- Email: [email protected]
Ledipasvir With or Without Ribavirin for 12 or 24 Weeks in Treatment-Naive Genotype 1 HCV-Infected Patients: The Phase 3 ION-1 Study
AGA Abstracts
secondary efficacy variables were colonic GC4 and GC48h, colonic filling at 6h (CF6), T1/ 2 of ascending colon (AC) emptying and bowel functions (analysis of variance, ANOVA, on ranks). Dunnett’s test compared each dose with placebo. A per protocol analysis (PPA) of time to first BM was assessed using a proportional hazards model. Results: There were 57 participants (56 female, 1 male; mean age 42.8±1.3y; mean BMI 25.3±0.5kg/m2) with baseline GE T1/2 of 125.0±4.3min (SEM) and GC24 of 1.83±0.05 respectively; 55 patients completed the study. YKP10811 was associated with accelerated GI transit (CF6), AC T1/ 2, and colonic transit at 4, 24, and 48h. PPA also showed overall acceleration of GE T1/2. YKP10811 was associated with accelerated time to pass BM after first dosing, and increased stool consistency over the 8-day treatment period. There were no deaths and no serious adverse events. Two subjects discontinued prematurely (1 on placebo, 1 on 20mg YKP10811). Conclusion: YKP10811 enhances GI and colonic transit and improves bowel functions, particularly stool consistency and time to first BM, during an 8-day treatment trial. Funding: Supported by a grant from SK Life Science. Tu2038 All Oral Fixed-dose Combination Sofosbuvir/Ledipasvir With or Without Ribavirin for 12 or 24 Weeks in Treatment-Naive Genotype 1 HCV-Infected Patients: The Phase 3 ION-1 Study Ira M. Jacobson, Patrick Marcellin, Alessandra Mangia, Paul Y. Kwo, Graham Foster, Maria Buti, Norbert Brau, Andrew J. Muir, Jenny C. Yang, Hongmei Mo, Xiao Ding, Phil Pang, William T. Symonds, John G. McHutchison, Stefan Zeuzem, Nezam H. Afdhal Background and Aims: The Phase 3 ION-1 study is evaluating whether the fixed-dose combination of sofosbuvir 400mg/ledipasvir 90mg (SOF/LDV) can effectively treat a population of treatment-naïve patients with genotype 1 HCV-infection and to determine if ribavirin (RBV) or longer treatment duration is required to achieve a high SVR rate. Methods: HCVinfected patients in the United States and Europe were randomized 1:1:1:1 to receive SOF/ LDV±RBV for 12 or 24 weeks. Randomization was stratified by HCV subtype and presence of cirrhosis. The primary endpoint was SVR12. Results: 865 patients were treated; baseline characteristics and SVR rates are shown in the table. In the 12-Week groups combined (n= 431), a total of 11 (2.5%) patients failed to achieve SVR, with only 1 patient that relapsed and 10 patients that were lost to follow-up. Efficacy from the 24 Week groups (n=434) will be presented. The most frequent AEs reported for SOF/LDV were headache (25%), fatigue (23%), and nausea (12%). Thirty-two patients (4%) had treatment-emergent SAEs. No patients receiving 12-Weeks of treatment and 10 patients receiving 24-Weeks of treatment, discontinued therapy due to an AE. No AE leading to discontinuation occurred in >1 patient. Hemoglobin <10 g/dL occurred in 8% of patients taking SOF/LDV+RBV and no patients taking SOF/LDV. No other significant laboratory abnormalities were observed. Conclusions: A single tablet regimen of sofosbuvir/ledipasvir administered once daily for 12 weeks is highly effective and well tolerated in treatment-naïve, genotype 1, HCV-infected patients, including those with cirrhosis. The addition of RBV did not enhance the SVR rate. Tu2039 TURQUOISE-II: SVR12 Rates of 92%-96% in 380 Hepatitis C Virus Genotype 1-Infected Adults with Compensated Cirrhosis Treated with ABT-450/r/ABT267 and ABT-333 plus Ribavirin (3D+RBV) Kris V. Kowdley, Fred Poordad, Roger Trinh, Christophe Hezode, Stefan Zeuzem, Kosh Agarwal, Mitchell L. Shiffman, Heiner Wedemeyer, Thomas Berg, Eric M. Yoshida, Xavier Forns, Sandra S. Lovell, Barbara DaSilva-Tillmann, Andrew L. Campbell, Thomas Podsadecki Background: ABT-450 is an HCV NS3/4A protease inhibitor (dosed with ritonavir 100mg, ABT-450/r) identified by AbbVie and Enanta. ABT-267 is an NS5A inhibitor, and ABT-333 is an NS5B RNA polymerase inhibitor. We report safety and efficacy of 3D+RBV in treatmentnaïve and treatment-experienced adults with HCV genotype 1 infection and compensated cirrhosis. Methods: In this open-label study, subjects with Child-Pugh A cirrhosis were randomized to receive 3D+RBV for 12 (Arm A) or 24 (Arm B) weeks, stratified by prior treatment experience and HCV subgenotype. Key eligibility criteria included: serum albumin ≥2.8 g/dL; total bilirubin <3 mg/dL; serum alpha-fetoprotein ≤100ng/mL; INR ≤2.3; and platelet count ≥60,000 cells/mL. Results: 380 subjects received 3D+RBV for 12 (Arm A, n= 208) or 24 (Arm B, n=172) weeks. All primary endpoints were achieved. SVR12 rates were 91.8% and 95.9% in Arms A and B (intent-to-treat, Table); the difference between treatment arms was not statistically significant. The 3 most common adverse events in Arms A and B were fatigue (32.7% and 46.5%), headache (27.9% and 30.8%) and nausea (17.8% and 20.3%). Discontinuations due to adverse events were noted in approximately 2% of subjects. Conclusions: In this first and to date, only, phase 3 study of an all-oral, interferon-free regimen exclusively in cirrhotic HCV genotype 1-infected patients, treatment with 3D+RBV resulted in high rates of SVR12 in both the 12- and 24-week treatment arms. The safety profile is consistent with results in non-cirrhotic populations using this regimen.
S-903
AGA Abstracts
secondary efficacy variables were colonic GC4 and GC48h, colonic filling at 6h (CF6), T1/ 2 of ascending colon (AC) emptying and bowel functions (analysis of variance, ANOVA, on ranks). Dunnett’s test compared each dose with placebo. A per protocol analysis (PPA) of time to first BM was assessed using a proportional hazards model. Results: There were 57 participants (56 female, 1 male; mean age 42.8±1.3y; mean BMI 25.3±0.5kg/m2) with baseline GE T1/2 of 125.0±4.3min (SEM) and GC24 of 1.83±0.05 respectively; 55 patients completed the study. YKP10811 was associated with accelerated GI transit (CF6), AC T1/ 2, and colonic transit at 4, 24, and 48h. PPA also showed overall acceleration of GE T1/2. YKP10811 was associated with accelerated time to pass BM after first dosing, and increased stool consistency over the 8-day treatment period. There were no deaths and no serious adverse events. Two subjects discontinued prematurely (1 on placebo, 1 on 20mg YKP10811). Conclusion: YKP10811 enhances GI and colonic transit and improves bowel functions, particularly stool consistency and time to first BM, during an 8-day treatment trial. Funding: Supported by a grant from SK Life Science. Tu2038 All Oral Fixed-dose Combination Sofosbuvir/Ledipasvir With or Without Ribavirin for 12 or 24 Weeks in Treatment-Naive Genotype 1 HCV-Infected Patients: The Phase 3 ION-1 Study Ira M. Jacobson, Patrick Marcellin, Alessandra Mangia, Paul Y. Kwo, Graham Foster, Maria Buti, Norbert Brau, Andrew J. Muir, Jenny C. Yang, Hongmei Mo, Xiao Ding, Phil Pang, William T. Symonds, John G. McHutchison, Stefan Zeuzem, Nezam H. Afdhal Background and Aims: The Phase 3 ION-1 study is evaluating whether the fixed-dose combination of sofosbuvir 400mg/ledipasvir 90mg (SOF/LDV) can effectively treat a population of treatment-naïve patients with genotype 1 HCV-infection and to determine if ribavirin (RBV) or longer treatment duration is required to achieve a high SVR rate. Methods: HCVinfected patients in the United States and Europe were randomized 1:1:1:1 to receive SOF/ LDV±RBV for 12 or 24 weeks. Randomization was stratified by HCV subtype and presence of cirrhosis. The primary endpoint was SVR12. Results: 865 patients were treated; baseline characteristics and SVR rates are shown in the table. In the 12-Week groups combined (n= 431), a total of 11 (2.5%) patients failed to achieve SVR, with only 1 patient that relapsed and 10 patients that were lost to follow-up. Efficacy from the 24 Week groups (n=434) will be presented. The most frequent AEs reported for SOF/LDV were headache (25%), fatigue (23%), and nausea (12%). Thirty-two patients (4%) had treatment-emergent SAEs. No patients receiving 12-Weeks of treatment and 10 patients receiving 24-Weeks of treatment, discontinued therapy due to an AE. No AE leading to discontinuation occurred in >1 patient. Hemoglobin <10 g/dL occurred in 8% of patients taking SOF/LDV+RBV and no patients taking SOF/LDV. No other significant laboratory abnormalities were observed. Conclusions: A single tablet regimen of sofosbuvir/ledipasvir administered once daily for 12 weeks is highly effective and well tolerated in treatment-naïve, genotype 1, HCV-infected patients, including those with cirrhosis. The addition of RBV did not enhance the SVR rate. Tu2039 TURQUOISE-II: SVR12 Rates of 92%-96% in 380 Hepatitis C Virus Genotype 1-Infected Adults with Compensated Cirrhosis Treated with ABT-450/r/ABT267 and ABT-333 plus Ribavirin (3D+RBV) Kris V. Kowdley, Fred Poordad, Roger Trinh, Christophe Hezode, Stefan Zeuzem, Kosh Agarwal, Mitchell L. Shiffman, Heiner Wedemeyer, Thomas Berg, Eric M. Yoshida, Xavier Forns, Sandra S. Lovell, Barbara DaSilva-Tillmann, Andrew L. Campbell, Thomas Podsadecki Background: ABT-450 is an HCV NS3/4A protease inhibitor (dosed with ritonavir 100mg, ABT-450/r) identified by AbbVie and Enanta. ABT-267 is an NS5A inhibitor, and ABT-333 is an NS5B RNA polymerase inhibitor. We report safety and efficacy of 3D+RBV in treatmentnaïve and treatment-experienced adults with HCV genotype 1 infection and compensated cirrhosis. Methods: In this open-label study, subjects with Child-Pugh A cirrhosis were randomized to receive 3D+RBV for 12 (Arm A) or 24 (Arm B) weeks, stratified by prior treatment experience and HCV subgenotype. Key eligibility criteria included: serum albumin ≥2.8 g/dL; total bilirubin <3 mg/dL; serum alpha-fetoprotein ≤100ng/mL; INR ≤2.3; and platelet count ≥60,000 cells/mL. Results: 380 subjects received 3D+RBV for 12 (Arm A, n= 208) or 24 (Arm B, n=172) weeks. All primary endpoints were achieved. SVR12 rates were 91.8% and 95.9% in Arms A and B (intent-to-treat, Table); the difference between treatment arms was not statistically significant. The 3 most common adverse events in Arms A and B were fatigue (32.7% and 46.5%), headache (27.9% and 30.8%) and nausea (17.8% and 20.3%). Discontinuations due to adverse events were noted in approximately 2% of subjects. Conclusions: In this first and to date, only, phase 3 study of an all-oral, interferon-free regimen exclusively in cirrhotic HCV genotype 1-infected patients, treatment with 3D+RBV resulted in high rates of SVR12 in both the 12- and 24-week treatment arms. The safety profile is consistent with results in non-cirrhotic populations using this regimen.
S-903
AGA Abstracts