In the Journals

Grazoprevir plus ribavirin linked to rapid, sustained suppression of HCV RNA

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.

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.