Dataset Information

Efficacy and safety of elbasvir/grazoprevir in treatment-naive Chinese adults with hepatitis C virus infection: A randomized trial.

ABSTRACT:

Background and aim

In China, clinical experience with direct-acting antiviral treatments for hepatitis C virus (HCV) infection is still emerging. C-CORAL is a phase 3, multinational, placebo-controlled, double-blind trial of elbasvir/grazoprevir (EBR/GZR) in participants with HCV infection from the Asia-Pacific region and Russia. Here, we report the data from participants enrolled in China.

Methods

Treatment-naive participants with chronic HCV genotype (GT) 1, GT4, or GT6 infection were randomly assigned to receive 50?mg EBR/100?mg GZR for 12?weeks (immediate-treatment group, ITG) or placebo followed by deferred treatment with EBR/GZR (deferred-treatment group, DTG). The primary efficacy end-point was sustained virologic response at 12?weeks after completing treatment (SVR12), and the primary safety end-point was a comparison of safety between participants receiving EBR/GZR and placebo (NCT02251990; Protocol PN-5172-067).

Results

A total of 152 participants in China were randomly assigned (ITG, n = 115; DTG, n = 37). SVR12 was achieved in 96.7% (146/151) participants overall and in 97.3% (142/146) of those with GT1b infection. Four participants relapsed (GT1b, n = 3; GT6a, n = 1). Drug-related AEs were reported in 25 (21.7%) and 9 (24.3%) participants receiving EBR/GZR and placebo, respectively; no drug-related serious adverse events (AEs) occurred. Two (1.7%) participants receiving EBR/GZR had late hepatic transaminase elevations. Patient-reported outcomes indicate improved quality of life at follow-up week 4 in participants receiving EBR/GZR compared to placebo.

Conclusion

EBR/GZR administered for 12?weeks represents a highly effective and safe treatment option for Chinese individuals with HCV GT1 infection.

SUBMITTER: Wei L

PROVIDER: S-EPMC7731814 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Publications

Efficacy and safety of elbasvir/grazoprevir in treatment-naive Chinese adults with hepatitis C virus infection: A randomized trial.

Wei Lai L Jia Ji Dong JD Duan Zhong Ping ZP Wang Fu Sheng FS Niu Jun Qi JQ Xie Wen W Huang Wen Xiang WX Zhang Ming Xiang MX Huang Yan Y Wang Mao Rong MR Wu Shan Ming SM Zhao Ying Ren YR Jia Zhan Sheng ZS Zhao Xu Min XM Mu Sheng Mei SM Liang Li Wen LW Wang Zaiqi Z Puenpatom Amy A Hwang Peggy P Robertson Michael N MN Ingravallo Paul P Asante-Appiah Ernest E Wei Bo B Evans Barbara B Hanna George J GJ Talwani Rohit R

JGH open : an open access journal of gastroenterology and hepatology 20200715 6

<h4>Background and aim</h4>In China, clinical experience with direct-acting antiviral treatments for hepatitis C virus (HCV) infection is still emerging. C-CORAL is a phase 3, multinational, placebo-controlled, double-blind trial of elbasvir/grazoprevir (EBR/GZR) in participants with HCV infection from the Asia-Pacific region and Russia. Here, we report the data from participants enrolled in China.<h4>Methods</h4>Treatment-naive participants with chronic HCV genotype (GT) 1, GT4, or GT6 infectio ...[more]

PMID: 33319038

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Project description:Purpose:People chronically infected with hepatitis C virus (HCV) have diminished patient-reported outcomes (PROs). This study aimed to compare the impact of elbasvir/grazoprevir (EBR/GZR) treatment versus sofosbuvir with pegylated interferon and ribavirin (SOF/PR) on changes in PROs: 1) during the treatment period and 2) at posttreatment follow-up. Patients and methods:PRO data collected during the Phase III C-EDGE Head-2-Head (H2H) open-label study was analyzed. In this trial, patients infected with HCV were randomized 1:1 to receive either EBR/GZR or SOF/PR for 12 weeks. Patients self-administered the Short Form-36 version 2 (SF-36v2®) Health Survey Acute (1-week recall) Form and the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Scale at baseline, during treatment, and posttreatment. Between-group differences in mean change of PRO scores from baseline were estimated during the treatment period and also at the posttreatment follow-up. Effect sizes were calculated to evaluate if the detected change in mean PRO scores is clinically meaningful between groups. Results:There were 255 patients (99.2% White, 54.1% female, 74.9% treatment naïve) included in the analysis. During the treatment period, significant declines in SF-36v2 scores were observed across all domains for the SOF/PR group. Compared to the SOF/PR group, the EBR/GZR group reported more improvement in scores across all SF-36v2 domain scores at the end of the treatment period. At treatment week 12, the between-group differences for 6 out of the 8 domain scores for these patients reflected at least moderate effects (effect sizes >0.5). No significant between-group differences in change in SF-36v2 scores from baseline were detected posttreatment. The decline in SF-36v2 scores observed during the treatment period for the SOF/PR group returned to near baseline scores or above posttreatment. Treatment with EBR/GZR did not impact fatigue scores, but treatment with SOF/PR led to increased fatigue scores during treatment which resolved by posttreatment follow-up week 12. Conclusion:This study demonstrated that HCV treatment with EBR/GZR resulted in a significantly better PRO profile as compared to SOF/PR. PROs are an important consideration as worsening PROs experienced during treatment may negatively influence adherence and ultimately contribute to an unfavorable clinical outcome. Clinicaltrialsgov Identifier:NCT02358044.

Project description:Concomitant proton pump inhibitor (PPI) use reduces plasma concentrations of certain nonstructural protein 5A inhibitors, which are key components of modern hepatitis C infection (HCV) treatments. These reduced concentrations may decrease efficacy, leading to challenging treatment failures due to the development of resistance-associated substitutions. This post-hoc analysis assessed 12-week sustained viral response (SVR12) and pharmacokinetics of fixed-dose combination elbasvir/grazoprevir (EBR/GZR) in patients with HCV infection and self-reported PPI use. Data were derived from six phase 3 EBR/GZR trials with treatment-naive or treatment-experienced genotype 1- or 4-infected patients, with or without compensated cirrhosis. Baseline PPI use was defined as ?7 consecutive days of use between study days -7 and 7. Bivariate analyses assessed PPI use and factors associated with SVR12 with sex, age (continuous and dichotomous), cirrhosis status, prior treatment status, baseline HCV RNA (continuous and dichotomous), HCV genotype, and baseline resistance-associated substitutions as variables in the models. Overall, 12% (162/1,322) of EBR/GZR-treated patients reported baseline PPI use. Of those, 96% achieved SVR12. In patients without PPI use, 97% achieved SVR12. PPI use was not a predictive factor in achieving SVR12 based on a univariate analysis (P = 0.188). In the bivariate models, none of the interaction terms involving PPI use were statistically significant. There was no significant effect of PPI usage, regardless of adjustment for considered factors. The estimated area under the curve and maximum concentration values for EBR were comparable among patients with and without reported PPI use. Conclusion: These results demonstrate that PPI use with EBR/GZR had no clinically significant effect on SVR12 rates in genotype 1/4-infected patients with or without compensated cirrhosis. (clinicaltrials.gov identifiers: NCT02092350, NCT02105467, NCT02105662, NCT02105688, NCT02105701, NCT02358044) (Hepatology Communications 2017;1:757-764).

Dataset Information

Efficacy and safety of elbasvir/grazoprevir in treatment-naive Chinese adults with hepatitis C virus infection: A randomized trial.

Background and aim

Methods

Results

Conclusion

Publications

Efficacy and safety of elbasvir/grazoprevir in treatment-naive Chinese adults with hepatitis C virus infection: A randomized trial.

Similar Datasets

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