title: Tolerability, pharmacokinetics and antiviral activity of rHSA/IFNα2a for the treatment of chronic hepatitis B infection.
abstract: A recombinant human serum albumin-interferon alpha2a fusion protein (rHSA/IFNα2a) is expected to extend the half-life of IFNα2a. This study aims to evaluate the tolerability, safety and efficacy of rHSA/IFNα2a.
  
  
  
  This is an open, randomized, positive control, multiple-dose ascending Phase Ib study. A panel of 32 treatment naïve and non-cirrhotic chronic hepatitis B patients were divided into four cohorts, and each received 600, 750 or 900 μg of rHSA/IFNα2a or 180 μg of PEG-IFNα2a for 3 months. Tolerability, pharmacokinetics and antiviral responses were assessed.
  
  
  
  Thirty-one of 32 enrolled patients completed the treatment study. The rHSA/IFNα2a treatment was better tolerated than the PEG-IFNα2a 180 μg treatment, as evidenced by blood cell counts and higher serum albumin levels. Half-life (t1/2) of rHSA/IFNα2a was estimated to be 120-140 h, and is potentially suitable for a dosing interval of 2 weeks or longer. Pharmacokinetics of the last dose between rHSA/IFNα2a 750 μg and PEG-IFNα2a 180 μg, with the exception of t1/2, was comparable, and a similar kinetics of inhibiting HBV DNA replication was observed in both groups. Mean reductions in serum HBV DNA levels after treatment were -1.32, -2.13, -1.10 and -2.48 log10 IU/ml in the 600, 750 and 900 μg rHSA/IFNα2a groups and PEG-IFNα2a group, respectively.
  
  
  
  The rHSA/IFNα2a treatment was well tolerated and can be administered biweekly. Similar efficacy in inhibiting HBV replication was observed in both PEG-IFNα2a and rHSA/IFNα2a 750 μg groups.
authors.affiliation: Phase I Clinical Research Center, The First Hospital of Jilin University, Jilin, China.
authors.forename: Yanhua
authors.initials: Y
authors.lastname: Ding
authors.affiliation: Phase I Clinical Research Center, The First Hospital of Jilin University, Jilin, China.
authors.forename: Jinfeng
authors.initials: J
authors.lastname: Lou
authors.affiliation: Phase I Clinical Research Center, The First Hospital of Jilin University, Jilin, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Chen
authors.affiliation: Phase I Clinical Research Center, The First Hospital of Jilin University, Jilin, China.
authors.forename: Xiaojiao
authors.initials: X
authors.lastname: Li
authors.affiliation: Phase I Clinical Research Center, The First Hospital of Jilin University, Jilin, China.
authors.forename: Min
authors.initials: M
authors.lastname: Wu
authors.affiliation: Phase I Clinical Research Center, The First Hospital of Jilin University, Jilin, China.
authors.forename: Cuiyun
authors.initials: C
authors.lastname: Li
authors.affiliation: Phase I Clinical Research Center, The First Hospital of Jilin University, Jilin, China.
authors.forename: Jingrui
authors.initials: J
authors.lastname: Liu
authors.affiliation: Phase I Clinical Research Center, The First Hospital of Jilin University, Jilin, China.
authors.forename: Chengjiao
authors.initials: C
authors.lastname: Liu
authors.affiliation: Phase I Clinical Research Center, The First Hospital of Jilin University, Jilin, China.
authors.forename: Qingmei
authors.initials: Q
authors.lastname: Li
authors.affiliation: Phase I Clinical Research Center, The First Hospital of Jilin University, Jilin, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Phase I Clinical Research Center, The First Hospital of Jilin University, Jilin, China.
authors.forename: Junqi
authors.initials: J
authors.lastname: Niu
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D004279:DNA, Viral / Q000097:blood; D004334:Drug Administration Schedule; D005260:Female; D006207:Half-Life; D019694:Hepatitis B, Chronic / Q000188:drug therapy*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000008:administration & dosage; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D000075462:Serum Albumin, Human / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D014779:Virus Replication / Q000187:drug effects; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D004279:DNA, Viral; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; C100416:peginterferon alfa-2a; D000075462:Serum Albumin, Human
keywords: HBV; albumin-interferon; antiviral responses; pharmacokinetics