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 Aims:Tenofovir alafenamide(TAF)has similar efficacy to tenofovir disoproxil fumarate(TDF)but with improved renal and bone safety in chronic hepatitis B patients studied outside of China.We report 3-year...Background and Aims:Tenofovir alafenamide(TAF)has similar efficacy to tenofovir disoproxil fumarate(TDF)but with improved renal and bone safety in chronic hepatitis B patients studied outside of China.We report 3-year results from two phase 3 studies with TAF in China(Clinicaltrials.gov:NCT02836249 and NCT02836236).Methods:Chinese hepatitis B e antigen(HBeAg)-positive and-negative chronic hepatitis B patients with viremia and elevated alanine aminotransferase were randomized 2:1 to TAF or TDF treatment groups and treated in a double-blind fashion for 144 weeks(3 years).Efficacy responses were assessed by individual study while safety was assessed by a pooled analysis.Results:Of the 334 patients(180 HBeAg-positive and 154 HBeAg-negative)randomized and treated,baseline characteristics were similar between groups.The overall mean age was 38 years and 73%were male.The mean HBV DNA was 6.4 log10 IU/mL.The median alanine aminotransferase was 88 U/L,and 37%had a history of antiviral use.At week 144,the proportion with HBV DNA<29 IU/mL was similar among the two groups,with TAF at 83%vs.TDF at 79%,and TAF at 93%vs.TDF at 92%for the HBeAg-positive and-negative patients,respectively.In each study,higher proportions of TAF than TDF patients showed normalized alanine aminotransferase(via the American Association for the Study of Liver Diseases and the China criteria)and showed loss of HBsAg;meanwhile,the HBeAg seroconversion rates were similar.Treatment was well-tolerated among the TAF patients,who showed a smaller median decline in creatinine clearance(−0.4 vs.−3.2 mL/min;p=0.014)and less percentage change in bone mineral density vs.TDF at hip(−0.95%vs.−1.93%)and spine(+0.35%vs.−1.40%).Conclusions:In chronic hepatitis B patients from China,TAF treatment provided efficacy similar to TDF but with better renal and bone safety at 3 years.展开更多
Background and Aims:After 3-years(144 week)of double-blind treatment in Chinese chronic hepatitis B patients in two ongoing phase 3 studies,tenofovir alafenamide(TAF)showed similar efficacy to tenofovir disoproxil fum...Background and Aims:After 3-years(144 week)of double-blind treatment in Chinese chronic hepatitis B patients in two ongoing phase 3 studies,tenofovir alafenamide(TAF)showed similar efficacy to tenofovir disoproxil fumarate(TDF),with improved renal and bone safety.In this study,we aimed to report the 5-year results from 2 years into the open-label TAF treatment phase.Methods:All participants completing the 144-week double-blind treatment were eligible to receive open-label TAF 25 mg once daily up to week 384.Serial analysis of viral suppression(hepatitis B virus DNA<29 IU/mL),alanine aminotransferase normalization,serological responses,and safety outcomes at year 5(week 240)was performed.Results:The openlabel phase included 93%(311/334)of the enrolled participants,which included 212 who switched from double-blind TAF to open-label TAF(TAF-TAF)and 99 who switched from double-blind TDF to open-label TAF(TDF-TAF).Baseline characteristics were comparable.Week 240 viral suppression rates were similar between groups[93.4%vs.93.9%;difference:-1.5%,(95%CI:-6.4 to-3.5),p=0.857].Alanine aminotransferase normalization and serological response rates were higher in the TAF-TAF group than in the TDF-TAF group.The frequencies of adverse events and laboratory abnormalities were low and similar between groups.Both groups had similar small numerical declines from baseline in estimated glomerular filtration rate at year 5(week 240,-2.85 mL/min vs.-3.29 mL/min,p=0.910).The greater declines in renal and bone parameters in the TDF-TAF group through week 144 improved after switching to TAF.Conclusions:The 5-year TAF treatment efficacy was high and similar to that of 3-year TDF followed by 2-year TAF in Chinese chronic hepatitis B patients.Favorable effects on bone and renal parameters were sustained with TAF treatment alone and were observed following the switch from TDF to TAF.展开更多
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 study was sponsored by Gilead Sciences,Inc.
文摘Background and Aims:Tenofovir alafenamide(TAF)has similar efficacy to tenofovir disoproxil fumarate(TDF)but with improved renal and bone safety in chronic hepatitis B patients studied outside of China.We report 3-year results from two phase 3 studies with TAF in China(Clinicaltrials.gov:NCT02836249 and NCT02836236).Methods:Chinese hepatitis B e antigen(HBeAg)-positive and-negative chronic hepatitis B patients with viremia and elevated alanine aminotransferase were randomized 2:1 to TAF or TDF treatment groups and treated in a double-blind fashion for 144 weeks(3 years).Efficacy responses were assessed by individual study while safety was assessed by a pooled analysis.Results:Of the 334 patients(180 HBeAg-positive and 154 HBeAg-negative)randomized and treated,baseline characteristics were similar between groups.The overall mean age was 38 years and 73%were male.The mean HBV DNA was 6.4 log10 IU/mL.The median alanine aminotransferase was 88 U/L,and 37%had a history of antiviral use.At week 144,the proportion with HBV DNA<29 IU/mL was similar among the two groups,with TAF at 83%vs.TDF at 79%,and TAF at 93%vs.TDF at 92%for the HBeAg-positive and-negative patients,respectively.In each study,higher proportions of TAF than TDF patients showed normalized alanine aminotransferase(via the American Association for the Study of Liver Diseases and the China criteria)and showed loss of HBsAg;meanwhile,the HBeAg seroconversion rates were similar.Treatment was well-tolerated among the TAF patients,who showed a smaller median decline in creatinine clearance(−0.4 vs.−3.2 mL/min;p=0.014)and less percentage change in bone mineral density vs.TDF at hip(−0.95%vs.−1.93%)and spine(+0.35%vs.−1.40%).Conclusions:In chronic hepatitis B patients from China,TAF treatment provided efficacy similar to TDF but with better renal and bone safety at 3 years.
文摘Background and Aims:After 3-years(144 week)of double-blind treatment in Chinese chronic hepatitis B patients in two ongoing phase 3 studies,tenofovir alafenamide(TAF)showed similar efficacy to tenofovir disoproxil fumarate(TDF),with improved renal and bone safety.In this study,we aimed to report the 5-year results from 2 years into the open-label TAF treatment phase.Methods:All participants completing the 144-week double-blind treatment were eligible to receive open-label TAF 25 mg once daily up to week 384.Serial analysis of viral suppression(hepatitis B virus DNA<29 IU/mL),alanine aminotransferase normalization,serological responses,and safety outcomes at year 5(week 240)was performed.Results:The openlabel phase included 93%(311/334)of the enrolled participants,which included 212 who switched from double-blind TAF to open-label TAF(TAF-TAF)and 99 who switched from double-blind TDF to open-label TAF(TDF-TAF).Baseline characteristics were comparable.Week 240 viral suppression rates were similar between groups[93.4%vs.93.9%;difference:-1.5%,(95%CI:-6.4 to-3.5),p=0.857].Alanine aminotransferase normalization and serological response rates were higher in the TAF-TAF group than in the TDF-TAF group.The frequencies of adverse events and laboratory abnormalities were low and similar between groups.Both groups had similar small numerical declines from baseline in estimated glomerular filtration rate at year 5(week 240,-2.85 mL/min vs.-3.29 mL/min,p=0.910).The greater declines in renal and bone parameters in the TDF-TAF group through week 144 improved after switching to TAF.Conclusions:The 5-year TAF treatment efficacy was high and similar to that of 3-year TDF followed by 2-year TAF in Chinese chronic hepatitis B patients.Favorable effects on bone and renal parameters were sustained with TAF treatment alone and were observed following the switch from TDF to TAF.
