Sunday, January 15, 2017

January 2017 Update - Recruiting and upcoming hepatitis C clinical trials

Recruiting and upcoming hepatitis C clinical trials

The clinical trials listed on this page can be found online at ClinicalTrials.gov. A Web site maintained by the National Library of Medicine (NLM) at the National Institutes of Health (NIH). This is not a complete list of clinical trials, to find out if a study is enrolling patients in your area please click here

For viral hepatitis clinical trials listed by state visit CenterWatch.
CenterWatch does not conduct clinical research. CenterWatch is a publishing company that posts clinical trials information on behalf of sponsor companies, contract research organizations, clinical research sites and other interested parties.

HCV Advocate
Users can search for a hepatitis C clinical trial by category (genotype), or learn how to evaluate a clinical trial and become familiar with commonly used terms. HCV Advocate offers an easy to navigate HCV Medications Blog as well, organized by HCV genotype.

On This Blog 
Click on the menu located across the top of the page to review research articles that correlate with the drugs used in the following clinical trials.

Sponsor:
This study is currently recruiting participants
United States, Texas, New Zealand
Efficacy and Safety of MK-3682 + Ruzasvir (MK-8408) in Treating Hepatitis C Virus Infection Genotypes 1-6 (MK-3682-041)
ClinicalTrials.gov Identifier:
NCT02956629
Purpose
This is a nonrandomized, multi-site, open-label trial to evaluate a novel two-drug combination regimen (MK-3682 450 mg + ruzasvir [RZR; MK-8408] 180 mg once daily [q.d.] for 12 weeks) in male and female treatment-naïve (TN) or treatment-experienced (TE) participants with chronic hepatitis C virus (HCV) infection genotype (GT) GT1, GT2, GT3, GT4, GT5, or GT6 who have not previously received HCV direct-acting antiviral (DAA) therapy. Cirrhotic (C) and non-cirrhotic (NC) participants with and without human immunodeficiency virus (HIV) co-infection will be enrolled.

Condition Intervention Phase
Hepatitis CDrug: MK-3682
Drug: Ruzasvir
Drug: Ribavirin
Phase 2
_________________________________________

Sponsor:
This study is currently recruiting participants
United States
Efficacy and Safety of MK-3682 With Ruzasvir (MK-8408) in Adults With Chronic Hepatitis C Genotype 1, 2, 3, 4, 5 or 6 Infection (MK-3682-035)
ClinicalTrials.gov Identifier:
NCT02759315
Purpose
The study is a single-center, multiple-arm investigation of co-administration of MK-3682 450 mg and Ruzasvir (MK-8408) 60 mg in participants with chronic Hepatitis C Virus (HCV) Genotype (GT)1, GT2, GT3, GT4, GT5, or GT6. The impact of the study treatment regimen on Sustained Virologic Response (SVR)12 (undetectable HCV ribonucleic acid [RNA] 12 weeks after ending study treatment) for each HCV Genotype will be evaluated in cirrhotic participants and non-cirrhotic participants.
Condition Intervention Phase
Hepatitis C, Chronic
Drug: MK-3682 450 mg
Drug: Ruzasvir 60 mg
_________________________________________

Collaborators:
Patient-Centered Outcomes Research Institute
Merck Sharp & Dohme Corp.
AbbVie
This study is currently recruiting participants
45 Study Locations United States
Study of Oral Treatments for Hepatitis C (PRIORITIZE)
ClinicalTrials.gov Identifier:
NCT02786537
Purpose
The study will compare the effectiveness of 3 approved HCV treatment regimens to learn whether they work equally well under real-world conditions. Patients receiving HCV therapy in community and academic clinics will be offered the opportunity to consent to be randomly assigned to one of three regimens and then observed for outcomes. Once randomized, all medical care, laboratory testing, and any disease or side effect management will be assumed by usual care conditions, and patient-reported outcomes will be collected outside clinic in keeping with pragmatic design principles.
Condition Intervention Phase
Chronic Hepatitis C
Drug: sofosbuvir/ledipasvir
Drug: ombitasvir/paritaprevir/ritonavir
Drug: elbasvir/grazoprevir
Drug: Dasabuvir
Phase 4
_________________________________________

Sponsor:
This study is currently recruiting participants
United States, Maryland
ClinicalTrials.gov Identifier:
NCT02468648

Condition Intervention Phase
Chronic Hepatitis CDrug: Sofosbuvir
Drug: GS-5816
_________________________________________

Sponsor:
This study is currently recruiting participants
Australia, New South Wales
A Phase II Trial of Sofosbuvir (SOF) and GS-5816 for People With Chronic Hepatitis C Virus Infection and Recent Injection Drug Use
ClinicalTrials.gov Identifier:
NCT02336139
Purpose
To evaluate the proportion of patients with undetectable HCV RNA at 12 weeks post end of treatment (SVR12) following sofosbuvir/GS-5816 therapy for 12 weeks in people with chronic HCV infection and recent injection drug use. 
Intervention Phase
Hepatitis C
Drug: Sofosbuvir (SOF)/GS-5816
Phase 2
_________________________________________

Sponsor:
Some locations recruiting participants
40 Study Locations China Malaysia Singapore Thailand Vietnam
Efficacy and Safety of Sofosbuvir/Velpatasvir Fixed Dose Combination for 12 Weeks in Participants With Chronic HCV
ClinicalTrials.gov Identifier:
NCT02671500
Purpose
This study will evaluate the efficacy, safety, and tolerability of treatment with sofosbuvir (SOF)/velpatasvir (VEL; GS-5816) fixed-dose combination (FDC) for 12 weeks in treatment-naive and treatment-experienced participants with chronic hepatitis C virus (HCV) infection.
Condition Intervention Phase
Hepatitis C Virus InfectionDrug: SOF/VELPhase 3
_________________________________________

Sponsor:
Collaborators:
Unity Health Care, Inc.
Gilead Sciences
This study is currently recruiting participants
United States, Maryland
Safety, Tolerability and Efficacy of Sofosbuvir, Velpatasvir, and GS-9857 in Subjects With Previous DAA Experience (RESOLVE)
ClinicalTrials.gov Identifier:
NCT02745535
Purpose
This study will evaluate the safety, tolerability, and efficacy of sofosbuvir/velpatasvir/GS-9857 (SOF/VEL/GS-9857) in adults with chronic hepatitis C infection who have failed to eradicate hepatitis C despite previous combination directly acting antiviral therapy.
Condition Intervention Phase
Chronic Hepatitis C
Drug: Sofosbuvir/Velpatasvir/GS-9857
Phase 2
_________________________________________

Sponsor:
Collaborator:
National Institute of Allergy and Infectious Diseases (NIAID)
This study is currently recruiting participants
United States
12 Weeks of Ledipasvir (LDV)/Sofosbuvir (SOF) With Weight-based Ribavirin vs. 24 Weeks of LDV/SOF
ClinicalTrials.gov Identifier:
NCT02605304
Purpose
People who are infected with Hepatitis C Virus (HCV) have a great chance of being cured of the infection when they are treated with sofosbuvir. However, in some instances, treatment with sofosbuvir-containing therapy does not work. It is not known if treating people with sofosbuvir again (retreatment) after it did not work the first time will work. There is an important need to understand retreatment options in those instances. This study is being done to see if two different regimens, ledipasvir with sofosbuvir and ribavirin for 12 weeks (Group A) and ledipasvir with sofosbuvir for 24 weeks (Group B) are well tolerated in HCV-infected persons where previous treatment with sofosbuvir failed. This study will also look at the safety of each regimen and how well the combination treatment of ledipasvir/sofosbuvir works in people who have cirrhosis (scarring of the liver) or HIV.
Condition Intervention Phase
HIV-1 Infection
Hepatitis C
Drug: Ledipasvir/sofosbuvir
Drug: Ribavirin
_________________________________________

Sponsor:
This study is currently recruiting participants
United States
LIVE-C-Free: Early and Late Treatment of Hepatitis C With Sofosbuvir/Ledipasvir in Liver Transplant Recipients
ClinicalTrials.gov Identifier:
NCT02631772
Purpose
The predominant remaining questions for post-transplant treatment of HCV in the DAA era are whether a ribavirin-free regimen is possible and whether pre-emptive treatment is now a potential option to prevent long-term damage to the allograft.

Our aim is to provide answers to these primary questions with our multicenter, prospective, randomized, open-label intent-to-treat phase IV study

Condition Intervention Phase
Hepatitis CDrug: Sofosbuvir/Ledipasvir x 8 weeks
Drug: Sofosbuvir/Ledipasvir x 12 weeks
Drug: Sofosbuvir/Ledipasvir + Ribavirin x 12 weeks
Phase 4
_________________________________________

Sponsor:
Most locations recruiting participants
51 Study Locations United States Australia Belgium India Italy New Zealand United KingdomSafety and Efficacy of Sofosbuvir + Ribavirin in Adolescents and Children With Genotype 2 or 3 Chronic HCV Infection
ClinicalTrials.gov Identifier:
NCT02175758
Purpose
This study will have two parts as follows:
The PK Lead-in Phase of the study will evaluate the steady state pharmacokinetics (PK) and confirm the dose of sofosbuvir (SOF) in hepatitis C virus (HCV)-infected pediatric participants. The PK Lead-in Phase will also evaluate the safety and tolerability of 7 days of dosing of SOF+ribavirin (RBV) in HCV-infected pediatric participants.
The Treatment Phase will be initiated by age cohort after confirmation of age-appropriate SOF dosage levels. Participants from the PK Lead-in Phase will immediately rollover into the Treatment Phase with no interruption of study drug administration. The Treatment Phase will evaluate the antiviral efficacy, safety, and tolerability of SOF+RBV for 12 or 24 weeks in pediatric participants with genotype 2 or 3 HCV infection, respectively. 
Condition Intervention Phase
Hepatitis C Virus Infection
Drug: SOF (oral tablets)
Drug: RBV
Drug: SOF (oral granules)
Phase 2
_________________________________________

Sponsor:
This study is currently recruiting participants
34 Study Locations United States United Kingdom New Zealand Australia United Kingdom
Safety and Efficacy of Ledipasvir/Sofosbuvir Fixed Dose Combination +/-Ribavirin in Adolescents and Children With Chronic HCV-Infection
ClinicalTrials.gov Identifier:
NCT02249182
Purpose
This study will have two parts as follows:
The PK Lead-in Phase of the study will evaluate the steady state pharmacokinetics (PK) and confirm the dose of ledipasvir/sofobuvir (LDV/SOF) fixed dose combination (FDC) in hepatitis C virus (HCV)-infected pediatric participants. The PK Lead-in Phase will also evaluate the safety, tolerability, and antiviral activity of 10 days of dosing of LDV/SOF FDC in HCV-infected pediatric participants.
The Treatment Phase will be initiated by age cohort after confirmation of age-appropriate LDV/SOF FDC dosage levels. Participants from the PK Lead-in Phase will immediately rollover into the Treatment Phase with no interruption of study drug administration. The Treatment Phase will evaluate the antiviral efficacy, safety, and tolerability of LDV/SOF FDC +/- Ribavirin (RBV) for 12 or 24 weeks in pediatric participants with HCV.
Condition Intervention Phase
Hepatitis C Virus Infection
Drug: LDV/SOF
Drug: Placebo to match LDV/SOF
Drug: RBV
Phase 2
_________________________________________

Sponsor:
This study is currently recruiting participants
United States, Nebraska
Determine the Efficacy and Safety of Harvoni in Genotype 1 Chronic Hepatitis c Infected People Who Are Alcoholics
ClinicalTrials.gov Identifier:
NCT02759861
Purpose
To determine the efficacy and safety of Harvoni in treatment-naïve alcoholic subjects with Genotype 1 HCV infection
Intervention Phase
Genotype 1 Hepatitis C Virus
Drug: harvoni
Phase 4
_________________________________________

Sponsor:
Collaborator:
AbbVie
This study is currently recruiting participants
United Kingdom, New Zealand, Australia
ClinicalTrials.gov Identifier:
NCT02634008
Purpose
An open label, multicentre, international pilot study of paritaprevir/ritonavir, ombitasvir, dasabuvir with or without ribavirin for people with recently acquired hepatitis C virus infection with or without HIV co-infection.

Condition Intervention Phase
Hepatitis C, AcuteDrug: Paritaprevir/ritonavir/ombitasvir
Drug: Dasabuvir
Drug: Ribavirin
Phase 4
_________________________________________

Sponsor:
This study is currently recruiting participants
33 Study Locations United States 
Evaluating the Safety and Effectiveness of Interferon-Free Treatment of Hepatitis C Virus Infection in HIV-Coinfected Adults on Antiretroviral Therapy
ClinicalTrials.gov Identifier:
NCT02194998
Purpose
HIV and hepatitis C virus (HCV) infection are diseases that share the same risk factors and routes of transmission. For this reason, many people infected with HIV are also infected with HCV. Interferon (IFN) is a drug used to treat HCV; however, in people coinfected with HIV and HCV, IFN treatment often does not work well and can cause unwanted side effects. The purpose of this study is to evaluate the safety, tolerability, and effectiveness of IFN-free HCV treatment in HIV/HCV coinfected adults who are taking antiretroviral (ARV) therapy.
Condition Intervention Phase
HIV Infections
Drug: Paritaprevir/ritonavir/ombitasvir (PTV/r/OBT)
Drug: Dasabuvir (DSV)
Drug: Ribavirin (RBV)
Phase 2
_________________________________________

Sponsor:
This study is currently recruiting participants
Australia, New South Wales
A Phase IV Trial of Paritaprevir/Ritonavir, Ombitasvir, Dasabuvir for Chronic Hepatitis C Genotype 1 Virus Infection
ClinicalTrials.gov Identifier:
NCT02498015
Purpose
A total of 100 people with chronic HCV and recent injection drug use or recipients of opioid substitution therapy will be enrolled in 5 countries and 21 study sites. Participants with genotype 1a infection or cirrhosis will receive 12 weeks of open-label paritaprevir/ritonavir/ombitasvir and dasabuvir ("3D"), and twice-daily ribavirin. Participants with genotype 1b infection without cirrhosis will receive 12 weeks of open-label "3D". The study consists of a screening phase (6 weeks), treatment phase (12 weeks) and follow-up phase (96 weeks) to evaluate treatment response and reinfection.
Condition Intervention Phase
Hepatitis C, Chronic
Drug: "3D" regimen
Drug: "3D" regimen with ribavirin
________________________________________

Sponsor:
This study is not yet open for participant recruitment
A Study of of Glecaprevir/Pibrentasvir in Adults With Chronic Hepatitis C Virus (HCV) Genotype 5 or 6 Infection
ClinicalTrials.gov Identifier:
NCT02966795
Purpose
A Phase 3b, open-label, multicenter study to evaluate the efficacy and safety of glecaprevir (ABT-493)/pibrentasvir (ABT-530) for an 8- or 12-week treatment duration in participants with chronic Hepatitis C Virus (HCV) genotype (GT) 5 or 6 infection, with or without compensated cirrhosis, who are either HCV treatment-naïve or treatment experienced with interferon (IFN) or pegylated interferon (pegIFN) with or without ribavirin (RBV) (defined as P/R treatment-experienced) or sofosbuvir (SOF) plus RBV with or without pegIFN (defined as SOF plus RBV treatment-experienced).

Condition Intervention Phase
Chronic Hepatitis C Virus (HCV) Genotype 5 or 6 InfectionDrug: Glecaprevir/PibrentasvirPhase 3
_________________________________________

Sponsor:
This study is currently recruiting participants
26 Study Locations United States Canada United Kingdom Switzerland Spain Puerto Rico Germany Belgium
A Study to Evaluate Treatment of Hepatitis C Virus Infection in Pediatric Subjects
ClinicalTrials.gov Identifier:
NCT02486406
Purpose
The purpose of this three part study is to evaluate the pharmacokinetics (Part 1), safety/efficacy (Part 2), and long-term follow-up (Part 3) of ombitasvir (OBV), paritaprevir (PTV), ritonavir (RTV) with or without dasabuvir (DSV) and with or without ribavirin (RBV) in pediatric subjects with genotype 1 or 4 chronic hepatitis C virus (HCV) infection.

Condition Intervention Phase
Chronic Hepatitis C InfectionDrug: ombitasvir
Drug: paritaprevir
Drug: ritonavir
Drug: dasabuvir
Drug: ribavirin
________________________________________

Sponsor:
This study is not yet open for participant recruitment
Purpose
This study is a phase IV, open-label, single arm, multicentre study whose aim is to assess whether interferon-free and ribavirin-free Direct Acting Antiviral (DAA) Hepatitis C Virus (HCV) therapy with grazoprevir/elbasvir, will be feasible for the treatment of People who inject drugs (PWID) with recent injecting drug use and chronic HCV genotype 1 or 4 infection.

Arms Assigned Interventions
Experimental: Grazoprevir/elbasvir
Grazoprevir/elbasvir (100mg/50mg) daily taken orally for 12 weeks.
Drug: Grazoprevir/elbasvir
Grazoprevir/elbasvir (100mg/50mg) once daily for 12 weeks.
Other Name: Zepatier
________________________________________

Sponsor:
This study is not yet open for participant recruitment
Efficacy of GZR/EBR in Early Chronic Hepatitis C in HIV/HCV Co-infected Patients
ClinicalTrials.gov Identifier:
NCT02897596
Purpose
Evaluate the efficacy of 12 or 8 weeks treatment with Grazoprevir/Elbasvir in Early Chronic Hepatitis C GT1,4 in HIV co-infected patients and evaluate the safety and tolerability of Grazoprevir + Elbasvir in HIV-HCV co-infected patients. 
Intervention Phase
Hepatitis C
HIV
Drug: Grazoprevir 100 mg/d 8 weeks
Drug: Elbasvir 50 mg/d 8 weeks
Drug: Grazoprevir 100 mg/d 12 weeks
Drug: Elbasvir 50 mg/d 12 weeks
_________________________________________

Sponsor:
Some locations - recruiting participants
Canada Singapore Spain Poland Germany Belgium
Efficacy and Safety of Combinations of AL-335, Odalasvir (ODV) and Simeprevir (SMV) in the Treatment of Chronic Hepatitis C Infection
ClinicalTrials.gov Identifier:
NCT02765490
Purpose
The purpose of this study is to evaluate the efficacy (proportion of subjects with SVR12), safety, tolerability and pharmacokinetics of an 8- and 6-week treatment regimen of AL-335, odalasvir (ODV) and simeprevir (SMV) in chronic HCV genotype 1, 2, 4, 5 or 6 infected subjects without cirrhosis. 
Condition Intervention Phase
Hepatitis C, Chronic
Drug: AL-335
Drug: Odalasvir
Drug: Simeprevir

This is not a complete list of clinical trials, to find out if a study is enrolling patients in your area please click here.
_________________________________________

Friday, January 13, 2017

Real-world use, effectiveness, safety of anti-viral treatment in chronic hepatitis C genotype 3

Original Article
Alimentary Pharmacology & Therapeutics
Early View, Version of Record online: 12 JAN 2017

Real-world use, effectiveness and safety of anti-viral treatment in chronic hepatitis C genotype 3 infection
Authors M. Cornberg, J. Petersen, A. Schober, S. Mauss, K. H. W. Böker, R. Link, R. Günther, Y. Serfert, H. Pfeiffer-Vornkahl, M. P. Manns, C. Sarrazin, D. Hüppe, T. Berg, C. Niederau
First published: 12 January 2017
Full publication history DOI: 10.1111/apt.13925

Summary
Background
Treatment of chronic hepatitis C genotype 3 (GT3) is more challenging compared with other genotypes. Since 2014, several new treatment regimens have been approved but sometimes based on limited data.

Aim
To validate the use, effectiveness and safety of anti-viral treatment in chronic hepatitis C genotype 3 infection under real-word conditions.

Methods
The German Hepatitis C-Registry is a large national non-interventional real-world study for patients with chronic hepatitis C. A total of 1322 GT3 patients were enrolled (211 untreated and 1111 treated patients).

Results
Between February 2014 and September 2015, five different treatment strategies have been used (PegIFN+RBV, PegIFN+RBV+SOF, SOF+RBV, DCV+SOF±RBV, LDV/SOF±RBV). Treatment uptake and use of treatment concepts changed markedly and rapidly during the study influenced by new approvals, guideline recommendations, and label updates. PegIFN-based therapies constantly declined while DCV-based therapies increased with one interruption after the approval of LDV/SOF, which was frequently used until new guidelines recommended not using this combination for GT3. Per-protocol SVR ranged from 80.9% in the PegIFN+RBV group to 96.1% in PegIFN+RBV+SOF treated patients. Treatment-experienced patients with cirrhosis showed a suboptimal SVR of 68% for SOF+RBV but a high SVR of 90–95% for DCV+SOF±RBV. The safety analysis showed more adverse events and a stronger decline of haemoglobin for RBV containing regimens.

Conclusions
Real-world data can validate the effectiveness and safety for treatment regimens that had previously been approved with limited data, in particular for specific subgroups of patients. The present study demonstrates how rapid new scientific data, new treatment guidelines, new drug approvals and label changes are implemented into routine clinical practice today.

Discussion Only
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Treatment of chronic hepatitis C has markedly been improved with the introduction of IFN-free DAA therapies in 2014. In contrast to genotype 1, there have still been more challenges for treatment of patients with GT3.[5] Several DAA had not been approved for GT3 and for several combinations, that is, PegIFN+RBV+SOF, DCV+SOF+RBV and LDV/SOF+RBV data had been limited.[8-10, 13] The present real-world study shows that the use of DAA combinations has significantly changed several times within a short period of 20 months. Despite the approval of SOF+RBV in January 2014, 22% of patients still received dual PegIFN+RBV in the first time period of the present study. More than 93% of patients treated with PegIFN+RBV at that time were therapy-naïve patients without cirrhosis. In fact, response-guided therapy with PegIFN+RBV for 16–24 weeks in therapy-naïve noncirrhotic patients was at that time a reasonable alternative compared to 24 weeks SOF+RBV in particular when considering costs.[14] The most frequently used regimen with >50% of all patients treated during the first 7 months after approval of SOF was 12 weeks PegIFN+RBV+SOF. Interestingly, this treatment showed numerically the best SVR among all regimens. Thus, the present real-world data confirms the efficacy of PegIFN+RBV+SOF reported in the BOSON phase III trial[15] and is in line with other recent real-world data.[16, 17] Based on our data, treatment with PegIFN+RBV+SOF for 12 weeks can achieve a PP SVR >95% in patients without cirrhosis and a SVR >85% in patients with cirrhosis. Thus, this combination is an effective option if other DAA are not available or not recommended due to economical considerations, which is the reality in many countries up to now, i.e. in Poland.[18] After the approval of DCV, the use of PegIFN-based therapies declined constantly in this German study probably also because the German Guidelines published in October 2014 recommended not to use IFN anymore.[19] Despite limited data for GT3, uptake for DCV-based therapies was fast and reached almost 50% in the 3 months period following EMA approval and more than 80% after the label update for noncirrhotic patients. More than 120 noncirrhotic patients have been treated with the recommended 12 weeks DCV+SOF regimen. The SVR of 93% was comparable to the result from the ALLY3 phase III trial.[11] However, 12 week DCV+SOF+RBV reached even 100% SVR in patients without cirrhosis. In general, RBV should be avoided if possible because it is associated with a higher frequency of AEs and anaemia as confirmed in this study. For GT3 it may, however, remain a cornerstone, if baseline NS5A resistant associated substitutions (RAS) are present[20] or patients have unfavourable baseline characteristic. This appears to be true even for the recently approved combination of velpatasvir and sofosbuvir (VEL/SOF), which has become another new standard therapy for GT3.[21, 22] The current EASL clinical practice guidelines recommend treating IFN treatment-experienced GT3 patients without cirrhosis with VEL/SOF or DCV+SOF plus RBV if baseline NS5A RAS testing is not available.[23] However, we have only observed a small (3%) but not significant difference between naïve and IFN treatment-experienced noncirrhotic patients who have been treated with 12 weeks DCV+SOF, but there may be a bias because physicians may have selected RBV or longer treatment durations for more difficult-to-treat patients. In fact, only 27% of all 12-week DCV+SOF treated patients were treatment-experienced but 42% of 12-week DCV+SOF+RBV treated patients.
Patients with well-compensated compensated cirrhosis achieved excellent SVR with 12 weeks DCV+SOF+RBV like in the ALLY3+ trial[24] although the number of cirrhotic patients treated with this regimen was small in the present registry. For patients with advanced cirrhosis, we suggest 24 weeks DCV+SOF with or without RBV; the SVR was nominally higher in the RBV containing cohort but the limitations of a non-interventional registry have to be considered before recommending to add RBV in all patients with advanced cirrhosis. However, addition of RBV with a rapid dose reduction in the case of AEs may be a reasonable approach.
Costs and availability will remain major factors for the decision between a one-pill-fits-all concept and an individualised approach.[25] However, economic considerations can be problematic if newly approved therapies are used too fast without robust data available. This had been the case for the use of LDV/SOF, which had a lower price, compared with the use of DCV+SOF. After the approval of LDV/SOF there was a rapid uptake in the real-world setting accounting for almost 30% of all GT3 therapies although the study data were based on limited phase II data showing a SVR between 64 and 100%.[13] However, not a single patient in recent studies received LDV/SOF+RBV for 24 weeks as recommended in the label. Our data show that treatment with LDV/SOF+RBV for just 12 weeks is suboptimal and only reaches the SVR seen with SOF/RBV. Our present data are similar to the data of the UK early access program (EAP), which showed a SVR of only 61% for 12 weeks LDV/SOF±RBV in patients with advanced cirrhosis.[26] Interestingly, sequence analysis of GT3-infected patients with failure to LDV/SOF-based therapy from a large European Resistance Databank showed no selection of NS5A RAS.[27] This indicates a low anti-viral activity of LDV against GT3 isolates. However, patients treated according to the label for 24 weeks with LDV/SOF+RBV showed a SVR >90% in difficult-to-treat patients, which may be explained by some additional efficacy of the administration of LDV, if given for a longer period despite a low anti-viral activity against GT3. Retrospectively, the label recommendation proved to be appropriate but a treatment period of 24 weeks with LDV/SOF+RBV may only be considered if no other NS5A inhibitor is available. One more interesting aspect of our data is that the use of LDV/SOF dramatically declined after the International Liver Congress of EASL in 2015 at which the UK EAP data and the new EASL guidelines recommended not to use LDV/SOF in GT3.[28] This clearly demonstrates the importance of scientific meetings and guidelines for the real-world setting and also shows how rapid such recommendations are implemented into clinical practice today.
One important aim of the real-world registry was to validate the data of treatment with SOF+RBV for 24 weeks, which became available as the first IFN-free therapy for GT3 after the approval of SOF in January 2014. However, SOF+RBV was only used in approximately one quarter of patients and this figure did not show dramatic changes over time. The uncertainty of data in difficult-to-treat patients and the high costs were probably main reasons for the hesitant use of SOF+RBV. In fact, our data confirm that the SVR is suboptimal for that regimen in IFN-experienced patients with cirrhosis. This observation was similar in other real-world studies.[16, 17] Thus, SOF+RBV should not be used if VEL/SOF or DCV+SOF are available.
The suboptimal effectiveness of SOF+RBV in difficult-to-treat patients and the lack of robust data for other therapies might be a reason why treatment has been delayed in GT3 patients more often when compared with GT1 patients in the present German cohort. The frequency of patients who were screened but not treated was higher for GT3 when compared with the non-GT3 cohort. In addition, GT3 patients were underrepresented in this study with around 15% of all HCV patients when compared with 28% seen in a former large German real-life registry.[29] Patients in the nontreated cohort were younger and more often treatment-naïve; they also had less frequently cirrhosis but more frequently had an opiate substitution therapy. These characteristics may have been reasons to delay treatment until more reliable data or better treatment options became available. Indeed, shortly after the GT3 12 week label update of DCV the frequency of nontreated patients dropped from 18% to 4%.
A strength of the present study is the fact that it included almost 200 sites with many of them treating <10 patients. Thus, the present registry reflects not a multicentre study of academic centres but a true real-world cohort covering more than 30% of all therapies initiated in Germany during that time period. The present study shares the limitations of all real-world studies with data not as complete and controlled when compared with phase II/III studies.
In conclusion, the present analysis shows that real-world data can validate the effectiveness and safety for treatment regimens that had previously been approved with limited data in particular for subgroups of patients. The present study also demonstrates how rapid new scientific data, new treatment guidelines, new drug approvals and label changes are implemented into routine clinical practice today.

http://onlinelibrary.wiley.com/doi/10.1111/apt.13925/full

Thursday, January 12, 2017

Antiviral Drug Prevents Recurrence of Hepatitis C in Liver Transplant Patients

Antiviral Drug Prevents Recurrence of Hepatitis C in Liver Transplant Patients
By Anna Williams on Jan 9, 2017

Patients with hepatitis C virus infection who received an antiviral drug around the time they underwent liver transplantation saw a high rate of sustained virologic response, according to a Northwestern Medicine phase II clinical trial. The finding suggests that the therapy might be an effective approach to preventing reinfection in such patients.

Josh Levitsky, MD, MS, professor of Medicine in the Division of Gastroenterology and Hepatology, was the corresponding author of the paper, published in the New England Journal of Medicine.

Infection with the blood-borne hepatitis C virus (HCV) can lead to severe liver damage. As such, HCV-associated cirrhosis is currently the leading indication for liver transplantation. But because almost all patients with the virus experience a recurrence of infection after they receive a transplant, there tend to be high rates of graft failure.

In the trial, patients with chronic HCV were given a single dose of the antiviral drug ledipasvir-sofosbuvir the day they arrived at the hospital for liver transplantation, and they continued to take the antiviral drug once per day for four weeks post-surgery.

At the end of the four weeks, 88 percent of the study participants achieved a sustained virologic response, meaning the virus had been eradicated from their blood.

While direct-acting antiviral agents such as ledipasvir-sofosbuvir have been shown to be effective in treating recurrent HCV infections, this is the first study to investigate how the drugs might prevent reinfection at the time of liver transplantation.

“Modifications of this approach might also be applicable to other transplant settings to prevent donor transmission of hepatitis C infection,” Levitsky said.

The study was supported by Gilead Sciences, which manufactures the drug. Levitsky has received speaking fees from Gilead.