Efficacy and Safety of 8 Weeks of Glecaprevir/Pibrentasvir in Treatment-Naïve, HCV-Infected Patients with APRI ≤ 1 in a Single-Arm, Open-Label, Multicenter Study

Abstract

Introduction: The presence or absence of cirrhosis in patients with chronic hepatitis C virus (HCV) infection influences the type and duration of antiviral therapy. Non-invasive markers, like serum aspartate aminotransferase (AST) to platelet ratio index (APRI), may help identify appropriate HCV treatment-naive patients for 8-week treatment with the pangenotypic regimen of glecaprevir/pibrentasvir.

Methods: This single-arm, open-label, international, prospective study (NCT03212521) evaluated the efficacy and safety of 8-week glecaprevir/pibrentasvir regimen in HCV treatment-naïve adults with chronic HCV genotypes 1-6 infection, APRI ≤ 1, and no prior evidence of cirrhosis. The primary and secondary outcomes were sustained virologic response at 12 weeks post-treatment (SVR12) by modified intent-to-treat (mITT) and intent-to-treat (ITT) analyses, respectively. Additional endpoints included virologic failures, treatment adherence, and genotype-specific SVR12 rates.

Results: Among the 230 patients enrolled, most were less than 65 years old (90%); 37% and 43% had a history of injection drug use or psychiatric disorders, respectively. SVR12 rates were 100% (222/222; 95% CI 98.3-100%) and 96.5% (222/230; 95% CI 94.2-98.9%) by mITT and ITT analyses, respectively. There were no virologic failures. ITT SVR12 rates were greater than 94% for all HCV genotypes. In patients with available data, treatment adherence was 99% (202/204). There were no grade 3 or higher laboratory abnormalities in alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin, and low rates of serious adverse events (2%).

Conclusions: Glecaprevir/pibrentasvir was highly efficacious and well tolerated in HCV treatment-naïve patients with APRI ≤ 1 and no prior evidence of cirrhosis.

Trial registration: ClinicalTrials.gov number, NCT03212521.

Funding: AbbVie. Plain language summary available for this article.

Keywords: Chronic hepatitis C; Direct acting antiviral; Glecaprevir/pibrentasvir; Infectious diseases; Simplification.

Figures

Fig. 1

Trial profile. *Patients who were screening failures are counted under each reason given for screen fail; therefore, the sum of the counts given for the reasons for screen fail may be greater than the overall number of screen failures. †Majority of patients who did not meet the eligibility criteria was not due to failure to meet APRI score of ≤ 1 at the time of screening

Fig. 2

Efficacy of 8-week G/P regimen in HCV treatment-naïve patients with APRI ≤ 1. G/P efficacy, defined as SVR12, is reported overall using modified intent-to-treat (mITT; blue) and intent-to-treat (ITT; green) analyses. Bar graphs show mean with 95% confidence intervals and include reasons for non-response. Dotted lines indicate threshold above which lower bound of mITT and ITT analysis must be greater than in order to meet primary and secondary endpoint, respectively. *Includes two patients who prematurely discontinued because of a serious AE (see Table 2). †All five patients missing SVR12 data had no detectable HCV RNA at the end of treatment

Fig. 3

Efficacy by genotype for 8-week G/P regimen in HCV treatment-naïve patients with APRI ≤ 1. G/P efficacy, defined as SVR12, is reported by HCV genotype using modified intent-to-treat (mITT; blue) and intent-to-treat (ITT; green) analyses. Bar graphs show mean with 95% confidence intervals. *One GT1 patient with subtype GT1i achieved SVR12