Trial pitfalls

[mike716]

Hi, everyone! It's been a looong time since I posted here, but I hope some of my friends in the forum will remember me. I'm the wise-a$$ (some say "funny") New Yorker with HCV gt1b A2F2 who's living in Buenos Aires, where my hospital isn't giving me tx so far.

A woman at another hospital called me a coupla days ago and offered to let me into their tx trial. It seems they're part of an upcoming international protease inhibitor trial and need subjects. She wouldn't answer any questions over the phone (natch) so I made an appointment with her. I want to get my questions lined up before going over there, which is the reason for this post. I know this stuff has been asked a million times before. So be patient with me, okay?

What are the main pitfalls of the trials, aside from that you aren't told which leg you're in?

I seem to recall that one of the bad things that can happen is that you have a side effect like severe anemia and sometimes they won't give you the meds to counteract it so that you can go on with the tx. Is that right? So should I ask if I can get something in writing about save drugs? (Maybe I should bring my lawyer with me...Ooops, there I go again...)

I guess another problem could be that their viral load test isn't sensitive enough to read down to a true "undetectable' amount (which I believe is now considered to be below 10/ml).

Then there's the question whether or not they're going to do the viral load PCR - even if they have the right test - at 4 weeks, to see if I'm having an RVR.

That's all I could think of. What are the other things I should ask about?

Help here will be much appreciated.

Mike

[GreatBird]

1. what phase trial is this? (1, 2, 3?)

2. if you are on a placebo arm and don't clear will they give you the trial meds later so you have a chance?

3. do they give and pay for rescue drugs? (procrit, neupogen)

4. what is the name of the PI?

5. can you have a copy of the consent form (do they do consent forms?) so you can review it before you need to sign it

That's all I can think of right now but yesterday was shot day and . . . I'm shot.

[annieCinMD]

I'm in a trial, and I DO know which arm (or leg as you call it lol!). I didn't know before I got put in it, but I was told before I ever starting an Tx. The one I'm in has no placebo arms, so you get treatment, it just depends which arm your in, whether you get Peg/Riba only or the study drug in addition to Peg/Riba.  I am in Peg/Riba only. My trial does Pcr at 2, 4, 8, 12 and I think monthly after that, if your still in. I will get option to add the study drug at week 12 if I made the 2 log drop, but not UND. If you don't have the 2 log drop at week 12, Tx is discontinued. I was told my doctor will prescribe rescue drugs if I need them. I'm in one of the Schering-Plough studies by the way. Hope it helps some, even though I'm not sure if things are different outside of US.

[GSDgirl]

Hey, I do remember you.  I can't help you with your questions but am wishing you luck!!

Denise

[jmjm530]

I'm the wise-a$$ (some say "funny") New Yorker with HCV
---------
I probably would have stuck with "wise a$$", nevertheless :)

Of course you are remembered. How many people commute from NY to Buenos Aires to get their teeth cleaned and as long as they are down there have their liver's checked at the same time?

As to the trial (Buenos Aires or NY?) first of all you want to know what particular trial you may (or may not) be getting into. If you can get the specific name of the trial before you appointment, then you will have a little more heads-up time to do some homework and maybe ask some questions here to some who may have been in that particular trial.

Some things to be considered in a trial are what drugs are used, what doses, what phase trial it is, how many "Arms" or subgroups and what is the protocol for each Arm.

You also want to know if helper drugs (Procrit/Neupogen) are allowed and with what criteria. Also, when you will be tested for viral load, with what tests will be used and at what sensitivity.

You also want to know any "stop" criteria such as if you don't have a certain viral response by week such and such. Another question might be what will you be offered if you don't meet the requirements and/or relapse. Will they roll you over into another protocol or simply say sayonora.

Anyway, a lot of these answers should be in the trial particular which hopefully you can get in writing at your meeting, but if not perhaps someone here can fill in some blanks if you give us the trial's name. If I remember correctly, you still had not gotten a biopsy (or perhaps it was a recent biopsy?) . Any movement in that area?

As to "pitfalls", first and foremost it's a "trial", in other words you're more of a guinea pig than the rest of us guinea pigs who are taking drugs out of trial. You also could end up in a placebo arm, meaning you won't get the super PI that the trial is focusing on. Also, you might get the PI but at a less than optimum dose or time frame which may not be discovered until the trial is over. Helper drugs may not be available and if you don't like your medical team youre more or less stuck unless you drop out of the trial. That's for starters. Still, some very promising trials out there and if someone finds the right trial to match their stats it seems a very reasonable way to go these days. Lots of success stories here.

All the best,

-- Jim

[Marcia2202]

I don't know anything about trial, just wanted to give you a big 'holllllleeerrrr'. Good to see you posting my friend.

[portann]

I may not be a lady but I also want to say hi.

Port

[Willy50]

Nice to see you again.

Request the trial agreement.  Much will be spelled out in that.

Look the trial over also in Clinical trials (could it even be FDA?) but generally speaking there will be lots more info in the trial agreement.

I would read up on the drug, compare it to other drugs and see what else may be in you area.  You don't say; could this be FDA approved in B.A.?  I assume not but you may also have to evaluate the agency.  Trials are probably safer in the USA.  The downside with safety is it can also take more time for approval.  You may not want to participate in a trial where intro to approval takes 16 months.  ; )  I joke but you follow my drift.  You need to make sure that you are comfortable with the approval agency.
If it's the "chinese FDA" I might pass.  ; )

Google the PI and see if you can research it.

Generally I agree with whatever everyone else said.  You have to think the process through; what happens when "X" happens?  When "Y" happens, etc.  

A few examples; having rescue drugs paid for or allowed makes no difference if they reduce dosing first; what are the cut-off levels?

IF you are exposed to a PI and get underdosed, or pulled of the trial before clearing, or treating at sub-optimal levels so that you are more likely to break through, respond slowly or relapse....then you may be burning a bridge that you will need in the future.  If you fail this trial and were exposed to PI's you may come to wish you had not participated.

Play detective and you can always report back here with questions but I would have the agreement first, the name of the compound before even casually considering it.
I hate to question the agency but that could also factor in my decision.  There was an absolutely *from hell* trial about 3-4 years ago that pretty much damaged or killed everyone who got the compound. It was phase 1, caused extensive organ damage, and the company went bankrupt.  Lest you think it can only happen in "the third world"....this happened in Great Britain.

Sometimes it's good to get the placebo...  

Best,
Willy

[annieCinMD]

Willy's right about that agreement.  I've had about 3 addendums to mine so far due to some minor change in verbage.  I have to intitial every page, and sign and date the last page. My study coordinator gives me copies. I've never had to ask. They spell out the study in detail, and with the signing, I think they really want you to have read it.  I think mine actually is a clinical trial. Not sure of the difference?? I can't complain about it. I'm sure even with the good insurance that I have, being that there are no generic equivalents of these drugs, I'd be paying a pretty penny. Getting free meds and being watched a bit closer because of the study.  

[Trish77]

Hiya Mike.  Good to hear from you again.  Trials have "arms" Mike .. not legs. :)

I'll end up repeating some things but it's too much work to go back and look through everyone's submissions...so my apologies for any repeats.

Get the name of the drug and look at the past trial history of the drug - you're looking for side effects and you're looking at statistics on effectiveness.

Read the trial agreement and look closely at the various arms.  See if there are any arms that are dealbreakers and that make SOC look to be a better option.  Check out the interferon and ribavirin dosages and compare them to SOC to see how much of a risk you're taking.

Ask if they'll be letting you know the results of your PCR's and when.  Some trials won't tell you the results of your PCR's at all until you're well along in your treatment.  My trial told me the results of my PCR's all the way through from Day 1.  

Ask how often you'll get a PCR and if it's qualitative or quantitative and what the sensitivity of the PCR is.

Ask about rescue drugs - do they allow them and will they introduce a rescue drug before they will reduce dosages? Which rescue drugs will they allow and who pays for them?  How long will it take to get them if you need them?  Here in Canada, it can take awhile to get the government approval to cover the cost of the rescue drugs so you're either paying out of your pocket for awhile or if you can't afford them then you have to wait to get them until the approval goes through.

Ask about dosage reductions - what scenario would necessitate a dosage reduction?  For example, at what point will they automatically reduce your ribavirin or your interferon or both as in what's their threshold for your hemoglobin (ribavirin impacts this) or your ANC - Absolute Neutrophil Count (interferon impacts this).  In my trial, if HGB dropped below 10.0, it was automatic riba reduction.  If ANC and lymphocytes dropped below certain amounts it was automatic interferon reduction.  The level at which they will force a dosage reduction on a trial is usually higher and more cautionary than it would be on SOC.  They're dealing with a trial drug combined with SOC drugs and they don't call it a trial for nuthin.  So trials are more cautionary when it comes to how much risk they'll take with these things.  

What Phase is the trial?  Phase III trials are the best of course because they've got most of the kinks worked out compared to the earlier Phases and are refining their best dosage combinations by that point.

Who pays for the drugs?

If you end up relapsing or not responding for whatever reason, do they offer a rollover into SOC at their cost?

Is the drug known to build up a resistance to it?

At what point will they consider that treatment has failed?  

Study the arms of the trial, Mike.  See if there are any that are too reckless.  And study what's known of the drug and it's past history.  Pay really good attention to that, Mike.

And...post it here.  I did that before I went on my trial and I got really good feedback.  Everybody had different opinions and insights and it helped broaden my thinking towards making a decision that was good for me.

If I remember anything else, I['ll post it.  If you wouldn't mind, post the details of the trial.  It's good to know what's going on in the world of Hep C out there these days.

Take care and all the best to you, Mike.  Nice to have you back again. :)

Trish

[merryBe]

of course we remember you...look 2 main things....if it's not phase 3 run, don't walk away.
Unless you are desparate or at deaths door you don't want be the first of 20 human guinea pigs...sometimes what looks good in a petre dish or mouse turns out to be Darth Vader in human tissues.

2. All the PI's knock the virus out faster, which is why everyone is pushing in invent the first great PI....but PI's also have a nasty rep for knocking the blankety blank out of your white cells...and the riba, usually still on board albeit at reduced dosages is heck on the red cells....so make sure they will allow rescue drugs. You might recover or survive ok without them if treating only 6 months, but don't bank on that, especially with the PI's..
Usually on SOC people see a gradual drop in WBC but NOT true with PI's..nosedives are common there.
plus a couple PI's have been pulled in phase 1 or 2.....I'd want to know which company was making it and whether they had substantially changed the molecule from the one pulled...if they had the bad drug...sometimes they just remove one isotope and try again, until they get it right..it would be better to get in a good trial that treats their patients compassionately...like the Shlering-P does.

anyway, those are my 2 biggies, phase 3 and recue drugs.
Hope the study can help you.

mb

[mike716]

Thanks a million, everybody. This is a great help. I´ve got to run off to the hospital now for my interview, and at least I feel ready to ask the right questions and stick up for myself. I´ll post back with some answers to the above posts, and a few more questions, after the interview.

Cheers!

Mike

[mike716]

Hi, everyone! I'm back with the trial particulars.

First I want to thank you all again for the help with questions for my trial interview. I went in there not only prepared but secure in the support of all the great people in this forum, which makes all the difference in these tricky confrontations with the medical profession. Reading all these warm and generous replies I felt again that wonderful feeling of belonging that I felt when I joined the forum a year ago, a feeling so nourishing that it's surely the best of all therapies.

I also want to thank especially Denise, Jim, Marcie, Trin, Willy, Trish, and MerryB for remembering me with such kind words. Being remembered like that is awfully nice, and flattering. I may have to revise my image of myself; maybe I'm not such a &%$# after all...

Now for the trial. It's a phase II, double-blind, placebo-controlled trial of Boehringer-Ingelheim's protease inhibitor BI201335. There are five arms (I personally prefer "legs" but appreciate the correction) designed to test dosage and timing, quite similar to other protease inhibitor trials.

They gave me the trial prospectus which I have now read, for whatever it's worth (not much, as it's pretty confusing).

I don't know if they will give me a copy of the consent form prior to signing it. Doesn't really matter, actually (see below).

They weren't very forthcoming with answers to my questions. They did tell me that all blood samples go to Germany for analysis, but that leaves a lot of holes, for example: who will do the weekly exams?, who will monitor my side-effects?. Stuff like that. And when I asked about rescue drugs, they seemed reluctant to commit. They suggested maybe I could get them from my regular hospital where I'm a health plan member, which is ridiculous. When I put pressure on, they admitted they had the rescue drugs there at the study hospital, but I had to twist their arm to get them to say they would give them to me. And when I asked if having anemia or other adverse reactions would curtail the trial or result in dose reduction, they wouldn't answer except by saying that "Boehringer makes all the decisions".

Needless to say, I was not happy with the interview. I had the feeling they were participating in the trial strictly for the money (Boehringer pays the "fees" of the doctors conducting it), and that their attention to patients would be minimal. It certainly was in this first interview. They made appointments for me and fourteen others at the same hour, and we had to wait in a room with no windows, no air conditioning (it's summer here), no telephone, and no water!

Furthermore, I now suspect that the reason this public hospital initially refused me antiviral therapy was so that they could get me into one of these trials. When I left the clinic yesterday I chatted outside with a patient who's on therapy for the third time, no problem getting the meds (I accompanied her to the hospital pharmacy where she collected her weekly doses of Pegasys and Copegus!). She said she knew lots of people getting treatment there and couldn't understand why they had refused me.

By the way, this is the hospital that asked to borrow the biopsy specimen taken at my health plan hospital in order to do their own pathology of it, and then didn't return it, thereby getting me into trouble with my own hospital. Apparently something untoward happened to the specimen in their hands and they don't want anyone to see it. They may even have thrown it out. So If I need to have a second biopsy in a couple of years, my hospital's pathology department may refuse to do it because I never returned the original one. So as you can imagine (and even given that I am a cynic and long-time hater of doctors) I was not exactly well-disposed towards these people to begin with.

As a final red flag, I found the following in an online news item (http://www.hivandhepatitis.com/2008icr/aasld/docs/111108_c.html):
"Investigational HCV Protease Inhibitor BI 201335
• A majority of patients in all dose groups experienced viral load rebound during the first 14 days of monotherapy"
Cheery, huh?

So, all things considered, I'm not going to do the trial. I'd rather wait until my regular hospital decides to give me tx, even if it means waiting another couple of years for approval of a good med combination. I've got analyses coming up in April, so I should have a better idea how the disease is progressing then. And I might even be able to convince the people in Sevilla to do follow-up FibroTCs, which are much less invasive than biopsies. (If someone can tell me how to post a .pdf file to the forum, I will post the results (images) of my FibroTC, which is a very interesting alternative diagnostic for fibrosis.)

Thanks again to everyone for your help with this. You guys make all the difference. I love ya.

Mike

[mike716]

Hi, GreatBird! Thanks for the suggestions. I hope you are feeling less shot today.

Mike

[mike716]

Hi, Annie. I hope your trial is going okay.  What's the study drug?

I was interested that you have an option to add the study drug later. I never heard of that before. What's the rationale for adding the study drug if you have a 2log drop but not if you're UND? Do you know?

Cheers!

Mike

[mike716]

Denise!, my favorite GSDgirl (whatever that means), how the heck are ya?

I thank you sincerely for your wishes of luck, Deni. As a matter of fact I do seem to have a lot of luck. Unfortunately, it's mostly not of the good variety. However, as my shrink says, it's all my own fault. (I accept that. I am making progress. My shrink likes me. I pay the bills on time and never argue. How can you argue with a shrink?)

Tell me, Denise, what's it like in Pittsburg these days? After being disindustrialized, the last thing that city needs is an economic collapse. Do you still get running water and electricity? Is there garbage disposal? Can you go out at night?

I may decide some day to return to the States, so your replies to these important questions will be studied carefully.

Mike

[mike716]

Hiya, Jim! So, you remembered my crazy story about going to Bs As for my teeth and getting dioagnosed HCV+ as a sort of "side benefit" of the trip? I feel kinda embarrassed by the whole thing, frankly, and will appreciate it if you wouldn't bring it up again  because the lovely demoiselles in the forum who seem to like me for some reason might decide, realizing how coocoo I am, that it's dangerous to have anything to do with me.

Kidding aside (?), I did finally have a biopsy. The pathologist gave it the following:
IAH: A:2, B:0, C:2, D:3 = 7/18
Estado 2/6
Metavir: A:2, F:1

Not sure what all these sawbones hieroglyphics mean, but my hep MD said I had light to moderate fibrosis and moderate inflammation. How bad is that? Your guess is as good as mine.

Thanks for all the suggestions and info.

Mike (Guinea Pig XR49T00825)

[mike716]

Marcie, my dear, how goes it in Copenhagen? Or are you back in the tropics?

You never answered my last note, you naughty girl. I know, I know, your social life is just sooo busy...

M.

[mike716]

Hiya, Trin. How's tricks? (That´s a suggestive salutation from the netherworld of my mis-spent youth.)

I don't know why the ladies here are so friendly to me, Trin. Do you think it could be that they sense I need mothering?

Mike

[mike716]

Hi, Port. Now, just exactly what do you mean by saying that you may not be a lady? Tsk-tsk. Would you care to enlarge on that? Details would be helpful.

Mike

[mike716]

Hello, Willy. Thanks for the good words.

You have put the fear of g*d into me with your tale of mayhem in Great Britain.

Any idea where I can get info on the effects of failing a protease inhibitor trial, especially as regards drug-resistant viral variants? These protease and polymerase inhibitors haven't been around very long, but there must be some studies of the consequences. I wonder if they don't make your infection a whole lot more intractable if you happen to not clear the virus. I think something of the sort happened with HIV, didn´t it?

"Sometimes it's good to get the placebo..." I hear ya.

Mike

[jmjm530]

I have not tested these individuals sites but I think you can upload files for public viewing for free.

http://www.uploading.com/

http://www.filefront.com/

[mike716]

Trish, you sweetie-pie, have you reclaimed life yet? For that matter, is life truly reclaimable? It would be good to have some clear evidence of that, if you have any.

My own experience (admittedly a particularly sad case) has been that no claims at all can be made on life, and that the so-called human species is in itself a horrendous epidemic. But we would have to question the frogs and dandelions about this.

Arms? Not legs? Why?

Your admonitions about rescue drugs are well taken. Thanks. All your explanations are a big help in sorting out so many preoccupattions, whether I do a trial or wait for approval.

If there's nothing in the trial particulars about rolling over into SOC if you fail, does that mean they won't do it? Or should I query them on every point? (Even if I don't do this trial, I want to make up a list of all necessary questions, for the future.)

I don't know how to post the trial details except to scan the document they gave me, and I don´t have a scanner. Anyway, it's in Spanish (translated by the usual aphasics).

Mike

[mike716]

Hi, Merry! I have decided to run not walk away from this phase 2 trial, as you suggest. I am good at running away.

Still, it would be nice to get revenge on them for the shoddy way they treated me at the interview. So I may not so much run as zig-zag, fake to the side, and dart over the line to kick their captain in the shin before speeding out of their grasp.

I considered blowing the whistle on them to the Boehringer boys in Berlin, but they have my address and I fear retaliation from the Argentine Medical Hit Squad.

So, a quick one to the shins and I'm away.

Mike

[mike716]

Thanks for the URLs Jim. However, the Sevilla people asked me to be carefull where I post the results. I trust Medhelp would be okay for them, but I haven´t figured out how to do it. Maybe someone else here knows. Must be some way.

M.

[jmjm530]

Gotcha. Well, you can post picture files on your profile page somewhere. So maybe try converting the pdf into a jpeg or pic file, or whatever kind of file MH accepts. Maybe it will even accept a pdf, don't know, never tried it. If you don't have a converter, maybe you can find a free one online or some nerd will show up and offer to do it for you if you email them the file.

[jmjm530]

Sorry, I think the word is "geek", not "nerd" LOL

[jmjm530]

Two-Day Results Predict Ultimate Response to Therapy in Chronic Hepatitis C

A new study suggests that previously noted low rates of successful hepatitis C virus (HCV) therapy in African Americans are in large part due to very early differences in the antiviral activity induced by interferon. The study is published in the April 15 issue of The Journal of Infectious Diseases, now available online.

More than 3 million Americans are infected with HCV, and in some countries more than 10 percent of the population is infected. Chronic HCV infection is the leading cause of liver failure worldwide. Response to standard therapy with peginterferon and ribavirin varies widely. Those infected with one strain of the virus—genotype 1—are the least likely to have a successful response to therapy, known as a sustained virological response (SVR). About one-half of patients infected with genotype 1 do not achieve SVR.

Studies have shown that African Americans have consistently lower rates of SVR to interferon-based therapy, compared to Caucasian Americans. A recent study of those with chronic genotype 1 HCV infection found that only 28 percent of African American patients attained SVR, compared with 52 percent in Caucasian Americans. This new study shows that the variation in therapy responsiveness between African Americans and Caucasian Americans can be partly explained by differences in viral response noted as early as one to two days after the first dose of peginterferon.

The study, conducted by a collaborative group of eight medical centers throughout the United States, monitored 341 patients with chronic HCV, genotype 1, who underwent therapy with peginterferon and ribavirin for at least 24 weeks. It focused on response rates to interferon therapy within the first 28 days of therapy, noting viral factors such as HCV RNA levels and host factors such as race, gender, and weight.

Results showed that HCV RNA levels decreased in almost all patients, and that the degree and pattern of decrease, as expected, was different between African and Caucasian Americans. Most important was the new finding that these differences were statistically significant by day 2 of treatment, and that this early viral kinetic measurement was a reliable predictor of ultimate SVR rates.  After 28 days of treatment, 22 percent of Caucasian Americans, but only 12 percent of African Americans, were HCV RNA negative.

These findings are particularly important because they point toward the presence of some block or defect in the immediate antiviral response of those who do not respond to therapy. As the authors summarize, “The underlying cause of virological non-response and the reasons why it is more common among African Americans than Caucasian Americans are not clear. [But] the current analyses demonstrated that these differences are fundamentally biologic and become apparent within 24 to 48 hours of starting therapy.” As a next step, future research should focus on these host biologic factors that are induced by interferon in an attempt to improve therapy response rates.

In an accompanying editorial, Andrew W. Tai, MD, PhD, and Raymond T. Chung, MD, of Massachusetts General Hospital agree that the findings will prove vital for future research into HCV, remarking, “[this study] demonstrates that the low rates of SVR in African American patients in response to IFN-based therapy appear to result, in large part, from impaired early viral kinetics. Further studies are necessary to uncover the relevant mechanisms that underlie this defect in IFN signaling… with the hope that such mechanisms can be manipulated to restore interferon responsiveness in the otherwise nonresponsive host.”

###
Founded in 1904, The Journal of Infectious Diseases is the premier publication in the Western Hemisphere for original research on the pathogenesis, diagnosis, and treatment of infectious diseases; on the microbes that cause them; and on disorders of host immune mechanisms. Articles in JID include research results from microbiology, immunology, epidemiology, and related disciplines. JID is published under the auspices of the Infectious Diseases Society of America (IDSA). Based in Arlington, Va., IDSA is a professional society representing more than 8,600 physicians and scientists who specialize in infectious diseases. For more information, visit www.idsociety.org.

http://www.idsociety.org/Content.aspx?id=13720

[jmjm530]

Sorry that last post does not belong in this thread.

[GSDgirl]

GSD=German Shepherd Dog, which I have shown, bred, and trained and got the first title on one of mine.  I am waiting for that female to come in heat and hopefully I will have a pup of hers to train.

Running water??? hmmmm. I have chickens to get my own fresh eggs, we are tilling a large garden for veggies, buy a whole pig & half a cow every summer (organic) for fresh meat, hubby hunts deer.........just in case we really collapse LOL.  That stuff is true except for the collapse.  I live 20 miles south of the 'berg on 15 acres and would never go to Pittsburgh at night. I avoid it in the day too, hate the city.  Sorry about the trial mess-up

Denise

[annieCinMD]

The study drug is SCH 900518, a protease inhibitor, taken along with Ritonavir, which slows down the rate at which the body removes SCH 900518.  If at 12 weeks, you show a partial response to treatment, but not UND, you get the option to switch into the crossover arm and add the other 2 drugs.  I assumed this meant a 2 log drop, but it doesn't say that exactly.  It just says that if the levels are detectable and shows an insufficient response to treatment, you will discontinue treatment. They call the situation that gets the crossover option, a partial response to treatment.  If you are UND at week 12, you continue with Peg/Riba only for the duration of the 48 weeks. Hope this helps!

[Trish77]

Hiya Mikey.  (Sorry, couldn't resist.  My brother's name is Mike and my dad's name is Mike.  My dad was called Mikey by everyone in the family despite him being the oldest and tallest.  An affectionate moniker. Didn't realize until I was older how cute that really was that they all called him Mikey...but I digress.)

Here's a link to your trial, Mike, on www.clinicaltrials.gov.

http://www.clinicaltrials.gov/ct2/show/study/NCT00774397?intr=%22BI+201335%22&rank=1

Unfortunately, it doesn't go into much detail about what the five arms consist of and indeed, it doesn't really talk about the arms at all.  I'd be very interested in knowing what the dosages for the arms are, if you could assuage my curiosity and post at least that much?

My treatment centre in Toronto is also running this polymerase inhibitor Phase II trial and are also currently recruiting.  It's for treatment naive and

I don't quite agree that one should avoid all Phase II trials.  It all depends.  Not just because I just went through a Phase II trial - it simply depends on the trial itself.  Phase III trials are best, granted.  But I wouldn't dismiss a Phase II trial out of hand.  MerryBe and I differ on that point.  (Qu'el surprise.)

As for how they treated you in your interview - they are partly correct, Mike.  The trial sponsor does call the shots. So they might be telling the truth in that one in that, depending on what you asked them, the trial sponsor would make the judgment call.  There seems to be a certain amount of leeway the trial centres have and beyond that, it's the trial sponsor who calls the shots.  That's my understanding of it anyway and someone please correct me if you know otherwise.

To my understanding, rescue drugs aren't paid for by the trial.  It's a question to ask but if I misled you into thinking they SHOULD pay for them, I apologize.  It's simply collecting facts upon which to make a decision.  To my knowledge, rescue drugs aren't paid for by the trial sponsors.  The BIG question is whether they allow them or not - and if they allow them, will they offer rescue drugs instead of reducing dosages.  I paid for my own rescue drugs and thankfully I had drug coverage for 80% and got some coverage for the rest but it took months and months to get reimbursed for it.

As for the 14 day monotherapy result, you're mis-stating it.  This drug dropped the VL quite a bit in the very beginning of the 14 day monotherapy - a >2 log drop for 100% of persons within the first few days and yes, the VL rebounded but did not rebound fully and then started to decline again and continued to decline for the 28 day duration of the Phase I trial to maintain a >2 log drop at 28 days for 96.2% of participants.  14 days of monotherapy and then an additional 14 days of SOC combined with the PI.  That's with 14 days of monotherapy and 14 days of SOC....so a 14 day lead-in with the PI and then 2 weeks of treatment basically.  Here's a link to comprehensive results of the Phase I trial for this drug - both for you and for others, as here we have yet another polymerase inhibitor being put through it's paces and moving on to a Phase II trial:

http://www.hivandhepatitis.com/2008icr/aasld/posters/BI_AASLD_TN_Poster_FINAL.pdf

The current Phase II trial has the PI with SOC for 24 weeks, however the details are sketchy if they'll continue to 48 weeks without the PI - I would suspect so.  That's how my trial was supposed to go - the PI until 24 weeks with SOC and then continue on the remaining 24 weeks with SOC only.  The stated purpose of the trial you were just interviewed for is to determine how effective it is with SOC - the quest continues for a polymerase or protease inhibitor that delivers results and reduces treatment for Geno 1's in particular and then hopefully likewise for the other Geno's if it works for Geno 1's.

"Secondary Outcome Measures:

    * W2VR, W4VR, EVR, cEVR, ETR1335, ETR1335+4, ETR+12, time to VL BLD, time to loss of virological response"

That tells me you'd be getting PCR's at the least at Week 2, 4, and inbetween to Week 12 - you'd know how you were doing.  So decent frequent PCR testing happening there.

As for adverse effects, the Phase I trial showed no difference in adverse effects between those getting the placebo and those getting any of the dosages of the trial drug for the first 14 days.  After 28 days, there were some incidences of hyperbilruminemia at the higher dosages.

I wouldn't be so quick to dismiss this out of hand just yet, Mike....although, honestly...I'm not sure you can handle the nature of a trial.  Not quite sure your personality is a good fit, to be blunt.  :)  You're not a guy who likes to be restricted much and trials certainly have their restrictions.  SOC has far less and you might be a better SOC candidate.  Your liver damage doesn't put you in critical territory just yet but that's a personal judgment call and two people with the same stats could look at that different ways.

If you have them, would you mind posting the details on the dosages for the 5 arms?  I'm dying to know what they are, Mike.  Thanks much.

Trish

[Willy50]

Mike; here ya go.  Probably one of the scariest things that I have read.  Can you imagine being one of the people just waiting for the other shoe to drop.  I would love to hear what happened to these poor participants....especially after the bankruptcy.

Closer to home, B.I. is a real pharm and produced the first or one of the first PI's.  It was successful with a great viral decline but was found to have some cardio issues.  Another drug pulled about 2 summers ago caused a few cases of LFT's in the 500 range that *did not immediately resolve* after cessation of the drug.  The drug got pulled.... but I don't think I ever heard about the people.  It is probably in the blanket agreement; you cannot discuss the drug, the trial, etc.

Sorry to be so cheeeery.  If I read that story again I don't know if I will be able to sleep tonight..... but for the good of the forum, I'll post it.
---------------------------------------------

http://www.cnn.com/2006/HEALTH/03/16/uk.clinical/index.html?eref=aol

LONDON, England (CNN) -- A man who took part in trial tests of a new drug that left six people in serious condition said the experience was "like Russian Roulette."

Raste Khan, one of eight people who volunteered for the London trial, said he watched in horror as six other people became violently ill within minutes of receiving the drug.

"This one man was yelling 'doctor, my head hurts, my back hurts. I need help, I can't breathe.' He was just shouting and rambling to himself," said Khan, one of two men given a placebo.

"Everyone was continuously vomiting," Khan said in an interview broadcast Thursday on Sky News.

"It was like Russian Roulette -- two of us got away and were lucky."

One victim, whose head and neck were reported to have increased to three times normal size, was later described by a friend as resembling "the Elephant Man."

The six men remain in serious condition in Northwick Park Hospital in north London. Two of them are listed in critical condition, the hospital said.

They were admitted late Monday to the intensive care unit from an independent medical research unit at Northwick Park Hospital.

The men were paid to take part in a routine drug trial for TGN-1412, designed by German biopharmaceutical company TeGenero to treat autoimmune and inflammatory conditions, as well as leukemia.

"The four who are seriously unwell are continuing to show signs of improvement but it is still early," according to the statement from Ganesh Suntharalingham, the director of critical care at London's Northwick Park Hospital.

"The other two men remain critical and it could be a while until they show significant change."

Marion Flanagan said she thinks the doctors are not sure how to treat her son and the other five patients.

"They don't know what to give them or what to do with them," she said.

Freak show figure
Myfanwy Marshall said her 28-year-old "young, fit, healthy, gorgeous" boyfriend now resembled a 45-year-old heart attack patient.

"His face is bloated out, like elephant man," she said, referring to freak show figure in Victorian Britain whose head ballooned outwards until his skull was wider than his waist.

"They're recycling his blood trying to clean it out, it's affected every organ."

The hospital statement said some of the physical effects, like the swelling described by Marshall, were temporary side effects of getting the patients the fluid they need to survive.

"This is distressing for relatives to see, but it does go away on recovery and it has no long-term effects," the statement said.

The publicly traded, U.S.-based company Parexel ran the trial and many other trials on behalf of drug companies.

Parexel said it followed all the procedures for drug trials established in Britain. Health authorities have suspended the drug trial and have alerted hospitals around the world to make sure no one else is taking the drug.

An attorney for the trial participants urged the drug companies to provide her clients and the medical staff taking care of them all relevant information "to make decisions about their treatment."

"So far as my clients are concerned, what they need to know is a great deal more information about what was involved in this trial and what went wrong and how it was allowed to go wrong," Ann Alexander said.

Alexander also asked for a formal apology from Parexel and TeGenero.

"I haven't seen anything in writing from them, I haven't heard the words 'I am sorry' being used," she said. "I know that both of the companies have expressed the view, and they used the word 'devastated,' I think we're all devastated."

Tom Edwards, 21, said he decided not to participate in the test because the literature he was given did not fully explain the effects of the drug.

"I went through and read ... the consent form they got me to sign while rushing me," he said. "It didn't really explain it fully in there, so when I tried to contact them, there was no answer and no return of my message so I just left it at that and decided not to pursue it."

Dr. Thomas Hanke, TeGenero's chief scientific officer, said Wednesday that TGN1412 had not caused any problems in previous testing. Later, when asked by reporters if the company had apologized, he replied "yes."

Khan said he and the other volunteers were paid about £2,000 ($3,500) to participate in the trial, which was in the first phase of testing on healthy humans.

The UK medicines watchdog -- the Medicines and Healthcare products Regulatory Agency (MHRA) -- immediately started an investigation.

Professor Kent Woods, Chief Executive Officer at MHRA, told the UK Press Association: "Our immediate priority has been to ensure that no further patients are harmed.

"We will now undertake an exhaustive investigation to determine the cause and ensure all appropriate actions are taken."

Copyright 2006 CNN. All rights reserved.This material may not be published, broadcast, rewritten, or redistributed. Associated Press contributed to this report.

[Trish77]

"Trish, you sweetie-pie, have you reclaimed life yet? For that matter, is life truly reclaimable? It would be good to have some clear evidence of that, if you have any.

My own experience (admittedly a particularly sad case) has been that no claims at all can be made on life, and that the so-called human species is in itself a horrendous epidemic. But we would have to question the frogs and dandelions about this."

Oh my, yes.  I have most certainly reclaimed life.  Fought like he!! for it and sweetly won.  I have never been busier and happier than I am at this point in my life and I show no signs of slowing down.  On the contrary, I expect to be accelerating and I'm working on making my life as efficient as possible so that I can get maximum returns for my efforts.  Final test results come in April ... I'm *this* close to SVR but not taking anything for granted....taxi-ing up the runway though...this jet is getting ready for *takeoff*!!!  I am doing well finally.  I'm not 100% physically what I was before but have reclaimed and old ground and charted much new ground and have no plans to stop any time soon and not ever.

Yes, ask about the rollover into SOC.  It's worth knowing about at the least.  You can ask about all that stuff but not ALL of it matters.  It's simply gathering information and then taking all the answers and going through the sifting process.

"Arms? Not legs? Why?"

Arms - because they run simultaneously.
Legs- because they run consecutively.

Affectionately,

Trish

[GreatBird]

BTW--the clinical trial I am on (for boceprevir) does pay for rescue drugs. So far they have given me procrit.

[mike716]

Hi, Annie. So, if I understand you right, in your trial the protease inhibitor is only given after doing peg/riba for 12 weeks. That´s an unusual protocol, isn´t it? The other trials I´ve read about that add a PI to SOC (includin the one offered to me) add it either before or at the same time. Do you know what the rationale for waiting with the PI is? Is yours a special trial to see if a PI can be used as a response booster in people whose response to SOC is deficient? Or is this PI not designed to work the same way as the others?

I hope these detailed questions aren´t an annoying burden for you, but I´m interested in the differences between the many PI trials and the way the drugs are being used.

Cheers!

Mike

[annieCinMD]

Actually, most of the arms include the trial drug at some point. I can't verify it right now because my info sheet is at home and I'm at work : )
I think some of them add it right away, at the onset, some of them refrain from adding the Riba until week 4, some of them add it later. There are about 7 arms in this study.  I believe some of the trial drug arms stop at 24 weeks (all participants are treatment naive, genotype 1).  Apparently, the PIs are really good at stopping the virus from replicating, so should I show some response, but not fully UND at week 12, I get the option to add the PI. If that is the case, I will probably go with that option.  So, that being said, I think this PI is just like the others.

[Tippyclubb]

There is another trial going on now by Vertex Pharmaceuticals which is in currently in phase 3.  The PI being used is Telaprevir.    I happen to be in this trial now and am very lucky because its a NO PLACEBO trial.  I get SOC drugs, plus the PI for the first 12 weeks.

The great thing about this trial is has a higher success rate of up to 75% for tx naive patients. Not sure what the rate is for people who have tx before, someone will know.  Also Telaprevir could shorten tx time to 6 months. That's what this trial is about.

If all goes well this drug Telaprevir should be FDA approved within 2 years.  I'm not sure about how that would work for you seeing as you live in Buenos Aires, and if it would be available to you then?  Something you may want to consider and check into when you decide to tx and adding a PI.

Theres a gentlemen on this forum Andiamo you may remember him, but he treated 7 or 8 times and failed every time.  He treated with Telaprevir and finally went UND and SVR a year later. I do believe he tx a year though.  Theres another one tx with Telaprevir named Miked and he tx for 6 months and is also SVR a year later.  Theres more on the forum who cleared virus with this new PI but can't recall names.

By the way I lived in NYC for a few years and absolutely loved it there.  I liked it because it was action packed and always something to do.

Take Care

[mike716]

Hi, Trish. I don´t mind being called Mikey. I kinda like it. Sounds affectionate. (Aw, gee...)

Thanks for the trial link.

The dosages for the arms are:
- 240mg PI + SOC for 24 weeks, then SOC alone for different amounts of time;
- 120 mg PI + SOC, the SOC as above.
There are some arms where they try starting the PI a few days after starting SOC.

Do you want more details, Trish? The varied arms are pretty complicated. There are three pages of explanations.

Your comments on my preoccupations with what I was told are well taken. Perhaps I misjudged. But the bottom line is that I don´t trust the study center people. After they lied to me about returning my biopsy specimen, how can I?

Regarding rescue drugs, I think it´s an outrage that the drug company won´t pay for them. If their trial drugs make you sick, why the heck shouldn´t they have to pay for the medicine?

In any case, I´m not going to pay for rescue drugs while the trial drug company and the hospital are making money using me as a guinea pig. If I´m conrolling tx, that´s different.

I think this whole thing has gone too far. The HCV epidemic was caused by the medical profession in the first place. They started it and they spread it. THEY should be paying for therapy, not us or the insurance companies. Making us pay for rescue drugs when we´re in a trial is nothing short of theft.

Re the 14 day monotherapy result, I copied it out of the news article. I haven´t read the original scientific paper. So, thanks very much for the link, and I will read the results carefully. From what you say, the PI sounds very effective. I have no idea why they reported the results that way in the news.

Thanks for the clues for how to read the Secondary Outcome Measures re PCR.

Re adverse effects from PI, I think I´ve read that the protease inhibitors can cause a much more severe rash than SOC, and that this is the primary reason for stopping treatment. Is that right?

I think you may be right about my no bein a good candidate for trials. I hate for other people to control what´s happening to me. Absolutely hate it. I think I´d prefer to sell my apartment and pay for the tx myself. The only problem right now is that these PIs aren´t approved yet. That´s the big hitch. Oherwise, my health plan hepMD would have me in treatment, and he´s not going to do anyrhing without discussing ir first with me. We have a good relationship. Not like with this trial hospital.

Anyway, let me know if you want more info on the arms.

Mike

[mike716]

Okay, Annie, gotcha. Thanks.

Mike

[mike716]

Horrible! Adds to my feelings - all negative - about what the pharmaceutical companies are doing. Their only interest is making money and they don´t give a rap about the health of their guniea pig "patients". These are neoliberal, globalized profit-tanks, many if not all of them created and financed by the very banks and financial companies that are now going bankrupt and being "bailed out" with our tax money.

The hepatitis virus, just like HIV, has probably always existed, but there was no epidemic until the doctors and hospitals started using unsafe practices like giving blood and blood products without proper screening and microbe-clearance, using inadequately sterilized instruments and injection materials, etc. These doctors and hospitals are now making money treating the people they made ill. It´s a fabulous business for them, no different as far as they are concerned from the banks and financial companies converting people´s savings into phoney "credit" and then stealing our tax money to make up their losses.

Personally, I think HCV-infected people should form an international association and sue governments and medical associations for causing this epidemic, and force them to pay for treatment.

But so long as overnment sides with big business, we are going to continue to be exploited. What happened to those victims of the London disaster is just the visible part of the iceberg.

Frankly, I can´t believe it when I learn such things as that the drug companies performing drug trials on us won´t pay or rescue drugs when their trial drugs make us sick. I mean, how rotten can this system get before people will do something about it?

Having to sign that gag agreement is one of the main reasons why I don´t want anything to do with trials. And I´ll bet there´s something in the fine print where we have to agree to "arbitrate" and not sue them in court if their drugs harm us, and to not form class action lawsuits. The lawyers from the financial companies that finance the pharmaceutical corporations are sure to have snuck that in.

Well, your article has made me so angry I´ve gotta stop writing. You did right to post it. Everybody should post whatever news is available about drug companies and trials, i we could only get it.

Mike

[mike716]

You are an inspiration.

And I like your explanation of the arms/legs thing :-]

ike

[mike716]

Hi, Tippy! Thanks for the info on the Telaprevir trial you´re in, and about the people who were SVR with PI. Hearing good news helps a lot.

I think my hepMD will put me on tx as soon as a good PI is approved.

Yeah, New York jumps. But living in the suburbs as I do (or did before getting stuck in Buenos Aires) puts a damper on things. There´s nowhere to park in the city, and public transportation at night isn´t good. At least it´s relatively safe now. It was scary in the ´seventies.

Why did you leave?

Mike

[mike716]

Well, this thread has certainly come to a sudden grinding halt. Did I say the wrong thing? Stub someone's toe? Probably. I usually do. Seems to be my nature. Trying too hard for a laugh.

Thanks everyone for your help. Frankly, without it I'd be a basket case by now.

I love all you dear sweet people!

Mike

[jmjm530]

Mike,

I don't think you did anything wrong and in fact you got lots of answers. These threads just kinda die out after people give their opinions or after they get pushed to the bottom. If you have more questions, maybe post another thread or maybe someone else will have something to say here now that it's been pushed to the top.

All the best,

-- Jim

[Trish77]

No, you didn't do anything wrong. I'm thinking it's just because you posted about this particular trial and then after doing all your sifting decided definitively not to do this trial so discussion is a fait accompli - comprende? :)  

Take care, darlin .. and no worries.  You're still loved.

Trish

[Marcia2202]

We love you Mike..... I hadn't gone back to this thread and just realized all the fun I missed...

Btw, my Mike (whom I call Mikey most of the time) He still asks how you are doing. He still hasn't gotten over your Dr. D. story...lol...

[GSDgirl]

How ya doin' ?  Hows the weather in Buenos Aries?  Here is my post answering all your questions, now you gotta sort thru 47 posts to see exactly what questions you asked me LOL.  Now you can see why it is good to just start another thread.  LOL LOL LOL
We still love you.

Denise

GSD=German Shepherd Dog, which I have shown, bred, and trained and got the first title on one of mine.  I am waiting for that female to come in heat and hopefully I will have a pup of hers to train.

Running water??? hmmmm. I have chickens to get my own fresh eggs, we are tilling a large garden for veggies, buy a whole pig & half a cow every summer (organic) for fresh meat, hubby hunts deer.........just in case we really collapse LOL.  That stuff is true except for the collapse.  I live 20 miles south of the 'berg on 15 acres and would never go to Pittsburgh at night. I avoid it in the day too, hate the city.  Sorry about the trial mess-up

[mike716]

Thank you all, my confidence is restored. Jim´s right, why waste time on a thread that´s served its purpose? People have more serious things to think about than my weird jokes.

BTW, I´ll finally be posting, sometime next week, the FibroTC images I promised a while ago but couldn´t figure out how to extract and upload. I know how thrilled everyone will be to see them [grin].

Cheers! (as the English say) and saludos! (as they say down here in tango-town).

Mike

[Marcia2202]

Great Mike, am getting a fibroscan done in July. It will be interesting to compare pics!