Study Design: Treatment, Randomized, Double-Blind, Placebo Control, Parallel Assignment, Safety/Efficacy Study

What exactly does the following sentence mean about the VX-950 Phase II clinical trial?

Study Design: Treatment, Randomized, Double-Blind, Placebo Control, Parallel Assignment, Safety/Efficacy Study

Does this mean that the trial will have a placebo arm of the study?  

If a person is in the placebo arm will they be offered VX-950 at some point?  As a geno 1b viral breakthrough guy I'm not particularly excited about signing up for x months of torture (INF + RBV only) that we all know will not work.

What went on in the Prove 1 trials?

I have a lot of questions today.

Mike

[purplecat]

Placebo means no VX950 but blank pill. I'm one of those placebo groups from Prove1. Very disappointed but I knew going in that was a possibility. The negatives is you could also get placebo or your virus could start going wild from the VX.  One person from my center did get VX and virus dropped dramatically then started rising rapidly.  That is a sign of virus mutating and they pulled him off VX early and he is completing regular treatment. Others got VX now UND and going great. I feel most for the wild virus person than myself.  He knows VX950 is not a chance for him and must keep waiting for future research.  I have chance to get VX950 when approved sometime in2008. We are blinded as to the PCR levels on treatment so with 1B I did not know 4,8,12,20 weeks where my VL's were.  Studies show that 1A/B if not UND at week 12 98% do not reach SVR I read. Since I did not get VX950 these numbers are so important to know. They also made me lower my IFN week 9,10,11 because of neup count. They don't let you take rescue drugs weeks 1-12 while possibly taking VX950. This effected my overall chance for SVR. I maybe have been going through additional weeks of hell. I'm on week 21 and still waiting for Vertex to release my PCR levels so I can make decision to go on or find out I'm a nonresponder. Due to my SX ear problem-see my thread from 27Jan below-waiting is hell.  

[mremeet]

Are you a non-responder to SOC (IFN+riba)? If so I don't believe there's a placebo group in the Prove 3 trial (prove 3 being for non-responders). I'm pretty sure everyone gets the VX in that trial, I don't believe they would subject a non-responder to the same thing (i.e. SOC alone) they failed on before (I don't think the FDA would allow that).

There is a placebo/control group in Prove 1 (and 2 I believe), because these trials are for treatment naive folks only. I think what you're reading is referencing the use of placebo in these trials and not for the Prove 3 non-responder group. Might want to check on these statements, but I believe they're accurate.

[APKhaos]

Where did 'the VX-950 Phase II clinical trial?' statement come from? Prove 1, prove 2 [both for treatment naives] and Prove 3 [for relapsers] are all FDA Phase I trials.

Don't think we've seen any Phase III VX950 trials announced yet, but I maybe you have found something new here.

[APKhaos]

The liver center that ran our Prove 1 group are participating in Prove 3 also. The coordinators were up in MA at Vertex last week for Prove 3 training.

Maybe the person you spoke to did not know, but it seems that most east coast centers would have been at the same Prove 3 training session.

[purplecat]

Asked at center when I was there friday about Prove3 and they did not know if they will be selected for study yet. They haven't gotten anything from Vertex yet. Since they handled Prove1 in my area they are likely to handle Prove3 I would think but really do not know anything yet.
http://www.clinicaltrials.gov/ct/show/NCT00420784?order=75
Or contact Vertex.

[Hepatitis Researcher]

Unfortunately, the official FDA description of the Prove3 trial is quite clear:
Placebo control included, on subjects who have not achieved a sustained viral response (SVR) with a previous treatment of interferon therapy.

Just go to clinical trials.gov and look for telaprevir.
Identifier: NCT00420784

[mremeet]

Ahh, thanks for the correction hr. I tried to look up the details of Prove 3 at the Vertex site before posting, but they didn't mention a placebo or control group. I was told by my study nurse that the FDA usually will structure these trials so that you would have at the very least what SOC provides in terms of efficacy (for the treatment naive). So I thought for the non-responders it would be almost unethical to subject them to the whole thing over again, with limited chances of success (especially without increasing dosage and/or duration beyond what the standard treatment protocol dictates). Although scientifically I can see where a control group would be helpful.

Seems almost cruel to subject someone who's already failed one course of SOC (possibly lasting 48 weeks or more) to another whole 48 weeks of treatment with limited chances of success. Especially if they deprive them of rescue drugs during the early VX dosing period like they did with us in Prove 1. That could really put the hurt on a non-responder's ability to SVR. Man I'd be hot if I found out I was in that group and later relapsed again. But I guess you sign the dotted line informed, and you take your chances...or not.

[jmjm530]

I agree with Mre's assessment. All current information suggests that treating a non-responder with the same drugs for the same length of time will not offer a very good chance of SVR. In fact, on face value it seems so irresponsible that I called Vertex this morning to confirm --  as there may be some caveats such as very early stop rules with the option then to start Vertex, etc,  or perhaps info posted on clinical options is simply wrong as sometimes happens.

Needless to say, the girl who answered the phone didn't even understand the question. Obviously, this is no accident and they probably want to make sure that any info released  in a more formal fashion by those higher up. However, I would think, that those at the study sites might be able to offer more on this. If I were looking into the trial, I'd be calling several study sites now and try and determine exactly how the placebo group arm would be handled.

-- Jim

[jmjm530]

I understand you probably can't comment on it in a public forum but something sounds very wrong on face value and I don't really understand why the FDA would basically send a bunch of heppers (placebo group) out to certain slaughter. My hunch is that it won't go down exactly like it seems at face value. The fact that it's so hard to get any info from Vertex on this suggests things may not be settled yet.

[jmjm530]

Or maybe they'll only accept those who previously took monotherapy (peg no riba). Like yourself, I can't believe they're going to take a group of peg/riba 48-week non-responders, and give them peg and riba for 48 weeks. In fact, look for the placebo arm to be dropped entirely if the prelimary SVR data comes out looking good with the current trial. Details are hard-to-find to non-existent on the Vertex site, and it's not hard to believe that meetings will go on right until the trials begin on this and other issues. But I think we both agree that anyone signing up for Prove 3 should get all pertinent information before the first shot, even if not available today.

-- Jim

[jmjm530]

re: first sentence -- that would be "interferon, no riba" as they didn't have "peg" back then.

[Hepatitis Researcher]

The inclusion criteria on the fda website state "Must have chronic hepatitis C (genotype I) and have already received at least one prior course of peginterferon WITH ribavirin."

[mremeet]

Another thing is that they were tweaking and fine tuning the Prove 1 test protocol all the way up until the start of the trial. For instance, the 12 week group was originally the same size as the other groups (~80 people). But apparently the FDA directed them to shrink that group down to 20 people shortly prior to trial commencement, thereby lessening the odds you could end up in that group. The reason being is that the suspected odds of achieving an SVR might not be very good. Plus, as hr has explained (for mono-therapy), if you were in that group and later relapsed because of too short a course, you'd likely retain/breed the "memory" of PI and/or SOC resistant strains into your virus - thereby lessening your odds of successful treatment later, even with access to VX-950 again. Although on the other hand it's not monotherapy, so hopefully this memory effect would not be as distinct and pronounced as it would be after only taking a PI alone.

Anyway, I'd suspect (or hope) the FDA will be structuring this trial so that if the placebo participants either fail to go UND within a reasonable period of time or have a rebound, then they would have immediate access to VX in addition to SOC. They might also shrink the control group like they did with the 12 week group in Prove 1. Hopefully they will anyway. I mean, if I underwent a whole 48 weeks, especially if I experienced dose reductions early on due to anemia, only later to relapse and find out I was on placebo?? Wow, to say I'd be "disappointed" would be putting it mildly. (especially considering how badly these drugs affect me personally)

[purplecat]

Originally when I discussed the Prove1 study with my Hep Dr July of 2005 there was not supposed to be a placebo group.  Drug politics took over and finally by Aug 2006 double blinded and placebo group was added. The political process can be ugly, we know it is crazy for placebo group especially with nonresponders but Vertex have to play the game to get the drug through the approval process. The same political power who insisted on placebo group for Prove1 to proceed seemed to also won out in Prove3, I'm sad to hear that.

[Tallahassee]

As HR stated, only patients treated by peg. interferon with riba will be qualified for this study.  I was told by Dr.N from University of FL in August 2006, that I will not qualify since I never had peg. interferon before (though I have 11-12 years history with all kinds of interferon treatments with and without riba).  But (!) he thinks that later Vertex should have a study accepting patients treated with any interferon(s).

[miked]

Been traveling, sorry for the delay.

Thanks for all of your replies.  Yes I'm considered a non-responder even though I had an initial 3log drop then a slow gradual VL decline until it started to go back UP.  I told the doc to increase or change INF but Dr. Smartypants wouldn't hear of it.

Anyway what I don't want to do is be in a placebo group and suffer the sides of tx for no reason.

My question is IF a person is in the placebo group and was a prior non-responder, at some point during the trial will Vertex say, "OK, this person isn't responding again to INF + RBV just like we thought therefore we will NOW give them VX-950 so they can achieve SVR"?

[purplecat]

I'm placebo Prove1 and the answer is NO. They add this control group to have a real comparison for the VX950 groups. Seems crazy since they have all the stats on SOC TX. I remember my high school biology teacher saying, to prove any result you must have a control group in your study at the same time or you don't prove anything. I fortunately hit UND at 12 weeks so I'm continuing and my result will help vertex get VX950 approved.