nitazoxanide/Alinia Phase II Trial

This week I got screening bloods back, and had my eye exam, and am all set to start this trial.  I get randomized, and get baseline bloodwork drawn, on 2/25, and the first day of meds is 2/26.  I get to spend 12 hours at the hospital that day, as they draw blood every hour -- looking for how the drug enters the blood stream, I guess.

The chances of actually getting nitazoxanide is 2/3.  The protocol is 4 weeks of nitazoxanide, 500mg, PO, BID; followed by the same dosing of study drug plus SOC (Pegasys/Copegus) for 48 weeks, followed by a 24 week followup.

At the 8 week mark (after 4 weeks of triple therapy), they expect at least a 1-log drop in viral load to continue.  At the 16 week mark (after 12 weeks of triple therapy) they expect another 1-log drop (at least 2-log down from baseline) to continue.  And, at the 28 week mark (after 24 weeks of triple therapy), they expect UND (<50) to continue.

This will be my third IFN/RVN go-round, the second with the pegylated flavor of battery acid.  Both times previously, I went to quantitative 0 but qualitative detectable (<600) and stopped at 6 months.  I've been off IFN maint. therapy for 3 months now.  My viral load hovers around 2x10**6, ALT/AST hovers around 125-225.   I am genotype 1A, and have had this for 30 years or so...  I am 50, wht, male...

Last biopsy showed 3/3 about 15 months ago.  Last CT and U/S showed possible early cirrhosis.  Otherwise, I'm in pretty good health.  I'm about 75 pounds lighter than the last time I treated, so, I am hopeful.  

Wheee!  Here I go again...  :)

[Myown]

Third go round? Sheesh, I hope all goes well, that you get the Alinia and you SVR!!
Keep us posted!
MO

[dointime]

Thanks for your very informative post.  I think we are so lucky that you've come to the forum.  This trial is very important because all the drugs are already on the shelf.  If you SVR, and I am really hoping that you will, then anybody who just can't wait to treat would have a case for going for this combo.  

So fingers crossed and good luck,

dointime.        

[neptune235]

Thanks, guys, for the well wishes!  

I've actually been here on and off for a few years, more off than on, mostly lurking, but occasionally posting.

I'm hoping this does the trick, because the next thing to do will be daily CIFN+RBV, and we'd probably add Alinia to that mix as well.  Would love to get into one of the PI trials, too.

I wish the brand of IFN in use was pegIntron instead of Pegasys, though.  The first two tx were with the Schering-Plough battery acid, and the 15 months of maint I did (last nine months at full dose) didn't budge my viral load one bit.  But...the cost is right. :)

[neptune235]

An update...I've been on the nitazoxanide (NTZ) for just under four weeks now.  Pretty sure I've gotten the NTZ and not the placebo, due mainly to dayglo yellow urine.  That is the only side effect (am taking a pro-biotic, as per recommendation of several here.)

Next week I begin the SOC part of this triple therapy.  Oh joy...

[Forseegood]

but I'm about to go on personal treatment and I've been pre-loading on alinia (hardly any sides at all, can't be that bad!) and the alinia was very easy to get...just fyi....

[neptune235]

Yeah...of course, it's already FDA approved, and so your hep-doc can write an off-label script.  The trial that I'm in is also providing the SOC -- at their expense.  Not a bad deal...

[dointime]

Are they giving you your VL numbers as you go along?  Or when do you get to find out how your VL is reacting to the meds?

Thanks
dointime

[neptune235]

I'm 4 weeks in, and they've drawn blood every week.  Now, they'll draw blood at week 4, 6, 8, 12, 16, etc...

I see the doc Monday, and will find out what viral load numbers they've done so far.  

At the 8 week mark (which is the 4 week mark for NTZ + SOC), I'm supposed to have a 1 log drop compared to baseline.  At the 16 week mark, it's another 1 log drop, so 2 log compared to baseline.

At the 28 week mark, I need to be UND (<50).  Each of these milestones must be met, or I'm out of the study.  

If that happens, I will likely begin NTZ off label, combined with Infergen and Riba.

[neptune235]

My baseline, week1 and week2 (week3 not back yet, week4 was today) viral loads are all in the range of 1.0-2.0 * 10**7.

Not really expecting them to change much on NTZ monotherapy...they should start going down (hopefully) this Friday, when starting up SOC.

Ugh...I can hardly wait...  :)

[neptune235]

Hey All,

Just checking in...I had my 8 week blood draw last Wednesday.  This is four weeks into the SOC + NTZ point, and I need to show a 1-log drop in VL to continue the trial.  

I should get the safety labs back Monday (CBC and chem panel -- I suspect I'm trending towards anemia, but I think my HGB will be in the 12-13 range, dropping from a baseline of 14,5).  We shall see.  Turns out my baseline VL was 3.5 * 10**7, so the number needs to be below 3.5 Million.  Will let you all know...

The sides have been tolerable -- weariness, mainly, but I'm still working my tail off, so nothing life changing.

[gauf]

Thanks for the update, I am predosing Alinia right now. Awaiting your results with interest.

[neptune235]

Thanks...really very little sides from the Alinia, I thought -- same for you?  I'm hoping to keep going, at least past the 16 week milestone (2-log down at 12wk SOC+NTZ).

The last two times on SOC, both with the Schering flavor of battery acid, I was 2-log down at 12 weeks.  Never cleared, though, out to six months.

Hoping the Alinia is the extra push needed.

When do you start with the SOC?

[gauf]

Me too, 2 failed tox. I have a good feeling about the Alinia. No sides and currently out of my probiotic/prebiotic, but still no problems. If only the other drugs were this easy, eh?
I am also titering up with the Riba and pushing to drop just a little more weight before round 3. Figure I will have to start on or before mid May or people will start accusing me of pulling a "4C" stall!

[gauf]

Oh yah, the Alinia makes my urine a kind of neon yellow, so if yours is too, you probably got the real stuff.... unless they were clever enough to add the same dye to the placedo!

[neptune235]

Heh!  Oh yeah...dayglow!  The Research Coord., plus the Hepatologist both said they wouldn't put dye in the placebo, so I figure it's real.  Keeping fingers crossed for overall success.  

[ClippedWings]

I added Alinia 8 weeks into SOC and like you the most obvious side effect was the bizzare urine.  I had to give a urine sample at one point and I was embarrassed at turning it into the lab tech it looked so weird! Mine looked like neon Mountain Dew (almost a yellow-green color).  The only other side I had was a loose stool.  Both side effects were easily tolerated and cleared within two days of stopping the Alinia.  Alinia did nothing for me, but I did not start taking it until I had been on SOC for two months.  I'm hoping that the predosing is the trick as the drug is pretty easy on the body as you know.  I was taken off treatment after 16 weeks (8 weeks Peg/Riba/Alinia) because I never even saw a one log drop.   Hope your story has a better ending.  

[gauf]

Yah, Mountain Dew is the color!  Good luck next round.

[giddyup]

hey nep Just wanted you to know I'm on the same trial. I start soc next week after 30 days pre dose.I'm with ya man!

[eureka254]

Neptune/all:

Thanks for the updates!  It's always great to get feedback/input from people in trials since we're all looking forward towards 'better' treatments, but especially of interest are those that involve meds already approved by the FDA, "drugs already on the shelf".  As a genotype 1 and stage IV, my husband may not have the time to wait for Telaprivir and other PIs to get approval, so a better than 50% SVR "cocktail" would be very, very exciting.

Keep us posted!

[willing]

while the mechansism of ntz-alinia remains to be worked out, the current working assumption is that it enhances the anti-viral activity of some of the pathways activated by ifn:
http://www.****.gov

unfortunately this suggests it may not do much for ifn non-responders, as you experienced. inhibitors with a low viral escape mutation profile (which at this point seem to include  r1626 and r7128) may be your best bet.

[ClippedWings]

I agree.  The hepatologist I saw at UW recommended the same.  I was eager to jump into another treatment with concensus interferon but the hepatologist thought I'd be better off waiting for the PIs. I was worried that my stage IV meant I was staring the grim reaper in the face, but the new doc told me that as long as my liver shows no signs of decompensation and I stay meticulous with my diet I can go a long time with cirrhosis.  So that's become my new plan- Get in better shape, eat better than I ever have, maybe start with some the things on Gauf's supplement list and wait for something better.  I'll get my liver panel checked every three months and add a ultrasound and AFP every six months.  At one point I was on Pegasys, Ribavirin, Alinia, Lipitor, Lexapro, and Actigal.  Kinda nice getting off all that ****!  I felt lousy for a month after I stopped treatment but now I feel great.

[neptune235]

Finally got some numbers back.  The VL from a couple of days shy of the four week mark were about 6 million, down from the baseline 35 million.

This is about 0.74 log drop.  They were ready to drop me from this study, but we argued variability in the VL numbers, and the fact that I had been partial EVR two times previously, so Romark agreed to retest.

They drew the retest 1 day shy of the five week mark (in other words, the day before injection 6.)  My VL dropped an additional little bit to just under 5 million, or about 0.81 log drop from baseline.

Not the full 1-log drop required to remain in the study, so I am officially out.

I am trying to scramble to get a script for Peg/riba through my insurance so that I can continue uninterrupted.  I'll try to continue on Alinia (likely on my dime) as well.  I want to get out to the 12 week mark, to see if I get to 2-log down from baseline.

My doc is out of town, but is responsive to emails etc, so I think there is a reasonable chance of doing this uninterrupted.  We shall see...

Not too happy about this, but hopeful about the 12 week milestone.  If that fails, I guess CIFN is in my future...