Phase ll R1626 participant results

[soooby]

Feedback from someone who completed clinical trials for phase ll 1626, I'm considering participation in phase lll trials, I have Hep C type 1B and have fibrous stage 3(Isacs rating) viral loads very high, have been asked if I want to enter phase lll trials for 1626. Do you still have to take the inteferon with the treatment?? I've been told the rate of clearing the virus was 100% for those that finished phase ll trials at a boston hospital.  Any feedback from anyone who started and quite as well as those finishing the trials would be appreciated.  Trying to decide what treatment to use

thanks for any info you can provide

[Emilio44]

I was involved in this trial R1626 (RO4588161 whatever), however failed to get 2 log by 12 weeks and then rolled over to SOC (48 weeks), I achieved 1.9 log by 12.  After reading this thread I enquired about the 'unblinding' and found out that I was in tx arm 'E' which was 90 ug wk Peg, 1000 mg bid R1626 and 1000 mg Ribavirin.  Trish, SG and myself had a little wager about tx arms, I believed I was in tx F which was not far out.  Upshot is the 1/2 dose of Peg really reduced my chances regardless of r1626, along with a riba absorbtion problem, I needed 1200 riba. By the time I got educated around the riba issue (thanks heppers on medhelp) it was too late.   Anyway it was a lesson that has helped me with my continuing journey. Lessons for me: 1) Be wary of phase II trials as the dosing is can be overly ambitious and 2) Ribaviron is the key and dose according to blood results not to SOC (Note:  not recommending just my opinion as it has worked for me). 3) Well-read and experienced heppers on medhelp are more informative than most specialists.  4) HR rocks the hepper world.  Currently 34/63 weeks and going okay, most on this trial should be just about done over the next 12 weeks or so and I wish all of you well, pioneers indeed!  Still can't understand all the drama with the trial drug, from what I have witnessed it is still pretty impressive as a 12 week regime, regardless of the lymphosite issue.  Onward. Emi

[Trish77]

Thank you for sharing this.  I'll look into it.  My trial nurse is away for a week now and if this is the case, then I'd like to know if trial regulations still apply, as it would seem not and that would change some things for me.

Makes me wonder if the impact of the trial drug is a permanent one or linked to continuing interferon use and if stopping interferon brings things back to normal or not.  

Can you tell me how your various white counts are doing, specifically your lymphocytes?  What week did you stop treatment at?

I'm very happy to know you cleared early and that you're UND 30 days post tx .. interesting to note you were in the control arm because, if I recall, you cleared at 2 weeks and I recall thinking you must be getting trial drug.  Good luck to you with your 12 week test, you're looking very good so far!!!  Please stay in touch.

Trish

[links1999]

I haven't checked in here in a while and saw this post about R1626. I finished tx in this study about 3 months ago (und at 30 days post-tx; 12 week test 10/29). The doctor I was seeing told me that R1626 was not going to Phase III. He was very certain of this. Also found out yesterday the study has been unblinded. I was in the control arm, SOC tx with no study drug. Trish, if you haven't already found out, you shoudl be able to learn what arm you were in. Good luck to everyone.

[Trish77]

Thanks for the kind words....I depend/ed just as much on my colleagues in the trial for the information they had to share that I didn't have.  It's been great to have a venue for us all to find each other and keep each other informed and educated.  Speaking of which.. probably time for us to do a roll call ...

[fretboard]

TY for chiming in on this as you're my favorite pioneer in this study and the best to comment on it, hope you're doing well.  God Bless
Sooby, it hasn't been shelved.  later

R1626 plus peginterferon Alfa-2a provides potent suppression of hepatitis C virus RNA and significant antiviral synergy in combination with ribavirin.

Pockros PJ, Nelson D, Godofsky E, Rodriguez-Torres M, Everson GT, Fried MW, Ghalib R, Harrison S, Nyberg L, Shiffman ML, Najera I, Chan A, Hill G.
Division of Gastroenterology and Hepatology, Scripps Clinic, La Jolla, CA 92037, USA.

R1626, a prodrug of the hepatitis C virus (HCV) RNA polymerase inhibitor R1479, showed time-dependent and dose-dependent reduction of HCV RNA levels in a previous study. The present study evaluated the efficacy and safety of R1626 administered for 4 weeks in combination with peginterferon alfa-2a +/- ribavirin in HCV genotype 1-infected treatment-naive patients. Patients were randomized to: DUAL 1500 (1500 mg R1626 twice daily [bid] + peginterferon alfa-2a; n = 21); DUAL 3000 (3000 mg R1626 bid + peginterferon alfa-2a; n = 32); TRIPLE 1500 (1500 mg R1626 bid + peginterferon alfa-2a + ribavirin; n = 31); or standard of care (SOC) (peginterferon alfa-2a + ribavirin; n = 20). At 4 weeks HCV RNA was undetectable (<15 IU/mL) in 29%, 69%, and 74% of patients in the DUAL 1500, DUAL 3000, and TRIPLE 1500 arms, respectively, compared with 5% of patients receiving SOC, with respective mean reductions in HCV RNA from baseline to week 4 of 3.6, 4.5, 5.2, and 2.4 log(10) IU/mL. Synergy was observed between R1626 and peginterferon alfa-2a and between R1626 and ribavirin. There was no evidence of development of viral resistance. Adverse events (AEs) were mainly mild or moderate; seven patients had nine serious AEs (including one patient with one serious AE in SOC). The incidence of Grade 4 neutropenia was 48%, 78%, 39%, and 10% in DUAL 1500, DUAL 3000, TRIPLE 1500, and SOC, respectively, and was the main reason for dose reductions. Conclusion: A synergistic antiviral effect was observed when R1626 was combined with peginterferon alfa-2a +/- ribavirin; up to 74% of patients had undetectable HCV RNA at week 4. Dosing of R1626 was limited by neutropenia; a study of different dosages of R1626 in combination with peginterferon alfa-2a and ribavirin is underway.

PMID: 18570306 [PubMed - indexed for MEDLINE

[Trish77]

I'm in the R1626 trial and yes, the R1626 was pulled at Week 12 instead of Week 24.  I didn't hear anything about it being SHELVED though. One person did post that there wouldn't be any further R1626 trials but I haven't heard that myself, don't know what is going on with that. Definite concerns or they wouldn't have pulled it across the board at 12 weeks instead of 24 .. so I guess we'll see how that all shakes out.  Perhaps they had to pull it for everyone instead of only pulling it for those in the heavier dosage arms.  Keeps the integrity of the existing data perhaps and doesn't invalidate the whole trial? I still happen to think it's a promising drug and not sure we know enough about what has happened across the board in the trial yet or the data to write it off or write it up.  I'm done on Jan. 30th and then have to get to the six month post test and then data needs to be put out there so I'm a little surprised to see someone posting they've been asked if they want to do Phase III trials for R1626?  Can you elaborate with more details?  I'm especially curious to know more, particularly since I'm currently in Phase IIb.

Thanks!

Trish

[fretboard]

Yeah, your right the trial was at least pulled from the phase 2 trials like at 10 weeks or something like that depending on what part of the world you were in.  I think it's kind of in limbo, but I'm not sure.  On the link I left up top the R1626 is still on there as being in the middle of phase 2.  I'm sure somebody will be able to share the truth on whether there will be a phase 3 or if it's still glitchified.  I know one of my favorite pioneers made it through the first 12 weeks very well.  Some one will chime in later, for sure.  later

[dointime]

Huh?

I thought R1626 was shelved following unacceptable incidence of neutropenia in phase 2 trials.

Hopefully somebody will be along with enlightenment.  

dointime

[fretboard]

As far as I know the Phase II trials are not yet completed.  Here's a website and it will show you all the new drugs and what stage they are in as far as what Phase they are in and other information.  From what I've heard about the R1626 trials everything is going smoothly now, after a rocky start if my memory serves me correctly.  You need to register to view the new drugs and how they're doing, but it's worth it and nobody will contact you as far as I know, I've never heard from anyone.  Also, maybe later somebody will chime in who is actually on one of the Phase II trial and they will be able to give you more information.  later

http://.hcvdrugs.com/forum/list.php?16