Background and Aims:Ravidasvir(RDV)is a new generation pangenotypic hepatitis C virus(HCV)NS5A inhibitor,with high barrier to baseline resistance-associated species.This is the first phase 2/3 study conducted in China...Background and Aims:Ravidasvir(RDV)is a new generation pangenotypic hepatitis C virus(HCV)NS5A inhibitor,with high barrier to baseline resistance-associated species.This is the first phase 2/3 study conducted in China's Mainland confirming the efficacy and safety of RDV+ritonavir-boosted danoprevir+ribavirin for 12 weeks in treatment-naive noncirrhotic patients with genotype 1 infection in a large population.Methods:In this multicenter,randomized,doubleblinded,placebo-controlled phase 2/3 trial(NCT03362814),we enrolled 424 treatment-nafve,noncirrhotic adult HCV genotype 1 patients.All patients were randomized at 3∶1 ratio to receive a combination of RDV 200mg once daily plus ritonavir-boosted danoprevir 100mg/100mg twice daily and oral ribavirin 1000/1200mg/day(body weight<75/≥75 kg)(n=318)or placebo(n=106)for 12 weeks.The primary end-point was the rate of sustained virologic response 12 weeks after the end of treatment,and the safety was evaluated and compared between treatment and placebo groups.Results:The overall rate of sustained virological response at 12 weeks after treatment is 99%(306/309,95%,CI:97%-100%)under per protocol set analysis.All patients harboring baseline NS5A resistance-associated species in the treatment group(76/76,per protocol set)achieved sustained virological response at 12 weeks after treatment.No treatment-related serious adverse events were reported.Laboratory abnormalities showed mild or moderate severity(grade 1 and grade 2)in liver function tests.Conclusions:In treatment-na(i)ve,noncirrhotic HCV Chinese patients infected with HCV genotype 1,all-oral regimen of RDV+ritonavir-boosted danoprevir+ribavirin for 12 weeks was highly efficacious,safe,and well tolerated.展开更多
Background and aim:Real-world data on the effectiveness and safety of treatment with the direct-acting antiviral agent-based regimen are limited on the Chinese mainland.The aim of this study was to conduct a multicent...Background and aim:Real-world data on the effectiveness and safety of treatment with the direct-acting antiviral agent-based regimen are limited on the Chinese mainland.The aim of this study was to conduct a multicenter,prospective,real-world study of ombitasvir/paritaprevir/ritonavir(OBT/PTV/r)combined with dasabuvir(DSV)in hepatitis C virus(HCV)genotype 1b-infected non-cirrhotic or compensated cirrhotic Chinese adult patients.Materials and methods:Genotype 1b-infected patients were enrolled at eight sites in China.Patients received 25/150/100 mg of OBT/PTV/r once daily combined with 250 mg of DSV twice daily for 8 weeks or 12 weeks.Sustained virological response at 12 weeks post-treatment(SVR12)and the incidence of adverse events were assessed.We have also evaluated the effect of intensive questioning of patients who were overdue for SVR12 testing.Intention-to-treat(ITT)and modified ITT(mITT)populations were used in the analysis.Results:One hundred forty patients were included,among whom 90.0%(126/140)were newly diagnosed,9.3%(13/140)had compensated cirrhosis,92.9%(130/140)received 12 weeks of treatment,and 7.1%(10/140)received 8 weeks of treatment.In the mITT population,the virological response rate at week 4 was 96.4%(108/112),and at the end of treatment was 100%(102/102).Among these patients,139 patients completed 12 weeks of treatment,and 73 patients were followed-up.All followed-up patients achieved SVR12.There was no adverse event-related discontinuation.Serious adverse events during treatment were reported in two(1.4%)patients,and none were considered to be drug-related.Sixty-six(47.1%)patients did not return to receive the HCV RNA test at 12 weeks post-treatment.Conclusions:The rate of SVR12 was consistent with Phase III clinical studies.OBT/PTV/r combined with DSV showed effectiveness in Chinese adult patients,and both tolerability and safety profile were favorable.However,patient compliance should be further improved in the real world.展开更多
基金supported by the National Natural Science Foundation of China (U21A20119)the championship prize funded by Shenzhen Leaguer Co., Ltd.supported in part by the Fundamental Research Funds for the Central Universities。
基金Ascletis BioScience Co.,Ltd.provided financial support for this study
文摘Background and Aims:Ravidasvir(RDV)is a new generation pangenotypic hepatitis C virus(HCV)NS5A inhibitor,with high barrier to baseline resistance-associated species.This is the first phase 2/3 study conducted in China's Mainland confirming the efficacy and safety of RDV+ritonavir-boosted danoprevir+ribavirin for 12 weeks in treatment-naive noncirrhotic patients with genotype 1 infection in a large population.Methods:In this multicenter,randomized,doubleblinded,placebo-controlled phase 2/3 trial(NCT03362814),we enrolled 424 treatment-nafve,noncirrhotic adult HCV genotype 1 patients.All patients were randomized at 3∶1 ratio to receive a combination of RDV 200mg once daily plus ritonavir-boosted danoprevir 100mg/100mg twice daily and oral ribavirin 1000/1200mg/day(body weight<75/≥75 kg)(n=318)or placebo(n=106)for 12 weeks.The primary end-point was the rate of sustained virologic response 12 weeks after the end of treatment,and the safety was evaluated and compared between treatment and placebo groups.Results:The overall rate of sustained virological response at 12 weeks after treatment is 99%(306/309,95%,CI:97%-100%)under per protocol set analysis.All patients harboring baseline NS5A resistance-associated species in the treatment group(76/76,per protocol set)achieved sustained virological response at 12 weeks after treatment.No treatment-related serious adverse events were reported.Laboratory abnormalities showed mild or moderate severity(grade 1 and grade 2)in liver function tests.Conclusions:In treatment-na(i)ve,noncirrhotic HCV Chinese patients infected with HCV genotype 1,all-oral regimen of RDV+ritonavir-boosted danoprevir+ribavirin for 12 weeks was highly efficacious,safe,and well tolerated.
基金This work was supported by a grant for clinical investigation from Key Projects of Guangdong Science and Technology Plan of China(2014B020212025).
文摘Background and aim:Real-world data on the effectiveness and safety of treatment with the direct-acting antiviral agent-based regimen are limited on the Chinese mainland.The aim of this study was to conduct a multicenter,prospective,real-world study of ombitasvir/paritaprevir/ritonavir(OBT/PTV/r)combined with dasabuvir(DSV)in hepatitis C virus(HCV)genotype 1b-infected non-cirrhotic or compensated cirrhotic Chinese adult patients.Materials and methods:Genotype 1b-infected patients were enrolled at eight sites in China.Patients received 25/150/100 mg of OBT/PTV/r once daily combined with 250 mg of DSV twice daily for 8 weeks or 12 weeks.Sustained virological response at 12 weeks post-treatment(SVR12)and the incidence of adverse events were assessed.We have also evaluated the effect of intensive questioning of patients who were overdue for SVR12 testing.Intention-to-treat(ITT)and modified ITT(mITT)populations were used in the analysis.Results:One hundred forty patients were included,among whom 90.0%(126/140)were newly diagnosed,9.3%(13/140)had compensated cirrhosis,92.9%(130/140)received 12 weeks of treatment,and 7.1%(10/140)received 8 weeks of treatment.In the mITT population,the virological response rate at week 4 was 96.4%(108/112),and at the end of treatment was 100%(102/102).Among these patients,139 patients completed 12 weeks of treatment,and 73 patients were followed-up.All followed-up patients achieved SVR12.There was no adverse event-related discontinuation.Serious adverse events during treatment were reported in two(1.4%)patients,and none were considered to be drug-related.Sixty-six(47.1%)patients did not return to receive the HCV RNA test at 12 weeks post-treatment.Conclusions:The rate of SVR12 was consistent with Phase III clinical studies.OBT/PTV/r combined with DSV showed effectiveness in Chinese adult patients,and both tolerability and safety profile were favorable.However,patient compliance should be further improved in the real world.
