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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
that is awsome Hector! I really hope everything works out way better then expected! Looking forward to hearing about the happy ending to your story!
Praise God! I will keep you in my prayers. I am HCV Genotype 6 and just missed a Trial by its cutoff, (hard to find GT6 in the USA) but am still looking as time and God allows. Keep us posted, OK? Your success is ours also!
God Bless!
Karen
God Bless!
Karen
Congratulations on getting into the trial...looking forward to good things for you!
Best wishes,
Laura
Best wishes,
Laura
Hector, I read your story last night and woke up this morning thinking what a miraculous turn of events for you. From being closer to the end of the road than any of us wants to get, you may soon have a fully functional liver that is virus free. You won the lottery but better.
I'll be watching with my fingers crossed all the way for you,
dointime
I'll be watching with my fingers crossed all the way for you,
dointime
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