Its a lot of reading but this is a draft and they are looking for input from the Drug company's and trial participants. I actually called and talked to Kimberly Struble who works at the Division of Antiviral Drug Products, she confirmed that the FDA is concerned about how all the new DAA's will work in re-treatment of relapsed patients and this new draft will go a long way in giving guidance to how the drug company's handle there HCV trials that include multiple DAA's in all phases and rescue approaches of relapsed patients during trials.
My main concern is how guarded big Pharma is about disclosing the reason there participants failed or relapsed, you would think they would have the propriety to disclose to us individually the how and why we failed there trial. Maybe they will after they submit for approval but in some cases that could be years and that is not fair or ethical to the trial participants, doctors, and nurses.
I will be submitting a whole list of items to the draft from the viewpoint of the trial participants, because they need to hear how the the patient feels before during and after the trial.
Its not that I am not aware of the cost involved and its fortuitous nature but its the lack of training of the do's and don't s what if's and understanding the stress and psyche of the participants is very important to the success of every trial.
Well more complaining is only going to get me ticked off, got put it in writing and send it off to the FDA
Matt
-- Edited by Matt Chris on Sunday 17th of November 2013 12:36:12 AM
-- Edited by Matt Chris on Sunday 17th of November 2013 02:29:35 AM
Matt Chris said
Nov 16, 2013
Hey RH
Read about you latest turn in the HCV road , it's a shame that it can happen and can be very depressing the first month afterword but life go's on and more importantly your life will go on for many, many more years. Some of us have to take a longer road but we will arrive as the same place.
You might like me wonder the why and how it could happen, those answers might be hard to come by but in time Gilead might disclose the info. In my case I am still waiting for Abbvie to disclose to me about my relapse. Abbvie is offering re-treatment with two of the three DAA's I already had with Peg & Riba but they will test for Rav's before treatment and if highly detectable will not treat.
The reason I bring this up is the FDA is writing a new HVC Trials Guideline for DAA's in development and they are addressing the scenario of re-treatment of failed DAA HCV participants.
checkout this excerpt from the Document.
Multiple rounds of DAA treatment failure may severely limit treatment options for subjects;
therefore, initial trials in DAA-experienced subjects should include regimens and treatment
durations (e.g., at least 24 weeks) that are predicted to provide subjects with the best chance of achieving SVR. For example, exploration of relatively short treatment durations should be considered only after proof-of-concept efficacy has first been demonstrated for longer treatment durations. Also, because of the number of promising DAA classes in development that would be appropriate to test in DAA-experienced populations, we strongly encourage cross-company collaboration when needed to construct a scientifically justified regimen.
So the FDA is encouraging those that need re-treatment would be better off in using DAA's with different approach from other companies because the odds go up. But in one of the abstracts from the 2013 Nov. Liver Convention a person who relapsed on Sofosbuvir was retreated for an additional 24 weeks and cleared even though they developed Rav's . So it shows sometimes it's a duration issue and sometimes it's a Rav's issue, I will be considering trying to convince Abbvie to include Sofosbuvir with my re treatment and remind them that the FDA is strongly encouraging cross-company collaboration for re treatment participants.
RH whatever happens at least we know that there will be a lot more options coming down the pike in the coming years.
Matt
HR said
Nov 16, 2013
Hey Matt,
Thanks for that info. Yes I wonder why this happened. I took my meds at the same time everyday and followed the trial perfectly. I exercised during treatment and still continue to exercise. The only thing that I can figure is maybe I had a little more damage to my liver than the biopsy showed. Remember I was 3-4 on the Ischank (sp) scale that goes from 0-6. That puts me right in the middle. Evidently I fall into the hard to treat category.
It's interesting about the FDA's comments. Do you and I wait for a couple of years to see what comes out or do we jump at the first thing that's available that looks good? I have to admit, your post has got me thinking about retreatment options.
Take Care
-- Edited by RH on Saturday 16th of November 2013 12:14:05 PM
-- Edited by RH on Saturday 16th of November 2013 12:26:27 PM
HR said
Nov 15, 2013
Thanks guys. It just wasn't my time. I believe round 2 will do the trick.
Now let's keep these SVR's coming.
Take Care
sofi moore said
Nov 15, 2013
RH, I'm so sorry. You started this thread and gave us a place to go. Thank you. I am going to believe that you will conquer it next time.
Sofi
Misfis said
Nov 15, 2013
Thanks, Millani, that was extremely informative. I goofed, though, and meant to ask if the participants in the Lonestar trial were on the same dosage of Sofos/ledispavir as us ION 3 people, but it sounds like we were from what you said. Thanks so much for being such a great source of information. I have a curious mind and always want to understand things that effect me.
mallani said
Nov 15, 2013
Hi Misfis,
All the Ion patients are on the same fixed dose combination (400mg sofos/90mg Ledip). Phase 2 Trials are smaller ( 100-300 patients), and just a step along the Regulatory process. Usually different arms of the Trial use different dosage of the drug being Trialled, and there are usually placebo arms. Obviously, any side effects have to be documented. The ION Trials are all Phase 3, which typically involve 1000-3000 patients. Phase 3 Trials should include all Rx groups, and in our disease, this should mean all fibrosis stages, ages, and Rx-naive and Rx-experienced patients. Different Rx lengths are tried, if the results from Phase 2 are not definite. Obviously, any side effects are to be noted. The FDA usually require several Phase 3 Trial results to consider, and then may order more Trials as desired. Cheers.
Misfis said
Nov 14, 2013
Hi Millani, Do you know if the participants in the ION 3 trial received the same dosage of sofo/ledis as we did--that 400 mg of sofos, and the 90 mg of ledis combination? Also, how is a phase 2 different from what we were on? I guess I could look this up on on the internet, but thought I might get a more specific answer from you.
I also wonder why the ION 2 is so shrouded in secrecy. It seems that it is not even common knowledge amongst many of us that there even was a ION 1 and 2 trial. Thanks for all your information on all of this.....
Cinnamon Girl said
Nov 14, 2013
Really sorry to hear this, RH, bad luck. It seems that 12 weeks wasn`t long enough for you but you`ll stand a much better chance next time round with a 24 week course.
You`ll get there in the end, take care of yourself and keep your chin up!
mallani said
Nov 14, 2013
Hi RH,
I'm sorry to hear the news. As I said in our PM's, a rise in ALT after EOT used to be regarded as a sign of relapse, and I guess it still applies.
I'm surprised Gilead isn't giving us some progress data from the ION Trials. Lonestar results are old hat, and it was a small Phase 2 Trial anyway. Ion-2 and Ion-3 have been going since Jan 2013 so surely there is some data available. Ion-2 is the only one with Rx experienced patients, and the comparison between 12 and 24 weeks of Rx will be very important, as well as the +/- Riba arms. When Victrelis and Incivek were approved, it was obvious that there was insufficient data for cirrhotics and Rx length was a lottery.
The good news is that Gilead have no problem repeating Rx for relapsers, so regard this as a temporary setback.
Misfis said
Nov 14, 2013
RH, I'm so sad and sorry to hear this! What a shock when we are feeling so optimistic. I admire your attitude about this-- it's good modeling for the rest if us. Hang in there.
Ckncali said
Nov 14, 2013
RH,
I am so very sorry to hear your news. I remember when you posted that you were not feeling so good and that must have been when it came back. It sounds like Gilead is going to take care of you and get you on this 24 week treatment. I am sure with the longer treatment they will get you cured. My heart goes out to you. We will be here for you to cheer you on.
HR said
Nov 14, 2013
Hey Everyone,
I got some bad news yesterday. I went to my private Dr. a couple of weeks back and got my blood work done.
ALT/AST came back 150/84. Dr then decided to run VL test and it came back 1.9mil
I know it happened a week after my 4th week EOT blood work. I started feeling like I was coming down with something. I just kept feeling that way for weeks. In the back of my mind I knew what it was but didn't want to believe it.
There is some good news.(not really but at this point its good news) I am going to be retreated soon. I don't have the details on which combo but I heard it's going to be for 24 weeks. I will know more in a few weeks.
Hang in there everyone, I will be 9 months or so behind you. Let's keep the SVR's coming.
Take Care
Karen said
Nov 12, 2013
Hi Ckncali,
4wk has just past-will not know the outcome until after 12wk Dec 20th-when I get an invite back for a 24wk or not. Thanks for asking!
How are you doing?
Cinnamon Girl said
Nov 12, 2013
Well done, Reg, congratulations to you on SVR12! Great news!
And a very big `thank-you` to you all for taking part in this trial, and other clinical trials, you are all trail blazers, leading the way for others to follow!
Thanks Lil Eddie for posting the link and details of the Lonestar results, that is excellent news! I`m going to post it in the `HCV News` section too, for anyone who doesn`t see it here. Cheers!
HR said
Nov 12, 2013
Great job Reg..
Ckncali said
Nov 12, 2013
Hi,
Lil Eddie, Thank you for posting that.
The Lonestar results mystery is now revealed. The results are spectacular. We are so lucky to have been able to participate in this trial. The article states that even those with mutations at baseline were able to achieve SVR. That is such good news for those of you who have relapsed on other trials. The article mentions one person that was lost to followup which means they did not return for their blood draw so can't be counted in the results. Everyone please return for your follow up blood draws so that the ION3 trial will have accurate results.
I wish they had stated what the two serious adverse events were.
Reg, Congratulations on SVR12!!
Misfis, Good luck on your big day tomorrow.
Sofie and SoCal, We did it! Thanks so much for your support. I felt like I went through this trial with both of you and it was so helpful to be able to support each other through the trial.
Karen, Have you had SVR4 test done yet? How are you doing?
Good luck to all the rest of the 12 week ION3 participants.
Biggyb said
Nov 12, 2013
Good job to all you guys on the trials, without you all we would be lost in Hepc land..
Great job folks !!!
suziq said
Nov 12, 2013
All I can say is "WOW".
Hope my Merck trial does as well. They posted similar results at the convention for the earlier data from their last study. Currently going into my 10th week with ribavirin. Weeks 4 and 8 I was UND.
It is so nice to hear all the positive results. I got rejected for an earlier Gilead study at my current center in Arlington Texas because I now have cirrhosis. Can't remember why I didn't apply for this trial. San Antonio is about 150 miles south of me. Think they had either an age or distance restriction.
Hearing your results makes my anxiety levels drop--well, a little. We are all so fortunate to be a part of these new studies. Happy SVR to all of you.
SuziQ
Karen said
Nov 12, 2013
It is a beautiful morning:)
Misfis said
Nov 12, 2013
OMG! thanks so much for posting this!!!We are so lucky to have been a part of this ION 3 test! I'm off to my 12 week EOT draw tomorrow with a happy smile on my face. Am planning on taking myself out to lunch afterwards at my fav Italian restaurant in SF. Good luck to everyone!!!
Lil Eddie said
Nov 12, 2013
Finally, The results from Lonestar with SVR12 and SVR24.
Eric Lawitz of Texas Liver Institute presents results of the LONE STAR study. Photo by Liz Highleyman, hivandhepatitis.com
At least 95% of newly treated people with genotype 1 hepatitis C and prior non-responders achieved sustained virological response using a fixed-dose combination of sofosbuvir plus ledipasvir, with or without ribavirin, according to findings from the LONESTAR study presented at The Liver Meeting 2013, the 64th annual meeting of the American Association for the Study of Liver Diseases (AASLD) in Washington, DC. While response rates were high overall, the two relapsers in the trial were not taking ribavirin.
The advent of direct-acting antiviral agents has revolutionised treatment of chronic hepatitis C. While these agents were initially tested as add-ons to interferon-based therapy, many people with hepatitis C virus (HCV) and their care providers are awaiting all-oral regimens that dispense with pegylated interferon and its difficult side-effects.
Eric Lawitz of the Texas Liver Institute reported results from the phase 2 LONESTAR study, which evaluated a fixed-dose combination pill containing Gilead Sciences' HCV polymerase inhibitor sofosbuvir (formerly GS-7977) plus the NS5A inhibitor ledipasvir (formerly GS-5885), taken with or without ribavirin for 8 or 12 weeks.
LONESTAR enrolled two cohorts at a single centre in the United States. Cohort 1 included 60 treatment-naive individuals (people who had not taken treatment before) who did not have liver cirrhosis. Cohort 2 included 40 people, about half with cirrhosis, who did not achieve a cure with the current standard of care: triple therapy with the approved HCV protease inhibitors boceprevir (Victrelis) or telaprevir (Incivo or Incivek) plus pegylated interferon/ribavirin.
Overall, two-thirds of participants were men, 9% were black and the mean age was 50 years. Most (87%) had harder-to-treat HCV genotype 1a and only 15% had the favourable IL28B CC gene variant associated with interferon responsiveness. In Cohort 2, 55% had cirrhosis at study entry. Just over half (55%) had previously been treated with boceprevir while 45% had used telaprevir. All experienced prior virological failure; people who stopped previous therapy due to adverse events were excluded.
Participants in Cohort 1 were randomly assigned (1:1:1) to receive the once-daily fixed-dose tablet containing 400mg sofosbuvir and 90mg ledipasvir either with or without 1000-1200mg/day weight-based ribavirin for 8 weeks, or without ribavirin for 12 weeks. Treatment-experienced patients were randomised to receive sofosbuvir/ledipasvir either with or without ribavirin for 12 weeks.
All participants completed therapy except for one who withdrew consent. In Cohort 1, 95% of treatment-naive patients treated with sofosbuvir/ledipasvir for either 8 or 12 weeks achieved sustained virological response, or continued undetectable HCV RNA at 12 weeks post-treatment (SVR12). The SVR12 rate was 100% in the 8-week sofosbuvir/ledipasvir plus ribavirin arm.
In Cohort 2, SVR12 rates were 95% for sofosbuvir/ledipasvir and 100% for sofosbuvir/ledipasvir plus ribavirin given for 12 weeks. All patients without cirrhosis achieved sustained response, as did all but one of the people with cirrhosis (91%).
Response rates for all arms remained the same at 24 weeks post-treatment (SVR24). These results compared favourably to historical SVR24 rates of about 70% for people without cirrhosis and 44% for people with cirrhosis in pivotal trials of boceprevir or telaprevir plus pegylated interferon/ribavirin.
The 95% response rates reflected three people who did not achieve SVR12/24. One patient in Cohort 1 who received sofosbuvir/ledipasvir alone for 8 weeks and one in Cohort 2 who received sofosbuvir/ledipasvir for 12 weeks experienced viral relapse, while one person in Cohort 1 who received sofosbuvir/ledipasvir for 12 weeks was lost to follow-up after reaching SVR8. Both relapsers had HCV genotype 1a. No one who took ribavirin relapsed.
Seven of the nine people with NS5A resistance mutations and all 28 people with NS3/4A (protease) resistance mutations at baseline nevertheless achieved sustained response. One patient had evidence of the S282T mutation and multiple NS5A resistance mutations at the time of relapse at week 8. This individual was retreated with sofosbuvir/ledipasvir plus ribavirin for 24 weeks and went on to achieve SVR12.
Sofosbuvir/ledipasvir was generally safe and well-tolerated with or without ribavirin. Two people receiving sofosbuvir/ledipasvir alone and two receiving ribavirin experienced serious adverse events, but no one discontinued treatment for this reason. Grade 3 to 4 adverse events (0 vs 14%) and grade 3 to 4 laboratory abnormalities (7 vs 14%) were more common among those taking ribavirin. Anaemia was seen only in the ribavirin arms (19%).
Asked whether ribavirin is still important, Lawitz said these results confirm that "for a large proportion of patients we can remove ribavirin without impacting SVR," and "outside clinical trials, anything we can do to improve compliance is a benefit".
The phase 3 ION trials are currently underway, testing sofosbuvir/ledipasvir with or without ribavirin for 8, 12 or 24 weeks in treatment-naive patients with genotype 1 and prior non-responders, Lawitz noted.
Results from the phase 2 ELECTRON trial, also reported at the Liver Meeting, showed that Gilead's non-nucleoside polymerase inhibitor GS-9669 as a third agent instead of ribavirin also led to SVR12 rates of 100% for difficult-to-treat genotype 1 patients.
Matt Chris said
Nov 12, 2013
Hey Reg
Congrats, that is super fantastic news, a day that you will always remember.
Another great day for Hepcfriends
matt
Misfis said
Nov 12, 2013
Congratulations Reg! You are the first of us non ribiviron people to report back!!!! So happy for you!
lauralou57 said
Nov 12, 2013
Congragulations!
REG said
Nov 12, 2013
Hi everyone -
Just wanted to let everyone know that I got my 12-week EOT results today and SVR12!! I was on the 12 week no riba arm.
sofi moore said
Nov 11, 2013
Congrats Ckncali! That is fantastic! I feel like we have gone through this together.
Still holding a good thought for all.
Also, I know I have sounded looney and believe me, I was looney and even more so than you all know, so I want to thank you all for not telling me to go away. Also, a big thank you to the ones who private messaged me to see if I was ok. Yes, the forum is invaluable.
Misfis said
Nov 7, 2013
Wow, thanks Millani and Jill. Ditto on what RH said--this forum is invaluable!!!
HR said
Nov 7, 2013
Thanks guys for the answer. I don't see how anyone could go through treatment without THIS forum.
mallani said
Nov 7, 2013
Hi Misfis and RH,
Just a brief addition to what Jill posted. <25 means the LLOQ for that particular PCR test, and the test may have a LLOD (Lowest Limit of Detection) which is less than that, often around 10 or 7. Undetected means that no viral RNA can be detected. So, you could have ,e.g. 5 viral particles/ml of blood and still be called Undetected. Experience has shown that this amount of virus is not significant. The virus is the same, and it continues to replicate, but the body has learned how to control such tiny amounts of virus using the immune system. Whether the virus replicates in liver, blood monocytes or other tissues is unknown, but it is not important. The important thing is that the virus has been effectively neutralised. However there is still a tiny chance of passing on the virus, so the usual sensible precautions should continue to be used.
In time, it is hoped that a more sensitive test will be available, that can measure down to zero viral particles. Maybe then we can call ourselves cured, in the true sense of the word.
Misfis said
Nov 7, 2013
Thanks for that input, Cinnamon girl. It's great to have knowledgeable people on board to answer these vexing questions. Hard to wait until the next time to ask the research people these questions!
HR said
Nov 7, 2013
Great question Misfis. I would like to know that answer as well.
I had a 10 week or so blood draw last week with my private Dr and will get the results tomorrow at 2:30 when I see him. I'm a little nervous about it. I will post results as soon as I get them.
Gilead sure has been tight lipped about the ION 's and it's annoying the hell out of me.
Good luck everyone
Misfis said
Nov 7, 2013
So I have a question----if people are coming up with < 25 SVR at 12 weeks and this is considered cured, what happens with those few viral cells that are noted? Are these just some strange viral cells that don't continue to replicate? Are they in some way different from the regular HCV cells that were part of the original millions that defined us as having chronic active Hep c? Let me know what people know about this.
Lil Eddie, RH, myself and a few others here are part of the ION 3 arm of 12 weeks with sofos and ledispavir--no ribi. I think we are all around November 13th for our 12 wee EOT blood draw. I guess we will be the first to be able to report back, hopefully in the week of the 20th of November, about our results. Wish us all luck!!
HR said
Nov 7, 2013
Good job CK.. That is great news.
take care
Biggyb said
Nov 6, 2013
Very good news you guys,
Ckncali i am pretty sure SVR24 is called cured. All the best to you.
Karen said
Nov 6, 2013
Happy days!!!
Congrats Ckncali...
All the best
Ckncali said
Nov 6, 2013
Hi,
Just got the news. I am SVR12! I was told to return in 3 months which means the virus was not detected. I was also told that so far they had not gotten any alerts which means that no one at their clinic has had the virus return. I hope this news bring relief to some of you who are still waiting to hear about your 12 week after EOT results.
I did ask if they consider SVR12 a cure and was told that at this point they have not determined that SVR12 is a cure but that it is highly unlikely the virus could return when it is no longer detected 12 weeks after EOT.
Today is a good day.
Cinnamon Girl said
Nov 6, 2013
Hi Misfits, well if your viral load result comes back as < 25 (less than 25) and `undetected`, or `not detected`, it just indicates that the particular PCR v l test being used is only able to quantify down to that level, so it`s considered as no virus undetected. So there may or may not actually be any virus particles remaining but the test isn`t sensitive enough to detect anything less than 25. Hope that helps!
Congrats to to you, Ckncali, sound good to me!! SVR12 is generally considered `cured` for most clinical trials, and yes, it`s rare for anyone to relapse after 12 weeks post tx.
Best of luck RH, and everyone!!
Loopy Lisa said
Nov 5, 2013
Congratulations, all you people that do these trials are a life line to many people, you should be very proud of what you have done. Enjoy life again without the burden. x
mallani said
Nov 5, 2013
Hi Sofi,
Congrats on a great result! Hard to believe this can happen with only 8 weeks of Rx. You guys are inspirational. Enjoy SVR. Cheers.
suziq said
Nov 5, 2013
Hi Everyone,
Just glanced through the posts. Congratulations to all of you!!! I am still in my Merck trial with riba. Starting week 8 tomorrow and labs on Wednesday--results several days after that. The Merck results released at the conference yesterday look great, but they didn't do cirrhotics in that trial. How great that there were others here you could communicate with while on your trial. Didn't see anyone else on my Merck trial.
I see you all agree that a major side effect of these trials is the waiting--creates anxiety.
Just wanted to say hi and congratulate you all.
Suziq
Cinnamon Girl said
Nov 5, 2013
Great news, Sofi, very pleased for you! Congratulations!!
I hope you`re feeling a lot better now, you didn`t have an easy time of it. You must be so relieved to have it all behind you now, time to enjoy your new virus-free life!
Terry said
Nov 4, 2013
Congratulation's Sofi That's is great news ! Enjoy your new life and relax and put your feet up.
That`s fantastic news, Michele, congrats to you!
And all the best of luck to you, Lil Eddie, hoping for more good news!
Hey Michele-that is outstanding news!
Also nice to have a trial nurse that will share that kind of info....
Congratulations!
Keep it going Lil Eddie...
That is great news Misfis !!! Great job!!!
Good luck to the rest of you.
Great news Michele, hang in there. Fingers crossed for the big 6 month test.
Positive thoughts coming your way, Lil Eddie! Good luck!
Great news!!!!!
I went today for my 12 week post treatment blood draw. Keeping postive thoughts!!!!
Hey all, I got a call from my research person this morning, and I'm SVR 12-- no detectable virus!!!
Hey RH
Thought I would provide the link to the FDA Document
-- Edited by Matt Chris on Sunday 17th of November 2013 12:36:12 AM
-- Edited by Matt Chris on Sunday 17th of November 2013 02:29:35 AM
Hey Matt,
Thanks for that info. Yes I wonder why this happened. I took my meds at the same time everyday and followed the trial perfectly. I exercised during treatment and still continue to exercise. The only thing that I can figure is maybe I had a little more damage to my liver than the biopsy showed. Remember I was 3-4 on the Ischank (sp) scale that goes from 0-6. That puts me right in the middle. Evidently I fall into the hard to treat category.
It's interesting about the FDA's comments. Do you and I wait for a couple of years to see what comes out or do we jump at the first thing that's available that looks good? I have to admit, your post has got me thinking about retreatment options.
Take Care
-- Edited by RH on Saturday 16th of November 2013 12:14:05 PM
-- Edited by RH on Saturday 16th of November 2013 12:26:27 PM
Thanks guys. It just wasn't my time. I believe round 2 will do the trick.
Now let's keep these SVR's coming.
Take Care
RH, I'm so sorry. You started this thread and gave us a place to go. Thank you. I am going to believe that you will conquer it next time.
Sofi
Thanks, Millani, that was extremely informative. I goofed, though, and meant to ask if the participants in the Lonestar trial were on the same dosage of Sofos/ledispavir as us ION 3 people, but it sounds like we were from what you said. Thanks so much for being such a great source of information. I have a curious mind and always want to understand things that effect me.
Hi Misfis,
All the Ion patients are on the same fixed dose combination (400mg sofos/90mg Ledip). Phase 2 Trials are smaller ( 100-300 patients), and just a step along the Regulatory process. Usually different arms of the Trial use different dosage of the drug being Trialled, and there are usually placebo arms. Obviously, any side effects have to be documented. The ION Trials are all Phase 3, which typically involve 1000-3000 patients. Phase 3 Trials should include all Rx groups, and in our disease, this should mean all fibrosis stages, ages, and Rx-naive and Rx-experienced patients. Different Rx lengths are tried, if the results from Phase 2 are not definite. Obviously, any side effects are to be noted. The FDA usually require several Phase 3 Trial results to consider, and then may order more Trials as desired. Cheers.
Hi Millani, Do you know if the participants in the ION 3 trial received the same dosage of sofo/ledis as we did--that 400 mg of sofos, and the 90 mg of ledis combination? Also, how is a phase 2 different from what we were on? I guess I could look this up on on the internet, but thought I might get a more specific answer from you.
I also wonder why the ION 2 is so shrouded in secrecy. It seems that it is not even common knowledge amongst many of us that there even was a ION 1 and 2 trial. Thanks for all your information on all of this.....
Really sorry to hear this, RH, bad luck. It seems that 12 weeks wasn`t long enough for you but you`ll stand a much better chance next time round with a 24 week course.
You`ll get there in the end, take care of yourself and keep your chin up!
Hi RH,
I'm sorry to hear the news. As I said in our PM's, a rise in ALT after EOT used to be regarded as a sign of relapse, and I guess it still applies.
I'm surprised Gilead isn't giving us some progress data from the ION Trials. Lonestar results are old hat, and it was a small Phase 2 Trial anyway. Ion-2 and Ion-3 have been going since Jan 2013 so surely there is some data available. Ion-2 is the only one with Rx experienced patients, and the comparison between 12 and 24 weeks of Rx will be very important, as well as the +/- Riba arms. When Victrelis and Incivek were approved, it was obvious that there was insufficient data for cirrhotics and Rx length was a lottery.
The good news is that Gilead have no problem repeating Rx for relapsers, so regard this as a temporary setback.
RH, I'm so sad and sorry to hear this! What a shock when we are feeling so optimistic. I admire your attitude about this-- it's good modeling for the rest if us. Hang in there.
RH,
I am so very sorry to hear your news. I remember when you posted that you were not feeling so good and that must have been when it came back. It sounds like Gilead is going to take care of you and get you on this 24 week treatment. I am sure with the longer treatment they will get you cured. My heart goes out to you. We will be here for you to cheer you on.
Hey Everyone,
I got some bad news yesterday. I went to my private Dr. a couple of weeks back and got my blood work done.
ALT/AST came back 150/84. Dr then decided to run VL test and it came back 1.9mil
I know it happened a week after my 4th week EOT blood work. I started feeling like I was coming down with something. I just kept feeling that way for weeks. In the back of my mind I knew what it was but didn't want to believe it.
There is some good news.(not really but at this point its good news) I am going to be retreated soon. I don't have the details on which combo but I heard it's going to be for 24 weeks. I will know more in a few weeks.
Hang in there everyone, I will be 9 months or so behind you. Let's keep the SVR's coming.
Take Care
Hi Ckncali,
4wk has just past-will not know the outcome until after 12wk Dec 20th-when I get an invite back for a 24wk or not. Thanks for asking!
How are you doing?
Well done, Reg, congratulations to you on SVR12! Great news!
And a very big `thank-you` to you all for taking part in this trial, and other clinical trials, you are all trail blazers, leading the way for others to follow!
Thanks Lil Eddie for posting the link and details of the Lonestar results, that is excellent news! I`m going to post it in the `HCV News` section too, for anyone who doesn`t see it here. Cheers!
Great job Reg..
Hi,
Lil Eddie, Thank you for posting that.
The Lonestar results mystery is now revealed. The results are spectacular. We are so lucky to have been able to participate in this trial. The article states that even those with mutations at baseline were able to achieve SVR. That is such good news for those of you who have relapsed on other trials. The article mentions one person that was lost to followup which means they did not return for their blood draw so can't be counted in the results. Everyone please return for your follow up blood draws so that the ION3 trial will have accurate results.
I wish they had stated what the two serious adverse events were.
Reg, Congratulations on SVR12!!
Misfis, Good luck on your big day tomorrow.
Sofie and SoCal, We did it! Thanks so much for your support. I felt like I went through this trial with both of you and it was so helpful to be able to support each other through the trial.
Karen, Have you had SVR4 test done yet? How are you doing?
Good luck to all the rest of the 12 week ION3 participants.
Good job to all you guys on the trials, without you all we would be lost in Hepc land..
Great job folks !!!
All I can say is "WOW".
Hope my Merck trial does as well. They posted similar results at the convention for the earlier data from their last study. Currently going into my 10th week with ribavirin. Weeks 4 and 8 I was UND.
It is so nice to hear all the positive results. I got rejected for an earlier Gilead study at my current center in Arlington Texas because I now have cirrhosis. Can't remember why I didn't apply for this trial. San Antonio is about 150 miles south of me. Think they had either an age or distance restriction.
Hearing your results makes my anxiety levels drop--well, a little. We are all so fortunate to be a part of these new studies. Happy SVR to all of you.
SuziQ
It is a beautiful morning:)
OMG! thanks so much for posting this!!!We are so lucky to have been a part of this ION 3 test! I'm off to my 12 week EOT draw tomorrow with a happy smile on my face. Am planning on taking myself out to lunch afterwards at my fav Italian restaurant in SF. Good luck to everyone!!!
Finally, The results from Lonestar with SVR12 and SVR24.
LOOKS GOOD!!!
http://www.aidsmap.com/Fixed-dose-sofosbuvirledipasvir-with-or-without-ribavirin-cures-most-genotype-1-hepatitis-C-patients-LONESTAR-study-shows/page/2801641/
Fixed-dose sofosbuvir/ledipasvir with or without ribavirin cures most genotype 1 hepatitis C patients, LONESTAR study shows
At least 95% of newly treated people with genotype 1 hepatitis C and prior non-responders achieved sustained virological response using a fixed-dose combination of sofosbuvir plus ledipasvir, with or without ribavirin, according to findings from the LONESTAR study presented at The Liver Meeting 2013, the 64th annual meeting of the American Association for the Study of Liver Diseases (AASLD) in Washington, DC. While response rates were high overall, the two relapsers in the trial were not taking ribavirin.
The advent of direct-acting antiviral agents has revolutionised treatment of chronic hepatitis C. While these agents were initially tested as add-ons to interferon-based therapy, many people with hepatitis C virus (HCV) and their care providers are awaiting all-oral regimens that dispense with pegylated interferon and its difficult side-effects.
Eric Lawitz of the Texas Liver Institute reported results from the phase 2 LONESTAR study, which evaluated a fixed-dose combination pill containing Gilead Sciences' HCV polymerase inhibitor sofosbuvir (formerly GS-7977) plus the NS5A inhibitor ledipasvir (formerly GS-5885), taken with or without ribavirin for 8 or 12 weeks.
LONESTAR enrolled two cohorts at a single centre in the United States. Cohort 1 included 60 treatment-naive individuals (people who had not taken treatment before) who did not have liver cirrhosis. Cohort 2 included 40 people, about half with cirrhosis, who did not achieve a cure with the current standard of care: triple therapy with the approved HCV protease inhibitors boceprevir (Victrelis) or telaprevir (Incivo or Incivek) plus pegylated interferon/ribavirin.
Overall, two-thirds of participants were men, 9% were black and the mean age was 50 years. Most (87%) had harder-to-treat HCV genotype 1a and only 15% had the favourable IL28B CC gene variant associated with interferon responsiveness. In Cohort 2, 55% had cirrhosis at study entry. Just over half (55%) had previously been treated with boceprevir while 45% had used telaprevir. All experienced prior virological failure; people who stopped previous therapy due to adverse events were excluded.
Participants in Cohort 1 were randomly assigned (1:1:1) to receive the once-daily fixed-dose tablet containing 400mg sofosbuvir and 90mg ledipasvir either with or without 1000-1200mg/day weight-based ribavirin for 8 weeks, or without ribavirin for 12 weeks. Treatment-experienced patients were randomised to receive sofosbuvir/ledipasvir either with or without ribavirin for 12 weeks.
All participants completed therapy except for one who withdrew consent. In Cohort 1, 95% of treatment-naive patients treated with sofosbuvir/ledipasvir for either 8 or 12 weeks achieved sustained virological response, or continued undetectable HCV RNA at 12 weeks post-treatment (SVR12). The SVR12 rate was 100% in the 8-week sofosbuvir/ledipasvir plus ribavirin arm.
In Cohort 2, SVR12 rates were 95% for sofosbuvir/ledipasvir and 100% for sofosbuvir/ledipasvir plus ribavirin given for 12 weeks. All patients without cirrhosis achieved sustained response, as did all but one of the people with cirrhosis (91%).
Response rates for all arms remained the same at 24 weeks post-treatment (SVR24). These results compared favourably to historical SVR24 rates of about 70% for people without cirrhosis and 44% for people with cirrhosis in pivotal trials of boceprevir or telaprevir plus pegylated interferon/ribavirin.
The 95% response rates reflected three people who did not achieve SVR12/24. One patient in Cohort 1 who received sofosbuvir/ledipasvir alone for 8 weeks and one in Cohort 2 who received sofosbuvir/ledipasvir for 12 weeks experienced viral relapse, while one person in Cohort 1 who received sofosbuvir/ledipasvir for 12 weeks was lost to follow-up after reaching SVR8. Both relapsers had HCV genotype 1a. No one who took ribavirin relapsed.
Seven of the nine people with NS5A resistance mutations and all 28 people with NS3/4A (protease) resistance mutations at baseline nevertheless achieved sustained response. One patient had evidence of the S282T mutation and multiple NS5A resistance mutations at the time of relapse at week 8. This individual was retreated with sofosbuvir/ledipasvir plus ribavirin for 24 weeks and went on to achieve SVR12.
Sofosbuvir/ledipasvir was generally safe and well-tolerated with or without ribavirin. Two people receiving sofosbuvir/ledipasvir alone and two receiving ribavirin experienced serious adverse events, but no one discontinued treatment for this reason. Grade 3 to 4 adverse events (0 vs 14%) and grade 3 to 4 laboratory abnormalities (7 vs 14%) were more common among those taking ribavirin. Anaemia was seen only in the ribavirin arms (19%).
Asked whether ribavirin is still important, Lawitz said these results confirm that "for a large proportion of patients we can remove ribavirin without impacting SVR," and "outside clinical trials, anything we can do to improve compliance is a benefit".
The phase 3 ION trials are currently underway, testing sofosbuvir/ledipasvir with or without ribavirin for 8, 12 or 24 weeks in treatment-naive patients with genotype 1 and prior non-responders, Lawitz noted.
Results from the phase 2 ELECTRON trial, also reported at the Liver Meeting, showed that Gilead's non-nucleoside polymerase inhibitor GS-9669 as a third agent instead of ribavirin also led to SVR12 rates of 100% for difficult-to-treat genotype 1 patients.
Hey Reg
Congrats, that is super fantastic news, a day that you will always remember.
Another great day for Hepcfriends
matt
Congratulations Reg! You are the first of us non ribiviron people to report back!!!! So happy for you!
Congragulations!
Hi everyone -
Just wanted to let everyone know that I got my 12-week EOT results today and SVR12!! I was on the 12 week no riba arm.
Congrats Ckncali! That is fantastic! I feel like we have gone through this together.
Still holding a good thought for all.
Also, I know I have sounded looney and believe me, I was looney and even more so than you all know, so I want to thank you all for not telling me to go away. Also, a big thank you to the ones who private messaged me to see if I was ok. Yes, the forum is invaluable.
Wow, thanks Millani and Jill. Ditto on what RH said--this forum is invaluable!!!
Thanks guys for the answer. I don't see how anyone could go through treatment without THIS forum.
Hi Misfis and RH,
Just a brief addition to what Jill posted. <25 means the LLOQ for that particular PCR test, and the test may have a LLOD (Lowest Limit of Detection) which is less than that, often around 10 or 7. Undetected means that no viral RNA can be detected. So, you could have ,e.g. 5 viral particles/ml of blood and still be called Undetected. Experience has shown that this amount of virus is not significant. The virus is the same, and it continues to replicate, but the body has learned how to control such tiny amounts of virus using the immune system. Whether the virus replicates in liver, blood monocytes or other tissues is unknown, but it is not important. The important thing is that the virus has been effectively neutralised. However there is still a tiny chance of passing on the virus, so the usual sensible precautions should continue to be used.
In time, it is hoped that a more sensitive test will be available, that can measure down to zero viral particles. Maybe then we can call ourselves cured, in the true sense of the word.
Great question Misfis. I would like to know that answer as well.
I had a 10 week or so blood draw last week with my private Dr and will get the results tomorrow at 2:30 when I see him. I'm a little nervous about it. I will post results as soon as I get them.
Gilead sure has been tight lipped about the ION 's and it's annoying the hell out of me.
Good luck everyone
Lil Eddie, RH, myself and a few others here are part of the ION 3 arm of 12 weeks with sofos and ledispavir--no ribi. I think we are all around November 13th for our 12 wee EOT blood draw. I guess we will be the first to be able to report back, hopefully in the week of the 20th of November, about our results. Wish us all luck!!
Good job CK.. That is great news.
take care
Very good news you guys,
Ckncali i am pretty sure SVR24 is called cured. All the best to you.
Happy days!!!
Congrats Ckncali...
All the best
Hi,
Just got the news. I am SVR12! I was told to return in 3 months which means the virus was not detected. I was also told that so far they had not gotten any alerts which means that no one at their clinic has had the virus return. I hope this news bring relief to some of you who are still waiting to hear about your 12 week after EOT results.
I did ask if they consider SVR12 a cure and was told that at this point they have not determined that SVR12 is a cure but that it is highly unlikely the virus could return when it is no longer detected 12 weeks after EOT.
Today is a good day.
Hi Misfits, well if your viral load result comes back as < 25 (less than 25) and `undetected`, or `not detected`, it just indicates that the particular PCR v l test being used is only able to quantify down to that level, so it`s considered as no virus undetected. So there may or may not actually be any virus particles remaining but the test isn`t sensitive enough to detect anything less than 25. Hope that helps!
Congrats to to you, Ckncali, sound good to me!! SVR12 is generally considered `cured` for most clinical trials, and yes, it`s rare for anyone to relapse after 12 weeks post tx.
Best of luck RH, and everyone!!
Congratulations, all you people that do these trials are a life line to many people, you should be very proud of what you have done. Enjoy life again without the burden. x
Hi Sofi,
Congrats on a great result! Hard to believe this can happen with only 8 weeks of Rx. You guys are inspirational. Enjoy SVR. Cheers.
Hi Everyone,
Just glanced through the posts. Congratulations to all of you!!! I am still in my Merck trial with riba. Starting week 8 tomorrow and labs on Wednesday--results several days after that. The Merck results released at the conference yesterday look great, but they didn't do cirrhotics in that trial. How great that there were others here you could communicate with while on your trial. Didn't see anyone else on my Merck trial.
I see you all agree that a major side effect of these trials is the waiting--creates anxiety.
Just wanted to say hi and congratulate you all.
Suziq
Great news, Sofi, very pleased for you! Congratulations!!
I hope you`re feeling a lot better now, you didn`t have an easy time of it. You must be so relieved to have it all behind you now, time to enjoy your new virus-free life!
Congratulation's Sofi That's is great news !
Enjoy your new life and relax and put your feet up.