Albinterferon Alfa-2b was not inferior to pegylated interferon-α in a randomized trial of patients with chronic hepatitis C virus genotype 2 or 3

Abstract

Background & aims: A phase 3 active-controlled study was conducted to assess the efficacy/safety of albinterferon alfa-2b (albIFN), a novel, long-acting, genetic fusion polypeptide of recombinant human albumin and interferon alfa-2b, in patients with chronic hepatitis C virus (HCV) genotype 2/3.

Methods: In all, 933 patients were randomized to open-label subcutaneous treatment with pegylated interferon-alfa-2a (Peg-IFNalfa-2a) 180 μg/wk, or albIFN 900 or 1200 μg every 2 weeks for 24 weeks, each administered with oral ribavirin 800 mg/day. The primary end point of the study was sustained virologic response (SVR) (HCV-RNA level, <15 IU/mL at week 48). During the study, the data monitoring committee recommended dose modification for all patients receiving albIFN 1200 μg to 900 μg, impacting 38% of this treatment arm.

Results: By intention-to-treat analysis, SVR rates were 84.8% (95% confidence interval, 80.4%-88.6%), 79.8% (95% confidence interval, 74.9%-84.1%), and 80.0% (95% confidence interval, 75.1%-84.3%) with Peg-IFNalfa-2a, and albIFN 900 and 1200 μg, respectively. The primary hypothesis of noninferiority of SVR was established for albIFN 900 μg (P = .009) and 1200 μg (P = .006). Independent positive predictors of SVR by multivariate regression analysis were pretreatment HCV-RNA level less than 400,000 IU/mL, age younger than 45 years, body mass index less than 30 kg/m(2), genotype 2, normal γ-glutamyl transpeptidase and increased alanine aminotransferase levels at baseline, fibrosis stage F0-F2, no steatosis, and Asian geographic region (Peg-IFNalfa-2a only). The 3 treatment groups showed similar rates of serious (7%-8%) and severe (13%-16%) adverse events, and discontinuations owing to adverse events (3.6%-5.5%).

Conclusion: Albinterferon alfa-2b 900 μg every 2 weeks provides an alternative efficacious treatment option in patients with chronic HCV genotype 2 or 3.

Trial registration: ClinicalTrials.gov NCT00411385.

Figure 1

Disposition of patients. ¹Randomized to Peg-IFNalfa-2a 180-μg/wk group. 2As treated; 1 patient was randomized to Peg-IFNalfa-2a 180-μg, but received albIFN 900 μg every 2 weeks. EVR12, early virologic response at week 12.

Figure 2

SVR rates (overall and in genotype 2 or 3).

Figure 3

Predictors of SVR by multivariate regression model. Model-based adjusted odds ratios and associated 95% CIs for factors provided along the y-axis. Plotting symbol represents odds ratio; horizontal line spans coverage of CI. Vertical reference line at odds ratio of 1 indicates no difference. Note: Asian region subgroup shown at top of figure is post hoc analysis. ALT, alanine aminotransferase; BMI, body mass index; F, fibrosis score; GGT, γ-glutamyl transpeptidase; ULN, upper limit of normal; wt, weight.