- Email: [email protected]
HCV-coinfected patients with and without portal hypertension
POSTERS HCV RNA was detectable in 8 patients with a median of 125 IU/mL. Despite having a significant decrease in cholesterol level from 143 to 123 mg/dL (p = 0.04) after 12 weeks of treatment, plasma viral load decreased only 0.3 log (p = 0.2) in plasma. Similarly, non-significant decreases in bile and stool viral load were found (see table).
Age, years, mean±SD Male gender, n (%) Cirrhosis, n (%) HCV genotype, n 1a / 1b / 3a Body weight, kg, mean±SD BMI, kg/m2 , mean±SD ALT, U/mL, mean±SD AST, U/mL, mean±SD Bilirubin, mg/dL, mean±SD Glucose, mg/dL, mean±SD Plasma total cholesterol, mg/dL, mean±SD Plasma LDL cholesterol, mg/dL, mean±SD Plasma HDL cholesterol, mg/dL, mean±SD Plasma triglycerides, mg/dL, mean±SD Plasma viral load, mean log IU/mL ±SD Bile viral load, mean log IU/mL ±SD Stool viral load, mean log IU/g ±SD
Baseline
12 weeks
p
62.6±7.7 5 (50%) 5 (50%) 1/8/1 66.97±15.3 24.52±2.69 86±68 78±67 1.0±0.75 99±19 143±36 64±25 54±15 86±44 5.93±1.39 1.84±1.81 1.71±1.02
− − − − 67.26±15.2 24.62±2.53 86±56 79±58 1.1±0.8 105±49 123±30 51±15 56±22 84±44 5.65±1.31 1.16±1.10 1.65±0.99
− − − − 0.39 0.41 0.99 0.89 0.70 0.58 0.04* 0.04* 0.59 0.82 0.23 0.12 0.87
Conclusions: Our results show that HCV RNA can be found and measured in bile and stools of infected patients. No significant changes in plasma, bile or stool viral load were demonstrated after ezetimibe treatment. The lack of response in humans, despite encouraging in vitro data, may be explained by a low expression level of NPC1L1 in the liver compared to the gut or by the lower exposure of liver NPC1L1 to ezetimibe in vivo. P0883 TREATMENT FOR HEPATITIS C VIRUS INFECTION AMONG PEOPLE WHO INJECT DRUGS IN THE OPIOID SUBSTITUTION SETTING: THE ETHOS STUDY M. Alavi1 , J. Grebely1 , M. Micallef1 , A. Dunlop2,3 , A. Balcomb4 , C. Day5,6 , C. Treloar7 , N. Bath8 , P. Haber5,9 , G. Dore1 . 1 Kirby Institute, UNSW Australia, Sydney, 2 University of Newcastle, 3 Drug and Alcohol Clinical Services, Hunter New England Local Health District, Newcastle, 4 Clinic 96, Kite St Community Health Centre, Orange, 5 Drug Health Service, Royal Prince Alfred Hospital, 6 Discipline of Addiction Medicine, Central Clinical School, University of Sydney, 7 Centre for Social Research in Health, UNSW Australia, 8 NSW Users and AIDS Association, Inc., 9 Sydney Medical School, University of Sydney, Sydney, Australia E-mail: [email protected] Background and Aims: Assessment and treatment for hepatitis C virus (HCV) among people who inject drugs (PWID) is low and strategies are needed to enhance access to care. This study aims to evaluate the effectiveness of HCV treatment among PWID. Methods: Enhancing Treatment for Hepatitis C in Opioid Substitution Settings (ETHOS) is a prospective observational cohort, evaluating a model for the provision of HCV assessment and treatment among people with a history of injecting drug use and chronic HCV. Recruitment occurred through six opioid substitution treatment (OST) clinics, two community health centres and one Aboriginal community controlled health organisation in NSW, Australia. Participants initiating pegylated interferon/ribavirin (PEG-IFN/RBV) treatment between February 2009 and December 2012 (genotype 1, G1) or June 2013 (genotypes 2 and 3, G2/3) were included, to allow for adequate post-treatment follow-up. Statistical analyses were performed using Chi-squared or Fisher’s exact tests, as appropriate. Results: Among 415 participants, 27% (n = 111) commenced treatment. Among those treated between 2009 and 2013 (n = 104, mean age 43 years, 77% male), 36% (n = 37) had injected drugs in the
past six months and 62% (n = 64) were currently receiving OST. In an intent-to-treat analysis, the sustained virological response (SVR) was 65% overall (68 of 104), 69% in G1 (20 of 29) and 64% in G2/3 (48 of 75). There was no difference in SVR between those never (74%, 23 of 31) and currently (66%, 42 of 64, P = 0.484) receiving OST. SVR was similar among those who had injecting drugs in the past six months (70%, 26/37) compared to those who had not (64%, 43/67, P = 0.665). Conclusions: Response to treatment in this population was high and active injecting drug use did not compromise treatment response. This data suggests that targeted initiatives to enhance HCV treatment in OST or community health clinics can be successful. P0884 INTERFERON AND RIBAVIRIN-FREE THERAPY WITH SOFOSBUVIR AND DACLATASVIR IN A REAL-LIFE COHORT OF DIFFICULT-TOTREAT HIV/HCV-COINFECTED PATIENTS WITH AND WITHOUT PORTAL HYPERTENSION M. Mandorfer1 , S. Steiner1 , P. Schwabl1 , M.C. Aichelburg2 , K. Grabmeier-Pfistershammer2 , A. Rieger2 , M. Trauner1 , T. Reiberger1 , M. Peck-Radosavljevic1 , on behalf of Vienna HIV & Liver Study Group. 1 Division of Gastroenterology and Hepatology, Department of Internal Medicine III, 2 Division of Immunology, Allergy and Infectious Diseases, Department of Dermatology, Medical University of Vienna, Vienna, Austria E-mail: [email protected] Background and Aims: Despite promising results for the combination of sofosbuvir and daclatasvir (SOF/DCV) in patients with HCV-monoinfection, there are currently no reports on its use in HIV/HCV-coinfected patients (HIV/HCV). The aim of our study was to investigate the use of SOF/DCV in HIV/HCV, who have an urgent need for effective treatment options. Methods: All patients were treated with once-daily SOF (400 mg) and DAC. The dose of DAC was adjusted to the cART regimen, as recommended by the European label. The following treatment durations will be applied: HCV-genotype (HCV-GT) 1/4 with previous HCV protease inhibitor (PI) failure or cirrhosis: 24 weeks; HCV-GT3: 24 weeks; all other patients: 12 weeks. HCV-RNA was assessed using the Abbott RealTime HCV assay with a lower limit of quantification (LLOQ) and detection of 12 IU/mL. Results: All of the 15 patients who have started SOF/DAC were on cART. Six (40%) patients were treatment experienced, including 2 (13%) patients with previous PI failure. The majority of patients had HCV-GT1a (10 [67%]), while HCV-GT3 and 4 were observed in 4 (27%) patients and 1 (7%) patient, respectively. Eleven (73%) patients had high baseline HCV-RNA levels (>600,000 IU/mL) and 14 (93%) patients had the IL28B non-C/C genotype. All patients had either F3 fibrosis (5 [33%]), cirrhosis (7 [47%]), or an extrahepatic manifestation of CHC (3 [20%]). These were cryoglobulinemia with leg ulcers, cryoglobulinemia with glomerulonephritis and end stage renal disease, as well as primary central nervous system lymphoma. The median liver stiffness was 10.2(12.7) kPa and the mean hepatic venous pressure gradient (HVPG) among patients with advanced fibrosis was 9.1±4.5 mmHg. Portal hypertension (HVPG ≥6 mmHg) and clinically significant portal hypertension (CSPH; HVPG ≥10 mmHg) were observed in 9 (60%) and 5 (33%) patients, respectively. At week 4, 1/5 patients had HCV-RNA
Journal of Hepatology 2015 vol. 62 | S263–S864
S673
POSTERS our thoroughly documented real-life cohort will provide important evidence for the use of SOF/DCV in this special population. P0885 MOST PATIENTS OF HEPATITIS C VIRUS INFECTION IN INDIA PRESENT LATE FOR ANTIVIRAL TREATMENT: AN EPIDEMIOLOGICAL STUDY FROM A NORTH INDIAN CENTER V. Gupta1 , A. Kumar1 , P. Sharma1 , A. Arora1 . 1 Department of gastroenterology and hepatology, Sir Ganga Ram Hospital, New Delhi, India E-mail: [email protected] Background and Aims: Antiviral therapy with Peg-interferon and Ribavirin is offered only to those patients of HCV who are in stage of chronic hepatitis or early cirrhosis. Patients of advanced liver disease do not tolerate this therapy. Since HCV is asymptomatic in early stages and usually presents with advanced disease, the eligibility for antiviral therapy is thus limited. There are no studies from India, which look into clinical spectrum of HCV infection at presentation, with reference to the eligibility and success of antiviral treatment. Our aim is to study the spectrum of presentation of HCV infection, determine their eligibility for antiviral treatment, and follow those treated for treatment response. Methods: The records of all consecutive patients of HCV, >14 years age, who presented to our department between 2010 and 2014, were analyzed for categorization into chronic hepatitis, cirrhosis and hepatocellular carcinoma; and to assess eligibility for antiviral treatment. Patients with detectable HCV RNA who have chronic hepatitis or Child A cirrhosis were considered eligible for antiviral treatment with Peg-Interferon and Ribavirin. Patients who received treatment were followed for sustained viral response. Results: A total of 777 patients (median age 49 [range 15–95] years, males 69%) presented during the study period with HCV. Cirrhosis was the most common presentation (56%) followed by chronic hepatitis (37%) and HCC (7%). Of patients who had cirrhosis (including those with HCC) 36% had Child A cirrhosis; 51% had Child B cirrhosis and 14% had Child C cirrhosis. Out of all the 777 HCV patients only 347 (45%) were eligible for antiviral treatment. Among the remaining 430 patients, in 326 (76%) the disease was far too advanced to offer any antiviral treatment. Of patients eligible for antiviral treatment only 54% (189/347) actually received antiviral treatment and 81% (153/189) patients could complete the antiviral course. Of them 70% (107/153) only could achieve the SVR (Figure 1). Conclusions: Most patients of HCV infection in India present late and only about 45% are eligible for antiviral treatment with Peginterferon and Ribavirin. At presentation 56% patients already have cirrhosis and 7% have HCC. Since HCV is usually asymptomatic at treatable stage, awareness about screening should be increased so that more patients are diagnosed at treatable stage.
P0886 EFFICACY AND SAFETY OF GRAZOPREVIR/ELBASVIR +/− RBV FOR 12 WEEKS IN PATIENTS WITH HCV G1 OR G4 INFECTION WHO PREVIOUSLY FAILED PEGINTERFERON/RBV: C-EDGE TREATMENT-EXPERIENCED TRIAL P. Kwo1 , E. Gane2 , C.-Y. Peng3 , B. Pearlman4 , J. Vireling5 , L. Serfaty6,7,8 , M. Buti9 , S. Shafran10 , P. Stryszak11 , L. Lin11 , J. Gress11 , M. Robertson11 , J. Wahl11 , E. Barr11 , B. Haber11 . 1 Indiana University, Indianapolis, 2 Auckland Clinical Studies, Auckland, United States; 3 China Medical University Hospital, Taichung, Taiwan; 4 Center for Hepatitis C, Atlanta Medical Center, Atlanta, 5 Baylor College of Medicine, Baylor-St. Luke’s Medical Center, Houston, United States; 6 Service d’H´epatologie, Hˆ opital Saint-Antoine, 7 APHP, 8 UPMC, Paris, France; 9 Hospital General Universitari Vall d’Hebron, Barcelona, Spain; 10 University of Alberta, Alberta, Canada; 11 Merck & Co. Inc., Whitehouse Station, United States E-mail: [email protected] Background and Aims: Efficacious, well-tolerated, interferon/ribavirin (RBV)-free, short-duration regimens are desirable for HCV-infected patients who failed prior therapy. In the Phase 2 C-WORTHY study, 12- or 18-weeks’ dosing of once daily grazoprevir (GZR) 100 mg + elbasvir (EBR) 50 mg, ± twice-daily RBV, resulted in SVR12 in >90% of cirrhotic HCV genotype (GT) 1-infected patients with prior null response to peginterferon/RBV (PR). The Phase 3 C-EDGE Treatment-Experienced (TE) study is evaluating the efficacy and safety of once-daily, GZR/EBR 100 mg/50 mg fixeddose combination (FDC) tablet, ± twice-daily RBV, for 12 or 16 weeks in cirrhotic or non-cirrhotic HCV GT1-, 4-, or 6-infected patients who have failed prior PR therapy. Methods: This trial enrolled cirrhotic and non-cirrhotic HCV GT1-, 4-, or 6-infected patients who failed prior PR therapy. HIV coinfected patients were not excluded. Patients were randomized in a 1:1:1:1 ratio to receive GZR/EBR QD for 12 or 16 weeks, ± twice-daily RBV. Arms were stratified for cirrhosis status and prior PR treatment response. HCV RNA was assessed using COBAS TaqMan v2.0 (LLoQ 15 IU/mL). The primary endpoint was HCV RNA <15 IU/mL 12 weeks after end of treatment (SVR12). Table: SVR4 by patient characteristics
SVR4, n/N (%) Overall GT1a GT1b (or other than GT1a) GT4 Null responder Partial responder or Relapse HIV/HCV Cirrhosis Virologic failure Breakthrough Relapse Discontinued Total Of which due to AE a b
GZR/EBR for 12 weeks (N = 105)
GZR/EBR + RBV for 12 weeks (N = 104)
100/105 (95%) 55/58 (95%) 38/38 (100%) 7 a /9 (78%) 42/45 (93%) 59/60 (98%) 6/6 (100%) 34/37 (92%)
102/104 (98%) 54/56 (96%) 33/33 (100%) 15/15 (100%) 42/44 (95%) 60/60 (100%) 5/5 (100%) 35/36 (97%)
0 4
0 2
2 a,b 1
0 0
Death – Cirrhotic, GT4-infected subject died of lymphoma. Discontinued study med at week 6 due to mood lability: achieved SVR4.
Results: This study is fully enrolled; complete SVR12 data from the 12 week arms will be available at the ILC meeting. Of 209 patients enrolled in the 12-week arms; 66% were male, 34% were cirrhotic, 5% were HIV co-infected, 23% were Black, and 9% were Hispanic. No GT6-infected patient were randomized to 12 weeks treatment. Mean viral load at baseline was 6.3log10 IU/mL. Previous response to PR: relapse in 35%, partial response in 22% or null response in 43%. All patients in 12-week arms have completed 4 S674
Journal of Hepatology 2015 vol. 62 | S263–S864
Age, years, mean±SD Male gender, n (%) Cirrhosis, n (%) HCV genotype, n 1a / 1b / 3a Body weight, kg, mean±SD BMI, kg/m2 , mean±SD ALT, U/mL, mean±SD AST, U/mL, mean±SD Bilirubin, mg/dL, mean±SD Glucose, mg/dL, mean±SD Plasma total cholesterol, mg/dL, mean±SD Plasma LDL cholesterol, mg/dL, mean±SD Plasma HDL cholesterol, mg/dL, mean±SD Plasma triglycerides, mg/dL, mean±SD Plasma viral load, mean log IU/mL ±SD Bile viral load, mean log IU/mL ±SD Stool viral load, mean log IU/g ±SD
Baseline
12 weeks
p
62.6±7.7 5 (50%) 5 (50%) 1/8/1 66.97±15.3 24.52±2.69 86±68 78±67 1.0±0.75 99±19 143±36 64±25 54±15 86±44 5.93±1.39 1.84±1.81 1.71±1.02
− − − − 67.26±15.2 24.62±2.53 86±56 79±58 1.1±0.8 105±49 123±30 51±15 56±22 84±44 5.65±1.31 1.16±1.10 1.65±0.99
− − − − 0.39 0.41 0.99 0.89 0.70 0.58 0.04* 0.04* 0.59 0.82 0.23 0.12 0.87
Conclusions: Our results show that HCV RNA can be found and measured in bile and stools of infected patients. No significant changes in plasma, bile or stool viral load were demonstrated after ezetimibe treatment. The lack of response in humans, despite encouraging in vitro data, may be explained by a low expression level of NPC1L1 in the liver compared to the gut or by the lower exposure of liver NPC1L1 to ezetimibe in vivo. P0883 TREATMENT FOR HEPATITIS C VIRUS INFECTION AMONG PEOPLE WHO INJECT DRUGS IN THE OPIOID SUBSTITUTION SETTING: THE ETHOS STUDY M. Alavi1 , J. Grebely1 , M. Micallef1 , A. Dunlop2,3 , A. Balcomb4 , C. Day5,6 , C. Treloar7 , N. Bath8 , P. Haber5,9 , G. Dore1 . 1 Kirby Institute, UNSW Australia, Sydney, 2 University of Newcastle, 3 Drug and Alcohol Clinical Services, Hunter New England Local Health District, Newcastle, 4 Clinic 96, Kite St Community Health Centre, Orange, 5 Drug Health Service, Royal Prince Alfred Hospital, 6 Discipline of Addiction Medicine, Central Clinical School, University of Sydney, 7 Centre for Social Research in Health, UNSW Australia, 8 NSW Users and AIDS Association, Inc., 9 Sydney Medical School, University of Sydney, Sydney, Australia E-mail: [email protected] Background and Aims: Assessment and treatment for hepatitis C virus (HCV) among people who inject drugs (PWID) is low and strategies are needed to enhance access to care. This study aims to evaluate the effectiveness of HCV treatment among PWID. Methods: Enhancing Treatment for Hepatitis C in Opioid Substitution Settings (ETHOS) is a prospective observational cohort, evaluating a model for the provision of HCV assessment and treatment among people with a history of injecting drug use and chronic HCV. Recruitment occurred through six opioid substitution treatment (OST) clinics, two community health centres and one Aboriginal community controlled health organisation in NSW, Australia. Participants initiating pegylated interferon/ribavirin (PEG-IFN/RBV) treatment between February 2009 and December 2012 (genotype 1, G1) or June 2013 (genotypes 2 and 3, G2/3) were included, to allow for adequate post-treatment follow-up. Statistical analyses were performed using Chi-squared or Fisher’s exact tests, as appropriate. Results: Among 415 participants, 27% (n = 111) commenced treatment. Among those treated between 2009 and 2013 (n = 104, mean age 43 years, 77% male), 36% (n = 37) had injected drugs in the
past six months and 62% (n = 64) were currently receiving OST. In an intent-to-treat analysis, the sustained virological response (SVR) was 65% overall (68 of 104), 69% in G1 (20 of 29) and 64% in G2/3 (48 of 75). There was no difference in SVR between those never (74%, 23 of 31) and currently (66%, 42 of 64, P = 0.484) receiving OST. SVR was similar among those who had injecting drugs in the past six months (70%, 26/37) compared to those who had not (64%, 43/67, P = 0.665). Conclusions: Response to treatment in this population was high and active injecting drug use did not compromise treatment response. This data suggests that targeted initiatives to enhance HCV treatment in OST or community health clinics can be successful. P0884 INTERFERON AND RIBAVIRIN-FREE THERAPY WITH SOFOSBUVIR AND DACLATASVIR IN A REAL-LIFE COHORT OF DIFFICULT-TOTREAT HIV/HCV-COINFECTED PATIENTS WITH AND WITHOUT PORTAL HYPERTENSION M. Mandorfer1 , S. Steiner1 , P. Schwabl1 , M.C. Aichelburg2 , K. Grabmeier-Pfistershammer2 , A. Rieger2 , M. Trauner1 , T. Reiberger1 , M. Peck-Radosavljevic1 , on behalf of Vienna HIV & Liver Study Group. 1 Division of Gastroenterology and Hepatology, Department of Internal Medicine III, 2 Division of Immunology, Allergy and Infectious Diseases, Department of Dermatology, Medical University of Vienna, Vienna, Austria E-mail: [email protected] Background and Aims: Despite promising results for the combination of sofosbuvir and daclatasvir (SOF/DCV) in patients with HCV-monoinfection, there are currently no reports on its use in HIV/HCV-coinfected patients (HIV/HCV). The aim of our study was to investigate the use of SOF/DCV in HIV/HCV, who have an urgent need for effective treatment options. Methods: All patients were treated with once-daily SOF (400 mg) and DAC. The dose of DAC was adjusted to the cART regimen, as recommended by the European label. The following treatment durations will be applied: HCV-genotype (HCV-GT) 1/4 with previous HCV protease inhibitor (PI) failure or cirrhosis: 24 weeks; HCV-GT3: 24 weeks; all other patients: 12 weeks. HCV-RNA was assessed using the Abbott RealTime HCV assay with a lower limit of quantification (LLOQ) and detection of 12 IU/mL. Results: All of the 15 patients who have started SOF/DAC were on cART. Six (40%) patients were treatment experienced, including 2 (13%) patients with previous PI failure. The majority of patients had HCV-GT1a (10 [67%]), while HCV-GT3 and 4 were observed in 4 (27%) patients and 1 (7%) patient, respectively. Eleven (73%) patients had high baseline HCV-RNA levels (>600,000 IU/mL) and 14 (93%) patients had the IL28B non-C/C genotype. All patients had either F3 fibrosis (5 [33%]), cirrhosis (7 [47%]), or an extrahepatic manifestation of CHC (3 [20%]). These were cryoglobulinemia with leg ulcers, cryoglobulinemia with glomerulonephritis and end stage renal disease, as well as primary central nervous system lymphoma. The median liver stiffness was 10.2(12.7) kPa and the mean hepatic venous pressure gradient (HVPG) among patients with advanced fibrosis was 9.1±4.5 mmHg. Portal hypertension (HVPG ≥6 mmHg) and clinically significant portal hypertension (CSPH; HVPG ≥10 mmHg) were observed in 9 (60%) and 5 (33%) patients, respectively. At week 4, 1/5 patients had HCV-RNA
Journal of Hepatology 2015 vol. 62 | S263–S864
S673
POSTERS our thoroughly documented real-life cohort will provide important evidence for the use of SOF/DCV in this special population. P0885 MOST PATIENTS OF HEPATITIS C VIRUS INFECTION IN INDIA PRESENT LATE FOR ANTIVIRAL TREATMENT: AN EPIDEMIOLOGICAL STUDY FROM A NORTH INDIAN CENTER V. Gupta1 , A. Kumar1 , P. Sharma1 , A. Arora1 . 1 Department of gastroenterology and hepatology, Sir Ganga Ram Hospital, New Delhi, India E-mail: [email protected] Background and Aims: Antiviral therapy with Peg-interferon and Ribavirin is offered only to those patients of HCV who are in stage of chronic hepatitis or early cirrhosis. Patients of advanced liver disease do not tolerate this therapy. Since HCV is asymptomatic in early stages and usually presents with advanced disease, the eligibility for antiviral therapy is thus limited. There are no studies from India, which look into clinical spectrum of HCV infection at presentation, with reference to the eligibility and success of antiviral treatment. Our aim is to study the spectrum of presentation of HCV infection, determine their eligibility for antiviral treatment, and follow those treated for treatment response. Methods: The records of all consecutive patients of HCV, >14 years age, who presented to our department between 2010 and 2014, were analyzed for categorization into chronic hepatitis, cirrhosis and hepatocellular carcinoma; and to assess eligibility for antiviral treatment. Patients with detectable HCV RNA who have chronic hepatitis or Child A cirrhosis were considered eligible for antiviral treatment with Peg-Interferon and Ribavirin. Patients who received treatment were followed for sustained viral response. Results: A total of 777 patients (median age 49 [range 15–95] years, males 69%) presented during the study period with HCV. Cirrhosis was the most common presentation (56%) followed by chronic hepatitis (37%) and HCC (7%). Of patients who had cirrhosis (including those with HCC) 36% had Child A cirrhosis; 51% had Child B cirrhosis and 14% had Child C cirrhosis. Out of all the 777 HCV patients only 347 (45%) were eligible for antiviral treatment. Among the remaining 430 patients, in 326 (76%) the disease was far too advanced to offer any antiviral treatment. Of patients eligible for antiviral treatment only 54% (189/347) actually received antiviral treatment and 81% (153/189) patients could complete the antiviral course. Of them 70% (107/153) only could achieve the SVR (Figure 1). Conclusions: Most patients of HCV infection in India present late and only about 45% are eligible for antiviral treatment with Peginterferon and Ribavirin. At presentation 56% patients already have cirrhosis and 7% have HCC. Since HCV is usually asymptomatic at treatable stage, awareness about screening should be increased so that more patients are diagnosed at treatable stage.
P0886 EFFICACY AND SAFETY OF GRAZOPREVIR/ELBASVIR +/− RBV FOR 12 WEEKS IN PATIENTS WITH HCV G1 OR G4 INFECTION WHO PREVIOUSLY FAILED PEGINTERFERON/RBV: C-EDGE TREATMENT-EXPERIENCED TRIAL P. Kwo1 , E. Gane2 , C.-Y. Peng3 , B. Pearlman4 , J. Vireling5 , L. Serfaty6,7,8 , M. Buti9 , S. Shafran10 , P. Stryszak11 , L. Lin11 , J. Gress11 , M. Robertson11 , J. Wahl11 , E. Barr11 , B. Haber11 . 1 Indiana University, Indianapolis, 2 Auckland Clinical Studies, Auckland, United States; 3 China Medical University Hospital, Taichung, Taiwan; 4 Center for Hepatitis C, Atlanta Medical Center, Atlanta, 5 Baylor College of Medicine, Baylor-St. Luke’s Medical Center, Houston, United States; 6 Service d’H´epatologie, Hˆ opital Saint-Antoine, 7 APHP, 8 UPMC, Paris, France; 9 Hospital General Universitari Vall d’Hebron, Barcelona, Spain; 10 University of Alberta, Alberta, Canada; 11 Merck & Co. Inc., Whitehouse Station, United States E-mail: [email protected] Background and Aims: Efficacious, well-tolerated, interferon/ribavirin (RBV)-free, short-duration regimens are desirable for HCV-infected patients who failed prior therapy. In the Phase 2 C-WORTHY study, 12- or 18-weeks’ dosing of once daily grazoprevir (GZR) 100 mg + elbasvir (EBR) 50 mg, ± twice-daily RBV, resulted in SVR12 in >90% of cirrhotic HCV genotype (GT) 1-infected patients with prior null response to peginterferon/RBV (PR). The Phase 3 C-EDGE Treatment-Experienced (TE) study is evaluating the efficacy and safety of once-daily, GZR/EBR 100 mg/50 mg fixeddose combination (FDC) tablet, ± twice-daily RBV, for 12 or 16 weeks in cirrhotic or non-cirrhotic HCV GT1-, 4-, or 6-infected patients who have failed prior PR therapy. Methods: This trial enrolled cirrhotic and non-cirrhotic HCV GT1-, 4-, or 6-infected patients who failed prior PR therapy. HIV coinfected patients were not excluded. Patients were randomized in a 1:1:1:1 ratio to receive GZR/EBR QD for 12 or 16 weeks, ± twice-daily RBV. Arms were stratified for cirrhosis status and prior PR treatment response. HCV RNA was assessed using COBAS TaqMan v2.0 (LLoQ 15 IU/mL). The primary endpoint was HCV RNA <15 IU/mL 12 weeks after end of treatment (SVR12). Table: SVR4 by patient characteristics
SVR4, n/N (%) Overall GT1a GT1b (or other than GT1a) GT4 Null responder Partial responder or Relapse HIV/HCV Cirrhosis Virologic failure Breakthrough Relapse Discontinued Total Of which due to AE a b
GZR/EBR for 12 weeks (N = 105)
GZR/EBR + RBV for 12 weeks (N = 104)
100/105 (95%) 55/58 (95%) 38/38 (100%) 7 a /9 (78%) 42/45 (93%) 59/60 (98%) 6/6 (100%) 34/37 (92%)
102/104 (98%) 54/56 (96%) 33/33 (100%) 15/15 (100%) 42/44 (95%) 60/60 (100%) 5/5 (100%) 35/36 (97%)
0 4
0 2
2 a,b 1
0 0
Death – Cirrhotic, GT4-infected subject died of lymphoma. Discontinued study med at week 6 due to mood lability: achieved SVR4.
Results: This study is fully enrolled; complete SVR12 data from the 12 week arms will be available at the ILC meeting. Of 209 patients enrolled in the 12-week arms; 66% were male, 34% were cirrhotic, 5% were HIV co-infected, 23% were Black, and 9% were Hispanic. No GT6-infected patient were randomized to 12 weeks treatment. Mean viral load at baseline was 6.3log10 IU/mL. Previous response to PR: relapse in 35%, partial response in 22% or null response in 43%. All patients in 12-week arms have completed 4 S674
Journal of Hepatology 2015 vol. 62 | S263–S864