Randomized Trial of Albinterferon Alfa-2b Every 4 Weeks for Chronic Hepatitis C Virus Genotype 2/3

S. Pianko; S. Zeuzem; W.-L. Chuang; G. R. Foster; S. K. Sarin; R. Flisiak; C.-M. Lee; P. Andreone; T. Piratvisuth; S. Shah; A. Sood; J. George; M. Gould; P. Komolmit; S. Thongsawat; T. Tanwandee; J. Rasenack; Y. Li; M. Pang; Y. Yin; G. Feutren; I. M. Jacobson

Disclosures

J Viral Hepat. 2012;19(9):623-634. 

In This Article

Abstract and Introduction

Abstract

Albinterferon alfa-2b (albIFN) is a fusion protein of recombinant human albumin/recombinant interferon (IFN)-α-2b, with ~200-h half-life. Safety/efficacy of albIFN q4wk was evaluated in 391 treatment-naive patients with chronic hepatitis C virus (HCV) genotype 2/3. Patients were randomized 3:4:4:4 to one of four open-label treatment groups: pegylated IFN (Peg-IFN)-α-2a 180 μg qwk or albIFN 900, 1200 or 1500 μg q4wk, plus oral ribavirin 800 mg/day, for 24 weeks. Primary efficacy endpoint was sustained virologic response (SVR; HCV RNA <20 IU/mL 24 weeks post-treatment). SVR rates were as follows: 85%, 76%, 76% and 78% with Peg-IFNα-2a and albIFN 900, 1200 and 1500 μg, respectively (P = NS); corresponding rapid virologic response rates (HCV RNA <43 IU/mL at week 4) were as follows: 78%, 49% (P < 0.001), 60% (P = 0.01) and 71%. SVR rates were not influenced by interleukin 28B genotype, although rapid virologic response rates were greater with interleukin 28B CC (P = NS). Serious adverse event rates were as follows: 4%, 11%, 3% and 3% with Peg-IFNα-2a and albIFN 900, 1200 and 1500 μg, respectively. No increase in serious/severe respiratory events was noted with albIFN. Fewer absolute neutrophil count reductions <750/mm3 occurred with albIFN (P = 0.03), leading to fewer IFN dose reductions. Haemoglobin reductions <10 g/dL were less frequent with albIFN 900 and 1200 μg vs 1500 μg and Peg-IFNα-2a (P = 0.02), leading to fewer ribavirin dose reductions. albIFN administered q4wk produced fewer haematologic reductions than Peg-IFNα-2a, but had numerically lower SVR rates (P = NS) in patients with chronic HCV genotype 2/3.

Introduction

Hepatitis C virus (HCV) is endemic in most parts of the world, with an estimated overall prevalence of 3% (or 170 million infected individuals), and is a frequent cause of liver disease, including liver failure and hepatocellular carcinoma.[1] HCV genotypes (Gt) 2 and 3 represent 20–40% of chronic HCV infections in North America and Western Europe, and 60% in Southeast Asia.[2] Twenty-four-week combination therapy with pegylated interferon (Peg-IFN)-α injected once weekly (qwk) plus daily oral ribavirin (RBV) has become the standard of care for treatment of chronic HCV Gt 2 or 3.[3] Pegylated IFNα injections are, however, associated with postinjection symptoms such as chills, fever, myalgia, arthralgia, fatigue and headache, which often necessitate concomitant therapy with antipyretics and analgesics. In addition, weekly injections create a burden for the patient with respect to convenience, fear of self-injection and travel when the treatment needs to be administered at a healthcare centre. Fewer injections may, therefore, be an important factor in the decision to undergo treatment and in adherence to therapy.

Albinterferon alfa-2b (albIFN) is a fusion polypeptide of recombinant human albumin and recombinant IFNα-2b, with a half-life of ~8 days and IFNα-like pharmacodynamic properties.[4] A phase 2 dose-ranging study, in which patients with chronic HCV Gt 1 received two albIFN injections (200–1200 μg) 14 days apart, demonstrated that albIFN levels were consistently detectable 28 days after the second injection and antiviral activity was maintained with the higher dose.[5] Recent phase 3 studies of albIFN 900 and 1200 μg injected every 2 week (q2wk) in combination with RBV showed efficacy similar to Peg-IFNα-2a for the treatment of chronic HCV Gt 1 or 2/3.[6,7] In the phase 3 studies, increased rates of pulmonary adverse events (AEs) were noted with albIFN, including interstitial lung disease, compared with those seen with Peg-IFNα. In this study, lower doses of albIFN were investigated, and respiratory assessments were performed prospectively to assess whether any respiratory signals were present when injection frequency was reduced. In addition, albIFN was investigated as a once-every-4-wk (q4wk) regimen with the aim of further reducing injection burden and improving treatment convenience over standard qwk therapy with Peg-IFNα.

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