Randomized, controlled pharmacokinetic and pharmacodynamic evaluation of albinterferon in patients with chronic hepatitis B infection

J Gastroenterol Hepatol. 2015 Jan;30(1):184-91. doi: 10.1111/jgh.12671.

Abstract

Background and aims: Albinterferon is a fusion of albumin and interferon-α2b developed to improve the pharmacokinetics, convenience, and potential efficacy of interferon-α for the treatment of chronic hepatitis infections.

Methods: This open-label, randomized, active-controlled, multicenter study investigated the safety and efficacy of albinterferon in patients with chronic hepatitis B virus (HBV) infection who were e-antigen (HBeAg) positive. One hundred and forty-one patients received one of four albinterferon doses/regimens or pegylated-interferon-α2a. Primary efficacy outcomes were changes in serum HBeAg and antibody, HBV-DNA, and alanine aminotransferase. Principal safety outcomes were changes in laboratory values, pulmonary function, and adverse events.

Results: The study was prematurely terminated as phase III trials in hepatitis C infection indicated noninferior efficacy but inferior safety compared with pegylated-interferon-α2a. Here, all treatment groups had a significant reduction in HBV-DNA from baseline. Reductions in HBV-DNA were not significantly different, except the 1200 μg every 4 weeks albinterferon dose which was inferior compared with pegylated-interferon-α2a. The serum alanine aminotransferase levels decreased in all arms. The per-patient incidence of adverse events was not significantly different for albinterferon (96.4-100%) and pegylated-interferon-α2a (93.1%). Total adverse events, however, were higher for albinterferon and correlated to dose. Decreased lung function was found in all arms (∼93% of patients), and was more common in some albinterferon groups.

Conclusions: Albinterferon doses with similar anti-HBV efficacy to pegylated-interferon-α2a had higher rates of certain adverse events, particularly changes in lung diffusion capacity (http://www.clinicaltrials.gov number NCT00964665).

Keywords: albinterferon; hepatitis B; lung diffusion capacity.

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Alanine Transaminase / blood
  • Albumins / administration & dosage*
  • Albumins / adverse effects
  • Antiviral Agents / administration & dosage*
  • Antiviral Agents / adverse effects
  • Biomarkers / blood
  • DNA, Viral / blood
  • Female
  • Hepatitis B e Antigens / blood
  • Hepatitis B virus / genetics
  • Hepatitis B virus / immunology
  • Hepatitis B, Chronic / diagnosis
  • Hepatitis B, Chronic / drug therapy*
  • Hepatitis B, Chronic / virology
  • Humans
  • Interferon-alpha / administration & dosage*
  • Interferon-alpha / adverse effects
  • Male
  • Polyethylene Glycols / administration & dosage
  • Polyethylene Glycols / adverse effects
  • Recombinant Proteins / administration & dosage
  • Recombinant Proteins / adverse effects
  • Treatment Outcome
  • Young Adult

Substances

  • Albumins
  • Antiviral Agents
  • Biomarkers
  • DNA, Viral
  • Hepatitis B e Antigens
  • Interferon-alpha
  • Recombinant Proteins
  • Polyethylene Glycols
  • albinterferon alfa-2b
  • Alanine Transaminase
  • peginterferon alfa-2a

Associated data

  • ClinicalTrials.gov/NCT00964665