A Phase II, Randomized, Double-Blind, Placebo-Controlled Study of Nitazoxanide Plus Peginterferon and Ribavirin in Naïve Patients With Chronic Hepatitis C Genotype 1 Infection: Final Report

Abstract

Treatment of chronic hepatitis C (CHC) with nitazoxanide (NTZ) and peginterferon (PegIFN) with or without ribavirin (RBV) improves sustained virologic response (SVR) rates in naïve genotype 4 patients (Gastroenterology 2009;136:856). The aim of this study was to determine the efficacy of NTZ plus PegIFN and RBV in naïve patients with CHC genotype 1 infection; the final sustained viral response (SVR) rates are reported. One hundred twelve treatment-naïve patients with CHC genotype 1 underwent 2:1 randomization in 13 US centers in this double-blind, placebo-controlled study of NTZ (n = 75) vs placebo (n = 37) twice daily over a 4-week lead-in followed by continued NTZ or placebo plus PegIFN alfa-2a 180 μg weekly and weight-based RBV (1000–1200 mg/d) for 48 weeks. Serum HCV RNA was measured using the Roche Cobas Taqman assay (LOQ = 50 IU/mL). Mean ages (± SD) in the NTZ and placebo groups were 50 ± 7 and 51 ± 8 years, respectively, and 65% of patients were men in both groups. Mean baseline HCV RNA was 6.3 ± 0.7 log10 IU/mL in the NTZ group and 6.4 ± 0.7 log10 IU/mL in the placebo group. Analysis was by intention-to-treat for patients who received any dose of PegIFN. Results are shown in Table 1. In patients with HCV RNA levels >800,000 IU/mL, SVR rates were also higher in the NTZ (n = 62) vs placebo (n = 31) group (42% vs 29%). In sites with customary standard of care response rates, SVR rates were higher in the NTZ group: 57% (n = 49) vs 42% (n = 24), and 55% vs 35% in patients with high viral load. There were no significant differences in adverse events, except for mild intermittent diarrhea in patients receiving NTZ; there were no significant differences in serious adverse events between the 2 treatment groups.Table 1ResultsTreatment groupRVRcEVRETRSVRNTZ + PegIFN + RBV (n = 73)9 (12%)45 (62%)46 (63%)32 (44%)Placebo + PegIFN + RBV (n = 37)7 (19%)18 (49%)17 (46%)12 (32%) Open table in a new tab Consistent with previously reported results in naïve genotype 4 patients, the addition of NTZ increased the SVR rate in genotype 1 naïve patients by more than one third. NTZ 675 mg tablets will be used in phase III studies with the goal of further improving SVR rates.