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 μgto 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/m2, 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.

IFN‐α subtypes: distinct biological activities in anti‐viral therapy

“…The efficacy of alb-IFN was evaluated in clinical phase IIb studies with IFN-naive patients chronically infected with HCV, in which it was administered every 2 or 4 weeks (Zeuzem et al, 2008). The clinical studies showed that alb-IFN had similar anti-viral effects to pegIFN-a (Nelson et al, 2010;Zeuzem et al, 2010). However, in phase III studies, a higher incidence of serious pulmonary adverse events was observed in alb-IFN-treated patients, which resulted in the cessation of further development by Novartis and Human Genome Sciences in 2010.…”

Immune-modulators to combat hepatitis B virus infection: From IFN-α to novel investigational immunotherapeutic strategies

“…Hence Peg-IFN-2a (Pegasys; Hoffmann-La-Roche) and Peg-IFN-2b (PegIntron; 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 10 Schering Plough), which consist respectively of a single (40 kDa) or several (12 kDa) polyethylene-glycol (Peg) chain(s) added to IFN backbone are currently used to treat CHB patients (Foster, 2010). Other modification included the addition of human albumin moiety to IFN backbone to generate a long half-life fusion protein (albinterferon), which was evaluated in stage III clinical trial in the context of HCV infections and showed no superiority to Peg-IFN (Nelson et al, 2010;Subramanian et al, 2007;Zeuzem et al, 2010). Moreover, in the context of HBV infection, albinterferon has shown higher rates of certain adverse effect as compared to Peg-IFN-, thus likely limiting its further development (Colvin et al, 2015).…”

Patterns of Interferon-Alpha–Induced Thyroid Dysfunction Vary with Ethnicity, Sex, Smoking Status, and Pretreatment Thyrotropin in an International Cohort of Patients Treated for Hepatitis C

“…Rates of each IITD subtype were not different by treatment arm (v 2 = 7.1, p = 0.3). This was expected because randomization was effective and the originally published safety analysis found that the treatment arm did not impact rates of thyroid disease by several different definitions (29). Thus, all further investigations were collapsed across treatment arm.…”

“…Details of the original clinical trial design have been previously described (29). In brief, otherwise healthy adults with liver biopsy-proven chronic hepatitis C genotype 2 or 3 infection without prior IFNa therapy were recruited between 2007 and 2008 at 136 sites in India, Asia/Pacific, North and South America, and Europe.…”