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Hep C Discussion Forum -> Clinical Trial Participants -> How to evaluate a Clinical Trial- extra consideration
Post Info TOPIC: How to evaluate a Clinical Trial- extra consideration
Canuck


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How to evaluate a Clinical Trial- extra consideration
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Mallani,

Thank you very much for sharing your wide knowledge on these topics. It helps, a lot. Being "new" to this territory and to this website, there is so much to learn (and read). The more I explore the site, the more info I discover (that you and the others have already written). I do thank you for the time you take to explain complicated matters succinctly in simple terms (I still have to crack open my notebook though). Being that my query was narrow to a specific trial and GT, your info on RAV's/Sofo/Velpa is very helpful. I doubt I will be in a position to be invited into this particular NCT 02607800 Gilead trial I was reviewing, which will be disappointing, given that it sounds like my best bet. But - knowledge is power, and my notebook is open! I will look forward to following lucky "Tig56's" progress into this trial. 

Sorry - an edit/correction - I meant "tkflex36" (entering the trial), not Tig56.

 Canuck  - Newly diagnosed but longstanding (4+decades) 3a, F3, high load, TN



-- Edited by Canuck on Thursday 24th of December 2015 09:41:50 AM

__________________

HCV/HBV 1973. HBV resolved. HCV undiagnosed to 2015. 64 y.o. F. Canada.

GT3a, Fibroscan F3/12 kPa - F4/12.6 kPa, VL log 7.01 (10,182,417), steatosis, high iron load.

SOF/VEL with/without GS-9857 trial - NCT02639338.

SOT March 10 - EOT May 5, 2016 - SOF/VEL/VOX 8 week trial.

 

(SEE UPDATES IN BIO)
mallani


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Hi Canuck,

Some of my posts are getting out-dated, as new evidence is being produced all the time. I'll revise them when I get time.

The RAVs responsible for treatment failure are now pretty well documented, for each Genotype and each DAA.

As a Geno 3a, you will know there are naturally occurring RAVs that decrease the chance of SVR. Some of these are- Q30E, Y93N and L23F. Pre-treatment testing is not cost effective.

RAVs from previous treatment failures are specific to each DAA and Genotype. RAVs against the common NS-5A blockers, Ledipasvir, Daclatasvir and Ombitasvir have been shown to have considerable overlap.

The new generation NS-5A blockers e.g. Velpatasvir (formerly GS-5816), should help this problem.

The over-riding key to success is Sovaldi. This is effective against all known NS-5A RAVs.

For Geno 3a's, a combination of Sovaldi and Velpatasvir should have the highest possible SVR rate. Cheers.



__________________

Geno 1b, IL28B CT,  x3 prior relapser,  ex-cirrhotic, 75 yo, did 48 weeks with Victrelis/Peg./Riba.  VL 1.28m at start, UNDET. at 8 ,12 ,16 ,24 ,30  and 48 weeks.  EOT 15 Feb 2013 , UNDET. at EOT + 28 weeks. SVR!  Still Undet. at EOT +5 years

Malcolm
Canuck


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Mallani wrote:

... "There is one point that should be considered. 'What happens if I don't achieve SVR?' This is especially of interest to those with significant liver damage i.e. the F3-4 and F4 (cirrhotic) patients. These are the people who are most in need of fairly urgent treatment.

If you are on a Trial and suffer breakthrough or relapse, you will have RAV's (Resistance Altered Variants or drug-resistant mutations) to one or more of the DAA's.  That limits your chance of re-treatment, as your cannot be re-treated with the same type of DAA.  There are Trials using short treatments durations, 8 weeks or 12 weeks.  For cirrhotics, this is probably not long enough.  If I was a cirrhotic patient (or even a F3-4) and particularly if I was Geno 1a, I would not consider a Trial where I may be included in a short-treatment group.

The Abbott Trialists are in a difficult situation. The Abbott drugs block NS3/4A, NS5A and NS5B.  If a patients relapses, all the new DAA's and even Incivek and Victrelis, are off-limits for re-treatment. This is the current situation. I am not sure what the future holds for those with RAV's.

I know this sounds a bit depressing, but patients with significant liver damage should avoid short-duration Trials, and always ask 'What are the options if I relapse or fail treatment'." ...

As a longstanding 3a, F3, high load, TN considering the "few" trials, that "might" be left, to be available to me - such as NCT 02607800 - please counsel me, how can I tread more carefully into what treatment to try first, to make allowances for possible failure?? Trials are getting fewer and fewer, and shorter and shorter.

You spoke of 1a's and Abbott trials, what of this Gilead trial for 3a's then (in this same perspective)?? I would appreciate your thinking on this Gilead trail as well.

Canuck



__________________

HCV/HBV 1973. HBV resolved. HCV undiagnosed to 2015. 64 y.o. F. Canada.

GT3a, Fibroscan F3/12 kPa - F4/12.6 kPa, VL log 7.01 (10,182,417), steatosis, high iron load.

SOF/VEL with/without GS-9857 trial - NCT02639338.

SOT March 10 - EOT May 5, 2016 - SOF/VEL/VOX 8 week trial.

 

(SEE UPDATES IN BIO)
mallani


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Hi all,

Just an update on this old post.

New research has identified most RAV's associated with the early antiproteases. These are DAA- specific and also Genotype-specific. Some of the new antiproteases are active in the presence of RAV's ( eg from Victrelis or Incivek).  MK-5172 is a good example.  Olysio has it's problems if the Q80K polymorphism is present, but Olysio will shortly disappear. We have not heard much about the Abbvie antiprotease.

Sovaldi is a nucleotide anti-polymerase (blocks the NS-5B active site). The best known variant is S282T. RAV's do develop in the rare case where Sovaldi doesn't work, but these are transient, so Sovaldi may be reused. The non-nucleotide anti-polymerases(blocks the inactive NS-5B site) have not been fully investigated. These have a low barrier to resistance and RAV's may be a problem. None have been FDA approved, and will probably find little use- apart from the Abbvie trio.

The NS-5A blockers are Ledipasvir and Daclatasvir. This site is resistance prone, and we will need more time to see whether RAV's are a problem. They will both be used with Sovaldi in most cases, and RAV's probably won't be significant. Trials for DAA's will wind down when these last two are approved.



__________________

Geno 1b, IL28B CT,  x3 prior relapser,  ex-cirrhotic, 75 yo, did 48 weeks with Victrelis/Peg./Riba.  VL 1.28m at start, UNDET. at 8 ,12 ,16 ,24 ,30  and 48 weeks.  EOT 15 Feb 2013 , UNDET. at EOT + 28 weeks. SVR!  Still Undet. at EOT +5 years

Malcolm
Matt Chris


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Hey Garfield 

Excellent questions you asked your Hepatologist. 

My question is, with all the dozens of vials blood that they take during the trial don't they have all the data regarding our bodies reactions / resistance to the Meds and the Ravs that are developing during the treatment. Will they share them with us relapsers for future options?

Most of these 2nd generation DAA's have a higher barrier to resistance but not all, Abbvie quad therapy was design to limit Ravs by boxing in Ravs by having more bases covered.

From what I read the 1st generation DDA's (Telaprevir and Boceprevir) do have a lower resistance to Ravs and the goal of all these new DAA's is the have a drug the has a super high barrier to resistance, and actually Gilead's new Sofosbuvir has this new high barrier to resistance thats why most Doctors consider this the best of the new meds coming out.  

Its hard to figure out what went wrong when a person has no data, all I can do is guess... is it duration or being Geno 1A or ??? 

They are making great progress understanding HCV so in the next 5 years we should know a whole lot more. Hope I am around.

Matt

 



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"And in the end, the love you take is equal to the love you make"

61 year old Geno type A1, F4 Cirrhotic, started 24 weeks on Harvoni 12-17-14 ,EOT-5 week = UND, 8-31-15 =UND , SVR-24 Baby YES! 
britlitkaren


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This is all so confusing! Thanks for breaking it down. I get a lot of questions about relapse. Fortunately, I'm good for now. 1 year labs are coming up. It's been 14 mos and I"m going about believing I am still SVR.
I have a cirrhotic friend who is on short term after a non responder to triple. I'm holding my breath.
BTW - my transplant doc has treated several hundred on triple and called them back in a few months ago for VL. Only 3 had relapsed and he wasn't sure if it were reinfection. That was positive news. The odds sound good.
My best to all of you. xo Karen:)

__________________
Diag 8-10. 1st VL 600,000. Gen 1a. Grade 4 Stage 4 cirrhosis w/ Esophogeal varices level 2. Viral load 1,750,000 7/12/10. Triple Therapy w/ Telaprevir began 7-15-11
ios9


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Thank you Malcom, this is very important to know.

When I signed for TURQUOISE II they did not mention that if patients relapse, there will be RAV.

By now, it's too late but I will forward on the French forum your message.

Once again : thank you so much for the info.



__________________

Geno 1b. VL 17. M. AbbVie Turquoise II. UND EOT 4. 8. 12. SVR.

"Our task must be to free ourselves by widening our circle of compassion to embrace all living creatures and the whole of nature and its beauty."Albert Einstein

 

 

 
garfield


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Hi,

   When signing the study, I thought it's an good idea to fight the virus from all sides and don't reflect upon relaps.

Because of mallanis posting I visited my doctor ( one of the leading hepatologist ) on July 7th, my EOT of the Sapphire study, to ask him:

1.  what can we do to reduce the risk of relaps and 2. what will happen in case of relaps.

About my first question he wasn`t very amused. To my second I got the answer, we have rescue therapies.

On my demand if he has only an idea or an elaborated plan, he was also not very amused. I think that'd be like opening a can of worms. 

He threw with examples around: if I have RAV's against NS3/4A than Sofosbuvir and ...., if against NS5A Sofosbuvir and ....., and so on.

And my chance to relaps will be only 5 % and what is more, that the condition of my liver is good.

I think this is the big difference between me (Sapphire) and the cirrhotics (Turquoise). The therapy was an easy walk.

I wouldn't have treated with Telaprevir. If I relaps I have enough time to wait, but unfortunately not the cirrhotics.

 

 

 



-- Edited by garfield on Thursday 11th of July 2013 12:27:32 PM

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Cinnamon Girl


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Good post, Malcolm, this is very useful additional info to have here, especially for anyone who is cirrhotic.  Thanks, as always.



__________________

Jill 

(71 yo, lives in UK)

Was Gen 3a, 

24wks Peg Ifn/Riba, Sep 2010 - Mch 2011

UND @ Wk.4, UND @ EOT, 

SVR Nov 2011 --> Still UND @ EOT + 4 yrs.

 

 
Biggyb


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Thanks, good to know Malcolm. I am printing this out for future reference.
But hopefully i wont need it..



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58 yo..Relapsed in 99 and again in 2004. Started triple therapy with Victrelis July 22,2012.  genotype 1a. week 8,12,16,24 VL Undetectable..E.O.T -- 6-22-2013,,,EOT + 24., UND. 

SVR !!!

 

~Bob~
mallani


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Jill (Cinnamon Girl) has published to link to 'How to evaluate a Clinical Trial'. This is great info.

I sincerely hope that all who are on Trials achieve SVR.

There is one point that should be considered. 'What happens if I don't achieve SVR?' This is especially of interest to those with significant liver damage i.e. the F3-4 and F4 (cirrhotic) patients. These are the people who are most in need of fairly urgent treatment.

If you are on a Trial and suffer breakthrough or relapse, you will have RAV's (Resistance Altered Variants or drug-resistant mutations) to one or more of the DAA's.  That limits your chance of re-treatment, as your cannot be re-treated with the same type of DAA.  There are Trials using short treatments durations, 8 weeks or 12 weeks.  For cirrhotics, this is probably not long enough.  If I was a cirrhotic patient (or even a F3-4) and particularly if I was Geno 1a, I would not consider a Trial where I may be included in a short-treatment group.

The Abbott Trialists are in a difficult situation. The Abbott drugs block NS3/4A, NS5A and NS5B.  If a patients relapses, all the new DAA's and even Incivek and Victrelis, are off-limits for re-treatment. This is the current situation. I am not sure what the future holds for those with RAV's.

I know this sounds a bit depressing, but patients with significant liver damage should avoid short-duration Trials, and always ask 'What are the options if I relapse or fail treatment'.

 



__________________

Geno 1b, IL28B CT,  x3 prior relapser,  ex-cirrhotic, 75 yo, did 48 weeks with Victrelis/Peg./Riba.  VL 1.28m at start, UNDET. at 8 ,12 ,16 ,24 ,30  and 48 weeks.  EOT 15 Feb 2013 , UNDET. at EOT + 28 weeks. SVR!  Still Undet. at EOT +5 years

Malcolm
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