Week 12 - Not UND

Well, got my VL results for week 12. Not UND, but < 25.

The nurse seems to think this is just Jim Dandy, but I'm seriously considering stopping the trial. Isn't the common knowledge nowadays if not UND at Week 12, then quit?

I suspect I'm probably in the SoC arm only, since over 85% of the people who got the real thing were RVR in Phase 1 trials. Of course, I could be in that 15%.

Oh well, sometimes we win, sometimes we lose. Guess I need to make a decision before my next shot, Wednesday.

Thanks

RBW

[RobertBeWell]

Guess I should point out that I started with a VL of 3 million, so this is what, about a 10 log drop?

This is gonna be a tough call. I hate to waste the 12 weeks... and since I'm so close, I might at least go another 4 weeks till week 16. I already have the meds.

[spectda]

Hi Robert,
I am sorry that you didn't get the und yet. Of course we want to be und as early as possible, but I also think it's not as bad as you think. I was und at week 10, <25 at week 12, and und at week 14 and thereafter. My doc said that at <25 the margin of error is in question. Who knows the truth, but it would make me think about stopping yet if I was you.

Many of the studies and projections for svr were done with pcr tests that are not as sensitive as the one you are being monitored with. Many of the people on this forum who are svr who might have thought they were und at week 12 probably were at least <25
You are so close to und that I would personally keep going for at least another 2-4 weeks. Also the fact that your liver damage isn't bad increases your odds.

I know you are well aware of all this and I am no expert. I am sorry that you didn't get the response we all hope for each other. whatever you decide you have options and you will svr before long.

We all want to see you succeed as I am sure you are aware.

Take Care,
Dave

[RobertBeWell]

Yah, I'm kind of sitting here thinking the same thing Dave. Who knows, if I tested one day later, I may have been UND. Still, I did not achieve RVR at week 4, that's certain.

But perhaps you are right. I am very, very close. I guess it would be one thing if my sides were terrible, but they are very mild.

Ahh decisions, decisions. I hate to waste 12 weeks of treatment, but then at least now I know if I keep rolling, I'm going to have to go the full 48.

It's a tough call. Thanks for the input bro!

RBW

[copyman]

Tough call man. What lousy news for the holiday. Just plain stinks.

Can you get your own private PCR done right away? ask your primary doc for a lab slip? perhaps get the Quest test that measures down to <5 or Labcorps that measures down to <2.

Since you know you weren't UND at 4 and now at 12 you may want to consider stopping and wait for the new PI's. Especially if you have minimal fibrosis?

How often are they going to test? If not UND by 16 it is a no brainer you have to stop. Don't let them tell you that 24 week UND is the standard. That is old school and would mean you would have to treat 72 weeks!

hang in there and good luck

[RobertBeWell]

Something just occurred to me as I was reading some studies. All the IFN/Riba studies that I can find have defined UND as < 50 IU/ml. So, technically, by those standards, I am in fact UND. Plus, my earlier results are blinded. I have no way of knowing how long I've had this low a virus level. I may have been < 25 for weeks now.

Pretty much decided that I'd be stupid to stop at this point. I mean, who knows... my actual level might be a paltry 3 IU/ml.

At any rate, with my cEVR (UND at week 12, where UND < 50 IU/ml) is about a 65-70% predictor for SVR.

That's damn good odds - pretty close to what the PI's are going to offer.

Thanks Dave!

[pcds]

you are in the exact place I was.  Still detec at the first day of the 13th week. VL 348.  I had prepared myself with discussions with my doc.  He said any virus detec after 12 weeks I should stop,  odds are not in my favor, with possible relapse after 48 wks.  So I was sure I was going to stop if detec.  and I did.  More recently I went to Mayo just to chat with "an expert"  in prep for the new meds nex year.  Like a job interview, I decided I wanted to check out docs familiar with the new PI, the trials in AZ were done at Mayo.  This mayo doc, actually was a liver transplant guy, not the trial guy, but certainly a top notch doctor.   He told me he would have had me continue the medication.

I liked my doc who I was in tx with.  I'm OK with having stopped.  In fact I wish I stopped earlier.  With the old SOC, if not a RVR you might as well wait for the new stuff with a better chance of SVR.  I am enjoying life now.  I too feel like I wasted 13 weeks with no good payback.  But 13 weeks wasted is easier then 48 weeks with poor odds at SVR.

To All:  I am not advising anyone to do anything.  Just giving my thoughts how I feel about what happened to me.

[RobertBeWell]

Heh, the only trouble with a trial is - I won't actually know what my counts are from weeks 2-10.

I've made up my mind I'm going to 16 weeks at least. With almost zero sides, I'd be stupid to stop when I'm this close. I'll reevaluate at that point.

I knew going in there were no guarantees. Fortunately, I have time to wait if needed. But I'm still very hopeful I'll make it this time around.

Thanks!

[pcds]

If you have low or no sides, go for it.  My 2 cents.

[Trinity4]

Until today I might have tossed around the fact that I wasted 72 weeks.  However, consult with my doc today shows pathology from 12/2 biopsy at stage 2/3.  Diagnosis mild to moderate fibrosis.  Inflammation grade 1.   11/7 biopsy stage 3/4 -  Inflammation grade 3.  Enzymes and blood values all within normal range.  No supplements, no LDN IV's, no herbs, no hemopurifiers, no low voltage electricity, I eat red meat and I like sugar.
Even without an SVR, I like to think I bought myself some time while waiting for the PI's.  So whose to say what's good and bad in the big scheme of things.

Trinity  

[Bali05]

When I contemplated all the issues before starting tx it became clear
that the one of the toughest decisions would be knowing when to stop.

I decided upfront that I would want to be UND by a very sensitive test
by wk12 , if not stop.

Before making a final decision I would want to rerun immediately one of the tests
that copyman mentioned (btw they can take longer for result up to 2 wks)
and I would want to know my viral load at week 4 and if they did one
wk8.
Propably even add the IL28 test to get as much info you can to make
this tough call.

You are stage 1 from what I see and geno 1a. Many hepatologists would
propably tell you to wait for Tela. even without these trial results.

I am currently going into wk33 and I would not want to do this if the odds were
not in my favor and I had a better options in the near future.

[Trinity4]

11/07 biopsy stage 3/4

[willbb]

Bali o5

"You are stage 1 from what I see and geno 1a. Many hepatologists would
propably tell you to wait for Tela. even without these trial results."

That would make sense,however their is now an 80% chance that in this study he is taking Tela (or Tela like PI).

That has to enter the equation,does it not and also is their a resistance issue here?

WILL

[Bali05]

I was assuming he got SOC only arm.
Is there anyway to find ?

[willbb]

none unfortunately

[RobertBeWell]

Unfortunately, there is no way to know what you are getting until the study is complete. That's one of the drawbacks of a trial. The manufacturer sets the rules.

On the bright side, all my blood work is excellent. Also as part of week 12, they do all the obscure tests that they do on Day 1 as well, all the thyroid stuff, etc. My blood work, except for my lower HgB and WBC counts, is as robust as Day 1.

It's just my feeling that I am getting placebo. The initial results of this drug we so impressive that on'y 15% of the patients failed to achieve RVR, and only ONE patient failed to become UND at week 12. It was a small study however.

[RobertBeWell]

This drug, like all the current crop of DAA drugs, absolutely has a resistance profile. The good part is, the study we're in is an NS5A inhibitor - which will have absolutely no cross resistance with Telaprevir/Boceprevir (which works on the NS3 viral unit (or NS4, don't remember exactly).

As a matter of fact, that's the only reason I took a chance with this study - because I knew that the 2011 PI's would be an option to me should this trial not work out.

At the very least, I found out that I respond very well to SoC, which is gonna be around for quite a while longer. If I am getting SoC, a 10+ log drop at week 12 is DEFINETELY an impressive result. Not the best, but I'm certainly not a non-responder in any sense of the word.

[willbb]

That is the way that I understood the resistance issue also however glad that you confirmed it for me.

Given all you know right now, it is still my feeling that it is best to plunge ahead till at least 16  and revisit then.

All the best friend

WILL

[RobertBeWell]

And to correct a misstatement, I keep tossing around a 10 log drop, but that's not correct. My starting viral load was 2.95 million, and just for grins, if I assume that I am currently 24, then my drop was:

log(2.95 million) - log (24) = 6.47 - 1.38 = 5.09 log drop.

Heh, to get a 10 log drop, you'd have to have a starting counting up there in the jigga-watt range or whatever they used in Back to the Future

RBW

[James10500]

Hi,

When I get a PCR it says <43, when I got my heptamax test it was <5, meaning the lowest detectable level was 43, and 5.  A VL was not detected above those levels,thus undetected.  If your test result was <25 doesn't that mean not detectable greater than 25, there for UND given the parameters of the test ?

[willbb]

Was kinda wondering about that 10 log thing, didn"t think you started at 3 billion?  :)

[willing]

bummer - but knowing you're a responder is definitely a big plus. It's a hard call. I think Bali makes a very good point about making these cut point decisions before starting. Once you're invested it's emotionally harder to pull the plug.

I suspect you're right about the placebo given the very strong results for bms790052. Not having any interim data makes it impossible to know if this is an insignificant  one time spike. Pushing on based on the information available  has more of a 'I'm feeling lucky'  feel than I would opt for. Did they say anything about w12VL being a discontinuation criterion?

Best wishes!

[copyman]

I agree with James if the test read <25 then you are UND by their test. If you were not UND they would have given you a specific viral load #.

You should still do your own  "sensitive" PCR. Having this information will allow you to make informed decisions moving forward.

I did my own PCR's during the Telaprevir study I was in. It was an open label study where everyone got the real drug. But the PCR's were blinded. I decided before study started I would have my primary order all the important tests, 4,8,12,16,24 weeks. I felt I needed to know this to make decisions regarding "my health". Sure enough at 24 weeks I was randomized to the 48 week group and because of my private PCR's knew I was UND from 4 weeks on. So I made a decision to stop around 30 weeks. Just did my 1 yr PCR a few months ago and still UND.
My tests were all the Labcorp Quantasure <2. Also had the UltraQual done at the same time.

[RobertBeWell]

We had a brief thread about what UND actually was a while back. The < 25 thing just means that's the lower COUNTABLE limit from the test. The actual wording from my lab result is:

"TAQ/PCR < 25 IU/ml. Virus detected but unable to quantitate."

Means the test found some virus, but the amount was too small to be counted by this particular test.

[RobertBeWell]

I can see your point about getting my own tests, but what purpose would it serve at this point in time? If I had gotten them from Day 1, I could put this current result in perspective, but without weeks 2-10 there's not much information to be gained from it.

In other words, would it make any difference if my count was 24 vs 12 at this point in time?

[willing]

you might want to PM frijole. We went around that same line of argument around the time of her w12  which came in at something like 12 if I recall.  Many published studies use a lower limit of detection of 50  which would have classified her as und. She relapsed. I've gotten VERY paranoid of vl anywhere  near w12.

agreed about checking the manufacturer's specs for the test, but I assume the nurse would have known the difference. Sometimes testing labs can confuse the difference between  below-limit-of-quantification and und . For example both labcorp and quest include the widely used Roche CAP/CTM in their test menu (for labcorp it's 550080). For that test LOQ is 43 and LOD is about 15 but the labs collapse the bottom two categories and report both as lt 43.

[RobertBeWell]

"Not having any interim data makes it impossible to know if this is an insignificant  one time spike. Pushing on based on the information available  has more of a 'I'm feeling lucky'  feel than I would opt for. Did they say anything about w12VL being a discontinuation criterion? "

Agreed. As I understand it, as long as you've had the old "2 log drop" by week 12, you can continue in the study. If you have breakthrough, you're out. If you have significant health problems related to treatment, you're out.

As others have mentioned, at this point, I'm hopelessly emotionally involved in this now, and to be honest, I guess I am "feeling lucky", or maybe just in denial. No, no, I still feel that's being overly dramatic.

Needless to say, I'm not feeling giddy over this result, but putting things in perspective, I really do stand a reasonable chance to SVR based on these numbers. Heck, as far as the FDA approved tests go, I am in fact undetected, and have achieved complete EVR. Odds of SVR when cEVR occurs are about 65%. The new PI's won't give me much better than that, and I'm already three months into this ordeal.

I'm just too close to quit without continuing to Week 16. Since I have no sides to speak of, and I already have the meds, it won't kill me. I can re-evaluate at Week 16.

The other important thing to note is that I *may* have gotten a treatment re-assignment at Week 12. That is, if I was on placebo, I could now be on the real thing.

This study was a roll of the dice. I'm a gambling man, and I'm willing to stay at this table a while longer.

RBW

[willing]

>I *may* have gotten a treatment re-assignment at Week 12.

ahh - now that puts a different spin on it! I sure  hope they won't  be too stingy with the good stuff. I wish you all the best. I've just gotten paranoid by getting  burned  - in fact many do walk away from the table winners notwithstanding riskier odds.  

[Kristina538]

For what it's worth (G3 here), I needed the UND at week 4 and came back with "<43".
After checking out what that meant, I was devastated and wanted to extend.  My hep doctor had been ecstatic about my response and full of congratulations, because it was still an excellent response, and as he put is "as good UND", which, as I was progressing, would've likely been a matter of days later.  

I didn't have much choice but to plod and pray, so there wasn't much gambling involved, but I just wanted to say congrats at the big log drop and the response!!

[Trish77]

"The other important thing to note is that I *may* have gotten a treatment re-assignment at Week 12. That is, if I was on placebo, I could now be on the real thing. "

IF you can, I'd get another test done simply as a "2nd opinion" so to speak, and I wouldn't wait too long.  

I don't know the particulars of your trial or the reassignment part (have a link to your trial's particulars? would love to read them) but if you do indeed have an 80% chance of reassignment then...the variable you have is the trial drug potentially being introduced now, which is almost like starting over again, as if your first 12 weeks were a lead-in so to speak.  If your other folks got RVR at 85%, then if you are on the trial drug and you looked at it as this being Day 1 from this point forward, then you would potentially be at RVR in four weeks and then continue for the balance.

I know that's a certain amount of "ifs" but if you truly have an 80% chance of the trial drug at this point AND a potential UND that arrived anywhere between 2-12 weeks, then....I'd say the odds are more in your favour of continuing and getting SVR than not.  

On my own trial, it had a number of ups and downs and finally got pulled at 34 weeks when they stopped the trial universally at all trial centres. I went UND at 6 weeks. I found out later that I'd had interferon at 1/2 dose for the first 12 weeks and the middle dosage amount of the trial drug.  Then no trial drug from 12 weeks forward as that's when they pulled the drug rather than at the 24 week mark.  Then INF reduction at week 25 onwards.  Then pulled the trial at 34 weeks.  I am SVR.  Just enough of that trial drug I guess to do the job without an RVR.   Not a very conventional situation, was it.  Sometimes it works.  Sometimes it doesn't.  If it hadn't worked, I wouldn't have beat myself up over it, I went into the trial knowing I was taking a roll of the dice and also knowing I was Stage 1 going in.  That's what trials are.

So...you don't have to make a perfect decision, you couldn't possibly.  You just make one and take what what comes.  Wish you the *very* best on this, Robert.

Trish

[James10500]

It does get confusing.  As there is no test that measures to 0 for hep C.  I've heard there is one used in A research setting, but as far as the tests we take, the most accurate is Labcorps <2. which still means you could have 1 copy of the virus.

[RobertBeWell]

Thanks all for the food for thought. That's one of the invaluable things about this board, so many different perspectives. After some research late into the evening, and sleeping on it, I've come to the decision that I'm too close now to just stop. I have to continue for at least another 4 weeks.

All the published studies I've read define UND as < 50 IU/mL. I have beaten that. Who knows, my viral load at this point may be 3, but the point is, it's far, far less than 50. As Dave (spectda) pointed out, many who have achieved SVR and were measured at week 12 as UND may have, in fact, still had detectable virus had a more sensitive test been used. My response, while not exactly what I wanted, has in fact been EXCELLENT, especially in light of the fact that I have almost no sides.

So, I'm going to continue to Week 16. My reasoning is as follows:

1. By all the published studies on PEG/Riba treatment I could find, I have achieved complete early viral response (UND at w12, where UND < 50). With this response, I have a 70-80% chance of achieving SVR.

2. I may have just received a drug re-assignment (I have no way to know for sure) but I may be getting the real thing now. Waiting four weeks will allow this to take effect.

3. I have no side effects to speak of. My blood work is rock solid. Even the auto-immune stuff is all normal.

4. I already have all the meds on hand to continue until week 16,

5. My study blood work from now on includes viral load counts. So at my next visit (week 16) I'll have another VL test to base my final decision on. It won't cost me anything.

I'm thinking I have absolutely nothing to lose by going another 4 weeks. It might be a different story if I was beaten down, unable to work, tons of sides, and being pumped full of rescue drugs. But I'm not. My life, besides little odds and ends, has not changed during treatment. I still work full time, and do all the things I used to do.

Thanks again for all the ideas. It has really spurred me on to gather the data I need to make this tough call. I hope this information is useful to those in the future who face a similar dilemma.

Be Well!

Robert

[nygirl7]

As someone who was not und until after 12 but before 24 I can sympathize - it totally *****. Of course I had to extend to get  to SVR (I was a stage 3) but if I were stage 1 I am not sure I would go for it. Of course whether you  got the real deal or not is a big part of the equation. What a crap shoot it all really is at the end of the day.

I'm sorry I know how much you want to post I'm UND...took me forever to get that post in!

[meakea]

This thread makes my heart smile...not because you had a difficult choice to deal with...but because you have (and continue to) educated yourself about Hep C and all the issues surrounding treatment outcomes and because there are so many knowledgeable people here that help in the decision making.  All of that made your decision making "easier" and it sounds like a very solid and wise decision.

We see so many people who get into Hep C treatment not knowing anything about it and then when a difficult decision arises they don't know anything about it other than what their doctor tell them (and we all know that the docs aren't always as up on Hep C as they should be).  

Kudos to you Robert for being on top of things; along with the others here who know more than the average joe.  

There's no doubt in my mind that you will get where you want to be with this!!  Go get em!!

[iwillbeatthis]

<For what it's worth (G3 here), I needed the UND at week 4 and came back with "

Now I'm a bit confused. I'm g3 too, My 2 week VL test was 55, My 4 week and 12 week VL tests both say
HCV RNA PCR QUANT  <43  <1.63
Isn't that UND? Is there another test I should be taking?

[Susan_1a_CC]

I admire the approach you've used to reach your decision.  Being one of those coming up behind you, you've set an excellent example and I want to say thank you for sharing your information and getting the multiple feedbacks.  I'm pretty certain that with your odds I would also continue to roll the dice.  Keeping positive thoughts for your next 4 weeks.

[iwillbeatthis]

After reading posts on Robert's thread:
Now I'm a bit confused. I'm G3, My 2 week VL test was 55, My 4 week and 12 week VL tests both say
HCV RNA PCR QUANT  <43  <1.63
Isn't that UND? Is there another test I should be taking?

[iwillbeatthis]

sorry meant to start a new thread

[Bali05]

From what I am told most people that are UND <43 or 50 are UND even with a more
sensitive test. I would want to make sure I am not somehow stuck <25.
Also as with any important test result it is a good idea to confirm it
with a second test.Samples do get cross contaminated at the labs sometimes.

[RobertBeWell]

Thanks guys for the kind words. That's what this site is all about, sharing the info. Perhaps the information contained in this little self-centered thread of mine will help another faced with the same decision in the future.

I'm still very hopeful at this point. My odds are at least as good as with the new PI's, though I will admit they start dropping dramatically with each passing week that I still have detectable virus.

Week 16 will be the tipping point for me.

Merry Christmas to all!

Robert

[paen53]

You've put alot of time and thought into this trial and I wish you the best going forward. You've really got nothing to lose staying in the game with minimal sx and the meds there for the taking. And if you indeed get a reassigment, so much the better.

Hang in there!

Pam

[RobertBeWell]

"After reading posts on Robert's thread:
Now I'm a bit confused. I'm G3, My 2 week VL test was 55, My 4 week and 12 week VL tests both say HCV RNA PCR QUANT  <43  <1.63 Isn't that UND? Is there another test I should be taking? "

Well, by most all published studies, it meets the criteria for UND (< 50). It just depends on how the lab reports it. With the exact information you state above, it doesn't technically say "undectected".  But again, it just depends on how the lab reports it.

With G3, and such an impressive 2 and 4 week result, you have nothing to worry about. The odds are very, very, VERY  strongly in your favor.

Rest easy, all is well ;-)

[GreatBird]

You have no way of knowing if you have already tested UND and then got a blip. I had a blip at week 20-something (so soon we forget) and it turned out to be a big nothing, although it was rather concerning at the time.

I think you are making the right decision. Good luck!

[iwillbeatthis]

so some labs say undetected and some don't?
I went back to read mine and they all said the same thing, just the <43.
is there a test I can request that will actually says undetected?

Thanks, and good luck to you Robert.

[RobertBeWell]

"You have no way of knowing if you have already tested UND and then got a blip. I had a blip at week 20-something (so soon we forget) and it turned out to be a big nothing, although it was rather concerning at the time."

Absolutely. Thats the peril of a trial :-)

RBW

[RobertBeWell]

"so some labs say undetected and some don't?
I went back to read mine and they all said the same thing, just the <43.
is there a test I can request that will actually says undetected? "

That's my understanding. You should talk to you doctor and the laboratory for the specifics. That's really the only way I would know to confirm an actual UND.

You have to remember that I'm in a drug trial, so every "i" is dotted, and every "t" has to be crossed. My tests are going to be very, very specific, and state that.

Talk to your doctor. But seriously, you have no reason to get worked up over this in my opinion.

[GreatBird]

Being on a trial has nothing to do with it, although being blinded for VL adds to the uncertainty. My trial wasn't blinded for VL so I had them all as I was going along and had tested UND from week 12 until I got the blip. Since that blip I've tested UND--up to and including the most recent 1 year post PCR.

Hang in there.

[spectda]

If they are using the taqman 2 as many clinical trials seem to these days and a person was und, the report from roche will merely sate  "HCV RNA not detected" without parameters.

This test was only recently approved by the fda but has been used in the clinical trials for a while. I don't have my printout before me but I believe that when I was under 25 it read: detected <25

If it is indeed the taqman 2 they either are unable to quantify or not approved to report a quantifiable number under 25 iu/ml. The lower limit of detection of the test is 10 iu/ml so <25 would mean RNA somewhere between 10-25 iu/ml. If it is above 25 iu/ml of course it will quantify it.

Robert-
There are at least a few people here who have SVRd and reported a blip at or after week 12 and you have no way of knowing if this is one or not. As you said it can't hurt to go another 4 weeks since you aren't feeling poorly. Good luck my friend!


Bree-
They used less sensitive test for you and it is reported differently. You can always ask for a more sensitive test if it would make you more comfortable.

All the odds are in your favor as everyone has mentioned. It's not over till it's over of course, and it's only natural to worry a bit, but I would be shocked if you are not und for real and if you don't svr.

Happy Holidays Everyone,
Dave

[iwillbeatthis]

thank you, you know when you are going through this, I'm very positive about achieving SVR, but once in a while, you just freak a little, when you hear technicalities like this, and then I snap out of it. I will ask my doctor about a more sensitive test, just because.

[RobertBeWell]

Oh, I did receive a lot of recommendations for a private PCR immediately. Not ignoring that advice, but I just can't afford to do that right now, especially at Christmas time. And by the time I had it done, it would be time for my Week 16 visit anyhow, when I can get one done without having to pay for it myself.

Thanks guys!

[fretboard]

Well it sounds like you came to a decision with this unwelcome news to tx another 4wks.  Good for you and I hope it works out well.  good luck!    

[murariji]

Definitely right decision to continue. Very little to lose and so much to gain. Stick with your decision. Bin your doubts and and worries and that'll take care of whatever is left.

Good luck

[RobertBeWell]

Heh, I'm a worrier by nature. I wish I could "bin them" but they just hanging around. Part of the problem is that I went into this trial with very, very high expectations. Heck, I was sure I would clear the virus by week 4 (which I had an 85% chance of doing if I were getting the real thing).

So even though by SoC standard my treatment is going really quite well, by my expectations, it is going poorly at best.

We'll see at week 16. Thanks for the encouragement brah!

Robert

[babs824]

so sorry this is looking more complicated. i can only offer support for what ever you decide. i have not spent time in the research many of the heppers have. my 64 year old riba brain has to keep it simple. if your sx are minimal i see no reason not to stick by a bit longer. wishing u a comfortable resolution soon as the fence is uncomfortable. all the best, babs

[uncledudeness]

I am so happy that you responded as well as you did. you are going to beat this thing. if it was me i would stay with it too...keep fighting.

...and if you see any BMS people, give them a kick in the nads for me....imagine, rejecting me for this trial....the nerve...bwahahaha...

you are doing great Robert...a wonderful Christmas present indeed....good luck

the dude