Elbasvir/grazoprevir in Asia‐Pacific/Russian participants with chronic hepatitis C virus genotype 1, 4, or 6 infection

Abstract

The prevalence of hepatitis C virus (HCV) infection in Asian countries is high. This study assessed the efficacy and safety of elbasvir/grazoprevir (EBR/GZR) in participants with HCV infection from Asia‐Pacific countries and Russia. In this phase 3, randomized, placebo‐controlled, double‐blind study, treatment‐naive participants with HCV genotype (GT) 1, 4, or 6 infection were randomized to EBR 50 mg/GZR 100 mg (immediate‐treatment group [ITG]) or placebo (deferred‐treatment group [DTG]) once daily for 12 weeks (Protocol PN‐5172‐067, NCT02251990). The primary efficacy variable was a nonrandomized comparison of sustained virologic response at 12 weeks after the end of therapy (SVR12) for the ITG with a historical control. The primary safety outcome was a randomized comparison between the ITG and DTG. Three hundred thirty‐seven participants were randomized to the ITG (n = 251) or DTG (n = 86); 199 (59.2%) participants were Asian, and 250 (74.4%) had HCV GT1b infection. Overall, 232/250 (92.8%) participants in the ITG achieved SVR12 (97.5% confidence interval, 89.1, 96.5). Of the 18 participants who failed to attain SVR12, 1 was lost to follow‐up and 17 had virologic failure, 13 of whom had HCV GT6 infection. The incidence of adverse events was similar between participants receiving EBR/GZR and placebo (50.8% versus 51.2%; difference, −0.3%; 95% confidence interval, −12.3, 11.9). Conclusion: EBR/GZR for 12 weeks provides an effective and well‐tolerated regimen for chronic HCV GT1 infection in treatment‐naive people from Asia‐Pacific countries and Russia, particularly for the large population with GT1b infection. EBR/GZR is not recommended for the treatment of individuals with HCV GT6 infection. (Hepatology Communications 2018;2:595‐606)

The efficacy and safety of elbasvir/grazoprevir treatment in HCV genotype 1 patients in Taiwan

“…According to the results of large‐scale clinical trial studies, such as C‐EDGE TN, C‐EDGE, TEC‐CORAL, and CO‐INFECTION, the usage of EBR/GZR elicits mostly mild or moderate side effects. The most common side effects include headache (17%), fatigue (15%), and nausea (9%).…”

“…Currently, six HCV genotypes (GTs) are known, with most infections being GT 1 (49.1% of the global HCV‐infected population), followed by GT 3 (17.9%), GT 4 (16.8%), GT 2 (11.0%), and GT 5 or GT 6 (<5%) . The prevalence of hepatitis C is approximately 4.4% in Taiwan . Populations with HCV GT 1b are mainly found in North America (26%), Latin America (39%), Europe (50%), and Asia.…”

Safety and efficacy of elbasvir/grazoprevir in Asian participants with hepatitis C virus genotypes 1 and 4 infection

“…All participants provided voluntary written informed consent before trial entry. The detailed methodology and primary outcomes from these studies have been published previously (C‐SURFER [NCT02092350/Protocol PN052]; C‐EDGE CO‐INFECTION [NCT02105662/Protocol PN061]; C‐EDGE [Treatment‐Naive] [NCT02105467/Protocol PN060]; C‐EDGE [Treatment‐Experienced] [NCT02105701/Protocol PN068]; C‐WORTHY [NCT01717326/Protocol PN035]; C‐EDGE CO‐STAR [NCT02105688/Protocol PN062]; C‐EDGE Head‐2‐Head [NCT02358044/Protocol PN077]; Japan phase 2/3 study [NCT02203149/Protocol PN058]; C‐EDGE‐IBLD [NCT02252016/Protocol PN065]; C‐SCAPE [NCT01932762/Protocol PN047]; and C‐CORAL [NCT02251990/Protocol PN067]). The C‐SALT (NCT02115321/Protocol PN059) study has not yet been published in full.…”

“…While worldwide access to DAA therapies has been variable and limited in resource‐constrained settings, EBR/GZR has been extensively studied in the Asia‐Pacific region. High rates of sustained virologic response at 12 weeks after completion of therapy (SVR12) were achieved in a Japanese phase 2/3 clinical trial and in the C‐CORAL study, which included participants from across the Asia‐Pacific region. EBR/GZR has demonstrated high efficacy across a diverse range of individuals, including those with compensated cirrhosis, people who inject drugs, people with inherited blood disorders, those with HIV co‐infection, and people with end‐stage renal disease .…”

The accuracy of baseline viral load for predicting the efficacy of elbasvir/grazoprevir in participants with hepatitis C virus genotype 1a infection: An integrated analysis

“…This is a post hoc, integrated analysis of data from 11 clinical trials in the EBR/GZR phase 2/3 clinical development program. The methodology and primary outcomes from these studies have been published previously (C‐SURFER [NCT02092350/Protocol PN052]; C‐EDGE CO‐INFECTION [NCT02105662/Protocol PN061]; C‐EDGE Treatment‐Naive [NCT02105467/Protocol PN060]; C‐EDGE Treatment‐Experienced [NCT02105701/Protocol PN068]; C‐WORTHY [NCT01717326/Protocol PN035]; C‐EDGE CO‐STAR [NCT02105688/Protocol PN062]; C‐EDGE Head‐2‐Head [NCT02358044/Protocol PN077]; Japan phase 2/3 study [NCT02203149/Protocol PN058]; C‐EDGE‐Inherited Blood Disorders [NCT02252016/Protocol PN065]; and C‐CORAL [NCT02251990/Protocol PN067]). The C‐SALT [NCT02115321/Protocol PN059] study has not been published in full.…”