Efficacy of Elbasvir and Grazoprevir in Participants With Hepatitis C Virus Genotype 4 Infection

A Pooled Analysis

Tarik Asselah; Hendrik Reesink; Jan Gerstoft; Victor de Ledinghen; Paul J. Pockros; Michael Robertson; Peggy Hwang; Ernest Asante-Appiah; Janice Wahl; Bach-Yen Nguyen; Eliav Barr; Rohit Talwani; Lawrence Serfaty

Disclosures

Liver International. 2018;38(9):1583-1591. 

In This Article

Materials and Methods

Treatment-naïve and treatment-experienced (previously failed pegylated interferon-based HCV therapy) participants 18 years of age or older with chronic HCV GT4 infection and baseline HCV RNA ≥10 000 IU/mL who were enrolled in the Phase 2 and Phase 3 clinical study programme for EBR/GZR were included in the analysis. Participants with HIV co-infection and well-compensated Child-Pugh A cirrhosis were included in the study. Cirrhosis was defined as liver biopsy consistent with METAVIR F4 at any time prior to entry into the study; FibroScan >12.5 kPa within 12 months of study entry; or AST to platelet ratio (APRI) >2.0 and FibroTest >0.75 within 12 months of study entry. The analysis population was the full analysis set (FAS; all participants who received at least 1 dose of study medication). The primary endpoint was sustained virologic response at week 12 (SVR12; HCV RNA less than the lower limit of quantitation at 12 weeks after the completion of study therapy). Participants with present or past decompensated liver disease (as evidenced by a presence or history of ascites, oesophageal or gastric variceal bleeding, hepatic encephalopathy or other signs of advanced liver disease) or evidence of hepatocellular carcinoma were excluded from the study.

Of the >1500 participants in the EBR/GZR Phase 2/3 clinical programme, 155 participants infected with HCV GT4 (111 treatment-naïve and 44 treatment-experienced) were included in this analysis (Figure 1). Most participants (101 treatment-naïve and 16 treatment-experienced) were treated with 12 weeks of EBR/GZR and some participants were treated with 12 weeks of EBR/GZR plus ribavirin (RBV) or 16 weeks of EBR/GZR ± RBV (Figure 1).

Figure 1.

Participant disposition. Among the >1500 participants in the Phase 2 and Phase 3 clinical trials of EBR/GZR, there were 155 HCV GT4-infected participants who were part of the pooled analysis. There were 111 GT4-infected participants who were HCV treatment-naïve and 44 GT4-infected participants who were peg-interferon and ribavirin treatment-experienced. The numbers of GT4-infected participants who received 12 or 16 wk of EBR/GZR, and the presence or absence of ribavirin in the regimens received by the participants is shown

Analyses

This is an integrated retrospective analysis of data from 8 international phase 2/3 clinical trials (Table S1, and the references below). All studies were carried out in accordance with the Declaration of Helsinki, current guidelines on Good Clinical Practices and local ethical and legal requirements. For each of these 8 clinical studies, independent institutional review boards or ethics committees reviewed and approved the protocol and applicable amendments for each participating institution (Table S2). All participants provided voluntary written informed consent before trial entry. The detailed methodology and primary outcomes from these studies have been published or presented previously (C-SCAPE [NCT01932762; Protocol PN047[26]]; C-EDGE TREATMENT-NAÏVE [NCT02105467; Protocol PN060[23]]; C-EDGE CO-INFECTION [NCT02105662; Protocol PN061[22]]; C-EDGE CO-STAR [Participants on opioid substitution therapy; NCT02105688 Protocol PN062[27]]; C-EDGE Inherited blood disorders [NCT02252016; Protocol PN065[28]]; C-CORAL [Asia-Pacific participants; Protocol PN067[29]]; C-EDGE TREATMENT EXPERIENCED [NCT02105701; Protocol PN068[30]]; C-EDGE Head-2-head [NCT02358044; Protocol PN077[31]]). Efficacy analyses were based on the full analysis set (FAS) population which included all randomized subjects who received ≥1 dose of drug. Safety analyses were also provided.

Comments

3090D553-9492-4563-8681-AD288FA52ACE

processing....