Aa
nul-responder now on triple therapy
Hello,
I am a nul-responder to the standard treatment + 100mg of sofusbuvir. I was in a clinical trial and i got pulled early. I am now in another clinical trial of the standard care + 400mg of sofusbuvir. I am having trouble getting reliable data on nul-responders response to this 400mg sofusbuvir dose. Does anyone have knowledge on my odds. I get 50% - 80% when I search it, but there have been so few patients like me that I feel uninformed still.
I am a nul-responder to the standard treatment + 100mg of sofusbuvir. I was in a clinical trial and i got pulled early. I am now in another clinical trial of the standard care + 400mg of sofusbuvir. I am having trouble getting reliable data on nul-responders response to this 400mg sofusbuvir dose. Does anyone have knowledge on my odds. I get 50% - 80% when I search it, but there have been so few patients like me that I feel uninformed still.
Thanks for the additional details.
If I recall correctly, I actually have not read about any cases such as yours, but that does not mean there have not been any. I treated with Inf., Riba, and Telaprevir and attained SVR in Feb. of this year so I have not researched all of the trials and studies going on. I do read about new developments and new drugs in the pipeline, but I just don't recall reading about a study with people taking Inf., Riba, and 100 mg of Sofosbuvir.
You may have read this but, if not, here is a summary of the Neutrino Study (Inf., Riba, and 400 mg Sofosbuvir). SVR was not 100% but it was very good.
NEUTRINO: Sofosbuvir Plus Peginterferon/Ribavirin Achieves High SVR12 Rate, Well Tolerated in Treatment-Naive Patients With Genotype 1, 4, 5, or 6 HCV
Date posted: 4/28/2013
NEUTRINO: nonrandomized, open-label, single-arm phase III trial[1,2]
Summary of Key Conclusions
Sofosbuvir plus peginterferon/ribavirin for 12 weeks achieved very high sustained virologic response rate at 12 weeks posttreatment (SVR12) in treatment-naive patients chronically infected with genotype 1, 4, 5, or 6 HCV
90% SVR12 in overall patient population vs 60% for prespecified historical control (P < .001)
≥ 80% SVR12 in all patient subgroups, including black patients, patients with cirrhosis, and patients with IL28B non-CC genotype
97% SVR12 rate in patients with genotype 4, 5, or 6 HCV
Relapse was reason for all cases of virologic failure; no virologic breakthrough and no viral resistance detected
Regimen generally well tolerated
Background
Sofosbuvir (formerly GS-7977), potent uridine nucleotide analogue that inhibits HCV NS5B polymerase
Sofosbuvir plus peginterferon/ribavirin for 12-24 weeks previously demonstrated favorable results in phase II ATOMIC trial in treatment-naive patients with genotype 1, 4, and 6 HCV (Capsule Summary)[3,4]
SVR24: 87% to 89% in genotype 1, 82% in genotype 4, and 100% in genotype 6 HCV
No virologic breakthrough in any treatment arms or genotype groups
Low rate of virologic relapse
Current study evaluated efficacy and safety of sofosbuvir plus peginterferon/ribavirin for 12 weeks in large group of treatment-naive patients chronically infected with genotype 1, 4, 5, or 6 HCV[1,2]
Summary of Study Design
Inclusion criteria
Chronic infection with genotype 1, 4, 5, or 6 HCV
No previous HCV treatment
Cirrhosis allowed
No upper limits on age or body mass index (BMI)
Opioid substitution allowed
Adequate hematologic function
Platelet count ≥ 90,000 cells/mm3
Neutrophil count ≥ 1500 cells/mm3 (≥ 1000 cells/mm3 in black patients)
All patients received 12 weeks of triple therapy
Sofosbuvir 400 mg/day
Peginterferon alfa-2a 180 µg/week
Weight-based ribavirin 1000-1200 mg/day
Main Findings
98% of patients completed all study therapy; only 7 patents (2%) discontinued therapy
Reasons for discontinuation: adverse events (AEs) (n = 5), protocol violation (n = 1), consent withdrawal (n = 1)
90% overall SVR 12 rate with sofosbuvir and peginterferon/ribavirin, meeting primary endpoint of superiority to 60% historical control rate (P < .001)
HCV RNA < LLOQ
Week 2: 91%
Week 4: 99%
Week 12 (end of treatment): 99%
SVR12: 90%
High SVR12 rates across all genotypes, with lowest rate (89%) among patients with genotype 1 HCV
All patient subgroups attained SVR12 rates ≥ 80% with sofosbuvir plus peginterferon/ribavirin, including HCV genotype/subtype (1, 1a, 1b, or 4, 5, 6) cirrhosis (presence or absence), race (black or nonblack), baseline HCV RNA level ( 1000 IU/mL
No S282T mutations identified by population sequencing or deep sequencing
Other NS5B genetic variants not associated with any change in phenotypic susceptibility to sofosbuvir or ribavirin
It is possible that someone in the tread about Sofosbuvir will know more about your situation. Here is a link to that thread. There are many posts in that thread but it appears that people are continually reading and posting in the thread. It may be beneficial for you to post in that thread and ask your question. Just go to the bottom of the posts in that thread and then post your question.
http://www.medhelp.org/posts/Hepatitis-C/Starting-Sofosbuvir-GS-5885/show/1875802
If I find anything more I will post it.
If I recall correctly, I actually have not read about any cases such as yours, but that does not mean there have not been any. I treated with Inf., Riba, and Telaprevir and attained SVR in Feb. of this year so I have not researched all of the trials and studies going on. I do read about new developments and new drugs in the pipeline, but I just don't recall reading about a study with people taking Inf., Riba, and 100 mg of Sofosbuvir.
You may have read this but, if not, here is a summary of the Neutrino Study (Inf., Riba, and 400 mg Sofosbuvir). SVR was not 100% but it was very good.
NEUTRINO: Sofosbuvir Plus Peginterferon/Ribavirin Achieves High SVR12 Rate, Well Tolerated in Treatment-Naive Patients With Genotype 1, 4, 5, or 6 HCV
Date posted: 4/28/2013
NEUTRINO: nonrandomized, open-label, single-arm phase III trial[1,2]
Summary of Key Conclusions
Sofosbuvir plus peginterferon/ribavirin for 12 weeks achieved very high sustained virologic response rate at 12 weeks posttreatment (SVR12) in treatment-naive patients chronically infected with genotype 1, 4, 5, or 6 HCV
90% SVR12 in overall patient population vs 60% for prespecified historical control (P < .001)
≥ 80% SVR12 in all patient subgroups, including black patients, patients with cirrhosis, and patients with IL28B non-CC genotype
97% SVR12 rate in patients with genotype 4, 5, or 6 HCV
Relapse was reason for all cases of virologic failure; no virologic breakthrough and no viral resistance detected
Regimen generally well tolerated
Background
Sofosbuvir (formerly GS-7977), potent uridine nucleotide analogue that inhibits HCV NS5B polymerase
Sofosbuvir plus peginterferon/ribavirin for 12-24 weeks previously demonstrated favorable results in phase II ATOMIC trial in treatment-naive patients with genotype 1, 4, and 6 HCV (Capsule Summary)[3,4]
SVR24: 87% to 89% in genotype 1, 82% in genotype 4, and 100% in genotype 6 HCV
No virologic breakthrough in any treatment arms or genotype groups
Low rate of virologic relapse
Current study evaluated efficacy and safety of sofosbuvir plus peginterferon/ribavirin for 12 weeks in large group of treatment-naive patients chronically infected with genotype 1, 4, 5, or 6 HCV[1,2]
Summary of Study Design
Inclusion criteria
Chronic infection with genotype 1, 4, 5, or 6 HCV
No previous HCV treatment
Cirrhosis allowed
No upper limits on age or body mass index (BMI)
Opioid substitution allowed
Adequate hematologic function
Platelet count ≥ 90,000 cells/mm3
Neutrophil count ≥ 1500 cells/mm3 (≥ 1000 cells/mm3 in black patients)
All patients received 12 weeks of triple therapy
Sofosbuvir 400 mg/day
Peginterferon alfa-2a 180 µg/week
Weight-based ribavirin 1000-1200 mg/day
Main Findings
98% of patients completed all study therapy; only 7 patents (2%) discontinued therapy
Reasons for discontinuation: adverse events (AEs) (n = 5), protocol violation (n = 1), consent withdrawal (n = 1)
90% overall SVR 12 rate with sofosbuvir and peginterferon/ribavirin, meeting primary endpoint of superiority to 60% historical control rate (P < .001)
HCV RNA < LLOQ
Week 2: 91%
Week 4: 99%
Week 12 (end of treatment): 99%
SVR12: 90%
High SVR12 rates across all genotypes, with lowest rate (89%) among patients with genotype 1 HCV
All patient subgroups attained SVR12 rates ≥ 80% with sofosbuvir plus peginterferon/ribavirin, including HCV genotype/subtype (1, 1a, 1b, or 4, 5, 6) cirrhosis (presence or absence), race (black or nonblack), baseline HCV RNA level ( 1000 IU/mL
No S282T mutations identified by population sequencing or deep sequencing
Other NS5B genetic variants not associated with any change in phenotypic susceptibility to sofosbuvir or ribavirin
It is possible that someone in the tread about Sofosbuvir will know more about your situation. Here is a link to that thread. There are many posts in that thread but it appears that people are continually reading and posting in the thread. It may be beneficial for you to post in that thread and ask your question. Just go to the bottom of the posts in that thread and then post your question.
http://www.medhelp.org/posts/Hepatitis-C/Starting-Sofosbuvir-GS-5885/show/1875802
If I find anything more I will post it.
Genotype?
Hello,
Liver Biopsy result? My liver is in great shape. This is not an issue.
Previous treatment? The one time I did treatment i was in a clinical trial for the same drug i'm on now, Sofosbuvir. It was phase II, and i was randomized to the 100mg group (educated guess by the clinic). I was on Sofosbuvir, Interferon (Pegasus), and Ribavirin. I have genotype 1.
How long were you in the first trial? And just verifying that it was with SOC and Sofosbuvir 100 mg? I was in the first trial for maybe 6 weeks. I was the first patient to go zero virus but then on the next blood draw I was back to my starting levels. This makes me odd. According to my Doctor, the reason I can't find stats on cases like mine is because there are none. So yes, SOC and Sofosbuvir, probably 100mg.
When did you go UND in this second trial with SOC and Sofosbuvir 400 mg.? And how long is the trial? I am getting my third weekly injection tomorrow. I will most likely get my blood counts then. They take blood weekly. This trial is for 90 days.
From what I gather, 90 days of SOC + Sofosbuvir 400mg has had a 100% cure rate. But, few people have been tested. 25 people? Not sure if that number is just SF. I'm worried it will not work and that I am building up resistances. It does not appear to build resistance from what I read. The next trial is without interferon, just Sofosbuvir and ribavirin. It looks to me like the two drug therapy is just as effective as the three.
Hello,
Liver Biopsy result? My liver is in great shape. This is not an issue.
Previous treatment? The one time I did treatment i was in a clinical trial for the same drug i'm on now, Sofosbuvir. It was phase II, and i was randomized to the 100mg group (educated guess by the clinic). I was on Sofosbuvir, Interferon (Pegasus), and Ribavirin. I have genotype 1.
How long were you in the first trial? And just verifying that it was with SOC and Sofosbuvir 100 mg? I was in the first trial for maybe 6 weeks. I was the first patient to go zero virus but then on the next blood draw I was back to my starting levels. This makes me odd. According to my Doctor, the reason I can't find stats on cases like mine is because there are none. So yes, SOC and Sofosbuvir, probably 100mg.
When did you go UND in this second trial with SOC and Sofosbuvir 400 mg.? And how long is the trial? I am getting my third weekly injection tomorrow. I will most likely get my blood counts then. They take blood weekly. This trial is for 90 days.
From what I gather, 90 days of SOC + Sofosbuvir 400mg has had a 100% cure rate. But, few people have been tested. 25 people? Not sure if that number is just SF. I'm worried it will not work and that I am building up resistances. It does not appear to build resistance from what I read. The next trial is without interferon, just Sofosbuvir and ribavirin. It looks to me like the two drug therapy is just as effective as the three.
Sorry to hear treatment did not work for you the first time.
I am just wondering .... can you give us a few more details to your situation.
Genotype?
Liver Biopsy result?
Previous treatment?
How long were you in the first trial? And just verifying that it was with SOC and Sofosbuvir 100 mg?
When did you go UND in this second trial with SOC and Sofosbuvir 400 mg.? And how long is the trial?
I am just wondering .... can you give us a few more details to your situation.
Genotype?
Liver Biopsy result?
Previous treatment?
How long were you in the first trial? And just verifying that it was with SOC and Sofosbuvir 100 mg?
When did you go UND in this second trial with SOC and Sofosbuvir 400 mg.? And how long is the trial?
Have an Answer?
You are reading content posted in the Hepatitis C Community
Learn about this treatable virus.
Getting tested for this viral infection.
3 key steps to getting on treatment.
4 steps to getting on therapy.
What you need to know about Hep C drugs.
How the drugs might affect you.
These tips may up your chances of a cure.
A list of national and international resources and hotlines to help connect you to needed health and medical services.
Herpes sores blister, then burst, scab and heal.
Herpes spreads by oral, vaginal and anal sex.
STIs are the most common cause of genital sores.
Condoms are the most effective way to prevent HIV and STDs.
PrEP is used by people with high risk to prevent HIV infection.
