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Accepted into Gilead GS-7977/RBV Phase II trial!!!
I am happy to report that today I got accepted into the "An Open-Label Study to Explore the Clinical Efficacy of GS 7977 With Ribavirin Administered Pre-Transplant in Preventing Hepatitis C Virus (HCV) Recurrence Post-Transplant".
I will be 1 of only 40 people in the U.S., Europe and New Zealand in this trial.
I am planning on receiving a liver transplant in 5-6 months due to my HCC (liver cancer). My hepatologist will be leading the trial here at UCSF. I am a previous null-responder to treatment so the chance to try an all oral treatment is my best chance of curing my hepatitis C. This could free me from having to worry that my hepatitis will destroy my donor liver too in 5-10 years. This could increase my longevity to be on par with others post transplant that don't have hep C.
The approach of this study is to make the viral load undetectable while treating up to 24 and at some point before 24 weeks have a transplant. We will then be followed post transplant to see if the virus reoccurs.
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Purpose
The primary objective is to determine if the administration of a combination of GS 7977 and ribavirin to HCV-infected subjects with hepatocellular carcinoma (HCC) meeting the MILAN criteria prior to undergoing liver transplantation for up to 24 weeks can prevent post-transplant re-infection as determined by a sustained post-transplant virological response (HCV RNA <LLoQ) at 12 weeks post-transplant.
Condition:
Hepatitis C
Hepatocellular Carcinoma
Purpose/Abstract:
Hepatitis C virus (HCV) affects an estimated 170 million people worldwide with approximately 4 million of these infected individuals residing within the United States. Of those infected with HCV, approximately 80% develop chronic disease often marked by progressive hepatic fibrosis resulting in cirrhosis and eventually liver failure or hepatocellular carcinoma. The current licensed therapy aimed at treating HCV genotype 1 (GT-1) infection is the combination of an HCV protease inhibitor (telapravir or bocepravir) in combination with interferon-alpha and ribavirin. However, this treatment regimen is hampered by drug interactions and significant clinical toxicity in this population. The complications of chronic hepatitis C account for the most common indication for liver transplantation in the United States. Despite this, HCV infection recurs in every patient transplanted and often retreatment with the standard interferon based regimen is poorly tolerated and ineffective [1]. There is currently no effective therapy aimed at preventing infection of a transplanted liver. The urgent need for an effective therapy for HCV has spurred extensive research into the viral life cycle. Replication of the viral genome by the NS5B polymerase and cleavage of the polyprotein precursor by the NS3/NS4A protease are two life cycle events being targeted by antiviral drugs in various stages of development. The HCV NS5B polymerase has been demonstrated to be a viable target for the development of HCV therapies.
GS-7977 is a potent and specific nucleotide analog NS5B polymerase inhibitor for HCV and has been shown to inhibit HCV replication in treatment naïve individuals.
PRIMARY AND SECONDARY OBJECTIVES
Primary:
-To determine if the administration of a combination of GS-7977 and ribavirin to HCVinfected patients with hepatocellular carcinoma (HCC) meeting the MILAN criteria prior to undergoing liver transplantation for up to 24 weeks can prevent post-transplant re-infection as determined by a sustained post-transplant virological response (HCV RNA
Secondary:
-To determine if the administration of a combination of GS-7977 and ribavirin to HCVinfected patients with HCC meeting the MILAN criteria prior to undergoing liver transplantation can elicit a sustained viral response as determined by HCV RNA -To evaluate the safety and tolerability of a combination of GS-7977 and ribavirin in HCVinfected patients prior to undergoing liver transplantation.
-To evaluate the HCV RNA viral kinetics during the treatment phase and following liver transplant and correlate results with the duration of study treatment prior to liver transplant (LT).
-To explore the presence or absence of HCV RNA in the liver explants
and correlate with plasma HCV RNA viral kinetics during therapy,
plasma GS-7977 and metabolite exposure (GS-566500 and GS-331007,
if possible), duration of therapy, duration of plasma HCV RNA negativity.
-To explore the dynamics of non-tumor MELD score during the study.
-To determine concentrations of GS-7977 and metabolites (if suitable analytical methods can be developed) in the liver explants in a subset of patients who cease GS-7977 therapy within 24 hours of Liver Transplantation.
Overall Risk/Benefit Assessment
There is currently no standard of care therapy available for patients awaiting liver transplantation re-infection of the transplanted liver is ubiquitous. Complications of re-infection in patients receiving immunosuppressive medications are common and can be both serious and severe due to the accelerated natural history of recurrent HCV infection.
As described above, during clinical trials with GS-7977 in combination with pegylated interferon and ribavirin for durations of up to 12 weeks, GS-7977 was safe and well tolerated, and the adverse events profile was comparable to PEG/RBV. Across all Phase 1 and Phase 2 studies to date, no unique safety issues related to GS-7977 have been identified. Results from ELECTRON suggest that GS-7977 in combination with RBV will be well tolerated and may yield substantial SVR rates in patients with HCV and HCC.
In clinical studies to date evaluating GS-7977, no resistant virus has been identified. The possible emergence of HCV resistant to GS-7977 cannot be excluded, but given the expected very low incidence of resistance, the likely clinical impact would be small.
If moderate to high rates of SVR can be obtained with an interferon-free regimen, the only regimen available to patients with HCC awaiting transplantation and re-infection of the liver can be prevented, significant morbidity for patients would be avoided. This offers a very favorable riskbenefit determination for individuals with chronic HCV infection.
Cheers!
Hector
I will be 1 of only 40 people in the U.S., Europe and New Zealand in this trial.
I am planning on receiving a liver transplant in 5-6 months due to my HCC (liver cancer). My hepatologist will be leading the trial here at UCSF. I am a previous null-responder to treatment so the chance to try an all oral treatment is my best chance of curing my hepatitis C. This could free me from having to worry that my hepatitis will destroy my donor liver too in 5-10 years. This could increase my longevity to be on par with others post transplant that don't have hep C.
The approach of this study is to make the viral load undetectable while treating up to 24 and at some point before 24 weeks have a transplant. We will then be followed post transplant to see if the virus reoccurs.
--------------------------------------------------------------------------------------------------
Purpose
The primary objective is to determine if the administration of a combination of GS 7977 and ribavirin to HCV-infected subjects with hepatocellular carcinoma (HCC) meeting the MILAN criteria prior to undergoing liver transplantation for up to 24 weeks can prevent post-transplant re-infection as determined by a sustained post-transplant virological response (HCV RNA <LLoQ) at 12 weeks post-transplant.
Condition:
Hepatitis C
Hepatocellular Carcinoma
Purpose/Abstract:
Hepatitis C virus (HCV) affects an estimated 170 million people worldwide with approximately 4 million of these infected individuals residing within the United States. Of those infected with HCV, approximately 80% develop chronic disease often marked by progressive hepatic fibrosis resulting in cirrhosis and eventually liver failure or hepatocellular carcinoma. The current licensed therapy aimed at treating HCV genotype 1 (GT-1) infection is the combination of an HCV protease inhibitor (telapravir or bocepravir) in combination with interferon-alpha and ribavirin. However, this treatment regimen is hampered by drug interactions and significant clinical toxicity in this population. The complications of chronic hepatitis C account for the most common indication for liver transplantation in the United States. Despite this, HCV infection recurs in every patient transplanted and often retreatment with the standard interferon based regimen is poorly tolerated and ineffective [1]. There is currently no effective therapy aimed at preventing infection of a transplanted liver. The urgent need for an effective therapy for HCV has spurred extensive research into the viral life cycle. Replication of the viral genome by the NS5B polymerase and cleavage of the polyprotein precursor by the NS3/NS4A protease are two life cycle events being targeted by antiviral drugs in various stages of development. The HCV NS5B polymerase has been demonstrated to be a viable target for the development of HCV therapies.
GS-7977 is a potent and specific nucleotide analog NS5B polymerase inhibitor for HCV and has been shown to inhibit HCV replication in treatment naïve individuals.
PRIMARY AND SECONDARY OBJECTIVES
Primary:
-To determine if the administration of a combination of GS-7977 and ribavirin to HCVinfected patients with hepatocellular carcinoma (HCC) meeting the MILAN criteria prior to undergoing liver transplantation for up to 24 weeks can prevent post-transplant re-infection as determined by a sustained post-transplant virological response (HCV RNA
Secondary:
-To determine if the administration of a combination of GS-7977 and ribavirin to HCVinfected patients with HCC meeting the MILAN criteria prior to undergoing liver transplantation can elicit a sustained viral response as determined by HCV RNA -To evaluate the safety and tolerability of a combination of GS-7977 and ribavirin in HCVinfected patients prior to undergoing liver transplantation.
-To evaluate the HCV RNA viral kinetics during the treatment phase and following liver transplant and correlate results with the duration of study treatment prior to liver transplant (LT).
-To explore the presence or absence of HCV RNA in the liver explants
and correlate with plasma HCV RNA viral kinetics during therapy,
plasma GS-7977 and metabolite exposure (GS-566500 and GS-331007,
if possible), duration of therapy, duration of plasma HCV RNA negativity.
-To explore the dynamics of non-tumor MELD score during the study.
-To determine concentrations of GS-7977 and metabolites (if suitable analytical methods can be developed) in the liver explants in a subset of patients who cease GS-7977 therapy within 24 hours of Liver Transplantation.
Overall Risk/Benefit Assessment
There is currently no standard of care therapy available for patients awaiting liver transplantation re-infection of the transplanted liver is ubiquitous. Complications of re-infection in patients receiving immunosuppressive medications are common and can be both serious and severe due to the accelerated natural history of recurrent HCV infection.
As described above, during clinical trials with GS-7977 in combination with pegylated interferon and ribavirin for durations of up to 12 weeks, GS-7977 was safe and well tolerated, and the adverse events profile was comparable to PEG/RBV. Across all Phase 1 and Phase 2 studies to date, no unique safety issues related to GS-7977 have been identified. Results from ELECTRON suggest that GS-7977 in combination with RBV will be well tolerated and may yield substantial SVR rates in patients with HCV and HCC.
In clinical studies to date evaluating GS-7977, no resistant virus has been identified. The possible emergence of HCV resistant to GS-7977 cannot be excluded, but given the expected very low incidence of resistance, the likely clinical impact would be small.
If moderate to high rates of SVR can be obtained with an interferon-free regimen, the only regimen available to patients with HCC awaiting transplantation and re-infection of the liver can be prevented, significant morbidity for patients would be avoided. This offers a very favorable riskbenefit determination for individuals with chronic HCV infection.
Cheers!
Hector
Wow Hector this is fantastic. I am so glad all your research and efforts are paying off and enabling you to participate in what is sure to be ground breaking research. I know reinfection post-transplant is a crucial issue and up to know virtually unavoidable. I hope and pray this all falls into place and you are free of this beast!
Yes, yes, yes, yes !!!!!
Can you see me jumping up and down across the bay ??
Getting a transplant AND being hep C free~ what a wonderful concept.
Can you see me jumping up and down across the bay ??
Getting a transplant AND being hep C free~ what a wonderful concept.
HECTOR!!! I am so thrilled for you-been holding my breath all this time, my son even made his special trip to the Wall in your honor---yes dearest guy you are going to do it! SOOOO happy.
That is such wonderful news...was headed to bed when I saw your post. What a great way to end the night. Am so very happy for you!!! I know your success will pave the way for others in the future. And hope the other 39 will be successful as well!
Warmest regards!
Margaret
Warmest regards!
Margaret
Wouldn't it be wonderful to have a solution to stop the recurrence of the hepatitis C virus in the donor liver? To not have to worry about developing cirrhosis and liver failure within a few years after having gone through the whole process of getting that first liver transplant. Isn't it bad enough to have one liver destroyed by the virus over 20-40 years then to have to worry about the accelerated process happening again due to immunosuppressants and steroids? This could be a huge milestone in the treatment of those receiving transplants because of liver disease caused by hepatitis C, which is the majority of transplant recipients in the U.S.
From HCV Advocate...
"Furthermore, the natural history of recurrent HCV following LTx appears to be significantly accelerated compared to that in non-LTx cases. Rather than the 20% figure quoted for non-LTx cases who may develop cirrhosis after 20-30 years, anywhere from 10 to 30% of LTx recipients with recurrent HCV have advanced fibrosis (scarring) or full-blown cirrhosis within only 5 years. Another problem is that, once cirrhosis develops post-LTx, complications occur more rapidly than in non-LTx cases. If another LTx is required, the outcome is usually not as favorable and some liver transplant centers refuse to offer a second LTx on this account.
In some instances, a particularly aggressive form of recurrent HCV develops within only a few months post-LTx and this condition has been labelled “fibrosing cholestatic hepatitis” (FCH). "
Hector
From HCV Advocate...
"Furthermore, the natural history of recurrent HCV following LTx appears to be significantly accelerated compared to that in non-LTx cases. Rather than the 20% figure quoted for non-LTx cases who may develop cirrhosis after 20-30 years, anywhere from 10 to 30% of LTx recipients with recurrent HCV have advanced fibrosis (scarring) or full-blown cirrhosis within only 5 years. Another problem is that, once cirrhosis develops post-LTx, complications occur more rapidly than in non-LTx cases. If another LTx is required, the outcome is usually not as favorable and some liver transplant centers refuse to offer a second LTx on this account.
In some instances, a particularly aggressive form of recurrent HCV develops within only a few months post-LTx and this condition has been labelled “fibrosing cholestatic hepatitis” (FCH). "
Hector
This is great news. I am a post liver patient currently on tx. I am so happy that you have a chance to be Hep c free going into your "receiving the gift of life" tranx.. I had a living donor (my sister) and after she gave me the "gift of life" and have this virus damage that gift, seems so senseless. I can only wish you the very best. I know how sick you are and have been and it will get soooo much better. Good luck!
you deserve to live a hepc free new life Hector. Although we don't know each other was rather impressed by your life story. Wishing you all the best and hope to see you for a long long time in Liver Communities health forums. i'll pray for u.....
Wow! Haven't been on for a bit and am so glad I came on to get this incredible news. The word on the street is that the 7977 has minimal sides, so you get to kick the virus to the curb without having to endure the current triple therapy side effects. Things are really looking up for you, Hector. Very much looking forward to your first UND result, then the successful transplant news. Congratulations, sir.
From the studies I've seen with GS-7977 and ribavirin, everyone including us previous "null-responders" are UND by week 4. The problem has been when some groups of patients stop treatment, they relapse.
The nice thing about this study is there is NO STOPPING of treatment. (!) We take the treatment drugs up to and on the day of our liver transplant. We will have a viral load test at the time of transplant. Take the old cancerous liver out and put in a new shiny nutmeg brown donor liver. Put us back together and hope that since we where UND at the time of transplant, there will be no hepatitis C virus in our blood stream to reinfect our new liver.
I will also be donating samples of my explanted liver to study its genetics, the amount of GS-7977 in my liver, any hepatitis C in my liver and to look for any changes in the blood cells of my liver. They can have it. All I ask is for a photo of my 60 year old liver after they take it out.
They will also store my blood samples for future testing from all my pre and post blood draws.
The proof will be in the pudding. Or should I say my post transplant viral load tests at weeks 1,2,3,4,8,12,24,48.
This is by far my best chance to clear my hepatitis C after living with it for the last 43 years. Long enough in my opinion.
Hector
The nice thing about this study is there is NO STOPPING of treatment. (!) We take the treatment drugs up to and on the day of our liver transplant. We will have a viral load test at the time of transplant. Take the old cancerous liver out and put in a new shiny nutmeg brown donor liver. Put us back together and hope that since we where UND at the time of transplant, there will be no hepatitis C virus in our blood stream to reinfect our new liver.
I will also be donating samples of my explanted liver to study its genetics, the amount of GS-7977 in my liver, any hepatitis C in my liver and to look for any changes in the blood cells of my liver. They can have it. All I ask is for a photo of my 60 year old liver after they take it out.
They will also store my blood samples for future testing from all my pre and post blood draws.
The proof will be in the pudding. Or should I say my post transplant viral load tests at weeks 1,2,3,4,8,12,24,48.
This is by far my best chance to clear my hepatitis C after living with it for the last 43 years. Long enough in my opinion.
Hector
You know, I've seen plenty of sad things on this board, but I cannot think of anything right now to me that seems like better news than this thread. I'm just so happy for you.
Happy that you may soon be cleared of the virus and happy to see you ARE getting a new liver.
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"I will be 1 of only 40 people in the U.S., Europe and New Zealand in this trial.
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.......and with due respect..... you aren't "1 in 40". I think it's more like one in a million.
What a wonderful bit of news. Crossing fingers till then.
willy
Happy that you may soon be cleared of the virus and happy to see you ARE getting a new liver.
---------------------------------------------------------------
"I will be 1 of only 40 people in the U.S., Europe and New Zealand in this trial.
----------------------------------------------------------------
.......and with due respect..... you aren't "1 in 40". I think it's more like one in a million.
What a wonderful bit of news. Crossing fingers till then.
willy
hector, i'm so very happy for you. no one here deserves this chance more than you. you're such an inspiration and a wealth of knowledge for all of us. good luck with your trial. may your sx be mild and your outcome be SVR. best wishes. belle
This is GREAT news!!! : ) You have helped me numerous times, with expert advice, and more than that, you have helped me to feel grounded, via your participation in this website.
If you ever need anything, I just want you to know that I am always
right here for you also~
If you ever need anything, I just want you to know that I am always
right here for you also~
Fantastic news Hector. It would be wonderful if you could rid yourself of the virus prior to transplant. Big smiles. Keep us updated. You know we're all rooting for you.
Ah, such a wonderful piece of news from you. I can imagine that you are *smiling* now! Long distance hugs and prayers coming your way. So very happy for you,
Susan
Susan
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