Aa
RG7128 + Danoprevir
Has anyone seen anything about this recently?
Oral combination therapy with a nucleoside polymerase inhibitor (RG7128) and danoprevir for chronic hepatitis C genotype 1 infection (INFORM-1): a randomised, double-blind, placebo-controlled, dose-escalation trial
Dr Edward J Gane MD a , Stuart K Roberts MD b, Catherine AM Stedman MD c, Prof Peter W Angus MD d, Brett Ritchie MD e, Rob Elston PhD f, David Ipe MS f, Peter N Morcos PharmD f, Linda Baher BS f, Isabel Najera PhD f, Tom Chu MD f, Uri Lopatin MD f, M Michelle Berrey MD g, William Bradford MD h, Mark Laughlin MD f, Nancy S Shulman MD f, Patrick F Smith PharmD f
Summary
Background
Present interferon-based standard of care treatment for chronic hepatitis C virus (HCV) infection is limited by both efficacy and tolerability. We assessed the safety, tolerability, and antiviral activity of an all-oral combination treatment with two experimental anti-HCV drugs—RG7128, a nucleoside polymerase inhibitor; and danoprevir, an NS3/4A protease inhibitor—in patients with chronic HCV infection.
Methods
Patients from six centres in New Zealand and Australia who were chronically infected with HCV genotype 1 received up to 13 days oral combination treatment with RG7128 (500 mg or 1000 mg twice daily) and danoprevir (100 mg or 200 mg every 8 h or 600 mg or 900 mg twice daily) or placebo. Eligible patients were sequentially enrolled into one of seven treatment cohorts and were randomly assigned by interactive voice or web response system to either active treatment or placebo.
Patients were separately randomly assigned within each cohort with a block size that reflected the number of patients in the cohort and the ratio of treatment to placebo. The random allocation schedule was computer generated. Dose escalation was started in HCV treatment-naive patients; standard of care treatment-experienced patients, including previous null responders, were enrolled in higher-dose danoprevir cohorts. Investigators, personnel at the study centre, and patients were masked to treatment allocation. However, the pharmacist who prepared the doses, personnel involved in pharmacokinetic sample analyses, statisticians who prepared data summaries, and the clinical pharmacologists who reviewed the data before deciding to initiate dosing in the next cohort were not masked to treatment allocation. The primary outcome was change in HCV RNA concentration from baseline to day 14 in patients who received 13 days of combination treatment. All patients who completed treatment with the study drugs were included in the analyses. This study is registered with ClinicalTrials.gov, NCT00801255.
Findings
88 patients were randomly assigned to a study drug treatment regimen (n=74 over seven treatment groups; 73 received at least one dose of study drug) or to placebo (n=14, all of whom received at least one dose).
The median change in HCV RNA concentration from baseline to day 14 ranged from −3·7 to −5·2 log10 IU/mL in the cohorts that received 13 days of combination treatment. At the highest combination doses tested (1000 mg RG7128 and 900 mg danoprevir twice daily), the median change in HCV RNA concentration from baseline to day 14 was −5·1 log10 IU/mL (IQR −5·6 to −4·7) in treatment-naive patients and −4·9 log10 IU/mL in previous standard of care null responders (−5·2 to −4·5) compared with an increase of 0·1 log10 IU/mL in the placebo group. The combination of RG7128 and danoprevir was well tolerated with no treatment-related serious or severe adverse events, no grade 3 or 4 changes in laboratory parameters, and no safety-related treatment discontinuations.
Interpretation
This oral combination of a nucleoside analogue polymerase inhibitor and protease inhibitor holds promise as an interferon-free treatment for chronic HCV.
Oral combination therapy with a nucleoside polymerase inhibitor (RG7128) and danoprevir for chronic hepatitis C genotype 1 infection (INFORM-1): a randomised, double-blind, placebo-controlled, dose-escalation trial
Dr Edward J Gane MD a , Stuart K Roberts MD b, Catherine AM Stedman MD c, Prof Peter W Angus MD d, Brett Ritchie MD e, Rob Elston PhD f, David Ipe MS f, Peter N Morcos PharmD f, Linda Baher BS f, Isabel Najera PhD f, Tom Chu MD f, Uri Lopatin MD f, M Michelle Berrey MD g, William Bradford MD h, Mark Laughlin MD f, Nancy S Shulman MD f, Patrick F Smith PharmD f
Summary
Background
Present interferon-based standard of care treatment for chronic hepatitis C virus (HCV) infection is limited by both efficacy and tolerability. We assessed the safety, tolerability, and antiviral activity of an all-oral combination treatment with two experimental anti-HCV drugs—RG7128, a nucleoside polymerase inhibitor; and danoprevir, an NS3/4A protease inhibitor—in patients with chronic HCV infection.
Methods
Patients from six centres in New Zealand and Australia who were chronically infected with HCV genotype 1 received up to 13 days oral combination treatment with RG7128 (500 mg or 1000 mg twice daily) and danoprevir (100 mg or 200 mg every 8 h or 600 mg or 900 mg twice daily) or placebo. Eligible patients were sequentially enrolled into one of seven treatment cohorts and were randomly assigned by interactive voice or web response system to either active treatment or placebo.
Patients were separately randomly assigned within each cohort with a block size that reflected the number of patients in the cohort and the ratio of treatment to placebo. The random allocation schedule was computer generated. Dose escalation was started in HCV treatment-naive patients; standard of care treatment-experienced patients, including previous null responders, were enrolled in higher-dose danoprevir cohorts. Investigators, personnel at the study centre, and patients were masked to treatment allocation. However, the pharmacist who prepared the doses, personnel involved in pharmacokinetic sample analyses, statisticians who prepared data summaries, and the clinical pharmacologists who reviewed the data before deciding to initiate dosing in the next cohort were not masked to treatment allocation. The primary outcome was change in HCV RNA concentration from baseline to day 14 in patients who received 13 days of combination treatment. All patients who completed treatment with the study drugs were included in the analyses. This study is registered with ClinicalTrials.gov, NCT00801255.
Findings
88 patients were randomly assigned to a study drug treatment regimen (n=74 over seven treatment groups; 73 received at least one dose of study drug) or to placebo (n=14, all of whom received at least one dose).
The median change in HCV RNA concentration from baseline to day 14 ranged from −3·7 to −5·2 log10 IU/mL in the cohorts that received 13 days of combination treatment. At the highest combination doses tested (1000 mg RG7128 and 900 mg danoprevir twice daily), the median change in HCV RNA concentration from baseline to day 14 was −5·1 log10 IU/mL (IQR −5·6 to −4·7) in treatment-naive patients and −4·9 log10 IU/mL in previous standard of care null responders (−5·2 to −4·5) compared with an increase of 0·1 log10 IU/mL in the placebo group. The combination of RG7128 and danoprevir was well tolerated with no treatment-related serious or severe adverse events, no grade 3 or 4 changes in laboratory parameters, and no safety-related treatment discontinuations.
Interpretation
This oral combination of a nucleoside analogue polymerase inhibitor and protease inhibitor holds promise as an interferon-free treatment for chronic HCV.
I am on a similar combo. Copegus, Ritonavir, the RO, and danoprevir. Started this past week. So far the only sides are mild itching ans fatigue. I
Yes, they do like to play the name change
RG7128/ Mericitabine is derived from PSI-6130, has been renamed, RO5024048.
I am on a trail with RG7128, danoprevir boosted with Ritonavir plus the SOC.
Anyone else trying this combination?
This is my 3rd try at treatment, I am genotype 1a, IL28B - CT
RG7128/ Mericitabine is derived from PSI-6130, has been renamed, RO5024048.
I am on a trail with RG7128, danoprevir boosted with Ritonavir plus the SOC.
Anyone else trying this combination?
This is my 3rd try at treatment, I am genotype 1a, IL28B - CT
You should see a dermatologist. This actually sounds like porphyria which can happen with HCV. There is a blood test for cryo.
http://clinicaltrials.gov/ct2/show/study/NCT01278134?intr=%22RO5024048%22&rank=7&show_locs=Y#locn
I wish they wouldn't keep changing the names of these drugs. R7128 is now RO5024048. Makes it so much harder to keep track.
dointime
I wish they wouldn't keep changing the names of these drugs. R7128 is now RO5024048. Makes it so much harder to keep track.
dointime
Hi, How do you know when you have cryoglobulinemia? I have recently broke out with blisters on my hands, could this be a sign. Is there a blood test I can ask for to test for this?
I am on a clinical trial with RG7128, danoprevir, pegasys and copegasys.
This is my 3rd try at treatment, I am genotype 1a, IL28B - CT.
I started with 12,000,000 was 109 by week 1 and UND end of 2nd week.
Anyone else on this quad treatment?
This is my 3rd try at treatment, I am genotype 1a, IL28B - CT.
I started with 12,000,000 was 109 by week 1 and UND end of 2nd week.
Anyone else on this quad treatment?
I had been wondering about what happened to the INFORM-1 pts for a while. Their fate came up again in the discussion of the EASL'11 Pharmasset new-miracle-in-town which echoed the INFORM-1 EASL'09 Inform-1 announcement.
The following quote from a recent review by Pockros seems to clear up the mystery:
"The promise of these agents will be realized when they are successfully combined with PIs or other DAAs to create an effective and safe interferon (IFN)-free regimen. This promise has been heightened with the results of the first study that combined a potent NPI and a potent PI, INFORM-1.[16] The trial demonstrated that both treatment-naı ̈ ve G1 and null nonresponder G1 patients were able to achieve viral load reductions less than LLOQ in 88% and 50% of cases, respectively, with only 2 weeks of this IFN-free combination. All patients were then placed on PegIFN/ribavirin therapy, so we must await the results of INFORM-2 (where patients will be left on this combination for 12–24 weeks) to determine if an SVR is possi- ble without the addition of PegIFN/ribavirin."
from
http://www.ncbi.nlm.nih.gov/pubmed/21319865
Since all patients were then switched to soc, Roche never bothered announcing the final results.
The following quote from a recent review by Pockros seems to clear up the mystery:
"The promise of these agents will be realized when they are successfully combined with PIs or other DAAs to create an effective and safe interferon (IFN)-free regimen. This promise has been heightened with the results of the first study that combined a potent NPI and a potent PI, INFORM-1.[16] The trial demonstrated that both treatment-naı ̈ ve G1 and null nonresponder G1 patients were able to achieve viral load reductions less than LLOQ in 88% and 50% of cases, respectively, with only 2 weeks of this IFN-free combination. All patients were then placed on PegIFN/ribavirin therapy, so we must await the results of INFORM-2 (where patients will be left on this combination for 12–24 weeks) to determine if an SVR is possi- ble without the addition of PegIFN/ribavirin."
from
http://www.ncbi.nlm.nih.gov/pubmed/21319865
Since all patients were then switched to soc, Roche never bothered announcing the final results.
Yes I read about it in the paper yesterday & again this morning it is very exciting stuff. I think the hospital clinic I go to is one of the ones doing the trials but I wasn't eligible because I have cryoglobulinemia.
Here's what I have read.
http://www.hep.org.au/index.php?article=latest-news
http://hepatitiscnewdrugs.blogspot.com/2011/03/rg7128-and-danoprevir-australians.html
Lee
I love Australia!!
Here's what I have read.
http://www.hep.org.au/index.php?article=latest-news
http://hepatitiscnewdrugs.blogspot.com/2011/03/rg7128-and-danoprevir-australians.html
Lee
I love Australia!!
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