be prior to treating -- i.e. not enrolling in the trial if that might be a problem -- as opposed to at this juncture."

I have no argument with that. But I didn't dictate or suggest he extend treatment beyond what his assigned group was, I didn't in my previous posts to him nor have I in this thread. I merely found it odd he didn't voice any reservations or worries about it previously. It *is* possible to adhere to your preassigned group duration and yet still have, acknowledge and voice reservations/concerns regarding the historically abbreviated 24 week treatment cycle...especially when viewed within the context of the issues spelled out in my previous post. There is no logical paradox or contradiction in terms in doing so either. The so called "moral issue" concerning trial duration adherance does not negate/preclude/make inappropriate an open and honest discussion regarding the implications and plain facts surrounding an (historically) abbreviated geno-1 treatment cycle. Many, if not most people find these concepts "mutually exclusive". i.e. by simply even openly discussing them, then you are therefore by definition advocating non-adherence to your pre-assigned group: absolutely not true. The two concepts are not mutually exclusive, sorry.

Furthermore, the legitimacy of the so called "moral issue" surrounding group adherance is another topic that is absolutely debatable for a wide range of perfectly valid reasons (which have already been discussed, with no desire to revisit)...not the least of which is as you yourself stated: "Unless, of course, something happened during the trial -- such as a late response -- that wasn't anticipated and might suggest the shorter course would be too risky."

"Personally, I think this hypothetical person, given an RVR, stands a very good chance of SVR without subjecting themself to a years worth of toxic medications, but I don't know any more than anyone else, in fact probably a lot less."

That's just it, no one knows. And using the existing established statisical data that suggests SOC patients who RVR have significantly increased rates of SVR to extrapolate/forecast (likely) similar performance to a 24 week VX+SOC trial participant, is almost certainly comparing apples to oranges. The two situations are clearly different in very significant ways. The historical SOC (i.e. non VX) patients who achieved RVR and their subsequent SVR (even on truncated courses less than 48 wks), usually did/do so due to (1) favorable starting VL/fibrosis/age/BMI/etc criteria and/or (2) because they (or their virus) were particularly sensitive to IFN and/or ribavirin, and/or (3) because they happened to have a relatively weak/non-robust strain of HCV. And specifically in the case of those patients who are especially sensitive to SOC drugs, they derive the benefit of this high sensitivity throughout their entire treatment cycle (which is almost always for 48 weeks for geno 1, not 24 weeks as in apk's case). They experience an RVR because this sensitivity initially knocks the VL down rapidly, keeps the virus fully suppressed, and eventually permanently "eradicates" it (whatever that might mean)...all as an ongoing consequence of their high sensitivity to the IFN and/or riba alone. Obviously the reason for most EVR's in the case of the VX trial participants will not be because of this reason, but instead will be because of the addition of a direct acting antitviral drug (and again not solely because of a supertuned immune system occurring as a result of #2 above). In my view this is especially important because the VX dosing cycle only lasts for 12 weeks (with viable virus probably still present in the body at that point), the latter dosing period (be it 12 or 36 more weeks) will have the patient flying solo on SOC alone. And unless you happened to be one of the fortunate few who would have EVR-ed anyway without the the help of a PI (quite statisically unlikely considering apk's particular starting criteria), then that patient's SOC stimulated immune response will almost certainly not be as "hostile" to the remaining virus as it would be for an SOC EVR/SVR patient.

As a further hypothetical/speculative aside, there are even some who postulate that an SVR's virus is merely being continually held in check by an immune system that was "trained/tuned" during their treatment cycle. Not that I buy into that opinion, but it is a possibility that must be considered on some level, especially in lieu of the recent findings suggesting low level viral persistence in long term SVR patients. And if this scenario does have at least some validity to it, then adding VX into the mix and halving the treatment cycle may not necessarily achieve the same immune system "training" effect.

[jmjm530]

Thanks for clarifying the discussional aspect of all this as opposed to suggesting people deviate from trial protocol. In previous threads, some of this seemed to get mixed up and I'm not necessarily referring to your posts per se, but just in general.

I carefully tried to avoid the "moral" issue this time around and was simply stating that 24 or 48 (or even 12) weeks should come as no surprise to anyone enrolled in the study and that some  pre-thought should have gone into this prior to starting, with one option being that a trial is not right for a particular patient, medicially and/or psychologically.

Not so sure that APK was avoiding the potential downsides of being in the 24-week group, as much as pumping himself up as many of us do after making a tx decision or having one made for oneself as in a trial. I know I psyched myself up at various junctures in treatment -- didn't want to hear boo from anyone at those times :) -- and it was a necessary tool for me to be able to get over certain humps.  Or maybe, APK genuinely has an instinctual feel -- combined with non VX RVR studies -- that 24 weeks is the magic number. I happen to have that feeling myself, but I really can't speak for APK or anyone else.

As to our hypothetical patient and how he might do with let's say a shortened VX plus SOC versus SOC alone, etc -- and whether the predictive meaning of current RVR (or SVR figures for that matter) correlate with VX RVR figures -- all that and more is hopefully what we will soon find out in these trials.

All the best luck to you and the rest of the VX crew as some go on, and some wait on post treatment labs. Forgot what group you are in or even if you've been unblinded at this point.

Be well,

-- Jim

[jmjm530]

MRE: "...The historical SOC (i.e. non VX) patients who achieved RVR and their subsequent SVR (even on truncated courses less than 48 wks), usually did/do so due to (1) favorable starting VL/fibrosis/age/BMI/etc criteria and/or (2) because they (or their virus) were particularly sensitive to IFN and/or ribavirin, and/or (3) because they happened to have a relatively weak/non-robust strain of HCV. And specifically in the case of those patients who are especially sensitive to SOC drugs, they derive the benefit of this high sensitivity throughout their entire treatment cycle (which is almost always for 48 weeks for geno 1, not 24 weeks as in apk's case).
-----------------
Think you've covered most of the bases although the genetic factor is being bandied around. Whatever the mechanism, the vigor of the response itself seems to trump the "why" of the response, at least according to some doctors I respect. So given the response (RVR), and going back to your example (2), this benefit *has* been shown to translate into comparable SVR data with shorter than 48 weeks (specifically 24 weeks) in those with a vigorous viral response. The big question again is how will RVR with VX play out vis a vie RVR with SOC. Vertex, APK, myself and others seem to be putting stock that it will play out the same -- or possibly even better. But even if if played out incrementally worse, given what appears to be such a very high percentage of RVRs with VX, then their SVR figures could still be significantly better than SOC even if their RVRs didn't translate over as well. Only time will tell.

-- Jim

[willows]

So, after consulting my PDR, I think you said that teleprevir has much value in the simple fact that it creates a very rapid response.  And LOTS of doctors have decided empirically that the RVR is a good thing, better than no RVR, when considering weeks and weeks of INF and riba.

In an earlier thread, someone posted about a PCR at 2 weeks, which supports your summation, and also what my own doctor told me.  If the VX950/IFN whammies the virus quick, well, a person can go on for 24 weeks, which is LONG enough for anyone to try IFN.  The lasting effects, after tx is stopped, are new frontiers, docs are learning more and more about hyperstimulating the immune system for long periods of time.

Or do I need to get the PDR out again?  Long live PCR's at 2 weeks and love live 24 weeks of tx.

Willow

[jmjm530]

Willows: If the VX950/IFN whammies the virus quick, well, a person can go on for 24 weeks, which is LONG enough for anyone to try IFN.
--------
Yes, that is the hope. That the rapid viral response (RVR) that VX delivers will translate into a sustained viral response (SVR). How many weeks of SOC are necessary after the initial 12-week dosing of VX and SOC, is what the current trials will help determine. In Europe, they are trialing some Arms without ribavirin, and if the results prove positive, no doubt we will see VX being trialed without ribavirin here as well. There was some talk at one point about trialing without peg as well, but I doubt if we will hear much on that for some time, if any, unless/until other antivirals are developed and a viable antiviral "cocktail" approach emerges worth trialing, similar to how HIV has been approached.

Willows: The lasting effects, after tx is stopped, are new frontiers, docs are learning more and more about hyperstimulating the immune system for long periods of time.
-----------------------------------
I suppose they are but so far the lion's share of time/study/emphasis has been on achieving SVR, not what happens to folks after they achieve SVR. This leads to a whole other discussion.

[jmjm530]

You seem to have a good grasp of the concepts but if you want to further your study here are some sites/links. Keep in mind the dates on articles as some preceed others.

http://www.hivandhepatitis.com/
http://www.hivandhepatitis.com/hep_c/hepc_news_svr.html
http://www.hivandhepatitis.com/hep_c/hepc_news.html
http://www.projectsinknowledge.com/ (free registration may be required)


http://www.clinicaloptions.com/Hepatitis.aspx (free registration required)

At clinical options site, link above, you might want to start with "Doc Eye for the Hep Guy" a video module on re-treatment protocols. Also, the Shiffman slide presentations are informative as well. Sometimes hard to navigate the site, so best use the "search" bar at the top and enter key words such as "doc eye ofr the hep guy", "shiffman", etc.

[copyman]

all i can say is congrats on finishing and thanks for trying the VX with a 24 week trial. i truly hope you stay svr so 1a's like me have some hope on doing shorter tx's. best of luck and god bless.

[APKhaos]

I happen to think that RVR and an extremely high rate of initial clearance are significant predictors of SVR. Call it informed opinion, having spent most of my professional life  making decisions based on imperfect, incomplete, and often conflicting data. Its goes with the turf if you work on the bleeding edge.

My VL at first screening was 20,600,000. At second screening it was 27,500,000. Immediately before the first dose of treatment, it was 28,600,000. It was below 30IU/ml after 14 days of TX, and UND from there on. I believe that this is a strong predictor of SVR after 24 weeks. Your mileage may vary.

[mremeet]

"Your mileage may vary."

For once you're right, my mileage may vary. ;-)

In the meantime, here's to our respective SVR's. I really hope we all make it, one way or another.

[lab-rat]

Congratulations to both of you!  I'm very jealous.  I appreciate you posting your experiences with the study so far.  It gives me some idea of what to expect as far as unbliding procedures, frequency of follow-up visits, etc (that consent form is pretty worthless).  I wish you both the best of luck for SVR.  Keep us posted!

[jmjm530]

Since I'm the only one in this thread who used the word "kinder" I suppose the preceding comments were directed at my statments in C10 above.

"Kinder" can be interpreted as one likes, but to me part of that equation is how long one is exposed to interferon, which many, including myself think may cause long-term, possibly permanent problems because of what it does to the immune system. As to how "harsh" VX-950 was, we're still waiting for complete data to flow in on that score. Hopefully, the skin problems some here have reported will be addressed in future trials as they seem to have a bead on exactly what day they began. But regardless, unless it turns out that the skin issues were significantly more severe and common than so far described, I'd personally take 24 over 48 weeks anyway. As bad as some of my sides were prior to 24 weeks -- and I did have my worst sides then with the anemia -- it was the grinding down of my body, mind and soul from week 24-54 that really put me in the treatment gutter. So, yes, I think 24 weeks is kinder even if parts of it are not. Hope you had a happy New Years.

-- Jim

[jmjm530]

Let me put it another way -- I've experienced far more physically traumatic conditions/illnesses in my life than combo treatment. This includes a motor vehicle accident and -- spare the laughter -- an extermely painful recovery from a hemmrhoid operation that literally had my in tears -- not to mentioned anchored to the bathroom -- for close to three weeks. Nothing, nothing, I experienced during combo treatment could even begin to compare to that recovery. That said, nothing, nothing in my life compared to combo treatment in terms of breaking me down physically and mentally. The hemmrhoid operation was history a month later, but hep c combo treatment has left a scar that hopefully will heal one day, and I believe it was the sheer length of the ordeal -- 54 weeks in my case -- that did as much damage as anything else.

-- Jim

[cuteus]

shorter tx does not equal kinder tx as seen in some of the guinea pigs reporting here.  It seemed that some got quite a harsh bout with severe sides that prompted the early termination of the offending drug.  To me, kinder tx is no sides or very mild ones.

[cuteus]

new years was great, hopefully yours was also.  We made it to Times Square for the first time in my life, BTW.

I guess it depends on how hard the tx hits a person, for me, most of the sides came and went, except for the mental exhaustion of not feeling well, and that one was not  unkind in the true sense of the word.  So for some, the new tx might seem kinder and gentler while for a large number, it might not, since most of the sides in SOC do not remain the full 48 wks, to our relief, they do ease off and most of the time they leave.  Perhaps the fact that your skin condition made you suffer the whole time plays a big role in your description and hopes for the new tx.  Good thing hemorrhoids did not flare as well.  
I have a family member who suffered through an anal fissure  and its repair and, well, I guess you can relate to his suffering better than I.
One nice long term effect from tx is that I am forgetting more and more how I felt then.
btw, I finally did get a cold, but still not a normal type since I only blew my nose twice in the few days it lasted. No nasal congestion per sae, or cough, just a mild throat soreness and hoarseness. I call it a cold because I did blow my nose  a couple of times and got hoarse, but it still was not my old type of cold.  I wonder if this virus was stronger than the others or if the immune system modification eventually wears off.
anything new has happened? any food fights I should know about? besides the booze threads...
be well

[jmjm530]

I think I saw you on TV as the ball dropped. Were you the one standing on that big guy's shoulders holding the bottle of Champagne :)

Ah, yes, the "booze" threads. As you mentioned, some things never change and I've limited myself either to not post, or simply post the facts as I know them and then leave the room.

I do agree that a significant part of our take on all this relates to our personal treatment experience, which puts us both at an advantage and disadvantage (at the same time) vis a vie the medical "experts" if you know what I mean.

And while my sfx may have been a bit harder than most, from what you've posted, I'd say yours were on the milder side. Maybe the "average tx experience", if there is such a thing, falls somewhere inbetween what we respectively experienced.

As to your family member with the anal fissure and repair. Whatever he said he was going through, it really was that bad.

All the best in the New Years and good luck with the little finches(?) you've adopted.

-- Jim