The combination of grazoprevir plus ribavirin for 12 or 24 weeks demonstrated fast and sustained suppression of hepatitis C virus RNA in treatment-naive patients with hepatitis C virus genotype 1 infection, according to study results.
“The aim of the present proof-of-concept study was to evaluate the interferon free, single direct-acting antiviral regimen of [grazoprevir] plus [ribavirin] in patients with HCV [genotype 1] infection,” Ed Gane, MB ChB, MD, FRACP, MNZM, of Auckland Clinical Studies in New Zealand, and colleagues wrote. “Based on the response guided treatment (RGT) regimens used with ﬁrst-generation protease inhibitors, this pilot study (the C-SPIRIT study) was designed to include an RGT treatment arm and also to assess the potential for a minimal drug regimen in patients with [genotype 1] HCV infection considered ‘easy to cure.’”
Sustained virologic response at follow-up week 12 (SVR12) was the primary endpoint, defined by researchers as HCV RNA below the lower limit of quantitation (LLoQ). On-treatment virologic response at weeks 2, 4 and 12, end-of-treatment response and SVR4 (<LLoQ), and time to first achievement of undetectable HCV RNA were included as secondary endpoints.
The researchers randomly assigned noncirrhotic patients (n = 26) expressing the IL28B CC genotype with HCV genotype 1 infection to grazoprevir 100 mg orally once per day plus ribavirin (weight-based dosing of 800 to 1400 mg/day) for 12 or 24 weeks.
At treatment week 4, patients in the 12-week arm with detectable HCV RNA had treatment extended to 24 weeks (response-guided therapy). Researchers included 22 patients from the total cohort in the per-protocol population. SVR12 in the response-guided therapy arm was 58.3% (7 of 12) and 90% (9 of 10) in the 24-week arm. Seven per-protocol patients experienced virologic failure, with one in the 24-week arm who relapsed after follow-up week 12.
Researchers found that all three breakthrough patients, which developed at treatment week 6 or treatment week 12, had wild-type virus at baseline with Y56H, A156T and D168A/N mutations. Four of the ﬁve relapse patients had wild-type virus at baseline (at relapse 3 had wild-type virus and 1 had V55A and D168A mutations), and one had S122A/T at baseline and S122T at relapse, according to the study data.
No serious adverse events, discontinuations due to adverse events or grade 3/4 elevations in total and/or direct bilirubin were found.
“Overall, the tolerability and safety proﬁle of [grazoprevir] plus [ribavirin] were largely consistent with the well-reported safety proﬁle of [ribavirin],” Gane and colleagues wrote. “The combination of [grazoprevir] plus [ribavirin] was associated with rapid virologic suppression, with 84% of patients in the [per-protocol] population achieving undetectable HCV RNA by [treatment week 4] and 88% (22/25) achieving undetectable HCV RNA at the end of 12 weeks of therapy.”—by Savannah Demko
Disclosures: The researchers report no relevant financial disclosures.